Objective To study the clinical effect of levosimendan combined with recombinant human brain natriuretic peptide(rhBNP)on patients with acute heart failure.Methods A total of 100 patients with acute heart failure in the hospital from December 2019 to December 2021 were selected as the research sub-jects.According to different treatment options,the subjects were divided into the control group,levosimendan group,rhBNP group and combined treatment group,with 25 cases in each group.The control group received traditional conventional diuretic,tube expansion and other treatment;the levosimendan group was treated with levosimendan on the basis of the control group;the rhBNP group was treated with rhBNP on the basis of the control group;the combined treatment group was treated with levosimendan and rhBNP on the basis of the control group.The improvement of New York Heart Association(NYHA)classification,death,rehospitaliza-tion rate,6-minute walking distance,improvement of serological indicators and adverse reactions were recor-ded in each group.Results Before treatment,there was no significant difference in baseline data between the groups(P>0.05).On the 1 st and 3 rd day after treatment,the improvement of NYHA classification in the combined treatment group was better than that in the other groups(P<0.05),and the improvement of NY-HA classification in the levosimendan group and rhBNP group was better than that in the control group(P<0.05).The readmission rate within 6 months after treatment in the combined treatment group was lower than that in the other groups(P<0.05).At 5 and 9 days after treatment,the 6-minute walking distance in the combined treatment group was longer than that in the other groups(P<0.05).At 9 days after treatment,the left ventricular ejection fraction(LVEF)in the combined treatment group was higher than that in the other groups(P<0.05),and the level of N-terminal B-type natriuretic peptide(NT-proBNP)in the combined treatment group was lower than that in the other groups(P<0.05).No significant difference was found in the comparison of the occurrence of adverse reactions among the four groups(P>0.05).Conclusion The combina-tion of levosimendan and rhBNP in the treatment of patients with acute heart failure is superior to traditional treatment and monotherapy in early clinical improvement,and dose not increase the incidence of adverse reactions.

In this article,the mechanism of Shanxian Granule in inhibiting liver cancer,lung cancer,sarcoma,melanoma and other tumors was reviewed,with a view to providing a theoretical basis for the clinical research of Shanxian Granules in the treatment of malignant tumors.Shanxian Granule are the pure Chinese medicine preparation for counteracting malignant tumor developed by the Oncology Research Team of Shaanxi University of Chinese Medicine on the basis of the theory of traditional Chinese medicine syndrome differentiation and treatment combined with decades of clinical experience as well as the achievements of modern pharmacological research.Shanxian Granule are mainly composed of Crataegi Fructus,Agrimoniae Herba,Panacis Quinquefolii Radix,Curcumae Rhizoma,Testudinis Carapax et Plastrum,Trionycis Carapax,Corydalis Rhizoma,and Polyporus,and have the actions of benefiting qi and nourishing yin,supporting healthy-qi and cultivating the essence,activating blood and removing stasis,and eliminating swelling and counteracting cancer.The compatibility of Shanxian Granule embodies the principle of supporting healthy-qi but avoiding maintaining pathogens,and eliminating pathogens but avoiding injuring healthy-qi.The granules can effectively inhibit the growth and metastasis of liver cancer,lung cancer,sarcoma,melanoma and other tumors both in vivo and in vitro,alleviate the clinical symptoms of tumor patients,and improve their prognosis.The anti-tumor mechanism of Shanxian Granules is related to the enhancement of body immune function,inhibition of tumor cell proliferation,enhancement of tumor cell apoptosis,inhibition of tumor cell invasion and metastasis as well as the tumor angiogenesis.

Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

OBJECTIVE To explore the specific application and evaluation effect of objective structured clinical examination(OSCE)-guided scenario-based practical teaching mode in training clinical pharmacists. METHODS Fifty-six trainees who participated in the clinical pharmacist training program in the Second Xiangya Hospital of Central South University from October 2020 to September 2022 were selected as the research objects. OSCE-guided teaching was conducted, and the application effect of OSCE-guided teaching mode in clinical pharmacist training was explored and analyzed by using theoretical examination results and OSCE assessment results as evaluation indicators. RESULTS Through comparative analysis, it was found that the OSCE-guided teaching mode not only enabled students to better grasp the theoretical knowledge points required by the training outline, but also improved their clinical thinking ability, problem-solving ability, and communication and coordination skills to varying degrees. CONCLUSION For clinical pharmacist trainees, the OSCE teaching mode is conducive to the comprehensive improvement of clinical pharmacist skills and is suitable for cultivating clinical pharmacists who are capable of independently carrying out clinical pharmacy services in the new situation.

Objective To investigate the effect of growth hormone(GH)pretreatment on the improvement of eu-ploid and pregnancy outcome.Methods A prospective analysis was conducted on 134 patients undergoing preim-plantation genetic testing for aneuploidy(PGT-A),among whom 30 patients were self-controlled and 104 patients were inter-group controlled.According to whether GH was added,the patients were divided into GH pretreatment group and GH non-pretreatment group.GH pretreatment included subcutaneous injection of GH 2U/day for 4-6 weeks before the start of gonadotropin(Gn),and the dose was doubled on the day of Gn until the trigger day.GH non-pretreatment meant no GH treatment,GH pretreatment was given when the previous PGT-A cycle failed within one year when the PGT-A was performed again,forming the self-control group.The basic situation,blastocyst situa-tion and pregnancy outcome were compared between the groups by inter-group and self-control.Results No matter in the group control or self-controlled group,the endometrial thickness on the day of HCG,ovarian sensitivity index(OSI),number of oocytes obtained,MII oocytes,2PN number,2PN fertilization rate,available oocyte rate,num-ber of biopsy blastocysts,number of euploid blastocysts,euploid blastocyst rate,and at least one euploid rate sig-nificantly increased after GH pretreatment,with statistically significant differences(P＜0.05).The total amount of Gn,Gn days,number of mosaic blastocysts,and mosaic blastocyst rate were not significantly changed after GH pretreatment,with no statistically significant differences.The implantation rate and clinical pregnancy rate in-creased after GH pretreatment,but with no statistically significant differences.Conclusion GH pretreatment can significantly improve the number and rate of euploid embryos in patients undergoing PGT-A,and has a tendency to improve pregnancy outcome.

Objective The study aimed to elucidate the evolution of the syndromes in Traditional Chinese Medicine(TCM)and TCM syndrome elements in different chronic stages of psoriasis vulgaris.Methods A database was constructed using electronic medical records collected from July 2019 to March 2024 from 1,049 patients with psoriasis vulgaris.The study used Sankey diagrams and network association graphs to analyze the evolution of TCM syndromes and their elements in patients at the different stages:initial diagnosis,progressive stage(Week 2-3),progressive stage(Week 4-5),skin lesion improvement stage(Week 6-7),and remission stage.The syndrome elements network was constructed using community detection algorithms,and the association rules between local skin lesion syndrome differentiation and overall syndrome differentiation were displayed using heatmaps.Results(ⅰ)Initial diagnosis.In the syndrome differentiation of local skin lesions,blood heat syndrome was the most common(79.79％);among the disease location of TCM syndrome elements(called"disease location"),liver was the most prevalent(35.62％);and among the pathological factors of TCM syndrome elements(called"pathological factors"),fire(heat)was the most common(75.48％).(ⅱ)Active stage(Week 2-3).In the syndrome differentiation of local skin lesions,blood heat syndrome remained the most prevalent(73.13％);among the disease location,liver was still the most prevalent(31.71％);and among the pathological factors,fire(heat)continued to be the most common(82.11％),while dampness(22.26％)and qi stagnation(8.39％)began to increase.(ⅲ)Active stage(Week 4-5).The syndrome differentiation of local skin lesions was dominated by blood heat syndrome(45.91％)and blood dryness syndrome(37.19％);among disease location,the interior was the most prevalent(15.25％);and among the pathological factors,fire(heat)remained the most common(50.66％),with an increase in yin deficiency(34.26％).(ⅳ)Skin lesion improvement stage(Week 6-7).In the syndrome differentiation of local skin lesions,both blood dryness syndrome(49.44％)and blood stasis syndrome(33.33％)increased;among the disease location,meridians increased most significantly and became the most prevalent(13.44％);and among the pathological factors,blood stasis increased most significantly and became the most prevalent(28.20％).(ⅴ)Remission stage.In the syndrome differentiation of local skin lesions,blood stasis syndrome became the primary(55.69％),while the percentage of blood dryness syndrome decreased(21.16％);meridians(25.71％)and blood stasis(62.34％)remained the most predominant syndrome elements related to disease location or pathological factors.Conclusion The overall pattern of TCM syndromes in psoriasis vulgaris evolved from excess to deficiency.From the initial diagnosis to the active phase(Week 2-3),heat syndrome dominated;during the active phase(Week 4-5),heat syndrome coexisted with damp syndrome or yin deficiency syndrome;changes in the syndrome element network were the most significant during the lesion improvement phase,with blood stasis gradually increasing and peaking during the remission phase.Blood stasis,dampness,and qi stagnation were pervasive throughout psoriasis vulgaris;qi stagnation and blood stasis may be the main elements causing further deterioration and prolonged course of the disease during the active phase in patients.

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 analyze the prenatal characteristics and pregnancy outcomes of fetuses with 17q12 microdeletion or microduplication.Methods:From January 2018 to December 2022, 14 fetuses diagnosed with 17q12 microdeletion and three with 17q12 microduplication by chromosomal microarray analysis folloning invasive prenatal diagnostic techniques at Nanjing Maternity and Child Health Care Hospital were retrospectively enrolled in this study. Relevant articles up to February 1, 2023, were retrieved from PubMed, Embase, China National Knowledge Infrastructure, Wanfang database, and Yiigle with the terms "17q12 microdeletion", "17q12 microduplication", "prenatal diagnosis", and "pregnancy outcome". Eighty-four 17q12 microdeletion cases and fourteen 17q12 microduplication cases were retrieved. Prenatal ultrasound features and pregnancy outcomes of those fetuses were analyzed and summarized.Results:In this study, ninety-eight 17q12 microdeletion cases and seventeen 17q12 microduplication cases were analyzed. (1) 17q12 microdeletion: The prenatal ultrasound showed all the 17q12 microdeletion cases had renal abnormalities (100.0%, 98/98), and renal hyperechogenicity was detected in 81.6% (80/98) of them; pedigree analysis suggested that 74.2% (49/66) mutations were de novo; 64.1% (41/64) of pregnant women chose to terminate the pregnancy and 35.9%(23/64) chose to continue pregnancy; eight out of 12 live births who were followed up had different degrees of abnormalities and four were normal during the follow-up period. (2) 17q12 microduplication: Among the 17 fetuses, 10 had upper gastrointestinal obstruction; pedigree analysis suggested that four were de novo mutations (4/13); nine out of 14 pregnant women with reported pregnancy outcomes chose to terminate the pregnancy, and five continued the pregnancy to delivery; follow up of the live births found that four neonates were normal and one had a good prognosis after surgery. Conclusions:Fetuses with 17q12 microdeletion often show renal hyperechogenicity in ultrasound images, and most mutations were de novo with poor prognosis. 17q12 microduplication in fetuses is often characterized by upper gastrointestinal obstruction, and most inherited from their parents.