Comparison of the efficacy and tolerability of different repetitive transcranial magnetic stimulation modalities for post-stroke dysphagia: a systematic review and Bayesian network meta-analysis protocol.

INTRODUCTION: Up to 78% of patients who had a stroke develop post-stroke dysphagia (PSD), a significant consequence. Life-threatening aspiration pneumonia, starvation, and water and electrolyte abnormalities can result. Several meta-analyses have shown that repeated transcranial magnetic stimulation (rTMS) improves swallowing in patients who had a stroke; however, the optimum model is unknown. This study will be the first Bayesian network meta-analysis (NMA) to determine the best rTMS modalities for swallowing of patients who had a stroke. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, Google Scholar, Cochrane, the Chinese National Knowledge Infrastructure, the Chongqing VIP Database and WanFang Data will be searched from their creation to 2 September 2023. All randomised controlled trials associated with rTMS for PSD will be included. Only Chinese or English results will be studied. Two researchers will independently review the literature and extract data, then use the Cochrane Collaboration's Risk of Bias 2.0 tool to assess the included studies' methodological quality. The primary outcome is swallowing function improvement, whereas secondary outcomes include side effects (eg, paraesthesia, vertigo, seizures) and quality of life. A pairwise meta-analysis and NMA based on a Bayesian framework will be conducted using Stata and R statistical software. The Grading of Recommendations Assessment, Development, and Evaluation system will assess outcome indicator evidence quality. ETHICS AND DISSEMINATION: As all data in this study will be taken from the literature, ethical approval is not needed. We will publish our work in peer-reviewed publications and present it at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023456386.

Clinical efficacy of ceftazidime/avibactam combination therapy for severe hospital-acquired pulmonary infections caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa.

OBJECTIVES: This retrospective study aimed to identify the effectiveness of ceftazidime/avibactam (CAZ/AVI) and its optimisation programs for severe hospital-acquired pulmonary infections (sHAPi) caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa (CRPA and DTR-P. aeruginosa). METHODS: We retrospectively analysed observational data on treatment and outcomes of CAZ/AVI for sHAPi caused by CRPA or DTR-P. aeruginosa. The primary study outcomes were to evaluate the clinical and microbiology efficacy of CAZ/AVI. RESULTS: The cohort consisted of 84 in-patients with sHAPi caused by CRPA (n = 39) and DTR-P. aeruginosa (n = 45) who received at least 72 h of CAZ/AVI therapy. The clinical cure rate was 63.1% in total. There was no significant difference in study outcomes between patients treated with CAZ/AVI monotherapy and those managed with combination regimens. CAZ/AVI as first-line therapy possessed prominent clinical benefits regarding infections caused by DTR-P. aeruginosa. The clinical cure rate was positively relevant with loading dose for CAZ/AVI (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.004-0.19; P < 0.001) and with CAZ/AVI administration by prolonged infusion (odds ratio 0.15; 95% confidence interval 0.03-0.77; P = 0.002). APACHE II score>15 (P = 0.013), septic shock at infection onset (P = 0.001), and CAZ/AVI dose adjustment for renal dysfunction (P = 0.003) were negative predictors of clinical cure. CONCLUSION: CAZ/AVI is a valid alternative for sHAPi caused by CPRA and DTR-P. aeruginosa, even when used alone. Optimisations of the treatment with CAZ/AVI in critically ill patients, including loading dose, adequate maintenance dose and prolonged infusion, were positively associated with potential clinical benefits.

Effects of breathing exercises on chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: A range of studies concerning the effects of breathing exercises on chronic low back pain (CLBP) have been proven inconclusive. OBJECTIVE: The study aimed to evaluate the effectiveness of breathing exercises for the treatment of CLBP. METHODS: We considered randomized controlled trials in English or Chinese that used breathing exercises for the treatment of CLBP. An electronic search was performed in the MEDLINE, EMBASE, Web of Science, Cochrane Library, CNKI, Wan Fang, and CBM databases for articles published up to November 2022. Two reviewers independently screened the articles, assessed the risk of bias using the Cochrane risk of bias tool, and extracted the data. The outcomes included pain, lumbar function and pulmonary function post-intervention. RESULTS: A total of thirteen studies (n= 677) satisfied the inclusion criteria. The meta-analysis results demonstrated a significant effect of breathing exercises on the Visual Analog Scale (VAS) score (SMD =-0.84, 95% CI: -1.24 to -0.45, P< 0.0001), the Oswestry Disability Index (ODI) score (SMD =-0.74, 95% CI: -0.95 to -0.54, P< 0.00001), Forced Vital Capacity (FVC) score (MD = 0.24, 95% CI: 0.10 to 0.37, P= 0.0006), Forced Expiratory Volume in 1 second /Forced Vital Capacity (FEV1/FVC) (MD = 1.90, 95% CI: 0.73 to 3.07, P= 0.001), although there was no significant difference between the breathing exercises and control interventions for Forced Expiratory Volume in the first second (FEV1) score (MD = 0.22, 95% CI = [0.00, 0.43], P= 0.05), and Maximal Voluntary Ventilation (MVV) score (MD = 8.22, 95% CI = [-4.02, 20.45], P= 0.19). CONCLUSION: Breathing exercises can reduce pain, assist people with lumbar disabilities, and improve pulmonary function, and could be considered as a potential alternative treatment for CLBP.

Effect of robot-assisted gait training on motor dysfunction in Parkinson's patients:A systematic review and meta-analysis.

BACKGROUND: Robot-assisted gait training (RAGT) has been reported to treat motor dysfunction in patients with Parkinson's disease (PD) in the last few years. However, the benefits of RAGT for treating motor dysfunction in PD are still unclear. OBJECTIVES: To investigate the efficacy of RAGT for motor dysfunction in PD patients. METHODS: We searched PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, Chinese Biomedical Literature Database (CBM), and Chinese VIP Database for randomized controlled trials investigating RAGT to improve motor dysfunction in PD from the databases' inception dates until September 1, 2022. The following outcome indexes were employed to evaluate motor dysfunction: the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), 10-Meter Walk Test gait speed (10-MWT), gait speed, stride length, cadence Unified Parkinson Disease Rating Scale Part III (UPDRS III), 6-Minute Walk Test (6MWT), and the Timed Up and Go test (TUG). The meta-analysis was performed using the proper randomeffect model or fixed-effect model to evaluate the difference in efficacy between the RAGT and the control groups. The Cochrane Risk of Bias Tool was used for the included studies and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to interpret the certainty of the results. RESULTS: The results consisted of 17 studies comprising a total of 670 participants. Six hundred and seven PD patients with motor dysfunction were included: 335 in the RAGT group and 335 in the control group. This meta-analysis results established that when compared with the control group, robot-assisted gait training improved the BBS results of PD patients (MD: 2.80, 95%CI: 2.11-3.49, P< 0.00001), ABC score (MD: 7.30, 95%CI: 5.08-9.52, P< 0.00001), 10-MWT (MD: 0.06, 95%CI: 0.03-0.10, P= 0.0009), gait speed (MD: 3.67, 95%CI: 2.58-4.76, P< 0.00001), stride length (MD: 5.53, 95%CI: 3.64-7.42, P< 0.00001), cadence (MD: 4.52, 95%CI: 0.94-8.10, P= 0.01), UPDRS III (MD: -2.16, 95%CI: -2.48--1.83, P< 0.00001), 6MWT (MD: 13.87, 95%CI: 11.92-15.82, P< 0.00001). However, RAGT did not significantly improve the TUG test result of patients with PD (MD =-0.56, 95% CI: -1.12-0.00, P= 0.05). No safety concerns or adverse reactions among robot-assisted gait training patients were observed. CONCLUSION: Even though RAGT can improve balance function, walking function, and gait performance and has demonstrated positive results in several studies, there is currently insufficient compelling evidence to suggest that it can improve all aspects of lower motor function.

A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia.

PURPOSE: Interferon-stimulated gene 15 (ISG15) deficiency, a rare human inborn error of immunity characterized by susceptibility to Bacillus Calmette-Guerin (BCG) diseases, neuropathic and dermatological manifestations. METHODS: The clinical and immunological features of two siblings with ISG15 deficiency combined with asymptomatic myeloperoxidase (MPO) mutations were analyzed, and their pathogenesis, as well as target therapeutic candidates, were explored. RESULTS: The manifestation in patient 2 was skin lesions, while those in patient 1 were intracranial calcification and recurrent pneumonia. Whole-exome identified novel, dual mutations in ISG15 and MPO. PBMCs and B cell lines derived from the patients showed hyper-activated JAK/STAT signaling. Normal neutrophil function excluded pathogenicity caused by the MPO mutation. RNA sequencing identified baricitinib as therapeutic candidate. CONCLUSIONS: We report two sibling patients harboring the same novel ISG15 mutation showing diverse clinical features, and one harbored a rare phenotype of pneumonia. These findings expand the clinical spectrum of ISG15 deficiency and identify baricitinib as therapeutic candidate.

An early-onset SLE patient with a novel paternal inherited BACH2 mutation.

BACH2-related immunodeficiency and autoimmunity (BRIDA) is an inborn error of immunity, newly reported in 2017, presenting with symptoms of immunoglobulin deficiency and ongoing colitis. Studies using a mouse model have demonstrated that BACH2 deficiency predisposes individuals to systemic lupus erythematosus (SLE); however, no BACH2 deficiency has been reported in SLE patients. Here we describe a patient with BRIDA presenting with early-onset SLE, juvenile dermatomyositis, and IgA deficiency. Whole exome sequencing analysis of the patient and her parents revealed a novel heterozygous point mutation in BACH2, c.G1727T, resulting in substitution of a highly conserved arginine with leucine (R576L), which is predicted to be deleterious, in the patient and her father. Reduced BACH2 expression and deficient transcriptional repression of the BACH2 target, BLIMP1, were detected in PBMCs or lymphoblastoid cell lines of our patient. Notably, extreme reduction of memory B cells was detected in the patient's father, although he had no obvious symptoms. SLE symptoms and recurrent fever were relieved by treatment with prednisone combined with tofacitinib. Thus, we present the second report of BRIDA and demonstrate that BACH2 may be a monogenic cause of SLE.

Adverse reactions after treatment with dasatinib in chronic myeloid leukemia: Characteristics, potential mechanisms, and clinical management strategies.

Dasatinib, a second-generation tyrosine kinase inhibitor, is recommended as first-line treatment for patients newly diagnosed with chronic myeloid leukemia (CML) and second-line treatment for those who are resistant or intolerant to therapy with imatinib. Dasatinib is superior to imatinib in terms of clinical response; however, the potential pulmonary toxicities associated with dasatinib, such as pulmonary arterial hypertension and pleural effusion, may limit its clinical use. Appropriate management of dasatinib-related severe events is important for improving the quality of life and prognosis of patients with CML. This review summarizes current knowledge regarding the characteristics, potential mechanisms, and clinical management of adverse reactions occurring after treatment of CML with dasatinib.

Patients' attitudes towards switching to national volume-based procurement (NVBP) Drugs-a qualitative investigation in Wuhan, China.

BACKGROUND: The implementation of the NVBP policy has generated considerable reductions in drug procurement prices and an increase in the market share of the NVBP drugs.This study aimed to investigate patients' attitudes towards switching to drugs of national volume-based procurement (NVBP) and identify their underlying influencing factors in Wuhan, China. METHODS: A total of 21 eligible patients from the Wuhan Union Hospital who were switched to NVBP drugs between January 2022 and May 2022 were included in our study. Semi-structured face-to-face interviews were conducted to collect interview information and the interview data was analyzed by the Colaizzi seven-step method. RESULTS: Twenty-one semi-structured face-to-face interviews were conducted. The duration of each interview was 25-35 min and three themes related to patients' attitudes and their influencing factors were extracted, including (1) Patients' perception of the NVBP drugs; (2) Family and social influence to patients; (3) Medication habits of patients. This study found: 1) 71.4% patients (15/21) showed a positive attitude towards switching to NVBP medicines; 2)80.9% patients (17/21) have felt a significant reduction in their medication cost after the implementation of the NVBP policy; 3)Advices from healthcare professionals and health insurance reimbursement policies showed great impacts on patients' attitude towards switching to NVBP drugs; 4)Attitudes towards switching to NVBP drugs varied considerably among patients with different severities of disease. CONCLUSION: The implementation of the NVBP policy has significantly reduced the cost of healthcare for patients and has been supported by71.4% (15 of 21) patients. However, some issues have been identified in the implementation of the policy in this study. Health professionals in general need to contribute more efforts to improve patients' preconceptions about the NVBP drugs and boost their confidence in the NVBP drugs.

Safety monitoring in inactivated COVID-19 vaccines by clinical pharmacists from a single center in China.

Given that vaccine-induced adverse effects were mostly based on previous laboratory research and clinical trials, real-world data on the safety of coronavirus disease 2019 (COVID-19) vaccination were lacking. This study reported the adverse events (AEs) among inactivated COVID-19 vaccine recipients. Data were collected from a total of 2,808 hospital employees and their family members in Wuhan, China, with all of them receiving the first dose of inactivated COVID-19 vaccines from two pharmaceutical companies. The first dose was given between 29th April and 13th May 2021. A total of 2,732 vaccinees received the second dose between 27th May and 8th July 2021. The whole process of receiving the vaccine was monitored by clinical pharmacists, and the information on AEs including demographics, occurrence, types, and severity was recorded through an online questionnaire and telephone follow-up. Most of the common AEs were mild and tolerable, and the overall incidence of AEs was lower than the data from the safety profile in clinical trials. Moreover, the incidence of AEs in the first dose (21.30%, 598) was higher than that in the second dose (16.07%, 439). Furthermore, the first injection had more severe AEs (4, 0.14%) than the second injection (2, 0.07%). The AEs involved the skin, muscle, respiratory tract, gastrointestinal tract, cardiovascular system, and other tissues and systems. The most common AE was pain at the injection site (first dose: 10.19%, second dose: 12.55%). All the vaccinees with AEs for both doses recovered fully in the end. It was noted that some AEs might cause blood coagulation disorder and bleeding risk. Therefore, ongoing monitoring of AEs after COVID-19 vaccination is essential in evaluating the benefits and risks of each vaccine.

Development of an Escherichia coli whole cell biocatalyst for the production of hyperoside.

OBJECTIVE: To produce high concentrations of hyperoside from quercetin using recombinant Escherichia coli with in situ regeneration of UDP-galactose. RESULTS: Sucrose synthase from Glycine max (GmSUS) was co-expressed with UDP-glucose epimerase from E. coli (GalE) in E. coli for regenerating UDP-galactose from UDP and sucrose. Glycosyltransferase from Petunia hybrida (PhUGT) was introduced to synthesize hyperoside from quercetin through the regeneration system of UDP-galactose. Co-expressing with molecular chaperones GroEL/ES successfully enhanced the catalytic efficiency of the recombinant strain, which assisted the soluble expression of PhUGT. By using a fed-batch approach, the production of hyperoside reached 863.7 mg L-1 with a corresponding molar conversion of 93.6% and a specific productivity of 72.5 mg L-1 h-1. CONCLUSION: The method described herein for hyperoside production can be widely applied for the synthesis of isorhamnetin-3-O-galactoside, kaempferol-3-O-galactoside and other flavonoids.

Clonal behaviour of myogenic precursor cells throughout the vertebrate lifespan.

To address questions of stem cell diversity during skeletal myogenesis, a Brainbow-like genetic cell lineage tracing method, dubbed Musclebow2, was derived by enhancer trapping in zebrafish. It is shown that, after initial formation of the primary myotome, at least 15 muscle precursor cells (mpcs) seed each somite, where they proliferate but contribute little to muscle growth prior to hatching. Thereafter, dermomyotome-derived mpc clones rapidly expand while some progeny undergo terminal differentiation, leading to stochastic clonal drift within the mpc pool. No evidence of cell-lineage-based clonal fate diversity was obtained. Neither fibre nor mpc death was observed in uninjured animals. Individual marked muscle fibres persist across much of the lifespan indicating low rates of nuclear turnover. In adulthood, early-marked mpc clones label stable blocks of tissue comprising a significant fraction of either epaxial or hypaxial somite. Fusion of cells from separate early-marked clones occurs in regions of clone overlap. Wounds are regenerated from several local mpcs; no evidence for specialised stem mpcs was obtained. In conclusion, our data indicate that most mpcs in muscle tissue contribute to local growth and repair and suggest that cellular turnover is low in the absence of trauma.

Generation of human induced pluripotent stem cell line from peripheral blood mononuclear cells from an activated phosphoinositide 3-kinase δ syndrome patient.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a rare autosomal dominant primary immunodeficiency disease (PID) which was caused by the acquired mutation of PIK3CD gene. In this study, we generated a human induced pluripotent stem cell (hiPSC) line CHCMUi001-A from the peripheral blood mononuclear cells (PBMCs) of a APDS patient, who has a heterozygous mutation (c.3061 G > A) in the PIK3CD gene. This iPSC line presented a normal karyotype and exhibited characteristics of pluripotent stem cells. This iPSC line can be very useful for not only studying disease mechanisms but also developing new potential clinical treatments for APDS patients.

Knowledge, attitudes, and practices toward cancer pain management amongst healthcare workers (physicians, pharmacists, and nurses): a cross-sectional study from first-tier cities in China.

PURPOSE: China is currently one of the countries with the largest increased number of new cancer cases in the world, but cancer pain management (CPM) is still inadequate. This study uses a questionnaire to demonstrate the status and differences in knowledge, attitude and practice (KAP) of CPM among healthcare workers (HCWs) in developed regions of China, to find deficiencies and priorities for improvement, from which areas and advantages of the role of pharmacists and mobile devices can be explored. METHODS: This study used data from a questionnaire on CPM from March to June 2019. The study population consisted of a total of 515 HCWs in four first-tier developed cities in China. The questionnaire has four major components, analysis of differences in KAP of different occupations through one-way analysis of variance (ANOVA). RESULTS: Among the respondents, the physicians had the highest knowledge scores toward CPM, pharmacists had the lowest practice scores. Around half of the respondents indicated that their hospital or department have a pharmacist participating in CPM. Physicians and nurses were more likely to expect pharmacists to provide drug counseling. The HCWs interviewed most expect that the mobile-based pain management system can automatically screen and mark patients with pain. CONCLUSION: From this study, it can be suggested that pharmacists and nurses in the CPM team should actively promote relevant knowledge. Besides, pharmacists should focus on improving practical ability such as increasing the frequency of pain assessment. Multidisciplinary collaboration and the introduction of mobile devices can improve and refine the CPM.

The role of probiotics in coronavirus disease-19 infection in Wuhan: A retrospective study of 311 severe patients.

PURPOSE: Researches revealed that probiotics maybe a potential strategy for COVID-19, whereas there is a lack of related evidence. This study aims to analyze the role of probiotics on severe COVID-19 patients. METHODS: In the current retrospective single-center study, we collected data of 311 consecutive severe patients with confirmed COVID-19 in Wuhan Union Hospital from Feb 3rd to Feb 20th, 2020. Epidemiological, clinical and medication characteristics were compared and analyzed between patients with or without probiotics. RESULTS: In total, 93 of the 123 patients (75.61%) who were treated with probiotics survived to hospital discharge with the median inpatient day of 32 days and mean virus clearance time of 23 days, which were significantly longer than those of patients without probiotics. There were no bias in laboratory parameters, except for IL-6 and ESR, which were significantly higher in patients treated probiotics. We tracked the dynamic changes of 8 selected laboratory parameters (IL-6, CRP, total T lymphocytes, NK cells, B lymphocyte, CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) and found that probiotics could not reduce the increased IL-6 levels but possessed the ability to moderate the immunity and decreased the incidence of secondary infection in COVID-19 patients. CONCLUSIONS: Probiotics could be an effective strategy for the treatment of COVID-19 patients to reduce the secondary infection and moderated the immunity.

Efficacy and Safety of Thalidomide As a Pre-Medication of Chemotherapy-Induced Nausea and Vomiting (CINV) Following Highly Emetogenic Chemotherapy (HEC): A Systematic Review and Meta-Analysis.

BACKGROUND: In China, thalidomide (THD) has been used to prevent chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC); however, there is limited evidence on the efficacy and safety of THD in this setting. The aim of this study was to evaluate the efficacy, safety, and impact on quality of life (QoL) of THD on CINV following HEC. METHODS: Electronic databases were systematically searched for all randomized controlled trials (RCTs) in HEC using THD. The primary outcomes were complete response (CR) and no nausea, Secondary outcomes were the incidence of adverse events and QoL related indicators. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a fixed-effects model. In the case of heterogeneity (I2≥50%), a random-effects model was performed. RESULTS: A total of 3168 patients were included from 34 RCTs. In terms of CR rate, THD plus 5-HT3 receptor antagonist (5-HT3RA) with or without dexamethasone (DEX) was significantly higher than 5-HT3RA with or without DEX in the acute phase (74.4% vs 67.4%; RR 1.10), delayed phase (70.6% vs 50.4%; RR 1.53), and overall phase (68.4% vs 53.4%; RR 1.28). In terms of no nausea rate, the THD group was also significantly higher than the control group in the acute phase (61.7% vs 55.5%; RR 1.12), delayed phase (50.5% vs 30.0%; RR 1.69), and overall phase (44.6% vs 29.9%; RR 1.50). There was no statistical difference in the incidence of fatigue, headache, diarrhea, rash, hepatorenal damage, and myelosuppression between those with and without THD. The incidence of increase in KPS scores, weight gain, appetite improvement, and sleep quality improvement were significantly higher with the addition of THD. CONCLUSIONS: THD may be effective and safe for the prevention of CINV patients treated with HEC and may improve QoL.

Analysis of Influencing Factors and Pharmaceutical Care of Patients with COVID-19 in Fangcang Shelter Hospital.

PURPOSE: In December 2019, coronavirus disease 2019 (COVID-19) was first identified in Wuhan, and rapidly spread throughout China. Patients with mild symptoms were admitted to Fangcang shelter hospitals for centralized quarantine. We aimed to clarify the medication usage, related adverse reactions, and pharmaceutical interventions in patients with mild COVID-19. PATIENTS AND METHODS: We innovatively carried out targeted pharmacy services. We provided online and off-line pharmaceutical services to patients in the Fangcang shelter hospital. The use of medication, related adverse reactions, and the effects of pharmaceutical intervention were analyzed. RESULTS: Lower blood lymphocyte count was proposed as the most significant risk factor in patients with mild illness. All patients received antiviral treatment (arbidol, oseltamivir, and ribavirin); 78.4% of patients received antibiotic therapy (moxifloxacin, levofloxacin, and cefdinir); patients in the moderate disease group received more antibiotic therapy than those in the mild disease group. Most of the patients were treated with traditional Chinese medicine. Patients with moderate disease preferred to receive sedative hypnotic therapy. Diarrhea, nausea and vomiting, insomnia, arrhythmia, and constipation were the most common adverse reactions. The rate of mild-to-moderate illness in the pharmaceutical intervention and non-intervention groups was 20.6% and 31.7%, respectively. CONCLUSION: Most patients with mild illness were treated with antiviral, antibiotic, and Chinese medicine therapy. However, attention should be paid to patients with mild illness presenting with hypertension and low lymphocyte count at the onset; these patients are more likely to develop moderate or severe disease. Moreover, there were many drug-related problems in Fangcang shelter hospital; pharmaceutical care might contribute to alleviate the progress of the patient's condition. Pharmacists should be prepared to provide skilled and effective services to patients, with the aim to ensure medication safety and promote the overall control of the COVID-19 pandemic.

NCK1-AS1 enhances glioma cell proliferation, radioresistance and chemoresistance via miR-22-3p/IGF1R ceRNA pathway.

Glioma is the deadliest disease in human central nerve system. Abnormal expression of long noncoding RNA (lncRNA) expression has been demontrated to be implicated in various cancers. The oncogenic role of lncRNA NCK1-AS1 has been validated in cervical cancer, wheras its role in glioma remians obscure. Our research findings suggested that NCK1-AS1 was upregulated in glioma tissues and cells. NCK1-AS1 deficiency hindered cell proliferation and enhanced cell apoptosis. Additionally, the chemoresistance and radioresistance of glioma cells were impaired by NCK1-AS1 depletion. Moreover, miR-22-3p, a downstream gene of NCK1-AS1, could weaken glioma cell chemoresistance and radioresistance. Similarly, IGF1R was the downstream target gene of miR-22-3p. Further mechanism and function assays demonstrated that NCK1-AS1 promoted glioma cell growth, chemoresistance and radioresistance via sponging miR-22-3p to upregulate IGF1R. Finally, the tumor facilitator function of NCK1-AS1 was also verified by in vivo experiments. Taken together, NCK1-AS1 contributes to glioma cell proliferation, radioresistance and chemoresistance via miR-22-3p/IGF1R ceRNA pathway, which might provide a new insight for improving the radiotherapy and chemotherapy treatments of glioma.

Enteric glia as a source of neural progenitors in adult zebrafish.

The presence and identity of neural progenitors in the enteric nervous system (ENS) of vertebrates is a matter of intense debate. Here, we demonstrate that the non-neuronal ENS cell compartment of teleosts shares molecular and morphological characteristics with mammalian enteric glia but cannot be identified by the expression of canonical glial markers. However, unlike their mammalian counterparts, which are generally quiescent and do not undergo neuronal differentiation during homeostasis, we show that a relatively high proportion of zebrafish enteric glia proliferate under physiological conditions giving rise to progeny that differentiate into enteric neurons. We also provide evidence that, similar to brain neural stem cells, the activation and neuronal differentiation of enteric glia are regulated by Notch signalling. Our experiments reveal remarkable similarities between enteric glia and brain neural stem cells in teleosts and open new possibilities for use of mammalian enteric glia as a potential source of neurons to restore the activity of intestinal neural circuits compromised by injury or disease.

Molecular and Phenotypic Characterization of Nine Patients with STAT1 GOF Mutations in China.

PURPOSE: Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes. METHODS: We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations. RESULTS: This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naïve and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression. CONCLUSIONS: Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed.

Analysis of Ornidazole Injection in Clinical Use at Post-marketing Stage by Centralized Hospital Monitoring System.

This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method, and investigate its widespread use in patients, in order to regulate and guide the rational drug use, improve the drug specificity and provide a basis for drug therapy. The study adopts a prospective, multi-center, large sample size, centralized hospital monitoring system. We selected five leading hospitals in Hubei province, and observed the inpatients who received the ornidazole injection from July 1, 2015 to October 31, 2015. The basic information of patients was recorded, as well as the drug use and adverse events. The statistical analysis was performed based on these data. A total of 4396 individuals were enrolled in this study, most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections, and surgical treatment of anaerobic infections, abdominal infections and pelvic infections. The irrational drug use existed mainly in the prescribing and administration process, including unreasonable dosing frequency, rapid intravenous drip speed and extended duration of drug use. Eleven cases of adverse reactions were collected during the monitoring, incidence rate of adverse reactions was 2.5‰; adverse drug reactions occurred within 30 min. The study results fully reflected the usage of ornidazole injection in the real world. Based on the study, we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection. Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.