Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

This study aims to investigate the effects of renin inhibitor aliskiren on kidney injury in human angiotensinogen-renin (AGT-REN) double transgenic hypertensive (dTH) mice and explore its possible mechanism. The dTH mice were divided into hypertension group (HT group) and aliskiren intervention group (HT+Aliskiren group), while wild-type C57BL/6 mice were served as the control group (WT group). Blood pressure data of mice in HT+Aliskiren group were collected after 28 d of subcutaneous penetration of aliskiren (20 mg/kg), and the damage of renal tissue structure and collagen deposition were observed by HE, Masson and PAS staining. The ultrastructure of kidney was observed by transmission electron microscope. Coomassie bright blue staining and biochemical analyzer were used to detect renal function injury. The expression of renin-angiotensin system (RAS) was determined by ELISA and immunohistochemistry. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney were determined by chemiluminescence method. The content of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47^phox, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine (3-NT), NADPH oxidase 2 (NOX2) and NADPH oxidase 4 (NOX4) were detected by Western blot analysis. The results showed that compared with WT group, the blood pressure of mice in HT group was significantly increased. The renal tissue structure in HT group showed glomerular sclerosis, severe interstitial tubular injury, and increased collagen deposition. In addition, 24 h urinary protein, serum creatinine and urea levels increased. Serum and renal tissue levels of angiotensin II (Ang II) were increased, serum angiotensin-(1-7) [Ang-(1-7)] expression was decreased, and renal Ang-(1-7) expression was elevated. The expressions of ACE, Ang II type 1 receptor (AT₁R) and MasR in renal tissue were increased, while the expression of ACE2 was decreased. MDA content increased, SOD content decreased, and the expressions of p47^phox, iNOS, 3-NT, NOX2 and NOX4 were increased. However, aliskiren reduced blood pressure in dTH mice, improved renal structure and renal function, reduced Ang II and Ang-(1-7) levels in serum and renal tissue, reduced the expression of ACE and AT₁R in renal tissue, increased the expression of ACE2 and MasR in renal tissue, and decreased the above levels of oxidative stress indexes in dTH mice. These results suggest that aliskiren may play a protective role in hypertensive renal injury by regulating the balance between ACE-Ang II-AT₁R and ACE2-Ang-(1-7)-MasR axes and inhibiting oxidative stress.
Animals ; Fumarates/therapeutic use* ; Mice ; Renin/antagonists & inhibitors* ; Amides/therapeutic use* ; Mice, Inbred C57BL ; Hypertension/physiopathology* ; Mice, Transgenic ; Kidney/pathology* ; Angiotensinogen/genetics* ; Renin-Angiotensin System/drug effects* ; NADPH Oxidases/metabolism* ; Male ; Antihypertensive Agents/pharmacology* ; Humans ; Superoxide Dismutase/metabolism* ; NADPH Oxidase 4

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

Kinesiophobia is prevalent among school-aged children with asthma,and severe kinesiophobia can hinder their participation in physical activities and disease control,adversely affecting their physical and mental health.This paper reviews the concept,development,assessment tools,influencing factors,and intervention strategies of kinesiophobia in school-aged children with asthma,analyzes existing challenges,and proposes directions for future research.It aims to provide insights for developing scientific and personalized intervention plans to enhance children's exercise levels and improve their quality of life.

Objective:To evaluate the technical feasibility and perioperative safety of pyeloplasty assis-ted by the CarinaTM modular laparoscopic surgical robotic system in patients with ureteropelvic junction obstruction(UPJO).Methods:From November to December 2024,five consecutive patients diagnosed with UPJO underwent robot-assisted pyeloplasty using the CarinaTM modular laparoscopic surgical system at Peking University First Hospital.Data on patient demographics,intraoperative parameters(including docking time,console time,and estimated blood loss),perioperative outcomes,follow-up results,and surgeons' subjective evaluations of system performance were prospectively collected.Descriptive statistics were used;continuous variables were presented as median(range),and categorical variables as frequen-cy and percentage.Results:The cohort included four females and one male.All the patients successfully completed the robotic procedure without conversion to open or conventional laparoscopic surgery.The me-dian age was 32 years(24-37 years),and the median body mass index was 21.6 kg/m2(15.8-27.3 kg/m2).The median docking time was 8 min(3-12 min),and the median console time was 91 min(71-125 min).Intraoperative blood loss was uniformly 20 mL.The median postoperative drainage du-ration was 3 d(0-4 d),and the median length of hospital stay was 4 d(4-9 d).No Clavien-Dindo grade Ⅲ or higher complications occurred.All the patients had their double-J stents removed at 2 months postoperatively,and pain in the ipsilateral flank,reported preoperatively by all the five patients,was al-leviated.The subjective surgical success rate was 100％.Surgeons reported stable system performance throughout all the procedures,with no instances of mechanical arm interference or visual drift affecting surgical fluency.Conclusion:Preliminary findings indicate that pyeloplasty using the domestically deve-loped CarinaTM modular laparoscopic robotic system is technically feasible and perioperatively safe for the treatment of UPJO.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.

This paper primarily investigated the protective effects and potential mechanisms of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma in alleviating isoprenaline(ISO)-induced hypertrophy and damage in H9c2 cardiomyocytes. Initially, H9c2 cardiomyocytes were used as the research subject to analyze the effects of ISO at different concentrations on cell hypertrophy and damage. On this basis, the H9c2 cardiomyocytes were divided into blank, model, and high-dose(200 μg·mL~(-1)), medium-dose(100 μg·mL~(-1)), and low-dose(50 μg·mL~(-1)) groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma. Cell hypertrophy and damage models were induced by treating cells with 400 μmol·L~(-1) ISO for 24 hours. The Incucyte live-cell analysis system was utilized to observe the status, size changes, and confluence of the cells in each group. Cell viability was detected by using the CCK-8 assay. Western blot analysis was employed to detect the expression of Ras-associated protein 7A(RAB7A), sequestosome 1(SQSTM1/p62), autophagy-related protein Beclin1, and microtubule-associated protein 1 light chain 3(LC3). Immunofluorescence was used to detect the expression level of the autophagy marker Beclin1 in H9c2 cells. The results demonstrated that compared with the blank group, the model group showed a significant reduction in cell viability(P<0.01) and a marked increase in cell hypertrophy, with an average cell length growth of 13.53%. Compared with the model group, the high-dose, medium-dose, and low-dose groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma exhibited reduced hypertrophy, with respective growths of 6.89%, 8.30%, and 8.49% and a significant decrease in growth rates(P<0.01). Cell viability in the high-dose of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma was also significantly increased(P<0.01). Western blot and immunofluorescence results indicated that compared with the blank group, the model group showed changes in Beclin1, RAB7A, and p62 expression, as well as the LC3Ⅱ/LC3Ⅰ ratio, although most changes were not statistically significant. In the groups treated with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma, the expression of autophagy-related proteins Beclin1 and RAB7A and the LC3Ⅱ/LC3Ⅰ ratio were significantly increased(P<0.05), while p62 expression significantly decreased(P<0.05). These findings collectively suggested that pretreatment of cells with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma significantly enhanced autophagy activity in cells. In summary, total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma inhibit ISO-induced hypertrophy and damage in H9c2 cells by promoting autophagy, demonstrating potential cardioprotective effects and providing new insights and scientific evidence for their preventive and therapeutic use in cardiovascular diseases.
Autophagy/drug effects* ; Saponins/pharmacology* ; Panax notoginseng/chemistry* ; Panax/chemistry* ; Animals ; Rats ; Cell Line ; Drugs, Chinese Herbal/pharmacology* ; Rhizome/chemistry* ; Isoproterenol/adverse effects* ; Myocytes, Cardiac/cytology* ; Hypertrophy/drug therapy*