Childhood is a critical period for growth and development, and the oral microbiota, as the second most diverse microbial community in the human body, plays a pivotal role in maintaining children's health. Recent studies have demonstrated that dysbiosis of the oral microbiota not only contributes to oral diseases such as dental caries and periodontitis but may also influence the development of children's skeletal, nervous, digestive, cardiovascular, and immune systems through mechanisms involving inflammatory responses, metabolic regulation, and cross-organ communication networks. This review systematically examines the role of the oral microbiota in childhood growth and development and, guided by the core principles of the "active health" model, proposes multiple intervention strategies—including probiotics, xylitol, and mouthwashes—to optimize children's health through early oral microbiota modulation.

Hereditary myopathy with early respiratory failure is a titin （TTN）-related myopathy caused by mutations in the A-band of the TTN gene.This condition is characterized by distinctive clinical and pathological features， as well as a typical skeletal muscle involvement pattern. We report a 43-year-old male patient with progressive distal limb weakness over the past three years. The initial symptom was difficulty in lifting both feet， followed by difficulty in extending the dorsum of both hands one year later. However， the patient never experienced dyspnea. The patient's past medical history was unremarkable， and there was no family history of inherited diseases.His parents were healthy. Physical examination revealed wrist drop and noticeable atrophy of the tibialis anterior in both calves. Muscle strength in the lower limbs was graded at 4 for proximal muscles and 2 for distal muscles.Laboratory tests showed a creatine kinase level of 375U/L（normal range：50~310）. Electromyography revealed myogenic injury in the bilateral tibialis anterior and the right extensor digitorum communis. Magnetic resonance imaging of the muscles showed isolated involvement of the semitendinosus muscle with severe fatty infiltration， along with significant fatty degeneration of the anterior calf muscles. Muscle biopsy of the proband showed subsarcolemmal “necklace-like” cytoplasmic bodies and the “erasure” phenomenon on NADH enzyme histochemistry. Both electrocardiogram and echocardiography showed no abnormalities. Exome sequencing of the proband identified a missense mutation in the TTN gene， c.95358C>G， p.Asn31786Lys. Sanger sequencing confirmed that the mutation was absent in both parents of the proband， indicating a de novo mutation.

Nanotechnologies seek to overcome inherent deficiencies of conventional diagnosis and treatment, which attracted sustained attention and a limited number of nanomedicines approved by the FDA. However, the critical gaps in clinical translation remain, and nanomedicines that were initially heralded as magic bullets have yet to reach their realistic potential. The major obstacles of fabrication technologies may be overlooked in the nanoparticles' journey. Suboptimal manufacturing strategies partly hampered the inefficient transformation. In this review, we discuss the nanoparticle manufacturing strategies of "Top-Down" and "Bottom-Up" on precise nanoscale fabrication, including artificial intelligence introduced to guided nanomedicine fabrication for accelerating the transformation. Re-engineering existing nanomedicine fabrication, individual manufacturing, and modular technology might highlight the dilemmas of nanomedicines to meet their initial expectations.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE To correctly identify and respond to severe systemic allergic reactions caused by Wujia shenghua capsules during the postpartum period， provide a reference for medication use in obstetrics and gynecology departments， and promote rational drug use. METHODS Clinical pharmacists participated in the pharmaceutical monitoring and treatment process for a case of severe systemic allergic reaction after using Wujia shenghua capsules during the postpartum period. They screened the medication used by the patient during hospitalization and evaluated the relationship between the allergic reaction and Wujia shenghua capsules， as well as the possible causes of the reaction. RESULTS & CONCLUSIONS The relationship between severe systemic allergic reactions in the patient and Wujia shenghua capsules is evaluated as “likely related”， suggesting that patients with the allergic constitution should be vigilant when using Wujia shenghua capsules during the postpartum period， and pharmaceutical monitoring should be strengthened to avoid the simultaneous use of drugs with the same mechanism or potential interactions.

Objective To analyze the current status and influencing factors of occupational stress among firefighters in Shenzhen City. Methods A total of 5 434 first-line firefighters in Shenzhen City was selected as the study subjects using the judgment sampling method. The Job Content Questionnaire was used evaluate the occupational stress level. Results The detection rate of occupational stress in the study subjects was 52.5% (2 854/ 5 434). The result of dichotomous logistic regression analysis results showed that the risk of occupational stress was higher in firefighters who had a bachelor's degree or above than in those who had junior high school or below (P<0.01), the risk of occupational stress in those with irregular meals was higher than those with regular meals (P<0.01), and the risk of occupational stress was lower in those who exercised 1-3 times a month or ≥3 times a week than in those who did no daily exercise (all P<0.05). The risk of occupational stress was higher with older the weekly working hours, the more frequent the injury and the more firefighting workload (all P<0.01). The risk of occupational stress in firefighters who stand for a long time was higher than that in workers who not-stand for a long time (P<0.05). Conclusion The detection rate of occupational stress among the firefighters in Shenzhen City is relatively high. Educational level, dietary habits, daily exercise, weekly working hours, injury frequency, long-standing work and firefighting workload are all influencing factors for occupational stress in firefighters.

Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO₂) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO₂ was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO₂ for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO₂ as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO₂ and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO₂ concentration was (32.18±10.36) μg/cm³. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T₁ group of NDVI, the risk of hypertension was lower in the T₃ group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T₁ group of NO₂, the risk of hypertension was higher in the T₂ and T₃ groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO₂ was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO₂ had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO₂ are associated with hypertension in older adults.
Aged ; Humans ; Female ; Nitrogen Dioxide ; Air Pollution ; Prevalence ; Hypertension/epidemiology* ; China/epidemiology* ; Particulate Matter/analysis*