ObjectiveDirected differentiation of human induced pluripotent stem cells （hiPSCs） into spinal cord γ-aminobutyric acid （GABA）-ergic progenitor cells were implanted into an decellularized optical nerve （DON） bioscaffold to construct a hiPSC-derived inhibitory neural network tissue with synaptic activities. This study aimed to provide a novel stem cell-based tissue engineering product for the study and the repair of central nervous system injury. MethodsThe combination of stepwise directional induction and tissue engineering technology was applied in this study. After hiPSCs were directionally induced into human neural progenitor cells （hNPCs） in vitro， they were seeded into a DON for three-dimensional culture， allowing further differentiation into inhibitory GABAergic neurons under the specific neuronal induction environment. Transmission electron microscopy and whole cell patch clamp technique were used to detect whether the hiPSCs differentiated neurons could form synapse-like structures and whether these neurons had spontaneous inhibitory postsynaptic currents， respectively， in order to validate that the hiPSC-derived neurons would form neural networks with synaptic transmission potentials from a structural and functional perspective. ResultsThe inhibitory neurons of GABAergic phenotype were successfully induced from hiPSCs in vitro， and maintained good viability after 28 days of culture. With the transmission electron microscopy， it was observed that many cell junctions were formed between hiPSC-derived neural cells in the three-dimensional materials， some of which presented a synapse- like structure， manifested as the slight thickness of cell membrane and a small number of vesicles within one side of the cell junctions， the typical structure of a presynatic component， and focal thickness of the membrane of the other side of the cell junctions， a typical structure of a postsynaptic component. According to whole-cell patch-clamp recording， the hiPSC-derived neurons had the capability to generate action potentials and spontaneous inhibitory postsynaptic currents were recorded in this biotissue. ConclusionsThe results of this study indicated that hiPSCs can be induced to differentiate into GABAergic progenitor cells in vitro and can successfully construct iPSC-derived inhibitory neural network tissue with synaptic transmission after implanted into a DON for three-dimensional culture. This study would provide a novel neural network tissue for future research and treatment of central nervous system injury by stem cell tissue engineering technology.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

To assess the clinical efficacy of traditional Chinese medicine injection for adjuvant treatment of mycoplasma pneumoniae pneumonia in children by network Meta-analysis method. We retrieved CNKI, WanFang, CBM, Cochrane Library, PubMed from the establishment to September 2018. Two reviewers independently screened out literatures, extracted data and assessed the methodological quality of included studies. The data were analyzed by Stata 13.0 software. Totally 89 RCTs were included, involving 8 kinds of traditional Chinese medical injections and 8 936 patients. According to the results of network Meta-analysis, the order by the total effective rate from high to low was Huangqi Injection>Xiyanping Injection>Tanreqing Injection>Compound Danshen Injection>Reduning Injection>Yanhuning Injection>Qingkailing Injection>Xixinnao Injection; the order by cooling time from high to low was Reduning Injection> Yanhuning Injection>Qingkailing Injection>Tanreqing Injection>Huangqi Injection>Xiyanping Injection>Xiexinnao Injection>Compound Danshen Injection; the order by the cough disappeared time from high to low was Compound Danshen Injection>Qingkailing Injection>Xiyanping Injection>Huangqi Injection>Yanhuning Injection>Reduning Injection>Tanreqing Injection>Xixinnao Injection; the order by the rales disappearing time from high to low was Qingkailing Injection>Yanhuning Injection>Reduning Injection>Huangqi Injection>Tanreqing Injection>Xiyanping Injection>Xixinnao Injection. The results show that traditional Chinese medicine injection has a significant clinical efficacy in the adjuvant treatment of various symptoms of mycoplasma pneumoniae pneumonia in children. Due to the small sample size, more studies are required to verify the strength of evidence.
Child ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Injections ; Medicine, Chinese Traditional ; Network Meta-Analysis ; Pneumonia, Mycoplasma/drug therapy*

Using silica gel column chromatography, gel chromatography and HPLC, we isolated secondary metabolites in fermentation broth of a rifamycin resistant mutation strain Streptomyces sp. HS-NF-1046R. Based on spectroscopic data, the chemical structures of three compounds were identified as 3-hydroxyl-2-N-propionyl- anthranilamide (1), 2,3-dihydro-8-hydroxy-2,2-dimethyl quinazolin-4-(1H)-one (2) and 2-aminobenzamide (3). Compounds 1 and 2, as new entities, were evaluated for cytotoxicity against A549, HepG2, HCT-116 and K562 cells using the SRB assay. Compounds 1 and 2 exhibited no cytotoxicity with IC₅₀ over 100 μmol·L^-1.

Objective To investigate the expressions,roles,and clinical significance of microRNA-365(miR-365)and E74-like factor 4(ELF4)in cervical cancer. Methods The expressions of miR-365 in normal cervical tissues(n=34),cervical intraepithelial neoplasia 1(CIN 1)(n=31),cervical intraepithelial neoplasia2-3(CIN 2-3)(n=37),squamous cell carcinoma of the cervix(SCC)(n=33),and three cervical cancer cell lines(C33A cells,Hela cells,and SiHa cells)were detected by real-time quantitative polymerase chain reaction(qPCR).Bioinformatic prediction and luciferase reporter gene assay were performed to verify whether ELF4 was a direct target of miR-365.Western blot and immunohistochemistry were used to detect ELF4 expression in cervical cancer cells and in different pathological cervix tissues.CCK8 assay was used to detect the effect of overexpression or inhibition of miR-365 on the proliferation of cervical cancer cells at different time points.The relationships among the miR-365 expression,ELF4 expression,and clinicopathological parameters of cervical cancer were analyzed by correlation analysis. Results qPCR results showed that compared with the normal cervical cell HcerEpic,the expressions of miR-365 in CIN1,CIN2-3,and cervical cancer tissues gradually decreased with the increased pathologic grade,and its expressions also decreased in different cervical cancer cell lines.The luciferase reporter gene assay confirmed that ELF4 was the direct target of miR-365.Western blot showed that the expression of ELF4 increased in all three cervical cancer cell lines compared with normal cervical epidermal cell(P=0.013,P=0.002,P=0.004).Immunohistochemistry showed that ELF4 expression was up-regulated in CIN and cervical cancer tissues.CCK8 assay showed that overexpression of miR-365 inhibited cell proliferation,while inhibition of miR-365 promoted the proliferation of three cervical cancer cells(P<0.05).Further analysis confirmed that there was a negative correlation between the expression levels of miR-365 and ELF4 in CIN2-3 and SCC(r=-0.351,P=0.045;r=-0.349,P=0.035).Clinical analysis showed that the expressions of both miR-365 and ELF4 were correlated with tumor size,pathological grade,and clinical stage in SCC(all P < 0.05).Conclusion The decreased expression of miR-365 in human cervical cancer cells relieves its inhibitory effect on ELF4,which promotes the proliferation of cervical cancer cells and the formation of tumor.
Cell Proliferation ; DNA-Binding Proteins ; genetics ; Female ; HeLa Cells ; Humans ; MicroRNAs ; genetics ; Transcription Factors ; genetics ; Uterine Cervical Neoplasms ; genetics

Objective To investigate the protective effect and the underlying mechanism of water soluble coenzyme Q10 (CoQ10)against rotenone induced injury on PC12 cells model.Methods PC12 cells were cultured with rotenone,water-soluble CoQ1 0 was added to the culture media 3 hours prior to the rotenone incubation.We determined cell viability by CCK8;reactive oxygen species (ROS)was detected by spectrophotometer;and Bcl-2, Bax,active Caspase-3,Caspase-9 and apoptosis-inducing factor (AIF)were measured by Western blotting after 24-hour rotenone incubation.Results After the treatment by rotenone,cell viability decreased significantly (P＜0.01)and ROS level increased (P＜0.01).CoQ10 could improve PC12 cell viability (P＜0.01)and reduce the level of ROS (P＜0.01).Western blotting experiments showed that CoQ10 could reduce rotenone-induced Caspase-9 (P＜0.05),active Caspase-3 (P＜0.05)and Bax (P＜0.01)expressions,increase the expression of Bcl-2 (P＜0.01),and prevent nuclear translocation of AIF (P＜0.05).Conclusion CoQ10 has a protective effect on rotenone-induced apoptosis in PC12 cells,the mechanism of which may be through scavenging ROS in cells;decreasing caspase-9 ,active caspase-3 and Bax expressions;and increasing the expression of Bcl-2 ;and preventing AIF nuclear translocation.

In the clinical practice, Professor Jiang Liangduo, a national senior Chinese medicine doctor, has created the theory of "sanjiao meridian stasis" from the theory of meridian dialectics and from the overall state. In this paper, the traditional Chinese medicine and Western medicine clinical characteristics of sanjiao meridian stasis theory which is often used by Professor Jiang Liangduo in the treatment of out-patient syndrome differentiation, were first studied and summarized to investigate its inherent regularity. First, the source of data and research methods were introduced, and then the Traditional Chinese Medicine Inheritance Support System was used with the method of data mining to retrospectively analyze the disease characteristics of Chinese and Western medicine in 279 patients with sanjiao meridian stasis diagnosed by Professor Jiang in 2014. Then the following main conclusions were made after research: sanjiao meridian stasis was more common in women as well as young and middle-aged population. Often manifested by prolonged treatment course, red tongue with yellowishfur, with good correlation between modern Western medicine diagnosis and TCM differentiation syndrome. The symptoms of sanjiao meridian stasis syndrome are mostly of heat syndromes, and middle-aged patients are the most common patients with stasis and stasis of sanjiao. Related information of Western medicine diagnosis can help to diagnose the "sanjiao meridian stasis".

OBJECTIVETo summarize the 23-year experience of laparoscopic biliary surgery in General Hospital of PLA and evaluate the application of laparoscopic surgery in the treatment of biliary diseases.

METHODSWe retrospectively analyzed the clinical data of 11 419 consecutive patients with biliary diseases undergoing laparoscopic surgery from April, 1992 and December, 2014. The disease spectrum was compared between patients treated before December 31, 2003 and those treated after the time point.

RESULTSThe 11419 patients receiving laparoscopic surgery accounted for 56.3% of the total patients undergoing biliary surgeries during the 23 years, including 4701 male and 6718 female patients with a mean age of 50.9∓13.2 years (6-93 years). Most (80.83%) of the patients received laparoscopic surgery for gallbladder stones, and 12.53% patients had the operation for gallbladder polyps. The laparoscopic operation rate was 84.81% in patients with gallbladder stones and 34.91% in patients with extrahepatic bile duct stones, but remained low in patients with biliary carcinoma. In laparoscopic operations, laparoscopic cholecystectomy was the most frequent (96.18%) followed by operations for extrahepatic bile duct stones, in which primary suture accounted for 1.38%, traditional T tube drainage for 0.90% and laparoscopic transcystic duct exploration for 0.72%. For malignant tumors, laparoscopic technique was used mainly for the purpose of exploration (0.34%). The application of laparoscopic technique in biliary surgery tended to increase after the year 2004, especially for benign gallbladder diseases and extrahepatic bile duct stones (P<0.05).

CONCLUSIONLaparoscopic technique in biliary surgery is gradually replacing the traditional open operation and becomes the gold standard for the treatment of benign biliary diseases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; surgery ; Bile Ducts, Extrahepatic ; Child ; Cholecystectomy, Laparoscopic ; Drainage ; Female ; Gallbladder Diseases ; surgery ; Gallstones ; surgery ; Humans ; Laparoscopy ; trends ; Male ; Middle Aged ; Retrospective Studies ; Young Adult