Myopia has become a significant eye health problem, which is thought to result from the complex interactions of genetic and environmental factors. This review focuses on two types of hereditary retinal diseases caused by mutations in photoreceptor genes, including rod-cone cell dystrophy(retinitis pigmentosa)and cone dysfunction syndromes(achromatopsia, blue cone monochromatism and Bornholm eye disease). It systematically explores the intrinsic connection between these diseases and the myopia phenotype, and elaborates on the core mechanisms by which pathogenic genes such as RPGR and OPN1LW/OPN1MW, which cause defects in ciliary structure and protein transport and interfere with the visual signal pathway, jointly induce choroidal thinning and scleral remodeling, ultimately driving the elongation of axial length and the occurrence of myopia. By tracing the association of photoreceptor gene mutations with myopia, this article provides a new perspective for in-depth understanding of the genetic mechanism of myopia and is of great significance for the development of early risk warning and targeted intervention strategies.

OBJECTIVES: To create a mixed valvular heart disease (MVHD)-related age-adjusted comorbidity index (MVACI) model for predicting mortality risk of patients with MVHD. METHODS: A total of 4080 patients with moderate or severe MVHD in the China-VHD study were included. The primary endpoint was 2-year all-cause mortality. A MVACI model prediction model was constructed based on the mortality risk factors identified by univariate and multivariate Cox regression analysis. Restricted cubic splines were used to assess the relationship between MVACI scores and 2-year all-cause mortality. The optimal threshold, determined by the maximum Youden index from receiver operator characteristic (ROC) curve analysis, was used to stratify patients. Kaplan-Meier method was used to calculate 2-year all-cause mortality and compared using the Log-rank test. Univariate and multivariate Cox proportional hazards models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI), evaluating the association between MVACI scores and mortality. Paired ROC curves were used to compare the discriminative ability of MVACI scores with the European System for Cardiac Operative Risk Evaluation Ⅱ(EuroSCORE Ⅱ) or the age-adjusted Charlson comorbidity index (ACCI) in predicting 2-year clinical outcomes, while calibration curves assessed the calibration of these models. Internal validation was performed using the Bootstrap method. Subgroup analyses were conducted based on etiology, treatment strategies, and disease severity. RESULTS: Multivariate analysis identified the following variables independently associated with 2-year all-cause mortality in patients: pulmonary hypertension, myocardiopathy, heart failure, low body weight (body mass index <18.5 kg/m²), anaemia, hypoalbuminemia, renal insufficiency, cancer, New York Heart Association (NYHA) class and age. The score was independently associated with the risk of all-cause mortality, and exhibited good discrimination (AUC=0.777, 95%CI: 0.755-0.799) and calibration (Brier score 0.062), with significantly better predictive performance than EuroSCORE Ⅱ or ACCI (both adjusted P<0.01). The internal validation showed that the MVACI model's predicted probability of 2-year all-cause mortality was generally consistent with the actual probability. The AUCs for predicting all-cause mortality risk were all above 0.750, and those for predicting adverse events were all above 0.630. The prognostic value of the score remained consistent in patients regardless of their etiology, therapeutic option, and disease severity. CONCLUSIONS The MVACI was constructed in this study based on age and comorbidities, and can be used for mortality risk prediction and risk stratification of MVHD patients. It is a simple algorithmic index and easy to use.
Humans ; Prognosis ; Comorbidity ; Heart Valve Diseases/epidemiology* ; Female ; Male ; Middle Aged ; Aged ; Proportional Hazards Models ; Risk Factors ; China/epidemiology* ; Age Factors ; Risk Assessment ; Adult ; ROC Curve

BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Dental trauma is one of the relatively common emergencies in clinical dental practice, with a high incidence rate, and the maxillary central incisors are the most frequently affected. This article reports a case of a 17-year-old female patient who suffered traumatic complete avulsion of teeth 11 and 21, with tooth 21 lost after avulsion. The prognosis for replantation was poor due to the absence of the buccal alveolar bone wall of tooth 11. Therefore, tooth 11 was treated with extracorporeal root canal therapy and then replanted into the alveolar socket of tooth 21, which had better conditions, followed by elastic splint fixation. After 20 months of follow-up observation, the affected tooth maintained a stable functional position, with no periapical inflammation or ankylosis observed. Subsequently, delayed implant restoration at the site of tooth 11 was performed, ultimately achieving a favorable treatment outcome. This case may provide new insights and references for future clinical practices in tooth replantation.
Humans ; Female ; Tooth Replantation/methods* ; Incisor/injuries* ; Adolescent ; Tooth Avulsion/therapy* ; Maxilla ; Root Canal Therapy

Objective: To investigate the health literacy and its influencing factors among residents in areas out of poverty in Kunming City, so as to provide insights into formulating health education strategies. Methods: A total of 1 916 permanent residents at ages of 15 to 69 years were sampled in three areas out of poverty in Kunming City using the multi-stage stratified random sampling method and probability proportionate to size sampling method from August to October, 2020. Health literacy was investigated using the Questionnaire on the Health Literacy among Chinese Residents, the level of health literacy was analyzed and weighted by the population of the China's Seventh National Population Census. Factors affecting health literacy among residents in areas out of poverty were identified using a multivariable logistic regression model. Results: A total of 1 916 questionnaires were allocated, and 1 908 valid questionnaires were recovered, with an effective recovery rate of 99.58%. The respondents included 997 men (52.25%) and 911 women (47.75%), and had a mean age of (45.58±14.28) years. The level of health literacy was 21.38%. Multivariable logistic regression analysis identified age (15 to 24 years, OR=5.087, 95%CI: 1.573-16.450; 25 to 34 years, OR=6.016, 95%CI: 1.991-18.183; 35 to 44 years, OR=7.526, 95%CI: 2.541-22.289; 45 to 54 years, OR=4.800, 95%CI: 1.640-14.050), educational level (junior high school, OR=5.333, 95%CI: 3.100-9.175; high school/vocational high school/technical secondary school, OR=19.895, 95%CI: 10.418-37.966; college or above, OR=27.580, 95%CI: 12.349-61.597) as factors affecting health literacy among residents in areas out of poverty in Kunming City. Conclusion The level of health literacy is 21.38% among residents in areas out of poverty in Kunming City, and age and educational level are associated factors.

Objective To systematically evaluate and sequentially analyze the clinical efficacy and safety of Baogong Zhixue Granules for the treatment of abnormal uterine bleeding due to ovulation disorder.Methods The randomized controlled trials(RCTs)of Baogong Zhixue Granules for the treatment of abnormal uterine bleeding due to ovulation disorder were retrieved from the databases of CNKI,Wanfang Data,VIP,China Biology Medicine,PubMed,Embase,and Cochrane Library from the establishment of the databases to January 5th,2023.Literature screening and data extraction were conducted according to Cochrane Handbook for Systematic Reviews of Interventions,and Meta-analysis was performed by RevMan 5.4.Results Totally 15 articles were included,involving 1 425 patients.Meta-analysis results showed that Baogong Zhixue Granules could effectively improve the clinical efficacy of abnormal uterine bleeding due to ovulatory disorder(RR=1.17,95%CI[1.13,1.23],P<0.000 01),shorten hemostasis time[bleeding control time(MD=-6.35,95%CI[-8.89,-3.81],P<0.000 01),complete hemostasis time(MD=-12.56,95%CI[-16.22,-8.89],P<0.000 01)],reduce endometrial thickness(MD=-1.26,95%CI[-1.71,-0.80],P<0.000 01),reduce hemoglobin loss(MD=13.35,95%CI[11.41,15.29],P<0.000 01),improve the score of uterine bleeding(MD=-2.22,95%CI[-2.43,-2.01],P<0.000 01),and reduce the recurrence of disease(RR=0.37,95%CI[0.19,0.72],P=0.004).There was no statistical significance between the test group and the control group in terms of adverse reactions(P=0.82).The trial sequential analysis of the total efficiency was carried out,and the cumulative included research passed the traditional threshold and trail sequential analysis threshold.Conclusion Baogong Zhixue Granules have a certain clinical efficacy in the treatment of abnormal uterine bleeding due to ovulation disorder,but there may be publication bias in the study,and higher quality clinical RCTs need to be carried out.

BACKGROUND:Recent studies have shown that connective tissue growth factor not only participates in the development of neurons,but also participates in the pathogenesis of neurodegenerative diseases,depression,epilepsy,etc.It can also be used as a therapeutic target to develop related drugs,thereby improving the patients'quality of life. OBJECTIVE:To summarize the biological functions of connective tissue growth factor and the mechanisms involved in neurodegenerative diseases and depression,as well as the progress in intervention with connective tissue growth factor and related emerging treatments. METHODS:The first author searched relevant articles published from January 1996 to December 2022 in PubMed and Web of Science.The key words were"connective tissue growth factor,nervous system,depression,Alzheimer disease,epilepsy,Parkinson disease,epilepsy,amyotrophic lateral sclerosis,FG-3019"in English.After reading,screening and sorting,the articles consistent with the content of the review were collected.Finally,51 articles were selected for review. RESULTS AND CONCLUSION:Connective tissue growth factor participates in multiple biological activities such as fibrosis,cell adhesion,and cell development under different conditions through four different structural domains.Connective tissue growth factor is up-regulated in lesion sites of neurodegenerative diseases,depression and epilepsy.After interfering with the expression of connective tissue growth factor,the symptoms improve or disappear,suggesting that connective tissue growth factor plays an important role in the progression of these diseases.The development of novel therapeutic strategies and intervention targets around connective tissue growth factor is very promising therapeutic research.More research is needed to identify the mechanism of action to transfer from basic medical studies to clinical studies and to achieve safer and more effective treatments.