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The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

COVID-19, referred to as new coronary pneumonia, is an acute infectious disease caused by a new type of coronavirus SARS-CoV-2. To evaluate the effect of integrated Chinese medicine and Western medicine in patients with COVID-19 from overseas. Data were collected from 178 COVID-19 patients overseas at First Affiliated Hospital of Xiamen University from April 1, 2021 to July 31, 2021. These patients received therapy of integrated Chinese medicine and western medicine. Demographic data and clinical characteristics were extracted and analyzed. In addition, the prescription which induced less length of PCR positive days and hospitalization days than the median value was obtained. The top 4 frequently used Chinese medicine and virus-related genes were analyzed by network pharmacology and bioinformatics analysis. According to the chest computed tomography (CT) measurement, abnormal lung findings were observed in 145 subjects. The median length of positive PCR/hospitalization days was 7/7 days for asymptomatic subjects, 14/24 days for mild subjects, 10/15 days for moderate subjects, and 14/20 days for severe subjects. The most frequently used Chinese medicine were Scutellaria baicalensis (Huangqin), Glycyrrhiza uralensis (Gancao), Bupleurum chinense (Chaihu), and Pinellia ternata (Banxia). The putative active ingredients were baicalin, stigmasterol, sigmoidin-B, cubebin, and troxerutin. ACE, SARS-CoV-2 3CL, SARS-CoV-2 Spike, SARS-CoV-2 ORF7a, and caspase-6 showed good binding properties to active ingredients. In conclusion, the clinical results showed that integrated Chinese medicine and Western medicine are effective in treating COVID-19 patients from overseas. Based on the clinical outcomes, the putative ingredients from Chinese medicine and the potential targets of SARS-CoV-2 were provided, which could provide a reference for the clinical application of Chinese medicine in treating COVID-19 worldwide.

To analyze the relationship between food intake and chronic diseases of Dulong minority residents living in Yunnan Province.460 Dulong minority residents 6-80-year-old among 304 families(male 191, female 269, children and adolescents aged 6-17 years old 56, aged 18-44 years old 229, aged 45-59 years old 123, aged 60-80 years old 52)in Gongshan County in Yunnan Province were selected with Stratified multistage cluster sampling method. To apply the method of food frequency questionnaire and questionnaire survey obtain the condition of dietary structure and overweight or obesity, diabetes and dyslipidemia among Dulong minority. Non-conditional Logistic regression analysis was utilized to analyze the correlation between food intake and chronic diseases.The prevalence of overweight or obesity, hypertension, diabetes and dyslipidemia were respectively 20.4%, 19.6%, 32.4% and 50.4% in 2016. Marital status and consumption of melons vegetables(OR=0.540, 95%CI 0.306-0.954), benevolence fruit kind fruit(OR=0.348, 95%CI 0.171-0.706) and low fat milk powder(OR=5.267, 95%CI 1.266-21.911) in the past 12 months were associated with hypertension among the Dulong minority population. For the Dulong minority residents, sex, eaten deep-fried dough stick(OR=0.403, 95%CI 0.182-0.894) in the past 12 months, solanaceous vegetables(OR=0.478, 95%CI 0.275-0.832) and whole milk powder(OR=2.090, 95%CI 1.372-3.184) have something to do with diabetes. Occupation, consumption of beancurd and bamboo vegetables(OR=4.753, 95%CI 1.079-20.937), solanaceous vegetables(OR=2.842, 95%CI 1.175-6.871) and edible fungi(OR=1.794, 95%CI 1.116-2.883) over the past 12 months were linked to the prevalence of overweight. Consumption of fresh legumes(OR=1.991, 95%CI 1.130-3.507), whole milk powder(OR=2.342, 95%CI 1.535-3.575), cooked poultry meat(OR=2.092, 95%CI 1.147-3.815), grass carp(OR=0.580, 95% CI 0.379-0.888)and fresh eggs(OR=0.432, 95%CI 0.196-0.950) and in the past 12 months were associated with dyslipidemia among the Dulong minority residents.The prevalence of overweight/obesity was mainly related to occupation, consumption of vegetables and products(solanaceous vegetables, edible fungi), and hypertension was mainly related to Marital status, and the intake of melons vegetables, benevolence fruit kind fruit, low fat milk powder), and diabetes was mainly related to sex, deep-fried dough stick, solanaceous vegetables and whole milk powder, and dyslipidemia was mainly related to Marital status, fresh legumes, whole milk powder, cooked poultry meat, grass carp, and fresh eggs for the Dulong nationality residents aged 6-80 years old in Gongshan County, Yunnan Province.

Prostate cancer (PCa) is the most common new cancer case and the second most fatal malignancy in men. Surgery, endocrine therapy, radiotherapy and chemotherapy are the main clinical treatment options for PCa. However, most prostate cancers can develop into castration-resistant prostate cancer (CRPC), and due to the invasiveness of prostate cancer cells, they become resistant to different treatments and activate tumor-promoting signaling pathways, thereby inducing chemoresistance, radioresistance, ADT resistance, and immune resistance. Nanotechnology, which can combine treatment with diagnostic imaging tools, is emerging as a promising treatment modality in prostate cancer therapy. Nanoparticles can not only promote their accumulation at the pathological site through passive targeting techniques for enhanced permeability and retention (EPR), but also provide additional advantages for active targeting using different ligands. This property results in a reduced drug dose to achieve the desired effect, a longer duration of action within the tumor and fewer side effects on healthy tissues. In addition, nanotechnology can create good synergy with radiotherapy, chemotherapy, thermotherapy, photodynamic therapy and gene therapy to enhance their therapeutic effects with greater scope, and reduce the resistance of prostate cancer. In this article, we intend to review and discuss the latest technologies regarding the use of nanomaterials as therapeutic and diagnostic tools for prostate cancer.

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.

Background Experimental and observational research suggests that combined epidural–general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural–general anesthesia improves long-term survival in elderly patients. Methods This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. Results Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural–general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural–general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural–general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural–general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. Conclusions In elderly patients having major thoracic and abdominal surgery, combined epidural–general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition. Case presentation A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up. Conclusions Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.

To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML).98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve.After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR1, P0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR1, P0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone.The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.基于决策曲线分析血清TGF-β1、EGFR水平对急性髓系白血病患者大剂量AraC治疗效果的影响.基于决策曲线分析血清转化生长因子-β1（TGF-β1）、表皮生长因子受体（EGFR）水平对急性髓系白血病（AML）患者大剂量阿糖胞苷（HD-AraC）治疗效果的影响.选取2019年1月-2020年6月本院收治的98例AML患者作为研究对象，所有患者均采用HD-AraC治疗，每周1个疗程，共治疗1个疗程。于治疗1个疗程时评估效果分为有效与无效2组，设计基线资料统计表，详细统计2组基线资料，比较2组基线资料及血清TGF-β1、EGFR水平，Logistic回归分析血清TGF-β1、EGFR水平与AML患者HD-AraC治疗效果的关系，绘制ROC曲线及决策曲线分析血清TGF-β1、EGFR水平预测AML患者HD-AraC治疗效果的价值.经1个疗程治疗后，98例患者中完全缓解26例，部分缓解38例，未缓解34例，总有效64例，占比65.31%；对比2组资料后经Logistics回归分析结果显示，治疗前血清EGFR过表达可能是AML患者HD-AraC治疗无效的风险因子（OR＞1，P＜0.05），治疗前血清TGF-β1过表达可能是AML患者HD-AraC治疗无效的保护因子（OR＜1，P＜0.05）； ROC曲线分析结果显示，治疗前血清EGFR、TGF-β1水平预测AML患者HD-AraC治疗无效风险的AUC均＞0.70，有一定的预测价值。绘制决策曲线结果显示，在阈值0.15-0.44范围内，联合血清EGFR、TGF-β1水平的预测模型预测AML患者HD-AraC治疗效果的净受益率优于单纯血清EGFR或单纯血清TGF-β1.血清TGF-β1、EGFR水平影响AML患者HD-AraC治疗效果，可增加治疗无效风险，血清TGF-β1、EGFR可用于AML患者HD-AraC治疗无效风险预测，且联合预测净受益率更高.

Chondroitin sulfate (CS) is a kind of linear polysaccharide that is covalently linked to proteins to form proteoglycans. Chondroitin sulfate proteoglycans (CSPGs) consist of a core protein, with one or more CS chains covalently attached. CSPGs are precisely regulated and they exert a variety of physiological functions by binding to adhesion molecules and growth factors. Widely distributed in the nervous system in human body, CSPGs contribute to the major component of extracellular matrix (ECM), where they play an important role in the development and maturation of the nervous system, as well as in the pathophysiological response to damage to the central nervous system (CNS). While there are more than 30 types of CSPGs, this review covers the roles of the most important ones, including versican, aggrecan, neurocan and NG2 in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The updated reports of the treatment of neurodegenerative diseases are involving CSPGs.

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson’s disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) −124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.

Background: Dysfunction of the corticostriatal network has been implicated in the pathophysiology of schizophrenia, but findings are inconsistent within and across imaging modalities. We used multimodal neuroimaging to analyze functional and structural connectivity in the corticostriatal network in people with schizophrenia and unaffected first-degree relatives. Methods: We collected resting-state functional magnetic resonance imaging and diffusion tensor imaging scans from people with schizophrenia (n = 47), relatives (n = 30) and controls (n = 49). We compared seed-based functional and structural connectivity across groups within striatal subdivisions defined a priori. Results: Compared with controls, people with schizophrenia had altered connectivity between the subdivisions and brain regions in the frontal and temporal cortices and thalamus; relatives showed different connectivity between the subdivisions and the right anterior cingulate cortex (ACC) and the left precuneus. Post-hoc t tests revealed that people with schizophrenia had decreased functional connectivity in the ventral loop (ventral striatum–right ACC) and dorsal loop (executive striatum–right ACC and sensorimotor striatum–right ACC), accompanied by decreased structural connectivity; relatives had reduced functional connectivity in the ventral loop and the dorsal loop (right executive striatum–right ACC) and no significant difference in structural connectivity compared with the other groups. Functional connectivity among people with schizophrenia in the bilateral ventral striatum–right ACC was correlated with positive symptom severity. Limitations: The number of relatives included was moderate. Striatal subdivisions were defined based on a relatively low threshold, and structural connectivity was measured based on fractional anisotropy alone. Conclusion: Our findings provide insight into the role of hypoconnectivity of the ventral corticostriatal system in people with schizophrenia.

The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

To analyzing the malnutrition status and influencing factors of children under 5 years in Yunnan Province.Multi-stage stratified sampling used in the national survey was performed. The subjects of the study were 2869 children under 5 years, selected from 13 counties(cities) in Yunnan Province from 2016 to 2017. The contents of the investigation included questionnaire survey and anthropometric measurement. Z-scores were calculated according to WHO growth standards by WHO Anthro V3.2.2 software. Non conditional Logistic regression model was used to analyze the multiple factors. SPSS 20.0 statistical software was used to calculate and analyze the malnutrition rate of children.A total of 2869 children under 5 years old were investigated in Yunnan Province, including 1433 boys(49.95%) and 1436 girls(50.05%). The prevalence of stunting, underweight and wasting of children under 5 years old were 3.46%, 6.37% and 3.42%. Logistic multifactor regression analysis showed that low birth weight(OR=4.368, 95% CI 2.057-9.275), rural area(OR=1.931, 95% CI 1.076-3.462), household use of unsanitary toilets(OR=1.688, 95% CI 1.022-2.790), children without supplemental food(OR=2.000, 95% CI 1.130-3.542) were the most important factors making the child more likely to become malnutrition in 6-23 month age group. Asking children for advice on food selection or cooking(OR=3.570, 95%CI 1.249-10.204) was the most important factors making the child more likely to become malnutrition in 6-23 month age group.The nutritional status of children under 5 years old in Yunnan Province has been improved, but the prevalence of malnutrition is still high.

Gliomas account for 75% of the primary malignant brain tumors and a majority of lower-grade gliomas (LGG) inevitably develop into glioblastoma. The dysregulation of lncRNAs play a crucial role in LGG. In the present study, we first screened out six differentially expressed lncRNAs (AC021739.2, AL031722.1, AL354740.1, FGD5-AS1, LINC00844, and NEAT1) based on TCGA and GTEx RNA-seq databases. LncRNA prognostic signature was then established by Kaplan-Meier and multivariate Cox proportional hazards regression, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. After lncRNA-miRNA-mRNA regulatory networks were established by Cytoscape 3.7.2, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, with results enriched in various malignancy-related functions and pathways. Finally, six putative drugs (irinotecan, camptothecin, mitoxantrone, azacitidine, mestranol, and enilconazole) were predicted by Connectivity Map. In conclusion, we identified a 6-lncRNA prognostic signature with its ceRNA networks, and six candidate drugs against LGG.

Human urine-derived stem cells (hUSCs) show multipotential differentiation ability and can differentiate into mesodermal cell lineages. Interstitial cells of Cajal-like cells (ICC-LCs) are crucial for the pace-making function of spontaneous contraction in the bladder. However, the mechanisms by which hUSCs generate ICC-LCs have not been elucidated. In this study, we developed a strategy for directional differentiation of hUSCs into ICC-LCs. hUSCs were transfected with lentiviral vectors encoding c-Kit, stem cell factor (SCF), hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4), and 5-azacytidine induced 2 (AZI2) genes, and the cells were cultured for an additional 7 days in specific medium. The expression of the surface marker c-Kit on ICC-LCs was determined at 7 days after transfection. hUSCs were successfully expanded and transfected with the four lentiviral vectors. hUSCs transfected with lentiviral-c-Kit, lentiviral-HCN4, and lentiviral-AZI2 showed higher expression of c-Kit 7 days after transfection, but only the lentiviral-HCN4-transfected cells showed morphological alterations in ICC-LCs. These cells also displayed visible HCN current amplitude and density. This approach may provide a new strategy for the treatment of underactive bladder.

Background Controlling the blood glucose level is an effective method to reduce type 2 diabetes and prevent diabetes-related complications. Ursolic acid is a plant extract that can reduce postprandial hyperglycemia effectively. This study aimed to explore the inhibitory effect and interaction mechanism of ursolic acid against α-amylase and α-glucosidase. Results In this study, the effect of ursolic acid on glycosidase was studied in vitro, in vivo, and in silico. The half-maximal inhibitory concentration (IC50 ) of ursolic acid on α-amylase and α-glucosidase was 0.482 ± 0.12 mg mL-1 and 0.213 ± 0.042 mg mL-1 , respectively. The results of enzymatic kinetics showed that ursolic acid inhibited α-amylase and α-glucosidase activity in a non-competitive manner. The fluorescence spectrum showed that the combination of ursolic acid and glycosidase caused the intrinsic fluorescence quenching of glycosidase. The observation of starch granules revealed that the activity of α-amylase was inhibited and the hydrolysis of starch granules was prevented in the presence of ursolic acid. Molecular docking results showed that ursolic acid bound to the inactive site of α-amylase and α-glucosidase through the formation of ursolic acid-glucosidase complex. Ursolic acid interacted with α-amylase and α-glucosidase mainly through hydrogen bonding. The postprandial hypoglycemic effect of ursolic acid in C57BL/6J mice showed that the high concentration of ursolic acid could quickly reduce postprandial blood glucose level. Conclusion Ursolic acid can be considered as a natural ingredient in functional foods to control postprandial blood glucose levels and prevent diabetes by delaying the digestion of starch in foods. © 2019 Society of Chemical Industry.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation has been clearly defined in congenital absence of the vas deferens (CAVD), which is an important cause of obstructive azoospermia. However, the association between oligoasthenospermia and CFTR gene mutation remains controversial. To confirm this issue, 151 infertile Chinese men were screened for CFTR mutation by NGS approach, including 18 CAVD patients, 72 patients with severe oligoasthenospermia and 61 controls with normal sperm parameters. Frequency of mutation in exons of CFTR gene were 66.7% in CAVD patients (12/18) (p 0.001) and 8.33% in severe oligoasthenospermic patients (6/72) (p 0.05), both of which were significantly more frequent than that in the controls (0/61). In terms of introns mutation of CFTR gene, there was no significant difference in frequency of 5T between oligoasthenospermic men (5/144, 3.47%) and the controls (4/122, 3.28%) (p = 0.645). In addition, 6 novel mutations in exons of CFTR gene in this study (c.3736AG, c.635TG, c.482delA, c.1858CT, c.2042AT, c.1586AC) have not been reported in the Cystic Fibrosis Mutation Database before. Thus, our study provides evidence that CFTR gene mutation may be the aetiology of severe oligoasthenospermia other than CAVD. It may be necessary to screen for CFTR mutations in men with severe oligoasthenospermia before receiving assisted reproductive technology.

Background Social support is an important health determinant and may affect dietary behaviors. The purpose of this study was to examine the relations between perceived social support and the Chinese Diet Balance Index-16 (DBI-16) among ethnic minority groups in Southwest China. Methods This cross-sectional study was conducted between May 2019 and August 2020 among six ethnic minority groups native to Yunnan Province (n = 3564). Perceived social support from family, friends and significant others were measured with the Multi-dimensional Scale of Perceived Social Support (MSPSS). Dietary data were obtained using a 100-item Food Frequency Questionnaire (FFQ) and a lifestyle questionnaire. Lower Bound Score (LBS), Higher Bound Score (HBS) and Diet Quality Distance (DQD) which represent inadequate, excessive and unbalanced food intake respectively were calculated to measure the compliance with the recommendations of the Dietary Guidelines for Chinese 2016. Results One thousand four hundred ninety-six men and two thousand sixty-eight women were included. 51.2% of the subjects had moderate or high levels of inadequate intake; 21.3% had moderate or high levels of excessive intake; and 74.0% had moderate or high levels of unbalanced dietary intake. With potential confounders adjusted, support from family was negatively associated with inadequate intake, while support from friends was positively associated with inadequate and excessive intake. No significant associations were found between perceived social support from significant others and diet quality indicators. Conclusions An unbalanced diet is common among adults of the ethnic minority groups in Yunnan Province, Southwest China. Social support should be taken into account in designing nutrition interventions rather than focusing solely on individuals.

Background Few studies have focused on the influencing factors of dietary practices among ethnic minority groups in China, particularly from a social capital perspective. Methods Between May and September 2019, we conducted a cross-sectional survey among adults (n = 1,813) from three ethnic minority communities (A Chang, De Ang and Jing Po) in Yunnan Province, Southwest China. Dietary intakes during the past 12 months were measured with a 100-item Food Frequency Questionnaire (FFQ), and two forms of social capital (bonding and bridging) were measured using the validated Personal Social Capital Scale 16 (PSCS-16). Principal component factor analysis was used to derive dietary patterns from 20 food groups. Multivariate linear regressions were used to examine the associations between social capital and dietary patterns. Results Two distinct dietary patterns were identified: the traditional and the modern. The traditional pattern was characterized by high consumptions of tubers, poultry, rice, fruits, vegetables and low consumptions of oil and salt, whereas the modern pattern was highly correlated with egg, nut, beverage, snack and oil consumptions. After adjusted for potential confounders, the modern pattern was positively associated with bonding capital (β = 0.066; 95%CI: 0.058, 0.075) and negatively associated with bridging capital (β = -0.017; 95%CI: -0.024, -0.010). Conclusion In conclusion, an unhealthy dietary pattern was identified among the ethnic minority groups in Southwest China. The influences of people’s social connections on dietary behaviors should be considered in designing and implementing nutrition intervention programs for the population.

Introduction Glioma is the most common primary brain tumour in adults. Numerous studies have shown that neuregulins (NRGs) may be involved in the formation of glioma. Although NRG1 has been extensively studied in glioma, the functions of NRG2 in glioma development remain elusive. Material and methods In the present study, we investigated the expression of NRG2 in different grades of human glioma samples, and analysed the functional effects of NRG2 in glioma cells mainly using wound healing assay and transmigration assay. Results We found that NRG2 was differentially expressed in different grades of human glioma/glioblastoma tissues. The data from wound healing assays demonstrated that NRG2 can differentially promote the migration of SHG44 human glioma, and U251 and U-87 MG human glioblastoma cells at different time points. The results of cell transmigration assays showed that, compared with the vehicle control, the number of cells that migrated to the underside of the insert was increased significantly for all the 3 cell lines treated with 5 nM of NRG2 for 12 hours. Conclusions In conclusion, our results demonstrated that NRG2 is expressed in gliomas to varying extents, and it may play roles in the migration of glioma cells in vitro. These data suggest that treatment targeting NRG2 signalling may partly reverse the migration-based metastasis of glioma cells.

Background Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural–general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. Methods Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. Results Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural–general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural–general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). Conclusions Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

This study aimed to assess the risk of coronavirus disease 2019 in the border areas of southwest China, so as to provide guidance to targeted prevention and control measures in the border areas of different risk levels. We assessed the dependence of the risk of an outbreak in the southwest China from imported cases on key parameters such as the cumulative number of infectious diseases in the border area of southwest China in the past 3 years; the connectivity of the neighboring countries with China's Southwest border, including baseline travel numbers, travel frequencies, the effect of travel restrictions, and the length of borders with neighboring countries; the cumulative number of close contacts of coronavirus disease 2019 patients; (iv) the population density in border areas; the efficacy of control measures in border areas; experts estimated risks in border areas based on experience and then given a score; Spearman correlation and Logistic regression models were used to analyze the associated factors of novel coronavirus. According to the correlation of various factors, we assigned values to each parameter, calculated the risk score of each county, and then divided each county into high, medium, and low risk according to the sick score and took different control measure according to different risk levels. Finally, the total risk level was evaluated according to the Harvard disease risk index model. The number of infectious diseases in the past 3 years, travel numbers, travel frequencies, experts estimated risk score, effect of travel restrictions, and the number of close contacts were associated with the incidence of new coronary pneumonia. It is concluded that bilateral transportation convenience is a risk factor for new coronary pneumonia, (odds ratio = 9.23, 95% confidence interval, 1.99-42.73); the number of observers is a risk factor for new coronary pneumonia (odds ratio = 1.04, 95% confidence interval, 1.00-1.08). We found that in countries with travel numbers, travel frequencies, and experts' estimated risk scores were the influencing factors of novel coronavirus. The effect of travel restrictions and the cumulative number of close contacts of the case are risk factors for novel coronavirus.

Transient receptor potential canonical 3 (TRPC3) is a nonselective cation channel, and its dysfunction is the basis of many clinical diseases. However, little is known about its possible role in the bladder. The purpose of this study was to explore the function and mechanism of TRPC3 in partial bladder outlet obstruction (PBOO)-induced detrusor overactivity (DO). We studied 31 adult female rats with DO induced by PBOO (the DO group) and 40 sham-operated rats (the control group). Here we report that the expression of TRPC3 in the bladder of DO rats increased significantly. Furthermore, PYR10, which can selectively inhibit the TRPC3 channel, significantly reduced bladder excitability in DO and control rats, but the decrease of the bladder excitability of DO rats was more obvious. PYR10 significantly reduced the intracellular calcium concentration in smooth muscle cells (SMCs) in DO and control rats. Finally, Na

To investigate the expression of CD73 in acute myeloid leukemia (AML) patients with NPM1 mutant and wild-type, and to evaluate the therapeutic efficacy and prognosis of CD73 to the AML patients.160 patients with AML treated in our hospital from June 2015 to June 2019 were enrolled, and 40 non-AML bone marrow samples from healthy people were selected as controls during the same period. The expression of CD73 in healthy people, NPM1 mutation and NPM1 wild-type AML patients were compared, and the relationship between the expression of CD73 and its clinicopathological characteristics, as while as efficacy in AML patients were analyzed. The patients were followed up, and the influence of CD73 to the prognosis of different AML patients was analyzed.The positive expression rate of CD73 in AML patients (23.75%) was significantly higher than that in the healthy control group (0.62%), and the positive expression rate of CD73 in AML patients with NPM1 mutation (74.75%) was significantly higher than that with NPM1 wild-type (25.51%) (both P0.001). AML patients with CD73 positive expression was associated with age, FAB typing, disease risk classification, and NPM1 gene mutation (both P0.05). The overall survival rate of AML patients with NPM1 gene mutation was 75.98%, which was significantly higher than the patients with NPM1 wild-type (34.68%)(P0.001), the median survival time of AML patients with NPM1 gene mutation in the CD73The expression of CD73 was increased in AML patients with NPM1 gene mutation, and CD73 showed different prognostic significance in AML patients with different NPM1 gene mutation. The combination of clinicopathologic features, CD73 expression and NPM1 gene in AML patients is helpful to determine their prognosis and guide the formulation of relevant treatment plans.CD73在NPM1突变型急性髓系白血病患者中的表达及其临床意义.探讨CD73在NPM1突变型及野生型急性髓系白血病（AML）患者中的表达及对其治疗疗效和预后的判断价值.选取2015年6月-2019年6月本院收治的初治AML患者160例，同期选取本院非AML者的骨髓样本40例作为对照，分别比较健康者、NPM1突变型AML及NPM1野生型AML患者中CD73的表达，分析CD73表达与其临床病理特征及疗效的关系，对患者进行随访，进一步分析CD73对不同AML患者预后的影响.CD73在AML患者中的阳性表达率（23.75%）显著高于健康对照组（0.62%），NPM1突变AML患者CD73CD73在NPM1基因突变AML患者中表达增加，CD73在不同NPM1基因突变型AML患者中有不同的预后意义。结合AML患者临床病理特征、CD73表达及NPM1基因情况有助于判断其预后，并指导有关治疗方案的制定.

In this study, we modified the well-known photothermal polydopamine nanoparticles with the poly[(2-methacryloyloxy)ethyl phosphorylcholine-b-(2-dimethylamino)ethyl methacrylate] (PMPC-b-PDMAEMA) diblock copolymers, containing both biocompatible cell membrane phosphorylcholine zwitterions segments and pH-responsive dimethylaminoethyl units on the polymer chains, to achieve both the photothermal property and pH-responsive release behavior. The results showed that the obtained nanoparticles had a narrow size distribution with the diameter about 220 nm. Besides, the modified polydopamine nanoparticles showed enhanced colloidal stability, pH-sensitive drug release behavior, excellent biocompatibility and remarkable near-infrared photothermal property. Thus, it is highly anticipated that PMPC-b-PDMAEMA modified polydopamine nanoparticles can serve as a powerful drug delivery system for combined pH-sensitive drug release and near-infrared photothermal therapeutic.

Chronic diarrhea is one of the most common complaints in clinical practice for both adults and children. The purpose of this study was to assess the commonly used Chinese herbal medicine navel therapy for the treatment of chronic diarrhea (traditional Chinese medicine syndrome of spleen deficiency). The literature search was up to June 2018. Four types of studies (clinical trials, case series, case reports, and experts' experience) researched on Chinese medicine navel therapy used alone or combined with other therapies for the treatment of chronic diarrhea all included. Information on prescriptions, effectiveness, and safety of intervention was collected. Traditional Chinese Medicine Inheritance Support System V2.5 was used to do data analysis. We included 416 studies. All these studies carried out in 194 cities of China. We obtained the most commonly used single herbs, herbal medicine combination, and Chinese patent medicine for both adults and children. The top 3 single herbs were Caryophylli Flos (Dingxiang), Cinnamomi Cortex (Rougui), and Euodiae Fructus (Wuzhuyu). The most frequently used Chinese patent medicines were Ding Gui Infantile Navel Paste and Huoxiang Zhengqi Liquid. The effectiveness assessment was based on clinical trials, but we did not perform a meta-analysis because of different study design and unsatisfactory methodological quality. No serious adverse reaction happened in original studies. The application of Chinese medicine navel therapy could be one of the ideal treatments for chronic diarrhea in the future, especially for children. However, high-quality studies are very needed to provide clear evidence.

The widespread adoption of genetically modified, glyphosate-tolerant corn and soybean varieties in US crop production has led to a dramatic increase in glyphosate usage. Though present at or below regulatory limits currently set for human foodstuffs, the concentration of glyphosate in companion animal feed is currently unknown. In the present study, 18 commercial companion animal feeds from eight manufacturers were analyzed for glyphosate residues using ELISA. Every product contained detectable glyphosate residues in the range of 7.83 × 101–2.14 × 103 μg kg−1 dry weight, with the average and medians being 3.57 × 102 and 1.98 × 102 μg kg−1 respectively. Three products were tested for within-bag variation and six were tested for lot to lot variation. Little within-bag variation was found, but the concentration of glyphosate varied by lot in half of the products tested. Glyphosate concentration was significantly correlated with crude fiber content, but not crude fat or crude protein. Average daily intakes by animals consuming feeds containing the median glyphosate concentration are estimated to result in exposures that are 0.68–2.5% of the Allowable Daily Intake (ADI) for humans in the US and EU, which are 1750 and 500 μg kg−1 respectively. Consumption of the most contaminated feed, however, would result in exposure to 7.3% and 25% of the above ADIs, though the relevance of such an exposure to companion animals is currently unknown. Companion animal feeds contained 7.83 × 101–2.14 × 103 μg kg−1 glyphosate which is likely to result in pet exposure that is 4–12 times higher than that of humans on a per Kg basis.

Extracellular plaque deposits of β-amyloid peptide (Aβ) are one of the main pathological features of Alzheimer's disease (AD). The aggregation of Aβ

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s13577-021-00499-y.

China has experienced an outbreak of COVID-19 since December 2019. This study investigated the differences between the imported and local cases of COVID-19 in Nanyang, China. In this study, a total of 129 COVID-19 confirmed cases with a clear epidemiological history admitted to hospitals in Nanyang from January 24 to February 26, 2020 were enrolled. Patients who had a travel history to or a residence history in Wuhan or in the surrounding areas in Hubei Province within 14 days before the illness onset were assigned to the imported group (n=70), and the others were assigned to the local group (n=59). The differences in epidemiological characteristics, clinical features, laboratory and imaging results, and prognosis were compared between the 2 groups. The early diagnosed cases were mainly imported cases, and the later diagnosed ones were mainly local cases. The most common first symptom was fever; moderate fever was commonly seen in imported cases whereas low fever was commonly seen in local cases. Lymphocyte counts in the imported group were lower than those in the local group. The imported group showed more advanced and severe abnormalities in the CT scan whereas the local group showed milder pulmonary abnormalities. The proportion of severe and critically severe patients in the imported group was higher than that in the local group. In conclusion, the imported cases have more severe or critically severe patients with a higher mortality rate than the local cases.

Objective This study aimed to systematically analyze the effectiveness and safety of the local application of vancomycin powder to prevent surgical site infection (SSI) after spinal surgeries and provide guidance for clinical practice. Methods Two researchers independently searched PubMed, Web of Science, Elsevier, and China National Knowledge Infrastructure using the MeSH terms “spinal surgery,” “vancomycin,” “local,” “topical,” “prophylactic,” “surgical site infection,” and “SSI” to identify studies published between January 2010 and January 2020 on the local application of vancomycin powder for preventing SSI after spinal surgeries. The outcome assessment indicators were analyzed using RevMan 5.3 software. Results Three randomized controlled trials, two prospective studies, and 26 retrospective studies were included in the current research. The results of the meta-analysis revealed significant differences between the vancomycin and control groups (non-vancomycin group) concerning the incidence of SSI (risk ratio = 0.39, 95% confidence interval = 0.28–0.55, Z = 5.46), indicating that local application of vancomycin powder can significantly reduce the incidence of SSI. Conclusion Local application of vancomycin powder is an effective and safe method to prevent SSI after spinal surgeries.

Primary brain tumors are a rare occurrence in comparison to other malignancies, the most predominant form being glioma. Commonly, exposure to ionizing radiations and inheritance of associated conditions such a neurofibromatosis and tuberous sclerosis are the most common causes of development of glioma. However, understanding of the molecular mechanisms that drive glioma development is limited. We explore the role of aberration of microRNA namely miR-494-3p through long noncoding RNA WT1-AS in the development of gliomas. In this study, we found that, levels of WT1-AS were significantly reduced in glioma tissues and cell lines. The miR-494-3p levels were negatively correlated with WT1-AS levels. The cellular proliferation and invasiveness decreased in WT1-AS transfected cell lines. Further the half maximal inhibitory concentration (IC50) of chemotherapeutic agent temozolomide was significantly reduced in the presence of WT1-AS. The cotransfection of WT1-AS and miR-494-3p reduced activation of phospho-AKT (p-AKT). Expression of miR-494-3p is modulated by binding to long noncoding RNA WT1-AS. Deregulation of WT1-AS leads to aberrant expression of miR-494-3p leading to hyperactivation of AKT. This malformation may result in altering protective immune responses in malignancies. Targeting of WT1-AS, miR-494-3p, and AKT may be novel therapeutic options in treatment of glioma.

The correlation between the water content and protein adsorption on the surface of polymer brushes is investigated quantitatively. Using a number of model systems such as poly N-isopropylacrylamide (PNIPAM), polyethylene glycol (PEG), poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC), poly(2-hydroxyethyl methacrylate) (PHEMA), and poly(2,2,3,4,4,4-hexafluorobutyl)methacrylate (PHFBMA) polymer brushes with various grafting densities, the amount of water hydrodynamically coupled inside the brushes and its correlation with protein adsorption (BSA and Fg proteins as model systems) were determined by quartz crystal microbalance with dissipation (QCM-D) and surface plasma resonance (SPR). The results demonstrate the negative correlation between the water content and protein adsorption - the more water is coupled inside the brushes, the more protein adsorption is suppressed. In particular for PNIPAM brushes with a high enough grafting density and with a water content greater than 250 ng cm-2, the protein adsorption is negligible.

Background/Aims: Chemoresistance is largely responsible for relapses of bladder cancer during clinical therapy. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Growing evidence supports the theory that microRNAs (miRNAs) play an important role in chemotherapeutic drug resistance because they are downregulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. More specifically, the extent and precise mechanism of the involvement of miR-34as in chemoresistance to epirubicin (EPI) in the treatment of bladder cancer remains unclear. Methods: In this study, real-time quantitative polymerase chain reaction (PCR) was used to analyze the expression of miR-34a in bladder cancer cell line BIU87 and its EPI chemoresistant cell line BIU87/ADR. The miR-34a profiles in bladder cancer tissues were obtained from The Cancer Genome Atlas database. The effect of miR-34a on chemosensitivity was evaluated by cell viability assays, colony formation assays, and in vivo experimentation. Apoptosis and the cell cycle were examined by flow cytometry. A luciferase reporter assay was used to assess the target genes of miR-34a. Western blot and qPCR were used to analyze the expression of target proteins and downstream molecules. Results: The downregulation of miR-34a in bladder cancer serves as an independent predictor of reduced patient survival. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to EPI, while miR-34a downregulation resulted in chemoresistance to EPI in vitro. Moreover, it was found that miR-34a increased the sensitivity of BIU87/ADR cells to chemotherapy in vivo. The luciferase reporter assay ascertained that TCF1 and LEF1 are direct target genes of miR-34a. It was found that miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis. Conclusions: The results of this study indicate that miR-34a contributes to the chemosensitivity of BIU87/ADR by inhibiting the TCF1/LEF1 axis. Consequently, miR-34a is a determinant of BIU87 chemosensitivity and may therefore serve as a potential therapeutic target in bladder cancer treatment.

Background Surgical site infection (SSI) is a common complication in spinal surgery, imposing a high burden on patients and society. However, information about its characteristics and related risk factors is limited. We designed this prospective, multicenter study to address this issue. Methods : From January 2015 through February 2016, a total of 1764 patients who had spinal trauma or degenerative spinal diseases were treated with instrumented surgeries and followed up for 1 year with complete data. Data on all patients were abstracted from electronic medical records, and SSIs were prospectively inspected and diagnosed by surgeons in our department. Any disagreement among them was settled by the leader of this study. SPSS 19.0 was used to perform the analyses. Results A total of 58 patients (3.3%, 58 of 1764) developed SSI; 1.1% had deep SSI, and 2.2% had superficial SSI. Of these, 60.6% (21 of 33) had a polymicrobial cause. Most of them (51 of 58) occurred during hospitalization. The median occurrence time was 3 days after operation (range: 1–123 days). SSI significantly prolonged hospital stays, by 9.3 days on average. The univariate analysis revealed reason for surgery as the only significant risk factor. The multivariate analysis, however, revealed 8 significant risk factors, including higher BMI, surgical site (cervical), surgical approach (posterior), surgery performed in summer, reasons for surgery (degenerative disease), autograft for fusion and fixation, and higher preoperative platelet level. Conclusion Identification of these risk factors aids in stratifying preoperative risk to reduce SSI incidence. In addition, the results could be used in counseling patients and their families during the consent process.

Cardiomyocyte apoptosis contributes to the pathological process of ischemic heart diseases, such as myocardial infarction. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathological process of myocardial infarction by regulating cardiomyocyte apoptosis. Previous studies have reported that miR-363 is an apoptosis-related miRNA. However, whether miR-363 is involved in regulating cardiomyocyte apoptosis remains unclear. This study aimed to investigate the potential role of miR-363 in the regulation of hypoxia-induced cardiomyocyte apoptosis. We found that miR-363 expression was significantly increased in hypoxic cardiomyocytes and that inhibition of miR-363 effectively protected cardiomyocytes against hypoxia-induced apoptosis. Bioinformatics analysis predicted that Notch1 is a potential target gene of miR-363. This finding was validated by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. miR-363 inhibition significantly promoted the activation of Notch signaling in hypoxic cardiomyocytes. However, knockdown of Notch1 markedly reversed the protective effects induced by miR-363 inhibition. Furthermore, blocking the Notch signaling also significantly abrogated the protective effects of miR-363 inhibition. Overall, these findings suggest that inhibition of miR-363 protects cardiomyocytes against hypoxia-induced apoptosis through promotion of Notch1 expression and activation of Notch signaling. Our study provides a novel understanding of the molecular basis of hypoxia-induced cardiomyocyte apoptosis and suggests a potential therapeutic target for myocardial infarction.

Background Thyroid metastases from colorectal cancer (CRC) are rare, both in clinical practice and in the literature; hence, their diagnosis, appropriate treatment, and prognostic factors require further investigations. Methods A retrospective analysis was performed for four cases of thyroid metastases from CRC, treated in our center between January 2005 and December 2015, and the relevant literature was searched using PubMed, resulting in the identification of 17 patients with detailed information available. The clinical data and follow-up information of our patients and the previously reported cases were collected and compared. Results The median age of the 21 patients was 59 years (44.5 and 66 years for our patients and the previously reported cases, respectively). Fifteen (71.4%) primary tumors were distributed throughout the distal colon or rectum (75% [3/4] in our center and 70.5% [12/17] in the previously reported cases). According to our analysis, we found that 81.0% of patients (17/21) showed concomitant lung metastasis. Among them, all four patients in our center showed lung metastasis, and 75% (3/4) developed thyroid metastases after the lung metastasis. In the previously reported cases, the corresponding proportions were 76.5 and 76.5% (13/17) of patients, respectively. The median time after primary tumor diagnosis to thyroid metastasis development was 28 months (26 months in our center and 35 months in the previously reported cases). One patient with advanced CRC in our center died 5 months after the thyroid metastasis was identified, while the remaining three patients are currently alive (longest follow-up time, 27 months). The median survival time after thyroid metastasis during 3 years of follow-up of the previously reported 17 patients was 12 months. There was no difference in the overall survival between patients treated non-surgically (8/21) and patients undergoing thyroidectomy alone or thyroidectomy with adjuvant therapy (13/21) (p = 0.388). In addition, we found that the overall survival of the patients whose other metastases were treated with radical treatment was superior to that in those treated with palliative treatment (p = 0.022). Conclusions Thyroid metastases from CRC are rare in clinical practice and are a manifestation of advanced CRC. The prognosis of patients with thyroid metastases from CRC is related to various factors, including the grade of malignancy of the primary lesion, the presence of other metastases, and whether the metastases are timely diagnosed and a radical treatment strategy is employed.

// Fangqi Liu 1, * , Cong Li 1, * , Huixun Jia 2, * , Li Yang 1 , Yuchen Wu 1 , Jiang Zhao 1 , Sanjun Cai 1 , Ji Zhu 3 and Ye Xu 1 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 2 Department of Clinical Statistics, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China * These authors contributed equally to this work and should be regarded as joint first authors Correspondence to: Ye Xu, email: xuye021@163.com Ji Zhu, email: leo.zhu@126.com Keywords: colorectal cancer, tumor location, prognosis, left-sided colon cancer, right-sided colon cancer Received: September 20, 2016 Accepted: February 21, 2017 Published: March 17, 2017 ABSTRACT Differences in epidemiology, pathological features, and molecular pathogeneses have been observed according to primary tumor location in colorectal cancer (CRC). However, predicting CRC survival by tumor location remains controversial. Therefore, we compared the pathological characteristics, molecular features, and prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC), and rectal cancer (RECC) among Chinese patients with CRC. We evaluated 4,426 patients with stage I–III CRC between January 2008 and July 2014from Fudan University Shanghai Cancer Center. All patients were grouped by the locations of tumors (RCC, LCC, and RECC). Patients with RCC were more likely to be women and older, have poorly differentiated tumors, microsatellite repair deficiency (dMMR), negative p53 expression, and the mucinous subtype. Unadjusted Kaplan-Meier survival curves revealed survival in RCC than in LCC and RECC. However, there were no significant differences in OS and DFS between LCC and RECC. The same results were observed for each disease stage. Unadjusted models revealed an increased risk of mortality, recurrence, or metastasis for RCC (OS: HR, 1.68, P =0.0002 and DFS: HR, 1.24, P =0.032), compared to LCC (all stages), and a similar result was observed for stage III patients (OS: HR, 1.79, P

Apple phlorizin has many biological activities, such as antioxidant and liver protection. The present study aimed to evaluate the roles of apple phlorizin against hydrogen peroxide (H2 O2 )-induced oxidative damage in HepG2 cells. In this study, treatment with apple phlorizin (100 and 150 μg/ml) decreased the production of reactive oxygen species and alleviated apoptosis as well as DNA damage in H2 O2 -induced HepG2 cells. These effects were associated with the increased activity of antioxidant enzymes, enhanced the ARE-driven phase II antioxidant gene expression and its upstream Nrf2 protein expression, and decreased apoptosis-related gene expression. However, the phase II antioxidant gene expression and Nrf2 protein expression upregulated by phlorizin were reversed by Nrf2 shRNA transfection. These results showed that phlorizin relieves oxidative stress, DNA damage, and apoptosis in H2 O2 -induced HepG2 cells, at least partially, by regulating the expression of Nrf2 protein and apoptosis-related genes. PRACTICAL APPLICATIONS: Apple phlorizin is a polyphenol compound extracted from apple or apple juice. This report highlighted a protective effect of phlorizin on antioxidant stress, DNA damage, and apoptosis in H2 O2 -induced HepG2 cells. These results suggested that phlorizin may be developed for functional foods.

Osteosarcoma (OS) is a common kind of aggressive tumor in bone which was mostly identified in children and adolescents with extremely high risk of death. Accumulating research works have displayed that long noncoding RNAs (lncRNAs) exert an essential role in the development of multiple cancers. It has been reported that TMPO-AS1 is an oncogene in cancers; nonetheless, its molecular mechanism in OS is totally unclear. Our present study elucidated that a remarkable overexpression of TMPO-AS1 was found in OS tissues and cells. Moreover, TMPO-AS1 depletion restrained Wnt/β-catenin pathway and cell proliferation as well as facilitated cell apoptosis. Further molecular mechanism investigations showed that TMPO-AS1 can sponge to miR-199a-5p. Moreover, miR-199a-5p was at a low level at OS cells. Importantly, miR-199a-5p's overexpression was associated with the OS cells' decreased proliferation and increased apoptosis. In addition, WNT7B was confirmed as a downstream gene of miR-199a-5p. Also the WNT7B expression was reversely modulated by miR-199a-5p and positively modulated by TMPO-AS1. Rescue experiments suggested that downregulated WNT7B rescued miR-199a-5p inhibitor-mediated repression on OS progression, but the treatment of LiCl counteracted the effect of WNT7B downregulation. In a word, TMPO-AS1 serves as a competing endogenous RNA to boost osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis, which provided an underlying therapeutic target for patients with OS.

Schizophrenia (SCZ) patients and their unaffected first-degree relatives (FDRs) share similar functional neuroanatomy. However, it remains largely unknown to what extent unaffected FDRs with functional neuroanatomy patterns similar to patients can be identified at an individual level. In this study, we used a multivariate pattern classification method to learn informative large-scale functional networks (FNs) and build classifiers to distinguish 32 patients from 30 healthy controls and to classify 34 FDRs as with or without FNs similar to patients. Four informative FNs-the cerebellum, default mode network (DMN), ventral frontotemporal network, and posterior DMN with parahippocampal gyrus-were identified based on a training cohort and pattern classifiers built upon these FNs achieved a correct classification rate of 83.9% (sensitivity 87.5%, specificity 80.0%, and area under the receiver operating characteristic curve [AUC] 0.914) estimated based on leave-one-out cross-validation for the training cohort and a correct classification rate of 77.5% (sensitivity 72.5%, specificity 82.5%, and AUC 0.811) for an independent validation cohort. The classification scores of the FDRs and patients were negatively correlated with their measures of cognitive function. FDRs identified by the classifiers as having SCZ patterns were similar to the patients, but significantly different from the controls and FDRs with normal patterns in terms of their cognitive measures. These results demonstrate that the pattern classifiers built upon the informative FNs can serve as biomarkers for quantifying brain alterations in SCZ and help to identify FDRs with FN patterns and cognitive impairment similar to those of SCZ patients.

Breastfeeding has a wide range of benefits for both infants and mothers. The identification of factors associated with exclusive breastfeeding (EBF) are important to increase the prevalence of EBF. The study aimed to determine the prevalence of EBF within the first six months and its associated factors in Kaiyuan, Yunnan Province, Southwest China. This cross-sectional study was conducted in Kaiyuan, a middle-sized city of Yunnan Province, Southwest China. Mothers of infants under twelve months were randomly selected for a face to face interview in four towns (two in urban areas and two in rural areas) in Kaiyuan. A structured questionnaire was applied for collection of sociodemographic information, mothers’ and infants’ health, and breastfeeding information. A 24-hour food recall survey was used to collect infant feeding information. A logistic regression analysis was performed to identify the factors independently associated with exclusive breastfeeding for infants up to six months of age. The number of 417 mothers with infants under six months was interviewed. The prevalence of EBF at six months was 27.34%. Logistic regression indicated that EBF within six months was more likely to be practiced by mothers who had higher average household income per year (OR = 2.09, 95% CI: 1.05–4.17 p = 0.037; OR = 1.85, 95% CI: 1.04–3.28 p = 0.037), and mothers who received breastfeeding information (OR = 2.46, (95%CI: 1.45–4.18, p = 0.0009). The prevalence of EBF in Kaiyuan, Southwest China is considerably lower than national and international recommendations. Yearly household income, and mothers who received breastfeeding information are associated with higher EBF prevalence. Breastfeeding information should be given to mothers in order to increase the prevalence of EBF.

Parkinson's disease (PD), the second most prevalent age-related neurodegenerative disease, occurs as a result of the loss of dopaminergic neurons in the substantia nigra. Long non-coding RNA-p21 (lnc-p21) has been demonstrated to be upregulated in PD. However, its role in PD is unknown. Here, the results showed that lnc-p21 was highly expressed in human neuroblastoma SH-SY5Y cells treated with MPP

Background Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is among the most commonly performed surgical procedure to treat lumbar degenerative disorders. In open TLIF procedure, usually rods were contoured to restore normal lumbar sagittal alignment. However, in MIS-TLIF procedure, contoured rods sometimes were easier to rotate and harder to be locked at the satisfactory position due to instrumentation design and limited exposure. Thus, straight rods had been used in single-level MIS-TLIF in our institution. However, the effect of rod contouring on sagittal parameters and clinical outcomes remains unclear. In the present study, we aim to evaluate the effects of single-segment MIS-TLIF with contoured versus straight rods on sagittal parameters and clinical outcomes. Methods A retrospective review of MIS-TLIF at L4/5 was performed between 2009 and 2013 in our hospital. Seventy-six cases were divided into contoured rod group (CR group, n = 35) and straight rod group (SR group, n = 41). Clinical outcomes and radiographic measurements at five years’ follow-up were evaluated by visual analog score (VAS), Oswestry disability index (ODI) and Japanese Orthopaedic Association (JOA) score, spino-pelvic parameters, disc height and fused segment angle. Fusion rate and cage subsidence were also measured. Results Preoperative VAS, JOA, ODI and radiographic parameters were comparable between two groups. The average follow-up was 63.72 ± 3.86 months. VAS, JOA and ODI were significantly improved at 5-year follow-up in both groups, and there were no significant differences between two groups(P > 0.05). Fused segment angle (FSA) was greater in CR group than SR group (P = 0.024), while the other radiographic parameters were not significantly different(P > 0.05). Rod process, fusion rate and cage subsidence were not risk factors of post-surgical malalignment, patients with pre-surgical sagittal imbalance was more prone to show post-surgical malalignment (P Conclusions Both CR and SR groups acquired satisfactory clinical results. Although contoured rods had better fused segment angle, contoured or straight rods at single L4/5 level had little effect on global spino-pelvic parameters and clinical outcomes in a 5-year follow-up.

Metastasis is the major cause of death among cancer patients, yet early detection and intervention of metastasis could significantly improve their clinical outcomes. We have sequenced and analyzed RNA (Expression) and DNA (Mutations) from the primary tumor (PT), tumor extension (TE) and lymphatic metastatic (LM) sites of patients with clear cell renal cell carcinoma (CCRCC) before treatment. Here, we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis. This mutation is un-detectable in the PT, becomes detectable in the TE and dominates the LM tissue. So while only a few primary cancer cells carry this mutation, the majority of metastatic cells have this mutation. The increasing frequency of this mutation in metastatic tissue suggests that this Plk5 deletion could be used as an early indicator of CCRCC metastasis, and be identified by low cost PCR assay. A large scale clinical trial could reveal whether a simple PCR assay for this mutation at the time of nephrectomy could identify and stratify high-risk CCRCC patients for treatments.

Glioblastoma (GBM) is the most common and most aggressive central nervous system tumor in adults. Due to GBM cell invasiveness and resistance to chemotherapy, current medical interventions are not satisfactory, and the prognosis for GBM is poor. It is necessary to investigate the underlying mechanism of GBM metastasis and drug resistance so that more effective treatments can be developed for GBM patients. sushi repeat-containing protein, X-linked 2 (SRPX2) is a prognostic biomarker in many different cancer cell lines and is associated with poor prognosis in cancer patients. SRPX2 overexpression promotes interactions between tumor and endothelial cells, leading to tumor progression and metastasis. We hypothesize that SRPX2 also contributes to GBM chemotherapy resistance and metastasis. Our results revealed that GBM tumor samples from 42 patients expressed higher levels of SRPX2 than the control normal brain tissue samples. High-SRPX2 expression levels are correlated with poor prognosis in those patients, as well as resistance to temozolomide in cultured GBM cells. Up-regulating SRPX2 expression in cultured GBM cell lines facilitated invasiveness and migration of GBM cells, while down-regulating SRPX2 through RNA interference was inhibitory. These results suggest that SRPX2 plays an important role in GBM metastasis. Epithelial to mesenchymal transition (EMT) is one of the processes that facilitate GBM metastasis and resistance to chemotherapy. EMT marker expression was decreased in SRPX2 down-regulated GBM cells, and MAPK signaling pathway marker expression was also decreased when SRPX2 is knocked down in GBM-cultured cells. Blocking the MAPK signaling pathway inhibited GBM metastasis but did not inhibit cell invasion and migration in SRPX2 down-regulated cells. Our results indicate that SRPX2 facilitates GBM metastasis by enhancing the EMT process via the MAPK signaling pathway.

Osteoarthritis (OA), a common form of degenerative joint disease, is typified by inflammatory response and the loss of cartilage matrix. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation and exert critical roles in diverse physiologic and pathogenic processes including OA. The lncRNA plasmacytoma variant translocation 1 (PVT1) has been implicated in cancer, diabetes and septic acute kidney injury. Recent research confirmed the elevation of PVT1 in patients with OA. However, its role in the development of OA remains poorly elucidated. In the present study, high expression of PVT1 was observed in cartilage of OA patients and IL-1β-stimulated chondrocytes. Moreover, cessation of PVT1 expression dramatically reversed the inhibition of IL-1β on collagen II and aggrecan expression, but suppressed IL-1β-induced elevation of matrix metalloproteinases (MMPs), including MMP-3, MMP-9 and MMP-13. Simultaneously, PVT1 inhibition also antagonized the production of inflammatory cytokines upon IL-1β stimulation, including prostaglandin E2 (PGE2), NO, IL-6, IL-8 and TNF-α. Further molecular mechanism analysis identified PVT1 as an endogenous sponge RNA that could directly bind to miR-149 and repress its expression and activity. More importantly, miR-149 inhibition reversed the protective roles of PVT1 cessation in attenuating IL-1β-evoked matrix aberrant catabolism and inflammation. Together, this research confirms that lowering PVT1 expression may ameliorate the progression of OA by alleviating cartilage imbalance toward catabolism and inflammatory response, thus supporting a promising therapeutic strategy against OA.

The pleiotropic effects of hyperthermia on cancer cells have been well documented, and microwave hyperthermia (MWHT) has been widely applied for multifarious cancer treatment. However, the mechanisms underlying the anticancer effect of MWHT combined with gemcitabine (GEM) remain poorly understood. The aim of the present study was to investigate the role of autophagy in the thermo‑chemotherapy of human squamous cell lung carcinoma cells. It was observed that MWHT combined with GEM potently suppressed the viability of NCI‑H2170 and NCI‑H1703 cells, and induced G0/G1 cell cycle arrest. Notably, MWHT with GEM induced autophagy, as indicated by the formation of autophagic vacuoles, downregulation of p62 and upregulation of light chain 3‑II. It was further demonstrated that the autophagy was due to the production of reactive oxygen species (ROS), whereas N‑acetyl cysteine, an ROS scavenger, attenuated the level of autophagy. However, when the autophagy inhibitor 3‑methyladenine was used, there was no significant change in the production of ROS. Furthermore, it was observed that MWHT combined with GEM downregulated the protein expression levels of phosphoinositide 3‑kinase (PI3K), phosphorylated (p)‑PI3K, protein kinase B (AKT), p‑AKT, mammalian target of rapamycin (mTOR), p‑mTOR, phosphorylated S6 (pS6) and p70 S6 kinase, which are associated with autophagy. In addition, the results demonstrated that ROS served as an upstream mediator of PI3K/AKT/mTOR signaling. In light of these findings, the present study provides original insights into the molecular mechanisms underlying the cell death induced by MWHT combined with GEM, and this may be a promising approach for the treatment of human squamous cell lung carcinoma.

Since lipid digestion is an interfacial process, food emulsions are increasingly being seen as a mechanism for controlling lipid uptake. Oil-in-water emulsions stabilized by whey protein (WP) and protein-xanthan gum (XG) mixtures were designed to investigate the influence of interfacial structures on lipid digestion using an in vitro digestion model. The interfacial layers with different structures were designed using microparticulated whey protein (MWP) and MWP-XG mixtures. The increase in the volume average diameter of proteins indicated that the WPs aggregated to form micro-particles during microparticulation. The increase in the protein surface hydrophobicity index and the measurement results from the Magnetic Resonance Imaging System indicated that the protein hydrophilic groups were embedded and that the protein hydrophobic groups were exposed. Under in vitro conditions, the emulsions stabilized by microparticulated whey proteins and protein-XG mixtures were more stable than the WP emulsions, and the microparticulated whey proteins and protein-XG mixtures were more effective for decreasing the digestion rate, as shown by the stability analysis and free fatty acid release rates. These results help elucidate the influence of the interfacial structure on lipid digestion. The control of lipid digestibility within the gastrointestinal tract might be important for the design and development of reduced-fat foods and novel functional foods for controlling bioactive release.