Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective:To analyze the genetic etiology and prognosis in fetuses with increased nuchal translucency (NT) in order to assist in the clinical prenatal genetic counseling and diagnosis.Methods:This study retrospectively enrolled 1 658 cases of singleton pregnancy (<35 years old) receiving invasive prenatal diagnosis, including karyotype analysis and/or chromosome microarray analysis or copy number variation (CNV) sequencing, due to NT value ≥2.5 mm in the first trimester in Henan Provincial People's Hospital from August 2014 to December 2021. They were divided into different groups according to the thickness of NT (≥2.5-<3.0, ≥3.0-<3.5, ≥3.5-<4.5, ≥4.5-<5.5, ≥5.5-<6.5 and ≥6.5 mm groups) and abnormal ultrasound findings (isolated increased NT group, increased NT complicated by soft markers/non-severe structural abnormality group and increased NT complicated by severe structural abnormality group). The results of invasive prenatal diagnosis and pregnancy outcomes were compared between different groups using Chi-square test and trend Chi-square test. Results:The detection rates of numerical abnormalities of chromosomes were 15.8% (262/1 658) and 17.6% (252/1 431) when the NT thickness cut-off value were 2.5 mm or 3.0 mm, respectively. Overall, the detection rate of numerical abnormalities of chromosomes increased with thickness of NT ( χ2trend=180.75, P<0.001), ranging from 6.6% (44/671) in the NT≥2.5-<3.5 mm group to 45.6% (113/248) in the NT≥5.5 mm group. The incidence of pathogenic/likely pathogenic CNV(P/LP CNV) did not increased with NT thickness ( χ2trend=3.26, P=0.071), and the highest detection rate was observed in the NT≥4.5-<5.5 mm group (9.0%, 19/211). The detection rate of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥2.5-<3.0 mm group and NT≥3.0-<3.5 mm group were 5.3% (10/188) and 9.6% (36/375), respectively, however, the difference was not statistically significant ( χ2=3.06, P=0.080). The detection rates of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥3.5-<4.5 mm group and NT≥2.5-<3.0 mm complicated by soft markers/ non-severe structural abnormality group were 12.7% (52/410) and 24.1% (7/29), respectively, and the risk were 2.6 times (95% CI: 1.3-5.2) and 5.7 times (95% CI: 2.0-16.4) of the isolated NT≥2.5-<3.0 mm group, respectively. The pregnancy termination rate increased with the NT thickness ( χ2trend=304.42, P<0.001), ranging from 10.8% (23/212) in the NT≥2.5-<3.0 mm group to 90.7% (117/129) in the NT≥6.5 mm group. After exclusion of the pregnancies terminated due to numerical abnormalities of chromosomes and P/LP CNV, 87.6% (862/984) of the fetus with increased NT were born alive. Conclusions:The detection rate of numerical abnormalities of chromosomes increases with the thickness of NT. Invasive prenatal diagnosis is required for non-advance aged singleton pregnant women when fetuses present with isolated NT≥2.5 mm with or without soft markers/structural abnormalities.

ObjectiveTo explore the comprehensive clinical value of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat stasis syndrome， and to provide evidence for the decision-making of clinical basic drug management. MethodBased on the "Guidelines for Comprehensive Clinical Evaluation of Drugs （Trial Version 2021）"， this study systematically reviewed the existing research on the treatment of chronic prostatitis with damp-heat stasis syndrome by Qianlieping capsules. Based on evidence-based medicine， clinical epidemiology， clinical medicine， evidence-based pharmacy， pharmacoeconomics， health statistics， health technology assessment， and other disciplines， the multi-criteria decision analysis model （MCDA） and CSC 2.0 software were used. The six dimensions of safety， effectiveness， economy， innovation， suitability， and accessibility of drugs， as well as traditional Chinese medicine（TCM） characteristics， were comprehensively evaluated qualitatively and quantitatively. ResultIn terms of safety， based on the spontaneous reporting system （SRS） of the National Center for ADR Monitoring， safety literature analysis， pharmacological and toxicological experiment report， and other evidence， the safety grade of Qianlieping capsules was evaluated as grade A， with good safety. In terms of effectiveness， based on the results of pharmacological and pharmacodynamic studies and Meta-analysis， and combined with the value and quality of the evidence for efficacy， the final efficacy grade of Qianlieping capsules was rated as B. In terms of economy， Qianlieping capsules was a class B drug of national medical insurance. Compared with those of similar Chinese patent medicines， the average daily cost of Qianlieping capsules was moderate， and there was no related cost increase during the administration process. Economic research showed that Qianlieping capsules combined with α-receptor blockers were more economical than α-receptor blockers alone. Based on the quality evaluation of economic evidence and the value evaluation of economic evidence， the economic grade of Qianlieping capsules was rated as B. In terms of innovation， Qianlieping capsules were a combination of cold and warm drugs， focusing on clearing heat， detoxifying， removing blood stasis， and relieving pain， with non-toxic medicinal materials. They obtained a number of invention patents. The enterprise service system was perfect， and the quality standard was higher than the international and Chinese standards. The innovation grade of Qianlieping capsules was rated as B. In terms of suitability， the results of the questionnaire survey showed that it had relatively good suitability for clinicians， nurses， pharmacists， and patients who used Qianlieping capsules. The information on Chinese patent medicines was complete and met the requirements of national standards. The suitability grade of Qianlieping capsules was rated as A. In terms of accessibility， Qianlieping capsules were moderately priced and affordable， with sufficient resources of medicinal materials， no shortage of medicinal materials， and good availability. The accessibility grade of Qianlieping capsules was rated as B. In terms of TCM medicine characteristics， the prescription of Qianlieping capsules was derived from Danshen Huoxue Decoction. The original prescription was used for the treatment of chronic prostatitis with blood stasis syndrome. The whole formula was recorded in The Complete Compendium of Fine Formulas （《良方大全》） published by Beijing Publishing Group Co.， Ltd. in 1991 and has been used for more than 30 years. The formula was a combination of warm and cold drugs， attacking pathogens without hurting healthy Qi. The grade of TCM characteristics of Qianlieping capsules was rated as B. ConclusionBased on the above "6+1" dimensions， the comprehensive evaluation result of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat and blood stasis syndrome is grade B， and it is recommended to convert it into the relevant policy results of basic clinical drug management according to the conditions.

Objective:To observe the morphological characteristics of urogenital hiatus in patients with gestational diabetes mellitus (GDM) after vaginal delivery.Methods:This study included 192 pregnant patients from Henan Provincial People′s Hospital who met the conditions between Jan.2020 and Aug.2021. All participants were screened for GDM by oral glucose tolerance test (OGTT) or fasting blood glucose at 24-28 weeks of pregnancy, and were divided into GDM group (34 cases) and non-GDM group (158 cases) based on the presence or absence of GDM. All participants underwent pelvic floor ultrasonography at the first trimester (6-8 gestational weeks), 3 days postpartum, 6 weeks postpartum, 6 months postpartum, and 1 year postpartum. Area of urogenital hiatus (AUH), transversal diameter of urogenital hiatus (TDUH) and anteroposterior diameter of urogenital hiatus (APDUH) were measured using Smart Pelvic. The Logistic regression model was used to calculate and match the propensity score between the GDM group and the non-GDM group.Results:In the non-GDM group, TDUH during rest maneuver at 6 weeks postpartum( P=0.319), the indicators during rest and contract maneuver at 6 months postpartum( P=0.586, 0.877, 0.164, 0.226, 0.465, 0.097), and TDUH during tension maneuver at 1 year postpartum( P=0.643) returned to the level of early pregnancy. In the GDM group, the indicators during rest maneuver and TDUH during contract maneuver at 6 months postpartum recovered to the level of early pregnancy ( P=0.647, 0.584, 0.376, 0.440), while APDUH and AUH during contract maneuver ( F=7.784, 9.785; P=0.005, <0.001) and the indicators during tension maneuver at 1 year postpartum( F=15.343, 11.974, 17.981; P<0.001) did not recover to the level of early pregnancy. After propensity score matching, APDUH and AUH during tension maneuver at 1 year postpartum in the GDM group were significantly greater than those in the non-GDM group( t=2.810, 2.926; P=0.006, 0.004). Conclusions:The pelvic floor muscles of GDM patients after vaginal delivery are more severely damaged, and the recovery speed is slower. Pelvic floor muscle exercise during pregnancy and enhanced postpartum follow-up are needed to prevent, diagnose and treat pelvic floor dysfunction early.

Objective To Investigate the cause of a food poisoning incident in a city in Dehong Prefecture， determine the scope of the incident， and to formulate effective prevention and control measures. Methods Field epidemiology and case-control study methods were used to formulate case definition； carry out case search； find suspicious food combined with clinical manifestations， dining history and other information； and collect samples from the suspicious food， cases and environment for laboratory testing. Results A total of 160 cases were found and the incidence rate was 26.02% （160/615）. The main clinical manifestations were diarrhea， leukocytosis， vomiting， nausea and abdominal pain. The average incubation period was 10.89±5.09 h， with 2 h as the shortest and 28 h as the longest. The epidemiological curve suggested the point source exposure mode. The results of case-control study showed that eating roast pork with green shoots was an independent risk factor （OR=13.09， 95%CI： 3.26‒52.54）.16 samples were tested by the local CDC laboratory. Proteus mirabilis was detected in two the anal swabs of two patients He and Chen. Both proteus pani and proteus mirabilis were detected in anal swab of patient Zhou and Proteus pani was detected in roast meat. There was no detection of pathogenic bacteria in other samples. Conclusion Based on the field epidemiological investigation and laboratory test results， we conclude that the food poisoning incident is caused by suspected proteus bacteria. We suggest that the market supervision department should strengthen the supervision of local food hygiene； clarify the sampling rights， responsibilities and technical procedures when medical institutions treat patients with foodborne diseases； ensure finding the causes in time； and take effective prevention and control measures to avoid similar food poisoning events.

The tea beverages will be endowed with distinct aroma and taste, as well as various biologically active compounds including probiotic factors, when fermented with lactic acid bacteria (LAB). However, at present, few studies on the dynamics of flavors in tea soup at different fermentation stages were conducted. In this study, the composition of monosaccharides, aromatic components, free amino acids, and organic acids were measured, when the black tea beverages were fermented with Lactobacillus coryniformis FZU63 which was isolated from Chinese traditional kimchi. The results indicated that monosaccharides including glucose, fructose, mannose and xylose in black tea beverages are the main carbon sources for fermentation. In addition, the abundance of aromatic compounds in black tea soup are increased significantly at different fermentation stages, which endow the fermented black tea soup with fruit aroma on the basis of flowery and nutty aroma. Moreover, some bitter amino acids are reduced, whereas the content of sweet and tasty amino acids is elevated. Furthermore, the levels of lactic acid, malic acid, citric acid and other organic acids are accumulated during the fermentation. Additionally, sensory evaluation displays that black tea beverage is acquired with comprehensive high-quality after being fermented for 48 h. This study provides a theoretical basis to steer and control the flavor formation and quality of the fermented tea beverages during LAB fermentation.
Tea/chemistry* ; Beverages/microbiology* ; Camellia sinensis ; Fermentation ; Acids ; Amino Acids ; Glucose

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

Objective To explore the sample type and drug resistance characteristics of Streptococcus pneu-monia(Spn)isolated from pediatric patients in Guangzhou district,and their age distribution to offer instruc-tions for prevention and clinical treatment.Methods Spn isolates were cultured and identified according to the national standard procedure for clinical laboratory operation,followed by analysis of sample type and age dis-tribution of pediatric patients with positive isolates of Spn in Guangzhou Women and Children′s Medical Cen-ter from 2013 Jan 1st to 2015 Dec 31st,drug resistance status was determined by MIC test.Results Totally, 1 243 strains of Spn were isolated,which were mainly from pediatric patients under 1 year old(42.80%).Spn isolates were mainly isolated from respiratory tract(72.81%),ear secretions(15.37%),blood(5.63%),cere-brospinal fluid(3.06%)and hydrothorax(2.01%).For all Spn isolates,the resistance rate to erythromycin, tetracycline and sulfamethoxazole was especially high as 94.93%,85.76%,73.53% respectively,with relative high resistance to penicillin G(24.70%),amoxicillin(39.59%),ceftriaxone(24.05%),meropenem(22.85%) and cefotaxime(19.89%),low resistance to quinolone antibiotics(<10.00%),and no resistance to vancomycin and linezolid.Conclusion The major age group of children with Spn infection is infants under one year old in Guangzhou,clinicians should be serious about the high resistant rate of Spn to erythromycin,tetracycline and sulfamethoxazole,the significantly increased resistant rate to penicillin,amoxicillin and ceftriaxone.Clinicians should choose antibiotics rationally according to the characteristics of drug sensitivity for better treatment.

Objective: To understand the serotypes, genotypes and transmission source of dengue viruses(DENV) isolated in Yunnan from 2013 to 2015. Methods: Viral RNA was extracted from serum samples of dengue fever(DF) cases at the acute stage in Yunnan, then the gene fragments of envelope protein(E) region were amplified by RT-PCR. The homology and phylogenetic analysis was made on the nucleotide and deduced amino acid sequences by bioinformatics softwares including Clustal X, DNAStar and MEGA5. Results: Viral nucleic acid detection and sequencing indicated that 40 E genes of DENV were obtained. The serotypes and genotypes of DENV were revealed by homology and phylogenetic analysis based on E genes of DENV. Fifteen virus strains belonged to DENV serotype 1(DENV-1), of these, 14(11 from Ruili, 1 from Lincang and 2 from Kunming) were genotype I(G-I), 1 from Kunming was G-V. Twenty-two virus strains belonged to DENV serotype 2(DENV-2), of these, 10 from Ruili were G-I and 12 from Xishuangbanna were G-IV. Two virus strains belonged to DENV serotype 3(DENV-3) and G-II. One virus strain belonged to DENV serotype 4(DENV-4) and G-I. All detected DENV genotypes were mainly predominant in Southeast Asia. All the 40 Yunnan DENV strains shared high homology with the DENV strains in Southeast Asia countries. Conclusions Four serotypes and multiple genotypes of DENV had been co-circulating in Yunnan from 2013 to 2015. The DENV transmitted from Southeast Asia countries was the main cause of DF in Yunnan. It is necessary to strengthen the surveillance and management on the imported cases of DF in Yunnan.

PurposeTo explore the value of ultrasound radio frequency technique in the quantitative evaluation of common carotid artery intima-media thickness (IMT) and elasticity change in patients with dyslipidemia, and to discuss the influence of high density lipoprotein cholesterol (HDL-C) upon carotid artery structure and elasticity function. Materials and Methods A hundred and fifty patients with abnormal serum lipid were selected as case group and further divided into three groups: group A--50 patients with hyperlipidemia and high HDL-C, group B--50 patients with hyperlipidemia and normal HDL-C, group C--50 patients with hyperlipidemia and low HDL-C. Meanwhile, 50 healthy people were enrolled in the study as control group (group D). The ultrasound radio frequency-data technique was employed to analyze the influence of hyperlipidemia and HDL-C upon IMT, CC,β, PWV and AIx.Results The IMT,β, PWV and AIx in group B were higher than those in group D, but group B had lower CC (the differences with statistic significance,t=5.141, 4.219, 4.898, 4.142 and-3.758,P<0.01). Compared with group A, group B had higher IMT,β, PWV and AIx and lower CC (the differences with statistic significance,t=3.425, 2.807, 2.913, 2.209 and-2.091,P<0.05 orP<0.01). Compared with group B, group C had higher IMT,β, PWV and AIx and lower CC (the differences with statistic significance,t=4.937, 2.195, 3.337, 2.067 and-3.049, P<0.05 orP<0.01). Group A had higher IMT and PWV than group D (the differences with statistic significance,t=2.236 and 2.407,P<0.05), but CC,β, and AIx showed no difference between group A and group D (t=-1.693, 1.845 and 1.967,P>0.05). In patients with hyperlipidemia, the increase of HDL-C led to the reduction of the common carotid artery IMT and wall stiffness and the increase of elasticity and vice versa.Conclusion The ultrasound radio frequency technique could measure the real-time common carotid artery IMT and elasticity automatically and accurately, thus provides reliable quantitative index for the evaluation of early artery structure and change of function in lipid lowering therapy.