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Abstract Background Chronic kidney disease (CKD) is a progressive disease for which there is no effective cure. We aimed to identify potential drug targets for CKD and kidney function by integrating plasma proteome and transcriptome. Methods We designed a comprehensive analysis pipeline involving two-sample Mendelian randomization (MR) (for proteins), summary-based MR (SMR) (for mRNA), and colocalization (for coding genes) to identify potential multi-omics biomarkers for CKD and combined the protein–protein interaction, Gene Ontology (GO), and single-cell annotation to explore the potential biological roles. The outcomes included CKD, extensive kidney function phenotypes, and different CKD clinical types (IgA nephropathy, chronic glomerulonephritis, chronic tubulointerstitial nephritis, membranous nephropathy, nephrotic syndrome, and diabetic nephropathy). Results Leveraging pQTLs of 3032 proteins from 3 large-scale GWASs and corresponding blood- and tissue-specific eQTLs, we identified 32 proteins associated with CKD, which were validated across diverse CKD datasets, kidney function indicators, and clinical types. Notably, 12 proteins with prior MR support, including fibroblast growth factor 5 (FGF5), isopentenyl-diphosphate delta-isomerase 2 (IDI2), inhibin beta C chain (INHBC), butyrophilin subfamily 3 member A2 (BTN3A2), BTN3A3, uromodulin (UMOD), complement component 4A (C4a), C4b, centrosomal protein of 170 kDa (CEP170), serologically defined colon cancer antigen 8 (SDCCAG8), MHC class I polypeptide-related sequence B (MICB), and liver-expressed antimicrobial peptide 2 (LEAP2), were confirmed. To our knowledge, 20 novel causal proteins have not been previously reported. Five novel proteins, namely, GCKR (OR 1.17, 95% CI 1.10–1.24), IGFBP-5 (OR 0.43, 95% CI 0.29–0.62), sRAGE (OR 1.14, 95% CI 1.07–1.22), GNPTG (OR 0.90, 95% CI 0.86–0.95), and YOD1 (OR 1.39, 95% CI 1.18–1.64,) passed the MR, SMR, and colocalization analysis. The other 15 proteins were also candidate targets (GATM, AIF1L, DQA2, PFKFB2, NFATC1, activin AC, Apo A-IV, MFAP4, DJC10, C2CD2L, TCEA2, HLA-E, PLD3, AIF1, and GMPR1). These proteins interact with each other, and their coding genes were mainly enrichment in immunity-related pathways or presented specificity across tissues, kidney-related tissue cells, and kidney single cells. Conclusions Our integrated analysis of plasma proteome and transcriptome data identifies 32 potential therapeutic targets for CKD, kidney function, and specific CKD clinical types, offering potential targets for the development of novel immunotherapies, combination therapies, or targeted interventions.

Background and objectivesGeographical variation existed in the incidences of Guillain-Barré syndrome (GBS), but no national population-based study has evaluated the incidences of GBS in China. This study aimed to estimate the incidence of GBS in urban China and evaluate the worldwide variation in the incidence of GBS.MethodsFirstly, we did a population-based study to calculate the incidence of GBS in urban China based on the National Urban Medical Insurance database from 2013 to 2017. To identify GBS cases, natural language processing was used first for handling the lengthy and unstructured diagnostic information and then checked by prestigious neurologists. Secondly, a systematic review and meta-analysis were performed to analyze the incidence of GBS worldwide. Up to July 4, 2022, Medline, Embase, and Web of Science were retrieved to identify the population-based studies regarding the incidence of GBS. The basic information and the statistics regarding incidence were extracted. Quality assessment considered sample representativeness, condition assessment, and statistical methods.ResultsA total of 1.44 billion person-years in insurance data was covered, with 3,534 GBS cases identified. The annual incidences of GBS in urban China between 2013 and 2017 ranged from 0.41 (95% CI: 0.27 to 0.58) to 0.58 (95% CI: 0.38 to 0.82) per 100,000 person-years. The incidence was the highest in Northwest China and the lowest in Northeast China. The meta-analysis included 122 articles. The quality assessment showed that the quality scores of 43.3% of studies were ≥ 0.75 (the total score is 1). The global incidence of GBS was 1.12 (95% CI: 0.98 to 1.27) per 100,000 person-years. The incidences in West Europe, South Asia, and North Europe were higher, while the incidences in Australia and New Zealand, Southeast Asia, and North Africa were lower. The incidence of enteric infections was positively associated with the incidence of GBS (coefficient=0.0000185, P=0.007). The incidence in Europe, Australia, and America rose significantly from 1960 to 2020 (coefficient=0.01, t=2.52, P=0.015).DiscussionThere is a clear regional variation of the GBS incidence at both national and global levels. Careful control of enteric infections should be conducted to reduce the disease burden.

Abstract The effect of influenza vaccination (FluVac) on the risk of neurodegenerative diseases has not been well evaluated in prospective populations. We aimed to assess the association between FluVac and the risk of dementia and Parkinson’s disease (PD) in people aged 60 years or older through a prospective population-based cohort from the UK Biobank. A time-varying Cox regression model adjusted for baseline and repeatedly measured covariates was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between influenza vaccination and risk of dementia/PD. We took into account 70,938 participants in the cohort, including 38,328 participants who got vaccinated. During a median follow-up period of 12.2 years, 2087 incident dementia cases occurred, including 281 cases who received FluVac and 1806 cases who were not vaccinated. In addition, 742 incident PD cases occurred, among whom 131 cases received FluVac and 611 PD cases did not receive FluVac. FluVac was associated with reduced dementia risk with an HR of 0.83 (95% CI, 0.72–0.95) but was not associated with PD incidence (HR = 1.07; 95% CI, 0.87–1.32) after controlling baseline and repeatedly measured covariates. Further, among all dementia cases, there were 733 Alzheimer’s disease (AD) (94 vaccinated cases and 639 non-vaccinated cases), 307 vascular dementia (VD) (34 vaccinated cases and 273 non-vaccinated cases), and 1047 cases with other dementias (OD) (153 vaccinated cases and 894 non-vaccinated cases). The HRs for the associations between FluVac and AD, VD, and OD were 0.79 (95% CI, 0.63–1.00), 0.58 (95% CI, 0.39–0.86), and 0.94 (95% CI, 0.78–1.14) respectively. A dose-response relationship was found in the association between FluVac and dementia but not in the association with PD. A major limitation of the study is the low accuracy in the diagnosis of dementia subtypes, namely AD, VD, and OD. However, Results of sensitivity analyses were consistent with the primary analyses. In conclusion, influenza vaccination is significantly associated with a reduced risk of incident dementia but not PD in community-dwelling adults in the UK Biobank population.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is gradually becoming a huge threat to public health. With complex working characteristics, female nurses had been found with high risk of NAFLD. To develop and validate a prediction model to predict the prevalence of NAFLD based on demographic characteristics, work situation, daily lifestyle and laboratory tests in female nurses. Methods This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), and data were extracted from the first-year follow data collected from 1st June to 1st September 2021 by questionnaires and physical examination records in a comprehensive tertiary hospital. The questionnaires included demographic characteristics, work situation and daily lifestyle. Logistic regression and a nomogram were used to develop and validate the prediction model. Results A total of 824 female nurses were included in this study. Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, HDL-C, UA, BMI, TBil and Ca were independent risk factors for NAFLD occurance. A prediction model for predicting the prevalence of NAFLD among female nurses was developed and verified in this study. Conclusion Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, UA, BMI and Ca were independent predictors, while HDL-C and Tbil were independent protective indicators of NAFLD occurance. The prediction model and nomogram could be applied to predict the prevalence of NAFLD among female nurses, which could be used in health improvement. Trial registration This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), which was a ambispective cohort study contained past data and registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572347 ) and the China Cohort Consortium ( http://chinacohort.bjmu.edu.cn/project/102/ ).

The 4-valent (4 v) and 9-valent (9 v) human papillomavirus (HPV) vaccines are approved in China for females aged 9–45 years. However, the real-world impact of 4vHPV or 9vHPV vaccination for the prevention of high-grade cervical disease in Chinese women is lacking. Two post-marketing surveillance studies will be conducted to measure the occurrence of high-grade cervical lesions in Chinese women who had received ≥1 dose of the 4vHPV (aged 20–45 years) or 9vHPV (aged 16–26 years) vaccine in Ningbo, China. Vaccination data will be extracted from the Ningbo Regional Health Information Platform (NRHIP) from the date of the first 4vHPV (January 9, 2018) or the first 9vHPV (January 25, 2019) vaccination to March 31, 2021. The primary 4vHPV and 9vHPV vaccinated cohorts will include women vaccinated per protocol. The 4vHPV/9vHPV vaccinated test-negative (cervical HPV negative; ThinPrep cytology test negative) and corresponding matched unvaccinated HPV test-negative sub-cohorts will also be assessed. Outcomes will be the occurrence of new-onset cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, and invasive cervical cancer. This study aims to demonstrate that such a methodological approach is feasible and can be used to assess the impact of HPV vaccination in other regions across China.

This protocol was developed to conduct population-wide surveillance of the bivalent HPV-16/18-AS04-adjuvanted human papillomavirus (HPV) vaccine in terms of uptake and safety outcomes including potential immune-mediated diseases (pIMDs) and pregnancy-related outcomes in China. The study will use electronic health records from 2010 to 2020 from the Yinzhou Regional Health Information Platform and include a population-based cohort of female permanent residents aged 9–45 years. Baseline and follow-up periods will be defined according to the 2017 introduction of HPV-16/18-AS04 in China. Patients with pIMDs and pregnancy-related outcomes will be identified using primary diagnostic codes from outpatient and inpatient electronic health records. A time trend analysis will be performed to describe the incidence of pIMDs and pregnancy-related outcomes during baseline and follow-up periods by age and overall, per calendar year. Depending on the number of safety outcomes and the size of the study population, incidence in vaccinated and unvaccinated cohorts will be compared using a Poisson regression model for pIMDs and a logistic regression model for pregnancy-related outcomes, adjusting for age and calendar year. Methods and findings from this study will provide valuable experience for designing future real-world studies and complement observations made during clinical trials and post-marketing studies.Study registration: http://www.chinadrugtrials.org.cn/index.html: CTR20210523.

BackgroundA phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited.MethodsTwo retrospective cohorts of newly diagnosed T2D patients from 2010–2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age 7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056–1.285) and 1.143 (95%CI, 1.044–1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis.ConclusionsPoor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

Abstract Primary health care (PHC) is the most effective way to improve people's health and well-being, and primary care services should act as the cornerstone of a resilient health system and the foundation of universal health coverage. To promote high quality development of PHC, an International Symposium on Quality Primary Health Care Development was held on December 4–5, 2023 in Beijing, China, and the participants have proposed and advocated the Beijing Initiative on Quality Primary Health Care Development. The Beijing Initiative calls on all countries to carry out and strengthen 11 actions: fulfill political commitment and accountability; achieve “health in all policies” through multisectoral coordination; establish sustainable financing; empower communities and individuals; provide community-based integrated care; promote the connection and integration of health services and social services through good governance; enhance training, allocation and motivation of health workforce, and medical education; expand application of traditional and alternative medicine for disease prevention and illness healing; empower PHC with digital technology; ensure access to medicinal products and appropriate technologies; and last, strengthen global partnership and international health cooperation. The Initiative will enrich the content of quality development of PHC, build consensus, and put forward policies for quality development of PHC in China in the new era, which are expected to make contributions in accelerating global actions.

Background Monitoring the risk of intussusception after the introduction of rotavirus vaccines is recommended by the World Health Organization (WHO). Although the validity of intussusception monitoring using electronic health records (EHRs) has been confirmed previously, no similar studies have been conducted in China. We aimed to verify the diagnosis and determine an algorithm with the best performance for identification of intussusception using Chinese EHR databases. Research design and methods Using the Regional Health Information Platform in Ningbo, patients aged 0–72 months from 2015 to 2021 with any related visits for intussusception were included. The algorithms were based on diagnostic codes or keywords in different clinical scenarios, and their performance was evaluated with positive predictive value (PPV) and sensitivity in line with the Brighton guidelines. Results Brighton level 1 intussusception was confirmed in 2958 patients with 3246 episodes. Fine-tuned algorithms combining the appearance of the relevant ICD-10 codes or the Chinese keyword ‘Chang Tao’ in any diagnostic reports with the results of enema treatments or related surgeries showed the highest sensitivity, while the highest PPV was obtained by further criteria based on typical radiographic appearances. Conclusion Intussusception could be identified and validated internally using EHRs in Ningbo.

Background The 9-valent human papillomavirus (9vHPV) vaccine was introduced in China in 2018. This study was conducted to monitor the occurrence of new-onset autoimmune diseases (AIs) in Chinese women vaccinated with the 9vHPV vaccine and adverse pregnancy outcomes in infants born to mothers with inadvertent pregnancy exposure. Research design and methods Women who received the first dose of the 9vHPV vaccine at age 16–26 years in Ningbo between January 2019 and March 2021 were monitored in the Ningbo Regional Health Information Platform. New-onset cases of seven pre-specified AIs diagnosed within six months after vaccination were collected. Cases of stillbirth and 23 major congenital anomalies diagnosed within three months of birth in target infants were collected. Results A total of 102,670 doses of the 9vHPV vaccine were administered to 41,609 women who had received no other HPV vaccine. New-onset AIs were diagnosed in 36 women, comprising 21 Hashimoto’s, 11 Graves’, and 4 uveitis disease cases. Among 50 women with maternal vaccination exposure, no stillbirths were observed. One case of microtia was observed. Conclusions In this first post-marketing surveillance of the 9vHPV vaccine in China, no safety signals were identified when putting the results in context to published data.

Abstract Background The relationship between obesity and hearing loss among the middle-aged and older population remained unclear. Moreover, few studies have focused on the impact of gender on this association. Methods This cohort study extracted the data from the China Health and Retirement Longitudinal Study, a national survey of adults aged 45 years or over. Waist circumference was categorized into three groups: normal, pre-central obesity, and central obesity. We classified BMI into four categories: underweight, normal weight, overweight, and obese. The primary endpoint was the incidence of self-reported hearing loss. Results Of the 14,237 participants, 1972 incidents of hearing loss were identified during a median 6.9 years of follow-up. The cumulative incidence of hearing loss was 13.9% (95% CI 13.3% -14.4%). Our study showed that central obesity was significantly associated with hearing loss (HR 0.84, 95%CI 0.75–0.94), and this relationship was more prominent in males (HR 0.76, 95%CI 0.63–0.91). Among male participants, the underweight group was at the highest risk of hearing loss (HR 1.39, 95%CI 1.08–1.79). Compared with the normal weight group, the adjusted HR for hearing loss in the obese groups was 0.69 (95%CI 0.51–0.94) among men. Among female participants, only the overweight group had a lower risk of hearing loss than the normal weight group (HR 0.83, 95%CI 0.71–0.96). Conclusions Being overweight and obese were significantly associated with a decreased risk of hearing loss, whereas being underweight was associated with an increased risk of hearing loss.

Some post-licensure studies have shown a potential increased risk of intussusception following vaccination with rotavirus vaccines. This is the first study that aimed to assess the incidence and risk of intussusception within 90 days after vaccination with RotaTeq in Chinese infants. A population-based birth cohort from 27th November 2018 to 30th June 2021 included all newborns in Ningbo city. The records of intussusception were identified through the ICD-10 code K56.1 or Chinese keywords “Chang Tao” from all hospital discharge records. Each episode was confirmed in line with the Brighton criteria, and only Brighton level 1 cases were included. The association of RotaTeq vaccination and intussusception was evaluated using the Poisson regression. A total of 108,405 eligible subjects from birth cohort were eligible, with 52.30% males. Among them, 26, 847 (24.77%) infants received at least one dose of RotaTeq, and 95.52% of them were fully vaccinated, with 76, 934 doses in total. After adjudication, none of the cases occurred post first, or second dose, the cumulative number of cases that occurred 1–7, 1–14, 1–21, 1–42, and 1–90 days post third dose was 0, 1, 1, 3, and 7, respectively. Adjusting for age, sex, birth year, birth season and location, the incidence rate ratio of intussusception after RotaTeq vaccination was 0.90 (90% two-sided CI: 0.46, 1.75). Increasing age and male gender were associated with higher risk of intussusception. In summary, no increased risk of IS was observed following 3 months of RotaTeq vaccination in this study.

Abstract Background Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose‐lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. Methods A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. Results A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person‐years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38–0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Conclusions Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9–45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1–3, and cervical cancer) in a cohort of females aged 9–70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010–2016) and post-launch (2018–2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

Abstract Objective: To determine if limb lengths, as markers of early life environment, are associated with the risk of diabetes in China. Design: We performed a cohort analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), and multivariable-adjusted Cox proportional hazard regression models were used to examine the associations between baseline limb lengths and subsequent risk of diabetes. Setting: The CHARLS, 2011–2018. Participants: The study confined the eligible subject to 10 711 adults aged over 45 years from the CHARLS. Results: During a mean follow-up period of 6·13 years, 1358 cases of incident diabetes were detected. When controlling for potential covariates, upper arm length was inversely related to diabetes (hazard ratio (HR) 0·95, 95 % CI (0·91, 0·99), P = 0·028), and for every 1-cm difference in knee height, the risk of diabetes decreased by about 4 % (HR 0·96, 95 % CI (0·93, 0·99), P = 0·023). The association between upper arm length and diabetes was only significant among females while the association between knee height and diabetes was only significant among males. In analyses stratified by BMI, significant associations between upper arm length/knee height and diabetes only existed among those who were underweight (HR 0·91, 95 % CI (0·83, 1·00), P = 0·049, HR 0·92, 95 % CI (0·86, 0·99), P = 0·031). Conclusions: Inverse associations were observed between upper arm length, knee height and the risk for diabetes development in a large Asian population, suggesting early life environment, especially infant nutritional status, may play an important role in the determination of future diabetes risk.

Abstract. Background:. Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. Methods:. Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. Results:. In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53–24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06–1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16–2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25–2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36–14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08–3.91). No significant difference in the risk for SAEs was found in any comparisons. Conclusions:. Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. Registration:. PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42021278149.

Abstract Background Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. Methods This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. Discussion This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9–45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. Trial registration This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.

Abstract The health burden of Parkinson’s disease (PD) and diabetes increases rapidly in China. However, no population-based study of the association between glucose lowering agents and PD incidence has been conducted in mainland Chinese population. Preclinical studies indicate that thiazolidinediones (TZDs) have neuroprotective effects against PD through stimulating peroxisome proliferator-activated receptor gamma. Nevertheless, debate remains in human studies. We assembled a retrospective cohort of type 2 diabetes mellitus (T2DM) patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) was applied to estimate the hazard ratio (HR) of PD incidence associated with the use of TZDs compared with AGIs. The final cohort included 12,704 new users of TZDs and 49,696 new users of AGIs. The incidence of PD was 135 per 100,000 person-years in TZD users and 203 per 100,000 person-years in the AGI group. An inverse association between use of TZDs and incidence of PD, with a HR of 0.74 (95% confidence interval, 0.59–0.92), was observed after adjusting for potential confounding using IPTW. The results of various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Our results indicated that the use of TZD is associated with a decreased risk of PD incidence in a mainland Chinese population with T2DM. Given the heavy disease burden of PD and diabetes in China, these findings could provide some evidence for developing effective prevention and control measures to reduce the future incidence of PD in China.

Background The coronavirus disease 2019 (COVID-19) pandemic has posed a great challenge to the healthcare system. This study evaluated the impact of the pandemic on the utilization of primary healthcare (PHC). Methods The outpatient data from 158 PHC institutions in Yinchuan from May 1, 2017 to April 30, 2020 were used. The difference in difference (DID) model was used to analyze the difference in the number of outpatient visits per day, total outpatient expenditure per day, and outpatient expenditure per visit between December 2019 and February 2020 compared with the same periods in two previous years. The autoregressive integrated moving average (ARIMA) modelling was used to investigate the association between the outpatient volume and the number of the last week’s new COVID-19 cases in Yinchuan, Ningxia, and China. Results From December 2019 to February 2020, the decline in the number of outpatient visits per day (DID: -367.21 times, P = .004) was larger than that in two previous years, and a similar trend can be seen in the outpatient expenditure per day. However, the rise in the outpatient expenditure per visit (DID: 19.06 thousand yuan, P = .003) was larger than that in two previous years. In 2020, the outpatient visits for most types of diseases decreased from week 3 and rebounded after week 5. The decline and rebound of outpatient visits in the population aged 45 years and older were steeper than in those younger. The outpatient volume was negatively associated with the number of the last week’s new COVID-19 cases. Conclusion This study indicated a significant impact of the pandemic on PHC service utilization. Since PHC service is the foundation of the healthcare system in most developing countries, measures should be taken to make PHC help cope with the crisis and relieve the burden of hospital care.

Abstract Background While the prevalence and disease burden of bronchiectasis are increasing, data in the world’s largest population are lacking. We aimed to investigate the prevalence and disease burden of bronchiectasis in Chinese adults. Methods We conducted a population-based study using data between 2013 and 2017 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China. Data from over 380 million patients aged 18 years and older during the study period were analyzed, and a total of 383,926 bronchiectasis patients were identified. Primary outcomes included the age- and sex-specific prevalence of bronchiectasis. Annual visits and hospitalizations, as well as annual costs were also calculated. Results The prevalence of bronchiectasis in Chinese adults increased 2.31-fold, from 75.48 (62.26, 88.69) per 100,000 in 2013 to 174.45 (137.02, 211.88) per 100,000 in 2017. The increase was more remarkable for patients aged over 50 years in both genders. The per-capita total cost and hospitalization cost of patients with bronchiectasis increased 2.18-fold and 1.83-fold from 2013 to 2017, respectively, mostly driven by non-bronchiectasis costs. The average annual hospitalization ranged from 1.20 to 1.24 times during the 5 years. Conclusion The prevalence and disease burden of bronchiectasis in Chinese urban adults ≥ 18 years had increased significantly between 2013 and 2017.

Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered—namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants’ onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.

Abstract Background Haemolytic uraemic syndrome (HUS) is a severe syndrome that causes a substantial burden for patients and their families and is the leading cause of acute kidney injury in children. However, data on the epidemiology and disease burden of HUS in Asia, including China, are limited. We aimed to estimate the incidence and cost of HUS in China. Methods Data about HUS from 2012 to 2016 were extracted from the Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) databases. All cases were identified by ICD code and Chinese diagnostic terms. The 2016 national incidence rates were estimated and stratified by sex, age and season. The associated medical costs were also calculated. Results The crude incidence of HUS was 0.66 per 100,000 person-years (95% CI: 0.35 to 1.06), and the standardized incidence was 0.57 (0.19 to 1.18). The incidence of HUS in males was slightly higher than that in females. The age group with the highest incidence of HUS was patients

Abstract Background Biomedical named entity recognition (BioNER) is a basic and important medical information extraction task to extract medical entities with special meaning from medical texts. In recent years, deep learning has become the main research direction of BioNER due to its excellent data-driven context coding ability. However, in BioNER task, deep learning has the problem of poor generalization and instability. Results we propose the hierarchical shared transfer learning, which combines multi-task learning and fine-tuning, and realizes the multi-level information fusion between the underlying entity features and the upper data features. We select 14 datasets containing 4 types of entities for training and evaluate the model. The experimental results showed that the F1-scores of the five gold standard datasets BC5CDR-chemical, BC5CDR-disease, BC2GM, BC4CHEMD, NCBI-disease and LINNAEUS were increased by 0.57, 0.90, 0.42, 0.77, 0.98 and − 2.16 compared to the single-task XLNet-CRF model. BC5CDR-chemical, BC5CDR-disease and BC4CHEMD achieved state-of-the-art results.The reasons why LINNAEUS’s multi-task results are lower than single-task results are discussed at the dataset level. Conclusion Compared with using multi-task learning and fine-tuning alone, the model has more accurate recognition ability of medical entities, and has higher generalization and stability.

In China, a free influenza vaccination policy is being implemented among individuals aged 70 years and over in Zhejiang province during the COVID-19 pandemic. The objective was to assess the effectiveness of influenza vaccine in reducing hospitalization and mortality in the elderly. We used data from the Regional Health Information Platform in Yinzhou located in Zhejiang province and applied a regression discontinuity design to estimate the intention-to-treat effect on admission and mortality rates by month of age in the population who was near the age of 70 years threshold. At age 70 years, the influenza vaccination rate increased by 29.1% (95% CI, 28.2% to 29.9%) compared to those under 70 in the study population. When turning age 70 years, the potential effectiveness of receiving influenza vaccine was 8.2% (95% CI, −36.8% to 51.3%) for total hospitalization and the evaluation of vaccine effectiveness was 13.1% (95% CI, −34.2 to 61.8) for the all-cause mortality. An increase in the influenza vaccination rate was associated with a weak decline in most outcomes, but no significance was found for all outcomes. Influenza vaccination had a limited effect on hospital admission and mortality for the free influenza vaccination program that can be related to the low vaccination rate among the Chinese elderly. Supplementation strategies and future studies may be needed to expand immunization coverage and validate this finding, and further provide a reference for other cities to promote the free influenza vaccination policy in China, especially under circumstances of the COVID-19 pandemic.

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54–1.97], p = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients.

ObjectiveThis study aimed to determine the efficacy, effectiveness, and cost-effectiveness of inactivated COVID-19 vaccines (CoronaVac and BBIBP-CorV) in China using existing international clinical trials and real-world evidence.MethodsThrough a search of PubMed, Embase, Web of Science, and CNKI, studies investigating the effectiveness of inactivated COVID-19 vaccines were identified, and a meta-analysis was undertaken to synthesize the vaccine efficacy and effectiveness data. Moreover, a decision-analytic model was developed to estimate the cost-effectiveness of inactivated vaccines for combating the COVID-19 pandemic in the Chinese context from a societal perspective. Results of the meta-analysis, along with cost data from official websites and works of literature were used to populate the model. Sensitivity analysis was performed to test the robustness of the model results.ResultsA total of 24 studies were included in the meta-analysis. In comparison to no immunization, the effectiveness of inactivated vaccine against COVID-19 infection, hospitalization, ICU admission and death were 65.18% (95% CI 62.62, 67.75), 79.10% (95% CI 71.69, 86.51), 90.46% (95% CI 89.42, 91.50), and 86.69% (95% CI 85.68, 87.70); and the efficacy against COVID-19 infection and hospitalization were 70.56% (95% CI 57.87, 83.24) and 100% (95% CI 61.72, 100). Inactivated vaccine vaccination prevented more infections, hospitalizations, ICU admissions, and deaths with lower total costs, thus was cost-saving from a societal perspective in China. Base-case analysis results were robust in the one-way sensitivity analysis, and the percentage of ICU admission or death and direct medical cost ranked the top influential factors in our models. In the probabilistic sensitivity analysis, vaccination had a 100% probability of being cost-effective.ConclusionInactivated vaccine is effective in preventing COVID-19 infection, hospitalization, ICU admission and avoiding COVID-19 related death, and COVID-19 vaccination program is cost-saving from societal perspective in China.

BackgroundThere has been a paucity of evidence examining whether preventable behavioral risk factors led to ethnic differences of gastric precancerous lesions (GPL). We aimed to investigate the ethnic disparity of associations between GPL and lifestyle factors in Mongolian and Han Chinese populations.MethodsThe study included participants aged 36-75 years enrolled in the Cancer Screening Program during 2016-2017 in Hohhot and Tongliao City, Inner Mongolia. GPL was defined as the gross cascading events (i.e., gastric ulcer, atrophic gastritis, intestinal metaplasia, and dysplasia) that preceded gastric cancer.ResultsA total of 61638 participants were included, of whom 6863(11·1%) were Mongolians. Alcohol consumption was positively associated with GPL risk in both ethnic groups, but the magnitude was greater in Mongolians (odds ratio (OR) 6·91, 95%CI 5·82-8·28) than in Han Chinese (OR 5·64, 95%CI 5·27-6·04), corresponding to a higher population attributable fraction (PAF) for Mongolians (53·18% vs 43·71%). Besides, the strength of the positive association between physical inactivity and GPL risk was greater among Mongolians (OR 2·02, 95%CI 1·70-2·41; OR 1·09, 95%CI 1·02-1·17 among Han Chinese) with a higher PAF. Smoking was strongly associated with GPL risk in both ethnic groups as well, but the association was more prominent among Han Chinese (OR 5·24 (1·70-2·41) for

Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown.Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China’s patients receiving XYP.Methods: A nested case–control study was conducted using the sampling data from 2015 China’s Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day.Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case–control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings.Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

BackgroundCurrent evidence of the association between the use of sulfonylurea and cancer risk is highly conflicting and little evidence of this association is from the mainland Chinese population. This study aimed to evaluate the potential effects of sulfonylurea use on cancer risk among patients with type 2 diabetes mellitus (T2DM).MethodsA retrospective cohort study of T2DM patients who were new users of sulfonylurea or metformin was conducted using the Yinzhou Regional Health Care Database. A marginal structural Cox model was used to estimate the hazard ratio (HR) of cancer associated with the use of sulfonylurea compared with metformin, with time-varying confounders controlled by inverse probability weighting. Secondary analyses using different glucose-lowering drugs (GLDs) as comparator and sensitivity analyses for potential bias due to latency period, model misspecification, missing data, analyses strategy (intention-to-treat and per-protocol), and diagnosis validation were performed to examine the robustness of the results.ResultsAfter fully controlling for time-varying confounding, baseline confounding, and competing risk, the use of sulfonylurea was not associated with the risk of any cancer (HR 1.09; 95% CI, 0.93–1.27), compared with the use of metformin. In the secondary analyses, compared with α - glucosidase inhibitors, thiazolidinediones, glinides, other GLDs except sulfonylure and insulin, and T2DM patients not treated with sulfonylureas, the HRs of the association between sulfonylurea use and cancer risk were 0.92 (95% CI; 0.78–1.08), 0.89 (95% CI; 0.66–1.19), 0.85 (95% CI; 0.71–1.02), 1.04 (95% CI; 0.89–1.22), and 1.07 (95% CI; 0.99–1.16), respectively. The results of analyses for various subgroups, risk of site-specific cancers, cumulative duration, dose-response relationship, and sensitivity analyses of different latency periods and missing data were generally consistent with the findings of the primary analyses.ConclusionNo association between sulfonylurea use and cancer risk was found in this study after properly controlling biases due to time-varying confounders and other sources. Further studies on the association between sulfonylurea use and the risk of cancer by using data from a Chinese population with higher representativeness are needed.

Abstract Background Extramammary Paget’s disease (EMPD) is an intraepithelial adenocarcinoma. The chronic relapsing clinical course and unbearable clinical symptoms of extramammary Paget’s disease usually result in a markedly diminished quality of life. No national data are available on descriptive epidemiology of EMPD in China, the most populous country over the world. This population-based study aimed to estimate the prevalence and associated sex and age patterns of EMPD in China. Methods This study was conducted using data from China’s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion Chinese urban residents in 2016. Patients with EMPD were identified based on the diagnostic names and codes in claim data. Results A total of 53 males and 31 females with EMPD were found. The crude prevalence in 2016 was 0.04 per 100,000 population [95% confidence interval (CI) 0.02–0.06], ranging from 0.01 (95% CI 0.00–0.02) in North or Northeast China to 0.08 (95% CI 0.03–0.16) in Southwest China. The rate was higher in males (0.05, 95% CI 0.03–0.08) compared with females (0.03, 95% CI 0.02–0.05). The mean age of patients was 65.87 (standard deviation: 14.21) years, with the peak prevalence appeared in patients aged 70–79 (0.28, 95% CI 0.16–0.42). Conclusions The prevalence of EMPD was markedly lower than those in the United States and Europe, and varied across regions in China. Chinese patients were much younger, with significant male predominance. Further studies are warranted to examine potential pathophysiologic mechanism.

In this study, the polyethyleneimine (PEI) modified waste bamboo powder (WBP-Na-PEI) was successfully prepared and applied to adsorbing Congo red (CR) dye from aqueous solution. The obtained materials were characterized by field emission scanning electron microscope, X-ray diffraction, Fourier transform-infrared, and thermogravimetric analysis. The results showed that WBP-Na-PEI(1.8 K-5) was synthesized successfully and PEI uniformly covered the WBP-Na-PEI(1.8 K-5) surface. In the process of adsorption, four kinds of influencing factors were discussed, and the adsorption mechanisms such as kinetics, isotherm, thermodynamics were explored. The maximum adsorption capacity of WBP-Na-PEI(1.8 K-5) was 992.94 mg·g−1 at 298 ± 1 K, and the removal efficiency was over 98%. Pseudo-first-order, pseudo-second-order and intra-particle diffusion models were studied, the results showed that the adsorption process conformed to the pseudo-second-order model, and the rate of this process was controlled by many steps. Furthermore, the removal efficiency of the adsorption kinetics reached 85% within 10 minutes. The results of the isotherm model and thermodynamics showed that the adsorption process was consistent with the Langmuir model and was mainly a spontaneous chemical endothermic process of monolayer. And the removal efficiency of the adsorbent reached 93% at the concentration of 400 mg/L, which can be expected to have a broad prospect in the treatment of CR industrial wastewater.

Abstract Background Information on incidence of gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumor in gastrointestinal tract, was limited in China. This study aimed to estimate the incidence of GIST in urban population from mainland China in 2016. Methods Urban Employee Basic Medical Insurance (UEBMI) and Urban Residence Basic Medical Insurance (URBMI) in China were used. The denominator of incidence was the total person‐years of insured individuals in 2016 in the database, covering approximately 0.43 billion individuals. The numerator was the number of incident GIST cases in 2016. Results The crude incidence in 2016 was 0.40 per 100,000 person‐years (95% CI, 0.06–1.03). Male incidence was higher than female incidence (0.44 vs. 0.36, rate ratio: 1.22, p

Abstract No national data have been available on descriptive epidemiology of mammary Paget’s disease (MPD) in China. This population-based study aimed to estimate the prevalence of MPD and its pattens by sex, age and area in China. We conducted a population-based study using data in 2016 from China’s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion residents. MPD cases were identified based on the diagnostic names and codes in claim data. A total of 825 patients of confirmed diagnosis of MPD were found during the study period. The prevalence of MPD in 2016 was 0.42 per 100,000 population (95% CI 0.19 to 0.73), with marked female predominance. The prevalence rates peaked at 40–59 years and ≥ 80 years in females and males, respectively. The prevalence rates varied among different regions, ranging from 0.06 (95% CI 0.00 to 0.23) in Northeast China to 1.21 (95% CI 0.07 to 3.72) in Northwest China. MPD showed marked female predominance in China. Chinese female patients were much younger, with lower prevalence than that in the United States. Obvious sex difference in the age pattern of MPD prevalence was also observed in China.

Abstract Background Studies regarding the lipid-cognition relationship have increasingly gained popularity but have generated much mixed results. To date, few studies have focused on the difference between sexes. Methods This study included 6792 Chinese adults aged over 45 years (women, 48.56%; mean age, 57.28 years), who were free of severe conditions known to affect cognitive function at the baseline (2011). Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were assessed at baseline, and both continuous and categorical values were used in final analyses. Global cognitive functions were assessed by the word recall test and the mental status test in 2011, 2013, and 2015, respectively. We graded participants into three groups according to the cognitive change slopes: no decline (≥ 0), moderate decline (median to 0), and severe decline (< median). Sex-specific associations between blood lipids and cognitive decline were analyzed using ordinal logistic models, adjusting for sociodemographic information, lifestyle behaviors, and health status. Results Higher baseline TC and LDL-C concentrations exhibited no significant association with 5-year cognitive decline in men but were significantly associated with greater 5-year cognitive decline in women [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.003, 1.050; OR 1.026, CI 1.002, 1.051, respectively]. For higher serum HDL-c levels, a significantly protective effect on cognition was observed in men, but a slightly adverse effect was found in women (not significant after Bonferroni correction). TG presented almost no effect on later cognition in either sex. Conclusion Different associations between sexes were observed for the lipid-cognition relationship, and maintaining serum cholesterol levels at an appropriate range may have a positive effect on cognitive health.

Background: The appropriateness of antibiotic prescriptions in primary care has not been well evaluated in China in recent years. Furthermore, the impact of coronavirus disease 2019 (COVID-19) on antibiotic prescriptions has not yet been investigated in China. We aimed to assess the appropriateness of antibiotic prescriptions and to evaluate the potential association between the COVID-19 pandemic and antibiotic prescriptions in primary care settings of Yinchuan, a city in China.Methods: This study included 155 primary care institutions and 10,192,713 outpatient visits. Outpatient prescriptions were classified as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use following a validated evaluation scheme. Interrupted time-series analyses were performed to assess the effects of the COVID-19 pandemic on antibiotic prescriptions in Chinese primary care facilities.Results: During the study period, 1,287,678 (12.6%, 95% confidence interval [12.6–12.7]) of 10,192,713 outpatient visits in primary care resulted in antibiotic prescriptions. Among 1,287,678 antibiotic prescriptions, 653,335 (50.7% [50.6–50.9]) were inappropriate, 463,081 (36.0% [35.8–36.1]) were potentially appropriate, 171,056 (13.3% [13.1–13.5]) were appropriate, and 206 could not be linked to any diagnosis. Furthermore, patient, physician, and institutional factors were associated with inappropriate antibiotic prescriptions; there was an overall decreasing trend in the proportions of inappropriate antibiotic prescriptions, with the highest level in 2017 (67.1% [66.8–67.5]) and the lowest in 2021 (40.8% [40.3–41.3]). A total of 1,416,120 individual antibiotics were prescribed, of which 1,087,630 (76.8%) were broad-spectrum and 777,672 (54.9%) were classified in the World Health Organization’s “Watch” category. In addition, the COVID-19 pandemic was associated with changes of −2.8% (−4.4 to −1.3) in the level and 0.3% (0.2–0.3) in the monthly trend of antibiotic prescription rates, as well as changes of −5.9% (−10.2 to −1.5) in the level and 1.3% (1.0–1.6) in the monthly trend of the proportions of inappropriate antibiotic prescriptions.Conclusion: More than half of the antibiotic prescriptions were inappropriate during the study period in primary care in Yinchuan. The COVID-19 pandemic may be associated with a decrease in the overall and inappropriate use of antibiotics in primary care settings in China.

BackgroundThere are limited data available on the impact of early (within 24 h of admission) β-blocker therapy on in-hospital outcomes of patients with ST-elevation myocardial infarction (STEMI) and mild-moderate acute heart failure. This study aimed to explore the association between early oral β-blocker therapy and in-hospital outcomes.MethodsInpatients with STEMI and Killip class II or III heart failure from the Improving Care for Cardiovascular Disease in China project (n = 10,239) were enrolled. The primary outcome was a combined endpoint composed of in-hospital all-cause mortality, successful cardiopulmonary resuscitation after cardiac arrest, and cardiogenic shock. Inverse-probability-of-treatment weighting, multivariate Cox regression, and propensity score matching were performed.ResultsEarly oral β-blocker therapy was administered to 56.5% of patients. The incidence of the combined endpoint events was significantly lower in patients with early therapy than in those without (2.7 vs. 5.1%, P < 0.001). Inverse-probability-of-treatment weighting analysis demonstrated that early β-blocker therapy was associated with a low risk of combined endpoint events (HR = 0.641, 95% CI: 0.486–0.844, P = 0.002). Similar results were shown in multivariate Cox regression (HR = 0.665, 95% CI: 0.496–0.894, P = 0.007) and propensity score matching (HR = 0.633, 95% CI: 0.453–0.884, P = 0.007) analyses. A dose-response trend between the first-day β-blocker dosages and adverse outcomes was observed in a subset of participants with available data. No factor could modify the association of early treatment and the primary outcomes among the subgroups analyses.ConclusionBased on nationwide Chinese data, early oral β-blocker therapy is independently associated with a lower risk of poor in-hospital outcome in patients with STEMI and Killip class II or III heart failure.

BackgroundMinimally invasive cardiac surgery-coronary artery bypass grafting (MICS-CABG) has emerged as a safe alternative to standard cardiac surgery. However, treatment preferences can decrease the generalizability of RCT results to the clinical population (i.e., reduce external validity) and influence adherence to the treatment protocol and study outcomes (i.e., reduce internal validity). However, this has not yet been properly investigated in randomized trials with consideration of treatment preferences.Study DesignIn this study, patients with a preference will be allocated to treatment strategies accordingly, whereas only those patients without a distinct preference will be randomized. The randomized trial is a 248-patient controlled, randomized, investigator-blinded trial. It is designed to compare whether treatment with MICS-CABG is beneficial in comparison to CABG. This study is aimed to establish the superiority hypothesis for the physical component summary (PCS) accompanied by the non-inferiority hypothesis for overall graft patency. Patients with no treatment preference will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoints are the PCS score at 30 days after surgery and the overall patency rate of the grafts within 14 days after surgery. Secondary outcome measures include the PCS score and patency rate at different time points. Safety endpoints include major adverse cardiac and cerebrovascular events, complications, bleeding, wound infection, death, etc.ConclusionsThis trial will address essential questions of the efficacy and safety of MICS-CABG. The study will also address the impact of patients' preferences on external validity and internal validity.

Background: Emerging studies suggest a positive association between air pollution exposure and risk of non-alcoholic fatty liver disease (NAFLD), however, the combined effects of long-term exposure to air pollution, physical activity (PA), and risk of NAFLD is unclear. Methods: We included 58,026 Taiwan residents who received a standard medical screening program between 2001 and 2016. Levels of fine particulate matter (PM2.5) at each participant’s residential address were estimated using multiple satellite-based aerosol optical depth data combined with a chemical transport model. PA volume was calculated as hours of metabolic equivalent tasks per week (MET-h/week) based on a standard self-administered questionnaire. Incident NAFLD was defined as the first occurrence of a fatty liver index (FLI) value > 30 or a hepatic steatosis index (HSI) value > 36 in participants without NAFLD at the baseline. Time-varying Cox regression was used to evaluate the combined effects of PA and PM2.5. Results: Exposure to PM2.5 was positively associated with NAFLD. A 1 μg/m3 increase in PM2.5 above 23.5 μg/m3 was associated with a hazard ratio (HR) of 1.06 (95% CI: 1.04, 1.09) and 1.05 (95% CI: 1.03, 1.07) for NAFLD identified by FLI and HSI, respectively. Performing PA was inversely associated with NAFLD. Compared with participants in high PM2.5 [≥ 27.5 μg/m3]–very low PA [

Background: For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns.Objective: This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis.Method: The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects.Conclusion: For the emergency management of anaphylaxis we conclude that:• NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis• Prompt and proper administration of epinephrine is critical.

Abstract Background Both intermittent intravenous (IIV) infusion and continuous intravenous (CIV) infusion of Endostar are widely used for NSCLC in China. We aimed to compare the efficacy and safety of CIV of Endostar versus IIV in combination with first-line chemotherapy for patients with advanced NSCLC. Methods RCTs, NRCTs and cohort studies which compared CIV of Endostar with IIV in advanced NSCLC patients and reported efficacy or safety outcomes were eligible. Two reviewers independently screened records, extracted data and assessed risk of bias. Pooled risk ratios (RRs) with 95% confidence intervals were calculated using random effects meta-analysis for short-term efficacy and safety outcomes, and hazard ratios (HRs) for survival outcomes. Results Finally nine studies involving 597 patients were included, containing two RCTs, three NRCTs and four cohort studies. For short-term efficacy, moderate quality of evidence showed that there were no significant differences between CIV of Endostar and IIV in objective response rate (ORR; RR 1.34, 95% CI 0.91–1.98, P = 0.14) and disease control rate (DCR; RR 1.11, 95% CI 0.94–1.30, P = 0.21). Very low quality of evidence indicated that CIV of Endostar significantly improved both overall survival (OS; HR 0.69, 95% CI 0.48–0.99, P = 0.046) and progression-free survival (PFS; HR 0.71, 95% CI 0.55–0.93, P = 0.01) compared with IIV. As for safety outcomes, moderate quality of evidence found that CIV of Endostar significantly reduced the risk of myelosuppression (RR 0.55, 95% CI 0.32–0.96, P = 0.03) and cardiovascular toxicity (RR 0.21, 95% CI 0.06–0.78, P = 0.02) compared with IIV. Conclusions In advanced NSCLC, compared with IIV, CIV of Endostar had similar short-term efficacy, and substantially lower risk of myelosuppression and cardiovascular toxicity. Although very low quality of evidence supported the survival benefit of CIV compared with IIV, large RCTs with long-term follow-up are needed to demonstrate survival benefits. Caution should be given for off-label use of CIV of Endostar.

Alzheimer’s disease (AD) has been a major causal factor for mortality among elders around the world. The treatments for AD, however, are still in the stage of development. Stem cell therapy, compared to drug therapies and many other therapeutic options, has many advantages and is very promising in the future. There are four major types of stem cells used in AD therapy: neural stem cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. All of them have applications in the treatments, either at the (1) cellular level, in an (2) animal model, or at the (3) clinical level. In general, many more types of stem cells were studied on the cellular level and animal model, than the clinical level. We suggest for future studies to increase research on various types of stem cells and include cross-disciplinary research with other diseases. In the future, there could also be improvements in the timeliness of research and individualization for stem cell therapies for AD.

Background: Drug-induced thrombocytopenia (DITP) is a severe adverse reaction and a significantly under-recognized clinical problem in children. However, for post-marketing pharmacovigilance purposes, detection of DITP signals is crucial. This study aimed to develop a signal detection model for DITP using the pediatric electronic medical records (EMR) data.Methods: This study used the electronic medical records collected at Beijing Children’s Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DITP. In the first stage, we calculated the crude incidence by mining cases of thrombocytopenia to select the potential suspected drugs. In the second stage, we constructed propensity score–matched retrospective cohorts of specific screened drugs from the first stage and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The novelty of the signal was assessed by current evidence.Results: In the study, from a total of 839 drugs, 21 drugs were initially screened as potentially inducing thrombocytopenia. In total, we identified 18 positive DITP associations. Of these, potential DITP risk of nystatin (OR: 1.75, 95% CI: 1.37–2.22) and latamoxef sodium (OR: 1.61, 95% CI: 1.38–1.88) were two new DITP signals in both children and adults. Six associations between thrombocytopenia and drugs including imipenem (OR: 1.69, 95% CI: 1.16–2.45), teicoplanin (OR: 4.75, 95% CI: 3.33–6.78), fusidic acid (OR: 2.81, 95% CI: 2.06–3.86), ceftizoxime sodium (OR: 1.83, 95% CI: 1.36–2.45), ceftazidime (OR: 2.16, 95% CI: 1.58–2.95), and cefepime (OR: 5.06, 95% CI: 3.77–6.78) were considered as new signals in children.Conclusion: This study developed a two-stage algorithm to detect safety signals of DITP and found eighteen positive signals of DITP, including six new signals in a pediatric population. This method is a promising tool for pharmacovigilance based on EMR data.

Background: Studies observing the relationship between pulmonary function and the risk of cognitive impairment in middle-aged and older adults was increasing, but the results were inconsistent. To date, evidence from longitudinal data is scarce and further research is urgently needed. Methods: We used data from the China Health and Retirement Longitudinal Study. Participants were enrolled in 2011/2013 and followed up in 2013, 2015 and 2018. Pulmonary function was assessed via peak expiratory flow (PEF). Cognitive function, measured by episodic memory and mental status, was assessed through a face-to-face interview in each survey. Results: A total of 8,274 participants (52.86% males; mean age, 56.44 years) were included. The scores of global cognition (12.46 versus 11.51, P < 0.001) of men were significantly higher than women at baseline, with a total of 5096 participants (61.59%) declining during the follow-up. Higher baseline PEF was associated with lower absolute decline in global cognition (OR per 1-SD difference 0.921; P = 0.031) and mental status (OR per 1-SD difference 0.9889; P = 0.002) during follow-up in men, and significant associations between higher baseline PEF and a lower absolute decline in the episodic memory were both found in men (OR per 1-SD difference 0.907; P = 0.006) and women (OR per 1-SD difference 0.915; P = 0.022). Second analysis showed that the significant associations between positive PEF variation and a lower rate of 4-year decline in global cognition, mental status and episodic memory were all only found in men. In subgroup analyses, higher PEF at baseline was significantly associated with a lower absolute decline of global cognition among male individuals >60 years. Significant associations between higher PEF at baseline and lower absolute decline in global cognition and episodic memory during follow-up were only found in never-smokers, while higher PEF was related to lower absolute decline in mental status among non-smoking and smoking males. Conclusions: Pulmonary function correlates with cognitive functions in middle-aged and older people, especially males. Additional studies characterizing early and long-term PEF changes are needed.

Background: Intravenous (IV) ribavirin is not approved in US and European Union, but it is authorized in China. Significant teratogenic and embryocidal effects of ribavirin have been found in almost all animal studies, it is critical to investigate the prevalence and trends of the utilization of IV ribavirin among reproductive age population.Objective: To evaluate the prevalence and trends of IV ribavirin use among reproductive-age population in 2010–2017.Methods: The study design of our study is retrospective cross-sectional study based on healthcare database. We identified and extracted the data of residents aged 18–44 years by using Yinzhou healthcare information database at 21 January, 2018. A cohort of IV ribavirin users were identified through outpatient prescription records in 3 general hospitals and 24 community health centers from 2010 to 2017. We reported the number, proportion, and prevalence of the exposure to IV ribavirin stratified by sex, age, marital status, education level, occupation, hospital level, calendar year, diagnosis, and dosage. The overall trends of IV ribavirin use, and the trends in different levels of hospital and common diagnoses were further analyzed and described.Result: During the study period, the prevalence of IV ribavirin use among reproductive-age adults was 6.02% (48,287/801,667). Relatively higher prevalence were found in adults aged 40–44 (8.04%, 95% CI: 7.90–8.17), unmarried patients (8.91%, 95% CI: 8.74–9.08), and who had more than 9 years of education (6.82%, 95% CI: 6.74–6.90). Compared to secondary and tertiary hospitals, IV ribavirin was more likely to be dispensed in primary hospitals (19.44%, 95% CI: 19.28–19.61). The most common diagnoses were acute upper respiratory infections (AURIs), accounting for 80% of the patients exposed to IV ribavirin. For patients with AURIs, the prevalence of IV ribavirin was nearly 30%. Overall, the prevalence of IV ribavirin use decreased from 1.72% in 2010 to 0.24% in 2017.Conclusion: We found IV ribavirin was mainly used for AURIs which suggested that a large amount of IV ribavirin use was probably inappropriate. The prevalence was decreasing by 87% over the past 8 years, and we encourage clinicians and pharmacists to continually avoid inappropriate use of IV ribavirin.

Purpose: Psychotropic medications are commonly used for treating mental disorders; however, there is currently no study on how commonly they are used in China. This study reported the trends in psychotropic medications prescriptions in urban China.Methods: A national population-based study was conducted using the China Health Insurance Research Association database to estimate the period prescription prevalence of 11 major classes of psychotropic medications annually during 2013–2017. The World Health Organization Anatomical Therapeutic Chemical (ATC) classification codes were used to identify psychotropic medications.Results: The prescription prevalence of any psychotropic medication increased from 8.110% (8.106–8.114%) in 2013 to 11.362% (11.357–11.366%) in 2017. The prescription prevalence of six classes increased significantly during 2013–2017, including sedatives-hypnotics (from 3.177 to 5.388%), anxiolytics (from 1.436 to 2.200%), antiepileptic drugs (from 1.416 to 2.140%), antipsychotics (from 0.809 to 1.156%), antidepressants (from 0.891 to 1.045%), and psycholeptic polypills (from 0.682 to 0.866%). The prescription prevalence of antidementia drugs increased from 0.069 to 0.122%, and mood stabilizers increased from 0.029 to 0.037%, although not statistically significant. The prescription prevalence of nootropic drugs, attention deficit hyperactivity disorder (ADHD) medications and drugs used in the treatment of addictive disorders was largely stable. Psychotropic medication prescription increased with age for all classes except for ADHD medications and mood stabilizers.Conclusion: Increasing trends in prescription prevalence were observed for most classes of psychotropic medications in urban China, although the prevalence was still lower than that in most developed countries. Further research is warranted to explore the potential treatment gap between China and most developed countries.