Objective To investigate the correlation of solute carrier protein 17 family member 1 (SLC17A1) gene single nucleotide polymorphisms (SNPs) and susceptibility to hyperuricemia (HUA) in automotive manufacturing workers. Methods A total of 192 Han male workers diagnosed with HUA were selected as the case group, 192 Han male workers without HUA from the same enterprises were selected as the control group. These workers were determined by the matching factor of age, total length of service, and body mass index by the 1∶1 case-control study method. Peripheral venous blood from the workers was collected for DNA extraction. Two SNPs of SLC17A1 were genotyped by MassArray system. Results The gene frequency distributions of SLC17A1 rs2096386 and rs1183201 of workers in the control group were in consistent with the Hardy-Weinberg equilibrium test (both P>0.05). The allele frequency distribution of rs2096386, and the genotype and allele frequency distribution of rs1183201 were significantly different between workers in the two groups (all P<0.05). There was no significant difference in genotype frequency distribution of rs2096386 between workers in the two groups (P>0.05). The results of conditional logistic regression analysis showed that workers with G allele at rs2096386 increased the risk of HUA [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.01-2.04], workers with T allele at rs1183201 increased the risk of HUA (OR=2.03, 95%CI =1.29-3.19), after adjusting for confounding factors such as serum creatinine, blood urea nitrogen, alanin aminotransferase and aspartate aminotransferase. While workers with TA and TA+AA genotypes at rs1183201 had a lower risk of HUA than those with TT genotype (OR=0.51, 95%CI =0.30-0.85; OR=0.50, 95%CI =0.30-0.83), workers with TA genotype at rs1183201 had a lower risk of HUA than those with TT+AA genotype (OR=0.53, 95%CI =0.32-0.88). Conclusion The polymorphisms at rs2096386 and rs1183201 of SLC17A1 gene may be correlated with HUA susceptibility among automobile manufacturing workers in Guangzhou City.

The long-term efficacy and complications of implantable diaphragm pacer (IDP) in a child with cervical spinal cord injury (CSCI) in the Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center in September 2022 were retrospective analyzed.A male child had quadriplegia without an obvious cause at the age of 12 years, and he was then lived completely with the assistance of mechanical ventilation.At the age of 14 years, he could wean off the ventilator in unilateral diaphragmatic pacing mode.However, mechanical ventilation was re-given for months after 5 years due to pneumonia, and then the IDP was re-given with the self-felt decreased pacing effect.After hospitalization, the patient was examined with mild diaphragmatic atrophy, secondary flat chest, and mild scoliosis.After optimization of the transdiaphragmatic pacing threshold and rehabilitation, his respiratory function improved.IDP can be used in CSCI for long time, while flat chest and scoliosis that limited the expansion of the lungs should be considered.At the meantime, the increased abdominal spasm affected the abdominal compliance, leading to the decrease in the efficiency of the diaphragm.

Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.

ObjectiveTo investigate the molecular mechanism of action of artemisinin in attenuating asthmatic airway inflammation and airway remodeling through the phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway. MethodFifty male SD rats were randomly divided into blank group， model group， and low-dose， medium-dose， and high-dose groups of artemisinin， with 10 rats in each group. The ovalbumin （OVA）-induced asthma model of the rats was established， and after successful modeling， the blank group and model group received tail vein injection of 1.0 mL·kg^-1 normal saline， while the low-dose， medium-dose， and high-dose groups of artemisinin received tail vein injection of 12.5， 25， and 50 mg·kg^-1 artemisinin daily for seven days. Airway resistance was measured by the acetylcholine chloride method. Cell number and species changes in the alveolar lavage fluid of each group were determined by flow cytometry. Morphological changes in airway endothelial tissue were determined by the hematoxylin-eosin （HE） staining method. Apoptosis was determined by CytoTox 96 method， and enzyme-linked immunosorbent assay （ELISA） method was used to determine the NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， interleukin-1β （IL-1β）， and interleukin-10 （IL-10） expression. Western blot method was used to detect the （p）-PI3K/p-Akt level in the alveolar bronchial tissue of each group. ResultCompared with the blank group， the total number of cells， total number of macrophages， total number of eosinophils， total number of lymphocytes， and total number of neutrophils were significantly higher in the model group （P<0.05）. HE staining showed that the airway mucosa of the rats had obvious edema， and a large number of inflammatory cells were infiltrated （P<0.05）. The rate of apoptosis was significantly higher （P<0.05）， and the levels of the inflammasome NLRP3， IL-1β， and IL-10 increased significantly （P<0.05）. p-PI3K/p-Akt level increased significantly （P<0.05）. Compared with the model group， the total number of cells， total number of macrophages， total number of eosinophils， total number of lymphocytes， and total number of neutrophils were significantly decreased after the intervention of artemisinin at low， medium， and high concentrations （P<0.05）. HE staining showed that the degree of edema of the airway mucosa of the rats was reduced， and the area of the inflammatory cell infiltration was drastically reduced （P<0.05）. The apoptosis rate was significantly reduced （P<0.05）， and the levels of the inflammasome NLRP3， IL-1β， and IL-10 decreased significantly （P<0.05）. p-PI3K/p-Akt level decreased significantly （P<0.05）. ConclusionArtemisinin significantly inhibits NLRP3 inflammasome activation， reduces cellular pyroptosis and inflammatory cell expression， and attenuates airway inflammatory manifestations and airway remodeling in asthmatic rats， which may be related to the regulation of p-PI3K/p-Akt， and the results may provide laboratory insights and basis for the treatment of bronchial asthma with artemisinin.

Objectives:To explore the effect of mammalian target of rapamycin (mTOR) antagonist rapamycin (RAPA) on the imbalance of regulatory immune T cell (Treg)/regulatory immune T cell (Th17) immune homeostasis in mice with heart failure (HF) by regulating mTOR signaling pathway. Methods:The model of heart failure after myocardial infarction was constructed by ligation of the left anterior descending coronary artery in 34 healthy C57BL/6 mice.The mice were randomly divided into sham operation group,heart failure (HF) group,low-dose (1 mg/[kg·d])RAPAgroup (RAPAL group),medium-dose (2 mg/[kg·d]) RAPA group (RAPAM group) group and high-dose (4 mg/[kg·d]) RAPA group (RAPAH group) according to the random number table method,with 6 mice in each group.RAPA was administered via tail vein for 4 weeks,and the other groups were injected with the same amount of normal saline by tail vein for 4 weeks.The cardiac structure and function of mice were evaluated by echocardiography.The morphological changes of myocardial tissue were observed by hematoxylin-eosin (HE) staining.The degree of myocardial fibrosis were observed by Sirius red staining The levels of Treg and Th17 cells in peripheral blood were detected by flow cytometry.Western blot was used to detect the protein expression of mTOR,phosphorylated-mTOR (p-mTOR) in myocardial tissue. Results:Echocardiography examination revealed that compared with sham operation group,left ventricular ejection fractions (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly lower ( both P<0.01),and Left ventricular end-diastolic Diameter (LVEDD) and Left ventricular end-systolic diameter (LVEDS) were significantly larger (both P<0.05) in HF group.Compared with HF group,LVEF in RAPAL group,RAPAM group and RAPAH group were significantly higher (all P<0.01),LVFS were significantly higher (all P<0.05).LVEDS in RAPAM and RAPAH groups were significantly lower than those in HF group (both P<0.05).HE staining and Sirius red staining showed that compared with the sham operation group,the myocardial tissue of the HF group was disordered,broken,and enriched with myocardial fibrosis.Compared with the HF group,the myocardial tissue disorder,breakage,and myocardial fibrosis of the RAPAL group,RAPAM group,RAPAH group were all improved.Flow cytometry and protein immunoblotting showed that compared with the sham operation group,the percentage of peripheral blood Treg cells in the HF group was decreased (P<0.01),the percentage of Th17 cells was increased (P<0.01),the Treg/Th17 ratio was decreased (P<0.01),and There was no significant difference in the expression of p-mTOR protein in myocardial tissue (P>0.05).Compared with the HF group,the percentage of peripheral blood Treg cells in the RAPAL group,RAPAM group,RAPAH group were increased (all P<0.01),the percentage of Th17 cells were decreased (all P<0.05),the ratio of Treg/Th17 in the RAPAM and RAPAH groups were all increased (P both<0.01),and the expression of p-mTOR protein in myocardial tissue were all downregulated (both P<0.01). Conclusions:Targeted inhibition of mTOR signaling can regulate the imbalance of Treg/Th17 immune homeostasis in HF mice,reduce myocardial fibrosis and improve cardiac function,among which the high-dose RAPA has the most significant effect.

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To analyze the changes of serum lipidomics in patients with sepsis and healthy controls, search for the differences of lipid metabolites, and reveal the changes of lipidomics in the process of sepsis.Methods:A prospective observational study was conducted. From September 2019 to April 2020, morning blood samples of upper extremity superficial veins were collected from 30 patients with definite sepsis diagnosed in intensive care unit (ICU) of Shanxi Bethune Hospital and 30 age-matched healthy subjects during the same period. Serum lipid metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and the quality control samples were analyzed by base peak spectroscopy (BPC) and verified experimental repetition. Student t-test and fold change (FC) were used for screening significant differences in lipid metabolites and determining their expression changes. Principal component analysis (PCA) and orthogonal projectionto latent structure discriminant analysis (OPLS-DA) were used to determine the entire allocation of experimental groups apiece, access the quality of being near to the true value of model, and screen the differential lipid metabolites with variable importance of projection (VIP). Finally, Metabo Analyst platform database was used to analyze lipid molecular metabolic pathways. Results:BPC results showed that the experimental repeatability was good and the experimental data was reliable. The main parameter model interpretation rate of PCA model R 2X = 0.511, indicating that the model was reliable. The main parameter model interpretation rate of OPLS-DA model R 2Y = 0.954, Q 2 = 0.913, indicating that the model was stable and reliable. With FC > 2.0 or FC < 0.5, P < 0.05, a total of 72 differential lipid metabolites were obtained based on VIP > 1. Based on Metabo Analyst 5.0, 24 distinguishable lipid metabolites were identified including 8 phosphatidylethanolamine (PE), 7 lysophosphatidylcholine (LPC), 6 phosphatidylcholine (PC), 2 lysophosphatidylethanolamine (LPE) and 1 phosphatidylserine (PS). Compared with healthy volunteers, the lipid molecules expression proved down-regulated in most sepsis patients, including PC, LPC, LPE, and some PE, while some PE and PS were up-regulated, which was mainly related to the PE (18∶0p/20∶4), PC (16∶0/16∶0) and LPC (18∶1) metabolic pathways in glycerophospholipids. Conclusions:There are significant differences in lipid metabolites between the sera of sepsis patients and healthy volunteers. PE (18∶0p/20∶4), PC (16∶0/16∶0) and LPC (18∶1) may be new targets for sepsis prediction and intervention.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.