This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Objective:To assess the association between diabetes mellitus and the risk of sudden cardiac death (SCD), and to identify potential contributing factors.Methods:This meta-analysis was an updated version of the original study Diabetes mellitus and the risk of sudden cardiac death： a systematic review and meta-analysis of prospective studies. The original review included all eligible case-control and cohort studies published in PubMed and Embase up to 2017 that investigated the association between diabetes and SCD risk. In this updated study, newly published studies were added, including those available in PubMed, Embase, China National Knowledge Infrastructure (CNKI), and WANFANG MED ONLINE up to December 3, 2023. Search terms included "diabetes""glucose""sudden cardiac death" "cardiac arrest" and their Chinese equivalent. The primary outcome was the risk of SCD, while factors such as country, ethnicity, skin color, follow-up duration, left ventricular ejection fraction (LVEF), baseline comorbidities, and other relevant variables were analyzed as potential influencing factors. Relative risk ( RR) was used as the summary measure. A random-effects model was used when significant heterogeneity was detected, otherwise a fixed-effects model was used. Cochran′s Q test was used for subgroup analysis to assess the influence of factors such as region, baseline diseases, LVEF, and ethnicity (based on skin color) on the outcomes. Results:A total of 32 cohort/case-control studies with a combined sample size of 3 252 954 individuals were included. The meta-analysis showed that the risk of SCD in patients with diabetes was double that of non-diabetics ( RR=2.00, 95% CI: 1.83-2.19, P<0.001). In Asian populations, the risk of SCD in diabetic patients was 1.78 times that of non-diabetic individuals ( RR=1.78, 95% CI: 1.51-2.10), 2.05 times that of in European populations ( RR=2.05, 95% CI: 1.79-2.34), and 2.12 times that of in American populations ( RR=2.12, 95% CI: 1.82-2.47), with no statistically significant heterogeneity between regions ( P=0.287). Among individuals without other baseline comorbidities, the risk of SCD was 2.12 times higher in diabetic patients than in those without diabetes ( RR=2.12, 95% CI: 1.89-2.38). In patients with baseline coronary heart disease, the risk was 1.75 times that of non-diabetics ( RR=1.75, 95% CI: 1.45-2.11). In those with baseline heart failure, the risk was 1.92 times that of non-diabetics ( RR=1.92, 95% CI: 1.51-2.43). In patients with baseline atrial fibrillation, the risk was 4.00 times that of non-diabetic individuals ( RR=4.00, 95% CI: 1.38-11.56). In patients undergoing hemodialysis due to renal failure, the risk was 1.76 times that of non-diabetic individuals ( RR=1.76, 95% CI: 1.25-2.48), with no statistically significant heterogeneity between groups ( P=0.262). In cardiac patients with LVEF>50%, the risk of SCD in diabetic patients was 2.08 times that of non-diabetic individuals ( RR=2.08, 95% CI: 1.57-2.75), and in those with LVEF<50%, the risk was 1.69 times that of non-diabetic individuals ( RR=1.69, 95% CI: 1.30-2.18), with no statistically significant heterogeneity between groups ( P=0.277). In yellow-skinned populations, the risk of SCD in diabetic patients was 1.80 times that of healthy individuals ( RR=1.80, 95% CI: 1.73-1.87), and in white-skinned populations, it was 2.18 times that of healthy individuals ( RR=2.18, 95% CI: 1.88-2.54), with statistically significant heterogeneity between groups ( P=0.014). Conclusions:Diabetes mellitus significantly increased the risk of SCD, and this effect may be more pronounced in white-skinned populations, while region, baseline comorbidities, and LVEF had no further effect.

Objective:To detect the factors related to hemocytopenia and interstitial lung disease (ILD) secondary to primary Sj?gren's syndrome (pSS) in in-patients.Methods:Clinical characteristics of patients with pSS hospitalized in China-Japan Friendship Hospital from March 2014 to October 2020 were retrospectively analyzed. Patients were divided into different groups according to hemocytopenia and ILD. Chi-square test and Mann-Whitney U test were used to compare data in subgroups, and logistic regression were used to detect factors related to hemocytopenia and ILD secondary to pSS. Results:Five hundred and seventy-one inpatients with pSS were included in this study and the female: male ratio was 8∶1. Two hundred and seventy five of included patients had hemocytopenia (48.2%) and 180 patients had ILD (31.5%). Compared with patients without hemocytopenia, patients with hemocytopenia had higher ratio in low C3 [ OR=2.326, 95% CI(1.483, 3.650), P<0.01] and elevation of erythrocyte sedimentation rate (ESR) [ OR=1.912, 95% CI(1.233, 2.964), PP<0.01) . Compared with patients without ILD, patients with ILD showed higher ratio in male[ OR=2.509, 95% CI(1.269, 4.959), P<0.01) and fatigue [ OR=5.190, 95% CI(5.190, 13.931), P<0.01) , lower positive rate of anti-SSA antibody [ OR=0.392, 95% CI(0.230, 0.668), P<0.01) and anti-CENPB [ OR=0.337, 95% CI(0.145, 0.782), P<0.01] antibodies, and lower ratio in low C3[ OR=0.332, 95% CI(0.189, 0.582), P<0.01]. Conclusion:Low C3 and high ESR may be risk factors for developing hemocytopenia in patients with pSS. Men with pSS may be susceptible to ILD, while pSS patients with ILD may have lower ratio in positive anti-SSA antibody, positive anti-CENPB antibody and low C3. All of these findings are yet to be validated by future prospective cohort studies.

Objective:To compare the clinical characteristics of patients with primary Sj?gren's syndrome (pSS) by gender and age of disease onset.Methods:Clinical data of hospitalized patients with pSS in China-Japan Friendship Hospital from March 2014 to August 2020 were retrospectively analyzed. Patients were divided into different groups according to their genders and ages of disease onset (young grong <30 years, middle-age group 30-59 years, elderly group ≥60 years). Chi-square test and Mann-Whitney U test were used to compare data in subgroups, and logistic regression was performed to analyze data after control covariates. Results:Five hundred and forty one patients with pSS were included in this study and 481 of them were women (88.9%) Women had higher ratio than men in dry mouth [ OR (95% CI) =2.172(1.091, 4.323), P=0.027], dry eyes [ OR(95% CI)=2.179(1.062, 4.469), P=0.034], leukocytopenia [ OR(95% CI)=3.789(1.150, 12.482), P=0.029], ANA titer≥1∶160 [ OR(95% CI)=2.233(1.279, 3.898), P<0.01], positive anti-SSA [ OR(95% CI)=2.919(1.644, 5.183), P<0.01], positive anti-Ro52 [ OR(95% CI)=3.018(1.685, 5.405), P<0.01], while men had higher ratio than women in parotid enlargement [ OR(95% CI)=2.345(1.281, 4.325), P<0.01], and interstitial lung disease (ILD) [ OR(95% CI)=2.593(1.460, 4.606), P<0.01]. Compared with patients in young group, patients in middles age group had higher ratio in dental caries [ OR(95% CI)=5.940(2.230, 15.819), P<0.01], xero-phthalmia [ OR(95% CI)=2.904(1.313, 6.425), P<0.01], arthralgia [ OR(95% CI)=1.959(1.039, 3.694), P=0.038] and ILD [ OR(95% CI)=2.247(1.018, 4.959), P=0.045], but lower ratio in renal involvement [ OR(95% CI)=0.402(0.211, 0.766), P<0.01]; patients in elderly group had higher ratio in dental caries [ OR(95% CI)=7.437(2.441, 22.656), P<0.01], xerophthalmia [ OR(95% CI)=6.084(1.901, 19.468), P<0.01], and ILD [ OR(95% CI)=4.857(2.029,11.627), P<0.01]. Compared with patients in elderly group, patients in young group had higher positive rate in anti-SSA [ OR(95% CI)=2.836(1.245, 6.459), P=0.013], anti-SSB [ OR(95% CI)=3.075(1.413, 6.690), P<0.01], rheumatoid factors (RF) [ OR(95% CI)=3.323(1.620, 6.817), P<0.01] and elevated immunoglobulin G (IgG)[ OR(95% CI)=3.567(1.747, 7.284), P<0.01]; patients in middle age group had higher positive rate in anti-SSB[ OR(95% CI)=2.330(1.315, 4.130), P<0.01], RF [ OR(95% CI)=2.026(1.279, 3.208), P<0.01], and elevated IgG [ OR(95% CI)=2.077(1.297, 3.327), P<0.01]. Conclusion:Women with pSS present a higher ratio in dry mouth, dry eyes, leukocytopenia and positive autoantibodies than men, while parotid enlargement and ILD are more common in men than women. Young patients are prone to renal involvement, middle-aged patients are prone to arthralgia, while elderly patients are prone to dental caries and xerophthalmia. With the growth of age, the positive rates of autoantibodies and elevated IgG are decreased gradually in patients with pSS, but the ratios of dental caries, xerophthalmia and ILD is increased gradually.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

OBJECTIVETo analyze the clinical features and genetic cause for a family affected with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

METHODSClinical manifestations, neuroimaging, and genetic analysis were performed.

RESULTSThe main clinical features have included stroke, emotional disturbance and history of migraine without progressive memory impairment. A positive family history was confirmed. Cranial MRI has revealed multi-infarct lesions and white matter hyperintensity involving bilateral basal ganglia, subcortex and brain stem. All such features were in keeping with the diagnosis of CADASIL. A rare 2182C>T mutation in exon 14 of the NOTCH3 gene was identified in all available cases.

CONCLUSIONBoth clinical and molecular features suggested that the family has been affected with CADASIL.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Migraine Disorders ; genetics ; Receptor, Notch3 ; Receptors, Notch ; genetics

Objective To study the technique and clinical effect of endoscopic surgery using high frequency electrotome with suction device for nasopharyngeal angiofibroma. Methods In this study, we retrospective analyzed the clinical data of 10 patients treated between January 2009 and December 2015. All these patients were treated by endoscopic surgery using high frequency electrotome with suction device. The average blood loss during surgery, tumor residual, recurrent tumor and duration of recovery were evaluated. Results The tumor was completely removed in all 10 patients. The average blood loss was 465 ml, there was no postoperative complication, all patients had no residual tumor, and there was no recurrent tumor over a follow-up of 6~18 months. Conclusion Though it was not preoperative transcatheter arterial embolization, the endoscopic surgery using high frequency electrotome with suction device can be used to treated nasopharyngeal angiofibroma which either limited to nasopharyngeal cavities and paranasal sinus with intraoperative blood pressure control.