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Quantifying the combined effects of semi-closed terrain and monsoon on PM2.5 and O3 pollution aggregation in the North China Plain.

The North China Plain (NCP) and its surrounding regions represent one of the key priority areas for air pollution control. As anthropogenic emissions decline significantly, the effect of terrain and meteorology on air pollution pattern has become increasingly prominent, particularly given the NCP's unique semi-closed terrain and East Asian monsoon dynamics. However, quantitative characterization of terrain-dominated blocking effects remains unexplored. Here we quantitatively assess the blocking effects of mountains and terrain-coupled meteorological factors on air pollutant dispersion. We find the NCP on the eastern side of the Taihang Mountains showed high PM2.5 and O3 pollution levels, with winter PM2.5 and summer O3 high-value zones showing opposite north-south aggregation patterns. PM2.5 and O3 concentrations were highest in plains, followed by platforms, hills, and finally mountains. Within the 120-km buffer zones of the typical mountains in the NCP and its surrounding regions, PM2.5 and O3 concentrations increased initially with altitude but then decreased markedly above a threshold altitude. Above the threshold altitude, mountain blocking effects became dominant. The effective blocking altitudes of typical mountains in the NCP and its surrounding regions ranged between 22 and 929 m for winter PM2.5 pollution, and between 19 and 1060 m for summer O3 pollution. The Terrain-Wind Close Index indicates that the terrain-coupled East Asian monsoon showed stronger blocking effects on PM2.5 dispersion in southern NCP during winter and on O3 diffusion in northern NCP during summer, matching observed high-pollution zones. This study offers key insights for regional joint air pollution mitigation strategies, as well as regional pollution assessment.

Particulate Matter

Assessment of Genetic Correlations Between Tobacco or Alcohol Use and Neurodegenerative Diseases Using East Asian Genetic Ancestry Genome-Wide Association Study Results.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.

Female

Pharmacokinetics of injectable favipiravir: phase I, randomized, double-blind, placebo-controlled study in healthy East Asian subjects.

Favipiravir, an oral antiviral medication, has been approved in Japan for the treatment of patients with novel or re-emerging influenza and severe fever with thrombocytopenia syndrome (SFTS). Randomized, double-blind, placebo-controlled trials were conducted in an East Asian population to characterize the pharmacokinetics and tolerability of an injectable favipiravir formulation. In the single-ascending dose trial, subjects received a single intravenous (IV) dose of 300-2,400 mg of favipiravir. In the multiple dose trial, 1,800 mg was administered twice daily on the first day, followed by 800 mg twice daily for the subsequent 10 days, which is the approved tablet dose for SFTS in Japan. This multiple-dose trial was divided into a cohort receiving intravenous administration throughout the treatment period (IV cohort) and a cohort switching to oral administration from Day 6 (Switching cohort). After a single administration of ≤2,400 mg, the pharmacokinetic parameters increased in a dose-dependent manner but showed slight deviation from linearity. The geometric mean maximum plasma concentration following a single 2,400 mg dose was 126 (range: 110 to 138) μg/mL. In the IV cohort, the trough (at 12 h post-dose) plasma concentrations were maintained at approximately 85 μg/mL after Day 2. These concentrations were approximately 20% higher than those achieved with the same oral doses. In the Switching cohort, these concentrations were maintained throughout the treatment. No serious adverse events were observed. These findings support advancing injectable favipiravir into clinical evaluation.CLINICAL TRIALSThis study is registered with the Japan Registry of Clinical Trials as jRCT2071210042 and jRCT2071210126.

Humans

Efficacy, Safety, and Pharmacokinetics of Upadacitinib Among Patients in East Asia With Moderately to Severely Active Ulcerative Colitis: A Post Hoc Subanalysis of Randomized Phase 3 Studies.

BACKGROUND AND AIM: Upadacitinib, a selective Janus kinase 1 inhibitor, is approved to treat moderately to severely active ulcerative colitis (UC). This post hoc subanalysis evaluated the efficacy, safety, and pharmacokinetics of upadacitinib in patients in East Asia. METHODS: U-ACHIEVE (UC1; NCT02819635) and U-ACCOMPLISH (UC2; NCT03653026) were Phase 3, multicenter, randomized, double-blind, induction studies evaluating upadacitinib 45 mg or placebo daily in adults with moderately to severely active UC. Clinical responders to 8 weeks of upadacitinib induction were eligible to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo daily in the 52-week U-ACHIEVE maintenance study (UC3; NCT02819635). Efficacy outcomes, safety, and pharmacokinetics were evaluated among East Asian patients. RESULTS: A higher proportion of East Asian patients achieved clinical remission with upadacitinib than placebo at induction Week 8 (UC1: n = 127, 31.4% vs. 7.3%; UC2: n = 114, 31.2% vs. 2.7%) and maintenance Week 52 (UC3: n = 184, upadacitinib 15 mg, 52.4%; upadacitinib 30 mg, 53.8%; placebo, 10.7%). Rates of endoscopic outcomes were higher with upadacitinib than with placebo across studies. No new safety signals were identified. Herpes zoster occurrences were low (UC1 and UC2: upadacitinib 45 mg, two events [in one patient]; placebo, zero events; UC3: upadacitinib 15 mg, five events; upadacitinib 30 mg, eight events; placebo, zero events). Pharmacokinetics and trends in the relationship between upadacitinib exposure and efficacy were consistent in the East Asian and global populations. CONCLUSION: Upadacitinib was generally well tolerated and effective for treating moderately to severely active UC in patients in East Asia, with a favorable benefit-risk profile consistent with the global population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02819635, NCT03653026.

Humans

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (&#x2264;1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: &#x2265;2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans

[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].

OBJECTIVE: To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM). METHODS: A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210). RESULTS: G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10. CONCLUSION: The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.

Humans

Feasibility and Efficacy of Lorlatinib in Japanese Patients With Relapsed/Refractory ALK-Aberrant Neuroblastoma.

Lorlatinib, a third-generation ALK inhibitor, was administered off-label to five heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma. ALK alterations included F1174L, R1275Q, BEND5::ALK fusion, and ALK amplification; three patients had MYCN amplification. Best responses were three partial responses and two disease progressions. The longest progression-free survival (6.7 months) occurred in a patient with F1174L and non-amplified MYCN, whereas rapid progression was observed in two MYCN-amplified cases. Lorlatinib was generally well tolerated with manageable adverse events. These findings suggest that lorlatinib is a feasible therapeutic option in ALK-aberrant neuroblastoma and that clinical heterogeneity in treatment response warrants further investigation.

Humans

[Analysis of a Chinese pedigree affected with Townes-Brocks syndrome due to a novel variant of SALL1 gene and a literature review].

OBJECTIVE: To analyze a novel exonic variant of the SALL1 gene and its impact on the binding site of SALL protein. METHODS: Clinical data of three children diagnosed with Townes-Brocks syndrome and their family members who had presented at the First Affiliated Hospital of Shandong First Medical University in April 2022 were retrospectively collected. The pathogenic variant was identified through whole-genome sequencing (WGS) and validated by Sanger sequencing. Protein structural prediction was performed using AlphaFold and PyMOL software to construct three-dimensional models of the wild-type and mutant proteins. Additionally, previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-386). RESULTS: The proband was one of triplet sisters born at 34+4 gestational weeks. All three cases had presented with anal atresia and rectovaginal fistula, and case 3 also had toe malformation of left foot. WGS revealed a novel heterozygous c.757C>T (p.Gln253*) variant in the SALL1 gene, which was predicted to be pathogenic. Sanger sequencing confirmed co-segregation of the variant with the disease within the family. Protein structural modeling demonstrated that the variant has introduced a premature stop codon at position 253, resulting in a truncated protein. CONCLUSION: Above finding has enriched the mutation spectrum of the SALL1 gene in association with Townes-Brocks syndrome, which also represented a rare case of anal atresia in triplets, and provided a basis for molecular diagnosis, genetic counseling, and further research.

Humans

Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis.

AIM: To assess the effects of mazdutide on body weight, HbA1c, metabolic outcomes, and adverse events in adults with overweight/obesity and/or type 2 diabetes (T2D). METHODS: This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing mazdutide with placebo or active comparators in adults with overweight/obesity and/or T2D, identified through PubMed, Scopus, Web of Science, and ClinicalTrials.gov to 20 February 2026. Co-primary outcomes were percent change in body weight and change in HbA1c. Secondary outcomes included other weight-related and metabolic outcomes, as well as safety. Random-effects models were used to generate pooled mean differences (MDs) or risk ratios with 95% confidence intervals, and the certainty of the evidence (COE) was assessed using GRADE. RESULTS: Nine RCTs (N&#x2009;=&#x2009;2292; most with low risk of bias) were included. In overweight/obesity without diabetes, mazdutide 3, 4, and 6&#x2009;mg reduced body weight more than placebo (MDs -6.56%, -9.92%, and -11.1%, respectively; very low COE due to substantial heterogeneity and few trials). In T2D, mazdutide 4 and 6&#x2009;mg reduced body weight and HbA1c versus placebo (moderate COE) and also outperformed dulaglutide for both outcomes. Mazdutide also improved waist circumference, lipids, liver enzymes, and uric acid levels. Gastrointestinal adverse events were more frequent, but serious adverse events and treatment discontinuation rates were comparable with those of the comparators. CONCLUSIONS: Mazdutide was associated with dose-dependent reductions in body weight and HbA1c, with broader metabolic benefits in predominantly Chinese adults with obesity and/or T2D. Longer-term, multi-ethnic studies are needed to confirm durability, generalizability, and cardiovascular safety.

Humans

A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants.

Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70&#xa0;mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).

Humans

Efficacy and Safety of iGlarLixi Versus IDegAsp by Baseline Age, Disease Duration and HbA1c in Chinese People With Type 2 Diabetes: Post Hoc Analyses of the Soli-D Study.

AIMS: To compare the efficacy and safety of insulin glargine 100&#x2009;U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS: In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24&#x2009;weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (<&#x2009;65, &#x2265;&#x2009;65&#x2009;years), T2D duration (<&#x2009;10, &#x2265;&#x2009;10&#x2009;years) and HbA1c (&#x2265;&#x2009;7% to &#x2264;&#x2009;8% [&#x2265;&#x2009;53 to &#x2264;&#x2009;64&#x2009;mmol/mol], >&#x2009;8% to &#x2264;&#x2009;9% [>&#x2009;64 to &#x2264;&#x2009;75&#x2009;mmol/mol], >&#x2009;9% [>&#x2009;75&#x2009;mmol/mol]). RESULTS: Among 582 participants (iGlarLixi n&#x2009;=&#x2009;291; IDegAsp n&#x2009;=&#x2009;291), baseline age was <&#x2009;65&#x2009;years in 442 and &#x2265;&#x2009;65&#x2009;years in 140; T2D duration was <&#x2009;10&#x2009;years in 366 and &#x2265;&#x2009;10&#x2009;years in 216; and HbA1c was &#x2265;&#x2009;7% to &#x2264;&#x2009;8% in 205, >&#x2009;8% to &#x2264;&#x2009;9% in 209 and >&#x2009;9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS: iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

Humans

Associations between multiple essential trace metal concentrations and risk of hyperuricemia: insights from a central Chinese population.

Previous studies have indicated that levels of individual essential trace metals are related to hyperuricemia (HUA), but evidence on their combined effects is limited. To address this gap,&#xa0;the associations of individual and joint levels of 12 essential trace metals (manganese, selenium, nickel, chromium, cobalt, tin, iron, molybdenum, zinc, strontium, vanadium, and copper) with the risk of HUA were investigated in&#xa0;2,021 adults recruited from Hunan Province, China. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to determine urinary metal concentrations. Logistic regression, Bayesian kernel machine regression (BKMR), and quantile g calculation (Qgcomp) were applied to evaluate the associations of single and mixture metal concentrations with HUA. Of the participants,&#xa0;516 (25.53%) were diagnosed with HUA. Inverse associations were found between vanadium, chromium, manganese, iron, cobalt, selenium, strontium, and molybdenum levels and HUA, with ORs ranging from 0.63 to 0.91. Conversely, a positive association was observed between zinc concentration and HUA [OR (95% CI): 1.17 (1.01, 1.37)]. Both BKMR and Qgcomp models showed a negative overall effect of essential trace metals on HUA risk, with strontium (-&#x2009;43.6%) and vanadium (-&#x2009;27.8%) being the main contributors. In addition, formal interaction tests revealed significant effect modification by age for tin and by BMI for zinc.&#xa0;In conclusion, the levels of essential trace metals were linked to a decreased risk of HUA, and these associations were modified by age and BMI only for specific metals.

Humans

Gender-specific pathways linking body dissatisfaction, self-disgust, and social anxiety in Chinese adolescents: A three-wave longitudinal study.

Adolescence is a critical period for physical and psychological development. Body dissatisfaction is a significant concern during this stage, contributing to psychological issues such as social anxiety. However, the longitudinal relationships among body dissatisfaction, self-disgust, and social anxiety, as well as the potential role of gender differences in these dynamics, remain unclear. A total of 1109 junior high school students in China completed the baseline survey, with data collected at three time points (Mage = 12.67 years, SD&#x202f;=&#x202f;0.68; 51.9% girls). Data were collected using the Body Areas Satisfaction Scale (BASS), the Self-Disgust Scale (SDS), and the Social Anxiety Scale for Children (SASC). Structural equation modeling (SEM) was employed to examine the longitudinal mediating effects among body dissatisfaction, self-disgust, and social anxiety, as well as to explore gender differences in these relationships. After controlling for autoregressive effects of self-disgust and social anxiety across waves, body dissatisfaction at T1 was found to indirectly predict social anxiety at T3 through self-disgust at T2, while indirectly predicting self-disgust at T3 through social anxiety at T2. Multi-group analyses revealed significant gender differences: for females, only the mediating pathway with self-disgust as the mediator was significant; for males, only the pathway with social anxiety as the mediator was significant. These findings contribute to a more nuanced understanding of the emotional mechanisms linking body dissatisfaction to social anxiety and highlight the importance of considering gender-specific pathways in prevention and intervention efforts.

Adolescent

[Analysis of clinical phenotypes and pathogenicity of a c.4476+5G>T variant of SCN1A gene in a Chinese pedigree affected with Genetic epilepsy with febrile seizures plus].

OBJECTIVE: To explore the pathogenicity and characteristics of a heterozygous splicing variant of SCN1A gene in a Chinese pedigree affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: A retrospective analysis was carried out on the clinical data and results of genetic testing of a GEFS+ pedigree consisting of 5 members who had visited the First Affiliated Hospital of Zhengzhou University on July 1, 2024. Pathogenicity of the splicing variant of the SCN1A gene was validated with a minigene splicing assay. This study was approved by the Medical Ethics Committee of the the First Affiliated Hospital of Zhengzhou University (Ethics No.: KS-2018-KY-36). RESULTS: The proband, a 24-year-old female, presented with FS in conjunct with focal seizures, and both of her younger brothers had Dravet syndrome. All of the three patients had carried a c.4476+5G>T variant of the SCN1A gene, which was unreported previously. Minigene experiment verified that the variant could cause loss of the first 7 bps of exon 24 and 138 bps from exon 23 of the SCN1A gene, resulting in alteration p.V1447_1495delfs*6 and affecting splicing. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.4476+5G>T variant at an intronic site of the SCN1A gene probably underlay the pathogenesis of GEFS+ in this pedigree.

Adult

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult

Life-course stress exposure and cognitive decline in middle-aged and older Chinese adults: The role of sex differences and educational protection.

BACKGROUND: Stressful life events (SLEs) across the life course have been associated with cognitive decline, but evidence on their cumulative impact and potential modifiers remains limited. We aimed to examine the associations between SLE exposure in childhood, adulthood, or both life stages and cognitive trajectories, and to investigate whether these associations vary by sex and education. METHODS: We used data from the China Health and Retirement Longitudinal Study, a nationally representative cohort of adults aged &#x2265;45 years. Participants with complete data on SLEs, cognition, and covariates were included (n&#x202f;=&#x202f;5922). SLEs were retrospectively assessed for childhood and adulthood. Cognitive function was measured using a composite score (range 0-21) across three waves (2011-2015). Linear mixed-effects models examined longitudinal associations, adjusting for sociodemographic factors, health behaviors, and chronic conditions, with interaction analyses for sex and education. RESULTS: Compared with participants reporting no SLEs, cumulative exposure showed the strongest association with cognitive decline (&#x3b2;&#x202f;=&#x202f;-0.52, 95% CI -0.69 to -0.35), followed by childhood-only (&#x3b2;&#x202f;=&#x202f;-0.34, -0.48 to -0.20) and adulthood-only exposure (&#x3b2;&#x202f;=&#x202f;-0.22, -0.37 to -0.07). Sex significantly moderated the associations for childhood and cumulative exposure, with women exhibiting greater cognitive vulnerability. Higher educational attainment attenuated the associations between single-period stress and cognitive decline, with only partial protection observed against cumulative adversity. CONCLUSION: Cumulative life-course stress is associated with accelerated cognitive decline in Chinese middle-aged and older adults. Women appear more vulnerable to stress-related cognitive effects, whereas higher education confers partial resilience, highlighting the need for sex-sensitive and education-informed prevention strategies.

Humans

Immersive virtual reality-assisted anatomy training improves endotracheal intubation performance in simulation: a randomized controlled trial among Chinese non-anesthesiology residents.

INTRODUCTION: This study aimed to compare immersive virtual reality (IVR)-assisted versus conventional anatomy training for teaching endotracheal intubation (ETI) to novice non-anesthesiology residents enrolled in China's Standardized Residency Training program. METHODS: A total of 90 non-anesthesiology residents without prior ETI experience were randomly assigned to either an IVR group receiving IVR-assisted anatomy training (n&#x2009;=&#x2009;45) or a control group receiving conventional anatomy training (n&#x2009;=&#x2009;45). All participants underwent a standardized teaching protocol. The primary endpoint was residents' ETI performance on a simulator, assessed using both the Global Rating Scale (GRS) and a task-specific checklist. The secondary endpoints included changes in written multiple-choice question (MCQ) scores and residents' evaluations of the course. RESULTS: In practical ETI assessments on a manikin, the IVR group achieved significantly higher scores on the task-specific checklist than the control group (90.34&#x2009;&#xb1;&#x2009;2.89 vs. 87.20&#x2009;&#xb1;&#x2009;3.29; p&#x2009;<&#x2009;0.001), whereas GRS scores were comparable between groups. Both groups showed significant post-training improvement in knowledge scores (p&#x2009;<&#x2009;0.001), with the IVR group showing a greater gain in theoretical knowledge (54.0% vs. 36.3%; p&#x2009;<&#x2009;0.001). Participants in the IVR group also expressed a stronger preference for their training method (80.8%) and reported higher levels of motivation, confidence, and enjoyment (all p&#x2009;<&#x2009;0.05). CONCLUSION: IVR-assisted anatomy training enhances the effectiveness of ETI training for novice non-anesthesiology residents, offering an interactive, engaging, and reproducible approach within China's Standardized Residency Training framework.

Humans

Effectiveness of physical activity intervention for depression, anxiety and comorbid symptoms during the perinatal period among Chinese primiparas.

BACKGROUND: To examine the effectiveness of a physical activity (PA) programme incorporating partner support and enjoyment in preventing perinatal depression, anxiety, and comorbid anxiety and depression (CAD) among Chinese primiparas. METHODS: A total of 120 eligible primiparas were randomised into intervention or control groups. The intervention group received the 13-week PA programme and the control group received the usual care. The outcomes were depression, anxiety, and CAD assessed at baseline, post-intervention, and 6 weeks after delivery. Differences were examined using generalised linear mixed models with intention-to-treat. RESULTS: A significant group&#x2009;&#xd7;&#x2009;time interaction was observed for depression score, anxiety score, anxiety incidence, and CAD incidence (all p&#x2009;<&#x2009;0.05). However, no significant interaction was found for depression incidence. Compared to the control, the intervention substantially reduced the scores of depression (MD: -2.67 (-4.16 to -1.17); -2.63 (-4.15 to -1.11)) and anxiety (MD: -4.95 (-9.23 to -0.67); -7.33 (-11.85 to -2.82)), as well as the rates of depression (OR: 0.40 (0.18 to 0.85); 0.44 (0.21 to 0.93)) and CAD (OR: 0.35 (0.14 to 0.87); 0.26 (0.11 to 0.62)) at post-intervention and 6-week postpartum. Notably, anxiety incidence showed significant reduction only at 6-week postpartum (OR: 0.34 (0.16 to 0.74)) (all p&#x2009;<&#x2009;0.05). Within the intervention group, no significant changes occurred in most outcomes from baseline to post-intervention and 6-week postpartum, except depression scores (MD:-1.60 (-2.79 to -0.41); -1.23 (-2.44 to -0.03); p&#x2009;<&#x2009;0.05). CONCLUSIONS: The PA programme (including partner support and enjoyment) may be effective in reducing perinatal depression, anxiety and CAD among primiparas.

Adult