[摘 要] 目的：探究花旗松素（TAX）通过Rac1/NF-κB/AKT信号通路调控人膀胱癌T24细胞的恶性生物学行为。方法：常规培养膀胱癌T24细胞，将其分为：Ctrl组（未处理）、TAX-L组（5 μmol/L TAX处理）、TAX-M组（10 μmol/L TAX处理 ）、TAX-H组（20 μmol/L TAX处理）、TAX-H + Rac1激活剂组（20 μmol/L TAX + 50 nmol/L ML-097处理）。CCK-8法、克隆形成实验、划痕愈合实验、Transwell小室实验和流式细胞术分别检测不同浓度TAX对T24细胞增殖、迁移、侵袭能力和凋亡的影响，WB法检测对各组T24细胞中细胞凋亡、上皮间充质转化、Rac1/NF-κB/AKT轴相关蛋白表达的影响；T24细胞裸鼠移植瘤实验检测TAX对移植瘤生长的影响。结果：TAX呈剂量依赖性地抑制T24细胞的增殖、迁移和侵袭能力，并促进其凋亡（均P < 0.05），促进凋亡蛋白BAX和E-cadherin、抑制Rac1/NF-κB/AKT信号通路相关蛋白的表达、Bcl-2和N-cadherin蛋白表达（均P < 0.05），抑制移植瘤的生长（P < 0.05），ML-097均可部分逆转上述作用（均P < 0.05）。结论：TAX通过抑制Rac1/NF-κB/AKT信号通路中抑制膀胱癌T24细胞的恶性生物学行为，促进其凋亡。

Objective To investigate the clinical features，laboratory findings，and prognosis of patients with autoimmune encephalitis positive for leucine rich glioma inactivated 1（LGI1）antibody. Methods We reviewed the clinical data of 11 patients with anti-LGI1 encephalitis hospitalized in Fu Yang People's Hospital from October 2019 to December 2024. Results All the 11 patients（100%）had cognitive function involvement，9（81.8%）had epileptic seizures，5（45.5%）had mental and behavioral abnormalities，4（36.4%）had sleep disorders，3（27.3%）had autonomic nervous dysfunction，2（18.2%）had faciobrachial dystonic seizures（FBDS），2（18.2%）had facial numbness，and 1（9.1%）had phantosmia and pruritus in both eyes and the neck. LGI1 antibody was positive in the serum of all the cases（100%）and present in the cerebrospinal fluid of 8 cases（72.3%）. Seven cases（63.6%）had hyponatremia，and 5 cases（45.5%）also had hypophosphatemia，hypocalcemia，and hypomagnesemia in addition to blood sodium lower than 134 mmol/L. Intracranial abnormalities were detected in 7 cases（63.6%）on magnetic resonance imaging. Electroencephalogram abnormalities were recorded in 6 cases（54.5%）. After immunosuppressive treatment，2 cases（18.2%）had recurrent symptoms，and 2 cases（18.2%）had residual mild memory impairment. In terms of prognosis，the modified Rankin Scale scores were generally favorable. Conclusion Anti-LGI1 encephalitis manifests as convulsions，FBDS，memory decline，mental and behavioral abnormalities，autonomic nervous dysfunction，sleep disorders，hyponatremia，and multiple electrolyte disorders such as hypomagnesemia，hypocalcemia，and hypophosphatemia when blood sodium is below 134 mmol/L. The prognosis with immunosuppressive treatment is favorable，but recurrent symptoms may occur.

Introduction: Early identification of patients at risk for severe multisystem inflammatory syndrome in children (MIS-C) is essential for favourable clinical outcomes. This study aims to identify the clinical characteristics, factors and outcomes associated with severe MIS-C. Materials and methods: In this retrospective cohort study involving 14 major hospitals in Malaysia, children <15 years who met the United States Centres for Disease Control and Prevention case definition for MIS-C were included. Severe MIS-C was defined as children who required inotropic support, ventilatory support (invasive or non-invasive ventilation), or left ventricular ejection fraction of <55%. The factors investigated for severe MIS-C were demographic characteristics, the presence of comorbidities, clinical characteristics, and laboratory measures. Multivariable logistic regression was used to compute the adjusted odds ratio (aORs) of factors associated with severe MIS-C. Results: Among the 155 patients, 91 (58.7%) presented with severe MIS-C. Severe MIS-C was more likely in patients aged ≥5 years old (aOR 2.13, 95% confidence interval [CI] 1.08-4.21), with dehydration (aOR 3.80, 95% CI 1.53-9.45), lethargy (aOR 2.02, 95% CI 0.97-4.18), tachycardia (aOR 8.33, 95% CI 3.27-21.22), albumin <30g/L (aOR 3.36, 95% CI 1.58-7.13), creatine kinase >200U/L (aOR 3.68, 95% CI 1.57-8.64), D-dimer >3.0µg/mL (aOR 2.11, 95% CI 1.08-4.13), ferritin >500ng/mL (aOR 3.77, 95% CI 1.88-7.55), prothrombin time >12.7 seconds (aOR 3.22, 95% CI 1.61-6.43), and urea >6mmol/L (aOR 5.09, 95% CI 2.04-12.71). Conclusion: Identification of these associated factors of severity in MIS-C could aid in early recognition and prompt escalation of care, leading to better outcomes.

Objective To investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Methods A retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. Based on the discharge INR values, patients were divided into two groups: an INR≤3.0 group and an INR>3.0 group. The factors associated with INR>3.0 at the time of discharge were analyzed. Results A total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. The gender, body mass index (BMI), New York Heart Association (NYHA) cardiac function grading, INR, glutamic oxaloacetic transaminase, and preoperative prothrombin time (PT) were statistically different between the two groups (P<0.05). Multivariate logistic regression analysis revealed that lower BMI, preoperative PT>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). Conclusion BMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.

Objective To investigate the correlation between the concentration of air pollutants (PM₁₀, SO₂, NO₂) and the number of outpatient and emergency visits for pediatric respiratory diseases in a general hospital in Shanghai. Methods Data including pediatric respiratory disease outpatient and emergency visits in a hospital in Pudong New Area of Shanghai from May 1, 2013 to March 20, 2022 were collected. Daily concentration of air pollutants including PM₁₀, SO₂ and NO₂ and meteorological data in Pudong New Area during the same period were collected. A case-crossover study with distributed lag non-linear model was conducted to explore the correlation between air pollutants (PM₁₀, SO₂, NO₂) and the number of outpatient and emergency visits for pediatric respiratory diseases. Results The concentrations of PM₁₀, SO₂ and NO₂ were positively with the number of outpatient and emergency visits for pediatric respiratory diseases. The strongest cumulative effect was observed on six days lag (Lag0-5) for PM₁₀. For a 10 μg/m³ increase of the concentrations of PM₁₀, the corresponding increase of cumulative pediatric respiratory disease outpatients was 1.10% (95%CI:0.97%, 1.23%) in Lag0-5. The strongest cumulative effect was observed on eight days lag (Lag0-7) for SO₂ and NO₂. For a 10 μg /m³ increase of the concentrations of SO₂ and NO₂, the corresponding increase of cumulative pediatric respiratory disease outpatients was 5.64% (95%CI:5.16%, 6.13%) and 5.41% (95%CI:5.15%, 5.66%) in Lag 0-7, respectively. The association of PM₁₀ and SO₂ with the number of pediatric respiratory disease visits in males was significantly stronger than that in females. The impact of PM₁₀ on the number of pediatric respiratory disease visits in children aged 0-6 was higher than that in children aged 7-14, while the impact of SO₂ and NO₂ on the number of pediatric respiratory disease visits in children aged 7-14 was higher than that in children aged 0-6. Conclusion The concentration of ambient PM₁₀, SO₂, and NO₂ is positively correlated with outpatient and emergency visits for pediatric respiratory diseases, with obvious lag and cumulative effect. Boys and children aged 0-6 are more susceptible to the hazard of air pollution.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

Objective To explore the correlation between clinical distribution characteristics of streptococcal pharyngitis in children and seasonal variations in Ziyang area, so as to provide basis for disease prevention and control. Methods A multistage and stratified random sampling technique was used to investigate 583 children with streptococcal pharyngitis attending Ziyang first people's Hospital from January 2022 to January 2023. The clinical data were recorded. The pharyngeal specimens were cultured for streptococci test. The number of streptococcal pharyngitis cases per season was counted. The metereological conditions (average barometric pressure, temperature, rainfall, and wind speed) were recorded. Pearson method was used to discuss the correlation between metereological factors and streptococcal pharyngitis onset. Results A total of the 583 children, 329 were male and 254 were female. The main age of onset was 7-12 years old, with a total of 227 cases (38.94%), followed by 199 cases (34.13%) aged 3-6 years old, 126 cases (21.61%) aged 1-2 years old, and 31 cases (5.32%) under 1 year old. A total of 614 strains of pathogenic bacteria were detected, of which 479 strains of Streptococcus hemolyticus were dominant, accounting for 78.01%, followed by 175 strains of Streptococcus pyogenes, accounting for 28.50%. Seasonally, 192 cases of streptococcal pharyngitis occurred in spring, 51 in summer, 72 in autumn and 268 in winter. In Ziyang, spring and winter were characterized by high mean wind speeds and barometric pressure, while summer and autumn were characterized by high mean temperatures and heavy rainfall. Pearson correlation analysis revealed that the prevalence rate streptococcal pharyngitis was positively correlated with average wind speed and barometric pressure (P<0.05), and negatively correlated with mean temperature and rainfall (P<0.05). Conclusion In Ziyang, streptococcal pharyngitis occurs mostly in children over 5 years old, and the main pathogen is Streptococcus hemolyticus. The onset of the disease is mostly in spring and winter, which is closely related to the seasonal variations of the region.

Objective To investigate the clinical efficacy of tiotropium bromide in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)complicated with acute respiratory failure.Methods A total of 106 patients with AECOPD complicated with acute respiratory failure admitted to the First People's Hospital of Huzhou from March 2019 to March 2022 were selected and divided into observation group and control group according to random number table method,with 53 cases in each group.Both groups were given routine treatment.The control group was treated with noninvasive biphasic positive airway pressure ventilation.The observation group was treated with tiotropium bromide on the basis of control group.Both groups were treated for 14 days.The clinical efficacy,lung function,blood gas index,inflammatory factors and adverse reactions were compared between two groups.Results The total effective rate of observation group was significantly higher than that of control group(94.34%vs.79.25%,χ2=5.267,P=0.023).After treatment,forced expiratory volume in one second(FEV1),FEV1/forced vital capacity,peak expiratory flow,pH,percutaneous arterial oxygen saturation and arterial partial pressure of oxygen in observation group were significantly higher than those in control group(P<0.05),while arterial partial pressure of carbon dioxide,interleukin-6,interleukin-8,tumor necrosis factor-α and hypersensitive C-reaction protein were lower than those in control group(P<0.05).There were no significant differences in the incidence of adverse drug reactions and ventilator adverse reactions between two groups(P>0.05).Conclusion Titropium bromide in the treatment of AECOPD complicated with acute respiratory failure can significantly improve the curative effect,improve pulmonary function and arterial blood gas,but attention should be paid to the timely treatment of adverse reactions of dry mouth.

Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

Objective : To investigate the role and mechanism of bone formation caused by the ratio of advanced platelet-rich fibrin (A-PRF) and β-tricalcium phosphate (β-TCP) in rabbit femur defect model, which provides a new idea for clinical treatment of bone defect. Methods : Twenty-four New Zealand white rabbits were divided into model group, 1∶1 complex group (A-PRF∶β-TCP=1∶1), 2∶1 complex group (A-PRF∶β- TCP=2∶1) and 4∶1 complex group (A-PRF∶β- TCP=4∶1）, with 6 rabbits in each group. Femoral defect models were constructed in each group. In the composite group, the bone defect was filled with composite material, while in the model group, no material was filled. After 8 weeks, the animals were euthanized and specimens were collected. Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.SP) and trabecular number (Tb.N) in femoral defect tissue were measured by micro-CT and photographed. Hematoxylin - eosin staining was used to detect the pathological changes of new bone tissue. The morphological changes of the new bone tissue were observed by scanning electron microscopy. Determination of phospho-mitogen activated protein kinase p38 (p-p38MAPK), CCAAT/enhancer binding protein homologous protein (CHOP) and phospho-cysteine aspartic protease-3 (p-Caspase3) in newborn femur by ELISA. The mRNA expressions of osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), receptor activator of nuclear factor kappa-B ligand (RANKL) and p38MAPK were detected by real-time quantitative PCR. The expression of OPG, BMP-2, RANKL, p-p38MAPK and p-Caspase3 protein in the new bone tissue was observed by immunohistochemistry. Results : In the model group, bone formation in the femoral defect area was slow and osteogenic quality was poor. Compared with the model group, the bone formation and neocapillaries of femoral defect area in the complex group was good, BMD, BV.TV, Tb.Th, Tb.N were increased, and Tb.Sp were decreased, the expressions of p-p38MAPK, CHOP and p-Caspase3 were decreased, and the mRNA and protein expressions of OPG and BMP-2 were increased. The mRNA expression of RANKL and p38MAPK was decreased. Apoptosis in new bone tissue of each group showed the lowest apoptosis rate in samples of the 2∶1 complex group (P<0.05); A-PRF: β-TCP=2∶1 ratio has the best osteogenic effect. Conclusion The complex composed of A-PRF and β-TCP can promote the expression of OPG, inhibit the expression of RANKL and phosphorylation of p38MAPK, reduce the apoptosis of new bone tissue cells, and promote osteogenic differentiation.