Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Biological factors driving colorectal cancer metastasis.

Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

A new benzophenone derivative from Aspergillus fumigatus WJ-131.

A new benzophenone derivative, 8'-hydroxymonomethylsulochrin (1), together with eighteen known compounds (2-19) were produced by the endophytic fungus Aspergillus fumigatus WJ-131, isolated from the stem of Gardenia jasminoides. The structure of 1 was determined by extensive spectroscopic analysis and X-ray crystallography. Under the condition of concentration of 20.0 µM, the splenic lymphocytes proliferation rates of compounds 1 and 7 induced by LPS were 39.4% and 38.1% (LPS, the splenic lymphocytes cell proliferation rates of 21.3%), and the splenic lymphocytes proliferation rate of compounds 7 induced by ConA is 44.6% (ConA, the splenic lymphocytes proliferation rates of 28.9%). Therefore, compounds 1 and 7 promoted the proliferation of ConA/LPS-stimulated splenic lymphocytes at 20.0 µM in vitro. In addition, compound 1 showed weak antibacterial activity against Fusarium oxysporum.

Macrostines A and B: Tetracyclic fisicoccane from the fungus Periconia macrospinosa WTG-10.

Two previous unreported fusicoccane diterpenoids macrostines A and B, together with seven known compounds were isolated from an extract of the fungus Periconia macrospinosa WTG-10. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Macrostines A and B showed no cytotoxicity, antimicrobial activity and inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. Compound 9 showed moderate activity against Bacillus subtilis.

O-arm navigation assisted hemivertebra resection and bone grafting and internal fixation for the congenital cervicothoracic hemivertebra / 中华骨科杂志

Objective:To investigate the clinical efficacy and precautions of O-arm combined with navigation-assisted steotomy and hemivertebra resection for congenital cervicothoracic hemivertebra.Methods:From February 2016 to October 2020, the clinical data of 12 patients with cervicothoracic hemivertebra admitted in Henan Provincial People's Hospital were retrospectively analyzed, including 5 males and 7 females, aged 9.4±2.6 years (range, 4-15 years). Intraoperative neural monitoring system was used to ensure the safety of surgical correction process and O-arm navigation system assisted the implantation of pedicle screws,hemivertebra resection, and scoliosis deformity correction. Postoperative CT was used to evaluate the accuracy of screw placement, and routine preoperative and postoperative X-ray films of the full-length spine in standing position were taken to measure the coronal and sagittal Cobb angles. The correction rate of scoliosis and kyphosis, internal fixation, shoulder height difference and bone graft fusion were calculated at the final follow-up.Results:A total of 108 pedicle screws were inserted in 12 patients, and the screw placement accuracy rate was 96.3% (104/108). The follow-up time was 37.9±10.2 months (range, 24-61 months). The number of fused segments was 5.4±1.1 (range, 4-7). One week after surgery, the correction rate of Cobb angle was 78.5%±3.2% for scoliosis and 70.1%±5.4% for kyphosis. There were statistically significant differences in side and kyphosis Angle and Scoliosis Research Society (SRS)-22 score between preoperative and 1 week after surgery ( P<0.05). There was no significant difference between the operation and the last follow-up ( P>0.05). At the last follow-up, all the 12 patients achieved gradeⅠ fusion. SI was 2.4±0.8 cm before operation, 1.0±0.6 cm at 1 week after operation, and 0.7±0.5 cm at last follow-up, and the difference was statistically significant ( F=38.30, P<0.001). No pseudojoint formation, significant loss of correction Angle, or rupture of internal fixation relaxant occurred during the operation or during follow-up. Conclusion:O-arm combined with navigation-assisted steotomy and hemivertebra resection for the treatment of congenital cervicothoracic hemivertebra has the advantages of good orthopedic effect, reduced radiation exposure and fewer complications, and accurate pedicle screw implantation and hemivertebra resection.

Efficacy of satellite rod revision surgery via a combined anterior and posterior approach for rod fracture after posterior vertebral column resection in patients with severe thoracolumbar kyphosis / 中华创伤杂志

Objective:To investigate the clinical efficacy of satellite rod revision surgery via a combined anterior and posterior approach for rod fracture after posterior vertebral column resection (PVCR) in patients with severe thoracolumbar kyphosis.Methods:A retrospective case series study was conducted on the clinical data of 11 patients with rod fracture after PVCR for severe thoracolumbar kyphosis, who were treated in Henan Provincial People′s Hospital from January 2013 to January 2021. There were 6 males and 5 females, with the age range of 21-62 years [(35.4±13.0)years]. Among them, 4 patients had traumatic kyphosis, 4 presented congenital kyphosis and 3 showed tuberculous kyphosis. All the patients had obvious low back pain. According to the American Spinal Injury Association (ASIA) score, 2 patients were found with grade C, 2 with grade D and 7 with grade E. All the patients underwent revision surgery for internal fixation using satellite rod via a combined anterior and posterior approach. The operation time, intraoperative blood loss and postoperative hospital stay were recorded. The imaging parameters such as kyphosis Cobb angle, scoliosis Cobb angle, distance between C 7 plumb line and central sacral vertical line (C 7-CSVL), and distance between C 7 plumb line and sagittal vertical axis (SVA) were measured preoperatively, at 1 week postoperatively and at latest follow-up. At the same time, the visual analogue scale (VAS), Oswestry dysfunction index (ODI), and simplified Chinese version of the scoliosis research society-22 (SRS-22) questionnaire were used to evaluate the clinical efficacy. At the latest follow-up, the osteotomy fusion was evaluated by Suk criterion and ASIA score was used to evaluate the recovery of neurological function. The complications were also recorded for the patients. Results:All the patients were followed up for 24-84 months [(47.5±16.2)months]. The operation time was 100-220 minutes [(149.4±37.6)minutes], with the intraoperative blood loss of 150-350 ml [(246.3±64.6)ml] and the postoperative hospital stay of 5-8 days [(6.1±1.1)days]. The kyphosis Cobb angles [(18.5±3.2)° and (19.3±2.9)°] and the scoliosis Cobb angles [(11.8±2.2)°, (11.1±2.2)°] at 1 week post-operation and at the latest follow-up were all improved significantly compared with the preoperative ones [(60.4±6.3)°, (21.7±5.5)°] (all P<0.01), with the average correction rates being 69.4% and 45.6%, respectively, with no significant differences between 1 week post-operation and latest follow-up (all P>0.05). The C 7-CSVL was reduced from preoperative (21.2±4.3)mm to (15.7±2.4)mm at 1 week post-operation, and to (15.9±2.2)mm at the latest follow-up (all P<0.01). The SVA was improved from preoperative (51.0±6.8)mm to (16.6±3.6)mm at 1 week post-operation, and to (15.3±3.9)mm at the latest follow-up (all P<0.01). There were no significant differences in C 7-CSVL or SVA at 1 week post-operation or at the latest follow-up (all P>0.05). The VAS [(2.5±0.9)points, (1.9±0.9)points], ODI (20.1±5.4, 18.4±5.2) and SRS-22 [(83.4±5.8)points, (85.0±4.1)points] at 1 week post-operation and at the latest follow-up were significantly improved compared with the preoperative ones [(6.0±1.4)points, 57.2±8.7, (62.0±9.1)points] (all P<0.01), but no significant differences were found between 1 week post-operation and latest follow-up (all P>0.05). At the latest follow-up, the bone grafts achieved osseous fusion in all the patients, and the ASIA grade was improved from grade C to grade D in 2 patients and from grade D to grade E in 2 patients. No complications such as serious neurological or vascular injury occurred during perioperative period. No pseudoarthrosis formation, internal fixation loosening or fracture occurred during follow-up. Conclusion:Satellite rod revision surgery via a combined anterior and posterior approach for rod fracture after PVCR in patients with severe thoracolumbar kyphosis has the advantages of less trauma and faster convalescence, excellent results of deformity correction, significant pain relief, functional improvement, and fewer complications.

IMM-H007 attenuates isoprenaline-induced cardiac fibrosis through targeting TGFß1 signaling pathway.

Upon chronic stress, ß-adrenergic receptor activation induces cardiac fibrosis and leads to heart failure. The small molecule compound IMM-H007 has demonstrated protective effects in cardiovascular diseases via activation of AMP-activated protein kinase (AMPK). This study aimed to investigate IMM-H007 effects on cardiac fibrosis induced by ß-adrenergic receptor activation. Because adenosine analogs also exert AMPK-independent effects, we assessed AMPK-dependent and -independent IMM-H007 effects in murine models of cardiac fibrosis. Continual subcutaneous injection of isoprenaline for 7 days caused cardiac fibrosis and cardiac dysfunction in mice in vivo. IMM-H007 attenuated isoprenaline-induced cardiac fibrosis, diastolic dysfunction, α-smooth muscle actin expression, and collagen I deposition in both wild-type and AMPKα2-/- mice. Moreover, IMM-H007 inhibited transforming growth factor ß1 (TGFß1) expression in wild-type, but not AMPKα2-/- mice. By contrast, IMM-H007 inhibited Smad2/3 signaling downstream of TGFß1 in both wild-type and AMPKα2-/- mice. Surface plasmon resonance and molecular docking experiments showed that IMM-H007 directly interacts with TGFß1, inhibits its binding to TGFß type II receptors, and downregulates the Smad2/3 signaling pathway downstream of TGFß1. These findings suggest that IMM-H007 inhibits isoprenaline-induced cardiac fibrosis via both AMPKα2-dependent and -independent mechanisms. IMM-H007 may be useful as a novel TGFß1 antagonist.

Clinical practice of percutaneous full-endoscopic modified posterior lumbar interbody fusion combined with pedicle screw fixation through paraspinal muscle clearance / 西安交通大学学报(医学版)

【Objective】 To study the clinical practice and early outcome of percutaneous full-endoscopic modified posterior lumbar interbody fusion（mPLIF）combined with pedicle screw fixation through paraspinal muscle clearance. 【Methods】 A retrospective study was conducted to analyze the clinical data of patients with lower lumbar spinal diseases treated from May 2019 to April 2020. All the enrolled patients received mPLIF combined with pedicle screw fixation through paraspinal muscle clearance. The follow-up period was more than 1 year； the general parameters included age， gender， duration of disease， diagnosis of disease， surgery segment， and postoperative hospitalization time. Operation parameters included operation time and blood loss. We obtained the clinical parameters such as visual analogue scale （VAS） score for back and lower extremity， Oswestry disability index （ODI） score， and Macnab satisfaction score at the last follow-up. We evaluated the imaging parameters including intervertebral disc height， segmental lordosis angle， lumbar lordosis angle， as well as fusion outcome of patients with single segmental lumbar disease. In addition， intraoperative and postoperative complications were recorded. 【Results】 Totally 18 patients met the inclusion criteria， among whom 8 were male and 10 were female， with the average age of （53.3±8.3） years old and the average duration of disease being （28.9±36.6） months. Among them 16 patients were diagnosed as lumbar degenerative disease and the other 2 had lumbar disc infection. One patient received L3-L4 and L4-L5 intervertebral fusion； the others had one-segmental fusion， among which 11 cases were L4-L5 and 6 cases were L5-S1. The average operation time was （207.8±31.7） min， and the average blood loss was （25.6±7.8） mL， and the mean postoperative hospitalization time was （6.56±2.30） days. VAS scores of back and lower extremities at postoperative 1 week， 6 months and the last follow-up were statistically significantly improved from the preoperative scores. ODI scores at postoperative 6 months and the last follow-up were also statistically significantly improved. The rate of excellent and good according to the Macnab criteria was 94.4%. For the 17 single-level fusion patients， intervertebral height was significantly higher postoperatively and at the last follow-up compared with that of the preoperative one （P<0.05）. Segmental lordosis angle was bigger postoperatively and at the last follow-up （P>0.05）， which was not statistically significant. Lumbar lordosis angle was significantly bigger postoperatively （P<0.05） and bigger at the last follow-up， but with no statistical significance （P>0.05）. The fusion rate at the last follow-up was 88.2%. The cage broke in the process of implantation in one patient. A cage retroposition occurred in one patient at the follow-up. 【Conclusion】 Percutaneous full-endoscopic modified posterior lumbar interbody fusion combined with pedicle screw fixation through bilateral paraspinal muscle clearance by one incision showed excellent clinical outcomes in treating many kinds of lower lumbar diseases. This operation should be an excellent option for lower lumbar fusion.

Clinical efficacy of screw placement assisted with the 3D printing pre-installed screw channel model in the single complete segmented congenital hemivertebrectomy / 中华实用儿科临床杂志

Objective:To explore the clinical effect of the 3D printing pre-installed screw channel model in assisting screw placement of single complete segmented congenital hemivertebrectomy.Methods:Clinical data of 13 children treated with single complete segmented congenital hemivertebrectomy in the Department of Spine and Spinal Surgery of Henan Provincial People′s Hospital from August 2016 to January 2019 were retrospectively analyzed.Among them, there were 5 males and 8 females with the mean age of 9.9 (5-14) years.Categorized by the lesion location, 3 cases were located at T 9, 2 cases at T 10, 5 cases at T 11, 1 case at T 12, and 2 cases at L 1.During the operation, the 3D printing pre-installed screw channel model was used to assist the placement of pedicle screws.The accuracy of screw placement was assessed by the postoperative CT.All children were routinely examined by full-length anterior and lateral X-ray of spine in the standing position before and after surgery to measure the Cobb angles at the coronal and sagittal view.Furthermore, the correction rate of scoliosis and kyphosis after surgery and during follow-up was also calculated.The One-Way repeated measures ANOVA was used to compare the Cobb angle of scoliosis and kyphosis before surgery, after surgery and during follow-up. Results:A total of 85 pedicle screws were placed in 13 children, with the accuracy rate of screw placement of 95.3%.The mean surgery time and intraoperative blood loss were (216.9±28.3) min, and (478.5±132.6) mL, respectively.Scoliosis Cobb was corrected from (57.1±12.7)° to (12.7±4.7)° with a correction rate of (78.4±5.9)%, which was (14.2±7.0)° at the last follow-up.Kyphosis angle was corrected from (46.2±8.4)° to (13.2±4.4)° with a correction rate of (72.6±7.0)%, which was (14.0±3.4)° at the last follow-up.None of the children had serious complications like vascular and nerve damage.The mean postoperative follow-up was 12.3 (6-18) months.No significant loss of angle was detected during the follow-up period.There were significant differences in the lateral and kyphotic angles after surgery and during follow-up compared with preoperative ones (all P<0.05). No significant difference was detected between the postoperative lateral and kyphotic angles and those at the last follow-up (all P>0.05). Conclusion:The 3D printing pre-installed screw channel model used to assist screw placement of single complete segmented congenital hemivertebrectomy can improve the precision of screw placement and the orthopedic effect on lateral kyphosis.

The reliability of the original smartphone scoliosis screening APP for measuring the Cobb angle of adolescent idiopathic scoliosis / 中华实用儿科临床杂志

Objective:To explore the accuracy and repeatability of the smartphone scoliosis screening APP developed by our team in the measurement of the Cobb angle of adolescent idiopathic scoliosis (AIS).Methods:Clinical data of 60 patients with AIS admitted to Department of Spine and Spinal Surgery, Henan Province People′s Hospital from August 2020 to February 2021 were analyzed retrospectively.Three surveyors measured the coronal main curvature Cobb angle, sagittal thoracic kyphosis (TK) angle, thoracolumbar kyphosis (TLK) angle and lumbar kyphosis (LL) angle on whole-spine lateral X-ray films of 60 patients with AIS by means of the protractor, scoliosis screening APP and computerized Picture Archiving and Communication System (PACS). The time and results of each measurement were recorded.The measurement was repeated once after 2 weeks.Paired t-test was used to compare the measurement time of the APP method and the protractor method.Taking the Cobb angle measurement results of the PACS system as the reference standard, the accuracy of Cobb angle measurement by the APP method was analyzed by paired t-test.The repeatability of the surveyor and the consistency between the surveyors was compared by intraclass correlation coefficient (ICC). Results:Among the 60 patients with AIS, there were 17 males and 43 females, aged from 10 to 16 years [(12.2±2.4) years]. The main bends were thoracic curvature (Lenke Ⅰ) in 23 cases, Lenke Ⅱ in 18 cases and thoracolumbar curvature/lumbar curvature (Lenke V) in 19 cases.The APP method took significantly less time to measure the Cobb angle than the protractor method ( P<0.05). There was no significant difference in the Cobb angle measured by the APP method and PACS method ( P>0.05). The results of the coronal main curvature Cobb angle, TK angle, TLK angle and LL angle measured by 3 surveyors through the APP method were all in good agreement (ICC=0.990, 0.988, 0.986, 0.987). The repeatability (ICC 0.973-0.982) of the coronal main curvature Cobb angle, TK, TLK and LL measured twice before and after the APP method were both better that of the protractor method (ICC 0.933-0.954). Conclusions:Compared with the traditional protractor, the smartphone scoliosis screening APP has the advantages of short measurement time, high efficiency, excellent accuracy and good repeatability in measuring the Cobb angle of AIS.

Computer-assisted pelvic osteotomy and 3D printing guide plate for developmental dislocation of hip surgery / 中华骨科杂志

Objective:To explore the scheme of accurate pelvic osteotomy parameters and to analyze the feasibility and efficacy of 3D printing navigation plate in developmental dysplasia of the hip surgery.Methods:From January 2015 to December 2017, a total of 18 children with DDH underwent computer-assisted Salter pelvic osteotomy (computer-assisted osteotomy group) and 25 children with DDH who underwent conventional Salter pelvic osteotomy (conventional osteotomy group) were selected for retrospective analysis. There were 11 males and 32 females with an average age of 3.2±2.5 (range 1-11) years. According to International Hip Dysplasia Institute (IHDI) classification, there were 20 cases of type 1, 9 of type 2, 12 of type 3 and 2 of type 4. All patients were unilateral dislocation, including 18 cases on the left and 25 on the right. All children underwent pelvic CT examination before operation. Further, the proximal femur was surgically corrected during the operation. According to the acetabular rotation angle (ATA) and bony acetabular index (BAI), the computer-assisted osteotomy group simulated the operation with Mimics software made 3D printing navigation plate through which an accurate osteotomy scheme was developed. The two groups were compared in operative duration, intraoperative blood loss, Japanese Orthopaedic Association (JOA) hip joint score. Acetabular index (AI), central edge (CE) angle, and acetabulum head index (AHI) were compared between the two groups by using postoperative X-ray. The acetabular tilt angle (ATA) changes before and after operation in the computer-assisted osteotomy group were compared through 3D CT.Results:The follow-up duration was 2.3±0.2 (2.0 to 2.5) years in the computer-assisted osteotomy group and 2.8±0.15 (2.5 to 3.0) years in the conventional osteotomy group. The operative duration in the computer-assisted osteotomy group was 127±20.6 min, which was significantly longer ( t=4.657, P<0.001) than that in the conventional osteotomy group (103±13.2 min). Intraoperative bleeding was 157±17.5 ml in the computer-assisted osteotomy group and 151±15.3 ml in the conventional osteotomy group without significant difference between the two groups ( t=1.195, P=0.239). At 2 years after surgery, the JOA score of the hip joint in the computer-assisted osteotomy group (86.7±8.5 points) was like that (84.8±10.0 points) in the conventional osteotomy group ( t=0.628, P=0.533). At the last follow-up, the CE angle in the computer-assisted osteotomy group (36.8°±5.2°) was significantly larger than that (31.8°±4.4°) in the conventional osteotomy group ( t=3.414, P<0.001). There was statistically significant difference in term of AHI between the computer-assisted osteotomy group (85.8%±6.6%) and the conventional osteotomy group (80.4%±8.3%, t=2.284, P=0.028). AI was 23.5°±5.5° in the computer-assisted osteotomy group and 25.2°±4.2° in the conventional osteotomy group without significant difference ( t=-1.150, P=0.257). The ATA of the affected side was 12.3°±1.4° in the computer-assisted osteotomy group which was similar ( t=0.614, P=0.547) to that of the healthy side (11.8°±2.8°). Conclusion:Based on specific anatomical parameters, computer-assisted preoperative planning can not only directly simulate the process of osteotomy, but also produce individualized 3D printed guide plates. Compared with conventional Salter pelvic osteotomy, computer-assisted osteotomy can achieve accurate radiographic correction of the hip joint in children with DDH, resulting in a better matching relationship between the femoral head and acetabulum.

Membrane nanotubes facilitate the propagation of inflammatory injury in the heart upon overactivation of the ß-adrenergic receptor.

Acute sympathetic stress quickly induces cardiac inflammation and injury, suggesting that pathogenic signals rapidly spread among cardiac cells and that cell-to-cell communication may play an important role in the subsequent cardiac injury. However, the underlying mechanism of this response is unknown. Our previous study demonstrated that acute ß-adrenergic receptor (ß-AR) signaling activates inflammasomes in the heart, which triggers the inflammatory cascade. In the present study, ß-AR overactivation induced inflammasome activation in both the cardiomyocytes and cardiac fibroblasts (CFs) of mice hearts following a subcutaneous injection of isoproterenol (ISO, 5 mg/kg body weight), a selective agonist of ß-AR. In isolated cardiac cells, ISO treatment only activated the inflammasomes in the cardiomyocytes but not the CFs. These results demonstrated that inflammasome activation was propagated from cardiomyocytes to CFs in the mice hearts. Further investigation revealed that the inflammasomes were activated in the cocultured CFs that connected with cardiomyocytes via membrane nanotubes (MNTs), a novel membrane structure that mediates distant intercellular connections and communication. Disruption of the MNTs with the microfilament polymerization inhibitor cytochalasin D (Cyto D) attenuated the inflammasome activation in the cocultured CFs. In addition, the MNT-mediated inflammasome activation in the CFs was blocked by deficiency of the inflammasome component NOD-like receptor protein 3 (NLRP3) in the cardiomyocytes, but not NLRP3 deficiency in the CFs. Moreover, ISO induced pyroptosis in the CFs cocultured with cardiomyocytes, and this process was inhibited by disruption of the MNTs with Cyto D or by the NLRP3 inhibitor MCC950 and the caspase-1 inhibitor Z-YVAD-FMK (FMK). Our study revealed that MNTs facilitate the rapid propagation of inflammasome activation among cardiac cells to promote pyroptosis in the early phase of ß-adrenergic insult. Therefore, preventing inflammasome transfer is a potential therapeutic strategy to alleviate acute ß-AR overactivation-induced cardiac injury.

α1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation.

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by ß-adrenergic receptors (ß-ARs). However, α1-adrenergic receptors (α1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α1-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α1-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 µM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/- mice compared with wild-type mice. In conclusion, α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

Manifestations of liver injury in 333 hospitalized patients with coronavirus disease 2019 / 中华消化杂志

Objective:To investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.

Clinical application of Tunnel-Plasty on modified pedicle subtraction osteotomy / 中华骨科杂志

Objective@#To summarize the technical points and clinical efficacy of pedicle subtraction osteotomy (PSO) in tunneling and to explore the related complications of this technique.@*Methods@#A total of 67 cases of old vertebral fractures of the thoracolumbar region from June 2012 to June 2017 were collected. According to the inclusion and exclusion criteria, a total of 41 cases were included in the study. There were 19 males and 22 females; aged 37-67 years, mean 60.1±12.7 years; 15 cases of non-surgical treatment after trauma, 13 cases of failure after surgery and 13 cases of osteoporosis. Injury segment: 9 cases of T11, 22 cases of T12, 8 cases of L1, 2 cases of LS. Preoperative patients were diagnosed by X-ray, CT plain and 3D reconstruction combined with MRI. There were 23 cases of intractable back pain, 16 cases of lower extremity root pain, and 2 cases of intermittent claudication. Patients were divided into the traditional PSO treatment group (21 cases) and modified PSO treatment group (20 persons) according to the random number method. The traditional group were treated with the "egg shell" technique, and the improved group were treated with tunnel forming technology. The procedure was divided into four steps: exposure (step 1), nail placement and resection of the posterior column complex (step 2), vertebral osteotomy (step 3), orthopedics and bone grafting (step 4). The operation time, bleeding volume and complications of each step were compared between the two groups. The clinical efficacy was evaluated using the visual analogue scale (VAS) score and the Oswestry disability index (ODI). The X-ray spine Cobb angle was measured to evaluate the Keloid deformity correction, and the bone graft fusion was observed by CT examination.@*Results@#All patients were followed up for 12 to 24 months. The total operation time of the traditional group was 273.3±21.1 min, and the total operation time of the modified group was 178.1±12.5 min, the difference between the two groups was statistically significant (t=8.981, P=0.0019). The differences between the two groups in steps 2 and 3 were statistically significant (t2=4.614, P2=0.036; t3=9.089, P3=0.020) . The difference in the total bleeding volume was statistically significant (t=8.529, P=0.011). The differences in the bleeding volume between the two groups in step 2 and step 3 were statistically significant (t2=11.933, P2=0.016; t3=6.972, P3=0.013). The Cobb angles of the traditional group before surgery, 1 week after surgery and half year after surgery were 40.2°±8.9°, 12.5°±6.8°, 10.4°±2.5°, respectively. The Cobb angles of the modified group before surgery, 1 week after operation and half year after surgery were 39.5°±6.3°, 10.4°±3.5°, 9.5°±1.9°, respectively. The differences in the Cobb angle between the preoperative, postoperative 1 week and postoperative half year were statistically significant(Fmodified group=189.573, Pmodified group=0.021; Ftraditional group=194.699, Ptraditional group=0.029). The bone fusion time in the osteotomy area was 3-6 months, with an average of 4.8 months. The VAC and ODI scores of half-year post operation of the traditional group were 2.1±0.3 and 34.1±4.3, and the improved group were 2.2±1.1 and 28.3±6.8, respectively, and the difference was not statistically significant. In the improved group, there were 1 case of over-excavation and 1 case of over-underexcavation (2/20), which were corrected in time during operation. In the traditional group, 4 cases (4/21) of dural tear occurred during the operation, and were repaired in time. Bone fusion was obtained half a year later. No clinical deaths, and no cases of surgical infection occured.@*Conclusion@#Tunnel forming technology is an alternative surgical procedure for treating old fractures of the thoracolumbar region with PSO, which can shorten the operation time, reducd intraoperative bleeding and reduce surgical complications.

Percutaneous fixation assisted by O-arm-based navigation for thoracolumbar fractures without neurologic deficits / 中华创伤杂志

Objective@#To investigate the clinical efficacy of percutaneous fixation assisted by O-arm-based navigation for thoracolumbar fractures without neurologic deficits.@*Methods@#A retrospective case control study was conducted to analyze the clinical data of 35 thoracolumbar fracture patients without neurologic deficits admitted to Henan Provincial People's Hospital from January 2018 to December 2018. There were 26 males and 9 females, aged 17-51 years, with an average age of 30.4 years. The injured segments were distributed at T11 in 10 patients, T12 in 15, L1 in 11, and L2 in 4 patients. A total of 19 patients (22 vertebrae, 98 pedicle screws) were treated with O-arm guided navigation assisted percutaneous internal fixation (Group A), and 16 patients (18 vertebrae, 82 pedicle screws) were treated with C-arm guided percutaneous internal fixation (Group B). The operation time, accuracy rate of nail placement, complications, Cobb angle of fracture vertebral body, visual analogue score (VAS) and Japanese Orthopaedic Association (JOA) score were recorded and compared before operation, 7 days after operation and at the last follow-up.@*Results@#The patients were followed up for 2-12 months [(7.2±2.9)months] in Group A and 3-13 months [(7.1±3.3)months] in Group B. The operation time was (70.5±11.2)minutes in Group A and (81.3±10.9)minutes in Group B (P<0.01). A total of 93 screws were completely placed in the pedicle in Group A (accuracy rate of 95%), and 74 screws in Group B (accuracy rate of 90%) (P<0.01). There were no complications such as infection, pulmonary embolism, spinal cord, nerve injury or lower extremity deep vein thrombosis in either group. The Cobb angle of the fractured vertebral body at day 7 after operation in Group A and Group B was (9.4±2.1)° and (10.4±2.5)° respectively, while the Cobb angle of the fractured vertebral body at the final follow-up in Group A and Group B was (9.7±2.3)° and (11.4±2.9)° respectively. The postoperative Cobb angle was significantly increased compared with the preoperative Cobb angle (P<0.05), but there was no significant difference between the two groups (P>0.05). The VAS at day 7 after operation was (2.3±1.1)points and (2.8±1.0)points in Group A and Group B, respectively, while the VAS at the final follow-up was (0.7±0.7)points and (0.8±0.7)points in Group A and Group B respectively. The postoperative VAS was significantly decreased compared with the preoperative VAS (P<0.05), but there was no significant difference between the two groups (P>0.05). The JOA at day 7 after operation was (21.1±2.2)points and (21.8±2.5)points in Group A and Group B respectively, while the JOA at the final follow-up was (24.9±2.2)points and (23.8±1.9)points in Group A and Group B respectively. The postoperative JOA was significantly increased compared with the preoperative JOA (P<0.05), but there was no significant difference between the two groups (P>0.05).@*Conclusion@#For thoracolumbar fractures without neurologic deficits, percutaneous fixation assisted by O-arm-based navigation can shorten the operation time and deliver a higher accuracy rate in the placement of pedicle screws, in addition to the similar effects with percutaneous fixation assisted by C-arm in pain relief, function improvement and correction of fracture vertebral kyphosis.

Modified posterior unilateral subtotal corpectomy osteotomy correction for old thoracolumbar vertebral fractures combined with kyphosis / 中华创伤杂志

Objective To evaluate the efficacy of modified posterior unilateral subtotal corpectomy osteotomy correction for old thoracolumbar vertebral fractures combined with kyphosis. Methods A retrospective case series study was conducted to analyze 18 patients with old thoracolumbar vertebral fractures combined with kyphosis admitted to the Henan Provincial People's Hospital from January 2012 to October 2016. There were 10 males and eight females, aged 25-70 years, with an average age of 38. 2 years. The injured segments and osteotomy segments included T11 in one patient, T12 in four, L1 in six, and L2 in seven. Five patients had neurological impairment symptoms classified as grade D according to Frankel's classification. All patients underwent the modified posterior unilateral subtotal corpectomy osteotomy correction. The operation time and intraoperative blood loss were recorded. The visual analogue score (VAS), Oswestry dysfunction index (ODI) and kyphosis Cobb angle were compared before operation, half a year after operation and at the last follow-up. The osteotomy fusion was evaluated by Suk criterion and Frankel grading was used to evaluate the recovery of nerve function. The complications were also recorded. Results All patients were followed up for 12-24 months, with an average of 17. 6 months. The operation time was 160-285 minutes [(190. 0 ± 42. 6) minutes, and the intraoperative blood loss was 500-800 ml [(610. 0 ± 134. 3) ml]. The difference of kyphosis Cobb angle between preoperative [(40.5±9.8)°] and [(5.5 ±1.6)°] at 6 months postoperatively had statistical significance (P <0. 05). Compared with the kyphosis Cobb angle of 6 months postoperatively [(5. 5 ± 1. 6)°], the Cobb angle at the final follow-up [(6. 2 ± 1. 5)°] did not change significantly (P>0. 05). The VAS score and ODI at 6 months after operation and at the final follow-up [(3. 1 ± 1. 3)points,(2. 7 ± 0. 7)points and 7. 5 ± 5. 1, 6. 4 ± 2. 5] were significantly different compared with those before operation [(7. 6 ± 2. 4)points, 68. 7 ± 10. 4] (P<0. 05). Bone cutting surface was healed osseously in all patients. The five patients with preoperative neurological impairment of grade D were assigned with grade E at the last follow up. There were two patients with dural rupture and one with pleural effusion during the operation. No complications such as nerve damage, infection or thrombosis occurred. No loosening, fracture or heterotopic ossification occurred during follow-up. Conclusion For old thoracolumbar vertebral fracture combined with kyphosis, the modified posterior unilateral vertebral column resection through unilateral approach can not only achieve the bone fusion between the injured vertebra and the adjacent vertebral body, but also avoid the shortening of the spine, correcting kyphosis and relieving pain, with low incidence of complications.

Unilateral approach painless vertebroplasty for osteoporotic vertebral compression fractures of critically ill patients under lateral decubitus position / 中华创伤杂志

Objective To investigate the clinical efficacy of unilateral approach painless vertebral augmentation in the treatment of severe osteoporotic vertebral compression fractures ( OVCFs) in the critically ill patients under lateral decubitus postition. Methods A retrospective case series study was conducted to analyze 97 patients with severe vertebral fractures admitted to the Henan Provincial People's Hospital from April 2004 to January 2017. There were 27 males and 70 females, aged 59-99 years [(78. 5 ± 13. 2) years]. There were 11 patients with three-segment fracture, nine patients with two-segment fracture and 77 patients with single fracture. All patients were treated with lateral decubitus unilateral approach for painless vertebral augmentation and received postoperative rehabilitation training guided by physicians. Preoperative and intraoperative blood loss were recorded. Preoperative and postoperative respiratory rate, heart rate, systolic pressure, oxygen saturation and acute physiology and chronic health evaluation score II ( APACHE II ) , height of vertebral compression site, and injured vertebrae Cobb angle were evaluated. The visual analogue scale ( VAS) and Oswestry dysfunction index ( ODI) were assessed to define function improvement. Meanwhile, the occurrence of re-fracture and complications were recorded. Results All patients were followed up for 3-8 months [(6.3 ±2.9)months]. The operation time was (69. 2 ± 25. 9) minutes, and the amount of intraoperative bleeding was (7. 5 ± 2. 6)ml. There were no significant differences in respiratory rate, heart rate, systolic blood pressure or oxygen saturation before operation and after operation ( P > 0. 05 ) . No surgical discontinuation or deterioration occurred. The APACHE II score was (15. 2 ± 3. 7) points before operation and (8. 4 ± 0.7)points at 24 hours after operation (P <0.05). The compression height parameter of the injured vertebraewas(17.2±3.6)mmbeforesurgery,(20.4±41.3)mmatoneweekaftersurgery,and(18.8± 1.3)mm at the last follow-up (P >0. 05). The Cobb angle was (25. 6 ± 9. 3)° before operation, (20.7±2.5)° at one week after operation and (18.5±3.1)° at the last follow-up (P>0.05). The VAS score was (8. 5 ± 1. 2)points before operation, (2. 1 ± 0. 3)points at one week after operation, and (3. 2 ± 1. 1)points at the last follow-up, respectively. The VAS scores at 1 week and the last follow-up were significantly improved compared with preoperative VAS ( P<0. 05 ) , but there was no significant difference between the former two (P>0. 05). The ODI value was 39. 9 ± 3. 4 before operation, 20. 2 ± 5. 2 at one week after operation, and 17. 2 ± 2. 0 at the last follow-up . The ODI values 1 week after operation and at the last follow-up were significantly improved compared with preoperative ODI ( P <0. 05),showing improvement trend during the follow-up (P<0. 05). No re-fracture occurred during the follow-up. No serious complications such as nerve injury, pulmonary embolism or death occurred during the operation and postoperative follow-up. Conclusions The unilateral approach painless vertebral augmentation for the treatment of severe OVCFs in critically ill patients under lateral decubitus position can improve the patient's operative tolerance and satisfaction, shorten the operation time, relieve postoperative pain and promote functional recovery. It is an alternative surgical procedure for the treatment of severe OVCFs in internal medicine.

Percutaneous fixation assisted by O-arm-based navigation for thoracolumbar fractures without neurologic deficits / 中华创伤杂志

Objective To investigate the clinical efficacy of percutaneous fixation assisted by O-arm-based navigation for thoracolumbar fractures without neurologic deficits.Methods A retrospective case control study was conducted analyze the clinical data of 35 thoracolumbar fracture patients without neurologic deficits admitted to Henan Provincial People's Hospital from January 2018 10 December 2018.There were 26 males and 9 females,aged 17-51 years,with an average age of 30.4 years.The injured segments were distributed at T11 in 10 patients,T12 in 15,L1 in 11,and L2 in 4 patients.A total of 19 patients(22 vertebrae,98 pedicle screws)were treated with O-arm guided navigation assisted percutaneous internal fixation(Group A),and 16 patients(18 vertebrae,82 pedicle screws)were treated with C-arm guided percutaneous internal fixation(Group B).The operation time,accuracy rate of nail placement,complications,Cobb angle of fracture vertebral body,visual analogue score(VAS)and Japanese Orthopaedic Association(JOA)score were recorded and compared before operation,7 days after operation and at the last follow-up.Results The patients were followed up for 2-12 months [(7.2 ±2.9)months] in Group A and 3-13 months [(7.1±3.3)months] in Group B.The operation time was(70.5±11.2)minutes in Group A and(81.3±10.9)minutes in Group B(P＜0.01).A total of 93 screws were completely placed in the pedicle in Group A(accuracy rate of 95％),and 74 screws in Group B(accuracy rate of 90％)(P＜0.01).There were no complications such as infection,pulmonary embolism,spinal cord,nerve injury or lower extremity deep vein thrombosis in either group.The Cobb angle of the fractured vertebral body at day 7 after operation in Group A and Group B was(9.4±2.1)° and(10.4±2.5)° respectively,while the Cobb angle of the fractured vertebral body at the final follow-up in Group A and Group B was(9.7±2.3)°and(11.4±2.9)° respectively.The postoperative Cobb angle was significantly increased compared with the preoperative Cobb angle(P＜0.05),but there was no significant difference between the two groups(P＞0.05).The V AS at day 7 after operation was(2.3±1.1)points and(2.8±1.0)points in Group A and Group B,respectively,while the VAS at the final follow-up was(0.7±0.7)points and(0.8±0.7)points in Group A and Group B respectively.The postoperative VAS was significantly decreased compared with the preoperative VAS(P＜0.05),but there was no significant difference between the two groups(P ＞0.05).The JOA at day 7 after operation was(21.1±2.2)points and(21.8±2.5)points in Group A and Group B respectively,while the JOA at the final follow-up was(24.9±2.2)points and(23.8±1.9)points in Group A and Group B respectively.The postoperative JOA was significantly increased compared with the preoperative JOA(P＜0.05),but there was no significant difference between the two groups(P＞0.05).Conclusion For thoracolumbar fractures without neurologic deficits,percutaneous fixation assisted by O-arm-based navigation can shorten the operation time and deliver a higher accuracy rate in the placement of pedicle screws,in addition to the similar effects with percutaneous fixation assisted by C-arm in pain relief,function improvement and correction of fracture vertebral kyphosis.

Comparison of percutaneous vertebroplasty with bone filling container and percutaneous kyphoplasty via unilateral puncture approach for osteoporotic vertebral compression fractures / 中华创伤杂志

Objective To investigate the clinical efficacy of percutaneous vertebroplasty (PVP) with bone filling container (BFC) and percutaneous kyphoplasty (PKP) by unilateral puncture approach in the treatment of osteoporotic vertebral compression fractures.Methods A retrospective case control study was conducted on 65 patients (65 vertebral bodies) with osteoporotic vertebral compression fractures (OVCF) who received PVP from March 2015 to March 2017 in Henan Provincial People's Hospital.There were 21 males and 44 females,aged 60-91 years,with an average of 76.2 years.The patients were divided into PVP with BFC group (BFC group) and PKP group treated by unilateral puncture approach.There were 10 males and 23 females in BFC group,with an average age of 75.8 years (range,60-91 years).The injured segments were distributed at T10 in seven patients,T11 in nine,T12 in eight,L1 in five,and L2 in four patients.There were 11 males and 21 females in PKP group,with an average age of 76.7 years (range,60-88 years).The injured segments were distributed at T10 in five patients,T11 in seven,T12 in ten,L1 in eight,and L2 in two patients.The operation time,cement leakage,as well as pain visual analogue score (VAS),modified Oswestry dysfunction index (ODI) and the Cobb angle of the fractured vertebral body at 3 days after operation and 12 months after operation were recorded and compared.Results All operations were completed successfully,without serious complications.The patients were followed up for 16-29 months [(21.2 ± 4.5) months] in BFC group and 15-32 months [(23.8 ± 6.2) months] in PKP group.The operation time was (27.8 ± 3.6) minutes in BFC group and (31.0 ± 5.2) minutes in PKP group (P ＜ 0.05).Postoperative X-ray and CT showed that bone cements leakage occurred in three patients of BFC group (9％) and in ten patients of PKP group (31％) (P ＜0.05).The VAS at 3 days after operation in BFC group and PKP group was (2.3 ± 1.0) points and (2.1 ±0.8)points respectively.The VAS at 12 months after operation in BFC group and PKP group was (0.7 ± 0.7) points and (O.8 ± 0.7) points respectively.The postoperative VAS was significantly decreased compared with the preoperative VAS (P ＜0.05),but there was no significant difference between the two groups (P ＞ 0.05).The modified ODI at 3 days after operation in BFC group and PKP group were (31.5 ± 4.7) ％ and (30.4 ± 5.7) ％,respectively.The modified ODI at 12 months after operation in BFC group and PKP group was (16.7 ±4.9)％ and (15.1 ±5.6)％,respectively.The postoperative ODI were significantly decreased compared with the preoperative ODI(P ＜0.05),but there was no significant difference between the two groups (P ＞ 0.05).The Cobb angle of the fractured vertebral body at 3 days after operation in BFC group and PKP group was (9.2 ± 3.0) ° and (10.0 ±2.9)°,respectively.The Cobb angle of the fractured vertebral body at 12 months after operation was (9.6 ± 2.8)° and (10.3 ± 3.0)°respectively.The postoperative Cobb angle was significantly decreased compared with the preoperative Cobb angle (P ＜ 0.05),but there was no significant difference between the two groups (P ＞ 0.05).Conclusions For OVCF,PVP with BFC by unilateral puncture approach can shorten the operation time and reduce the leakage rate of bone cement.It has similar effects with PKP in pain relief,function improvement of daily life and the correction of fracture vertebral kyphosis.