This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.

Objective To investigate the effects of tiotropium bromide combined with salmeterol fluticasone on postoperative lung function,blood gas index,and inflammatory response in patients with lung cancer complicated with stable chronic obstructive pulmonary disease(COPD).Methods Patients with lung cancer complicated with stable COPD after surgery were selected as research subjects and divided into control group and treatment group according to different treatment methods.The control group received 18 μg of tiotropium bromide powder for inhalation therapy,bid,for 3 days before surgery,while the treatment group received additional salmeterol inhalation powder treatment on basis of the control group's treatment,1 inhalation each time,bid,for 3 months.Lung function[forced vital capacity(FVC),forced expiratory volume in one second(FEV1),peak expiratory flow(PEF),FEV1/FVC],modified British Medical Research Council(mMRC)dyspnea scale,chronic obstructive pulmonary disease assessment test(CAT)score,quality of life questionnaire-C30(QLQ-C30)score,blood gas index[arterial oxygen pressure(PaO2),arterial blood oxygen saturation(SaO2),arterial carbon dioxide pressure(PaCO2)],inflammatory response indicators[interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α)],and occurrence of adverse drug reactions in the two groups with compared before and after treatment.Results Forty-seven and forty-five cases were included in the treatment and control groups,respectively.After treatment,the total effective rates of the treatment and control groups were 91.49％(43 cases/47 cases)and 75.56％(34 cases/45 cases)respectively,and the differences were statistically significant(P＜0.05).After treatment,the FEV1/FVC of the treatment and control groups were(0.62±0.10)％and(0.48±0.05)％;PEF were(1.94±0.20)and(1.02±0.11)L·s-1;mMRC scores were 2.01±0.25 and 2.26±0.23;CAT scores were 16.03±1.74 and 20.03±2.17;QLQ-C30 physical functioning scores were 79.31±8.92 and 75.04±7.86;PaO2 were(70.34±6.98)and(62.02±6.31)mmHg;IL-6 expression levels were(16.43±1.65)and(21.55±2.27)pg·mL-1.The above indexes in the treatment group compared with the control group were all statistically significant(all P＜0.05).The main adverse drug reactions in the treatment and control groups were skin allergies and nausea/vomiting,and the total incidence of adverse drug reactions in the treatment and control groups were 34.04％and 23.40％,with no statistically significant difference(P＞0.05).Conclusion Tiotropium bromide combined with salmeterol fluticasone is effective for patients with lung cancer complicated with stable COPD after surgery,which significantly improves their lung function,prognosis,and arterial blood gas levels.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

Ferroptosis is a novel form of cell death that has been discovered in recent years and differs markedly from previously known cell death. The mechanism of ferroptosis is the inactivation of glutathione peroxidase(GPX)and the accumulation of lethal intracellular lipid peroxides that occur on the basis of cellular iron overload. Changes such as cell membrane rupture, mitochondrial crest reduction, and outer mitochondrial membrane shrinkage rupture can be observed under electron microscopy. Current studies have found that many diseases in ophthalmology involve ferroptosis-related processes such as iron overload, the imbalance of redox homeostasis, the inactivation of GPX, and accumulation of lethal levels of lipid hydroperoxides, which identified the important role of ferroptosis in ocular disease. This review focuses on the mechanism of ferroptosis and its role in corneal injury, cataract, glaucoma, age-related macular degeneration and diabetic retinopathy, which helps to sort out the pathological mechanisms of common ocular diseases and provide new ideas for the prevention and treatment of ocular diseases.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 μg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 μg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.
Humans ; Female ; Pregnancy ; Pesticides/analysis* ; Pregnant Women ; China ; Neonicotinoids/analysis* ; Insecticides

Humans ; Factor XIII/genetics* ; Factor XIII Deficiency/genetics* ; Mutation ; Pedigree

OBJECTIVE: To explore the clinical outcomes of anteromedial combined with lateral locking plate for complex proximal humeral fractures in the eldery. METHODS: From June 2018 to October 2020, 30 patients who underwent surgical treatment for Neer grade 3 to 4 proximal humeral fractures, including 8 males and 22 females, aged from 51 to 78 years old with an average of (61.5±7.5) years old. Of them, 15 patients had fractures fixed with anteromedial combined with lateral locking plate(ALLP group), whereas 15 received internal fixation with proximal humerus locking plate only(PHLP group). The clinical data, simple shoulder test (SST), humeral head height loss, varus angle and shoulder range of motion were compared between the two groups. RESULTS: All fractures were healed. The follow-up time ranged from 12 to 24 months, with an average of(14.3±2.9) months. The operation time of ALLP group was longer than that of PHLP group (P<0.05). There was no significant difference in intraoperative blood loss between the two groups (P>0.05). There was no significant difference in SST score between the two groups at 1, 3 and 12 months after operation (P>0.05). In terms of radiographic measurement, there was no significant difference in humeral head height loss and varus angle between the two groups at 1 and 3 months after operation (P>0.05). At 12 months after operation, the height loss and varus angle of humeral head in ALLP group were lower than those in PHLP group (P<0.05). In shoulder range of motion, the range of forward elevation in ALLP group was larger than that in PHLP group 1 year after operation(P<0.05). There was no significant difference in external rotation between the two groups. CONCLUSION Anteromedial combined with lateral locking plate in the treatment of complex proximal humeral fractures in the elderly can increase the stability of the medial column and obtain a good fracture prognosis. But there are also disadvantages such as longer operation time, so it should be individualized according to the fracture type of the patient.
Male ; Female ; Humans ; Aged ; Middle Aged ; Treatment Outcome ; Shoulder Fractures/surgery* ; Fracture Fixation, Internal ; Shoulder ; Humeral Head ; Bone Plates ; Humeral Fractures/surgery*

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.
Mice ; Animals ; Powders ; Receptors, Tumor Necrosis Factor, Type I ; Glutamic Acid ; Tumor Necrosis Factor-alpha/metabolism* ; Galactose/adverse effects* ; Disease Models, Animal ; Cognitive Dysfunction/prevention & control* ; Chemokines ; Drugs, Chinese Herbal