OBJECTIVE To evaluate the efficacy and safety of three aromatase inhibitors （exemestane， anastrozole， letrozole） for postmenopausal hormone receptor （HR）-positive early breast cancer. METHODS PubMed， the Cochrane Library， Embase， CNKI， Wanfang Data， VIP and SinoMed were searched to collect randomized controlled trials （RCTs） of the above three drugs in the treatment of postmenopausal HR-positive early breast cancer patients. The retrieval time limit was from the establishment of the database to October 25， 2024. After literature screening， data extraction and literature quality evaluation， network meta-analysis was performed by using RevMan 5.3 and Stata 18.0 software. RESULTS A total of 15 RCTs involving 44 055 patients were included. The results of network meta-analysis showed that the objective response rate of letrozole group was significantly higher than anastrozole group （P＜0.05）， and the order of surface under the cumulative ranking curve （SUCRA） from high to low was letrozole （85.6%）＞anastrozole （61.5%）＞exemestane （2.8%）. The disease-free survival rate of anastrozole group was significantly higher than exemestane and placebo groups （P＜0.05）， and the order of SUCRA from high to low was letrozole （85.8%）＞ anastrozole （67.3%）＞exemestane （41.4%）＞placebo （5.5%）. The total incidence of adverse reactions in anastrozole group was significantly higher than letrozole and placebo groups （P＜0.05）， and the order of SUCRA from high to low was exemestane （87.4%）＞letrozole （63.9%）＞anastrozole （47.0%）＞placebo （1.7%）. The results of subgroup analysis according to the course of treatment≥104 weeks were consistent with them. CONCLUSIONS Compared with anastrozole， letrozole has better efficacy and safety in the treatment of postmenopausal HR-positive early breast cancer， and the efficacy of exemestane is limited.

To ensure the rights and safety of the subjects and improve the quality of clinical trials, the author analyzed and discussed the deviation type and typical cases from 184 cases of protocol violation reviewed by the ethics committee in 56 clinical trials in a tertiary hospital in 2020. Among the 184 cases of violating the protocol, there were 29 major protocol violation cases and its proportion is 16%; 99 cases (54%) violated the GCP principle; 56 cases of other violations of the protocol that require to be reported, accounting for 30%. Through the case analysis of the researcher gave the wrong doses to subjects without following the protocol and drug administration did not conform to the rules, analyzed and discussed from the five perspectives of the research protocol design, the researcher, the clinical trial institution, the sponsor and the ethics committee, and put forward solutions and suggestions, so as to provide reference to improve the compliance of clinical trial protocol, reduce the risk of subjects and protect their rights and safety and ensure the successful progress of clinical trials.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

This study explored the comorbidity mechanisms of coronary heart disease and depression from the perspectives of "constraint causing disease" and "disease causing constraint"， for which "constraint" is the link， and the key lies in the stagnation of qi. The heart storing manifestations in traditional Chinese medicine （TCM） encompasses most physiological processes of the circulatory system， the mental nervous system， and some functions of the endocrine system， and cardiovascular diseases and psychological disorders are closely related to it. In TCM， it is proposed that the stagnation of heart yang leading to "yang deficiency" is the pathogenesis of chest tightness， and emotional disturbance leading to the stagnation of yang qi aggravates the chest tightness， reflecting the process of "disease causing constraint". As the disease progresses， the appearance of phlegm and stasis further worsens the condition， reflecting the process of "constraint causing disease". Based on modern medical understanding， the abnormal accumulation of lipids， platelets， oxidative products， cytokines， and other substances constitute a form of "constraint"， which is also the material basis for the comorbidity of coronary heart disease and depression. These substances promote neuronal damage or apoptosis in the emotional and cognitive regions， inducing the onset of depression， reflecting the process of "disease causing constraint". Meanwhile， adverse emotions lead to sympathetic nerve excitement， resulting in the production of catecholamines， promoting platelet aggregation， elevating levels of inflammatory markers， and increasing the risk of coronary heart disease， reflecting the process of "disease causing constraint".

Objective:To investigate the perinatal prognosis and its impact factors for premature infants with twin-twin transfusion syndrome (TTTS) who were born at ≤34 weeks of gestation.Methods:A retrospective study was conducted on 68 pregnancies of TTTS with gestational age ≤34 weeks at delivery, among them 106 preterm infants (TTTS group) were admitted to the neonatal intensive care unit of the First Affiliated Hospital, Sun Yat-sen University from January 2003 to February 2019. During the same period, another 178 twins without TTTS, congenital malformation, and intrauterine intervention who matched the TTTS group in maternal age (differences within two years) and gestational age (differences within one week) were assigned as non-TTTS group. Perinatal prognosis of TTTS infants born at ≤34 weeks was analyzed by comparing the differences in postnatal early complications and perinatal outcomes (survival time morn than 28 days or not) between the TTTS and non-TTTS groups, recipient and donor twins, mild and severe TTTS infants, and among TTTS infants with different intrauterine interventions. The risk factors for perinatal survival in TTTS infants with gestational age ≤34 weeks were analyzed. Two independent samples t-test, one-way analysis of variance, rank-sum test, Chi-square test, and ordered logistic regression were used for statistical analysis. Results:(1) Among the 68 pregnancies, the overall perinatal survival rate of the neonates was 72.1% (98/136), the double-twin survival rate was 48.5% (33/68), and the rate of at least one survivor was 95.6% (65/68). (2) In the TTTS group, 62 were recipients and 44 were donors. Stage Ⅰ-Ⅱ TTTS was found in 41 cases (mild TTTS group) and stage Ⅲ-Ⅴ in 65 cases (severe TTTS group). (3) The rate of severe brain injury was higher in the severe-TTTS group than those in the mild-TTTS group [9.2% (6/65) vs. 0.0% (0/41), χ 2=4.01, P=0.045]. (4) Gestational age ≤28 weeks ( OR=101.90, 95% CI: 5.07-2 048.37), stage Ⅳ ( OR=14.04, 95% CI: 1.56-126.32) and stage Ⅴ TTTS ( OR=51.09, 95% CI: 3.58-728.81) were independent risk factors for death within 28 days (all P<0.05). (5) Compared with the non-TTTS group, the TTTS group had higher rates of neonatal anemia [51.9% (55/106) vs. 33.1% (59/178), χ 2=9.71], polycythemia [5.7% (6/106) vs. 0.6% (1/178), χ 2=7.18], neonatal persistent pulmonary hypertension [3.8% (4/106) vs. 0.0% (0/178), χ 2=6.81], sepsis [15.1% (16/106) vs. 7.3% (13/178), χ 2=4.40], state Ⅲ or higher retinopathy of prematurity [3.8% (4/106) vs. 0.0% (0/178), χ 2=6.81], congenital cardiac structural abnormality [19.8% (21/106) vs. 0.6% (1/178), χ 2=33.45], heart failure [8.5% (9/106) vs. 0.6% (1/178), χ 2=12.29], and renal insufficiency [14.2% (15/106) vs. 1.1% (2/178), χ 2=20.04] (all P<0.05). Conclusions:Compared with the twin premature infants without TTTS, those with TTTS and ≤34 gestational age were more likely to have cardiac, cerebral, and renal complications. The more severe the TTTS, the higher the incidence of severe brain injury. TTTS preterm infants with gestational age ≤28 weeks and stage Ⅳ or above have high risk of death.

To study the prevalence of depression, anxiety, and insomnia among social workers during the prolonged battle against the COVID-19 pandemic and explore the associated risk factors.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Chlorfenapyr,an emerging synthetic pesticide,has been linked to a growing number of poisoning incidents,attributed to heightened human exposure as its application becomes more widespread.However,the toxicokinetics and toxicology of chlorfenapyr remain incompletely understood.Research since the 1990s,including animal experiments,has illuminated the absorption,distribution,excretion,and metabolism of chlorfenapyr.Toxicological investigations have revealed that the primary toxicity of chlorfenapyr is the uncoupling of oxidative phosphorylation.Chlorfenapyr exposure in humans and other animals can lead to various toxic effects,including neurotoxicity,cardiotoxicity,skeletal muscle toxicity,genotoxicity,reproductive and developmental toxicity,renal toxicity,splenic toxicity,and hematotoxicity.This article presents a comprehensive review of the toxicokinetics and toxicology of chlorfenapyr,integrating data from animal experiments,human cell line studies,clinical reports,and human autopsy.Its objective is to raise clinical awareness regarding chlorfenapyr poisoning and offer valuable references for its treatment and management.

Objective To analyze the status quo and influencing factors of extubation due to complications of totally implantable access port in patients with liver cancer undergoing chemotherapy,to establish a risk prediction model,and to conduct internal validation of the model.Methods This study was a prospective nested case-control study.The patients with liver cancer undergoing chemotherapy for maintenance of totally implantable access port in a tertiary hospital in Shaanxi from October 2021 to September 2023 were selected as the investigation subjects.Patients with extubation due to complications were selected as an extubation due to complications group,and patients with planned extubation were randomly selected as a planned extubation group according to the matching number of 1∶10.Univariate analysis and Logistic regression analysis were used to explore the influencing factors of extubation due to complications.A visual nomogram risk prediction model was established,and the model was internally verified by receiver operating characteristic(ROC)curve,calibration curve and Hosmer-Lemeshow fit test.Results The incidence of extubation due to complications of totally implantable access port in patients with liver cancer undergoing chemotherapy was 7.0％.Infection(36.7％)and thrombosis(30.0％)were the main causes of extubation due to complications.BMI,TNM staging,diabetes,the number of catheter lumens in the access port and the chemotherapy times were the main influencing factors of extubation due to complications(P＜0.05).The area under ROC curve of the prediction model was 0.871;the best cut-off value was 0.106;the sensitivity was 0.800;the specificity was 0.820.The average absolute error between the actual and predicted values of the calibration curve was 0.011,and the calibration curve was close to the ideal curve.The Hosmer-Lemeshow goodness of fit test was x2=2.913(P=0.940).Conclusion The incidence of extubation due to complications of totally implantable access port in patients with liver cancer undergoing chemotherapy is low,and infection and thrombosis are the main reasons.Patients with a BMI≥ 24,TNM stage Ⅲ or Ⅳ,diabetes,double catheter lumens in the access port,and chemotherapy times＞5 were at higher risk of extubation due to complications.The risk prediction model developed in this study demonstrates good predictive accuracy,and it can serve as a valuable tool for healthcare professionals in early identification of patients at risk for extubation due to complications.

Objective To systematically explore the traditional Chinese medicine(TCM)common symptoms,syndrome elements,clinical syndrome differentiation,and medication rules of coronary microvascular disease(CMVD),and to provide a reference for quantitative criteria of clinical differentiation of CMVD,specification of the diagnosis and efficacy evaluation of TCM clinical syndrome,and guidance of clinical medication.Methods The databases including CNKI,Wanfang,VIP,and SinoMed were searched for research papers on the treatment of CMVD by TCM published from database inception to May 16,2023.Relevant information of the included literature was extracted and the database was established.Then,the frequency statistics of symptoms,syndrome elements,syndrome types and Chinese medicinals were carried out.Latent structural models were constructed using Latern 5.0 and Rstudio softwares respectively for comprehensive clustering and association rule analysis,so as to explore the symptom characteristics,syndrome elements distribution,common syndromes and medication rules for TCM treatment of CMVD.Results A total of 107 literature were included,involving 36 syndromes,17 syndrome elements,121 symptoms and 143 Chinese medicinals.It was speculated that the main syndrome element of CMVD was blood stasis,followed by qi deficiency,qi stagnation,phlegm turbidity,yin deficiency and yang deficiency.The main type of syndrome was qi deficiency and blood stasis,followed by heart blood stasis obstruction,qi stagnation and blood stasis,phlegm blended with stasis,qi-yin deficiency,etc..The main medicinals were Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Angelica Sinensis Radix and Astragali Radix.The medicinals used in the treatment of CMVD were classified as blood-activating and stasis-resolving drugs,deficiency-tonifying drugs,qi-regulating drugs in terms of their efficacy.Conclusion The location of CMVD is in heart,and related to liver and kidney.The syndrome of CMVD is deficiency in origin and excess in superficiality.Blood stasis runs through the development of the disease.The treatment is mainly to activate blood circulation and remove stasis,activate meridians and relieve pain,which should be supplemented with the therapies of tonifying and invigorating qi,soothing the liver and regulating qi,dispelling phlegm and dissipating masses according to the patients'syndromes.