Inorganic phosphate (Pi) is an essential nutrient for bacterial growth, metabolism and signal regulation. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, encounters restricted Pi availability inside host cells. The uptake and utilization of Pi are mainly accomplished by the phosphate-specific transport (Pst) system. The survival and pathogenicity of Mtb rely on its precise sensing and adaptation to the hostile intracellular environment. The Pst system not only mediates bacterial drug resistance, toxin production and invasion, but also regulates virulence expression, membrane vesicle biogenesis and the synthesis of the nucleotide signaling molecule (p)ppGpp via the Pst-SenX3-RegX3 signaling axis, exhibiting typical multifunctional characteristics. As a member of the ATP-binding cassette (ABC) transporter family, the Pst system in Mtb consists of PstS, PstC, PstA, PstB and PhoU-like proteins, with distinct physiological functions for different proteins and their isoforms.This review focuses on the molecular structure and function of key proteins in the Pst system, as well as the molecular mechanisms underlying Pi transport regulation and bacterial drug resistance, providing a reference for further exploring the relationship between this system and drug resistance, as well as the development of novel drugs targeting the Pst system.

OBJECTIVE To evaluate the long-term cost-effectiveness of canagliflozin or semaglutide in patients with type 2 diabetes mellitus（T2DM）poorly controlled with metformin. METHODS Based on the perspective of China’s health system， a Markov model was used to calculate the long-term costs and utilities of canagliflozin or semaglutide combined with metformin for T2DM patients in China for 30 years based on the data from SUSTAIN 8 study. The incremental cost-effectiveness ratio（ICER） and incremental net monetary benefit （INMB） were calculated using one time the 2024 per capita gross domestic product（GDP） as the willingness-to-pay（WTP） threshold. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were conducted to confirm the stability of the conclusions. RESULTS Compared with canagliflozin + metformin， ICER of semaglutide combined with metformin was 260 485.67 yuan/quality-adjusted life year （QALY），which was higher than the WTP threshold set in this study （95 749 yuan/QALY），and the corresponding INMB was －61 576.24 yuan，indicating that the canagliflozin + metformin regimen was more cost-effective. The cost of diabetes without complications treatment in the semaglutide + metformin group had the greatest influence on INMB，but changes in parameters within the selected range did not drive decision reversal. With the increasing of WTP threshold，the economic acceptability of semaglutide + metformin regimen increased. Under the current WTP threshold，the annual cost of semaglutide should be reduced by 42.95% to make the semaglutide + metformin regimen more cost- effective. CONCLUSIONS From the perspective of China’s health system， canagliflozin + metformin is more cost-effective than semaglutide + metformin for T2DM patients yueru. with poor glycemic control with metformin alone.

OBJECTIVE To evaluate the safety， efficacy， and cost-effectiveness of sodium-glucose co-transporter 2 （SGLT-2） inhibitors for treating type 2 diabetes mellitus （T2DM）. METHODS Retrieved databases such as PubMed， Cochrane Library， Embase， CNKI， as well as relevant health technology assessment （HTA） official websites， HTA reports， systematic review/meta- analysis and pharmacoeconomic studies about SGLT-2 inhibitors （including 12 types such as canagliflozin， dapagliflozin， and empagliflozin） in the treatment of T2DM were collected from the inception to January 28， 2025. After literature screening data extraction and quality assessment， a descriptive analysis was conducted on the results of the included studies. RESULTS A total of 38 articles were included， comprising 30 systematic reviews/meta-analyses， 4 pharmacoeconomic studies， and 4 HTA reports. In terms of effectiveness， most research results showed that canagliflozin was effective in controlling blood glucose， reducing body weight， and lowering blood pressure compared to other SGLT-2 inhibitors， while empagliflozin could effectively reduce all-cause mortality. In terms of safety， compared with other SGLT-2 inhibitors， empagliflozin has a lower overall adverse event rate and cardiovascular death risk， canagliflozin presented a higher risk of hypoglycemia， and dapagliflozin had a higher risk of urinary tract infections. In terms of economics， empagliflozin possessed greater economic advantages over both dapagliflozin and canagliflozin， while canagliflozin offered more benefits than dapagliflozin. CONCLUSIONS The selection of SGLT-2 inhibitors for the treatment of T2DM should be individualized. Canagliflozin is recommended for patients with high cardiovascular risk. Empagliflozin boasts the best overall safety profile. Dapagliflozin should be used with caution in patients at high risk of urinary tract infections. Based on foreign economic evidence， empagliflozin has economic advantages. In the future， drug economic studies under the Chinese health system need to be conducted.

Electroencephalography (EEG) is a powerful tool for investigating brain electrophysiology with high temporal resolution. In recent years, advancements in EEG signal analyses have expanded our research capabilities. Among these, microstate analysis has emerged as a promising approach, providing insights into the topographical distribution of EEG signals and capturing millisecond-scale brain network dynamics. This technique offers a window into the intrinsic activity of large-scale neural networks. A hallmark of disorders of consciousness (DoC) is the disruption of brain activity dynamics. Research shows that EEG microstate analysis can deeply assess the consciousness level and neural mechanism during recovery process in DoC patients, demonstrating significant value in diagnosis and prognosis evaluation of DoC. This article reviews the principles and parameters of microstate analysis, the correlation between microstates and brain networks, and the parameter changes under different states of consciousness, and explores its application value in the diagnosis, classification and prognosis assessment of DoC, with the aim of providing new ideas for DoC precise diagnosis and treatment.

Electroencephalography (EEG) is a powerful tool for investigating brain electrophysiology with high temporal resolution. In recent years, advancements in EEG signal analyses have expanded our research capabilities. Among these, microstate analysis has emerged as a promising approach, providing insights into the topographical distribution of EEG signals and capturing millisecond-scale brain network dynamics. This technique offers a window into the intrinsic activity of large-scale neural networks. A hallmark of disorders of consciousness (DoC) is the disruption of brain activity dynamics. Research shows that EEG microstate analysis can deeply assess the consciousness level and neural mechanism during recovery process in DoC patients, demonstrating significant value in diagnosis and prognosis evaluation of DoC. This article reviews the principles and parameters of microstate analysis, the correlation between microstates and brain networks, and the parameter changes under different states of consciousness, and explores its application value in the diagnosis, classification and prognosis assessment of DoC, with the aim of providing new ideas for DoC precise diagnosis and treatment.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Aim Investigating the effects of exercise during pregnancy on blood pressure and brain ischemia-reperfusion injury in 1-month-old(1M)and 3-month-old(3M)offspring of spontaneously hypertensive rat(SHR).Methods SHR and Wistar Kyoto rats(WKY)were selected,they were paired in a 1∶1 male-to-female ratio within the same strain,and the first day of pregnancy was confirmed by the presence of copulatory plugs and sperm on a vaginal smear.Pregnant rats were randomly divided into pregnancy sedentary group(p-WKY-SED,p-SHR-SED)and pregnancy exercise group(p-WKY-EX,p-SHR-EX).The rats in the exercise group were performed non-weight-bearing swimming for 60 minutes per day,6 days per week,in water 40 cm deep at a temperature of 34～35 ℃,until the 20th day of preg-nancy.The body weight of the pregnant rats,as well as physiological indicators such as fetal weight,body length,and placental efficiency were monitored to reflect the growth and development of the fetus.1M and 3M offspring were selected as research subjects,non-invasive blood pressure was measured in the tail artery,a rat middle cerebral artery occlusion(MCAO)model was prepared by using the thread embolism method,and the area of cerebral infarction was observed 24 hours after reperfusion.Results(1)Compared with p-WKY-SED group,the body weight of p-SHR-SED pregnant rats was significantly decreased(P＜0.01);there was no significant difference in the litter size among all groups of preg-nant rats(P＞0.05).(2)Compared with p-SHR-SED group,exercise during pregnancy can significantly increase the body weight and placental efficiency of both female and male fetal rats in the p-SHR-EX group(P＜0.05),and decrease the weight of the placenta(P＜0.05).(3)Compared with p-WKY-SED group,the body weight of both female and male offspring rats at 1M and 3M was significantly decreased in the p-SHR-SED group,and their blood pressure was significantly increased(P＜0.01);Compared with p-SHR-SED group,exercise during pregnancy had no significant effect on the body weight and blood pressure of 1M offspring in the p-SHR-EX group(P＞0.05),but it could significantly reduce the blood pressure of 3M male offspring in the p-SHR-EX group(P＜0.01);The body weight and blood pressure of 3M male off-spring were significantly higher in p-WKY-SED group and p-SHR-SED group than those of female in the same group(P＜0.01).(4)Compared with p-WKY-SED group,the infarct area of MCAO injury in both female and male offspring rats at 1M and 3M was significantly increased in the p-SHR-SED group(P＜0.01);Compared with p-SHR-SED group,exercise during pregnancy can significantly reduce the infarct area of MCAO injury in both female and male offspring at 1M and 3M in the p-SHR-EX group(P＜0.05).Conclusion Aerobic exercise during pregnancy can significantly improve blood pressure in the offspring of hypertensive rats,and reduce their susceptibility to ischemic reperfusion injury in the brain as adults.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To explore the machine learning model and risk factor analysis for hospital infection caused by carbapenem-resistant enterobacteriaceae(CRE).Methods The clinical data of totally 451 patients infected with extended-spectrum β-lactamases(ESBL)producing Enterobacteriaceae treated in the hospital from 2018 to 2022 were retrospectively collected.The patients were divided into CRE group(115 cases)and sensitive group(336 cases)according to the susceptibility of carbapenem.Four machine learning methods in-cluding Logistic regression analysis,random forest,support vector machine,and neural network were used to build prediction models and receiver operating characteristic curve was used to evaluate.Based on the predic-tion model with the best performance,risk factors for CRE infection were analyzed.Results Random forest model had the best performance,with the area under the curve of 0.952 3.The risk factors for predicting CRE infection by the random forest model included 15 clinical data items,namely fever for more than 3 days,cere-bral injury,drainage fluid sample,trunk surgery,first-level or special-level nursing,ICU treatment,procalcito-nin,anti-anaerobic bacteria,the use of third-generation cephalosporins,age,pre-albumin,creatinine,white blood cell count,and albumin.Conclusion The CRE prediction model developed in this study has good predic-tive value and the risk factors have guiding significance for the early prevention and treatment of CRE infec-tion in clinical practice.

OBJECTIVE To evaluate the safety， efficacy and economics of dapagliflozin in the treatment of type 2 diabetes mellitus （T2DM） combined with cardiovascular disease （CVD）， and provide an evidence-based basis for clinical treatment decisions. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CNKI， Wanfang data， VIP， SinoMed and official websites of domestic and foreign health technology assessment （HTA） organizations were systematically searched. HTA reports， systematic evaluations/meta-analyses， and pharmacoeconomic studies of dapagliflozin in the treatment of T2DM combined with CVD were searched. After data extraction and quality assessment， the results of the included studies were analyzed descriptively. RESULTS A total of 13 papers were included， of which 10 were systematic evaluations/meta-analyses and 3 were pharmacoeconomic studies. In terms of efficacy， dapagliflozin significantly reduced patients’ glycosylated hemoglobin， body weight， body mass index and blood pressure levels compared with placebo， without increasing the risk of all-cause mortality； in terms of safety， dapagliflozin did not increase the risk of overall adverse events， major adverse cardiovascular events， cardiovascular death， hospitalization for heart failure， myocardial infarction， stroke， bone fracture and renal hypoplasia； in terms of economics， the UK and Chinese studies found an economic advantage for dapagliflozin， the Thai study did not. CONCLUSIONS Dagliflozin has better efficacy and safety in the treatment of T2DM combined with CVD， and its economic findings are still controversial in different countries， with economic advantages in the context of current Chinese healthcare policies and drug prices.