BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To study the effect of reactive oxygen species(ROS)/p38 MAPK cascade reaction on the formation of kidney stones(KS)in rats and explore the mechanism.Methods Fifty SD rats were randomly divided into control group(normal feeding),N-acetylcysteine(NAC)group(intraperitoneally injected 200 mg/kg NAC),KS group(constructed calcium oxalate KS model),KS+NAC group(constructed calcium oxalate KS model,intraperitoneally injected 200 mg/kg NAC),KS+NAC+tunicamycin(TM)group(constructed calcium oxalate KS model,intraperitoneally injected 200 mg/kg NAC and 1 mg/kg TM),with 10 rats in each group.After 4 weeks of administration,24 hours urine volume and oxalic acid(Ox)of each group were measured,serum creatinine(Cr),urea nitrogen(BUN)and uric acid(UA)levels were detected by automatic biochemical analyzer.HE staining and Von Kossa staining were used to observe the histopathological changes and crystal deposition of the kidney.TUN EL staining was used to detect apoptosis of renal tissue cells.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in renal tissue were measured by the kit.DHE fluorescent probes detected the levels of reactive oxygen species(ROS)in kidney tissue.Immunohistochemical staining was used to detect the expressions of microtubule-associated protein 1 light chain 3 B(LC3B)and glucose regulatory protein 78(GRP78)in renal tissue,and the protein expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78,CCAAT/enhancer binding protein homologous protein(CHOP)in renal tissue was determined by Western blotting.Results Compared with the KS group,Ox in KS+NAC group decreased(P＜0.05),BUN,Cr and UA levels decreased(P＜0.05),renal tubule dilatation and calcium oxalate crystallization decreased,TUNEL positive cell rate decreased(P＜0.05),SOD activity increased and MDA content decreased(P＜0.05),ROS levels decreased(P＜0.05),LC3B and GRP78 positive staining levels decreased(P＜0.05),the relative protein expressions of p-p38 MAPK/p38 MAPK,LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78 and CHOP were down-regulated(P＜0.05).Compared with the KS+NAC group,Ox in KS+NAC+TM group increased(P＜0.05),BUN,Cr and UA levels also increased(P＜0.05),renal tubule dilated significantly,calcium oxalate crystals increased,TUNEL positive cell rate increased(P＜0.05),SOD activity decreased and MDA content increased(P＜0.05),ROS levels increased(P＜0.05),LC3B and GRP78 positive staining levels increased(P＜0.05),the relative protein expressions of p-p38 MAPK/p38 MAPK,LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78 and CHOP were also up-regulated(P＜0.05).Conclusion ROS/p38 MAPK cascade is involved in promoting KS formation in rats,which is related to the activation of endoplasmic reticulum stress-mediated autophagy pathway.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies ; Diabetes Mellitus/epidemiology* ; Humans ; Hyperlipidemias/epidemiology* ; Hypertension/epidemiology* ; Macular Degeneration/etiology* ; Risk Factors

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC₅₀ = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

【Objective】 To investigate the effect of transfusion-transmitted Zika virus (ZIKV) on the expression of non-coding circular RNA (hsa_circ_0001613) and the role of hsa_circ_0001613 in Zika virus replication. 【Methods】 Human adenocarcinomic alveolar basal epithelial cells (A549) were seeded on a 12-well plate at 1.8×10⁵/ well and infected with ZIKV at 0.05 MOI. The Total RNAs were isolated every day for 5 days after infection, and the relative expression level of hsa_circ_0001613 was detected by qRT-PCR. In addition, 10nM siRNA-hsa_circ_0001613 was transfected into 2×10⁵/ well A549 cells to specifically knock down the expression level of hsa_circ_0001613. 24h later, the cells were infected with ZIKV (MOI=0.05). Total RNAs were isolated at day 1-5 post-infection, proteins were extracted 96h post-infection. ZIKV replication, relative host antiviral gene expression, and interferon stimulated response element (ISRE) activity were tested using qRT-PCR, western blot and dual luciferase assay, respectively. 【Results】 The relative expression of hsa_circ_0001613 decreased significantly after 1-5 days of ZIKV infection. Knockdown of hsa_circ_0001613 inhibited ZIKV replication. Meanwhile, hsa_circ_0001613 knockdown significantly upregulated IFN-α/β and its downstream interferon-stimulated genes (ISGs) expression, also increased ISRE activity. 【Conclusion】 ZIKV infection significantly suppressed hsa_circ_0001613 expression in A4549 cells. Preliminary study indicated that hsa_circ_0001613 knockdown inhibited ZIKV replication possibly through activating type-Ⅰ IFN signaling pathway as showed by increased ISGs expression and ISRE activity.