This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Objective:To compare the imaging quality and metabolic quantitative parameters of pulmonary nodules between Q. Flex whole information five-dimensional (5D) and conventional three-dimensional (3D) PET/CT imaging for clinical evaluation.Methods:Fifty-four patients (30 males, 24 females, age: 60(42, 75) years; 78 solid pulmonary nodules (maximum diameter≤3 cm) with abnormal uptake of 18F-FDG) from Tianjin Cancer Hospital Airport Hospital between June 2022 and August 2022 were enrolled in this retrospective study. All patients underwent 5D scanning and 3D, 5D reconstruction. Image quality scores, signal-to-noise ratio (SNR), SUV max, SUV mean and metabolic tumor volume (MTV) of pulmonary nodules of 5D group and 3D group were evaluated and compared with χ2 test and Wilcoxon signed rank test. Correlation of quantitative parameters between 2 groups were analyzed by using Spearman rank correlation analysis. Results:Thirty-five of 78(45%) pulmonary nodules with image quality score≥4 were found in 5D group, which were more than those in 3D group (22/78(28%); χ2=4.67, P=0.031). Meanwhile, SNR, SUV max, SUV mean, and MTV were significantly positively correlated between the 2 groups ( rs values: 0.86, 0.86, 0.85, and 0.95, all P<0.001). SNR, SUV max and SUV mean of pulmonary nodules in 5D group were significantly higher than those in 3D group, which were 37.46(18.42, 62.00) vs 32.72(16.97, 54.76) ( z=-4.07, P<0.001), 9.71(5.48, 13.82) vs 8.96(4.82, 12.63) ( z=-3.05, P<0.001) and 6.30(3.39, 8.94) vs 5.61(2.99, 7.63)( z=-4.07, P<0.001) respectively. MTV of pulmonary nodules in 5D group was significantly lower than that in 3D group, which was 1.72(0.66, 2.74) cm 3vs 1.98(1.06, 4.63) cm 3 ( z=-7.13, P<0.001). Quantitative parameters of lower lung field and nodules with maximum diameters of >10 mm and ≤20 mm based on 5D scanning changed most significantly compared with those based on 3D scanning ( z values: from -5.23 to -2.48, all P<0.05). Conclusion:Q. Flex 5D PET significantly improves the quantitative accuracy of SUV and MTV of pulmonary nodules, and the improvement of image quality is substantial without increasing the radiation dose, which has clinical practical value.

Objective To investigate the risk factors of hip osteoarthritis(HOA)after hip arthroscopy in patients with femoro-acetabular impingement(FAI)syndrome,and to reduce and prevent HOA.Methods From September 2018 to Septem-ber 2020,106 patients with FAI underwent hip arthroscopy,including 40 males and 66 females,aged from 20 to 55 years old with an average age of(33.05±10.19)years old.The mechanism of injury included 51 cases for sports injury,36 for traffic ac-cidents,and 19 for blunt object injury.The duration of the disease ranged from 5 to 19 days with an average of(12.02±3.69)days.All patients were followed up for 18 months.Patients were divided into HOA group(23 cases)and non-HOA group(83 cases)according to the occurrence of HOA.Multivariate Logistic regression was used to analyze the risk factors of HOA after hip arthroscopy in FAI patients.Results By univariate analysis,aged from 50 to 70 years old,female,body mass index(BMI)＞30 kg·m-2,physical labor,cam type,postoperative infection,last follow-up hip degree of motion(range of motion,ROM)(flex-ion,abduction,adduction,internal rotation)and T?nnis grade 1 and above of the HOA group were higher than those of the non-HOA group(P＜0.05),and the relative appendicular skeletal muscle index(RASM)was lower than that of non-HOA group(P＜0.05).By multiple Logistic regression analysis,cam type,BMI＞30 kg·m-2,last follow-up hip internal rotation ROM and T?nnis grade 1 were risk factors for HOA after hip arthroscopy in FAI patients(P＜0.05).Conclusion FAI classification,body mass index,hip ROM and T?nnis grade are all related to HOA after hip arthroscopy in FAI patients.Follow-up and intervention should be strengthened in high-risk FAI patients to reduce the occurrence of HOA.

Objective To investigate the prognosis of patients with hepatitis B virus(HBV)-related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stage Ⅲ was an independent risk factor for postoperative RFS(HR=1.81,95%CI 1.04-3.14,P=0.037).Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence(HR=1.73,95%CI 1.07-2.77,P=0.024;HR=1.90,95%CI 1.12-3.24,P=0.017).There was no statistically significant difference in OS,RFS,and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+and Con-ICC patients(P<0.05),whereas HBsAg+/HBcAb+was a significant factor affecting postoperative OS(HR=0.32,95%CI 0.16-0.62,P=0.001),RFS(HR=0.32,95%CI 0.18-0.55,P<0.001),and early recurrence(HR=0.29,95%CI 0.15-0.54,P<0.001)in ICC patients.Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA-is better than that of Con-ICC patients.The prognosis of HBV-ICC patients with HBcAb+/HBsAg-is worse than that of HBV-ICC patients with HBcAb+/HBsAg+,but similar to Con-ICC patients.Therefore,the postoperative stratified management of HBV-ICC patients should be emphasized.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Objective:To explore the clinical efficacy of double traction-assisted reduction internal fixation and open reduction internal fixation in treating tibial plateau fractures.Methods:Data of patients with tibial plateau fracture admitted to West China Hospital of Sichuan University from January 2016 to December 2021 were retrospectively analyzed, and patients were divided into two groups according to treatment method: double traction-closed reduction internal fixation group (referred to as double traction group) and open reduction internal fixation group (referred to as open group). The double traction group included 21 patients, with 15 male and 6 female patients, with a mean age of 56.14±9.24 years (range, 45-72 years). Schatzker classification of fractures: 1 type I, 2 type II, 2 type III, 5 type IV, 6 type V, and 5 type VI. The open group included 29 patients, with 20 male and 9 female patients, with a mean age of 58.97±4.84 years (range, 47-70 years). Schatzker classification of fractures: 2 type I, 4 type II, 8 type III, 4 type IV, 5 type V, and 6 type VI. The surgical time, incision length, intraoperative blood loss, length of hospital stays, fracture healing time, postoperative time to full weight bearing, Rasmussen score, Hospital for Special Surgery (HSS) knee score, and complications were compared between the two groups of patients.Results:Both groups were followed up for 24 to 36 months, with an average of 30 months. There were significant differences in the operation time (92.61±6.22 min vs. 47.92±9.53 min), incision length (4.54±0.56 cm vs. 6.26±0.51 cm), and intraoperative blood loss (47.05±9.72 ml vs. 156.82±4.62 ml) between the group treated with closed reduction and double traction and the group treated with open reduction, with statistical significance ( t=18.83, 10.78, 53.24, P<0.001). There were also significant differences in the hospitalization time (5.35±0.41 d vs. 5.84±0.78 d), fracture healing time (3.72±0.74 months vs. 4.22±0.42 months), and time to full weight-bearing after surgery (11.29±1.10 weeks vs. 15.07±1.96 weeks) between the two groups, with statistical significance ( t=2.30, P=0.026; t=3.38, P<0.001; t=7.96, P<0.001). The HSS score at 6 months after surgery in the group treated with closed reduction and double traction was 81.61±2.32 points, which was higher than the score in the group treated with open reduction (77.66±4.01 points), with statistical significance ( t=4.07, P<0.001); at 12 months after surgery, the Rasmussen score in the group treated with closed reduction and double traction was 16.71±1.00 points, which was higher than the score in the group treated with open reduction (13.79±1.42 points), with statistical significance ( t=8.05, P<0.001). There was no fracture malunion or compartment syndrome occurred in both groups. The incidence of complications was 5% (1/21) in the group treated with closed reduction and double traction, and 10% (3/29) in the group treated with open reduction, with statistical significance (χ 2=0.52, P=0.473). Conclusion:The advantages of double traction-assisted reduction and internal fixation for tibial plateau fractures include minimal trauma, minimal bleeding, early mobilization, and shorter fracture healing time. It is a safe and reliable treatment method.

Objective:To analyze the various clinical presentations of anomalous aortic origin of a coronary artery (AAOCA) and determine factors related to myocardial ischemia.Methods:Children diagnosed with AAOCA on CT coronary angiography at Beijing Children′s Hospital, Capital Medical University from 1 January 2014 to 31 December 2022 were classified based on AAOCA type, age and high-risk anatomy.The clinical characteristics of the different AAOCA types and age groups were compared and the correlation between the severity of manifestations and high-risk anatomy was analyzed.Results:A total of 69 children with AAOCA[34 males and 35 females, aged (8.89±4.40) years] were included.Ten (14.5%) patients had anomalous origin of the left coronary artery (ALCA) from the right coronary artery sinus and 57 (82.6%) patients had anomalous origin of the right coronary artery (ARCA) from the left coronary artery sinus.In two (2.9%) patients, AAOCA did not arise from a coronary sinus.Nineteen (27.5%) patients were asymptomatic, including 35 (50.7%) cases presented with minor symptoms (chest tightness, chest pain, fatigue), 13 (18.8%) cases had severe symptoms (syncope), and two (2.9%) cases had atypical symptoms (paroxysmal crying). All children were successfully treated; no deaths were reported during follow-up.There were no significant differences in gender, clinical manifestations, positive myocardial injury markers, electrocardiogram and transthoracic echocardiography findings, and proportion of children with high-risk anatomy among the different AAOCA groups (ALCA, ARCA, and non-coronary sinus AAOCA). Divided by age, there were nine (13.1%) children in infant group, 11 (15.9%) in preschool group, and 49 (71.0%) in school age group.More infants were asymptomatic than preschoolers ( P<0.001). Forty-three (62.3%) patients had a high-risk anatomy: two patients with acute take-off angles, four patients with stenosis or slit-like orifices, and 37 patients with interarterial courses.The remaining patients (37.7%) had non-high-risk anatomies.Children with a high-risk anatomy had severe symptoms and were prone to cardiac syncope ( P<0.05). Logistic multivariate analysis suggested that high-risk anatomy was an independent risk factor for cardiogenic syncope( OR=9.026, 95% CI 1.071~76.084, P=0.043). Conclusion:There are no significant differences in the proportion of high-risk anatomy and clinical characteristics among children with different AAOCA types.Younger children are often misdiagnosed due to atypical or insignificant clinical symptoms.The severity of clinical symptoms is related to the high-risk anatomy.High-risk anatomy is an independent risk factor for cardiogenic syncope in children with AAOCA.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.