Objective To explore the effects of home-based exercise rehabilitation on cardiac structure, valvular function, and exercise capacity in patients with severe aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). Methods 49 patients with severe AS who underwent TAVR at Zhongshan Hospital, Fudan University, from January 2024 to February 2025 were enrolled. They were divided into an exercise group (n＝25) or a non-exercise group (n＝24) based on participating or not in home-based rehabilitation after TAVR. The exercise group received 12 weeks of home-based exercise training (aerobic exercise plus resistance training every week); the non-exercise group received routine care. Transthoracic echocardiography (TTE) was used to assess cardiac structural parameters before discharge (T0) and after 12 weeks of exercise (T1). Functional outcomes including the 6-minute walk test (6MWT), Duke Activity Status Index (DASI), and Short Physical Performance Battery (SPPB) were compared between the two groups. A linear mixed-effects model was used to analyze the effect of home-based rehabilitation on echocardiographic parameters. Patients were stratified by baseline 6MWT (＜240 m as low-function subgroup, ≥240 m as high-function subgroup) to compare exercise-related outcomes between subgroups. Results At T1, the exercise group had a longer 6MWT distance than the non-exercise group (P＝0.012). The linear mixed-effects model showed that after 12 weeks of exercise, the left ventricular end-diastolic diameter (LVEDD) decreased in the exercise group but slightly increased in the non-exercise group, with a significant difference in changes over time between the two groups (P_interaction＝0.030). The exercise group also showed greater improvement in effective orifice area index (P_interaction＝0.028) and effective orifice area (P_interaction＝0.042) than the non-exercise group. Subgroup analysis revealed that in the low-function subgroup, the exercise group showed greater improvement in the 6MWT (P_interaction＝0.035) and the effective orifice area index (P_interaction＝0.046) compared to the non-exercise group; in the high-function subgroup, the exercise group showed greater improvement only in LVEDD compared to the non-exercise group (P_interaction＝0.046). Conclusions Home-based exercise rehabilitation improves exercise capacity, optimizes left ventricular remodeling, and enhances valvular function in patients with severe AS after TAVR, with greater benefits observed in patients with lower baseline 6MWT.

Objective:To investigate the effects of cryopreservation on the results of nucleic acid detection and culture for Bordetella pertussis in residual culture-positive nasopharyngeal swab specimens, aiming to provide the basis for specimens preservation, transport and centralized detection. Methods:In this cross-sectional study, the residual nasopharyngeal swab specimens which were culture-positive for Bordetella pertussis were collected in the Children′s Hospital, Zhejiang University School of Medicine from January to August in 2022. The specimens were placed at ?20 ℃ and?70 ℃ by random number table method, respectively. Re-detection by culture and PCR for Bordetella pertussis were conducted after these specimens were frozen for 114.3±31.9 days. The specimens were grouped according to the cryopreservation temperature and the semi-quantitative results by bacteria culture. The positive rates of the results were compared with χ 2 test between groups. Results:A total of 244 nasopharyngeal swabs specimens were included and 166 were culture-positive after cryopreservation, the positive rate decreased by 32%. Among them, the positive rate of re-culture of specimens containing low bacterial loads decreased by 56% after cryopreservation. However, there was no significant difference in the positive rate of culture between the specimens freezing at ?70 ℃ and ?20 ℃ (χ2=1.65, P=0.20). The positive rate of DNA detection decreased by 10.6% (88.9% vs 78.3%) after cryopreservation. The positive rate of the ?70 ℃ storage group was significantly higher than that of the ?20 ℃ group (χ2=5.11, P=0.02). The positive rate of the re-detection of DNA of nasopharyngeal swabs with low bacteria loads in ?70 ℃ storage group was significantly higher than that of the ?20 ℃ group (χ2=4.86, P=0.03). While for the samples with a bacterial load of "+" or more, there was no significant difference in the positive rate of DNA detection after cryopreservation between the ?20 ℃ and -70 ℃ (χ2=1.25, P=0.26) groups. The positive rate of nasopharyngeal swab culture after cryopreservation was 68.0% (166/244), which was significantly lower than the DNA detection positive rate of 78.3% (191/244, χ2=6.52, P=0.01). Conclusions:Cryopreservation nasopharyngeal swabs specimens could be used for Bordetella pertussis culture and nucleic acid detection. The bacterial load in the original sample affects the positive detection rate after cryopreservation. Cryopreservation has less influence on the positive rate of the result of nucleic acid detection when compared with culture. Preservation at ?70 ℃ is superior to ?20 ℃.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective : To analyze the epidemiological characteristics and spatial clustering of brucellosis in Shanxi Province from 2019 to 2023, so as to provide a reference for formulating prevention and control measures of brucellosis. Methods: The case data of brucellosis in Shanxi Province from 2019 to 2023 were collected through the Infectious Disease Surveillance System of the Chinese Disease Prevention and Control Information System. The seasonal distribution, population distribution, and region distribution of brucellosis cases were described. Spatial autocorrelation analysis was applied to explore the spatial clustering characteristics of brucellosis. Results: A total of 21 241 human brucellosis cases were reported in Shanxi Province from 2019 to 2023, with an average annual reported incidence of 11.87/100 000, showing an upward trend (P<0.05). The peak incidence period was from March to August, with 14 163 cases reported cumulatively, accounting for 66.68% of the total. There were 16 336 male cases and 4 905 female cases, with a male-to-female ratio of 3.33:1. The high-incidence age group was 40-<70 years, with 15 675 cases accounting for 73.80%. The majority of patients were farmers, with 17 926 cases accounting for 84.39%. Spatial autocorrelation analysis showed that there was spatial clustering in the incidence of brucellosis from 2019 to 2023 (all Moran's I>0, P<0.05). The high-high clustering areas were mainly Datong City, and Shuozhou City in northern Shanxi, and Linfen City in the southern Shanxi. The low-low clustering areas were mainly Taiyuan City and Yangquan City in central Shanxi, and Changzhi City and Jincheng City in southeastern Shanxi. Conclusions From 2019 to 2023, the reported incidence of brucellosis in Shanxi Province showed an upward trend. The incidence peaked from March to August, and males, middle-aged and elderly people and farmers were the high-risk groups. There was spatial clustering and the high-high clustering areas gradually expanded from northern Shanxi to southern Shanxi.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective:To investigate the effects of cryopreservation on the results of nucleic acid detection and culture for Bordetella pertussis in residual culture-positive nasopharyngeal swab specimens, aiming to provide the basis for specimens preservation, transport and centralized detection. Methods:In this cross-sectional study, the residual nasopharyngeal swab specimens which were culture-positive for Bordetella pertussis were collected in the Children′s Hospital, Zhejiang University School of Medicine from January to August in 2022. The specimens were placed at ?20 ℃ and?70 ℃ by random number table method, respectively. Re-detection by culture and PCR for Bordetella pertussis were conducted after these specimens were frozen for 114.3±31.9 days. The specimens were grouped according to the cryopreservation temperature and the semi-quantitative results by bacteria culture. The positive rates of the results were compared with χ 2 test between groups. Results:A total of 244 nasopharyngeal swabs specimens were included and 166 were culture-positive after cryopreservation, the positive rate decreased by 32%. Among them, the positive rate of re-culture of specimens containing low bacterial loads decreased by 56% after cryopreservation. However, there was no significant difference in the positive rate of culture between the specimens freezing at ?70 ℃ and ?20 ℃ (χ2=1.65, P=0.20). The positive rate of DNA detection decreased by 10.6% (88.9% vs 78.3%) after cryopreservation. The positive rate of the ?70 ℃ storage group was significantly higher than that of the ?20 ℃ group (χ2=5.11, P=0.02). The positive rate of the re-detection of DNA of nasopharyngeal swabs with low bacteria loads in ?70 ℃ storage group was significantly higher than that of the ?20 ℃ group (χ2=4.86, P=0.03). While for the samples with a bacterial load of "+" or more, there was no significant difference in the positive rate of DNA detection after cryopreservation between the ?20 ℃ and -70 ℃ (χ2=1.25, P=0.26) groups. The positive rate of nasopharyngeal swab culture after cryopreservation was 68.0% (166/244), which was significantly lower than the DNA detection positive rate of 78.3% (191/244, χ2=6.52, P=0.01). Conclusions:Cryopreservation nasopharyngeal swabs specimens could be used for Bordetella pertussis culture and nucleic acid detection. The bacterial load in the original sample affects the positive detection rate after cryopreservation. Cryopreservation has less influence on the positive rate of the result of nucleic acid detection when compared with culture. Preservation at ?70 ℃ is superior to ?20 ℃.

Objective To investigate the risk factors for postoperative gastrointestinal bleeding (GIB) in patients with type A aortic dissection, and further discuss its prevention and treatment. Methods The clinical data of patients with type A aortic dissection admitted to the Department of Cardiovascular Surgery of the First Affiliated Hospital of Naval Medical University from 2017 to 2021 were retrospectively analyzed. Patients were divided into a GIB group and a non-GIB group based on the presence of GIB after surgery. The variables with statistical differences between two groups in univariate analysis were included into a multivariate logistic regression model to analyze the risk factors for postoperative GIB in patients with type A aortic dissection. Results There were 18 patients in the GIB group including 12 males and 6 females, aged 60.11±10.63 years, while 511 patients in the non-GIB group including 384 males and 127 females, aged 49.81±12.88 years. In the univariate analysis, there were statistical differences in age, preoperative percutaneous arterial oxygen saturation (SpO2)<95%, intraoperative circulatory arrest time, postoperative low cardiac output syndrome, ventilator withdrawal time>72 hours, postoperative FiO2≥50%, continuous renal replacement therapy (CRRT) rate, extracorporeal membrane oxygenation (ECMO) rate, infection rate, length of hospital stay and ICU stay, and in-hospital mortality (all P<0.05). In the multivariate logistic regression analysis, preoperative SpO2<95% (OR=10.845, 95%CI 2.038-57.703), ventilator withdrawal time>72 hours (OR=0.004, 95%CI 0.001-0.016), CRRT (OR=6.822, 95%CI 1.778-26.171) were risk factors for postoperative GIB in patients (P≤0.005). In the intra-group analysis of GIB, non-occlusive mesenteric ischemia (NOMI) accounted for 38.9% (7/18) and was the main disease type for postoperative GIB in patients with type A aortic dissection. Conclusion In addition to patients with entrapment involving the superior mesenteric artery who are prone to postoperative GIB, preoperative SpO2<95%, ventilator withdrawal time>72 hours, and CRRT are independent risk factors for postoperative GIB in patients with type A aortic dissection. NOMI is a major disease category for GIB, and timely diagnosis and aggressive treatment are effective ways to reduce mortality. Awareness of its risk factors and treatment are also ways to reduce its incidence.

It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.
Blood-Brain Barrier ; Algorithms ; Area Under Curve ; Databases, Factual ; Permeability

Objective To study stress relaxation behaviors of cartilage scaffolds under different degradation cycles by using finite element analysis combined with theoretical models. Methods Based on the established degradation theoretical model, the elastic modulus of the scaffold was calculated under different degradation cycles. The finite element model of cartilage scaffolds was established and stress relaxation simulation was performed to analyze the variation of scaffold relaxation stress with time. The stress relaxation constitutive model was established to predict mechanical properties of the scaffold. Results The elastic modulus of cartilage scaffolds at 14 th, 28th, 42nd, 56th day after degradation was 32. 35, 31. 12, 29. 91, 28. 74 kPa, respectively. The upper layer for cartilage scaffolds was the largest. The overall relaxation stress of the scaffold decreased rapidly with time and then tended to be stable. At 8th week after degradation, the stress which the scaffold couldwithstand was still within the physiological load range of the cartilage. The predicted results of the stress relaxation constitutive model were in good agreement with the finite element simulation results. Conclusions The elastic modulus of the scaffold gradually decreases with the increase of degradation time. The longer the degradation period is, the less stress the scaffold can withstand. At the same degradation period, the larger the applied compressive strain, the larger the stress on the scaffold. Both the finite element simulation and stress relaxation constitutive model can effectively predict stress variations of cartilage scaffolds under degradation

Different degrees of visual function impairment is the main reason for first visit of children with optic pathway glioma; it seriously affects the quality of life of children. Early diagnosis, timely treatment, maximum preservation or restoration of the children's vision function, and improvement of quality of life of children are major challenges. This article reviews the recent advance in visual function assessments for children with optic pathway glioma, aiming to provide some references for early clinical objective assessment of visual function impairment and clear diagnosis.