Objective: To explore the association between types of obesity and 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among hypertensive patients, so as to provide the basis for formulating ASCVD prevention strategies for hypertensive patients. Methods: From January to December 2021, hypertensive patients who were under follow-up management and completed health examinations at three community health service centers in Linping District, Hangzhou City were selected by a cluster sampling method. Basic information, lifestyle, disease history, height, weight, waist circumference (WC), and blood biochemical indicators were collected through health examination data. Based on assessments of body mass index (BMI) and WC, participants were categorized into four types: non-obese, general obesity only, central obesity only, and combined obesity. The Prediction for ASCVD risk in China (China-PAR) was used to assess 10-year ASCVD risk, which was categorized as low, moderate, and high risk. Multivariable logistic regression models were used to analyze the association between different types of obesity and ASCVD risk among hypertensive patients. Results: A total of 10 408 hypertensive patients were included, with a median age of 68.00 (interquartile range, 10.00) years. There were 4 301 (41.32%) males and 6 107 (58.68%) females. The proportions of non-obese, general obesity only, central obesity only, and combined obesity were 34.93% (3 635 individuals), 22.85% (2 378 individuals), 4.32% (450 individuals), and 37.90% (3 945 individuals), respectively. There were 3 389 (33.52%) cases at high risk of ASCVD. Among them, high ASCVD risk was observed in 1 107 (30.45%), 896 (37.68%), 122 (27.11%), and 1 364 (34.58%) patients with non-obese, general obesity only, central obesity only, and combined obesity, respectively. Multivariable logistic regression analysis showed that after adjusting for gender, age, smoking, drinking, physical activity, and diabetes, the risk of high ASCVD in hypertensive patients with general obesity only and combined obesity was 1.383 times (95%CI: 1.235-1.548) and 1.225 times (95%CI: 1.109-1.354) that of non-obese hypertensive patients, respectively. Conclusions General obesity only and combined obesity can increase the 10-year high risk of ASCVD among hypertensive patients. It is necessary to strengthen comprehensive management of body weight and WC among hypertensive patients to reduce the risk of ASCVD.

Objective: To analyze the process of handling a pulmonary tuberculosis(TB) outbreak among senior high school students in a boarding school in Chongqing, as well as to investigate the underlying causes of the outbreak, so as to provide evidence to inform TB prevention and control strategies in school settings. Methods: From November 2023 to April 2024, an epidemiological investigation was conducted into the TB outbreak in a grade 12 class from a boarding high school. Suspected cases were screened using symptom screening, tuberculin skin test (TST), and chest X-ray examinations. Confirmed cases underwent individual epidemiological interviews and sputum culture; Cultured positive mycobacterial strains were subjected to whole genome sequencing after identification as Mycobacterium tuberculosis. Results: A total of 10 active pulmonary TB cases were identified, all from the same class, yielding a student attack rate of 16.67%. Three isolates were culture positive, as well as all strains were of L2 type，and the WGS analysis of the strains suggested a common transmission chain. Excluding the index case, four additional cases were detected through symptom driven health care visits. Notably, 70% of patients presented with "chest tightness and chest pain" symptoms, and 50% had "cough" symptoms,but none were detected during morning health checks or tracking of absences due to illness. A total of 326 contacts were identified and underwent three rounds of screening and one follow up examination. In the initial screening, 35 close contacts from the same class showed strong TST positivity, corresponding to a strong positivity rate of 55.56%, significantly higher than the 20.76% observed among casual contacts ( χ 2=29.80, P <0.01). Among the 35 strongly TST positivvity close contacts and five individuals with moderate TST positivity whose induration had increased by ≥10 mm over two years, none received timely preventive treatment initially; five of them were subsequently diagnosed with active TB within three months. Following this, 25 individuals initiated preventive therapy, resulting in a preventive treatment initiation rate of 62.50%. Among TST negative classmates who converted to strong positivity on repeat TST testing at three months, 75.00% started preventive treatment, but only 22.22% completed the full course. Conclusion Inadequate implementation of morning health checks and cause tracking for absenteeism due to illness, poorly standardized screening procedures, and delayed preventive treatment may have been key factors contributing to the spread of the outbreak.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective To translate the Maternal Childbirth Fatigue Perception Questionnaire(MCFQ)into Chinese and examine its reliability and validity among women undergoing vaginal deliv-ery.Methods Following the Brislin translation model,the MCFQ was translated,back-translated,culturally adapted and pre-tested to develop a Chinese version.By using the convenience sampling method,574 parturients were selected for a questionnaire survey from January to April 2024,and the reliability and validity of the Chinese questionnaire were evaluated.Results The Chinese version of MCFQ consisted of 3 dimensions and 13 items,namely physical fatigue(7 items),perceived fatigue(3 items)and emotional fatigue(3 items).The item-level content validity index ranged from0.813 to 1.000,and the scale-level content validity index was 0.938.The overall Cronbach's α coefficient of the scale was 0.870,and the split-half reliability coefficient was 0.848.Confirmatory factor analysis demonstrated that the question naire had a good fit.Conclusion The Chinese version of MCFQ has good reliability and validity and can be used as an effective tool to assess the fatigue level of parturients during the delivery process.It is helpful for clinical medical staff to optimize the management of the la-bor process,improve the quality of delivery,and ensure the safety of mothers and infants.

Objective:To construct a mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases based on the Liverpool mindfulness model, providing practical guidance for improving their physical and mental symptoms.Methods:The system searched for relevant literature on the application of mindfulness intervention in patients with malignant hematological diseases retrieved from Cochrane Library, PubMed, CINAHL, PsycInfo, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. The search period was from January 1, 1982 to December 26, 2023. Using the Liverpool mindfulness model as the theoretical framework, based on the literature review, group meetings and semi-structured interviews, a preliminary draft of a mindfulness cancer rehabilitation training program for patients with malignant hematologic diseases was developed. After 2 rounds of Delphi expert consultation, the final version of the intervention plan was determined.Results:Among the 19 experts, there were 4 males and 15 females, aged 30-61 (47.11 ± 7.64) years old. The effective recovery rates of the two rounds of expert inquiry questionnaires were both 19/19, and the expert authority coefficients were both 0.88. The Kendall coordination coefficients for the two rounds of inquiry were 0.214 and 0.220, respectively ( χ2=77.37, 108.66, both P<0.01).A mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases was ultimately developed, including intervention subjects, intervention personnel, intervention sites and forms, intervention timing, intervention intensity, intervention process and training theme content. Conclusions:The mindfulness based cancer rehabilitation training program for patients with malignant hematologic diseases constructed based on the Liverpool mindfulness model is necessary, scientific, and clinically suitable, and can provide a basis for clinical psychological nursing practice for patients with malignant hematologic diseases.

Objective:To investigate the efficacy and underlying mechanism of modified Wubei powder combined with Banxia Xie Xin decoction in the treatment of reflux esophagitis (RE). Methods:A case-control study was conducted involving 82 patients with RE who received treatment at Department of Spleen and Stomach Diseases, Xi'an Hospital of Traditional Chinese Medicine from June 2022 to June 2023. The patients were randomly assigned to either a control group or an observation group, with 41 patients in each group. The control group received conventional treatment, while the observation group was given Wubei powder combined with modified Banxia Xie Xin decoction orally in addition to the conventional treatment. The traditional Chinese medicine symptom scores, lower esophageal sphincter relaxation rate (LESR), percentage of abnormal esophageal contractions, and levels of substance P (SP), cholecystokinin (CCK), motilin (MTL), gastrin (GAS), serum ghrelin, and vasoactive intestinal peptide (VIP) were compared between the two groups before treatment and at 2 and 4 weeks after treatment. Results:There was no statistically significant difference in traditional Chinese medicine symptom scores between the two groups before treatment ( P > 0.05). However, both groups showed lower symptom scores at 2 and 4 weeks after treatment compared with before treatment ( t = 6.87, 10.87, 9.59, 15.39, all P < 0.05). The observation group demonstrated significantly greater improvement in symptom scores at 2 and 4 weeks compared with the control group [(17.68 ± 2.13) vs. (23.76 ± 2.48); (11.44 ± 1.12) vs. (18.82 ± 1.85), t = 4.18, 4.35, both P < 0.05]. There were no statistically significant differences in LESR or percentage of abnormal contractions between the two groups before treatment (both P > 0.05). However, both LESR and the percentage of abnormal esophageal contractions improved at 2 and 4 weeks after treatment compared with before treatment ( t = 4.25, 5.73, 5.86, 6.49, 3.79, 4.84, 4.48, 5.56, all P < 0.05). Additionally, the observation group had significantly lower LESR at 2 and 4 weeks compared with the control group [(71.62 ± 6.37)% vs. (75.46 ± 6.89)%, (64.92 ± 5.82)% vs. (70.78 ± 6.45)%, t = 5.43, 5.86, both P < 0.05]. The percentage of abnormal esophageal contractions was also significantly lower in the observation group [(45.28 ± 5.18)% vs. (59.56 ± 5.84)%; (33.53 ± 4.24)% vs. (47.74 ± 5.31)%, t = 6.08, 7.24, both P < 0.05]. Before treatment, there were no statistically significant differences in levels of SP, MTL, GAS, or CCK between the two groups (all P > 0.05). The levels of SP, MTL, GAS, and CCK improved in both groups at 2 and 4 weeks compared with before treatment ( t = 4.67, 7.15, 7.24, 9.87, 3.62, 5.85, 4.58, 7.17, 3.55, 5.41, 5.42, 6.89, 3.53, 5.43, 5.39, 6.82, all P < 0.05). Furthermore, the observation group had significantly higher levels of SP, MTL, and GAS at 2 and 4 weeks compared with the control group ( t = 3.65, 4.12, 3.86, 4.25, 4.48, 5.36, all P < 0.05), while CCK levels were significantly lower in the observation group ( t = 4.38, 4.51, both P < 0.05). There were no statistically significant differences in ghrelin or VIP levels between the two groups before treatment (both P > 0.05). However, both ghrelin and VIP levels improved in both groups at 2 and 4 weeks after treatment compared with before treatment ( t = 3.35, 3.72, 3.69, 4.28, 3.76, 4.88, 4.11, 5.69, all P < 0.05). Additionally, the observation group had significantly higher levels of ghrelin compared with the control group ( t = 3.43, 4.11, both P < 0.05), while VIP levels were significantly lower in the observation group ( t = 4.59, 5.71, both P < 0.05). Conclusions:The addition of modified Wubei powder combined with Banxia Xie Xin decoction to conventional treatment can considerably alleviate clinical symptoms in patients with RE and improve esophageal pressure. Furthermore, this combined therapy can effectively regulate serum levels of SP, CCK, MTL, GAS, ghrelin, and VIP, thereby modulating the contraction and relaxation of gastrointestinal smooth muscle, enhancing lower esophageal sphincter pressure, and reducing reflux.

Objective:To summarize the clinical and genetic characteristics of 23 children with pathogenic ACAN gene variants, enhance the understanding of this disorder, and explore possible regulatory mechanisms. Methods:A retrospective case series summary.The clinical characteristics and genetic analysis results of 23 children with ACAN gene variants treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University from January 2016 and September 2024 were analyzed retrospectively.Transcriptome sequencing was performed on peripheral blood samples from 3 of affected children and 3 age-matched healthy children as controls.Differentially expressed genes (DEGs) in the peripheral blood transcriptome profiles were identified.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to explore the potential signaling pathways involved. Results:Among the 23 cases, there were 13 males and 10 females, aged from 2 years and 8 months to 12 years old, with 11 cases presenting advanced bone age.Thirteen cases were treated with growth hormone (GH), including 6 cases who received concomitant gonadotropin-releasing hormone analogue therapy.The treatment duration ranged from 3 to 70 months, resulting in varying degrees of height improvement in all treated patients.Transcriptomic analysis identified 811 DEGs, with 516 up-regulated and 295 down-regulated.GO and KEGG enrichment analyses revealed that the heterozygous ACAN variants were significantly associated with FcγR-mediated phagocytosis, nuclear factor-κB signaling pathway, the intestinal immune network for IgA production, rheumatoid arthritis, and systemic lupus erythematosus signaling pathways. Conclusions:The predominant clinical manifestations of patients with ACAN gene variants are short stature and advanced bone age.Although GH provocation tests may indicate normal GH levels, GH therapy can be effective in improving height.Immune-related factors may play a role in the pathogenesis of this disorder.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.