[Scoping review of progress in cohort studies of autism spectrum disorder].

Objective: To understand the status of autism spectrum disorder (ASD) cohort studies and explore the feasibility of constructing ASD disease-specific cohorts based on real-world data (RWD). Methods: ASD cohort studies published by December 2022 were collected by literature retrieval from major Chinese and English databases. And the characteristics of the cohort were summarized. Results: A total of 1 702 ASD cohort studies were included, and only 60 (3.53%) were from China. A total of 163 ASD-related cohorts were screened, of which 55.83% were birth cohorts, 28.22% were ASD-specific cohorts, and 4.91% were ASD high-risk cohorts. Most cohorts used RWD such as hospital registries or conducted community-based field surveys to obtain participant information and identified patients with ASD by scales or clinical diagnoses. The contents of the studies included ASD incidence and prognostic risk factors, ASD comorbidity patterns and the impact of ASD on self-health and their offspring's health. Conclusions: ASD cohort studies in developed countries have been in the advanced stage, while the Chinese studies are still in their infancy. RWD provides the data basis for ASD-specific cohort construction and offers new opportunities for research, but work such as case validation is still needed to ensure the scientific nature of cohort construction.

[Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review].

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

[Methodology progress and challenges on assessing the appropriateness of real-world data].

From the perspective of data users, ensuring the relevance and reliability of big data in healthcare and medicine via assessments on data appropriateness is a prerequisite for generating high-quality real-world evidence, which could guarantee good representativeness and generalizability of real-world studies. This review summarized the quality dimensions, definitions, evaluation indexes and calculating methods of assessment on the appropriateness of real-world data (RWD) according to guidance from different countries and international organizations, as well as exploring the opportunities and challenges for better assessing RWD appropriateness.

[Scoping review of active surveillance systems for vaccine safety world-wide].

Objective: To identify post-marketing active surveillance systems for vaccine safety around the world and understand their features and mechanisms, in order to provide guidance for vaccine administration activities in China. Methods: Following the steps of scoping review, literature about active surveillance system for vaccine safety and published by 30 June 2018 were identified by searching electronic databases, including PubMed, Scopus, and Cochrane Library. Grey literature were also sought by exploring relevant websites. Identified literature were screened according to eligibility criteria, and informative data from included literature were then charted. Framework Synthesis and Thematic Analysis were performed to integrate the charted data. Results: 97 pieces of literature were included for review, and 11 active surveillance systems for vaccine safety were identified, mostly located in developed countries. These systems were constructed by 3 types of organizations: administration departments, academic or research institutions, and health care providers. Their data sources included immunization registries, electronic medical records, claims data, case reports of adverse events following immunization electronic questionnaires, and epidemiologic study data. According to their operation procedures, these systems were grouped into 4 modes of active surveillance: Data Linkage, Investigator Network, Automatic Follow-up System, Studies Consortium. Conclusion: Practice of active surveillance for vaccine safety greatly varies across countries, with different conditions and advantages. It is suggested that developing countries should choose suitable mode of active surveillance considering their local situations.

[Family history and risk of coronary heart disease].

Objective: To evaluate the association of family history with risk of major coronary events (MCE) and ischemic heart disease (IHD). Methods: After excluding participants with heart disease, stroke or cancer at baseline survey, a total of 485 784 participants from the China Kadoorie Biobank, who had no missing data on critical variables, were included in the analysis. Cox regression analysis was used to estimate the hazard ratios (HR) and 95% CI. Subgroup analyses were performed according to the baseline characteristics. Results: During a median of 7.2 years of follow-up, we documented 3 934 incident cases of MCE and 24 537 cases of IHD. In multivariable-adjusted models, family history was significantly associated with risk of MCE and IHD. The adjusted HRs (95%CI) were 1.41 (1.19-1.65) and 1.25 (1.18-1.33), respectively. History of disease among siblings was more strongly associated with early-onset MCE than parental history (HR=2.97, 95%CI: 1.80-4.88). Moreover, the association of family history with MCE and IHD was stronger in persons who were overweight or obesive, and the association between family history and MEC was stronger in smokers. Conclusion: This large-scale, prospective study indicated that family history was an independent risk factor for MCE and IHD in China. The intervention targeting major known lifestyle risk factors and the management of chronic diseases should be strengthened for Chinese population, especially for the individuals with family history were at high risk.

Carvedilol alleviates the biliary cirrhosis through inhibiting the endoplasmic reticulum stress.

OBJECTIVE: To investigate the effects of carvedilol on inflammation, apoptosis, and hepatic fibrosis caused by biliary cirrhosis and its mechanisms in mice. MATERIALS AND METHODS: 60 male C57/BL6 mice were randomly divided into sham-operation group (Sham group, n=20), biliary cirrhosis group (BDL group, n=20) and carvedilol group (CAR group, n=20). The CAR group was treated with gavage using 12.5 mg/kg carvedilol, once a day for 14 consecutive days, while the Sham group and BDL group were treated with gavage using the equivalent normal saline. After that, the mice in Sham group received the laparotomy under chloral hydrate anesthesia, followed by direct abdominal closure. The mice in BDL group and CAR group received the common bile duct ligation after anesthesia for modeling. After modeling, the survival rate of mice in each group was detected, and the blood and liver tissues were taken for detection. The morphological changes in liver tissues and apoptosis in mice in each group were detected and compared. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), superoxide dismutase (SOD), malondialdehyde (MDA), hydroxyproline, and α-smooth muscle actin (α-SMA) were also detected. The mRNA expression levels of pro-inflammatory factors, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), transforming growth factor ß-1 (TGF-ß1), α-SMA and collagen-1 were detected via reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of CHOP (CCAAT-enhancer-binding protein homologous protein), activating transcription factor 4 (ATF4), ATF6, inositol-requiring enzyme 1 (IRE1), phosphorylated Jun N-terminal kinase (pJNK), α-SMA, and collagen-1, were detected via Western-blotting. RESULTS: Our study showed that carvedilol could significantly alleviate the biliary cirrhosis in mice, and improve the survival rate of mice. The ALT, AST and TBIL levels, severity of cirrhosis, and number of apoptotic cells in CAR group were significantly lower than those in BDL group. The levels of α-SMA and hydroxyproline in CAR group were also significantly lower than those in BDL group. The activity of SOD in CAR group was significantly higher than that in BDL group; the above differences were statistically significant (p<0.05). In addition, it was also found that carvedilol could down-regulate the mRNA expression levels of iNOS, COX-2 and TGF-ß1, down-regulate the mRNA and protein expression levels of α-SMA and collagen-1, and negatively regulate the ATF4-CHOP, ATF6-CHOP and IRE1-pJNK signaling pathways. CONCLUSIONS: Carvedilol has a significant effect on alleviating the biliary cirrhosis in mice, and its relevant mechanism may be that carvedilol inhibits the endoplasmic reticulum stress through the negative regulation of ATF4-CHOP, ATF6-CHOP and IRE1-pJNK signaling pathways, which needs to be confirmed by further in vitro experiments.

[Associations between season of birth and age both at menarche and at menopause].

Objective: To examine the associations between season of birth and factors as age at menarche, age at menopause and reproductive span. Methods: A total of 285 186 female from the China Kadoorie Biobank, with complete data on critical variables and had menarche at 9-18 years old, were included. A total of 132 373 female with natural menopause were included for the analysis on age at menopause and reproductive span. Multiple linear regression models were used to assess the associations of birth season and the age at menarche, menopause, and reproductive span. Subgroup analyses were performed on birth cohorts and urban/rural residence. Results: Compared with the Spring-born (March, April, and May), participants who were born in Summer (June, July, and August), Autumn (September, October, and November), and Winter (December, January, and February) appeared late on both age at menarche and menopause. Multivariable-adjusted coefficients (95% CI) appeared as 0.14 (95% CI: 0.13-0.16), 0.26(95% CI: 0.24-0.27), 0.10 (95% CI: 0.08-0.12) for age at menarche respectively and 0.14 (95%CI: 0.08-0.20), 0.18 (95%CI: 0.12-0.24), 0.09 (95%CI: 0.03-0.16) for age at menopause respectively. No statistically significant association was found between the season of birth and reproductive span. The association was consistent between urban and rural residents and across the birth cohorts. Conclusions: female born in spring showed both earlier age on both menarche and menopause, compared to the ones born in other seasons. Our findings suggested that exposures in early life with some degree of seasonal variation might influence the development of female reproductive system.

[Association between famine exposure during early life and BMI in adulthood].

Objective: To examine the influence of famine exposure during early life on BMI in adulthood. Methods: A total of 94 052 participants recruited in the baseline survey of China Kadoorie Biobank were included in this study. The participants who were born between October 1956 and September 1958, between October 1959 and September 1961 and between October 1962 and September 1964 were classified as group born before famine, group born during famine and group born after famine (control group). The regression coefficients and 95% confidence intervals (CIs) for BMI of famine exposure groups were estimated by linear regression model. And P values for interaction between famine and smoking, alcohol use, physical activity were estimated by likelihood ratio tests. Results: Compared with the group born after famine, in females, the group born during famine had higher BMI (coefficient: 0.12, 95% CI: 0.03-0.22) after adjusting other impact factors. Except physical activity (interaction: P<0.077), both smoking and alcohol use had modification effects on the associations between famine exposure and BMI (interaction: all P<0.001). Conclusion: Famine exposure during early life, especially during fetal period, might increase risks of overweight and obesity in females. Therefore, it is important to ensure the adequacy of nutrition during early life to prevent overweight or obesity in adulthood.