A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To explore the impact of high intensity focused ultrasound(HIFU)treatment on ovarian reserve capacity in adenomyosis.Methods Clinical data of 106 adenomyosis patients who underwent HIFU treatment from May 2019 to December 2020 at some hospital were analyzed retrospectively.All the patients were treated with HIFU,and color Doppler ultrasonography was performed before and after 6 months of treatment,respectively.The resistance index,pulsatility index,vascularization index,blood flow index,vascularization blood flow index and sinus follicle number were obtained,and serum anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH)and luteinizing hormone(luteinizing hormone)were measured.The correlation between serum AMH levels and FSH and LH levels was analyzed.SPSS 21.0 statistical software was used for data analysis.Results After 6 months of treatment serum FSH,LH,value of FSH/LH,resistance index and pulsatility index significantly decreased while vascularization index,blood flow index,vascularization blood flow index,number of sinus follicles,and serum AMH level obviously increased when compared with those before treatment,with the differences being statistically significant(P＜0.05).Serum AMH levels were negatively correlated with FSH and LH levels(r=-0.448,-0.527,P＜0.05)after 6 months of treatment.Conclusion HIFU treatment reduces sex hormone levels,elevates serum AMH levels and sinus follicle number,and may improve ovarian reserve capacity in patients with adenomyosis.[Chinese Medical Equipment Journal,2024,45(1):67-70]

Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML)patients with PTPN11 gene mutation.Methods Total 115 adult AML patients who underwent initial diagnosis,treatment,and second-generation sequencing(NGS)detecting at hospital were recruited in this study.Clinical da-ta included disease characteristics,treatment efficacy,long-term prognosis,immune cell subpopulations,and leu-kemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients with PTPN11 gene mutation.Results PTPN11 gene mutation rate in newly diagnosed adult AML was 9.57％,and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation.Compared with PTPN11 wild-type group,PTPN11 gene mutation group had a higher early mortality rate(18.18％vs 4.00％,P=0.048),a lower complete response rate(33.33％vs 67.71％,P=0.039),a higher recurrence rate(83.33％vs 42.31％,P=0.043),a shorter median overall survival time(9 months vs 20 months,P=0.026),a lower proportion of ef-fector T cells[(1.39±0.12)％vs(3.56±0.46)％,P=0.038],and a higher proportion of leukemia stem cells[(13.82±3.66)％vs(3.87±1.40)％,P=0.021].Conclusion PTPN11 gene mutation is a poor prognostic marker for AML.Those patients have a high early mortality rate,low complete remission rate,high recurrence rate,short median overall survival time,a low proportion of effector T cells,and a high proportion of leukemia stem cells.

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 evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective To explore the relationship between the status of infarct related artery(IRA)occlusion and thrombus types in patients with non-ST-segment elevation myocardial infarction(NSTEMI)using optical coherence tomography(OCT).Methods A total of 170 NSTEMI patients who underwent emergency percutaneous coronary intervention at Henan Provincial People1s Hospital from October 2021 to August 2023 and underwent OCT examination were included in the study.Among them,83 cases were in the total occlusion group and 87 cases were in the non-total occlusion group.The baseline characteristics,coronary angiography findings,and OCT results of the patients were compared and analyzed.Results Compared with the non-total occlusion group,the patients in the total occlusion group were more younger(P=0.013),the proportion of male was higher(P=0.026),and the proportion of patients with hypertension(P=0.010)and diabetes(P=0.033)was lower.In the total occlusion group,left circumflex artery(LCX)served as the main IRA,whereas in the non-total occlusion group,left anterior descending(LAD)was the predominant IRA(P=0.012);In addition,there was a significantly higher occurrence of rentrop grade Ⅱ～Ⅲ in the total occlusion group compared to the non-total occlusion group(P=0.022).The OCT results showed that in most cases,the total occlusion group was caused by plaque rupture events(P=0.014),mainly red/mixed thrombus(P＜0.001);The non-total occlusion group was more commonly associated with plaque erosion events(P=0.014),with white thrombus being the main cause(P＜0.001).Conclusions Total occlusion of infarct-related artery in NSTEMI patients often occurs in the LCX,and the patient is more younger,the thrombus type is mainly red/mixed thrombus,while non-total occlusion lesions are mainly white thrombus.