OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

Objective To investigate the risk factors of hemodynamic instability after carotid artery stenting by meta-analysis.Methods Ten databases were searched:PubMed,ProQuest,ScienceDirect,Embase,Cochrane Library,Web of Science,China Knowledge Network,Wanfang Data,VIP Information Database,and China Biomedical Database.The search date was from inception until 2 February 2024,and meta-analysis was performed using Stata 16.0 statistical software.Results A total of 27 studies with 4199 subjects and 22 influencing factors were included.The studies showed a 37.4％(95％CI 30.3％-44.8％)incidence of haemodynamic instability after carotid stenting,Meta-analysis determined that age＞60 years(P＜0.001),hypertension(P＜0.001),calcified plaque(P＜0.001),stenosis＞70％(P=0.008),eccentric plaque(P=0.002),distance from the largest stenosis to the carotid bifurcation≤ 10 mm(P＜0.001),stenosis involvement of the balloon or bifurcation(P＜0.001),balloon post-dilation(P=0.003),open-loop stenting(P＜0.001),dilated balloon diameter≥5 mm(P=0.002),repeat balloon dilation(P=0.011)and balloon dilation pressure≥8 atm(P＜0.001)are risk factors for intraoperative and postoperative haemodynamic instability in patients undergoing carotid artery stenting surgery.Statin use was a protective factor(P＜0.001).Conclusions Medical staff working in the clinic should assess the patient's condition preoperatively,identify risk factors that may lead to haemodynamic instability,and avoid unnecessary intraoperative stimulation of patients who are already in a high-risk state.Reduce postoperative clinical complications in patients with carotid artery stenosis and improve patient recovery.

Objective To investigate the risk factors of hemodynamic instability after carotid artery stenting by meta-analysis.Methods Ten databases were searched:PubMed,ProQuest,ScienceDirect,Embase,Cochrane Library,Web of Science,China Knowledge Network,Wanfang Data,VIP Information Database,and China Biomedical Database.The search date was from inception until 2 February 2024,and meta-analysis was performed using Stata 16.0 statistical software.Results A total of 27 studies with 4199 subjects and 22 influencing factors were included.The studies showed a 37.4％(95％CI 30.3％-44.8％)incidence of haemodynamic instability after carotid stenting,Meta-analysis determined that age＞60 years(P＜0.001),hypertension(P＜0.001),calcified plaque(P＜0.001),stenosis＞70％(P=0.008),eccentric plaque(P=0.002),distance from the largest stenosis to the carotid bifurcation≤ 10 mm(P＜0.001),stenosis involvement of the balloon or bifurcation(P＜0.001),balloon post-dilation(P=0.003),open-loop stenting(P＜0.001),dilated balloon diameter≥5 mm(P=0.002),repeat balloon dilation(P=0.011)and balloon dilation pressure≥8 atm(P＜0.001)are risk factors for intraoperative and postoperative haemodynamic instability in patients undergoing carotid artery stenting surgery.Statin use was a protective factor(P＜0.001).Conclusions Medical staff working in the clinic should assess the patient's condition preoperatively,identify risk factors that may lead to haemodynamic instability,and avoid unnecessary intraoperative stimulation of patients who are already in a high-risk state.Reduce postoperative clinical complications in patients with carotid artery stenosis and improve patient recovery.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective:To explore the risk factors of suicidal ideation in bereavement callers of Beijing psy-chological support hotline.Methods:Bereavement callers from 2022-2023 hotline callers who were assessed for grief reactions were included in this study.Callers were assessed for current suicidal ideation by asking them if they had suicidal ideation within two weeks.The general demographic data of bereavement callers were collected,and the distress,hope and suicide risk factors of bereavement callers were assessed by hotline interview.The depression de-gree of bereavement callers was assessed by diagnostic screening scale for depression.Logistic regression analysis was used to explore the risk factors of suicidal ideation.Results:Seventy-seven point two percent(1 028/1 332)of callers reported suicidal ideation.Those who were over 25 years old(OR=0.50),with 10-16 years of education(OR=0.59),with over 16 years of education(OR=0.28),and had a high sense of hope(OR=0.41)were less likely to have suicidal ideation.Those with previous suicide history(OR=2.70),high levels of distress(OR=1.72),and high levels of depression(OR=2.86)were more likely to have suicidal ideation.Conclusion:A history of previous suicide,high levels of distress,and high levels of depression among bereavement callers were risk fac-tors for suicidal ideation.

Objective It investigates the current status of negative defensive medical behavior tendencies among medical students and explores influencing factors,aiming to provide evidence for improving medical students' propensity for negative defensive medical practices.Methods In February 2023,a cluster sampling approach was employed to recruit 297 medical students from a medical college-affiliated hospital in Province H.Descriptive statistics,chi-square tests,and correlation analyses were conducted to assess negative defensive medical behavior tendencies.Structural equation modeling(SEM)was utilized to explore multidimensional influencing factors.Results 45％of medical students demonstrated high-level negative defensive medical behavior tendencies.Statistically significant differences were observed between genders(x2=5.569,P＜0.05)and only-child/non-only-child groups(x2=6.104,P＜0.05).Positive correlations were identified between negative defensive medical behaviors and role stress(r=0.217,P＜0.01),negative organizational environment evaluation(r=0.395,P＜0.01),and negative social environment evaluation(r=0.405,P＜0.01).Only-child status was confirmed as an influencing factor(β=-0.123,P=0.036).Negative organizational environment evaluation(β=0.504,P＜0.001)and negative social environment evaluation(β=0.193,P=0.039)showed significant positive effects.Conclusion Immediate interventions-including role-specific risk allocation,organizational ecosystem reconstruction,and social environment governance-require urgent implementation to address early-stage behavioral deviance,counteract the solidification of defensive medical thinking patterns,and reduce predispositions toward negative professional behaviors among medical trainees.

Small molecules generally refer to natural compounds with a molecular weight less than 1 kD,which have significant research value in many fields such as biological science,pharmaceutical and health care,and environmental science,etc.Aptamers,as a new type of bio-recognition element,can bind specifically to small molecules and other targets with high affinity.They are single-stranded short nu-cleotide sequences selected by the systematic evolution of ligands by exponential enrichment(SELEX)technology.Compared with aptamers of large molecules,aptamers of small molecules often exhibit disad-vantages such as difficult screening,low affinity,and poor specificity.To solve these bottleneck prob-lems,the article provides some strategies of screening and identification of aptamers for small molecules.Firstly,when designing the screening plan for aptamers of small molecules,this article suggests focusing on key points such as library design,SELEX methods,amplification methods,screening process monito-ring methods,and aptamer sequence analysis methods,then choosing or designing appropriate strategies based on the actual situation.Secondly,the structure and affinity of aptamers directly affect their applica-tions.The article briefly introduces methods for analyzing the secondary and tertiary structures of aptam-ers and six common methods for affinity determination.Finally,the article discusses some problems exist-ing in screening and identification of aptamers for small molecules and looks forward to future develop-ment prospects.The whole article aims to provide research strategies for multiple steps of screening and i-dentification of aptamers for small molecules and offer references for improving the efficiency of aptamer screening and identification.