Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats / 中国药理学通报

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Precise Clinical Positioning of Chinese Patent Medicine in Paradigm of "Target Spectral Effect of Prescription"： A Case Study of Qizhi Tongluo Capsules / 中国实验方剂学杂志

The clinical value of Chinese patent medicine is the core direction of the development of the traditional Chinese medicine industry. The precise clinical positioning determines the way to prove the value of the drug， and is a key link to highlight the clinical value. This paper presented a case study of clinical positioning for Chinese patent medicine， namely Qizhi Tongluo capsules， and the key technical framework of precise clinical positioning of Chinese patent medicine， which was manifested as a comparison of prescription target spectral effect， discovery of core value of prescription， and confirmation of clinical positioning trial. The technical framework was designed to address a range of issues in the realm of precise clinical positioning. Before the clinical positioning trial， based on the multi-component， multi-target， and multi-phenotype data of prescription and clinical indication， the multi-omics network analysis technology was used to identify the core value of the traditional Chinese medicine varieties and predict the potential clinical advantages. Then， based on the predicted clinical advantages， reasonable efficacy indicators were selected， and the clinical efficacy was judged and verified by dynamic and flexible innovative clinical trials to improve the success rate of clinical positioning. This research paradigm integrates "omics technology" with "evidence-based" principles and follows the "precise evidence-based" concept. This research aims to provide a new strategy and method for the precise medication and positioning of Chinese patent medicine with traditional Chinese medicine characteristics after being put into the market and provide more technical thinking for traditional Chinese medicine to move towards precise medicine.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.@*METHODS@#Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.@*RESULTS@#A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001).@*CONCLUSIONS@#In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Effects of Different Tidal Volumes and PEEPs on Cardiac Output in Pigs Measured by Pulmonary Artery Catheter， Pulse Contour Analysis and Transpulmonary Thermodilution / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of different tidal volumes and positive end expiratory pressures （PEEPs） during mechanical ventilation on the cardiac output of pigs measured by pulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis， and to explore their consistency in cardiac output determination. MethodsTwelve experimental pigs were selected and randomly divided into 3 groups， with 4 pigs in each. Cardiac output was measured by different methods， control group by pulmonary artery catheter， group A by transpulmonary thermodilution and group B by pulse contour analysis. Then we compared the effects of different tidal volumes and PEEPs on the cardiac output of pigs and to explore the consistency. The correlation coefficient between pulse contour analysis and pulmonary artery catheter was r=0.754， and they were positively correlated. The correlation coefficient between transpulmonary thermodilution and pulmonary artery catheter was r=0.771， and they were positively correlated. In determining cardiac output， pulse contour analysis was consistent with pulmonary artery catheter， with a relative error of 13.5% between them； transpulmonary thermodilution was consistent with pulmonary artery catheter， with a relative error of 12.9% between them. The cardiac output decreased significantly along with the increase of tidal volumes or PEEPs and the differences were statistically significant （P<0.05） ConclusionPulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis are well consistent with each other in measuring the cardiac output of pigs. The pigs’cardiac output gradually decreased along with the increase of tidal volumes or PEEPs during mechanical ventilation.

Genetic analysis of two children with Coffin-Siris syndrome due to variants of ARID1B gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.

Multisensory Conflict Impairs Cortico-Muscular Network Connectivity and Postural Stability: Insights from Partial Directed Coherence Analysis / 神经科学通报·英文版

Sensory conflict impacts postural control, yet its effect on cortico-muscular interaction remains underexplored. We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability. We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input, recorded EEG (electroencephalogram) and EMG (electromyogram) data, and constructed a directed connectivity network. The results suggest that, compared to sensory congruence, during sensory conflict: (1) connectivity among the sensorimotor, visual, and posterior parietal cortex generally decreases, (2) cortical control over the muscles is weakened, (3) feedback from muscles to the cortex is strengthened, and (4) the range of body sway increases and its complexity decreases. These results underline the intricate effects of sensory conflict on cortico-muscular networks. During the sensory conflict, the brain adaptively decreases the integration of conflicting information. Without this integrated information, cortical control over muscles may be lessened, whereas the muscle feedback may be enhanced in compensation.

ImmunoPET studies of 64Cu-labeled CD30 monoclonal antibody 64Cu-NOTA-CD30 in lymphoma models / 中华核医学与分子影像杂志

Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.

Mechanism of epidural scar hyperplasia after laminectomy induced by blood siltation / 中华骨科杂志

Objective:To explore the mechanism of epidural scar tissue hyperplasia induced by erythrocyte rupture and release of interleukin-33 (IL-33) after laminectomy in mice.Methods:In the zoological experiment, the operation group (Laminectomy) and the sham operation group were set, and HE staining and Masson staining were performed to test for blood accumulation in the operation area after laminectomy in mice. Then 12 wild-type mice with 6-8 week old were selected and divided into 4 groups: the sham operation group, the operation group (normal saline control), the pure red blood cell intervention operation group, the whole blood intervention operation group. The normal saline (100 mg/kg) was injected into the postoperative area. The red blood cells or whole blood with the same volume were injected into the postoperative area in the pure red blood cell intervention group and the whole blood intervention group. The postoperative recovery of mice in each group was observed. The levels of fibronectin in the postoperative scar tissues of mice in four groups were detected by western blot technology, and the degree of postoperative epidural scar hyperplasia was directly observed by immunohistochemistry. In the cytological experiment, the wild-type mouse erythrocyte normal saline group, the control group of IL-33 knockout mouse erythrocyte normal saline, the wild-type mouse erythrocyte lysis group, and the IL-33 knockout mouse erythrocyte lysis group were set. The levels of IL-33 in the red blood cells of four groups were detected by western blot. Then, a blank wild-type mouse erythrocyte control group, a wild-type mouse relative to the control group (only secondary antibody added to test for non-specific binding), a wild-type mouse erythrocyte group and an IL-33 knockout mouse erythrocyte group (to test for antigen specificity of the primary antibody) were set. Immunofluorescence staining was performed on the erythrocytes of four groups and the level of IL-33 was detected by flow cytometry.Results:HE staining and Masson staining after laminectomy showed that there was blood stasis in the local incision area of mice in the operation group. The epidural scar hyperplasia in the incision area of mice after whole blood or red blood cells intervention was higher, especially in the whole blood intervention group. IL-33 expression was almost undetectable in the wild-type erythrocyte normal saline control group, the IL-33-knockout erythrocyte normal saline control group, and the IL-33-knockout erythrocyte lysis group, while significant IL-33 expression was detectable in the wild-type erythrocyte lysis group. Immunofluorescence staining showed that IL-33 was expressed in and on the erythrocyte membrane of wild-type mice, while non-specific expression of IL-33 or a very small amount of IL-33 was almost undetectable in the other three groups. The immunofluorescence intensities of IL-33 in the four groups were 0.62±0.41, 60.17±4.39, 16.78±7.43 and 0.61±0.03, respectively ( F=281.90, P<0.001). The expression of IL-33 in the erythrocyte group of wild-type mice was the highest ( P<0.05). According to the results of flow cytometry, except for the trace amount of IL-33 detected in the wild-type mouse erythrocyte group, the expression of IL-33 in the other three groups was basically 0. The ratios of fibronectin to β-actin in the modeling area of the four groups gradually increased, and the ratios were 0.79±0.09, 1.26±0.23, 1.79±0.05 and 2.29±0.58, respectively, and the differences were statistically significant ( F=12.86, P=0.002). Fibronectin in the operation area of the three operation groups (normal saline control group, red blood cell intervention group and whole blood intervention group) was significantly higher than that of the sham operation group. The immunohistochemical staining results of fibronectin in the modeling area of the four groups were the same as those in western blot experiment. The average optical density values of fibronectin in each group were 0.09±0.01, 0.18±0.01, 0.22±0.01 and 0.24±0.01, respectively, and the difference was statistically significant ( F= 210.7, P<0.001). Conclusion:There is indeed blood accumulation in the surgical area after laminectomy in mice, and it can aggravate the hyperplasia of epidural scar tissue. Erythrocyte is the main component in blood, and there is a large amount of IL-33 expression in the inner and outer membrane of erythrocyte membrane. The mechanism of promoting the proliferation of epidural scar tissue may be related to the release of IL-33 by erythrocyte lysis.

Combination pattern of internal fixation for periprosthesis fractures of the proximal femur after hip replacement / 中华骨科杂志

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.

Application of real-time virtual sonography surgical navigation combined with indocyanine green fluorescence imaging technology during anatomical liver resection / 中华肝胆外科杂志

Objective:To analyze the clinical effect of real-time virtual sonography (RVS) surgical navigation combined with indocyanine green fluorescence imaging technology in the anatomical liver segmentectomy for hepatocellular carcinoma (HCC).Methods:The clinical data of 35 patients who underwent anatomical liver segmentectomy using RVS surgical navigation combined with indocyanine green fluorescence imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to January 2022 were retrospectively analyzed. There were 22 males and 13 females, aged (60.0±10.0) years. RVS is real-time virtual sonography, which fuses real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images to guide the surgical plane. Methods of operation, time of operation, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. Postoperative complications were graded by Clavien-Dindo system. The 1-year overall survival and tumor-free survival rates of patients were followed up by outpatient or telephone review.Results:Anatomical liver segmentectomy was performed on 36 patients, including 1 patient (2.9%) of segment Ⅱ, 1 patient (2.9%) of segment Ⅲ, 5 patients (14.3%) of segment Ⅳ, 6 patients (17.1%) of segment Ⅴ, 10 patients (28.6%) of segment Ⅵ, 7 patients (20.0%) of segment Ⅶ, 4 patients (11.4%) of segment Ⅷ, and 1 patient (2.9%) of segments Ⅴ+ Ⅷ. The operation time of 35 patients was (310.2±81.6) min, with an intraoperative blood loss of [ M( Q1, Q3)] 390.0(250.0, 500.0) ml. The hospital stay was (11.6±2.1) d. There was no postoperative death. Postoperative complications occurred in 3 cases (8.6%), of which 2 cases (5.7%) were ascites, Clavien-Dindo grade Ⅰ; Postoperative hemorrhage occurred in 1 case (2.9%), Clavien-Dindo grade Ⅱ. HCC was confirmed by pathology in all cases, and the operative margins were negative. The median follow-up time was 14 months (12 to 20 months). The 1-year overall survival rate after surgery was 100.0%(35/35), three patients (8.6%) had tumor recurrence, and the 1-year tumor-free survival rate was 91.4% (32/35). Conclusion:RVS surgical navigation combined with indocyanine green fluorescence imaging technology could be feasible in anatomical segmental hepatectomy for HCC.

Analysis of pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy / 中华肝胆外科杂志

Laparoscopic pancreaticoduodenectomy is an important surgical undertaking, mostly used for benign and malignant tumors in the pancreatic head and periampullary region. The postoperative pancreatic fistula is the main factor to cause death after pancreaticoduodenectomy, and pancreaticojejunostomy is an independent risk factor for pancreatic fistula. In order to reduce the incidence of pancreatic fistula, surgeons have proposed dozens of pancreaticojejunostomy, but so far there are no randomized trials proved which method of pancreaticojejunostomy is better than the others. This article reviews the methods and characteristics of different pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.

A resting-state functional MRI study on amplitude of low-frequency fluctuation and functional connectivity alteration of parkinson′s disease with apathy / 中华放射学杂志

Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.

Feasibility and accuracy of dual-energy CT multiparameter technique in evaluating myocardial scar in patients with heart failure / 中华放射学杂志

Objective:To evaluate the reliability of cardiac late iodine enhancement dual-energy CT (LIE-DECT) multiparameter post-processing technique for evaluating the presence, location, and extent of cardiac scars in patients with heart failure (HF), using cardiac MR (CMR) late gadolinium enhancement (LGE) as a reference standard.Methods:Thirty-nine HF patients who underwent cardiac LIE-DECT and LGE-CMR examinations in the Second Affiliated Hospital of Nantong University from November 2019 to November 2021 were prospectively collected, all enrolled HF patients underwent LIE-DECT post-processing to reconstruct monoenergetic plus (Mono+) map (40 keV), iodine map and Rho/Z map, to evaluate the enhancement degree, location and extent of left ventricular myocardial LIE on the left ventricular short-axis map, respectively, and compared with LGE-CMR. Cohen′s Kappa test was used to assess the intra-and inter-observer consistency of LIE by DECT multiparameter technique and the consistency of LIE presence and location by DECT multiparameter technique and by CMR. The diagnostic efficacy of DECT multiparameter technique in diagnosing myocardial scar was calculated.Results:Of the 39 patients included, 32 patients were detected by CMR with LGE in 147 segments, including 37 subendocardial patterns, 19 transmural patterns, 74 mid-wall patterns, and 17 epicardial patterns. The intra-observer consistency Kappa values of 40 keV Mono+map, iodine map and Rho/Z map were 0.878, 0.930 and 0.835 ( P all<0.001), respectively. The inter-observer consistency Kappa values were 0.838, 0.892 and 0.808 ( P all<0.001), respectively. The LIE of 40 keV Mono+map, iodine map and Rho/Z map were in good agreement with CMR, Kappa values were 0.903, 0.883 and 0.810 ( P all<0.001), respectively. For the per-patient analysis, the accuracies of 40 keV Mono+map, iodine map and Rho/Z map were 92.3% (36/39), 92.3% (36/39) and 82.1% (32/39), respectively. For the segment-based analysis, the accuracies of 40 keV Mono+map, iodine map and Rho/Z map accuracy were 96.1% (492/512), 95.3% (488/512) and 92.6% (474/512), respectively. In Bland-Altman analysis, the consistency bias between scar extent measured by 40 keV Mono+map, iodine map, Rho/Z map and that measured by LGE-CMR were -2.03%, -2.21%, -2.65%, and the 95% limit of agreement were -12.20%-8.14%, -12.69%-8.28% and -14.85%-9.58%, respectively. Conclusion:LIE-DECT multiparameter technique can detect myocardial scar in HF patients well, which is consistent with LGE-CMR.

Efficacy of second-stage Masquelet technique with 3D-printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures / 中华创伤杂志

Objective:To investigate the efficacy of 3D-printed quantitative bone implants assisting second-stage Masquelet technique for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures.Methods:A retrospective case series analysis was made on 26 patients with long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures treated in Wuxi Ninth People′s Hospital from July 2015 to December 2020, including 20 males and 6 females; aged 19-63 years [(46.5±4.5)years]. Gustilo classification was type IIIB in 23 patients and type IIIC in 3. In the first stage, all patients had thoroughly emergent debridement, removal of all free bone pieces, restoration of the length and force line plus externally fixion, and vacuum sealing drainage (VSD) of the residual wound. After 2-7 days, the external fixation was removed and replaced by internal fixation, with the bone cement filling in the defect area and the free flap covering the wound. The length of tibial bone defect was 5-14 cm [(6.3±0.4)cm], and the tibial defect volume was 12.2-73.1 cm 3 [(33.6±9.2)cm 3]. In the second stage (6-19 weeks after injury), the bone cement was removed, followed by autologous bone grafting. Prior to bone grafting, digital technology was used to accurately calculate the bone defect volume, and an equal volume of bone harvesting area was designe to produce the 3D printed osteotomy template. Bone grafting was conducted after bone removal according to the osteotomy template during operation. The success rate of one-time iliac bone extraction, bone harvesting time, and bleeding volume were recorded. Pain in the bone extraction area was evaluated by visual analogue score (VAS) at 1 day and 1 month after operation and at the last follow-up. Wound healing, complications, and bone healing were observed. Life quality was evaluated by health survey brief form (SF-36) including scores of physical component summary (PCS) and mental component summary (MCS) before bone grafting and at the last follow-up. Results:All the patients were followed up for 13-53 months [(32.3±12.5)months]. One-time iliac bone extraction was successful in all the patients. Bone harvesting time was 15-30 minutes [(21.0±2.5)minutes]. The bleeding volume was 50-120 ml [(62.3±29.0)ml]. The VAS was 1-4 points [(1.2±0.9)points] at 1 day after operation, higher than these (0.0±0.0)points at 1 month after operation and at the last follow-up (all P<0.01). Totally, 25 patients obtained wound healing after operation, except for 1 patient with superficial wound infection after bone grafting that was healed by dressing change. There was 1 patient with bone infection after 3 months of bone grafting that was healed by repeated surgery with Masquelet technique in the first and second stage. Besides, 2 patients had symptoms of cutaneous nerve injury in the iliac donor area. The time of bone healing was 4-7 months [(5.8±0.8)months]. The scores of PCS and MCS in SF-36 at the last follow-up were (73.6±12.8)points and (83.6±13.2)points, significantly higher than those before bone grafting [(46.8±0.5)points, (60.7±2.0)points] (all P<0.01). Conclusion:Second-stage Masquelet technique with 3D printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures is associated with shortened bone harvesting time, attenuated pain, reduced complications, accelerated bone healing and improved function.

Population survey of Pomacea spp. in Shandong Province and preliminary study on the risk of population infection with Angiostrongylus cantonensis / 中华地方病学杂志

Objective:To study the population distribution of Pomacea spp. in Shandong Province and the risk of angiostrongyliasis cantonensis in the local population, and to provide a basis for scientific prevention and control of related diseases. Methods:From July to December 2021, Yanzhou District of Jining City, Ningyang County of Taian City, and Dongying District of Dongying City were selected as surveillance sites to investigate the population and distribution range of Pomacea spp., live snail samples were collected for morphological and genetic identification, and Pomacea spp. infected with the larva of Angiostrongylus cantonensis was detected by lung test. At the same time, sentinel hospital case surveillance was carried out in Yanzhou District, Jining City, and questionnaire was used to study the local residents' awareness of angiostrongyliasis cantonensis and their personal health behaviors. Results:A total of 312 live snail samples were collected. After morphological identification, they were all Pomacea spp.. After gene sequencing, two populations of Pomacea canaliculata and Pomacea maculata were found. No positive snails infected with Angiostrongylus cantonensis were found. A total of 126 patients with headache as the main neurological symptom were admitted to the sentinel hospital, but there were no monitoring cases that met the inclusion criteria. Among the survey population, 48.38% (134/277) of the respondents had heard of angiostrongyliasis cantonensis, 44.77% (124/277) knew that eating Margarya melanioides might cause angiostrongyliasis cantonensis, and 83.39% (231/277) had no related unhealthy eating behavior. Conclusion:Pomacea spp. is found and reported for the first time in Shandong Province, and there is a risk of population infection with angiostrongyliasis cantonensis.

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity / 药物分析学报

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Application of continuous nursing based on hybrid electronic platform and fragmented time concept in out-of-hospital rehabilitation of patients with anterior cruciate ligament reconstruction / 中国实用护理杂志

Objective:To explore the application effect of continuous nursing based on hybrid electronic platform and fragmentation time in the out-of-hospital rehabilitation of patients with anterior cruciate ligament reconstruction.Methods:This was a randomized controlled study. From April 2020 to October 2021, a total of 90 patients undergoing anterior cruciate ligament reconstruction in Weifang People′s Hospital were selected as the research objects by convenience sampling. Forty patients from April to December 2020 were selected as control group, and 45 patients from January to October 2021 were selected as intervention group. The control group implemented routine discharge guidance and follow-up, while the intervention group was given continuous nursing plan based on the concept of hybrid electronic platform and fragmented time. Before operation and 1, 3 and 6 months after operation, the knee range of motion and Lysholm score of patients in the two groups were analyzed. At 1, 3 and 6 months after operation, the rehabilitation exercise compliance score, self-efficacy score and knee stability examination of the two groups were analyzed.Results:A total of 41 patients in each group completed the study. At 1 month after operation, the knee range of motion, Lysholm score, rehabilitation exercise compliance score and self-efficacy score of intervention group were (96.46 ±3.58) ° and (53.54 ± 6.57), (69.17 ± 6.27), (4.01 ± 0.38) points, respectively. In the control group, they were (89.02 ± 4.22)° and (45.02 ± 7.61), (56.78 ± 8.45), (3.61 ± 0.42) points. At 3 months after operation, they were (136.83 ± 4.30)° and (72.76 ± 4.96), (60.71 ± 5.87), (4.97 ± 0.32) points in the intervention group, (133.54 ± 3.58)° and (69.83 ± 6.65), (56.73 ± 8.57), (4.83 ± 0.45) points in the control group, respectively. At 6 months after operation, they were (139.39 ± 1.99)° and (85.61 ± 6.11), (57.71 ± 7.41), (6.58 ± 0.96) points in the intervention group, (138.29 ± 2.65)° and (81.80 ± 6.38), (47.90 ± 6.02), (6.35 ± 1.23) points in the control group, respectively. The knee range of motion, Lysholm score and rehabilitation exercise compliance score of the intervention group were better than those of the control group at 1, 3 and 6 months after operation, and the differences were statistically significant ( t values were 2.12-8.61, all P<0.05). The self-efficacy score of the intervention group was higher than that of the control group at 1 month after operation, and the difference was statistically significant ( t=4.57, P<0.05). Conclusions:The continuous nursing program based on hybrid electronic platform and fragmented time can improve the knee function of patients with anterior cruciate ligament reconstruction in the early postoperative period, improve the compliance of rehabilitation exercise and the level of early self-efficacy.

Risk factors and correlation with prognosis of epileptic seizures in 284 pediatric patients in pediatric intensive care unit with electroencephalography monitoring / 中华实用儿科临床杂志

Objective:To illustrate the onset of epileptic seizures in children with brain injury admitted in pediatric intensive care unit (PICU), and to explore the risk factors and the correlation between epileptic seizures and the prognosis.Methods:Clinical data of pediatric patients with brain injury who were admitted to PICU of Peking University First Hospital from January 2013 to December 2019, and monitored by video electroencephalography (VEEG) were retrospectively collected, including general demographic information, etiological data, clinical seizures prior to VEEG performing, in-hospital mortality, brain function score, VEEG manifestations, etc.Seizures detected by VEEG were the primary outcome, and prognosis when discharged from PICU was the secondary outcome. Logistic regression was used to analyze the factors associated with seizures and poor outcome. Results:A total of 284 children were included, involving 54.9%(156/284) males.The median age of included children was 1.7(0.5, 5.0) years.Stratified by the cause of disease, 45.1%(128/284) had epilepsy, 26.1%(74/128) had genetic metabolic disease, and 14.4%(41/284) had central nervous system infection.A total of 82.0%(233/284) children had abnormal VEEG background activities, and 59.5%(169/284) had interictal epileptic discharges.Seizures were detected in 106 cases, including 39.6%(42/106) of non-convulsive seizures and 24.5%(26/106) of non-convulsive epileptic states.There were 12.0% (34/284) had poor prognosis at discharge, including 24 patients died in-hospital, and Pediatric Cerebral Performance Category scores were increased in 10 survivors.Multivariate Logistic regression analysis showed that seizures existed before VEEG monitoring and interictal epileptiform discharge were the independent risk factors for seizure.Besides, mental retardation, sepsis related encephalopathy, consciousness abnormality during VEEG, abnormal VEEG background activity, and epileptic status were significantly correlated with the poor prognosis of children with brain injury in PICU. Conclusions:The incidence of electrographic seizure is higher in children with brain injury in PICU, and VEEG monitoring is beneficial to children with brain injury that achieves an early identification of seizures and prediction of prognosis.

Study on the regular pattern of "disease-syndrome-medicine" of different diseases with the same treatment for blood stasis syndrome based on complex network similarity analysis / 国际中医中药杂志

Objective:To reveal the regular pattern characteristics of different diseases with the same treatment in the most common diseases with blood stasis syndrome; To provide reference for the clinical treatment of blood stasis syndrome and the development of new drugs.Methods:RCTs of blood stasis syndrome were retrieved from CNKI, Chongqing VIP, Wanfang Data, SinoMed, and China Medical Journal Full-text Database from the establishment of the databases to December 31, 2022. Diseases, accompanied symptoms, prescriptions and medicines were extracted. The diseases with the highest frequency among the three disease systems with the highest frequency were collected, and their medication characteristics and prescription rules were analyzed using frequency statistics and association rules Apriori algorithm. The core prescriptions of blood stasis syndrome of three kinds of diseases were excavated and their network similarity was analyzed.Results:A total of 2 052 articles were included. Stable coronary heart disease, ischemic stroke and DN were more common diseases with blood stasis syndrome. The common drugs for the three diseases were Chuanxiong Rhizoma, Carthami Flos, Persicae Semen, Angelicae Sinensis Radix. The core prescription of stable coronary heart disease was Persicae Semen- Carthami Flos- Chuanxiong Rhizoma- Angelicae Sinensis Radix- Paeoniae Radix Rubra; the core prescription of ischemic stroke is Buyang Huanwu Decoction; the core prescription of DN was Persicae Semen- Carthami Flos- Chuanxiong Rhizoma- Angelicae Sinensis Radix- Cornus Officinalis- Dioscoreae Rhizoma- Astragali Radix. The similarity between stable coronary heart disease and ischemic stroke core prescription network was 0.35, the similarity between ischemic stroke and DN core prescription network was 0.29, and the similarity between stable coronary heart disease and DN core prescription network was 0.26. Conclusions:The theory of "different diseases with the same treatment" can profoundly guide clinical practice. The core medicines of blood stasis syndrome are Persicae Semen, Carthami Flos, Angelicae Sinensis Radix, and Chuanxiong Rhizoma. On this basis, combined with different diseases and syndromes to make changes of adding and subtracting.

Mechanism of Fuyuan Xingnao Decoction in the treatment of cerebral infarction based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the mechanism of Fuyuan Xingnao Decoction in treatment of cerebral infarction based on network pharmacology and molecular docking.Methods:The active components and action targets of Fuyuan Xingnao Decoction were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Traditional Chinese Medicine Integrated Database (TCMID),Bioactivity data of small organic molecules (PubChem),Universal Protein (Uniprot) and Swiss Target Prediction database platform. The databases of GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and Drug Bank and Pharmacogenomics Knowledgebase (PharmGKB) were used to screen targets of cerebral infarction. The drug target genes in Fuyuan Xingnao Decoction were intersected with those of cerebral infarction, the intersecting targets were introduced into Cytoscape 3.8.2 software to construct the component target network, and the PPI protein interaction network was constructed by using STRING analysis platform and Cytoscape 3.8.2 software to screen the core targets. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) function enrichment analysis were carried out on the common target genes of Fuyuan Xingnao Decoction and cerebral infarction disease to obtain the relevant signal pathways. Finally, AutoDock and Pymol software were used for molecular docking between the predicted target and its corresponding components.Results:After screening, 80 effective components of Fuyuan Xingnao Decoction for treatment of cerebral infarction and 214 common targets of Fuyuan Xingnao Decoction and cerebral infarction were obtained. The core targets such as MAPK1, RELA, TP53, JUN, AKT1 and HSP90AA1 were related to the key targets of cerebral infarction, and they participated in the biological process of regulating the response to drugs, lipopolysaccharide and oxygen level, etc. The cell composition involved membrane raft, membrane micro region and nerve cell body, etc. Molecular functions mainly focused on nuclear receptor activity, ligand activated transcription factor activity, DNA binding transcription factor binding, etc.; it also involved in signal pathway of lipid and atherosclerosis, chemical carcinogen and receptor activation, fluid shear stress and atherosclerosis, etc. Molecular docking showed that good binding activities were seen between Quercetin and HSP90AA1 (-9.4 kJ/mol), between Kaempferol and HSP90AA1 (-9.4 kJ/mol), between Isorhamnetin and HSP90AA1 (-9.1 kJ/mol), and between Quercetin and JUN (-8.6 kJ/mol).Conclusion:Fuyuan Xingnao Decoction can prevent and treat cerebral infarction by regulating vascular endothelial function, promoting blood circulation, repairing and improving neural function, protecting blood-brain barrier, reducing cell apoptosis, and regulating immune and inflammatory response.