This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVES: To study the epidemiological characteristics of respiratory syncytial virus (RSV) infection in hospitalized children with community-acquired pneumonia (CAP) in Hebei Province. METHODS: Hospitalized children with CAP who tested positive for RSV and were admitted to Hebei Children's Hospital from various cities and counties across Hebei Province between January 2019 and December 2023 were included in the study. Clinical data were collected and analyzed to assess epidemiological characteristics. RESULTS: The clinical data of 43 978 children with CAP were collected, with an overall RSV detection rate of 25.98%. The detection rate was higher during the implementation of non-pharmaceutical interventions (NPIs) (30.60%) than in the non-NPIs period. Winter and spring were the primary epidemic seasons for RSV each year except in 2022. The detection rate in males (26.62%) was higher than in females (25.06%) (P<0.001). The highest detection rate (59.18%) was found in infants aged 29 days to <1 year. Single RSV infection was more common, with rhinovirus being the most frequent co-infection. CONCLUSIONS The overall RSV detection rate in Hebei Province is influenced by NPIs, being higher during their implementation. RSV predominantly circulates in winter and spring. The detection rate of RSV is higher in males and infants. RSV infection is primarily single, most often co-occurring with rhinovirus.
Humans ; Respiratory Syncytial Virus Infections/epidemiology* ; Female ; Male ; Infant ; Child, Preschool ; Seasons ; China/epidemiology* ; Infant, Newborn ; Community-Acquired Infections/epidemiology* ; Child

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*