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Beibei Feng,1– 4,* Chen Gong,1,3,4,* Longfei You,1,3,4,* Yangyang Lin,1,3,4 Yafei Wang,1,3,4 Wing Yuk Ip,2 Yuling Wang1,3,4 1Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Orthopaedics & Traumatology, the University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 3Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China; 4Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuling Wang, Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, No. 26, Yuancun 2nd Cross Road, Guangzhou, 510655, People’s Republic of China, Tel + 86-20-38476737, Fax +86-20-38254221, Email wangyul@mail.sysu.edu.cn Wing Yuk Ip, Department of Orthopaedics & Traumatology, the University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China, Tel +852-22554581, Fax +852-28174392, Email wyip@hku.hkPurpose: Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS.Patients and Methods: Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS.Results: Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08– 1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88– 0.97) in the multivariate adjusted regression model.Conclusion: CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.Keywords: central sensitization, chronic pain, carpal tunnel syndrome, determinants

Yao Yao,1,* Liu Yang,1,* Zhe Zhang,1,* Binbin Wang,1 Baisui Feng,1 Zhanju Liu1,2 1Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, People’s Republic of China; 2Department of Gastroenterology, the Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanju Liu; Baisui Feng, Tel +86-18917683431 ; +86-18756585626, Email fbsktz@163.com; fengbs@zzu.edu.cnBackground: Anti-TNF medications are the first-line treatment for Crohn’s Disease (CD), despite the fact that a significant portion of the population continues to be ineffectively treated. This research aims to discover accurate intervention targets for the follow-up of anti-TNF non-responders using bioinformatics technology.Methods: GSE16879, GSE111761, and GSE52746 retrieved from the GEO database. Unbiased differentially expressed genes (DEGs) were discovered utilizing the limma and RobustRankAggreg (RRA) tools. Then, we used weighted gene co-expression network analysis (WGCNA) to identify the module most strongly associated with non responders and subjected this module to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis with overlapping genes of the DEGs. GSEA analysis applied to check the results of GO and KEGG. Using the Cytoscape program, the protein-protein interaction (PPI) network was constructed. The software’s MCODE addon and CytoHubba addon was used to find the most important modules and the hub genes. Subsequently, we employed reverse transcription-polymerase chain reaction (RT-PCR) to confirm hub gene expression from mucosal biopsy specimens.Results: There were a total of 142 genes co-upregulated and 65 genes co-downregulated. According to the WGCNA analysis, 42 genes were duplicated inside the light cyan module. GO and KEGG enrichment analyses of overlapped genes in nonresponders demonstrated an increase in the expression of genes associated with inflammation and immune response, consistent with GSEA results. The PPI network was constructed using 41 protein nodes and 177 edges. After validation, 8 of the top 10 genes were verified to be differentially expressed.Conclusion: Our investigation is the first to integrate three CD databases after the anti-TNF medication treatment. We identified IL1B, CCL4, CXCL1, CXCL10, CCL3, CSF3, TREM1, and IL1RN as potential therapeutic targets for patients whose anti-TNF treatment failed.Keywords: Crohn’s disease, weighted gene co-expression network analysis, robust rank aggreg, therapeutic targets

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Base-extracted particulate organic matter (BEPOM) collected in low (spring) and high (summer) runoff seasons in the Changjiang Estuary and adjacent nearshore/offshore shelf areas was examined using absorption and fluorescence spectroscopy. Parallel factor analysis (PARAFAC) identified two humic-like (C1p and C2p) biologically-refractory components and two protein-like (C3p and C4p) bioreactive components. Absorption coefficient a350p, C1p and C2p of BEPOM showed strong positive correlations with particulate organic carbon (POC), and were generally higher in spring than in summer. C4p correlated positively with Chl a, and was higher in summer than in spring. In the inner estuary, an anthropogenic POM signal from the highly polluted Huangpu River was effectively identified by the fluorescent component ratio (IT:IC)P. In the nearshore area during spring, resuspension within the well-developed turbidity maximum zone (TMZ) supplied large amounts of refractory POM into the water column. POM fractions from an autochthonous source (i.e., algal bloom) were dominant in the offshore area during the summer. A multivariate regression model inferred that POM export fluxes from the Changjiang River during spring had a higher percentage of labile POM fractions, which were subsequently retained by the TMZ. However, these labile fractions were discharged into the offshore shelf area contributing to hypoxia in the summer. The summer high runoff season also transported large amounts of refractory POM that was subsequently buried in the sediment. This study highlights the utilization of optical analyses to trace pollution sources and reveal POM fate and transport dynamics allowing better assessment of its ecological consequences in estuaries.

Xiangyu Gao,&ast; Hongmei Li,&ast; Yuan Yu, Xiaoyuan Huai, Bo Feng, Jun Song Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Song; Bo Feng, Department of Endocrinology, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of China, Tel/Fax +86 021-38804518, Email songjuntj@tongji.edu.cn; fengbodfyy@tongji.edu.cnPurpose: The dusk phenomenon refers to a spontaneous and transient pre-dinner hyperglycemia that affects glucose fluctuation and glycemic control, and the increasing use of continuous glucose monitoring (CGM) has facilitated its diagnosis. We investigated the frequency of the dusk phenomenon and its relationship with the time in range (TIR) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This study involved 102 patients with T2DM who underwent CGM for 14 days. CGM-derived metrics and clinical characteristics were evaluated. A consecutive dusk blood glucose difference (pre-dinner glucose minus 2-hour post-lunch glucose) of ≥ 0 or once-only dusk blood glucose difference of < 0 was diagnosed as the clinical dusk phenomenon (CLDP).Results: We found that the percentage of CLDP was 11.76% (10.34% in men, 13.64% in women). Compared with the non-CLDP group, the CLDP group tended to be younger and have a lower percentage of TIR (%TIR3.9-10) and higher percentage of time above range (%TAR> 10 and %TAR> 13.9) (P ≤ 0.05). Adjusted for confounding factors, the binary logistic regression analysis showed a negative association of CLDP with %TIR (odds ratio < 1, P < 0.05). We repeated the correlation analysis based on 70%TIR and found significant differences in hemoglobin A1c, fasting blood glucose, mean blood glucose, standard deviation of the sensor glucose values, glucose coefficient of variation, largest amplitude of glycemic excursions, mean amplitude of glycemic excursions, glucose management indicator, and percentage of CLDP between the two subgroups of TIR ≤ 70% and TIR > 70% (P < 0.05). The negative association between TIR and CLDP still remained after adjustment by the binary logistic regression analysis.Conclusion: The CLDP was frequently present in patients with T2DM. The TIR was significantly correlated with the CLDP and could serve as an independent negative predictor.Keywords: time in range, dusk phenomenon, type 2 diabetes, continuous glucose monitoring

Xue Lyu,&ast; Zhe Zhang,&ast; Xia Liu,&ast; Li Geng, Muhan Zhang, Baisui Feng Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baisui Feng, Email fbsktz@163.comBackground: Infliximab (IFX) has been widely used in ulcerative colitis (UC) patients. However, the subsequent effective treatment of IFX non-response in UC patients remains a challenge. This study aims to predict potential therapeutic targets for non-responders by performing a bioinformatic analysis of the data in the Gene Expression Omnibus (GEO) database and validation by biopsies.Methods: Colonic mucosal biopsies expression profiles of IFX-treated UC patients (GSE73661, GSE16879) were utilized to predict potential therapeutic targets. Bioinformatics analyses were used to explore potential biological mechanisms. CytoHubba was performed to screen hub genes. We used a validation dataset and colonic mucosal biopsies of UC patients to validate hub genes.Results: A total of 147 DEGs were identified (119 upregulated genes and 28 downregulated genes). GSEA showed that DEGs in GSE73661 were enriched in the pathways of the cytokine-cytokine receptor, the chemokine, and the adhesion molecules system. Based on the PPI network analysis, we identified four hub genes (and the transcription factor NF-κB). Then, we validate the expression of hub genes by reverse transcription-polymerase chain reaction (RT-PCR). We found higher expression of IL-6, IL1B, CXCL8, and CCL2 in non-responders compared to responders.Conclusion: In summary, four potential targets (IL-6, IL1B, CXCL8, and CCL2) were finally identified by performing a bioinformatics analysis of the datasets in the GEO database. Their expression was confirmed in colonic mucosal biopsies of patients with UC. These results can help to further explore the mechanism of non-responders to IFX in UC and to provide potential targets for their subsequent treatment.Keywords: ulcerative colitis, infliximab, GEO dataset, drug targets

Bo Feng,1,&ast; Xu Dong,1,&ast; Zhen Liu,2 Jie Zhang,3 Hongyu Liu,1 Yuan Xu1 1Department of Pharmacy, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 2Department of Neurology, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 3Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyu Liu; Yuan Xu, Department of Pharmacy, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China, Email liuhongyu@yzu.edu.cn; feebyxuyuan@163.comPurpose: Protein tyrosine phosphatases (PTPs) play an essential way in diseases including cancer, obesity, diabetes and autoimmune disorders. As a member of PTPs, low molecular weight PTP (LMPTP) has been a well-recognized anti-insulin resistance target in obesity. However, the number of reported LMPTP inhibitors is limited. Our research aims to discover a novel LMPTP inhibitor and evaluate its biological activity against insulin resistance.Methods: A virtual screening pipeline based on the X-ray co-crystal complex of LMPTP was constructed. Enzyme inhibition assay and cellular bioassay were used to evaluate the activity of screened compounds.Results: The screening pipeline rendered 15 potential hits from Specs chemical library. Enzyme inhibition assay identified compound F9 (AN-465/41163730) as a potential LMPTP inhibitor with a Ki value of 21.5 ± 7.3 μM. Cellular bioassay showed F9 could effectively increase the glucose consumption of HepG2 cells as a result of releasing insulin resistance by regulating PI3K-Akt pathway.Conclusion: In summary, this study presents a versatile virtual screening pipeline for potential LMPTP inhibitor discovery and provides a novel-scaffold lead compound that is worthy of further modification to get more potent LMPTP inhibitors.Graphical Abstract: Keywords: virtual screening, low molecular weight protein tyrosine phosphatase, LMPTP inhibitor, insulin resistance, molecular docking

Understanding interactions at the interfaces of carbon with ionic liquids (ILs) is crucially beneficial for the diagnostics and performance improvement of electrochemical devices containing carbon as active materials or conductive additives in electrodes and ILs as solvents or additives in electrolytes. The interfacial interactions of three typical imidazolium-based ILs, 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (AMImTFSI) ILs having ethyl (C2), butyl (C4) and octyl (C8) chains in their cations, with highly oriented pyrolytic graphite (HOPG) were studied in-situ by electrochemical scanning tunneling microscopy (EC-STM). The etching of HOPG surface and the exfoliation of graphite/graphene flakes as well as cation intercalation were observed at the HOPG/C2MImTFSI interface. The etching also takes place in C4MImTFSI at −1.5 V vs Pt but only at step edges with a much slower rate, whereas C8MIm+ cations adsorbs strongly on the HOPG surface under similar conditions with no observable etching or intercalation. The EC-STM observations can be explained by the increase in van der Waals interaction between the cations and the graphite surface with increasing length of alkyl chains.

Beibei Feng,1,2 Xiaoqian Hu,3 William Weijia Lu,2 Yuling Wang,1 Wing Yuk Ip2 1Rehabilitation Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China; 2Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Yuling Wang, Rehabilitation Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, No. 26, Yuancun 2nd Cross Road, Guangzhou, 510655, People’s Republic of China, Tel +86 20-38476737, Fax +86 20-38254221, Email wangyul@mail.sysu.edu.cn Wing Yuk Ip, Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People’s Republic of China, Tel +852 22554581, Fax +852 28174392, Email wyip@hku.hkBackground: Central sensitization (CS) is frequently reported in chronic pain, and the central sensitization inventory (CSI) is popularly used to assess CS. However, a validated Chinese CSI is lacking and its predictive ability for the comorbidity of central sensitivity syndromes (CSSs) remains unclear. Hence, this study aimed to generate the Chinese CSI (CSI-C) with cultural adaptation and examine its psychometric properties.Methods: The CSI-C was formulated through forward and backward translation, panel review and piloting and then validated among patients with chronic pain (n = 235). Its internal consistency, test–retest reliability, and concurrent validity were measured. An exploratory factor analysis (EFA) was performed for the construct validity. Receiver operating characteristic (ROC) analysis was employed to determine the discriminative ability in the presence of comorbidity of CSSs.Results: About 70% of the participants in the study experienced at least mild CS symptoms. CSI-C demonstrates a high internal consistency (Cronbach’s alpha = 0.896) and excellent test–retest reliability (ICC = 0.932). CSI-C scoring was significantly correlated with pain intensity (r = 0.188), EQ-5D index (r = − 0.375), anxiety (r=0.525), and depression (r = 0.467). The EFA generated a 5-factor model, including physical symptoms, emotional distress, hypersensitivity syndromes and so on. An CSI cutoff of 42 had a sensitivity of 71.4% and a specificity of 70% for identifying chronic pain patients with ≥ 2 CSSs.Conclusion: The CS manifestations are prevalent in those with persistent pain. CSI-C is a reliable and valid instrument for measuring CS. A CSI score ≥ 42 may predict the comorbidity of 2 or above CSSs in patients with chronic pain.Keywords: central sensitization, chronic pain, central sensitization inventory, Chinese, central sensitivity syndrome

This experimental study examined how depth of self-disclosure (baseline, peripheral, core) in support-seeking posts influenced forum viewers’ interaction involvement and reciprocal self-disclosure in their responses. A series of competing hypotheses derived from several theoretical frameworks were tested. Results obtained from computerized text analyses showed that self-concept self-disclosure was associated with higher levels of interaction involvement and reciprocal self-disclosure in viewers’ response messages. Implications of the findings and directions for future research are discussed.

Zhonglun Mai,1,&ast; Bin Feng,2,&ast; Qianwen He,3 Qixiao Feng1 1Department of Thoracic Oncology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510315, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510630, People’s Republic of China; 3Department of Geriatrics, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510315, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qixiao Feng Tel +86 18520088212Email cxhfqx@163.comZhonglun Mai Email maizhonglun@126.comPurpose: Malignant pleural effusion (MPE) is an intractable condition. The current mainstream therapies for MPE, ie, indwelling pleural catheter and pleurodesis, have some drawbacks. In this retrospective study, we explored the efficacy and safety of medical thoracoscopic thermal ablation (argon plasma coagulation, APC) therapy for metastatic pleural tumors with MPE.Patients and Methods: A total of 176 patients were enrolled and divided into catheter pleural drainage (CPD) group (n = 77), non-ablation group (n = 46), and thermal ablation group (n = 53). Propensity score matching (PSM) was used for between-group comparisons to minimize bias. The primary endpoints were pleural effusion objective response rate (ORR) and time to progression (TTP); secondary endpoints included overall survival (OS), chest-tube duration, and safety.Results: Thermal ablation group and non-ablation group showed significantly higher ORR and shorter chest-tube duration versus the CPD group (ORR: thermal ablation, 88.2% vs 66.7%, P = 0.004; non-ablation, 88.4% vs 64.4%, P = 0.042; chest-tube duration: thermal ablation, 4.90 vs 7.24 days, P < 0.001; non-ablation, 5.73 vs 7.33 days, P = 0.010). Thermal ablation group exhibited longer TTP than the CPD group (median, 13.7 vs 7.3 months, P = 0.001) and the non-ablation group (median, 13.6 vs 10.3 months, P = 0.037). OS in the thermal ablation group was numerically longer than that in the CPD group with marginally significant difference (P = 0.055). There was no significant difference in the frequency of adverse events or changes in vital signs between thermal ablation and non-ablation groups.Conclusion: Medical thoracoscopic thermal ablation (APC technique) therapy was effective and safe in the treatment of metastatic pleural tumors with MPE for improving ORR and TTP.Keywords: medical thoracoscopy, thermal ablation, argon plasma coagulation, metastatic pleural tumor, malignant pleural effusion, non-small-cell lung cancer

Bo Feng,&ast; Guang-Ming Dai,&ast; Yong-Jun Wang, Lan Zhang, Ke-Cheng Niu Department of Foot and Ankle Surgery, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, 014010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Feng Tel +86 13347173738Email femgbo@aliyun.comObjective: To summarize the clinical application effects of three different types of flaps for repairing soft tissue defects of the heel, and to discuss the importance of tissue repair and heel reconstruction.Methods: A total of 46 cases with skin tissue defects of the heel with deep tissue exposure were treated. The reasons for the defect were trauma (n = 26), burns and electric shocks (n = 12), chronic ulcers (n = 2), postoperative infection of the calcaneus and Achilles tendon (n = 5), and tumor resection (n = 1). The scope of wound defect was 2.0× 2.5 to approximately 15.0× 20.0 cm. The flaps used were medial plantar island flaps (n = 9), distal pedicled sural neurovascular island flaps (n = 23), and free anterolateral thigh (perforator) flaps (n = 14). The flap cutting range was 3.0× 3.5 to approximately 16.0× 22.0 cm.Results: After surgery, all 46 flaps survived. In two cases, patients experienced partial epidermal necrosis at the distal end of the flap that healed after local dressing exchange, and after this treatment, the complete skin grafts survived. Follow-up was conducted in 40 cases, with an average follow-up duration of 8.2 months (3– 44 months) and the two-point discrimination of 5– 14 mm. The average American Orthopaedic Foot and Ankle Society scale was 89.2 points with good flap color and texture, satisfactory appearance, and normal gait.Conclusion: The repair method should be selected according to the“ 5-zone method”: The plantar medial island flap is suitable for small area (< 5 cm) of medial, posterior and plantar defects. The distal pedicled sural neurovascular flap is suitable for lateral, posterior, and medium-range (6– 10 cm) joint area defects. The free anterolateral thigh perforator flap is suitable for large-scale (> 10 cm) joint area defects.Keywords: surgical flap, heel, functional reconstruction

Bing Feng,1,&ast; Xinling Meng,2,&ast; Hui Zhou,1,&ast; Liechun Chen,3 Chun Zou,3 Lucong Liang,3 Youshi Meng,3,4 Ning Xu,3,4 Hao Wang,3,4 Donghua Zou3,4 1Department of Neurology, The People’s Hospital of Guiping, Guigang, Guangxi, 537200, People’s Republic of China; 2Department of Endocrinology, The People’s Hospital of Guiping, Guigang, Guangxi, 537200, People’s Republic of China; 3Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 4Department of Neurology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Wang; Donghua ZouThe Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +86 7712636189Email bswanghao2010@163.com; danvor0922@hotmail.comObjective: Ischemic stroke (IS) is a major cause of severe disability. This study aimed to identify potential biomarkers closely related to IS diagnosis and treatment.Methods: Profiles of gene expression were obtained from datasets GSE16561, GSE22255, GSE112801 and GSE110993. Differentially expressed mRNAs between IS and controls were then subjected to weighted gene co-expression network analysis as well as multiscale embedded gene co-expression network analysis. The intersection of the two sets of module genes was subjected to analyses of functional enrichment and of microRNAs (miRNAs) regulation. Then, the area under receiver operating characteristic curves (AUC) was calculated to assess the ability of genes to discriminate IS patients from controls. IS diagnostic signatures were constructed using least absolute shrinkage and selection operator regression.Results: A total of 234 common co-expression network genes were found to be potentially associated with IS. Enrichment analysis found that these genes were mainly associated with inflammation and immune response. The aberrantly expressed miRNAs (hsa-miR-651-5p, hsa-miR-138-5p, hsa-miR-9-3p and hsa-miR-374a-3p) in IS had regulatory effects on IS-related genes and were involved in brain-related diseases. We used the criterion AUC > 0.7 to screen out 23 hub genes from IS-related genes in the GSE16561 and GSE22255 datasets. We obtained an 8-gene signature (ADCY4, DUSP1, ATP5F1, DCTN5, EIF3G, ELAVL1, EXOSC7 and PPIE) from the training set of GSE16561 dataset, which we confirmed in the validation set of GSE16561 dataset and in the GSE22255 dataset. The genes in this signature were highly accurate for diagnosing IS. In addition, the 8-gene signature significantly correlated with infiltration by immune cells.Conclusion: These findings provide new clues to molecular mechanisms and treatment targets in IS. The genes in the signature may be candidate markers and potential gene targets for treatments.Keywords: ischemic stroke, bioinformatics analysis, miRNAs, immune inflammatory response, candidate markers

Liying Chen,1,&ast; Dingqi Lu,2,&ast; Kai Yu,1 Shiya He,1 Liu Liu,1 Xvfeng Zhang,1 Bo Feng,3 Xinchang Wang4 1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang Province, 314001, People’s Republic of China; 4Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinchang WangDepartment of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of ChinaTel +86 13065714635Email ossani@126.comPurpose: Sjögren’s syndrome (SS) is a systemic autoimmune disease mainly characterized by dysfunction of exocrine glands. Studies on diagnosis models specific for SS patients are very limited. We aimed to use gene expression datasets from salivary glands to identify aberrant differentially expressed genes (DEGs) and pathways by bioinformatics and validate candidate genes by clinical minor labial gland biopsy (MSGB) samples, and finally build a combined gene quantitative diagnosis model of SS.Patients and Methods: Original datasets GSE23117, GSE7451, and GSE127952 were obtained from the Gene Expression Omnibus database (GEO) and integrated and analyzed for differentially expressed genes in SS salivary glands. ClueGO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of upregulated and downregulated DEGs were performed, and protein–protein interaction (PPI) networks were constructed using the STRING and Cytoscape database. H&E staining and immunohistochemistry were used to validate the expression levels of four hub genes in salivary glands. Finally, a receiver operating characteristic (ROC) curve of the combined diagnosis of four hub genes was analyzed in SS patients and non-SS patients in order to explore the diagnostic efficacy of these genes compared with conventional FS in SS.Results: Fifty-three upregulated genes and fifteen downregulated genes were identified. We analyzed the expression and function of four hub genes via H&E, immunohistochemistry, and ROC analysis. We then evaluated and verified the diagnosis value of four hub genes, STAT1, MNDA, IL10RA, and CCR1 in MSGB of SS and non-SS. A combined diagnosis model of four indicators was established to identify patients’ discrete data on the foci size (AUC=0.915).Conclusion: The expression of STAT1, MNDA, and IL10RA may be potential biological indicators for SS diagnosis. Compared with FS, a combined diagnosis model of quantitative gene expression could potentially contribute to improving the sensitivity and specificity of MSGB of SS.Keywords: Sjogren’s syndrome, bioinformatics analysis, hub genes, validation, diagnostic performance, focus score

Yonghui Xia, Huan Zhai, Xinlei Wang, Yudong Wang, Bo Feng Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Bo FengDepartment of Radiology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, People’s Republic of ChinaTel +8613898121986Email fbcmu@sina.comPurpose: In patients requiring percutaneous kyphoplasty (PKP) for painful cervical spine metastases (PCSMs), the surgical approach is of utmost importance. Anterolateral and transoral routes are generally used at present, whereas PKP as well as percutaneous pediculoplasty (PPP) via posterolateral transpedicular approach (PTPA) has yet to be pursued in the treatment of PCSMs. The study was designed to evaluate safety and efficacy of PKP procedures combined with PPP via PTPA as treatment of PCSMs.Patients and Methods: The patients with PCSMs were enrolled and housed in a database. The pain intensity of enrolled patients was gauged by Visual Analog Scale (VAS), ranging from 0 (none) to 10 (extreme). After preprocedural imaging assessment, combined PKP/PPP via PTPA was performed under the guidance of CT and fluoroscopic monitoring. Postprocedural VAS scores, complications, cement dosage, and hospitalization were recorded in the database for analysis. All cases were followed up for 6 months.Results: Adult enrollees (7 women, 4 men) with PCSMs successfully underwent PKP/PPP via PTPA between February 2019 and January 2020, injected with 3.7± 0.7 mL (range, 2.5– 4.8 mL) of cement on average. Other than a single instance of asymptomatic cement leakage into paravertebral soft tissues, no complications ensued. Significant analgesic effects observed 24 hours after procedures were sustained for up to 6 months in follow-up surveys. Postprocedural hospitalizations were as brief as 2.2± 0.8 days.Conclusion: Combined PKP/PPP via PTPA is safe and effective as treatment of PCSMs, enabling quick pain relief and patient recovery.Keywords: percutaneous vertebral augmentation, safety, efficacy, Visual Analog Scale

Junqiu Xiang, Long Han, Yanfei Fan, Bin Feng, Haoqing Wu, Chunmin Hu, Manli Qi, Huiping Wang, Quanzhong Liu, Yuanjun Liu Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of ChinaCorrespondence: Yuanjun LiuDepartment of Dermatovenereology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, People’s Republic of ChinaTel +86-22-60362902Fax +86-22-60362917Email liuyuanjun@tmu.edu.cnBackground: Human papillomavirus (HPV) is linked to various cancers in males and females. The prevalence and genotype distribution of HPV vary depending on geographical region and the immunity provided by vaccines. Investigation of HPV epidemiology is of great meaning for the development of prevention programs.Methods: From January 2017 to September 2019, using PCR-reverse dot blot hybridisation, we determined the HPV subtypes in 2801 patients 17– 89 years old at the sexually transmitted diseases (STD) clinic of Tianjin Medical University General Hospital.Results: The HPV infection rate was 50.79% in males and 50.64% in females. The most common HPV genotype in males and females was HPV6 (30.15% and 30.43%), followed by HPV16 (18.76% and 20.65%) and HPV11 (14.61% and 15.67%). Infection with a single HPV subtype predominated in both males and females, and the rate in males was higher than in females. By contrast, the rate of high-risk HPV (hrHPV) and low-risk HPV (lrHPV) mixed infection in females was higher than in males. Most HPV-positive patients were 20– 39 years of age. The prevalence of infection with only hrHPV differed among the age groups; the peak age was 50 to 59 years.Conclusion: The HPV prevalence was higher among the STD clinic outpatients than the general population. Therefore, a large-scale survey of high-risk populations is needed. It is anticipated that HPV vaccines, regular education and physical examinations may have a significant impact on the prevention of HPV-related diseases in high-risk groups.Keywords: human papillomavirus, prevalence, genotyping, HPV vaccination

Yanqiao Zhao,1,2,* Ziping Zhang,2,3,* Suimin Guo,2 Beibei Feng,2,4 Xiaoyu Zhao,2,5 Xueqiang Wang,1,6 Yuling Wang2 1Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of China; 2Department of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3School of Kinesiology, Shenyang Sport University, Shenyang, People’s Republic of China; 4Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5Department of Optometry, Fenyang College of Shanxi Medical University, Shanxi, People’s Republic of China; 6Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueqiang WangDepartment of Sport Rehabilitation, Shanghai University of Sport, 399 Changhai Road, Yangpu District, Shanghai, People’s Republic of ChinaEmail wangxueqiang@sus.edu.cnYuling WangDepartment of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-Sen University, No. 26, Erheng Road, Yuancun, Tianhe District, Guangzhou, People’s Republic of ChinaTel +86-20-38476737Email wangyul@mail.sysu.edu.cnBackground: Given the rapid growth of the global aging population, pain has become an unneglectable concern amongst the elderly. The quantity of scientific research outputs on pain in the elderly has increased over time, but only a small number of studies have used bibliometric methods to analyze scientific research in this field. This paper aimed to analyze scientific research on pain in the elderly published from 2000 to 2019 in a systematic manner using bibliometric methods.Methods: Articles on pain in the elderly published from 2000 to 2019 were retrieved from the Web of Science (WoS). Abstracts were coded on the basis of predetermined items (eg, type of article, topic, type of subjects, pain characteristics), and relevant information on the first author, citation scores, and article keywords were collected.Results: A total of 2105 articles were included in this study. Statistical analysis revealed that the publication of articles on pain in the elderly increased in frequency over time (P< 0.001). Most of the publications were original articles. Amongst the countries identified, the United States published the largest number of papers on this topic. Pain characteristics (50.21%), pain intervention (35.68%), and pain assessment (9.69%) were the main topics of research on geriatric pain. Back pain (12.30%) appeared to be the most popular pain type described in the included papers.Conclusion: This work provides researchers with an in-depth understanding of pain in the elderly by evaluating relevant publications in the past two decades. Researchers in this field are warranted to explore future directions on geriatric pain such as the transition from acute pain to chronic pain and the underlying mechanisms of pain in the elderly.Keywords: elderly, pain, bibliometric analysis

The current study examined the effect of the Integrated Model of Advice-giving (Emotional Support—Problem Inquiry and Analysis—Advice) on recipients’ responses to advice, exploring the mediating roles of perceived regard for face and normativeness. Participants read and responded to a conversation in which they received advice from a friend regarding a problematic situation. Results indicated that perceived regard for positive face mediated the relationship between the sequential placement of emotional support and recipients’ responses to advice. Neither perceived regard for face nor normativeness mediated the relationship between the sequential placement of problem inquiry and analysis and recipients’ responses to advice. Findings of this study suggest that the provision of emotional support has a primary role in IMA and is effective in addressing the positive face needs of advice recipient.

The electrochemical lithiation/delithiation of oxygen-containing functional groups (OCFGs) of nanocarbon materials, particularly graphene, have attracted intensive interest in recent years. Here, we propose a controllable potentiostatic oxidation approach to tune the OCFGs of as-prepared reduced graphene oxide (rGO) in a carbonate-based electrolyte to improve the specific capacity and rate capability. By X-Ray absorption spectroscopy in total fluorescence yield mode and X-Ray diffraction, we confirm that potentiostatic oxidations generate new OCFGs in the inner-layer of rGO. The content of OCFGs increases as oxidation potential being elevated. Such increasing of OCFGs in quantity significantly enhances the capacity. For instance, the specific capacity of 170.4 mAh g−1 for pristine rGO electrode is increased to 290.5 mAh g−1 after the oxidation at 5.0 V. We demonstrate that oxidations at moderate potentials can reduce the electrochemical and ohmic polarizations of rGO electrodes without deteriorating diffusion dynamic, thereby improving rate capability. After the optimal oxidation at 4.7 V, rGO electrode exhibits an excellent rate capability, delivering 58.4 mAh g−1 at 20 A g−1.

To reconstruct deep fluid chemical composition and increase the confidence in estimated reservoir temperatures, a more integral geothermometry method was compared to other classical geothermometers. Here, we apply the integrated multicomponent geothermometry (IMG) method using the GeoT code to estimate reservoir temperatures at the Tengchong geothermal field in Southwestern China. Results show reservoir temperatures calculated using the quartz geothermometer are closest to those estimated with the IMG method. The concentrations of Al and Mg, as well as selected minerals for geothermometry computations, are key factors for successfully using the IMG. Using the IMG method together with classical geothermometers can significantly increase confidence in reservoir temperature estimations. The methods presented and simulation program used here may be useful for analysis of other geothermal fields under similar conditions.

Jing Zhang,1 Feiyan Zhang,2 Jiye Fan,3,4 Bin Feng5 1Pharmacy Department, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei 050026, People’s Republic of China; 2Department of Outpatient Operating Room, Heze Municipal Hospital, Heze City, Shandong Province, 274000, People’s Republic of China; 3Department of Pharmaceutical Engineering, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei 050026, People’s Republic of China; 4College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, People’s Republic of China; 5Department of Gastrointestinal Surgery, Heze Municipal Hospital, Heze City, 274000 Shandong Province, People’s Republic of ChinaCorrespondence: Bin FengDepartment of Gastrointestinal Surgery, Heze Municipal Hospital, No. 2888, Caozhou Road, Mudan District, Heze City 274000, Shandong Province, People’s Republic of ChinaEmail 13020511011@163.comIntroduction: Gastric cancer is a kind of cancer with high mortality. TGIF1, as a transcription inhibitor, can inhibit the transcription of specific genes. The purpose of this study was to investigate the role of TGIF1 in gastric cancer by knocking down TGIF1.Methods: The expression of TGIF1 was detected by qPCR and Western blotting; CCK8 assay, colony formation assay, transwell, and wound-healing assay were used to evaluate the proliferation, migration, and invasion of gastric cancer cells; cell apoptosis was analyzed by flow cytometry and Hoechst-PI double staining; cell cycle was detected by flow cytometry. Gelatinase experiment was performed to detect the expression level of MMP-2; apoptosis related proteins and AKT singling pathway were assessed by Western blotting.Results: Knockdown of TGIF1 inhibited the proliferation, migration, and invasion of gastric cancer cells and promoted apoptosis. TGIF1 knockdown down-regulated the expression levels of MMP-2, Bcl2, CyclinD1, and p-Akt, and up-regulated the expression levels of Bax and Caspase3. These data suggested that knockdown of TGIF1 inhibited the development of gastric cancer via AKT signaling pathway.Conclusion: TGIF1 knockdown inhibited the proliferation, migration, and invasion and promoted apoptosis of gastric cancer cells via the AKT signaling pathway, suggesting that TGIF1 is considered a potential inhibitor in gastric cancer.Keywords: TGIF1, gastric cancer, AKT pathway, apoptosis, proliferation

Wenjie Zhu,1,* Zihan Zhao,1,* Baofu Feng,2 Wenhao Yu,3 Ji Li,3 Hongqian Guo,1 Rong Yang1 1Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing, 210008, People’s Republic of China; 2Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 3State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Yang; Hongqian Guo Email doctoryr@gmail.com; dr.ghq@nju.edu.cnIntroduction: Although immunotherapy works well in parts of patients with bladder cancer (BLCA), its overall response rate of anti-PD-1 inhibitors remains unsatisfactory. Besides, growing evidence shows that tumor-infiltrating lymphocytes (TILs) immunotherapy has demonstrated excellent efficacy in various cancers. Considering the huge heterogeneity and low overall survival rate of BLCA, it is urgent to explore the new immune checkpoints (ICs) or TILs therapy to improve the survival prognosis for BLCA patients.Materials and Methods: The public bioinformatics databases were used to explore the prognostic value of 5 potential ICs targets (TIM-3, LAG-3, OX40, 4– 1BB and CD39). A total of 46 BLCA patients undergoing surgical treatment at our hospital from May 2020 to October 2020 were enrolled in this study. The expressions of PD-1, TIM-3, LAG-3, OX40, 4– 1BB, and CD39 in T cells of BLCA patients were explored by flow cytometry, and the correlation between different subgroups of T cells and clinicopathological parameters was analyzed. Besides, the mouse CD4+CD39+ T cells, CD4+CD39- T cells, CD8+CD39+ T cells, and CD8+CD39- T cells were sorted and co-cultured with MB49 bladder cancer cell lines in vitro to investigate the potential biomarker of tumor-reactive TILs.Results: Public bioinformatics databases analyses show that only the high expression of CD39 was significantly associated with advanced tumor stage (P < 0.001) and tend to result in a worse survival rate. In our study, the elevated expression of CD39 in CD4+/CD8+ T cells were significantly associated with the pathological T stage (pT < 2, P = 0.041) and papillary tumor (P = 0.038). Moreover, the CD8+CD39+ T cells showed a stronger tumor-killing effect and produced a higher level of IFN-γ than other T cell populations.Conclusion: CD39 may be a potential prognostic marker in BLCA, and CD8+CD39+ T cells may be selected as tumor-reactive and killing T cells for TILs therapy.Keywords: CD8, CD39, T cells, anti-tumor cytotoxicity, bladder cancer, immunotherapy, TILs, immune checkpoint