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AbstractObjectiveTo estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).DesignLongitudinal observational cohort study.SettingUS Department of Veterans Affairs.ParticipantsNew users of PPIs (n=157 625) or H2 blockers (n=56 842).Main outcome measuresAll cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).ResultsThere were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).ConclusionsTaking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

This study aimed to determine the relationship between latent classes of adverse childhood experience (ACEs) and internalizing disorders (anxiety and depression) among US children. The 2016 National Survey of Children’s Health data for children aged 6–17 was used. Latent class analysis was performed to identify distinct sub-types of ACE exposures and survey-weighted logistic regression models were employed to determine whether these classes were associated with any or comorbid childhood internalizing disorders, after controlling for meaningful covariates. Four latent classes were identified: income hardship, divorce, mental health or substance abuse exposure, and high ACEs overall. Children in three of the four classes were significantly more likely to have any childhood internalizing disorder when compared to children reporting no ACEs, while children in all classes were significantly more likely to have a comorbid history of anxiety and depression. Thus, children exposed to ACEs should receive necessary mental health screenings and treatments.

ObjectiveProton pump inhibitors (PPIs) are widely used, and their use is associated with increased risk of adverse events. However, whether PPI use is associated with excess risk of death is unknown. We aimed to examine the association between PPI use and risk of all-cause mortality.DesignLongitudinal observational cohort study.SettingUS Department of Veterans Affairs.ParticipantsPrimary cohort of new users of PPI or histamine H2 receptor antagonists (H2 blockers) (n=349 312); additional cohorts included PPI versus no PPI (n=3 288 092) and PPI versus no PPI and no H2 blockers (n=2 887 030).Main outcome measuresRisk of death.ResultsOver a median follow-up of 5.71 years (IQR 5.11–6.37), PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28). Risk of death associated with PPI use was higher in analyses adjusted for high-dimensional propensity score (HR 1.16, CI 1.13 to 1.18), in two-stage residual inclusion estimation (HR 1.21, CI 1.16 to 1.26) and in 1:1 time-dependent propensity score-matched cohort (HR 1.34, CI 1.29 to 1.39). The risk of death was increased when considering PPI use versus no PPI (HR 1.15, CI 1.14 to 1.15), and PPI use versus no PPI and no H2 blockers (HR 1.23, CI 1.22 to 1.24). Risk of death associated with PPI use was increased among participants without gastrointestinal conditions: PPI versus H2 blockers (HR 1.24, CI 1.21 to 1.27), PPI use versus no PPI (HR 1.19, CI 1.18 to 1.20) and PPI use versus no PPI and no H2 blockers (HR 1.22, CI 1.21 to 1.23). Among new PPI users, there was a graded association between the duration of exposure and the risk of death.ConclusionsThe results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with prolonged duration of use. Limiting PPI use and duration to instances where it is medically indicated may be warranted.

Anti-Müllerian hormone (AMH) is a functional marker of fetal Sertoli cells. The germ cell number in adults depends on the number of Sertoli cells produced during perinatal development. Recently, AMH has received increasing attention in research of disorders related to male fertility. This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders. We have determined that follicle-stimulating hormone (FSH) promotes AMH transcription in the absence of androgen signaling. Testosterone inhibits the transcriptional activation of AMH. The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue, for example, that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis. The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Müllerian duct syndrome (PMDS), combined with clinical manifestations. The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development (DSD). Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells. Serum AMH levels are varying in patients with male fertility-related disorders, including pubertal delay, severe congenital hypogonadotropic hypogonadism, nonobstructive azoospermia, Klinefelter syndrome, varicocele, McCune-Albright syndrome, and male senescence.

Schistosoma japonicum has been successfully controlled in villages along Poyang Lake, the largest freshwater lake in China. In addition to synchronous chemotherapy for humans and cattle, successful interventions have included the removal of cattle from snail-infested grasslands, improvements in sanitation, and intensive health education. The use of such interventions has now been adopted as the national control strategy for China. Schistosoma japonicum has been successfully controlled in villages along Poyang Lake, the largest freshwater lake in China. In addition to synchronous chemotherapy for humans and cattle, successful interventions have included the removal of cattle from snail-infested grasslands, improvements in sanitation, and intensive health education. During the past five decades, the Chinese government has placed a high priority on the control of schistosomiasis and has carried out many control programs. 1 – 3 These efforts have resulted in a substantial reduction in the prevalence of infection with Schistosoma japonicum in humans, from approximately 11.6 million cases in the mid-1950s to 726,000 cases in 2004. 4 The number of provinces in which this disease is endemic has been reduced from 12 to 7. In spite of these achievements, progress in the control of this disease appeared to be stagnating. 5 , 6 National surveys of schistosomiasis in China showed that the . . .

Nanofluid that made up of fluid and solid nanoparticles has gained attention from diverse fields due to its superior thermophysical properties to enhance the performance of different systems which require flowing medium with excellent heat transfer behavior. Many past researchers have proven that conventional heat transfer fluid can be replaced by the rising nanotechnology–nanofluid which showed astonishing performance under different circumstances. In this paper, we attempt to present a recent review on the consequences of implantation of nanofluid, especially in vehicle engine cooling system and other heat transfer applications such as solar collector, electronics cooling system, flow boiling and thermal energy storage system. Thermophysical properties and heat transfer performance of nanofluids obtained in simulation, test rigs and even real vehicle engine experiments are discussed thoroughly. Models and correlations used by past researchers to compute thermophysical properties are also included. In the last part, various advantages from using nanofluid are summarized, and suggestions for research gap between past studies are discussed to further improve the investigation work in the future.

Study question The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. Summary answer A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy. What is known already Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF. Study design, size, duration A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022. Participants/materials, setting, methods This study included 462 patients in the RIF group and 4750 patients in the control group. The patients’ basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup ( n  = 116) and the no live birth subgroup ( n  = 200). Main results and the role of chance (1) An increased duration of infertility (1.978; 95% CI, 1.264–3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185–4.336), low AMH levels (0.504; 95% CI, 0.275–0.922), insulin resistance (3.548; 95% CI, 1.931–6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-β2-glycoprotein I antibody (A-β2-GPI Ab)-positive status (5.515; 95% CI, 1.481–20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870–0.929) for the training cohort and 0.895 (95% CI, 0.865–0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015–1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181–0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597–0.748). Limitations, reasons for caution This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients resulted in the inclusion of fewer covariates, and future studies with larger samples and the inclusion of more factors are needed for assessment and validation. Wider implications of the findings Prediction of embryo implantation prior to transfer will facilitate the clinical management of patients and disease prediction and further improve ART treatment outcomes. Study funding/competing interest(s) This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 82374212, 81971446, 82301871, and 82201792) and the Natural Science Foundation of Anhui Province (No. 2208085MH206). There are no conflicts of interest to declare. Trial registration number This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR1800018298 ).

The release of inflammatory cytokines, that plays a dominant role in local pancreatic inflammation and systemic complications in severe acute pancreatitis (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP. This current study aims to investigate possible role of HMGB1 in the intestinal mucosal barrier dysfunction of SAP, and the effect of anti-HMGB1 antibody treatment in intestinal mucosal injury in SAP. Our data revealed that the HMGB1 expression was significantly increased in AP mice induced by caerulein and LPS, and the inhibition of HMGB1 played a protective role in intestinal mucosal barrier dysfunction, reduced the serum level of other proinflammatory cytokines include IL-1β, IL-6, TNF-α. Next we investigated the downstream receptors involving in HMGB1 signaling. We found that the expressions of toll-like receptor (TLR) 4 and TLR9 were elevated in ileum of AP mice, the administration of HMGB1 neutralizing antibody significantly reduced the TLR4 and TLR9 expression. It was concluded that HMGB1 contributed the mechanism to the intestinal mucosal barrier dysfunction during AP. Blockade of HMGB1 by administration of HMGB1 neutralizing antibody may be a beneficial therapeutic strategy in improving intestinal mucosal barrier dysfunction in SAP.

Paeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P . ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P . ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P . ostii . Under the current environmental conditions in China, a total area of 20.31 × 10 5  km 2 is suitable for growing P . ostii , accounting for 21.16% of the country’s total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P . ostii .