ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.

OBJECTIVE: To investigate the clinical manifestations and genetic etiology of a fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities (NEDDFSA). METHODS: Clinical data of a NEDDFSA fetus diagnosed at the Affiliated Women and Children's Hospital Affiliated to Ningbo University in March 2025 was selected as the study subject. Whole-exome sequencing (WES) was carried out on the amniotic fluid and parental peripheral blood samples, and candidate variants was verified by Sanger sequencing. The pathogenicity of candidate variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: At 30 weeks of gestation, the fetus was found to have microcephaly, short femur and intrauterine growth restriction. WES revealed that the fetus harbored a de novo heterozygous frameshift variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene, which was rated as pathogenic (PM2_Supporting+PS2_Supporting+PVS1). Combined with 25 cases from the literature, the main manifestations of patients have included intellectual disability, growth retardation and cranio-limb skeletal dysplasia, albeit without clear genotype-phenotype correlation. CONCLUSION The de novo variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene probably underlay the NEDDFSA in this fetus. Genetic testing has enabled accurate prenatal diagnosis and provided evidence for genetic counseling and reproductive guidance of this family.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/genetics* ; Transcription Factors/genetics* ; Fetus/abnormalities* ; Exome Sequencing ; Prenatal Diagnosis

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Objective: To analyze the clinical characteristics and management strategies of metronidazole-associated Stevens-Johnson syndrome (SJS), and to provide a clinical basis for medication safety during the oral perioperative period. Methods: The study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Stomatological Hospital of Xi'an Jiaotong University. A retrospective analysis was conducted on a case of SJS following mandibular impacted tooth extraction, for which the patient had taken metronidazole. Additionally, a literature review was performed by searching databases including China National Knowledge Infrastructure, Wanfang, PubMed, and Web of Science to identify reported cases of metronidazole-associated SJS. Demographic features, medication regimens, latency periods, clinical signs, interventions, and prognosis were analyzed. Results: The patient presented with lip swelling, extensive erosion and ulceration of the oral mucosa, and severe odynophagia. Scattered erythematous macules and bullae were observed on the trunk and extremities, with a positive Nikolsky sign. Additionally, there was erosion of the perineal skin and glans penis mucosa, along with skin desquamation of the scrotum. The patient with SJS was managed in the hospital by discontinuing metronidazole and administering sequential treatments, including glucocorticoids, immunomodulators, intravenous immunoglobulin, and plasma exchange. The condition gradually improved; after a 14-month follow-up, only mild dry eye remained, with no significant scarring of the skin or mucosa. However, delayed recognition of early warning signs resulted in delayed drug withdrawal and intervention. The literature review identified 6 additional cases (3 males, 3 females) with a median age of 45.5 years (range 31-61). Indications for metronidazole included postoperative sepsis prophylaxis after duodenal ulcer perforation repair, digestive system infections, mucosal diseases, pelvic inflammatory disease, septic cellulitis with pneumonia, and gingivitis. Administration routes comprised oral (n = 2), intravenous (n = 3), and topical (n = 1). The latency period from drug administration to onset ranged from 0.25 to 7 days (median 4 days). All of the cases presented with oral mucosal erosion, and a positive Nikolsky’s sign was noted for five patients. Discontinuation of the causative drug was the cornerstone of treatment, supplemented by immunomodulatory therapy, symptomatic support, and multidisciplinary collaboration. Prognoses varied significantly: among the four patients treated with “drug withdrawal + glucocorticoids + supportive care,” three recovered fully and one improved; among the two patients receiving “drug withdrawal + simple supportive care,” one recovered and one died Conclusion Although metronidazole-associated SJS is rare, it progresses rapidly and frequently involves oral mucosal damage, typically occurring within one week of administering the medication. Early drug withdrawal and prompt initiation of glucocorticoid therapy can improve prognosis. During the oral perioperative period, strict adherence to metronidazole indications, enhanced monitoring for early warning symptoms, and the establishment of a multidisciplinary collaborative diagnosis and treatment model are essential to minimize the risk of severe adverse drug reactions.

Metabolic associated fatty liver disease （MAFLD） is a highly prevalent chronic liver disease worldwide， and the mechanism underlying its progression to metabolic associated steatohepatitis and liver fibrosis remain unclear. Endoplasmic reticulum stress （ERS） and ferroptosis （Fer） are deeply involved in the pathological evolution of MAFLD. This article systematically reviews the core regulatory mechanisms of ERS and its role in regulating lipid metabolism， inflammation response， and cell apoptosis in MAFLD. It also analyzes the core mechanism of Fer and discusses the predisposing factors for Fer in the pathological microenvironment of MAFLD， as well as the role of Fer in exacerbating hepatocyte death and activating the progression of liver fibrosis. This article proposes that the crosstalk between ERS and Fer is a key driver for the progression of MAFLD， which provides new references and ideas for the clinical intervention of MAFLD.

Investigator initiated trial （IIT） represents a primary format for clinical research in traditional Chinese medicine （TCM）. As key implementation sites for TCM-based IIT targeting malignant tumors， western medicine institutions often face unique challenges in conducting such studies， which limit their feasibility and standardization. This paper reviews the registration status of TCM-based IIT for malignancies conducted in western medical institutions and analyzes key difficulties， including complex project initiation and management processes， limited TCM knowledge and skills among western medicine physicians， and relatively low patient acceptance of TCM. From a practical perspective， the study proposes several optimization strategies. These include improving the review and management mechanisms of TCM-related IIT within western medical institutions， establishing multidisciplinary clinical research teams that integrate TCM and western medicine， and enhancing investigators' training in TCM theory and clinical skills. Additionally， the study suggests standardizing IIT operational procedures， objectifying the collection of TCM diagnostic information， refining subject recruitment methods， and increasing TCM involvement in patient follow-up and management. These investigator-oriented， TCM-featured， and operable strategies aim to promote the high-quality development of TCM-based IIT in western medicine institutions and enhance the clinical application of TCM.

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

In order to solve the problems of difficult test, high cost and long cycle in the development of large-scale airborne negative pressure isolation system, the simulation analysis of negative pressure response characteristics is carried out around various aviation conditions such as aircraft ascending, leveling and descending, especially rapid decompression, based on the computational fluid dynamics (CFD) method. The results showed that the isolation cabin could achieve -50 Pa pressure difference environment and form a certain pressure gradient. The exhaust air volume reached the maximum value in the early stage of the aircraft's ascent, and gradually decreased with the increase of altitude until it was level flying. In the process of aircraft descent, the exhaust fan could theoretically maintain a pressure difference far below -50 Pa without working; Under the special condition of rapid pressure loss, it was difficult to deal with the rapid change of low pressure only by the exhaust fan, so it was necessary to design safety valve and other anti-leakage measures in the isolation cabin structure. Therefore, the initial stage of aircraft ascent is the key stage for the adjustment and control of the negative pressure isolation system. By controlling the exhaust air volume and adjusting parameters, it can adapt to the change of low pressure under normal flight conditions, form a relatively stable negative pressure environment, and meet the needs of biological control, isolation and transport.
Aircraft ; Computer Simulation ; Aviation/instrumentation* ; Humans ; Hydrodynamics ; Air Pressure ; Equipment Design ; Pressure