Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective To explore the clinical efficacy,glucose and lipid metabolism,reproductive endocrine system,endometrial receptivity,ovarian responsiveness,and pregnancy effects of metformin(MET)on obese polycystic ovary syndrome(PCOS)with infertility.Methods Clinical data of obese PCOS patients with infertility admitted to Wuhan Sixth Hospital from June 2021 to January 2024 were retrospective ana lyzed.According to the medication regimens,they were divided into a control group(letrozole,LET)and a combination group(MET and LET).The treatment efficacy,glucose and lipid metabolism indicators[cholesterol(TC),triglycerides(TG),fasting blood glucose(FPG),fasting insulin(FIN),and insulin resistance index(HOMA-IR)],reproductive endocrine indicators[testosterone(T),estradiol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH),anti-miller's hormone(AMH),and LH/FSH],uterine content tolerance[endometrial thickness,spiral artery pulsatility index(PI),and resistance index(RI)],ovarian responsiveness[follicle formation time interval,the number of dominant follicles and ovulation rates],as well as pregnancy rate were compared after the treatment(3 months).In addition,adverse reactions related to drugs during treatment were recorded to evaluate the safety.Results A total of 99 patients were included in the study,with 53 in the combined group and 46 in the control group.The treatment efficiency of the combined group was significantly higher than that of the control group(P＜0.05).Before treatment,the differences in body mass index(BMI),TC,TG,FPG,FIN,HOMA-IR,T,E2,LH/FSH,AMH,endometrial thickness,PI and RI between the two groups were not statistically significant(P＞0.05);after treatment,BMI,TC,TG,FPG,FIN,HOMA-IR,T,E2,LH/FSH,AMH,endometrial thickness,PI and RI of the patients in both groups were significantly lower than before treatment(P＜0.05),and these indicators of the combined group were lower than those of the control group(P＜0.05).In addition,the follicle formation time of the combined group was shorter than that of the control group,the number of dominant follicles was more than that of the control group,and the ovulation rate and cycle pregnancy rate were significantly higher than those of the control group(P＜0.05);the difference in the incidence rates of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion MET can regulate glucose and lipid metabolism,reproductive endocrine indicators,improve endometrial receptivity,improve ovarian response,and thus increase ovulation and pregnancy rates.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Background Workers in printing jobs are exposed to a variety of organic solvents at low levels for a long period of time. Previous studies have focused on the main components in Material Safety Data Sheet or high-risk occupational hazardous agents, but have not been able to comprehensively and accurately identify the volatile organic compounds (VOCs) in printing jobs. Objective To qualitatively analyze the VOCs in ink, detergent, varnish, fountain solution, and other raw and auxiliary materials by headspace gas chromatography-mass spectrometry, and to accurately identify the occupational hazardous agents in printing jobs. Methods Raw and auxiliary materials used in printing jobs in 6 printing enterprises in Shanghai were sampled by headspace sampling, analyzed by gas chromatography-mass spectrometry, identified by National Institute of Standards & Technology ( NIST) Standard Library and retention time, and quantified by peak area percentage. Results A total of 181 VOCs were reported in the headspace of 25 organic solvent samples, with a total detection frequency of 337 items and 13.2±12.3 VOCs per sample. The most frequently detected VOCs category was naphthene, with a total of 69 items detected (22.5%), dominated by cyclohexane. The characteristics of VOCs components in the headspace of different types of samples were different. The largest number of VOCs was detected in the headspace of detergent samples, with an average of 31.5 VOCs detected. The characteristic components in detergent were aromatic hydrocarbons and ester compounds; alcohols were the characteristic components in varnish; and ester compounds were the characteristic components in ink. The results of cluster analysis showed that ethanol, toluene, ethyl acetate, cyclohexane, and acetone were occupational hazardous agents with high levels of exposure in printing jobs. Conclusion Many kinds of organic solvents used in printing process are difficult to identify by traditional methods. Headspace gas chromatography-mass spectrometry can help to accurately identify VOCs in the workplace, so as to more accurately assess the occupational hazards, and to provide a technical basis for guiding occupational health monitoring and implementing corresponding occupational health risk management and control.

Objective:To observe the intervention effect of aerobic Baduanjin exercise combined with treadmill train-ing on chronic obstructive pulmonary disease(COPD)complicated chronic heart failure(CHF).Methods:A total of 180 COPD+CHF patients who were treated in Mianyang Central Hospital from January 2019 to June 2021 were selected.They were equally divided into control group(basic treatment and intervention)and experimental group(received aerobic Baduanjin exercise combined with treadmill training based on control group)by random number table method,both groups were intervened for 12 weeks.COPD assessment test(CAT)score,left ventricular ejec-tion fraction(LVEF),left ventricular end systolic volume(LVESV),left ventricular end diastolic volume(LV-EDV),scores of modified medical research council(mMRC)and Minnesota living with heart failure questionnaire(MLHFQ)were compared between two groups before,4,8 and 12 weeks after intervention.Results:During 12-week intervention,CAT score,LVESV,LVEDV,scores of mMRC and MLHFQ showed a gradual decreasing trend,while LVEF showed a gradual increasing trend in two groups,P＜0.05 or＜0.01.Compared with control group after 12-week intervention,there were significant reductions in CAT score[(17.47±3.96)points vs.(13.36±3.42)points],LVEDV[(139.44±7.12)ml vs.(131.74±6.47)ml],LVESV[(81.84±8.54)ml vs.(74.29±9.18)ml],scores of mMRC[(1.67±0.47)points vs.(1.42±0.50)points],each dimension and total score of MLHFQ[(40.07±6.86)points vs.(32.54±6.61)points],and significant rise in LVEF[(41.29±4.76)％vs.(44.56±4.42)％]in experimental group(P＜0.001 all).Conclusion:Aerobic Baduanjin exercise combined with treadmill training based on basic treatment can significantly improve cardiopulmonary function,re-lieve dyspnea and improve quality of life in COPD+CHF patients,which is worth promoting.

Microplastics pose a serious threat to the environment and human health,but the circulating distribution and transport processes of microplastics in organisms have not been fully assessed.Therefore,it is of great significance to construct a probe that can image trace microplastics and visually monitor their circulation and transport in vivo.Afterglow semiconducting polymers are attractive for applications in biological imaging as they do not contain heavy metal ions,are easy to biodegrade and allow high signal-to-noise ratio afterglow imaging without continuous excitation.In this study,with styrene as reaction monomer,polyvinylpyrrolidone as surfactant,and sodium persulfate as initiator,afterglow polystyrene microspheres for in vivo imaging of microplastics were prepared.During the polymerization process,poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)](PF-MEHPPV)and photosensitizer silicon 2,3-naphthalocyanine bis(trihexylsilyloxide)(NCBS)were co-doped into polystyrene microspheres.The prepared afterglow polystyrene microspheres exhibited an afterglow duration of 96 h and a tissue penetration depth of 1.8 cm.It was found that co-doping of PF-MEHPPV and NCBS had little effect on the particle size and Zeta potential of the microspheres,and allowed to monitor the afterglow luminescence signal in vivo for 24 h.Imaging of mouse organs after anatomy showed that the afterglow signal was still observed in the stomach of mice 48 h after gavage.This study provided a new method for imaging and tracing microplastics in vivo.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]