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There is growing evidence that air pollution plays a role in TB, but few studies have comprehensively included the six common air pollutants. Our objectives were to investigate the association between short-term exposure to six common air pollutants and the risk of tuberculosis outpatient visits in Fuyang, China, during the period 2015-2020. We combined the two models to explore the effects of exposure to six air pollutants on the risk of tuberculosis outpatient visits, including Poisson generalized linear regression model and distributed lag non-linear model (DLNM). We performed stratified analyses for season, gender and age. We used the lag-specific relative risks and cumulative relative risk obtained by increasing pollutant concentration by per 10 units to evaluate the connection between six air pollutants and TB, PM2.5 (RR=1.0018, 95%CI: 1.0004-1.0032, delay of 12 days) and (RR=1.0169,95%CI: 1.0007-1.0333, lag 0-16 days), SO2 were 0.9549 (95%CI: 0.9389-0.9712, lag 0 days) and 0.8212 (95%CI: 0.7351-0.9173, 0-20 days lag). Stratified analyses showed that seasonal differences had a greater impact on TB, and male more likely to develop TB than female, older people more likely to develop TB than younger people. Exposure to O3, CO, PM10, PM2.5, and NO2 increases the risk of TB outpatient visits, except SO2 reduces the risk. Male and elderly people should be protected. We need to pay more attention to the impact of seasonal effects on TB.

Background/Purpose Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population. Methods The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions. Results The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population. Conclusion The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered.

Background In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. Methods Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. Results ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway. Conclusions This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

Circadian dysregulation involves malignant tumor initiation and progression, but the understanding of circadian rhythm's roles in bladder cancer (BCa) remains insufficient. The circadian rhythm-related genes were collected and clustered based on the Cancer Genome Atlas (TCGA), and the clustering was significantly associated with the prognosis and risk clinicopathological features. Through genomic difference analysis and gene pairing, a circadian rhythm-related signature was successfully established. Kaplan-Meier survival analysis and time-dependent receiver operating curves displayed that the prognosis model was a reliable prognosis biomarker both in the training cohort (n = 396, P = 2.687e-10) and external validation cohort (n = 224, P = 1.45e-02). The patients with high risk have high immune infiltration and high expression of immune checkpoint genes, which partly account for the poor prognosis. TIDE algorithm and the validation in IMvigor210 cohort indicated that the risk signature was a promising marker for the immunotherapeutic response. The risk model could also predict the therapeutic response of cisplatin, which was validated in the Genomics of Drug Sensitivity in Cancer database (P = 0.0049), TCGA (P = 0.038), and T24 BCa cells treated with cisplatin. The functional enrichment showed the risk model was significantly correlated with some malignant phenotypes, such as angiogenesis, epithelial-mesenchymal transition, and KRAS signaling pathway. Totally, we proposed a novel circadian rhythm-related signature for prognosis evaluation, which also helped to predict the immune infiltration and cisplatin sensitivity in BCa.

The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatality rate. Moreover, there is no effective drug that can limit the novel coronavirus thus far, so it is more needed to develop antiviral drugs for the SARS-CoV-2. In our research, we employed the techniques of molecular docking to screen 35 flavonoid compounds among which 29 compounds have Z-scores lower than − 6. Then, ( −)-gallocatechin gallate, ( +)-gallocatechin and baicalein were identified to have potent inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 5.774 ± 0.805 μM, 13.14 ± 2.081 μM and 5.158 ± 0.928 μM respectively by FRET assay. Molecular docking results also showed that ( −)-gallocatechin gallate, ( +)-gallocatechin and baicalein can non-covalently bind to Mpro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of ( −)-gallocatechin gallate and baicalein on cytokine storms using a mouse model of sepsis. ( −)-Gallocatechin gallate and baicalein significantly reduced sepsis of mouse models on weight, murine sepsis score, and survival rate and reduced the inflammatory factor levels, such as TNF-α, IL-1α, IL-4, and IL-10. Overall, ( −)-gallocatechin gallate and baicalein show certain potential of treatment against COVID-19.

Non-obstructive azoospermia (NOA) is among the most severe factors for male infertility, but our understandings of the latent biological mechanisms remain insufficient. The single-cell RNA sequencing (scRNA-seq) data of 432 testicular cells isolated from the patient with NOA was analyzed, and the cell samples were grouped into 5 cell clusters. A sum of 455 cell markers was identified and then included in the protein-protein interaction network. The Top 5 most critical genes in the network, including CCT8, CDC6, PSMD1, RPS4X, RPL36A, were selected for the diagnosis model construction through the random forest (RF). The RF model was a strong classifier for NOA and obstructive azoospermia (OA), which was validated in the training cohort (n = 58, AUC = 1) and external validation cohort (n = 20, AUC = 0.9). We collected the seminal plasma samples and testicular biopsy samples from 20 OA and 20 NOA cases from the local hospital, and the gene expression was detected via Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) and Immunohistochemistry. The RF model also exhibited high accuracy (AUC = 0.725) in the local cohort. In summary, a novel gene signature was developed and externally validated based on scRNA-seq analysis, providing some new biomarkers to uncover the underlying mechanisms and a promising clinical tool for diagnosis in NOA.

The Rab GTPase family contains almost 70 genes in the human genome and acts as the key regulator of intracellular membrane trafficking in human cells. The dysregulation of Rab GTPase has been shown to be associated with multiple human diseases, ranging from neurodegeneration, and infection to cancer. Rab GTPases not only play important roles in genome replication, morphogenesis and the release of hepatitis B virus (HBV) or hepatitis C virus (HCV), but also contribute to hepatitis-related hepatocarcinogenesis and hepatocellular carcinoma (HCC) progression. The alteration of Rab GTPase expression in HCC plays an important role in tumour cell proliferation, invasion and migration. Notably, the expression of Rab genes can be regulated by some noncoding RNAs, such as miRNAs and circRNAs. Thus, Rab GTPases can serve as promising rational and therapeutic targets for HCC treatments. In this review, we summarized recent advancements in this field focusing on Rab GTPases in HCC.

Necroptosis has been recently confirmed as a non-apoptotic form of programmed cell death. Discovery of novel chemical entities, capable of inducing necroptosis of cancer cells, is likely to act as an alternative strategy for dealing with drug resistance clinically. In this study, the identification of a novel Pleuromutilin derivative (compound 38) is presented, capable of significantly increasing the cellular level of ROS and inducing melanoma cancer cell death via necroptosis. Furthermore, compound 38 noticeably ablated various cancer stem cells and inhibited the growth of melanoma cancer cells both in vitro and in vivo. Moreover, 38 exhibited low toxicity in animal models and excellent PK properties, which is currently being verified as a potential anticancer drug candidate.

Objective To observe the clinical effect of quick puncture with collateral-pricking cupping for facial acne. Methods Twenty-eight patients with acne were treated with pricking acne spot and abdominal region of three toes for bloodletting combined with collateral-pricking cupping on the back, once every 5 days, for 3 weeks in succession. A 3-month follow-up was applied to observe the reducing rate and clinical effect of facial skin lesions after treatment. Results Of the 28 cases, 9 were cured, 12 remarkably effective, 5 effective, and 2 ineffective. The total effective rate was 92.86%. Conclusion The effect of pricking acne spot and abdominal region of three toes combined with collateral-pricking cupping on the back is good, being worthy of further clinical discussion to promote its application.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by epithelial cell damage, fibroblast activation, and collagen deposition. IPF has high mortality and limited therapies, which urgently needs to develop safe and effective therapeutic drugs. Bergenin, a compound derived from a variety of medicinal plants, has demonstrated multiple pharmacological activities including anti-inflammatory and anti-tumor, also acts as a traditional Chinese medicine to treat chronic bronchitis, but its effect on the pulmonary fibrosis is unknown. In this study, we demonstrated that bergenin could attenuate bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro studies indicated that bergenin inhibited the transforming growth factor-β1 (TGF-β1)-induced fibroblast activation and the extracellular matrix accumulation by inhibiting the TGF-β1/Smad signaling pathway. Further studies showed that bergenin could induce the autophagy formation of myofibroblasts by suppressing the mammalian target of rapamycin signaling and that bergenin could promote the myofibroblast apoptosis. In vivo experiments revealed that bergenin substantially inhibited the myofibroblast activation and the collagen deposition and promoted the autophagy formation. Overall, our results showed that bergenin attenuated the BLM-induced pulmonary fibrosis in mice by suppressing the myofibroblast activation and promoting the autophagy and the apoptosis of myofibroblasts.

Intra-tumor heterogeneity (ITH) was a potential mechanism of progression and drug resistance in bladder cancer (BCa). However, the understanding of ITH in BCa remains insufficient. Single-cell RNA sequencing (scRNA-seq) profiles of 2075 cells were analyzed, and 2940 cell markers were screened. The ITH of 396 cases was evaluated, and 96 ITH-related genes were identified. Based on the gene-pair strategy, 96 genes were cyclically paired, and an 8-gene-pair model was successfully established to evaluate the overall survival of BCa through Lasso and multivariate Cox regressions. The risk model showed high predictive value in the training dataset (n = 396, p = 0) and external validation datasets (n = 165, p = 2.497e-02; n = 224, p = 3.423e-02). The model was also valuable for the prediction of clinical treatment outcomes. Totally, a prognostic model based on scRNA-seq and ITH was successfully constructed and validated in large cohorts, providing novel clues for ITH study of BCa.

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg(−1) · d(−1)) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg(−1) · d(−1)) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.

Breast cancer is a complex and multifactorial disease which stems significantly from both environmental and genetic factors. A growing number of epidemiological studies have suggested that ambient air pollution (AAP) exposure may play an important role in breast cancer development. However, no consistency has been reached concerning whether high levels of air pollutant exposure were related to increased breast cancer risk among the current evidence. To further clarify such association of long-term AAP exposure with risk of breast cancer, a systematic review and meta-analysis of available evidence was performed. An extensive literature search in 3 academic databases was conducted before March 10, 2020. The risk of bias (RoB) for each individual study was evaluated with a domain-based assessment tool, developed by the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT). Meta-estimates for air pollutant–breast cancer combinations were calculated for a standardized increment in exposure by random-effect models. The confidence level in the body of evidence and the certainty of evidence was also assessed for each air pollutant–breast cancer combination. The initial search identified 5446 studies, and 18 of them were eligible. The pooled analysis found an increased risk of breast cancer was associated with an increase in each 10 μg/m3 in nitrogen dioxide (NO2) exposure (hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01, 1.04), while particulate matter with aerodynamic diameters ≤ 2.5 μm and 10 μm (PM2.5, PM10) revealed no statistically significant associations with breast cancer risk. Our evaluation on the certainty of evidence indicates that there was a “moderate level of evidence” in the body of evidence for an association of NO2 exposure with an increased breast cancer risk and an “inadequate level of evidence” in the body of evidence for an association of PM2.5 and PM10 exposure with an increased breast cancer risk. Our study suggests long-term exposure to NO2 is related to an increased risk of breast cancer. However, in consideration of the limitations, further studies, especially performed in developing countries, with improvements in exposure assessment, outcome ascertainment, and confounder adjustment, are needed to draw a definite evidence of a causal relationship.

BACKGROUND: Functional incomplete revascularisation (IR) is associated with a higher risk of major adverse cardiac events (MACE) during long-term follow-up in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). AIMS: This study aimed to investigate the prognostic ability of quantitative flow ratio (QFR)-guided residual functional SYNTAX score (Q-rFSS) and functional IR in STEMI patients undergoing PCI. METHODS: In total, 354 consecutive STEMI patients who successfully underwent PCI were included. Q-rFSS was defined as residual SYNTAX score (rSS) measured only in vessels with QFR ≤0.8. The primary outcome was MACE (a composite of all-cause mortality, myocardial infarction, and ischaemia-driven revascularisation) at 2 years. RESULTS: At two-year follow-up, functional IR (Q-rFSS ≥1) showed significantly higher risk for MACE than functional complete revascularisation (CR) (Q-rFSS=0) (functional IR vs CR, 22.0% vs 7.4%; hazard ratio [HR] 3.21; 95% confidence interval [Cl]: 1.74 to 5.91; p

Aim Given the increasing prevalence of hysteromyoma among the Chinese rural women of childbearing age, it is imperative that more attention should be given to researching risk factors that predispose women to this condition so that early preventive measures may be taken. Our study investigates potential risk factors for uterine fibroids such as participants' demographic characteristics (age, ethnicity, education), physiological characteristics (age at menarche, primiparous age), and the occurrence of several different female reproductive diseases (vaginitis, pelvic inflammatory disease). Methods 2200 rural women of reproductive age were screened from a cross-sectional study carried out in the northern Anhui province. Data were collected by questionnaire surveys, gynecological and laboratory examinations and were subjected to univariate and multivariate analysis to evaluate the risk factors for uterine fibroids. Results Of the 2200 women, 440 had uterine fibroids. In general, women with endometriosis, ovarian cysts and early menarche were more likely to suffer from hysteromyoma. Factors including higher parity, late age of first childbirth, and a regular menstrual cycle were associated with the reduced risk of uterine fibroids. Conclusions Our findings indicate that parameters such as earlier age of menarche, early primiparous age, lower parity and a variety of female reproductive diseases were associated with an increased risk of uterine fibroids. These findings may be used to guide the formulation of effective prevention and intervention protocols to improve the reproductive health of rural women.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

Objectives An increase in the incidence of congenital hypothyroidism (CH) with eutopic gland has been reported worldwide due to neonatal screening programs. In this study, we aimed to determine the prevalence of transient CH (TCH) and to investigate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid glands. Methods We retrospectively reviewed 508 children treated for CH with eutopic thyroid glands between June 1998 and June 2020 in Jiangxi Newborn Screening Center. All patients were treated with levothyroxine and underwent Diagnostic re-evaluation after 2–3 years of age. Patients were classified as having TCH or permanent CH (PCH) during follow-up. Results Of the 508 patients initially treated for CH with a normally located gland, 335 patients (65.9%) were classified in the TCH group and 173 (34.1%) in the PCH group based on the defined criteria. Multivariate analysis revealed that TCH was associated with a lower levothyroxine dose at 24 months of age (p Conclusions TCH presents a significant portion of patients with CH. The levothyroxine dose requirement at 24 months of age has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid glands.

Cheng-Kun Wu,1 Chien-Ning Hsu,2,3 Wei-Ru Cho,1 Shih-Cheng Yang,1 An-Che Liu,4 Wei-Chen Tai,1 Chen-Hsiang Lee,5 Yao-Hsu Yang,6– 8 Seng-Kee Chuah,1 Chih-Ming Liang1 1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 6Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 7Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan; 8School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, TaiwanCorrespondence: Chih-Ming LiangDivision of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dabi Road, Kaohsiung, 833, TaiwanTel +886-7-731-7123, ext. 8301Fax +886-7-732-2402Email gimy54861439@gmail.comBackground and Aim: Endoscopic sphincterotomy (ES) abolished the barrier between the hepatobiliary system and duodenum and might be at risk of pyogenic liver abscess (PLA). We aimed to identify the association factors of PLA in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) procedures for treatment of choledocholithiasis.Methods: This study was based on the Chung Gung Research Database (CGRD) between January 1, 2001 and December 31, 2018. Those who had an International Classification of Diseases, Ninth and Tenth Revision (ICD9 and ICD10) codes of choledocholithiasis and received ERCP were enrolled. After strict exclusions, 11,697 patients were further divided into the endoscopic sphincterotomy (ES) group (n=7,111) and other ERCP group (n=4,586) for analysis.Results: Patients receiving ES had significantly higher rates of PLA than those of the other ERCP group (5-year cumulative incidence 2.4% versus 1.7%; 10-year cumulative incidence 3.9% versus 3.2%, log-rank p=0.0177). Aging, male gender, surgery for hepato-pancreato-biliary system and hepatobiliary malignancy were significant association factors of PLA. On multivariate analysis, the ES increased the risk of PLA (adjusted hazard ratio [aHR]=1.49; 95% CI=1.12– 1.98; p=0.0058) but decreased the risks for acute pancreatitis (aHR=0.72; 95% CI=0.60– 0.85; p=0.0002) and cholangitis (aHR= 0.91; 95% CI=0.84– 0.99; p=0.0259). There was no significant difference about recurrent choledocholithiasis between groups.Conclusion: This study demonstrated a significant risk of PLA after patients receiving ES compared with the other ERCP group. We should also carefully monitor the association factors of PLA after ERCP treatment of choledocholithiasis including aging, male gender, surgery for the hepato-pancreato-biliary system and hepatobiliary malignancy.Keywords: pyogenic liver abscess, endoscopic sphincterotomy, choledocholithiasis, endoscopic retrograde cholangiopancreatography

Yao-Cheng Yang,1,2,* Jun-Jie Wang,3,4,* Yun Huang,1,2 Wei-Xin Cai,1,2 Qian Tao1,2 1Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510086, People’s Republic of China; 3Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 4School of Stomatology, Jinan University, Guangzhou, 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian TaoDepartment of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, People’s Republic of ChinaTel/Fax +86 20-83846030Email taoqian@mail.sysu.edu.cnPurpose: Ameloblastoma is a benign odontogenic neoplasm with a high local recurrence rate if the operation is not thorough. However, a useful clinical tool for the quantitative assessment of the prognosis and risk of postoperative recurrence of ameloblastoma has not yet been constructed. This study aims to develop a prognostic nomogram model for ameloblastoma of the jaw to assist surgeons in surgical decision-making.Patients and Methods: Patients who underwent initial surgery for ameloblastoma in our department from October 2004 to March 2020 were enrolled and randomly divided into training and validation sets. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors, from which a nomogram for predicting 3-, 5- and 10-year recurrence-free survival (RFS) of ameloblastoma was constructed using the training set and internally validated using the validation set. The model performance was assessed by Harrell’s concordance index (C-index) and calibration curves.Results: A total of 302 eligible patients with ameloblastoma were enrolled, 54 of whom were confirmed to relapse during the follow-up period of 6 to 191 months. Four independent predictors, including cortical bone perforation, root(s) resorption, WHO classification, and treatment pattern, were identified and included in the construction of a nomogram for recurrence-free survival (RFS), which showed promising calibration performance and discrimination in the training set (C-index 0.790, 95% confidence interval [CI] 0.735– 0.845) and the validation set (C-index 0.734, 95% CI 0.599– 0.869).Conclusion: A favorable nomogram was developed that accurately predicted the RFS of patients with ameloblastoma based on individual characteristics. Risk stratification using the nomogram could optimize tailored therapy and follow-up.Keywords: ameloblastoma, nomogram, prognosis, recurrence, recurrence-free survival

Cheng Yang,1 Han-Hua Zeng,1 Yan-Jia Du,1 Juan Huang,1 Qian-Yun Zhang,1 Kun Lin2 1Department of Pulmonary and Critical Care Medicine, Meizhou People’s Hospital, Meizhou, 5143031, Guangdong, People’s Republic of China; 2Department of Preventive Medicine, Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of ChinaCorrespondence: Qian-Yun ZhangDepartment of Pulmonary and Critical Care Medicine, Meizhou People’s Hospital, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of ChinaTel +86 07532202723Fax +86 07532204840Email zhqianyun@163.comKun LinDepartment of Preventive Medicine, Shantou University Medical College, No. 22 Xinling Road, Jinping District, Shantou, 515041, People’s Republic of ChinaTel +86 075488900445Fax +86 075482903637Email klin@stu.edu.cnBackground and Objective: Luminal mucus plugging in small airways is associated with lung function decline and death of patients with chronic obstructive pulmonary disease (COPD). However, little attention has been paid to the possible role of mucus in large airways in acute exacerbation of COPD (AECOPD). Therefore, this study aimed to explore the relationship between the luminal mucus score of large airways and other physiological parameters of severe AECOPD.Subjects and Methods: A total of 74 AECOPD inpatients were enrolled in this cross-sectional study. All patients underwent lung function tests and bronchoscopy, and their luminal mucus was observed and scored through bronchoscopy. Four questionnaires, including the St. George Respiratory Questionnaire (SGRQ), modified Medical Research Council dyspnea scale (mMRC), COPD Assessment Test (CAT) and Exacerbation of Chronic pulmonary disease Tool (EXACT), were used to assess health-related quality of life (HRQoL).Results: The luminal mucus score of large airways was significantly correlated with spirometry parameters and HRQoL score. Both mMRC grade and SGRQ score were significantly positively correlated with luminal mucus score (ρ=0.527, P< 0.001; ρ=0.441, P< 0.001, respectively). Forced expiratory flow at 25% to 75% of the FVC (FEF25%-75%) and FEV1% predicted, as functional measures reflecting small airway disease, were significantly negatively correlated with luminal mucus score (ρ=− 0.518, P< 0.001; ρ=− 0.498, P< 0.001, respectively). The stepwise multiple linear regression model suggested that mMRC grade and FEV1% predicted could predict luminal mucus score (R2=0.348, F=18.960, P< 0.001).Conclusion: For severe acute exacerbation of COPD, bronchoscopy-identified luminal mucus in large airways is associated with reduced lung function and worse health-related quality of life.Keywords: chronic obstructive pulmonary disease, acute exacerbation, luminal, mucus, bronchoscopy

Purpose Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era of immune checkpoint therapy. Methods To understand the CD8+ T cell dynamics in the tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate CD8+ proliferation (Ki67 co-expression) in tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic and 347 gastric cancer samples. Results The density and the percentage of proliferating (Ki67+) CD8+ T cells were both highly variable between tumor types as well as between patients with the same tumor type. Elevated density and percentage of proliferating CD8+ cytotoxic T cells were significantly associated with favorable tumor parameters such as low tumor stage, negative nodal stage (p ≤ 0.0041 each), prolonged overall survival (p ≤ 0.0028 each) and an inflamed immune phenotype (p = 0.0025) in colorectal cancer and, in contrast, linked to high tumor stage, advanced ISUP/Fuhrman/Thoenes grading (each p ≤ 0.003), shorter overall survival (p ≤ 0.0330 each) and an immune inflamed phenotype (p = 0.0094) in renal cell cancer. In breast, ovarian, pancreatic and gastric cancer the role of (Ki67+)CD8+ Tcells was not linked to clinicopathological data. Conclusion Our data demonstrate a tumor type dependent prognostic impact of proliferating (Ki67+)CD8+ Tcells and an inverse impact in colorectal and renal cell cancer.

Purpose. To evaluate the clinical outcome of the three-random-point (TRP) marking method for toric intraocular lens (IOL) alignment using the iTrace aberrometer (Tracey Technologies Corp., Houston, TX). Setting. Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People’s Hospital, Guangzhou, China. Design. Prospective, randomized comparative trial. Method. Thirty eyes of 30 patients undergoing cataract surgery with coexisting corneal astigmatism of over 1.0 D were included in this study. All patients were prospectively randomized into the TRP marking group or slit-lamp horizontal meridian (SHM) marking group. TRP marking involved marking three points randomly in the corneal limbus of the patients and accurately marking the horizontal meridian was not required. The follow-up duration was 3 months after cataract surgery. Results. Fifteen eyes of 15 patients were in the TRP marking group and 15 eyes of 15 patients in the SHM marking group. There was no statistically significant difference in BCVA, UDVA, preexisting corneal astigmatism, or residual astigmatism between the groups before or after surgery P > 0.05 . The mean toric IOL misalignment was lesser but without significance in the TRP marking group than in the SHM marking group after 3 postoperative months (2.66° ± 1.42° versus 3.29° ± 1.67°; P = 0.295 ). Conclusion. The TRP marking method using the iTrace aberrometer is simple and accurate for preoperative marking of toric IOLs. It can eliminate the potential systematic errors resulting from varying head positions during the preoperative keratometry measurement and from manual marking.

Background Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole–induced SCAR remains unclear. Objective We aimed to investigate the genetic predisposition of co-trimoxazole–induced SCAR. Methods We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole–induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. Results The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole–induced SCAR (P = 8.2 × 10−9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole–related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole–induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10−21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10−5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole–induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10−23; OR = 40.1). Conclusion This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole–induced SCAR in Asians.

BackgroundDermatitis is an important global health problem that not only affects social interaction and physical and mental health but also causes economic burden. Health problems or distress caused by dermatitis may be easily overlooked, and relevant epidemiological data are limited. Therefore, a better understanding of the burden of dermatitis is necessary for developing global intervention strategies.MethodsAll data on dermatitis, including atopic dermatitis (AD), contact dermatitis (CD) and seborrhoeic dermatitis (SD), were obtained from the Global Burden of Disease 2019 (GBD2019) database. The extracted age-standardized incidence rates (ASIR) and disability-adjusted life-years (DALYs) rates (ASDR) data were analysed by stratification, including by sex, country or region, and sociodemographic index (SDI) indicators. Finally, we analysed the correlation between the global burden of dermatitis and socioeconomic development status.ResultsAccording to the GBD 2019 estimate, the ASIR and ASDR for the three major types of dermatitis in 2019 were 5244.3988 (95% CI 4551.7244–5979.3176) per 100,000 person-years and 131.6711 (95% CI 77.5876–206.8796) per 100,000 person-years. The ASIR and ASDR of atopic dermatitis, contact dermatitis and seborrhoeic dermatitis are: Incidence (95%CI,per 100,000 person-years), 327.91 (312.76-343.67), 3066.04 (2405.38-3755.38), 1850.44 (1706.25- 1993.74); DALYs (95%CI, per 100,000 person-years), 99.69 (53.09-167.43), 28.06 (17.62-41.78), 3.93 (2.24-6.25). In addition, among the three dermatitis types, the greatest burden was associated with AD. According to the ASDR from 1990 to 2019, the burden of dermatitis has exhibited a slow downward trend in recent years. In 2019, the ASIR showed that the USA had the greatest burden, while the ASDR showed that Asian countries (such as Japan, Mongolia, Kazakhstan, and Uzbekistan) and some European countries (France, Estonia) had the greatest burden. According to SDI stratification and the three major dermatitis types, high ASIR and ASDR corresponded to high SDI areas (especially for AD).ConclusionThe burden of dermatitis is related to socioeconomic development status, especially for AD, which is positively correlated with the SDI. The results based on GBD2019 data are valuable for formulating policy, preventing and treating dermatitis and reducing the global burden of dermatitis.

Background Patients with type 2 diabetes mellitus (T2DM) have an increased risk of suffering from various malignancies. This study aimed to identify specific biomarkers that can detect lung adenocarcinoma (LAC) in T2DM patients for the early diagnosis of LAC. Methods The clinical information of hospitalized T2DM patients diagnosed with various cancers was collected by reviewing medical records in Wuxi People’s Hospital Affiliated to Nanjing Medical University from January 1, 2015, to June 30, 2020. To discover diagnostic biomarkers for early-stage LAC in the T2DM population, 20 samples obtained from 5 healthy controls, 5 T2DM patients, 5 LAC patients and 5 T2DM patients with LAC (T2DM + LAC) were subjected to sequential windowed acquisition of all theoretical fragment ion mass spectrum (SWATH-MS) analysis to identify specific differentially-expressed proteins (DEPs) for LAC in patients with T2DM. Then, these results were validated by parallel reaction monitoring MS (PRM-MS) and ELISA analyses. Results Lung cancer was the most common malignant tumor in patients with T2DM, and LAC accounted for the majority of cases. Using SWATH-MS analysis, we found 13 proteins to be unique in T2DM patients with early LAC. Two serum proteins were further validated by PRM-MS analysis, namely, pregnancy-zone protein (PZP) and insulin-like growth factor binding protein 3 (IGFBP3). Furthermore, the diagnostic values of these proteins were validated by ELISA, and PZP was validated as a novel serum biomarker for screening LAC in T2DM patients. Conclusions Our findings indicated that PZP could be used as a novel serum biomarker for the identification of LAC in T2DM patients, which will enhance auxiliary diagnosis and assist in the selection of surgical treatment at an early stage.

Background To observe the characteristics of binocular integration and stereopsis in children with television torticollis. Methods A retrospective study was carried out, where data were collected from 25 children with television torticollis as the disease group after refractive error correction and 25 normal children as the control group. A virtual reality system was used to assess and analyze the characteristics of binocular integration by a contrast balance test and binocular stereopsis. Results The 25 children in the disease group included 17 males and 8 females with an average age of 7.5 ± 1.9 years old and an average binocular spherical equivalent of − 0.35 ± 1.46D. The 25 children in the control group were also 17 males and 8 females with an average age of 7.3 ± 2.2 years old and the average binocular spherical equivalent of − 0.48 ± 0.93D. No significant differences were found in the horizontal bar contrast balance test between the 2 groups at near and far distances. Near-distance vertical bar contrast balance test was normal in 23 subjects and suppressed in 2 subjects in the control group, while it was normal in 13 subjects and suppressed in 12 subjects in the disease group, which showed a statistically significant difference (P = 0.002). Far distance vertical bar contrast balance test was normal in 24 subjects and suppressed in 1 subject in the control group, normal in 7 subjects and suppressed in 18 subjects in the disease group, showing a statistically significant difference (P = 0.000). All subjects in the 2 groups showed 100〞 as near distance stereoacuity. At far distance, the mean stereoacuity was 176.00〞 ± 92.56〞 in the control group, and 352.00〞 ± 270.99〞 in the disease group, with a statistically significant difference (P = 0.011). Conclusion By using virtual reality technology, defects in binocular visual function were found in children whose television torticollis persisted after regular refractive error correction. Television torticollis may be associated with the deficit of binocular integration for vertical bars and far distance stereopsis.

Meng-Tsang Hsieh,1– 3,* Kuo-Chang Huang,4,* Cheng-Yang Hsieh,5,6 Tzu-Tung Tsai,1 Li-Ching Chen,1 Sheng-Feng Sung7– 9 1Stroke Center and Department of Neurology, E-Da Hospital, Kaohsiung, Taiwan; 2School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Division of Neurosurgery, Department of Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan; 5Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan; 6School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan; 8Department of Information Management and Institute of Healthcare Information Management, National Chung Cheng University, Chiayi County, Taiwan; 9Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan, Taiwan*These authors contributed equally to this workCorrespondence: Sheng-Feng SungDivision of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, TaiwanTel +886 5 276 5041 Ext 7283Fax +886 5 278 4257Email richard.sfsung@gmail.comPurpose: The performance of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for identifying acute hemorrhagic stroke in Taiwan’s National Health Insurance claims database has not been assessed. This study aimed to construct and validate the case definitions for acute hemorrhagic stroke based on ICD-10-CM diagnostic codes.Patients and Methods: From January 2018 to December 2019, all inpatient records with ICD-10-CM code of I60 or I61 in any field of the discharge diagnoses were retrieved from the hospitalization claims data and all hospitalizations with a final diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) were identified from the stroke registry databases. The clinical diagnosis in the stroke registry was treated as the reference standard. For hospitalizations not recorded in the stroke registry, manual review of the medical records and images was done to ascertain the diagnosis. The positive predictive value (PPV) and sensitivity of various case definitions for acute hemorrhagic stroke were estimated.Results: Among the 983 hospitalizations, 860, 111, and 12 were determined to be true-positive, false-positive, and false-negative episodes of acute hemorrhagic stroke, respectively. The PPV and sensitivity of the ICD-10-CM codes of I60 or I61 for identifying acute hemorrhagic stroke were 88.6% and 98.6%, respectively. The PPV increased to 98.2%, whereas the sensitivity decreased to 93.1% when acute hemorrhagic stroke was defined as hospitalizations in which the primary diagnosis field contained I60 or I61. Hemorrhagic transformation of ischemic stroke and concomitant cerebrovascular diseases other than SAH or ICH were the main reasons for a false-positive and false-negative diagnosis of acute hemorrhagic stroke, respectively.Conclusion: This study demonstrated the performance of ICD-10-CM codes for identifying acute hemorrhagic stroke and may offer a reference for future claims-based stroke studies.Keywords: administrative claims data, diagnosis, ICD-10-CM, hemorrhagic stroke

Chitin is a potential resource for the production of renewable organonitrogen compounds, as it contains biologically fixed nitrogen. Hydrolysis of chitin followed by hydrogenation gives the sugar alcohol named 2-acetamido-2-deoxysorbitol (ADS). The dehydration condensation of ADS produces 2-acetamido-2-deoxyisosorbide (ADI), which is a prospective precursor of nitrogen-containing polymers. However, the conversion of ADS to ADI in previous works needed a large amount of CF3SO3H as a superstrong acid catalyst, which is high cost and requires special corrosion-resistant equipment. In this work, we have found that H3PO3, a weak acid, can convert ADS to ADI. Possibly, H3PO3 alters the reaction mechanism from a simple acid-catalysed dehydration cyclisation to a cyclisation via phosphite esters. Density functional theory calculations suggest that the modified pathway via the phosphite esters significantly reduces the activation energy. In addition, the reducing ability of the acid likely decreases the formation of condensation by-products.

Purpose The underlying pathophysiology of juvenile absence epilepsy (JAE) is unclear. Since cortical and subcortical brain regions are thought to be altered in genetic generalized epilepsy, the present study examined the resting-state functional network topology of the same regions in JAE. Methods Electroencephalography and functional magnetic resonance imaging (EEG-fMRI) were performed on 18 JAE patients and 28 healthy controls (HCs). The topology of functional networks was analyzed using the graph-theoretic method. Both global and nodal network parameters were calculated, and parameters differing significantly between the two groups were correlated with clinical variables. Results Both JAE patients and HCs had small-world functional network topological architectures. However, JAE patients showed higher values for the global parameters of clustering coefficient (Cp) and normalized characteristic path length (Lambda). At the nodal level, patients exhibited greater centrality at widespread cortices, including the left superior parietal gyrus, right superior temporal gyrus, right orbital part of middle frontal gyrus and bilateral supplementary motor area. Conversely, patients showed decreased nodal centrality predominantly in the limbic network, left thalamus and right caudate nucleus. Degree centrality in the right hippocampus and betweenness centrality in the right caudate nucleus positively correlated with epilepsy duration. Conclusion The global functional network of JAE shows small-world properties, but tends to be regular with higher segregation and lower integration. Regions in the basal ganglia-thalamo-cortical network have aberrant nodal centrality. The hippocampus and caudate nucleus may reorganize as epilepsy progresses. Our findings indicate the pathogenesis and compensatory mechanisms to seizure attacks and cognitive deficits of JAE.

Angiogenesis and immunosuppression have been described as closely related processes that can occur in parallel. As an inhibitor of matrix metalloproteinase, whether the level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in hepatocellular carcinoma (HCC) reflects a link between angiogenesis and immunosuppression is still unknown. We analyzed RNA expression, immune infiltration and survival of HCC from The Cancer Genome Atlas databases. Immune scores and stromal scores were calculated based on the ESTIMATE algorithm to quantify the immune and stromal components in HCC. The association between RECK and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high RECK expression was significantly better than that of patients with low RECK expression. High RECK expression was associated with high ESTIMATE Score, recruitment of more tumor-infiltrating lymphocytes, low tumor purity, and high PD-L1 expression. In addition, positive RECK expression was associated with a lower incidence of vascular invasion and recurrence, a lower level of alpha fetoprotein (AFP) and microvessel density and a better tumor differentiation. Multivariate analyses revealed that reduced RECK expression was an independent prognostic factor for recurrence and poor prognosis. In conclusion, high RECK expression reflects an immunogenic and hypovascularity status in HCC. RECK is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive anti-angiogenic therapy or immunotherapy.

BACKGROUND AND AIM Clopidogrel is widely prescribed for patients with of aspirin-related upper gastrointestinal bleeding (UGIB) history. This study aimed to compare the risk of a major adverse cardiovascular event (MACE), UGIB, and mortality between aspirin and clopidogrel in patients at risk of bleeding. METHODS We analyzed adult patients at high risk of UGIB following aspirin-related bleeding for secondary MACE prevention between 2000 and 2012. Secondary prevention was for those patients who had ever been hospitalized for cardiovascular disease and reused aspirin or changed to clopidogrel after discharge. Study endpoints were recurrence of MACE, UGIB, and death in 90 days of follow-up. The associations between study outcomes and the use of clopidogrel (vs aspirin) were analyzed. RESULTS Among 947 eligible patients, 653 reused aspirin (in combination with a proton-pump inhibitor), and 294 were treated with clopidogrel (in combination with a proton-pump inhibitor) after discharge for UGIB. Compared with aspirin treatment, clopidogrel showed an increased risk of MACE (adjusted hazard ratio [aHR] 1.65; 95% confidence interval [CI] 0.87-3.12) and UGIB (aHR 1.25; 95% CI 0.66-2.36), but without statistical significance in 90 days' follow-up. Clopidogrel use was associated with greater than four times the risk of any cause of mortality (aHR 4.84; 95% CI 1.59-14.75), but the significance did not hold in propensity score-matched cohort analysis (P = 0.06). CONCLUSIONS A nonsignificant difference between clopidogrel and aspirin for short-term MACE prevention as well as UGIB recurrence was found in the present study. Further research to assess 90-day mortality would assist clinical decision making.

Background: Vagus nerve stimulation (VNS) is used as an add-on treatment for epilepsy. This study aimed to use Taiwanese nationwide registry data to analyze the therapeutic effects of VNS in children with refractory epilepsy (RE) and try to explore predictive factors of VNS treatment effectiveness. Methods: This retrospective study collected data from December 2007 to December 2014. Patient variables included gender, age, VNS implantation date, epilepsy duration, seizure frequency, seizure type, etiology, and antiepileptic drug (AED) history. We divided patients into three groups: Group I as seizure frequency >80 times per month, Group II as seizure frequency 24–80 times per month, and Group III as seizure frequency

In this study, we aimed to investigate the impact of aspirin on the risk of pyogenic liver abscess caused by Klebsiella pneumoniae (KP-PLA) and invasive KP-PLA syndrome (IKPS) in diabetic patients. Diabetic patients who were propensity-score matched were retrospectively included from hospital-based database. Kaplan–Meier approach with a log-rank test was used to compare the cumulative incidences of KP-PLA including IKPS between aspirin users and non-users. Totally, 63,500 patients were analyzed after propensity-score matching (1:1). Compared with that of non-users, the incidence of KP-PLA was significantly reduced in aspirin users (0.31% vs. 0.50%, p p = 0.29). Patients taking aspirin for ≥ 90 days had a significantly lower risk for KP-PLA (hazard ratio, 0.67; 95%CI, 0.50–0.90). Females, taking clopidogrel or metformin for ≥ 90 days, and taking H2-blockers or proton pump inhibitors (PPIs) for ≥ 5 days were also associated with a lower risk of KP-PLA. However, cholangitis and a glycated hemoglobin ≥ 8.5% were associated with an increased risk of KP-PLA.

Over 1.5 million deaths worldwide are caused by neurocardiogenic syndromes. Furthermore, the consequences of deleterious brain-heart interactions are not limited to fatal complications. Cardiac arrhythmias, heart failure, and nonfatal coronary syndromes are also common. The brain-heart axis is implicated in post-stroke cardiovascular complications known as the stroke-heart syndrome, sudden cardiac death, and Takotsubo syndrome, among other neurocardiogenic syndromes. Multiple pathophysiological mechanisms with the potential to be targeted with novel therapies have been identified in the last decade. In the present state-of-the-art review, we describe recent advances in the understanding of anatomical and functional aspects of the brain-heart axis, cardiovascular complications after stroke, and a comprehensive pathophysiological model of stroke-induced cardiac injury.

Background People are at a high risk of gastric cancer if their first-degree relatives suffered from atrophic gastritis (AG), intestinal metaplasia (IM), intraepithelial neoplasia (IEN), dysplasia (DYS), or gastric cancer (GC). This study was performed to analyse the association between FDR-GC and GC precursors. Methods A cross-sectional study was performed to screen the prevalence of GC precursors from November 2016 to September 2019. A total of 1329 participants with FDR-GC, 193 participants with a family history of non-gastric cancer in FDRs (FDR-nGC), and 860 participants without a family history of cancer in FDRs (FDR-nC) were recruited in this study. The logistic regression model was used in this study. Results The prevalence of normal, Non-AG, AG/IM, IEN/DYS, and GC was 31.91, 44.21, 13.81, 8.73, and 1.34%, respectively. The prevalence of IEN/DYS was higher in people with FDR-GC and FDR-nGC (FDR-GC: odds ratio (OR) = 1.655; 95%CI, 1.153–2.376; FDR-nGC: OR = 1.984; 95%CI, 1.122–3.506) than those with FDR-nC. The younger the age at which FDRs were diagnosed with GC, the more likely the participants were to develop AG/IM (Ptrend = 0.019). The risk of precursors to GC was higher in participants whose FDR-GC was the mother than in those whose FDR-GC was the father or sibling (OR, non-AG: 1.312 vs. 1.007, 1.274; AG/IM: 1.430 vs. 1.296, 1.378; IEN/DYS: 1.988 vs. 1.573, 1.542). There was no statistically significant difference in non-AG (OR = 1.700; 95%CI, 0.940–3.074), AG/IM (OR = 1.291; 95%CI, 0.579–2.877), and IEN/DYS (OR = 1.265; 95%CI, 0.517–3.096) between participants with one or more FDR-GC. Conclusion People with FDR-GC and FDR-nGC are at a high risk of IEN/DYS. When an FDR was diagnosed at a younger age, the risk of AG/IM was higher. The risk of GC precursors was higher in people whose FDR-GC was the mother.

Background Although the latest Gleason grading system in 2014 has distinguished between Gleason 3 + 4 and 4 + 3, Gleason 8 and Gleason 9–10 are remained systemically classified. Methods A total of 261,125 patients diagnosed with prostate cancer (PCa) were selected between 2005 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching to balance clinical variables and then compared overall survival (OS) and cancer‐specific survival (CSS) between Gleason score subgroups. We further establish a new Gleason survival grading system based on the hazard ratio (HR) values of each Gleason subgroup. Cox proportional hazards models and Kaplan–Meier curves were used to compare patient survival. Results Among PCa patients with Gleason score 8 disease, patients with Gleason 5 + 3 had significantly worse OS and CSS than those with Gleason 3 + 5 (OS: HR = 1.26, p = 0.042; CSS: HR = 1.42, p = 0.005) and 4 + 4 (HR = 1.50 for OS and HR = 1.69 for CSS, p, We conducted a large‐scale statistical study to analyze the effects of different Gleason scores on overall survival. We further established a new Gleason survival grading system based on the hazard ratio values of each Gleason subgroup.

Objective To observe the clinical effect of electroacupuncture(EA) at Zhǒuling (Extra) and Ashi points in combination with blood-letting cupping for the treatment of external humeral epicondylitis (EHE). Methods Thirty EHE patients were treated with EA at Zhǒuling (Extra) and Ashi points in combination with blood-letting cupping, once every 2 days, twice a week, 4 times as one course of treatment, and 2 successive courses of treatment were given. Before treatment, after 1 course of treatment, and after 2 courses of treatment, the visual analogue scale (VAS) score and Mayo elbow performance score (MEPS) were adopted to evaluate the curative effect. Results Before treatment, the VAS score of patients was 7.81±1.39. After 1 course of treatment and after 2 courses of treatment, it was 4.77±1.56 and 2.95±1.23 respectively, lowered than before treatment, and the difference was statistically significant (both P Conclusion EA at Zhǒuling (Extra) and Ashi points and blood-letting cupping used in combination are remarkably effective in the treatment of EHE, being worthy for popularization.

Summary Background No standard treatment exists for advanced chordoma. Apatinib has been found to have promising efficacy and manageable adverse effects for the treatment of solid tumours. We aimed to investigate the safety and antitumour activity of apatinib in patients with advanced chordoma. Methods We did a single-arm, phase 2 study at one tertiary hospital in Shanghai, China. Eligible patients were aged 18–75 years, with histologically confirmed advanced chordoma that was unresectable or resectable only through demolitive surgery, who had previously received surgical treatment, with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evidence of tumour progression on enhanced CT or MRI in the previous 6 months, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients received oral 500 mg apatinib once daily until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival and objective response rate according to RECIST 1.1 and Choi criteria by investigator assessment. Progression-free survival was assessed in the intention-to-treat population. Objective response rate was assessed in the per-protocol population, which included all enrolled patients who were compliant with the protocol and had at least one post-baseline assessment. Safety was analysed in all patients with complete safety data. This study is ongoing, but recruitment is complete. This study is registered with Chictr.org.cn , ChiCTR-OIC-17013586. Findings Between Aug 21, 2017, and May 31, 2019, we screened 32 patients, of whom 30 were enrolled. Median follow-up was 14·2 months (IQR 9·4–19·7). Of the 27 patients included in the per-protocol population, one patient (3·7%; 95% CI 0–11·3) achieved an objective response according to RECIST, and seven patients (25·9%; 8·3–43·6) achieved an objective response according to Choi criteria. Median progression-free survival was 18 months (95% CI 3–34) according to RECIST and 18 months (3–33) according to Choi criteria. The most common treatment-related grade 3 adverse events were hypertension (seven [24%] of 29 patients) and proteinuria (two [7%]). No treatment-related grade 4 adverse events or treatment-related deaths were observed. Interpretation To our knowledge, this is the first trial of apatinib for the treatment of advanced chordoma. Apatinib shows promising activity and manageable toxicity and thus might be an option for the treatment of advanced chordoma. Funding None.

Objective Numerous types of nonepileptic paroxysmal events, such as syncopes and psychogenic nonepileptic seizures, may imitate epileptic seizures and lead to diagnostic difficulty. Such misdiagnoses may lead to inappropriate treatment in patients that can considerably affect their lives. Electroencephalogram (EEG) is a commonly used tool in assisting diagnosis of epilepsy. Although the appearance of epileptiform discharges (EDs) in EEG recordings is specific for epilepsy diagnosis, only 25%–56% of patients with epilepsy show EDs in their first EEG examination. Methods In this study, we developed an autoregressive (AR) model prediction error–based EEG classification method to distinguish EEG signals between controls and patients with epilepsy without EDs. Twenty-three patients with generalized epilepsy without EDs in their EEG recordings and 23 age-matched controls were enrolled. Their EEG recordings were classified using AR model prediction error–based EEG features. Results Among different classification methods, XGBoost achieved the highest performance in terms of accuracy and true positive rate. The results showed that the accuracy, area under the curve, true positive rate, and true negative rate were 85.17%, 87.54%, 89.98%, and 81.81%, respectively. Conclusions Our proposed method can help neurologists in the early diagnosis of epilepsy in patients without EDs and might help in differentiating between nonepileptic paroxysmal events and epilepsy. Significance EEG AR model prediction errors could be used as an alternative diagnostic marker of epilepsy.

Liver fibrosis is a disease caused by long‐term damage that is related to a number of factors. The current research on the treatment of liver fibrosis mainly focuses on the activation of hepatic stellate cell, in addition to protecting liver cells. byakangelicin has certain anti‐inflammatory ability, but its effect on liver fibrosis is unclear. This study aims to explore whether byakangelicin plays a role in the development of liver fibrosis and to explore its mechanism. We determined that byakangelicin has a certain ability to resist fibrosis and reduce liver cell damage in a model of carbon tetrachloride–induced liver fibrosis in mice. Thereafter, we performed further verification in vitro. The signalling pathways of two important pro‐fibrotic cytokines, transforming growth factor‐β and platelet‐derived growth factor, were studied. Results showed that byakangelicin can inhibit related pathways. According to the hepatoprotective effect of byakangelicin observed in animal experiments, we studied the effect of byakangelicin on 4‐HNE–induced hepatocyte (HepG2) apoptosis and explored its related pathways. The results showed that byakangelicin could attenuate 4‐HNE–induced hepatocyte apoptosis via inhibiting ASK‐1/JNK signalling. In conclusion, byakangelicin could improve carbon tetrachloride–induced liver fibrosis and liver injury by inhibiting hepatic stellate cell proliferation and activation and suppressing hepatocyte apoptosis.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with poor prognosis and high incidence. The clinical data analysis of liver hepatocellular carcinoma samples downloaded from The Cancer Genome Atlas reveals that the THO Complex 1 (THOC1) is remarkable upregulated in HCC and associated with poor prognosis. However, the underlying mechanism remains to be elucidated. We hypothesize that THOC1 can promote the proliferation of HCC. The present study aims to identify THOC1 as the target for HCC treatment and broaden our sights into therapeutic strategy for this disease. Methods Quantitative RT-PCR, Western blot, immunofluorescence and immunohistochemistry were used to measure gene and protein expression. Colony formation and cell cycle analysis were performed to evaluate the proliferation. The gene set enrichment analysis were performed to identify the function which THOC1 was involved in. The effects of THOC1 on the malignant phenotypes of hepatocellular cells were examined in vitro and in vivo. Results The gene set enrichment analysis reveals that THOC1 can promote the proliferation and G2/M cell cycle transition of HCC. Similarly, experimental results demonstrate that THOC1 promotes HCC cell proliferation and cell cycle progression. The knockdown of THOC1 leads to R-loop formation and DNA damage and confers sensitivity to cisplatin. In addition, in vivo data demonstrate that THOC1 can enhance tumorigenesis by increasing tumor cell proliferation. Furthermore, virtual screening predicts that THOC1 as a direct target of luteolin. Luteolin can induce DNA damage and suppress the proliferation of HCC by targeting THOC1. Furthermore, the inhibition of THOC1 activity by luteolin enhances the chemosensitivity of HCC tumor cells to cisplatin. Conclusions THOC1 was identified as a predictive biomarker vital for HCC-targeted treatments and improvement of clinical prognosis. Luteolin combined with cisplatin can effectively suppress HCC tumor growth, indicating a potential and effective therapeutic strategy that uses luteolin in combination with conventional cytotoxic agents for HCC treatment.

Metallothionein (MT) is a protein with function of heavy metal detoxification. However, studies about how single nucleotide polymorphisms (SNPs) of MT genes influence lead nephropathy are relatively scarce. Therefore, our aim is to investigate the association between blood lead levels and renal biomarkers and to study whether this association is influenced by the combination of MT1A and MT2A SNPs. Blood lead, urinary uric acid (UA), and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were analyzed from 485 participants. Genotyping were performed on MT1A SNPs (rs11640851 and rs8052394) and MT2A SNPs (rs10636 and rs28366003). The combined MT1A 2A SNPs were divided into 16 groups. Among renal biomarkers, urinary UA was negatively significant associated with the time-weighted index of cumulative blood lead (TWICL), while urinary NAG was positively significant with TWICL. Furthermore, the association between urinary UA and TWICL was significantly modified by group 6 of combined SNPs (MT1A 2 A SNPs combination were AAAGGGAA, ACAGGGAA, and ACGGGGAA). In conclusion, the negative association of urinary UA and TWICL is modified by group 6, which means participants of group 6 are more susceptible to lead nephrotoxicity.

Purpose Home-time has been found to correlate well with modified Rankin Scale (mRS) scores in patients with stroke. This study aimed to determine its correlations in patients with different types of stroke at various time points after stroke in a non-Western population. Methods This study used linked data from multi-center stroke registry databases and a nationwide claims database of health insurance. Functional outcomes as measured with the modified Rankin Scale were obtained from the registry databases and home-time was derived from the claims database. Spearman correlation coefficients were used to assess the correlation between home-time and mRS scores. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of home-time in predicting good functional outcome. Results This study included 7959 patients hospitalized for stroke or transient ischemic attack (TIA), for whom mRS scores were available in 6809, 6694, and 4330 patients at 90, 180, and 365 days, respectively. Home-time was highly correlated with mRS scores at the three time-points in patients with ischemic (Spearman's rho -0.69 to -0.83) or hemorrhagic (Spearman's rho -0.86 to -0.88) stroke, but the correlation was only weak to moderate in those with TIA (Spearman's rho -0.32 to -0.58). Home-time predicted good functional outcome with excellent discrimination in patients with ischemic (AUCs >0.8) or hemorrhagic (AUCs >0.9) stroke but less so in those with TIA (AUCs >0.7). Conclusion Home-time was highly correlated with mRS scores and showed excellent discrimination in predicting good functional outcome in patients with ischemic or hemorrhagic stroke. Home-time could serve as a valid surrogate measure for functional outcome after stroke.

Biomechanical changes caused by structural foot deformities predispose patients to plantar ulceration. Plantar ulcer recurrence often leads to osteomyelitis, which is more commonly observed in patients with diabetes. Once the infection of diabetic foot ulcer (DFU) spreads and is complicated by osteomyelitis, treatment becomes more complicated and difficult. Osteomyelitis treatment remains challenging because of low drug concentration within the tissue caused by poor circulation and inadequate localized nutrition. Moreover, tissues around plantar ulcers are fewer and are thin, making the formation of granulation tissues difficult due to elevated plantar pressure. Furthermore, the skin around the wound is excessively keratinized, and the epidermis is hard to regenerate. Meanwhile, skin grafting at that site is often not successful due to poor blood circulation. Therefore, it is technically challenging to manage diabetic pressure plantar ulcer with osteomyelitis and prevent its recurrence. Here, we present a case of chronic DFU complicated by osteomyelitis due to foot deformity. The ulcer was successfully healed using advanced wound repair technology comprising of surgical bone resection, vancomycin-loaded bone cement implant, negative-pressure wound therapy, and autologous platelet-rich gel. Subsequently, preventive foot care with custom-made offloading footwear was prescribed. The plantar ulcer did not recur and improvement in biomechanical parameters was observed after the intervention. This case represents an effective and comprehensive management strategy for limb salvage and prevention in patients with complicated foot conditions.

Early identification of borderline personality disorder (BPD) is important as timely interventions are beneficial and cost-effective. Unrecognized BPD not only results in suffering for individuals and their families, but also leads to considerable social costs. Although web-based measures have the potential to facilitate screening assessment of BPD for research and clinical purposes, little is known about whether the results of web-based measures of BPD are valid. This preliminary study aims to examine the validity of a web-based measure of BPD.We analyzed data from five independent samples (The web-based BPD measure had a consistent relationship with relevant variables, including trauma exposure, mental well-being, depression, post-traumatic stress, dissociation and psychotic features across samples. It was also strongly correlated with another BPD measure. The web-based BPD measure could discriminate between participants with and without BPD and the discrimination performance was excellent (area under the curve =.853).The initial findings suggest that the web-based BPD measure used in the present study is valid and may be helpful for research and screening purposes, although it should be followed up with a more comprehensive assessment in clinical settings. Implications are discussed. Given the limitations in this study, further studies are needed.

Conventional treatment for treating primary central nervous system lymphoma (PCNSL) has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy. However, delayed cognitive sequelae have emerged as a significant debilitating complication in PCNSL patients. A prospective observational case-series study with prospective assessments of neurocognitive functions (NCFs), neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken. A battery of neuropsychological measures, used to evaluate NCFs, is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. A total of 15 patients with newly-diagnosed PCNSL were consecutively enrolled in this study. Comparing the NCF scores between the baseline (before WBRT) and post-treatment (after combined chemoradiation therapy) intervals (Mean = 122.33 days, SD = 34.49, range = 77-196), neurobehavioral outcomes consistently remained improving or stable in almost each domain of NCF. Specifically, the scores on Paced Auditory Serial Addition Test-Revised (PASAT-R) were significantly improved between the baseline and post-chemoradiation assessment. Under the multidisciplinary treatment guidelines for treating patients with newly-diagnosed PCNSL, multi-domain NCF become stabilized and even improved after the course of conformal WBRT combined with or without MTX-based chemotherapy.

Epilepsy is a common neurological disorder that affects millions of people worldwide. Patients with epilepsy generally require long-term antiepileptic therapy and many of them receive polypharmacy. Certain medications, including older-generation antiepileptic drugs, have been known to predispose patients to developing diabetes. Although data mining techniques have become widely used in healthcare, they have seldom been applied in this clinical problem. Here, the authors used association rule mining to discover drugs or drug combinations that may be associated with newly diagnosed diabetes. Their findings indicate in addition to the most common culprits such as phenytoin and valproic acid, prescriptions containing carbamazepine, oxcarbazepine, or lamotrigine may be related to the development of newly diagnosed diabetes. These mined rules are useful as guidance to both clinical practice and future research.

Background. TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. Materials and Methods. TSC1-floxed mice (TSC1flox/flox) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth. Results. No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice. Conclusion. Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs.

1,4-Sorbitan and 1,4-mannitan are important precursors for synthesis of detergents and pharmaceuticals, derived from mono-dehydration of sugar alcohols (D-sorbitol and D-mannitol). In order to impr...