Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Potential mechanisms and drug prediction of Rheumatoid Arthritis and primary Sjögren's Syndrome: A public databases-based study.

Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease-gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA-gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA-gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA-gene network.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation.

To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL-1ß was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor-α (TNF-α) and IL-6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation-specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O-Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL-1ß-induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL-1ß-induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice.

The use of mammography-based radiomics nomograms for the preoperative prediction of the histological grade of invasive ductal carcinoma.

BACKGROUND: Accurate prediction of the grade of invasive ductal carcinoma (IDC) before treatment is vital for individualized therapy and improving patient outcomes. This study aimed to develop and validate a mammography-based radiomics nomogram that would incorporate the radiomics signature and clinical risk factors in the preoperative prediction of the histological grade of IDC. METHODS: The data of 534 patients from our hospital with pathologically confirmed IDC (374 in the training cohort and 160 in the validation cohort) were retrospectively analyzed. A total of 792 radiomics features were extracted from the patients' craniocaudal and mediolateral oblique view images. A radiomics signature was generated using the least absolute shrinkage and selection operator method. Multivariate logistic regression was adopted to establish a radiomics nomogram, the utility of which was evaluated using a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: The radiomics signature was found to have a significant correlation with histological grade (P < 0.01), but the efficacy of the model is limited. The radiomics nomogram, which incorporated the radiomics signature and spicule sign into mammography, showed good consistency and discrimination in both the training cohort [area under the curve (AUC) = 0.75] and the validation cohort (AUC = 0.75). The calibration curves and DCA demonstrated the clinical usefulness of the proposed radiomics nomogram model. CONCLUSIONS: A radiomics nomogram based on the radiomics signature and spicule sign can be used to predict the histological grade of IDC and assist in clinical decision-making for patients with IDC.

A comparison of the use of contrast media with different iodine concentrations for enhanced computed tomography.

Objective: In this study, we compared the enhancement of blood vessels and liver parenchyma on enhanced computed tomography (CT) of the upper abdomen with two concentrations of contrast media (400 and 300 mg I/mL) based on similar iodine delivery rate (IDR) of 0.88 and 0.9 g I/s and iodine load of 450 mg I/kg. Methods: We randomly assigned 160 patients into two groups: iomeprol 400 mg I/mL (A group) and iohexol 300 mg I/mL (B group). The CT attenuation values of the main anatomical structures in the two groups with different scanning phases were measured and the image quality of the two groups was analyzed and compared. The peak pressure and local discomfort (including fever and pain) during contrast medium injection were recorded. Results: The mean attenuation value of the abdominal aorta was 313.6 ± 29.6 in the A group and 322.4 ± 30.1 in the B group during the late arterial phase (p = 0.8). Meanwhile, the mean enhancement values of the portal vein were 176.2 ± 19.3 and 165.9 ± 24.5 in the A and B groups, respectively, during the portal venous phase (p = 0.6). The mean CT values of liver parenchyma were 117.1 ± 15.3 and 108.8 ± 18.7 in the A and B groups, respectively, during the portal venous phase (p = 0.9). There was no statistical difference in image quality, peak injection pressure (psi), and local discomfort between the two groups (p > 0.05). Conclusion: When a similar IDR and the same iodine load are used, CT images with different concentrations of contrast media have the same subjective and objective quality, and can meet the diagnostic needs.

[Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis].

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1ß, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1ß, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1ß, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.

Computed-tomography-based radiomic nomogram for predicting the risk of indeterminate small (5-20 mm) solid pulmonary nodules

PURPOSE: This study aims to develop a diagnostic model that combines computed tomography (CT) images and radiomic features to differentiate indeterminate small (5-20 mm) solid pulmonary nodules (SSPNs). METHODS: This study retrospectively enrolled 413 patients who had had SSPNs surgically removed and histologically confirmed between 2017 and 2019. The SSPNs included solid malignant pulmonary nodules (n = 210) and benign pulmonary nodules (n = 203). The least absolute shrinkage and selection operator was used for radiomic feature selection, and random forest algorithms were used for radiomic model construction. The clinical model and nomogram were established using univariate and multivariable logistic regression analyses combined with clinical symptoms, subjective CT findings, and radiomic features. The area under the curve (AUC) of the receiver operating characteristic curve was used to evaluate the performance of the models. RESULTS: The AUC for the clinical model was 0.77 in the training cohort [n = 289; 95% confidence interval (CI): 0.71-0.82; P = 0.001] and 0.75 in the validation cohort (n = 124; 95% CI: 0.66-0.83; P = 0.016). The AUCs for the nomogram were 0.92 (95% CI: 0.89-0.95; P < 0.001) and 0.85 (95% CI: 0.78-0.91; P < 0.001), respectively. The radiomic score (Rad-score), sex, pleural indentation, and age were the independent predictors that were used to build the nomogram. CONCLUSION: The radiomic nomogram derived from clinical features, subjective CT signs, and the Rad-score can potentially identify the risk of indeterminate SSPNs and aid in the patient's preoperative diagnosis.

Application of radiomics in predicting the preoperative risk stratification of gastric stromal tumors.

PURPOSE The stomach is the most common site of gastrointestinal stromal tumors (GISTs). In this study, clinical model, radiomics models, and nomogram were constructed to compare and assess the clinical value of each model in predicting the preoperative risk stratification of gastric stromal tumors (GSTs). METHODS In total, 180 patients with GSTs confirmed postoperatively pathologically were included. 70% was randomly selected from each category as the training group (n = 126), and the remaining 30% was stratified as the testing group (n = 54). The image features and texture characteristics of each patient were analyzed, and predictive model were constructed. The image features and the rad-score of the optimal radiomics model were used to establish the nomogram. The clinical application value of these models was assessed by the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). The calibration of each model was evaluated by the calibration curve. RESULTS The Area Under the Curve (AUC) value of the nomogram was 0.930 (95% confidence interval [CI]: 0.886- 0.973) in the training group and 0.931 (95% CI: 0.869-0.993) in the testing group. The AUC values of the training group and the testing group calculated by the radiomics model were 0.874 (95% CI: 0.814-0.935) and 0.863 (95% CI: 0.76 5-0.960), respectively; the AUC values calculated by the clinical model were 0.871 (95% CI: 0.811-0.931) and 0.854 (95% CI: 0.76 0-0.947). CONCLUSION The proposed nomogram can accurately predict the malignant potential of GSTs and can be used as repeatable imaging markers for decision support to predict the risk stratification of GSTs before surgery noninvasively and effectively.

Aloin A prevents ulcerative colitis in mice by enhancing the intestinal barrier function via suppressing the Notch signaling pathway.

BACKGROUND: Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered. METHODS: C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days. Concurrently, AA (25, 50 mg/kg) and 5-aminosalicylic (500 mg/kg) were administrated intragastrically from day 1 to day 7. Colitis was evaluated by disease active index (DAI), colon length, inflammation response, and intestinal barrier function. In vitro LS174T cells challenged with 50 ng/ml of lipopolysaccharides (LPS) were used to validate the modulatory action of AA on the Notch signaling pathway. RESULTS: Our results showed that oral administration with AA prominently prevented DSS-induced colitis symptoms in terms of decreased DAI, prevention of colon shortening, and reduced pathological damage. AA mitigated the inflammatory response evidenced by the decreased proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and increased anti-inflammatory cytokine (IL-10). Besides, AA inhibited apoptosis and facilitated proliferation in colons. Moreover, AA treatment up-regulated the expression of tight junction (TJ) proteins (ZO-1, Occludin) and promoted the secretion of MUC2 to decrease colon permeability. Mechanistically, AA inhibited the Notch pathway to promote the secretion of MUC2, which was consistent with LPS-challenged LS174 cells. CONCLUSION: These results suggested that AA could prevent colitis by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Thus, AA might be a prospective remedy for ulcerative colitis.

Modified acupuncture therapy, long-term acupoint stimulation versus sham control for weight control: a multicenter, randomized controlled trial.

Objective: Long-term acupoint stimulation (LAS), also called embedding acupuncture, is a modified acupuncture technique. The preliminary results have demonstrated its efficacy in body-weight control. However, the low quality of available trials limited its application. This study aimed to evaluate the efficacy and safety of LAS in body-weight control by using a randomized, parallel, sham-controlled clinical trial design. Methods: This was a randomized, single-blind, sham-controlled clinical trial including 84 adult participants (18-60 years) with a body mass index (BMI) of ≥ 24 kg/m2 conducted in three general hospitals in Shanghai, China. Participants were equally assigned to receive LAS or sham LAS (SLAS) once per 10 days, eight times in total. After completion, an additional intervention with a 3-month follow-up period was set to examine the continued effect of LAS. The primary outcome was the change in body weight from baseline to treatment endpoint within the intention-to-treat (ITT) analysis. Secondary outcomes contained changes in waist-to-hip ratio (WHR), lipid metabolism, and visceral and subcutaneous adipose tissues. Results: From 14 May 2018 to 03 November 2019, 84 participants out of 201 screened individuals met the eligibility criteria, were randomized, and were analyzed (42 participants in each group). From baseline to treatment endpoint, the body-weight reduction in the LAS group was significantly larger than in the sham control (net difference: 1.57 kg, 95% CI: 0.29-2.86, p = 0.012). The superior weight reduction effect persisted in the follow-up period (net difference: 3.20 kg, 95% CI: 1.17-5.21, p = 0.001). LAS therapy also showed improvement in triglyceride and subcutaneous adipose tissue (SAT) compared with sham control. One participant in the LAS group reported a slightly uncomfortable and tingling sensation after the additional intervention. No other adverse events (AEs) were documented. Conclusion: LAS, a modified acupuncture technique, is safe and effective in body-weight control. It could be used as an alternative choice to classical acupuncture for obesity management. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR1800015498].

Quercetin Impedes Th17 Cell Differentiation to Mitigate Arthritis Involving PPARγ-Driven Transactivation of SOCS3 and Redistribution Corepressor SMRT from PPARγ to STAT3.

SCOPE: Quercetin (QU) is one of the most abundant flavonoids in plants and has attracted the attention of researchers because of its remarkable antirheumatoid arthritis (RA) effects and extremely low adverse reactions. However, the underlying mechanism needs further study. METHODS AND RESULTS: Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay （ELISA）, and quantitative real-time polymerase chain reaction （qRT-PCR） reveal the obvious inhibitory effects of QU on Th17 cell differentiation in arthritic mice. More importantly, QU markedly limits the development of Th17 cell polarization, which is virtually compromised by the treatment with peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662 and knockdown of PPARγ. Additionally, molecular dynamics simulation and immunofluorescence exhibit QU directly binds to PPARγ and increases PPARγ nuclear translocation. Besides, QU confers its moderation effect on suppressor of cytokine signaling protein (SOCS3)/signal transducer and activator of transcription 3 (STAT3) axis partially depending on PPARγ. Furthermore, coimmunoprecipitation shows QU redistributes the corepressor silencing mediator for retinoid and thyroid-hormone receptors (SMRT) from PPARγ to STAT3. Finally, the inhibition of Th17 response and the antiarthritic effect of QU are nullified by GW9662 treatment in arthritic mice. CONCLUSION: QU targets PPARγ and consequently inhibits Th17 cell differentiation by dual inhibitory activity of STAT3 to exert antiarthritic effect. The findings facilitate its development and put forth a stage for uncovering the mechanism of other naturally occurring compounds with chemical structures similar to QU.

Capsular Healing in Interportal and Periportal Capsulotomy Methods of Hip Arthroscopy.

OBJECTIVE: To evaluate the midterm outcomes and the capsular healing in patients who had interportal capsulotomy versus periportal capsulotomy of hip arthroscopy. METHODS: Retrospectively reviewed 33 patients with labral tear received hip arthroscopy, with an average age of 41 (27-67) years, including 13 cases of Cam deformity and three cases of Pincer deformity. All patients had positive sign of flexion adduction internal rotation or flexion abduction external rotation. With MRI and radiographic (CT, X plain) imageological examination. MRI showed that all patients had labral tear. Radiographic finding (CT, X plain) showed the pathological changes of acetabular and femoral neck osteophyte. One group with 23 patients were treated with periportal capsulotomy. Another group with 10 patients were treated with interportal capsulotomy. All patients did not close the capsule. Clinical outcomes were measured with the Hip Outcome Score Activities of Daily Living (HOS-ADL) and the modified Harris Hip Score (mHHS), patient satisfaction measured with visual analogue scale (VAS). The healing of the capsule was evaluated by MRI. MRI showed continuous capsular indicated healing, discontinuous capsular indicated unhealing. Postoperatively 6 months, mHHS and HOS-ADL were obtained. Randomized controlled trials were used in this study for analysis. RESULTS: All patients were followed up with average time of 9.3 months(3-29 months). The postoperative symptoms were obviously relieved, the VAS decreased from (4.9 ± 0.6) to (1.2 ± 0.2) after 3 months postoperative. Follow up 6 months post-operation, patients in the interportal group, the mHHS and HOS-ADL scores improvement were respectively 69.4 ± 9.3 & 70 ± 8.8 pre-operation, and 92.5 ± 5.0 & 86.6 ± 5.4 post-operation (P < 0.05); Patients in the periportal group, the mHHS and HOS-ADL scores improvement were respectively 69.9 ± 15.8, 68.1 ± 15.0 pre-operation, and 90.1 ± 9.3 & 86.7 ± 7.9 post-operation (P < 0.05).The differences were statistically significant. Six months after operation, MRI showed that 23 patients with periportal capsulotomy, the capsule have healed, without other complications. Three of the ten patients with interportal capsulotomy were healed and seven were not. CONCLUSION: Interportal and periportal capsulotomy had good outcomes. The technique of periportal capsulotomy had little damage to the joint capsule. Although the capsule did not close, the capsule healed well in postoperative follow-up. The nonunion rate of the joint capsule was high in the interportal capsulotomy without close the capsule.

Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice.

BACKGROUND: Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative of 4,4'-dihydroxydibenzyl sulfoxide from a traditional Chinese medicine Gastrodia elata with anti-nociceptive effects, significantly alleviated neuropathic pain following intrathecal injection. Here, we aimed to investigate the underlying mechanisms of DS against neuropathic pain. METHODS: A chronic constrictive injury (CCI) mouse model of neuropathic pain induced by sciatic nerve ligation was performed to evaluate the effect of DS by measuring the limb withdrawal using Von Frey filament test. Immunofluorescence staining was used to assess the cell localizations and expressions of Iba-1, ASC, NLRP3, and ROS, the formation of autolysosome. The levels of NLRP3-related proteins (caspase-1, NLRP3, and IL-1ß), mitophagy-related proteins (LC3, Beclin-1, and p62), and apoptosis-related proteins (Bcl-XL and Bax) were detected by Western blotting. The apoptosis of BV-2 cell and caspase activity were evaluated by flow cytometry. RESULTS: DS significantly alleviated the neuropathic pain by increasing the mechanical withdrawal threshold and inhibiting the activation of NLRP3 in CCI-induced model mice. Our findings indicated that DS promoted the mitophagy by increasing the LC3II and Beclin 1 and decreasing the levels of p62 protein in BV-2 cell. This is accompanied by the inhibition of NLRP3 activation, which was shown as inhibited the expression of NLRP3 in lysates as well as the secretion of mature caspase-1 p10 and IL-1ß p17 in supernatants in cultured BV-2 microglia. In addition, DS could promote mitophagy-induced improvement of dysfunctional mitochondria by clearing intracellular ROS and restoring mitochondrial membrane potential. CONCLUSION: Together, our findings demonstrated that DS ameliorate chronic neuropathic pain in mice by suppressing NLRP3 inflammasome activation induced by mitophagy in microglia. DS may be a promising therapeutic agent for chronic neuropathic pain.

A preliminary evaluation study of applying a deep learning image reconstruction algorithm in low-kilovolt scanning of upper abdomen.

OBJECTIVE: To investigate feasibility of applying deep learning image reconstruction (DLIR) algorithm in a low-kilovolt enhanced scan of the upper abdomen. METHODS: A total of 64 patients (BMI<28) are selected for the enhanced upper abdomen scan and divided evenly into two groups. The tube voltages in Group A are 100kV in arterial phase and 80kV in venous phase, while tube voltages are 120kV during two phases in Group B. Image reconstruction algorithms used in Group A include the filtered back projection (FBP) algorithm, the adaptive statistical iterative reconstruction-Veo (ASIR-V 40% and 80%) algorithm, and the DLIR algorithm (DL-L, DL-M, DL-H). Image reconstruction algorithm used in Group B is ASIR-V40%. The different reconstruction algorithm images are used to measure the common hepatic artery, liver, renal cortex, erector spinae, and subcutaneous adipose in the arterial phase and the average CT value and standard deviation of the portal vein, liver, spleen, erector spinae, and subcutaneous adipose in the portal phase. The signal-to-noise ratio (SNR) is calculated, and the images are also scored subjectively. RESULTS: In Group A, noise in the aorta, liver, portal vein (the portal phase), spleen (the portal phase), renal cortex, retroperitoneal adipose, and muscle is significantly lower in both the DL-H and ASIR-V80% images, and the SNR is significantly higher than those in the remaining groups (P<0.05). The SNR of each tissue and organ in Group B is not significantly different from that in DL-M, DL-L, and ASIR-V40% in Group A (P>0.05). The subjective image quality scores in the DL-H and B groups are higher than those in the other groups, and the FBP group has significantly lower image quality than the remaining groups (P<0.05). CONCLUSION: For upper abdominal low-kilovolt enhanced scan data, the DLIR-H gear yields a more satisfactory image quality than the FBP and ASIR-V.

Predicting the effects of radiotherapy based on diffusion kurtosis imaging in a xenograft mouse model of esophageal carcinoma.

The aim of the present study was to assess the predictive value of diffusion kurtosis imaging (DKI) on the effects of radiotherapy in a xenograft model of esophageal cancer. A total of 40 tumor-bearing mice, established by injection of Eca-109 cells in nude mice, were used. The experimental group (n=24) received a single dose of 15 Gy (6 MV by X-ray), and the control group (n=16) did not receive any treatment. Tumor volume, apparent diffusion coefficient (ADC), mean kurtosis (MK) and mean diffusivity (MD) of the two groups were compared, and the expression of aquaporin (AQP) 3 and necrosis ratio at matched time points in xenografts were also observed. There was a significant difference between the two groups from the 7th day of radiotherapy onwards; the xenograft volume of the experimental group was significantly smaller compared with the control group (P<0.05). On the 3rd day, the ADC and MD of the experimental group was significantly higher compared with the control group, and MK was significantly lower compared with the control group (P<0.05). On the 3rd day, AQP3 expression in the experimental group was lower compared with the control group, and the proportion of necrotic cells was higher compared with the control group (P<0.05). Single large fraction dose radiotherapy inhibited the growth of a xenografted esophageal tumor. Changes in ADC, MK and MD were observed prior to morphological changes in the tumor. The change in AQP3 expression and necrosis ratio was in also agreement with the DKI parameters assessed. DKI may thus provide early predictive ability on the effect of radiotherapy in esophageal carcinoma.

Progress on haptoglobin and metabolic diseases.

Haptoglobin (Hp) is an acidic glycoprotein, existing in the serum and other body fluids of human beings and a variety of mammals. Hp is produced in the liver, white adipose tissue, and the kidney. The genetic polymorphisms and different phenotypes of Hp have different biological functions. Hp has antibacterial, antioxidant, and angiogenic effects and is associated with multiple diseases including simple obesity, vascular complications of diabetes mellitus, nonalcoholic fatty liver disease, hypertension, blood diseases, autoimmune diseases, and malignant tumors. Hp also participates in many life activities, indicating the importance of Hp in further studies. Previously, we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials. However, the specific mechanism of Hp in patients with simple obesity is still unclear. The purpose of this article is to introduce recent research progress on Hp, emphasizing the relationship between Hp and the development of metabolic disease, which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

Methotrexate enhances antigen presentation and maturation of tumour antigen-loaded dendritic cells through NLRP3 inflammasome activation: a strategy for dendritic cell-based cancer vaccine.

BACKGROUND: Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in adaptive cell-mediated immunity by priming and activating T cells against specific tumour and pathogenic antigens. Methotrexate (MTX), a folate derivative, functions as an immunoregulatory agent. However, the possible effect of MTX on tumour antigen-loaded DCs has not yet been investigated. METHODS: We analysed the effect of MTX on the maturation and function of DCs along with tumour cell lysates (TCLs). Using bone marrow-derived DCs, we investigated the effect of MTX combined TCL-loaded DCs on T cells priming and proliferation. We also tested the anti-tumour immune effect on DCs when treated with MTX and/or TCL in vivo. RESULTS: MTX combined with TCL not only enhanced DC maturation and stimulated cytokine release but also promoted CD8+ T cell activation and proliferation. The latter was associated with increased tumour antigen uptake and cross-presentation to T cells. Mechanistically, DC maturation and antigen presentation were partly modulated by NLRP3 inflammasome activation. Furthermore, immunisation of mice with MTX and TCL-pulsed DCs before a tumour challenge significantly delayed tumour onset and retarded its growth. This protective effect was due to priming of IFN-γ releasing CD8+ T cells and enhanced killing of tumour cells by cytotoxic T lymphocytes isolated from these immunised mice. CONCLUSION: MTX can function as a potent adjuvant in DC vaccines by increasing antigen presentation and T cell priming. Our findings provide a new strategy for the application of DC-based anti-tumour immunotherapy.