Objective: To systematically evaluate the relationship of exposure to five heavy metals, namely lead, arsenic, cadmium, mercury and aluminum with obesity in children and adolescents, so as to provide a scientific basis for subsequent research in the area. Methods: Four Chinese databasesc (CBM, VIP, CNKI and Wanfang) and four foreign databases (OVID, PubMed, Web of Science and EBSCO), were searched to collect relevant studies, and the search period was from the establishment of the database to May 5, 2024. After 2 investigators independently screened the literature, extracted the data and evaluated the risk of bias of the included studies, the results were analyzed quantitatively and summarized qualitatively. Results: A total of 5 cohort studies on lead exposure and 17 cross sectional studies involving exposure to lead ( n =13), cadmium ( n =8), mercury ( n =8), arsenic ( n =4), and aluminum ( n =1) were included. Meta analysis of the 2 cohort studies showed that lead exposure was not associated with the risk of overweight and obesity in children ( RR=0.76, 95%CI=0.50-1.16, P ＞0.05). The cross sectional study Meta-analysis results showed that lead exposure was negatively associated with the risk of childhood overweight ( OR=0.70, 95%CI =0.59-0.84, 2 studies) and obesity ( OR=0.71, 95%CI =0.58-0.87, 3 studies); cadmium exposure was negatively associated with the risk of childhood overweight ( OR=0.83, 95%CI =0.73-0.95, 2 studies) and obesity risk( OR=0.70, 95%CI =0.63-0.78, 3 studies); mercury exposure increased the risk of overweight/obesity ( OR=1.42, 95%CI =1.14-1.76, 2 studies) and abdominal obesity ( OR= 1.99, 95%CI =1.45-2.73, 2 studies) in children; the group with the highest concentration of arsenic in urine had a lower risk of developing obesity compared to the group with the lowest concentration ( OR=0.39, 95%CI =0.23-0.65, 1 study), and the group with the highest concentration of aluminum in urine had a lower risk of obesity compared with the group with the lowest concentration ( OR=0.52, 95%CI =0.31-0.86, 1 study)(all P <0.05). Conclusion Heavy metal exposure may be a risk factor for overweight and obesity in children and adolescents, but the conclusions are inconsistent and need to be validated in further high quality prospective cohort studies.

OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment， the ORR was significantly higher in the observation group than in the control group （P＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （P＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months]， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months） （P＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （P＞0.1， I 2＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （P＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （P＜0.05）， with greater reductions observed in the observation group （P＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （P＞0.05）. CONCLUSIONS For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine（TCM） through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects， they were divided into the "1-2 seven" group （under 21 years old）， "3 seven" group （21-27 years old）， "4 seven" group （28-34 years old）， "5 seven" group （35-41 years old）， "6 seven" group （42-48 years old） and "7 seven" and older group （49 years old and above）. The age， average menstrual cycle in the past 3 months， basic hormone levels including follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， testosterone （T） and FSH/LH value， and anti-müllerian hormone （AMH） levels were collected and compared. ResultsA total of 1221 cases were included. The differences in FSH， LH， FSH/LH values， E₂， T， AMH levels and average menstrual cycle among the groups were statistically significant （P＜0.05 or P＜0.01）. AMH peaked in the "3 seven" group. Compared to those in the "3 seven" group， the FSH/LH value in the "4 seven" group increased， while the LH， AMH and T levels decreased， and the menstrual cycle was shortened （P＜0.01）. The FSH/LH， LH， AMH， T and menstrual cycle in the "5 seven" group were consistent with the changing trend of those in the "4 seven" group， while the FSH and E₂ levels in the "5 seven" group were significantly higher （P＜0.05 or P＜0.01）. Compared to those in the "5 seven" group， the FSH， LH and E₂ levels of the "6 seven" group increased， and the AMH and T levels continued to decrease （P＜0.05 or P＜0.01）. Compared to those in the "6 seven" group， the FSH and LH levels of the "7 seven" and older group continued to increase， and the AMH and E₂ levels decreased （P＜0.01）. ConclusionThe law of women reproductive aging in the "seven-year period" theory is basically consistent with the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. The reproductive capacity reaches its peak in the "three-seven-year period" and gradually moves towards reproductive aging in the "four-seven-year period".

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg^-1）， high-dose JTTP group （7.2 g·kg^-1）， and metformin group （0.2 g·kg^-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

To provide a theoretical basis for different drug decision-making scenarios by conducting a comprehensive clinical evaluation of nusinersen.

Objective To investigate the relationship between dynamic electrocardiogram P-wave sign and new-onset atrial fibrillation(NOAF)in patients with acute myocardial infarction(AMI)(AMI-NOAF).Methods Totally 240 patients with AMI admitted to Wuwei Cancer Hospital were examined by dynamic electrocardiogram.P-wave sign pa-rameters and clinical data of holter electrocardiogram were collected.The relationship between P-wave sign and clini-cal parameters of AMI patients was analyzed.The patients were divided into NOAF group and nonoccurrence(non-NOAF)group and multivariate Logistic regression model was used to identify the influencing factors of NOAF occur-rence in AMI.Results Killip Ⅲ-Ⅳ grade minimum P wave duration(Pmin)level was shorter than that of Ⅰ-Ⅱ grade.Maximum P wave duration(Pmax)and P wave dispersion(Pd)level were higher than that of Ⅰ-Ⅱ grade(P<0.05).NOAF occurred in 47 of 240 AMI patients(19.58％).The level of Pmin in NOAF group was lower than that in non-NOAF group,and the level of Pmax and Pd in NOAF group was higher than that in non-NOAF group(P<0.05).The heart rate and the proportion of Killip grade Ⅲ-Ⅳ in NOAF group were higher than those in non-NOAF group(P<0.05).Multivariate Logistic regression analysis showed that Killip Ⅲ-Ⅳ grade,high level of Pmax and Pd were independent risk factors for NOAF in AMI(P<0.05).Conclusions The level of Pmin,Pmax and Pd are correlated with Killip grading in AMI patients.AMI-NOAF patients have abnormal P-wave sign in holter electrocardiogram.The high levels of Pmax and Pd are independent risk factors of AMI and NOAF.

Objective:To Explore the diagnosis, treatment and prognosis of FH-deficient renal cell carcinoma (FH-deficient RCC) with tumor thrombus, and share surgical experience.Methods:From August 2019 to October 2022, 6 cases of FH-deficient RCC with tumor thrombus were diagnosed and treated in our center, including 4 males and 2 females. The patients were aged 22 to 57 years, with 2 cases younger than 40 years, icluding 5 cases on the left and 1 case on the right. The median maximum diameter of the tumor is 8 (4.8, 14.0) cm. Operations were performed after complete examination (enhanced CT and other related examinations). One case underwent open surgery and palliative resection of the left kidney was performed because of severe adhesion of the inferior vena cava. Among the remaining 5 cases, 1 case underwent retroperitoneal laparoscopic right radical nephrectomy with inferior vena cava thrombectomy, 1 case underwent transabdominal laparoscopic left radical nephrectomy with inferior vena cava thrombectomy, and 3 cases underwent robot assisted laparoscopic left radical nephrectomy with inferior vena cava thrombectomy.Results:The median surgical time was 293 (185, 366) min, with blockage of the vena cava for 13 min and 28 min in 2 of 6 cases, respectively. The pathological report of renal tumor and tumor thrombus was FH-deficient renal carcinoma. The pathological features were as follows: the gross section of the specimen was gray yellow solid, often accompanied by necrosis, and the cystic cavity could be seen locally. Microscopically, the tumor extensively involved the renal parenchyma, with papillary, cribriform and tubular cystic structures. Immunohistochemistry showed FH (-), 2SC (+ ). The median postoperative hospital stay was 8 (4, 15) days. The median follow-up time was 13 (4, 27) months. One patient undergoing palliative resection of the left kidney underwent targeted therapy and radiotherapy after surgery (died 15 months after surgery due to gastrointestinal perforation). During the follow-up process, 4 cases experienced metastasis and received systematic treatment, with 1 death 27 months after surgery. Uterine leiomyomas were found in the remaining 1 case during follow-up.Conclusions:FH-deficient RCC with tumor thrombus is very rare. This disease is highly invasive, difficult to be diagnosed preoperatively and poor clinically prognostic. Operation combined with systemic therapy is an effective way to treat FH-deficient RCC with tumor thrombus.

Remote pharmaceutical care refers to the process that pharmacists provide pharmaceutical care to patients remotely through information technology. Remote pharmaceutical care in China starts late and develops slowly. Therefore ，this paper discusses the pharmaceutical care modes that pharmacists at home and abroad can provide under the remote mode by collecting literature. The results show that foreign remote pharmaceutical care starts early and is relatively mature. The service mainly included remote follow-up and intervention ，24-hour online prescription and order review ，24-hour online drug reorganization ，and guidance on rational drug use in remote areas or community hospitals. The service population covers patients with cardiovascular disease ， diabetes，asthma，AIDS and so on. Some hospitals have established an integrated pharmaceutical care system of “Internet+Medical Consortium”in China ，with which pharmacists can provide patients with pharmaceutical care such as remote follow-up and intervention，drug consultation and so on. With the promotion of telemedicine ，domestic pharmacists can gradually expand the scope of services ，expand pharmaceutical services such as remote consultation and remote popular science push ，and realize the sharing of high-quality pharmaceutical care for the whole people.

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

Objective:Healthy life expectancy (HLE), which combines life expectancy with health, is an essential comprehensive measure of life length and quality. This article aimed to systematically review the methods for defining and measuring HLE and describe application studies published, providing a reference for decision makers to select and develop methods suitable for China's conditions to measure HLE.Methods:Seven Chinese and English literature databases were searched up to May 7, 2022, and several related reviews and bibliography were manually retrieved. Systematic reviews and empirical research were included concerning HLE indicators and measurement of HLE. Information including the study area, type of the study, study population, HLE index, measurement method, data sources, and results from application studies published in the last five years were extracted. The evolution of the definition of HLE, the scope of different indicators, the measurement scale of health, and measurement methods, were all collected. Results of the empirical research related to measurement methods of indicators were summarized. The study followed the scoping review framework and was written according to the PRISMA-ScR statement.Results:A total of 84 articles were included, including 13 reviews, 17 original studies related to HLE index definition, ten original studies related to index measurement, and 44 empirical studies conducted in the past five years. There were as many as 20 indicators related to HLE, and each scale had its emphasis. A total of ten methods measuring HLE were identified, which vary in the definition of health, whether using weight, and the data type. The most commonly used indicators in the past five years were disability-free life expectancy and HLE. For the method of HLE calculation, Sullivan's method was mainly used for cross-sectional data, and the multistate life table was mainly used for longitudinal data.Conclusions:There are various definitions and measurement methods of HLE, but none are suitable for all scenarios. To summarize the HLE concept, health evaluation techniques, measurement methods, and application studies published worldwide can provide a reference for the localization of HLE measurement in China.