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Gouty arthritis (GA) is an inflammatory disease, and renal impairment may occur to varying degrees with the progress of disease. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker. In this study, we aimed to explore the association between NLR and renal impairment in GA.The subjects comprised 499 patients with gouty arthritis (GA) (473 men, 26 women; age range, 39-61 years old) from our hospital. They were divided into a chronic kidney disease (CKD) group (n = 206) and non-CKD group (n = 293) according to the glomerular filtration rate. Blood samples were collected during the gout flares. The differences in NLR, general data, and laboratory indexes of patients with GA between the two groups were compared, such as serum uric acid (SUA), serum creatinine (SCREA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), high-density lipoprotein (HDL), and low-density lipoprotein (LDL).NLR (3.38 vs. 2.38 (p 0.001)) was higher in the CKD group, compared to the non-CKD group. Similarly, both SUA (527 vs. 507 (p 0.05)) and SCREA (122 vs. 87 (p 0.001)) were higher in the CKD group than in the non-CKD group. Multivariate logistic regression analysis showed that NLR (OR = 1.122, p 0.05), age, hypertension, and SUA were risk factors for CKD in patients with GA, although HDL and HGB were protective factors. The receiver operating characteristic (ROC) curve analysis indicated that the area under the curve of NLR for predicting CKD in patients with GA was 0.646 (95% CI 0.597-0.694).Our data showed that NLR might be an important potential factor for evaluating renal impairment in GA during flares.

Background Fractures are a great health issue associated with morbidity, quality of life, life span, and health care expenditure. Fractures are correlated with cardiovascular disease, type 2 diabetes mellitus, cerebrovascular disease, and some psychiatric disorders. However, representative national data are few, and longitudinal cohort studies on the association between schizophrenia and the subsequent fracture risk are scant. We designed a nationwide population-based cohort study to investigate the association of schizophrenia with hip, vertebral, and wrist fractures over a 10-year follow-up. Methods Data of patients with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification code 295) and matched over January 2000–December 2009) were extracted from Taiwan National Health Insurance Research Database. A Cox proportional-hazards regression model was constructed to calculate hazard ratios (HRs) for fractures between the schizophrenia and control cohorts. Results Of 2028 people with schizophrenia (mean age: 36.3 years, 49.4% female), 89 (4.4%) reported newly diagnosed fractures—significantly higher than the proportion in the control population (257, 3.2%; P = 0.007). The incidences of hip (1.2%, P = 0.009) and vertebral (2.6%, P = 0.011) fractures were significantly higher in the schizophrenia cohort than in the control cohort. In Cox regression analysis, hip (adjusted HR: 1.78, 95% confidence interval [CI]: 1.08–2.93) and vertebral (adjusted HR: 1.40, 95% CI: 1.01–1.95) fracture risks were significantly higher in patients with schizophrenia. Furthermore, a sex-based subgroup analysis revealed that the risk of hip fracture remained significantly higher in female patients with schizophrenia (HR: 2.68, 95% CI: 1.32–5.44) than in female controls. On the other hand, there was no significant interaction between effects of sex and schizophrenia on the risk of fractures. Conclusions Over a 10-year follow-up, hip and vertebral fracture risks were higher in the people with schizophrenia than in the controls. The risk of fractures in patients with schizophrenia does not differ between female and male.

Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p, Final tumor grading of oral cavity squamous cell carcinoma (OCSCC) is assigned according to the most prevalent grade. Relapses of poorly differentiated OCSCC tended to occur regionally and distantly. Poor tumor differentiation was the second most relevant adverse risk factor after extranodal extension. The NCCN guidelines should include poor differentiation as an adverse risk factor.

Background We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. Methods A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score‐matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). Results Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3−4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5‐year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease‐free survival, 84%/83%/68%/52%; disease‐specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values 0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. Conclusions Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease., Patients with oral cavity squamous cell carcinoma and cN+pN0 disease are characterized by a higher prevalence of adverse risk factors. However, this was not found to translate into a less favorable prognosis; therefore, the presence of cN+pN0 disease should not be considered as an adverse prognostic factor

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss‐of‐function and gain‐of‐function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production., The expression of ME2 was significantly elevated in HCC tissues.ME2 promotes HCC progression by increasing triglyceride production.

The current study presents two patients who lived in a rural family with close contact and suffered from rapidly progressive pneumonia. Chest computed tomography images and lymphocytopenia indicated the possibility of COVID-19 infection, but antibody and nucleic acid tests excluded this possibility. Negative results were obtained from corresponding tests for pneumococcal, adenovirus, fungal and legionella infection. Metagenomics analysis and subsequent antibody tests confirmed mycoplasma pneumonia. After treating with moxifloxacin, both patients recovered well and left the hospital. In terms of complicated infectious disease, consideration of atypical pathogens and medical and epidemiological history were important for differential diagnosis of COVID-19; metagenomics analysis was useful to provide direct references for diagnosis.

Background Taurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation. Methods CKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet. Results Taurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P P P Conclusion In CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.

Background Esophageal cancer (EC) is a malignant tumor with high mortality. Nomogram is an important tool used in clinical prognostic assessment. We aimed to establish a novel nomogram to predict the overall survival (OS) of EC patients after radical esophagectomy. Methods Data pertaining to the survival, demography, and clinicopathology of 311 EC patients who underwent radical esophagectomy were retrospectively investigated. The nomogram was established based on Cox hazard regression analysis. The calibration curves and Harrell's concordance index (C‐index) were used to verify the predictive accuracy and ROC curves were used to assess the efficacy of the nomogram. Kaplan–Meier curves showed the prognostic value of the related risk classification system. Pearson correlation test was performed to determine the correlation between the risk classification system and TNM staging. Results The median OS and 5‐year survival rates in the primary and validation cohorts were 44 months and 29.8%, and 52 months and 27.1%, respectively. We used six independent prognostic factors—age, Sex, AGR, PRL, N stage, and PNI—in the nomogram. The C‐index of nomogram was 0.75 and 0.70 in the primary and validation cohorts, respectively. Calibration curves indicated high consistency between actual and predicted OS. ROC curves showed that nomogram has a better efficacy compared with TNM staging in both cohorts. Patients were divided into three risk groups according to the total nomogram score, the median OS in each group was significantly different in both cohorts. Furthermore, the risk classification system was strongly correlated with the T and N staging system and exhibited a better OS prediction capability. Conclusions We established a novel and practical nomogram with a subordinate risk classification system to predict the OS of patients after radical esophagectomy. Compared with AJCC staging, this nomogram had preferable clinical capability in terms of individual prognosis assessment., We built and validated a novel nomogram to predict OS in radical esophageal cancer resection patients, the nomogram showed considerable prognostic capability especially compared with AJCC staging. Furthermore, a related risk classification system was generated for clinical evaluation.

Background Peripheral gangrene is rarely documented as a possible complication of Kawasaki disease (KD). There are many causes of peripheral gangrene, and the common cause is in situ thrombosis or embolism. Most cases are reported to have regrettable outcomes (amputation or necrotic shedding). Herein, we report the successful management of KD complicated by peripheral artery thrombosis in an older Chinese boy, and a review of all cases of peripheral gangrene in KD in the literature. Case presentation We found that most of the children with this complication were under 1 year old, had a heavy inflammatory response combined with the use of cortisol and immunoglobulin, and most children had coronary artery lesions. In addition, Peripheral gangrene mainly occurred in the subacute or chronic stage, and the prognosis is poor. Conclusions In the presence of high risk factors, we consider it is necessary to monitor coagulation function and administer prophylactic anticoagulation therapy. When peripheral artery thrombosis or embolism occur, heparin and prostaglandins can be used for treatment.

This study investigated the anti-ascites effect of the total saponins of Phytolaccae Radix(PRTS) and the mechanism.H22 cell suspension was used(ip) to induce ascites in ICR male mice, and the model mice were randomized into model group, positive drug group(furosemide, 6 mg·kg~(-1)), total extract of Phytolaccae Radix(PRTE) group, and PRTS(1.29 g·kg~(-1)).Another 10 male mice were selected as the blank group.Mice in the blank group and model group were given(ig) normal saline containing 0.5% CMC-Na, and those in the positive drug group, PRTE group, and PRTS group received(ig) corresponding doses of drugs, once a day, for 8 consecutive days.The ascites volume, urine volume, and fecal water content in mice with ascites, serum levels of antidiure-tic hormone(ADH), renin in renin-angiotensin-aldosterone system(RAAS), angiotensin Ⅱ(AngⅡ), and aldosterone(ALD), expression of aquaporin(AQP)1-AQP4 in kidney, expression of AQP1, AQP3 in colon, and expression of phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt) pathway-related proteins were detected to explore the anti-ascites mechanism of PRTS.The results showed that the PRTS can increase the urine volume and fecal water content and decrease the ascites volume of ascites mice.Moreover, PRTS significantly reduced the expression of AQP1-AQP4 in kidney and AQP1, AQP3 in colon, serum levels of renin, AngⅡ, ALD, and ADH, and the expression of p-PI3 K and p-Akt in the kidney of ascites mice.PRTS exerts anti-ascites effect by promoting urination and defecation.The mechanism is that it inhibits the activities of RAAS and ADH and suppresses the phosphorylation of PI3 K/Akt signaling pathway, thereby restricting the expression of AQPs in the kidney and colon.

BackgroundThe role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians.MethodsThis is a retrospective, single-center study inspecting women receiving GnRH antagonist protocol and r-hFSH+hMG or r-hFSH+r-hLH regimen for over five days for COH in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in Taiwan from 2013 to 2018. The outcomes of IVF/ICSI cycles were analyzed after propensity score matching between the two groups. A subgroup analysis was conducted in cycles in which women underwent their first embryo transfer (ET), including fresh ET and frozen ET (FET).ResultsWith a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, pConclusionThe results support the hypothesis that the treatment of r-hLH+r-hFSH improves COH clinical outcomes in the IVF/ICSI cycle.

ObjectiveThe aims of the present study were to investigate gender differences in the clinicopathological features, distant metastasis and prognosis of pancreatic neuroendocrine neoplasms (pNENs) in a Chinese population, and to identify any important gaps in the classification and management of pNENs relative to gender.MethodsRetrospective collection of the clinicopathological data of 193 patients with pathologically confirmed pNENs were analyzed and follow up was extended to observe the prognosis of the disease. Differences between genders in basic characteristics, clinical symptoms, comorbidities, and tumor parameters were analyzed.ResultsThere was no significant difference in females and males, however, moderately higher for females (52.8% vs. 47.2%), with the largest subgroup being 40~60 years of age (54.9%). Age at onset (P=0.002) and age at diagnosis (P=0.005) were both younger in females compared to males. Males lived more in urban areas and females lived more in rural areas (P=0.047). The proportion of smokers and alcohol drinkers was significantly higher in males than in females (P < 0.001). Non-functional pNENs were more frequent in males and functional pNENs in females (P=0.032). In women, functional status of the tumor was significantly associated with metastatic outcome (P=0.007) and functional tumors proved to be a protective factor compared to non-functional tumors (OR=0.090,95% CI: 0.011~ 0.752). There were no gender differences in tumor size, location, grade, stage or prognosis.ConclusionsGender differences in some clinicopathological features, and distant metastasis in patients with pNENs were identified, which suggested certain management details that justified emphasis based on gender.

We analyzed the prognostic value of N6-methyladenosine (m6A) regulatory genes in lung adenocarcinoma (LADC) and their association with tumor immunity and immunotherapy response. Seventeen of 20 m6A regulatory genes were differentially expressed in LDAC tissue samples from the TCGA and GEO databases. We developed a five-m6A regulatory gene prognostic signature based on univariate and Lasso Cox regression analysis. Western blot analysis confirmed that the five prognostic m6A regulatory proteins were highly expressed in LADC tissues. We constructed a nomogram with five-m6A regulatory gene prognostic risk signature and AJCC stages. ROC curves and calibration curves showed that the nomogram was well calibrated and accurately distinguished high-risk and low-risk LADC patients. Weighted gene co-expression analysis showed significant correlation between prognostic risk signature genes and the turquoise module enriched with cell cycle genes. The high-risk LADC patients showed significantly higher PD-L1 levels, increased tumor mutational burden, and a lower proportion of CD8+ T cells in the tumor tissues and improved response to immune checkpoint blockade therapy. These findings show that this five-m6A regulatory gene signature is a prognostic biomarker in LADC and that immune checkpoint blockade is a potential therapeutic option for high-risk LADC patients.

SummaryBackground: Entrectinib is an oral, CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, tyrosine kinase ROS proto-oncogene 1, and anaplastic lymphoma kinase approved for use in patients with solid tumors. We describe 3 clinical studies, including one investigating the single/multiple dose pharmacokinetics of entrectinib in patients and two studies in healthy volunteers investigating the absorption/distribution/metabolism/excretion (ADME) of entrectinib, its relative bioavailability, and effect of food on pharmacokinetics. Methods: The patient study is open-label with dose-escalation and expansion phases. Volunteers received entrectinib (100–400 mg/m2, and 600–800 mg) once daily with food in continuous 28-day cycles. In the ADME study, volunteers received a single oral dose of [14C]entrectinib 600 mg. In the third study, volunteers received single doses of entrectinib 600 mg as the research and marketed formulations in the fasted state (Part 1), and the marketed formulation in the fed and fasted states (Part 2). Entrectinib and its major active metabolite M5 were assessed in all studies. Results: Entrectinib was absorbed in a dose-dependent manner with maximum concentrations at ~4 h postdose and an elimination half-life of ~20 h. Entrectinib was cleared mainly through metabolism and both entrectinib and metabolites were eliminated mainly in feces (minimal renal excretion). At steady-state, the M5-to-entrectinib AUC ratio was 0.5 (with 600 mg entrectinib research formulation in patients). The research and marketed formulations were bioequivalent and food had no relevant effect on pharmacokinetics. Conclusions: Entrectinib is well absorbed, with linear PK that is suitable for once-daily dosing, and can be taken with or without food.

Abnormalities in CD4+ T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve’s effect on differentiation of CD4+ T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4+ T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4+ T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4+ T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4+ T cells. The CD4+ T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4+ T cell differentiation in response to VMC.

Context Processing with vinegar could enhance the efficacy and reduce the toxicity of Curcuma phaeocaulis Valeton. (Zingiberaceae), a Chinese herbal medicine with anti-inflammatory and antitumor activities. Objective This study investigated the vinegar processing effects by evaluating anti-angiogenic effect and toxicity of C. phaeocaulis through zebrafish and rat models. Materials and methods Zebrafish embryos (AB and FLk-GFP strain) were applied to evaluate toxicity, cardiotoxicity and anti-angiogenic activity of volatile oil, and water decoction of the raw and vinegar-processed C. phaeocaulis. Meanwhile, a blood stasis syndrome rat model was applied to study the toxicity by measuring the ovarian and uterine coefficient. Results Curcuma phaeocaulis volatile oil and its vinegar-processed products in zebrafish had an LC50 of 67.315 and 95.755 μg/mL, respectively. Curcuma phaeocaulis water decoction and its vinegar-processed products had an LC50 of 161.440 and 206.239 μg/mL, respectively. The toxicity of vinegar-processed products was significantly lower than the raw, and the development characteristic of zebrafish embryos at different times confirmed these results. The volatile oil of vinegar-processed products could inhibit the growth of intersegmental blood vessels at the dose of 20 μg/mL, while the raw materials did not exhibit such effect at the same concentration. The rat experiment also confirmed that the volatile oil could reduce toxicity of ovarian and uterine. Discussion and conclusions The study indicated that processing using vinegar could decrease toxicity and increase anti-angiogenic activity of C. phaeocaulis, which could be applied for clinical treatment. Further in-depth study on the synergism and detoxification mechanism of vinegar processing technology is needed.

A disintegrin and a metalloprotease (ADAM)9 upregulated within human hepatocellular carcinoma (HCC) cells, but its effect on HCC radiosensitivity remains unknown. The present work aimed to examine the effect of ADAM9 on HCC radiosensitivity and to reveal its possible mechanism, which may be helpful in identifying a potential therapeutic strategy. Changes in ADAM9 expression after X-ray irradiation were identified using western blot, qRT-PCR, and immunofluorescence. ADAM9 stable knockdown and overexpression cell lines were constructed using lentivirus packaging. The radiosensitivity of HCC cells with altered ADAM9 expression was examined by CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays. This study also determined how autophagy affected HCC cell radiosensitivity. Furthermore, ADAM9, p62 and Bax expressions in HCC tissues that were removed after radiotherapy were detected by immunohistochemistry, and the relationship among the levels of these molecules was statistically analyzed. The level of ADAM9expression in HCC cells increased after X-ray irradiation. Through CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays, this work discovered the increased MHCC97H cell radiosensitivity after ADAM9 knockdown, and the radiosensitivity of Huh7 cells decreased after the overexpression of ADAM9. Furthermore, ADAM9 induced HCC cell autophagy via downregulating Nrf2 expression, while autophagy inhibition or induction reversed the effects of altered ADAM9 expression on radiosensitivity. Moreover, ADAM9 level showed a negative correlation with Bax and p62 expression within HCC tissues after radiotherapy. Taken together, ADAM9 decreased the radiosensitivity of HCC cells, and autophagy mediated this process.

Southwest China is home to numerous ethnic minorities, as well as many geographically and genetically isolated groups. However, the genetic substructure of these ethnic groups, especially the paternal genetic structure between groups, has not been comprehensively analyzed. In this study, we used Y chromosome capture and Illumina sequencing technologies to investigate the paternal genetic structure of three isolated groups of male unrelated individuals, including Baima in Pingwu, Sichuan Province, Muya in Shimian, Sichuan Province, and Kongge in Jinghong, Yunnan Province. We calculated the frequencies of related haplogroups by the fixed-point compound amplification method and direct counting method, and used the Past3.0 software to perform principal component analysis to draw a population clustering tree. we observed that Kongge had 3 Y chromosome haplogroups, Baima had 4 Y chromosome haplogroups, and Muya had 5 Y chromosome haplogroups. The results showed that Kongge was most closely related to the Wa, and the Y chromosome types of the Baima and Muya were mainly concentrated in the D haplogroup and its lower reaches. It has the closest relationship with the Tibetans in Qamdo and Nyingchi. The study on the genetic structure of different ethnic groups has enriched the genetic relationship of isolated populations and provided a new perspective for understanding Chinese ethnic groups.中国西南地区分布着众多少数民族,同时也包含许多地理和遗传隔离的人群,然而这些族群的遗传结构,特别是父系遗传结构缺乏深度解析。本研究采用Y染色体捕获及Illumina测序技术,对西南地区3个隔离人群男性无关个体样本,包括四川平武县的白马人、石棉县的木雅人及云南景洪市空格人,通过定点复合扩增检测,直接计数法计算相关单倍群频率,应用Past3.0软件进行PCA (principle component analysis, PCA)主成分分析并绘制群体聚类树,研究了3个族群的父系遗传结构,并探讨其遗传亚结构关系。本研究共观察到云南空格人三种Y染色体单倍群、四川白马人四种Y染色体单倍群以及木雅人五种Y染色体单倍群。结果表明,空格人与佤族的父系遗传关系最近;而白马人和木雅人主要集中在D单倍群及其下游,研究提示着白马人和四川羌族的父系遗传关系最近;木雅人与昌都地区藏族和林芝地区藏族父系遗传关系最近。本文对不同族群遗传结构的分析,丰富了我国隔离人群遗传关系的研究成果。.

Background. Associations between iodine intake and thyroid nodules (TNs) were not consistent. We aimed to illustrate the relationship between urinary iodine concentration (UIC) and TNs. Methods. A total of 12,698 participants were enrolled in analysis. All of the participants filled out questionnaires and underwent physical examinations, laboratory tests, and thyroid ultrasonography. UIC, serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured in the central laboratory. Results. The prevalence of TNs was 16.00%, and the median UIC was 206.1 μg/L. TNs and UIC were negatively related when UIC was less than 527 μg/L ( adjusted OR = 0.87 ; 95% CI, 0.80, 0.94), and the relationship between UIC and TNs was not statistically significant when UIC was greater than 527 μg/L ( adjusted OR = 1.25 ; 95% CI, 0.98, 1.60). In women, UIC was negatively associated with risk for TNs (adjusted OR 0.95; 95% CI, 0.91, 0.99). Conclusion. The relationship between TNs and UIC differed between men and women. The risk of TNs decreased with the elevation of UIC in men when UIC was lower than 527 μg/L, while UIC and the presence of TNs were negatively correlated in women. In the future, cohort studies or other studies that can explain causality must be conducted to explore the relationship between iodine status and TNs.

Objective To develop a fully automated AI system to quantitatively assess the disease severity and disease progression of COVID-19 using thick-section chest CT images. Methods In this retrospective study, an AI system was developed to automatically segment and quantify the COVID-19-infected lung regions on thick-section chest CT images. Five hundred thirty-one CT scans from 204 COVID-19 patients were collected from one appointed COVID-19 hospital. The automatically segmented lung abnormalities were compared with manual segmentation of two experienced radiologists using the Dice coefficient on a randomly selected subset (30 CT scans). Two imaging biomarkers were automatically computed, i.e., the portion of infection (POI) and the average infection HU (iHU), to assess disease severity and disease progression. The assessments were compared with patient status of diagnosis reports and key phrases extracted from radiology reports using the area under the receiver operating characteristic curve (AUC) and Cohen’s kappa, respectively. Results The dice coefficient between the segmentation of the AI system and two experienced radiologists for the COVID-19-infected lung abnormalities was 0.74 ± 0.28 and 0.76 ± 0.29, respectively, which were close to the inter-observer agreement (0.79 ± 0.25). The computed two imaging biomarkers can distinguish between the severe and non-severe stages with an AUC of 0.97 (p value < 0.001). Very good agreement (κ = 0.8220) between the AI system and the radiologists was achieved on evaluating the changes in infection volumes. Conclusions A deep learning–based AI system built on the thick-section CT imaging can accurately quantify the COVID-19-associated lung abnormalities and assess the disease severity and its progressions. Key Points • A deep learning–based AI system was able to accurately segment the infected lung regions by COVID-19 using the thick-section CT scans (Dice coefficient ≥ 0.74). • The computed imaging biomarkers were able to distinguish between the non-severe and severe COVID-19 stages (area under the receiver operating characteristic curve 0.97). • The infection volume changes computed by the AI system were able to assess the COVID-19 progression (Cohen’s kappa 0.8220). Electronic supplementary material The online version of this article (10.1007/s00330-020-07042-x) contains supplementary material, which is available to authorized users.

Currently, the prognosis of acute myeloid leukemia (AML) is poor. In the AML microenvironment, bone marrow (BM) mesenchymal stem cells (BMMSCs) serve an important role in protecting AML cells from chemotherapy‑induced apoptosis. The present study aimed to evaluate the expression of fibroblast activation protein α (FAPα) in BMMSCs and BM biopsy samples via flow cytometry, reverse transcription‑quantitative PCR and immunohistochemistry, as well as to identify the correlation between the expression of FAPα in BM with clinical parameters and survival of newly diagnosed patients with AML. Subsequently, the protective effect of FAPα on Cytosine arabinoside (Ara‑C)‑induced apoptosis in Kasumi‑1 cells was investigated via small interfering (si)RNA, and its underlying mechanism was examined by western blotting. The results demonstrated significant differences in FAPα expression in BMMSCs and BM biopsy samples between patients with AML and healthy donors. Furthermore, BMMSCs protected Ara‑C‑induced Kasumi‑1 cells from apoptosis, and knockdown of FAPα using siRNA decreased this protection. It was found that Kasumi‑1 cells expressed β‑catenin, which could be inhibited by Ara‑C, and β‑catenin expression was significantly activated when co‑cultured with BMMSCs, even in the presence of Ara‑C. Knockdown of FAPα with siRNA significantly suppressed the expression of β‑catenin. The present results indicated that FAPα serves an important role in the AML BM microenvironment, and that increased expression of FAPα in BM may be a poor prognostic factor in patients with AML. Moreover, the current findings demonstrated that BMMSCs protected AML cells from apoptosis, which was in part contributed by FAPα, and may occur via the β‑catenin signaling pathway.

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3‐internal tandem duplication (FLT3‐ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPA double mutation. In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse‐free survival (RFS), DNMT3A, FLT3‐ITD, or RUNX1 mutation predicted a higher likelihood of remission‐induction failure, whereas NRAS mutation or CEBPA double mutation predicted longer OS. Concurrent DNMT3A, FLT3‐ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation‐related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next‐generation sequencing screening., Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations.

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard regimen for patients with locally advanced rectal cancer (LARC). However, whether and to which extent neoadjuvant radiotherapy could be removed from nCRT for patients with LARC is still unclear. This was a multicenter, retrospectively recruited, prospectively maintained cohort study. A propensity score matching model was employed to minimize potential confounding factors between subgroup patients treated with neoadjuvant chemotherapy (nCT) or nCRT. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed between subgroup patients by Kaplan‐Meier analysis, log‐rank test, and Cox regression model. In total, 3233 consecutive patients, consist of 571 nCT and 2662 nCRT‐treated cases, were included. After propensity score matching (1:4), 565 nCT‐treated patients were matched to 1852 nCRT‐treated patients. Compared with nCT, nCRT treatment indeed decreased 3‐y local recurrence (10.0% vs 6.6%, P = .026), but had no impact on OS, DFS and DMFS (all P > .05) for LARC. Stratified analysis further confirmed that nCRT treatment was associated with higher 3‐y LRFS and 3‐y DFS than nCT treatment for baseline high‐risk subgroup (cT4, cN+, and cIII stage) patients (all P < .05). Conversely, for the baseline low‐risk subgroup patients (cT3, cN0, and cII stage), nCRT and nCT treatment had similar 3‐y OS, LRFS, DFS, and DMFS (all P > .05). The administration of neoadjuvant radiotherapy for LARC patients might be determined by baseline risk classification, the high‐risk individuals could be delivered while low‐risk patients might be omitted., Neoadjuvant radiotherapy could not increase survival for baseline low‐risk (cT3, cN0, cII stage) subgroup locally advanced rectal cancer patients. But neoadjuvant radiotherapy should not be removed from neoadjuvant treatment regimen for the baseline high‐risk (cT4, cN+, cIII) subset locally advanced rectal cancer patients.

Background/purpose Eosinophils are recruited to the brain of mice after infection with Angiostrongylus canonensis. Several factors produced by infected mice are well known playing the role to chemoattract eosinophils from the blood into the brain. The purpose of this study is to investigate whether Angiostronylus cantonensis young-adult worms (AcYA) have components which have eosinophilic chemotactic activity. Methods Eosinophil chemotactic activity of AcYA was tested by Boyden blind-well chamber technique. The components of AcYA were analysed by SDS-PAGE and Mass spectrometry. Furthermore, galectin-9 in the cerebrospinal fluid (CSF) of infected mice and galectin-9-like in AcYA were measured by ELISA technic and also were recognized by western blot analysis respectively. Results Excretory-secretory products of AcYA did not show eosinophil chemotactic activity. However, the extracts of AcYA showed protein concentration-dependent eosinophil chemotactic activity and reached the peak at the 24 μg/ml. The eosinophil chemotactic activity was significantly reduced by lactose. The components of AcYA at molecular weights of approximatively 15 kDa and 35 kDa showed several galectins component in Mass spectrometric analysis. Furthermore, galectin-9-like in AcYA was recognized by ELISA and western blot analysis. In parallel with increase of galectin-9 in the CSF, eosinophils were also significantly increased in mouse after infected with A. cantonensis. Conclusion Galectin-9-like in AcYA and galectin-9 in mouse CSF were confirmed demonstrating eosinophil chemotactic activity both in vitro study and in the infection of mouse in this study.

Tinnitus has been implied as a “soft” sign of neurodegenerative disease, which is characterized by progressive loss of neuronal function, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This study aimed to determine whether the risk of developing AD/PD increases after having tinnitus. We conducted a retrospective matched cohort study with 12,657 tinnitus patients and 25,314 controls from the National Health Insurance Research Database (NHIRD) in Taiwan with almost 10 years follow-up. Tinnitus-related risk on developing AD/PD followingly was determined by the Cox regression to identify potential confounding factors. Through the 10-year follow-up period, 398 individuals with tinnitus (3.1%) and 501 control individuals (2.0%) developed AD (P P P P

Background: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. Methods: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. Results: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P

The tripartite motif (TRIM) family proteins play a great role in carcinogenesis. However, the expression pattern, prognostic value and biological functions of tripartite motif containing 23 (TRIM23) in colorectal cancer (CRC) are poorly understood. Here, we found that TRIM23 is up‐regulated and associated with tumour size, lymph node metastasis, American Joint Committee on Cancer (AJCC) stage and poor prognosis in CRC. Multivariate Cox regression analyses revealed that TRIM23 overexpression could be identified as an independent prognostic factor for CRC. TRIM23 could promote the proliferation of CRC cell in vitro and in vivo; additionally, TRIM23 depletion induced G1­phase arrest. Gene set enrichment analysis (GSEA) revealed that P53 and cell cycle signalling pathway‐related genes were enriched in patients with high TRIM23 expression levels. We show in this study that TRIM23 physically binds to P53 and enhances the ubiquitination of P53, thereby promoting tumour proliferation. Thus, our data indicated that TRIM23 acts as an oncogene in colorectal carcinogenesis and may provide a novel therapeutic target for CRC management.

Exposure to organic solvent in industry, including n-hexane is correlated with central-peripheral axonopathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). However, the underlying mechanism is still largely unknown. Recently identified microRNAs (miRNAs) may play important roles in toxicant exposure and in the process of toxicant-induced neuropathys. To examine the role of miRNAs in HD-induced toxicity, neuropathic animal model was successfully built. miRNA microarray analysis revealed 105 differentially expressed miRNAs after HD exposure. Bioinformatics analysis showed that "Axon" and "Neurotrophin Signaling Pathway" was the top significant GO term and pathway, respectively. 7 miRNAs both related to "Axon" and "Neurotrophin Signaling Pathway" were screened out and further confirmed by Real-Time PCR. Correspondingly, the deregulation expression levels of proteins of four target genes (GSK3β, Map3k1, BDNF and MAP1B) were further confirmed via western blot, verifying the results of gene target analysis. Taken together, our results showed that the axon-related miRNAs to be associated with MAP1B or neurotrophin signal pathways changed in nerve tissues following HD exposure. These miRNAs may play important roles in HD-induced neurotoxicity.

Purpose This study was to investigate the mechanism of intestinal physical and immune barriers in the occurrence of high-intensive exercise-induced gastrointestinal symptoms. Methods An overtraining model of male C57BL/6 mice was established by running-to-exhaustive exercise. Then, the mice were sacrificed, and a series of evaluation indicators, including the routine blood analysis as well as histological examinations, inflammatory factors, ultrastructure observation, and intestinal permeability of the gut, were measured based on this model. The expressions of inflammatory factors tumor necrosis factor α, interferon-γ, and interleukin (IL)-6 as well as the tight junction and adherence junction proteins ZO-1, Occludin, Claudin-1, and E-cadherin were measured, respectively. Furthermore, the mRNA level of IL-22 and the proportion of ILC3 and IL-22 produced in CD4 T cells in lamina propria lymphocytes (LPL) were analyzed by flow cytometry. Besides, the liver glycogen and the expressions of sirtuins-3 and hypoxia-inducible factor-1a, which were associated with the intestinal metabolism phenotype, were analyzed by Western blotting. Results Exhaustive exercise induced a disrupted intestinal barrier integrity, an aggravated intestinal inflammation, increased gut permeability, and the reduced IL-22 mRNA level. Compared with the nonexercise mice, the IL-22 produced in LPL was reduced followed by exhaustive exercise, whereas the proportion of IL-22 produced in CD4 T cells was still unchanged. Significantly, the proportion of ILC3 in the LPL was decreased obviously, including the NCR ILC3. Furthermore, the intestinal metabolism phenotype assessment showed lower liver glycogen and blood glucose as well as higher blood lactic acid and hypoxia-inducible factor-1a, respectively. Conclusions The data indicated that the acute high-intensity running-induced gastrointestinal symptom is closely associated with a reduced percentage of ILC3 and IL-22 level in the LPL, possibly due to the glycogen exhaustion and intestinal mucosa hypoperfusion.

Objective The development of blood-based biomarkers for early diagnosis and treatment of Alzheimer’s disease (AD) is desirable. In AD model mouse brain and neuronal cells, Abelson helper integration site-1 (AHI1) protein is reduced. AHI1 facilitates intracellular amyloid precursor protein (APP) translocation to inhibit amyloidogenic pathology of AD , and thus may be an AD biomarker . Methods This study was conducted among 32 AD patients and 54 healthy control (HC) subjects. AHI1-related protein levels from initially collected serum samples in each group were screened using Western blotting . The protein concentrations of AHI1 and amyloid-β (Aβ), peptide(s) derived from APP, from all serum samples were analyzed using ELISA. Results In AD serum, AHI1 and a large truncated C-terminal APP fragment were significantly reduced. The average concentrations of serum AHI1 and Aβ in AD were significantly lower than those in HC. Notably, AHI1 concentration in HC serum was decreased in an age-dependent manner, while it was consistently low in AD serum and had no correlation with Aβ or mini-mental state examination score. The receiver operating characteristic analysis on all subjects demonstrated an area under curve (AUC) value of 0.7 for AHI1 on AD diagnosis, while the AUC increased to 0.82 on the subjects younger than 77 years old, suggesting a good diagnostic performance of serum AHI1 for AD especially at relatively young age. Conclusion An early event of AHI1 reduction in the body of AD patients was observed. Serum AHI1 may be valuable for early diagnosis of AD .

Patients with diabetes mellitus have a higher risk of developing Parkinson's disease (PD). However, the molecular links between PD and diabetes remain unclear. In this study, we investigated the roles of thioredoxin-interacting protein (TXNIP) in Parkin/PINK1-mediated mitophagy in dopaminergic (DA) cells under high-glucose (HG) conditions. In streptozotocin-induced diabetic mice, TXNIP was upregulated and autophagy was inhibited in the midbrain, while the loss of DA neurons was accelerated by hyperglycemia. In cultured PC12 cells under HG, TXNIP expression was upregulated and the intracellular reactive oxygen species (ROS) levels increased, leading to cell death. Autophagic flux was further blocked and PINK1 expression was decreased under HG conditions. Parkin expression in the mitochondrial fraction and carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced co-localization of COX IV (marker for mitochondria) and LAMP1 (marker for lysosomes) were also significantly decreased by HG. Overexpression of TXNIP was sufficient to decrease the expression of both PINK1 and Parkin in PC12 cells, while knockdown of the expression of TXNIP by siRNA decreased intracellular ROS and attenuated cellular injury under HG. Moreover, inhibition of TXNIP improved the CCCP-induced co-localization of COX IV and LAMP1 in PC12 cells under HG. Together, these results suggest that TXNIP regulates Parkin/PINK1-mediated mitophagy under HG conditions, and targeting TXNIP may be a promising therapeutic strategy for reducing the risk of PD under hyperglycemic conditions.

The accurate diagnosis of small cell lung cancer (SCLC) at initial presentation is essential to ensure appropriate treatment. No validated blood biomarkers that could distinguish SCLC from non-small cell lung cancer (NSCLC) has yet been developed. Dried blood spot (DBS) microsampling has gained increasing interest in biomarkers discovery. In this study, we first performed metabolomic profiling of DBS samples from 37 SCLC, 40 NSCLC, and 37 controls. Two gender-specific multianalyte discriminant models were established for males and females, respectively to distinguish SCLC from NSCLC and controls. The receiver operator characteristic (ROC) curve analysis showed the diagnostic accuracy of 95% (95% CI: 83%-100%) in males SCLC using five metabolites in DBS and 94% (95% CI: 74%-100%) for females using another set of five metabolites. The robustness of the models was confirmed by the random permutation tests (P < 0.01 for both). The performance of the discriminant models was further evaluated using a validation cohort with 78 subjects. The developed discriminant models yielded an accuracy of 91% and 81% for males and females, respectively, in the validation cohort. Our results highlighted the potential clinical utility of the metabolomic profiling of DBS as a convenient and effective approach for the diagnosis of SCLC.

Acute myeloid leukemia (AML) is a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is down-regulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. The present study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.

The insufficient volume of lip is one of the pathological problems of cleft lip, despite that the cleft lip the muscles and skin are repositioned. Autologous fat is an ideal material for soft tissue repair, including correction of contour deformity, restoration of volume insufficient, and even improvement of tissue characteristics. In this study, the authors evaluated the result of fat grafting in improvement of lip contour in secondary cleft lip deformity. The authors performed a retrospective analysis of their series of patients who underwent lip fat grafting. A total of 65 subjects with lip fat grafting for cleft lip revision were recruited for the study. The photographs documented the original malformation and the posttreatment photographs. The authors recruited female and male raters, who were experts in the field or lay persons to form a panel of 12 raters altogether. Symmetry and aesthetics were improved after fat grafting based on vermillion border (P = 0.02), symmetry of lip (P = 0.007), and nasal profile including upper lip (P = 0.04) using a 1- to 5-point scale. After treatment, both sides of the lip are more symmetrical, the thickness of the filling part is significantly increased, the filling area is soft, the appearance is satisfied. Fat grafting is an efficient secondary procedure to improve lip contour after cleft lip repairs.

Hydroxycinnamic acids (HAs) are widely spread in food and herbal medicines. The bioavailability of HAs largely depends on the absorption and metabolism in enterohepatic circulation, in which gut microbiota plays a vital role. The present research aims to investigate the metabolism of HAs by gut microbiota, together with the community changes of gut microbiota after cerebral ischemia-reperfusion (I/R) injury. The results showed that non-substituted cinnamic acid (NCA) and sinapic acid (SA) were stable to gut microbiota, while 4-hydrocinnamic acid (4-HA), caffeic acid (CA), and ferulic acid (FA) underwent decarboxylation and hydrogenation after anaerobic incubation. Time-course studies indicated that the gut microbiota from I/R injured rats can catalyze the same reaction, but with a decreased reaction rate. The 16S rRNA sequencing technique was applied to uncover the community changes of gut microbiota. In addition, the metabolites of the three HAs exhibited greater activity in scavenging the DPPH radical and protected PC12 cells against oxidative damage.

Emerging evidence is revealing that microRNAs (miRNAs) play essential roles in mechanosensing for regulating osteogenesis. However, no mechanoresponsive miRNAs have been identified in human bone specimens. Methods: Bedridden and aged patients, hindlimb unloaded and aged mice, and Random Positioning Machine and primary aged osteoblasts were adopted to simulate mechanical unloading conditions at the human, animal and cellular levels, respectively. Treadmill exercise and Flexcell cyclic mechanical stretching were used to simulate mechanical loading in vivo and in vitro, respectively. Results: Here, we found increased miR-138-5p levels with a lower degree of bone formation in bone specimens from bedridden and aged patients. Loss- and gain-of-function studies showed that miR-138-5p directly targeted microtubule actin crosslinking factor 1 (MACF1) to inhibit osteoblast differentiation under different mechanical conditions. Regarding translational medicine, bone-targeted inhibition of miR-138-5p attenuated the decrease in the mechanical bone anabolic response in hindlimb unloaded mice. Moreover, bone-targeted inhibition of miR-138-5p sensitized the bone anabolic response to mechanical loading in both miR-138-5p transgenic mice and aged mice to promote bone formation. Conclusion: These data suggest that miR-138-5p as a mechanoresponsive miRNA accounts for the mechanosensitivity of the bone anabolic response and that inhibition of miR-138-5p in osteoblasts may be a novel bone anabolic sensitization strategy for ameliorating disuse or senile osteoporosis.

Formononetin is a type of phytoestrogen obtained from the Chinese medical herb Red Clover. It exhibits anti-neoplastic hepatoprotective, and neuroprotective properties. However, the anti-inflammatory effect of formononetin in cerebral ischemia-reperfusion injury has not been reported.To explore the potential mechanism of action of formononetin in cerebral ischemia-reperfusion injury with regard to the JAK2/STAT3 signaling pathway.Male SD rats were used to establish a middle cerebral artery occlusion (MCAO) model and randomly divided into 5 groups: Sham, MCAO, JAK2 Inhibitor (Ag490), Formononetin, Inhibitor + Formononetin. The protective effect of formononetin in MCAO rats was detected by performing neurological deficit testing, TTC staining, HE staining, Nissl staining, ELISA, RT-PCR, western blotting and immunofluorescence.Formononetin significantly alleviated the neurological deficit and the pathological state of brain tissues, and reduced the volume of cerebral infarction, levels of IL-18 and TNF-α inflammatory factors in plasma, mRNA levels of IL-6 and IL-1β in rat brain tissue, and the protein levels of p-JAK2, p-STAT3, NLRP3, ASC, cl-Caspase-1, and cl-IL-1β in the MCAO rat brain tissue.Formononetin has anti-inflammatory effects. It may inhibit the relevant targets in the JAK2/STAT3 signaling pathway, thereby having a certain protective effect against cerebral ischemia-reperfusion injury.

ObjectiveMycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community acquired pneumonia. With the outbreak of coronavirus disease 2019 (COVID-19), the prevalence of some infectious respiratory diseases has varied. Epidemiological features of M. pneumoniae in children from Beijing (China) before and during the COVID-19 pandemic were investigated.MethodsBetween June 2016 and May 2021, a total of 569,887 children with respiratory infections from Children’s Hospital Affiliated to Capital Institute of Pediatrics (Beijing, China) were included in this study. M. pneumoniae specific-IgM antibody in serum specimens of these patients was tested by a rapid immunochromatographic assay kit. The relevant clinical data of M. pneumoniae-positive cases were also collected, and analyzed by RStudio software.ResultsThe results showed that 13.08% of collected samples were positive for M. pneumoniae specific-IgM antibody. The highest annual positive rate was 17.59% in 2019, followed by 12.48% in 2018, 12.31% in 2017, and 11.73% in 2016, while the rate dropped to 8.9% in 2020 and 4.95% in 2021, with significant difference. Among the six years, the positive rates in summer and winter seasons were significantly higher than those in spring and autumn seasons (p < 0.001). The positive rate was the highest in school-age children (22.20%), and lowest in the infant group (8.76%, p < 0.001). The positive rate in boys (11.69%) was lower than that in girls (14.80%, p < 0.001). There were no significant differences in different seasons, age groups, or genders before and during the COVID-19 pandemic (p > 0.05).ConclusionsOur study demonstrated that an M. pneumoniae outbreak started from the summer of 2019 in Beijing. After the COVID-19 pandemic outbreak in the end of 2019, the M. pneumoniae positive rates dropped dramatically. This may be due to the restrictive measures of the COVID-19 pandemic, which effectively controlled the transmission of M. pneumoniae. The relationships between M. pneumoniae positive rates and season, age, and gender were not statistically significant before and during the COVID-19 pandemic.

A new genus of the primitively segmented trapdoor spiders, which is endemic to the north of China, is described, Luthela gen. nov., and the status of Sinothela Haupt, 2003 and Sinothela sinensis (Bishop & Crosby, 1932) is discussed and both are treated as nomina dubia. The new genus Luthela gen. nov. is erected based on morphology and molecular data of the type species Luthela yiyuan sp. nov. A taxonomic revision of the new genus is given. Three Sinothela species are transferred to the new genus, L. luotianensis comb. nov. and L. schensiensis comb. nov. are redescribed using our newly collected specimens, include L. heyangensis comb. nov. as a junior synonym of L. schensiensis comb. nov., and describe six new species based on both male and female morphological characters: L. badong sp. nov., L. dengfeng sp. nov., L. handan sp. nov., L. taian sp. nov., L. yiyuan sp. nov., and L. yuncheng sp. nov.