Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective:To compare transperineal prostate biopsy(TPB)with transrectal ultrasound-guided prostate biopsy(TRUSB)in detection of clinically significant prostate cancer(csPCa)and insignificant PCa(insPCa).Methods:We conducted a prospective randomized clinical study on 279 patients receiving TPB(n=144)or TRUSB(n=135)from January 2022 to January 2023,and compared the detection rates of csPCa and insPCa between the two groups.Results:The detection rate of PCa was signifi-cantly higher in the TPB than in the TRUSB group(37.50％vs 28.15％,P=0.026).There were no statistically significant differ-ences between the TPB and TRUSB groups in the detection rates of insPCa(6.94％[n=10]vs 4.45％[n=6],P＞0.05)and csPCa(30.56％[n=44]vs 23.70％[n=32],P＞0.05),nor in the detection rate of csPCa between different groups of age,PSA concentration and prostate volume(P＞0.05).No statistically significant differences were observed between the TPB and TRUSB groups either in the positive rate of biopsy punctures([16.44±2.86]％vs[12.48±2.39]％,P＞0.05)or in the bi-opsy-related complications of urinary retention,urinary tract infection,hematuria and rectal bleeding(P＞0.05).Conclusion:TPB is more effective than TRUSB in detection of PCa,but there is no statistically significant difference between the two approaches in the detection rates of csPCa and insPCa.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Fourteen compounds were isolated from the n-butanol fraction of the 95% aqueous ethanol extract of the stems and twigs of Strychnos cathayensis by D101 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semipreparative RP-HPLC. Their structures were elucidated as ethyl 4-O-β-D-allopyranosyl-vanillate (1), n-butyl 4-O-β-D-allopyranosyl-vanillate (2), n-butyl 4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillate (3), n-butyl 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillate (4), n-butyl 4-O-(6′-O-syringoyl)-β-D-glucopyranosyl-vanillate (5), n-butyl 4-O-α-L-rhamnopyranosyl-syringate (6), methyl 3-methoxy-4-(β-D-allopyranosyloxy) benzoate (7), pseudolaroside B (8), butyl syringate (9), glucosyringic acid (10), methyl syringate (11), methyl 4-hydroxy-3-methoxybenzoate (12), clemochinenoside C (13), and clemoarmanoside A (14), respectively, on the basis of spectroscopic data interpretation and by comparison with literature information. Compounds 1-6 are artificial products of phenolic acid esterified by ethanol or n-butanol. It is noted that the precursors (4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillic acid and 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillic acid) of compounds 3 and 4 are new compounds. The hepatoprotective, anti-inflammatory, antioxidant and cytotoxic activities of compounds 1-13 were evaluated in vitro at a concentration of 10 μmol·L^-1. Compounds 1, 2 and 6-10 exhibited potential hepatic protection effects with cell survival rates ranging from 53.6% to 55.5% (acetaminophen, 45.4% at 8 mmol·L^-1). Compound 4 demonstrated anti-inflammatory activity with nitric oxide inhibitory rate of 74.6%. Compounds 3 and 5 showed potential antioxidant activities with malondialdehyde inhibitory rates of 53.2% and 56.1%, respectively.

The synthesis and decomposition of glycogen adjust the blood glucose dynamically to maintain the energy supply required by the cells. As the only hormone that lowers blood sugar in the body, insulin can promote glycogen synthesis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and increasing glucose transporter translocation, and inhibit gluconeogenesis to lower blood glucose. In the endometrium, glycogen metabolism is active, but gluconeogenesis does not occur. The glycogen metabolism in the endometrium is controlled not only by the classical glucose regulating hormones, but also by the ovarian hormones. The functional activities related to implantation of the endometrium during the implantation window require glucose as energy source. A large amount of glucose is used to synthesize glycogen in the endometrium before implantation, which could meet the increased energy demand for embryo implantation. In diabetes, glycogen metabolism in the endometrium is impaired, which frequently leads to implantation failure and early abortion. This article reviews the glycogen metabolism in the endometrium and discusses its role in embryo implantation, which provide new ideas for embryo implantation research and infertility treatment.
Blood Glucose/metabolism* ; Embryo Implantation ; Endometrium ; Female ; Glucose/metabolism* ; Glycogen/metabolism* ; Humans ; Insulin/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pregnancy

Adult ; Antibodies, Viral/isolation & purification* ; COVID-19/virology* ; Feces/chemistry* ; Female ; Humans ; Intestines/virology* ; Male ; RNA, Ribosomal, 16S/genetics* ; RNA, Viral/isolation & purification* ; SARS-CoV-2/pathogenicity*

The morbidity and mortality of cardiovascular diseases are very high, which has attracted more and more attention all over the world. Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting, which can quickly restore blocked coronary blood flow and reduce the infarct size. However, the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow, its pathological mechanism is complicated, and the Western medicine countermeasures are very limited. Among the current drugs for the treatment of cardiovascular diseases, traditional Chinese medicine has become a research hotspot due to its multiple targets, safety, and low side effects. Ginger is the fresh rhizome of Zingiber offici?nale Rosc., a perennial herbaceous plant in the ginger family. It is a dual-purpose resource of medicine and food. Ginger has the functions of relieving the appearance and dispelling cold, warming up and relieving vomiting, resolving phlegm and relieving cough, and relieving fish and crab poison. The chemical components of ginger mainly include volatile oil, gingerol, diphenylheptane, etc.. Among them, 6-gingerol, as the main active component of gingerols, has obvious phar?macological effects in myocardial protection, anti-oxidation, anti-inflammatory, etc.. Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress, anti-inflammatory, inhibiting cell apoptosis, and preventing cal?cium influx. ① Anti-oxidative stress: oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance, and it is also an important factor leading to myocardial damage. Many studies have confirmed that 6-gingerol has an antioxidant effect, and it is considered a natural antioxidant. 6-gingerol can significantly reduce the degree of oxi?dative stress and the level of reactive oxygen species caused by cardiomyocyte damage, and has a significant cardiopro?tective effect. ② Anti-inflammatory: inflammation can cause substantial cell damage and organ dysfunction, which is another important cause of myocardial damage. 6-gingerol can reduce the levels of inflammatory factors such as inter?leukin-6, interleukin-1β, and tumor necrosis factor-αin cardiomyocytes, and at the same time inhibit the TLR4/NF-κB sig?naling pathway, an important regulatory pathway of inflammation, showing that it may improve myocardial damage through anti-inflammatory effects. ③ Inhibition of apoptosis: apoptosis is a complex and orderly process in the autono?mous biochemical process of cells, and one of the main mechanisms of myocardial injury. This process can be roughly divided into three pathways: mitochondria, endoplasmic reticulum, and death receptors. Among them, the mitochondrial pathway plays an important role, and Bcl-2 and Bax located upstream of this pathway can regulate the entire process of cell apoptosis by regulating the permeability of the mitochondrial membrane. Studies have found that the preventive application of 6-gingerol can reduce cell damage, reduce the number of apoptotic cells, reduce the activity of Bax and caspase-3, and increase the expression of Bcl-2. Therefore, 6-gingerol pretreatment can reduce the damage of cardio?myocytes, and its mechanism may be related to the inhibition of apoptosis.④Prevent calcium influx:calcium overload is involved in the pathogenesis of myocardial ischemic injury, which may be related to excessive contracture, arrhythmia, and mitochondrial Ca2+accumulation that impairs myocardial function. 6-gingerol inhibits the increase of intracellular Ca2+concentration by inhibiting L-type calcium current, thereby reducing extracellular Ca2+ influx, thereby avoiding calcium overload and playing a cardioprotective effect. In summary, 6-gingerol can effectively treat and improve myocardial isch?emia/reperfusion injury, and it has great development potential in the fields of medicine and health products.

Betel nut is the dry and mature seed of Areca catechu L., which is originated in Malaysia and cultivated in Yunnan, Hainan and Taiwan and other tropical areas of China. It is also known as big belly, binmen, olive seed, green seed and so on. Betel nut is a dual-use resource for medicine and food, which was first contained in LI Dang's Pharma?ceutical Record. Betel nut tastes bitter, pungent, warm in nature, and belongs to the stomach and large intestine meridian. It contains a variety of chemical components such as alkaloids, phenolic compounds, polysaccharides, fatty acids, amino acids, flavonoids, minerals, terpenoids, and steroids. It has the advantages of promoting digestion, lowering blood pres?sure, anti-depression, anti-oxidation, anti-inflammatory, and anti-parasites, antibacterial and other activities. The content of total phenols in fresh fruits of areca nut was 31.1％, mainly including catechin, isorhamnetin, chrysopanthoxanthin, luteolin, tannin and other polyphenols. The commonly used methods for determination of polyphenols in areca are vanil?lin titration potassium permanganate titration and potassium ferricyanide spectrophotometry. The main activities and mechanisms of areca polyphenols include: ① Antidepressant effect: polyphenols bind to monoamine oxidase type A (MAO-A) receptors that inhibit the production of neurotransmitters, thereby increasing the content of amine transmitters in the brain and playing a therapeutic effect on depression. ② Antioxidant effect: polyphenols contain multiple adjacent hydroxyl groups, which are easily oxidized and can effectively remove superoxide anion free radical, hydroxyl free radi?cal, 1,1-diphenyl-2-picrylhydrazyl radical, showing good antioxidant activity.③Bacteriostatic effect:polyphenols can spe?cifically bind to the surface of bacteria, thus achieving bacteriostatic effect. Studies have found that betel nut polyphenols have varying degrees of inhibitory effects on a variety of bacteria. ④ Inducing apoptosis of lymphocytes: polyphenols deplete the mercaptan in lymphocytes and make them unable to survive, thus inducing apoptosis of lymphocytes.⑤Anti-aging effect: polyphenols have the effect of anti-hyaluronidase and anti-elastase, so as to protect elastin fiber and pro?mote collagen synthesis.⑥Anti-allergic effect:studies have found that polyphenols can reduce ovalbumin induced aller?gic reactions.⑦Other functions:betel nut can freshen breath, eliminate bad breath, and resist the activity of cobra venom. At present, domestic and foreign scholars' research on betel nut mainly focuses on arecoline and its carcinogenicity, mutagenicity, effects on reproductive function, addiction and toxicity to the nervous system, and there are few studies on the positive effects of betel nut, especially on it. There is less research on phenolic ingredients. Therefore, this article reviews the polyphenolic chemical constituents of betel nut, and fully excavates its pharmacological activity to provide a reasonable basis for the scientific use of betel nut.

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Stroke/drug therapy*