ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

ObjectiveTo investigate the effect of Danggui Shaoyaosan （DSS） on the morphology and function of mitochondria in rats model of Alzheimer's disease （AD） and its possible mechanism. MethodRats model of AD was established by injection of streptozocin （STZ） into bilateral ventricles of SD rats. The 40 rats were randomly divided into sham group， model group， low， medium and high dosages of Danggui Shaoyaosan （12，24，36 g·kg^-1·d^-1） groups，observed the morphological changes of mitochondria in hippocampus of rats by electron microscopy after 14 days of continuous gavage. In situ end labeling（TUNEL） staining used to detect apoptosis and immunofluorescencereactive used to observe the expression of reactive oxygen species （ROS） and peroxisome proliferators-activated receptor γ coactivator lalpha （PGC-1α），quantitative Real-time polymerase chain reaction（Real-time PCR）detected the mRNA expression of dynamin-related protein 1 （Drp1），mitochondrial fusion protein 2 （MFN2） ，cytochrome C oxidase subunit Ⅳ （COX Ⅳ） and PGC-1α. Western blot detected the protein expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK），phosphorylation（p）-AMPK，recombinant Sirtuin 1 （SIRT1） and PGC-1α. ResultCompared with the sham group，the results of model group showed that the damage of mitochondria in hippocampus was more obvious，accelerated the ROS production and apoptosis rate （P<0.01），decreased the mRNA level of MFN2，COX Ⅳ，PGC-1α，increased the mRNA level of Drp1，and descended the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.05，P<0.01）.Compared with the model group，the medium and high dose of DSS group notably improved the damage of mitochondria，reduced the production of ROS and apoptosis rate （P<0.01），promoted the mRNA expression of MFN2，COX Ⅳ，PGC-1α，inhibited the mRNA expression of Drp1，and up-regulated the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.01）. ResultDSS can significantly ameliorate the mitochondrial homeostasis imbalance in AD rats.

Objective:To characterize the knee gait maps of ordinary people, athletes and patients with anterior cruciate ligament (ACL) injury when walking on a level ground in order to identify potential kinematic indicators for early identification of ACL injury.Methods:From December 2021 to March 2022, 39 ordinary college students (normal group) and 39 college athletes (athlete group) were recruited in Southern Medical University, and 26 patients with ACL injury (patient group) were recruited at the Department of Orthopedics, Guangdong Provincial People＇s Hospital. The normal group consisted of 20 males and 19 females with a median age of 19 (18, 21) years; the athlete group consisted of 22 males and 17 females with a median age of 19 (18, 20) years; the patient group consisted of 23 males and 3 females with a median age of 20 (19, 20) years. A portable knee joint motion capture system was used to collect the knee gait maps of the subjects walking at a speed of 3 km/h on a treadmill. The knee varus and valgus angles, internal and external rotation angles, flexion and extension angles during the movement, and anteroposterior, medial-lateral superior-inferior displacements of the tibia relative to the femur were compared between the 3 groups.Results:There was no significant difference in the general data among the 3 groups except for gender, showing they were comparable ( P>0.05). There were significant differences in the varus and valgus angles during the whole gait cycle (1% to 100%), internal and external rotation angles during the weight-bearing response period (9% to 10%), flexion and extension angles during the stance phase and swing phase (1% to 27%, 29% to 100%), anteroposterior displacements during the weight-bearing reaction phase (1% to 3%) and at the end of the swing phase (96% to 98%), superior-inferior displacements at the middle support phase (15% to 19%), the end of the support phase (29% to 33%, 36% to 43%) and the swing phase (68% to 94%), and medial-lateral displacements at the middle stance phase and the middle swing phase (12% to 82%) among the 3 groups ( P<0.05). The maximum varus and valgus angles (-10.89°±4.55°, -12.20°±4.38°) of the subjects in the normal group and the athlete group were significantly greater than those in the patient group (-5.44°±3.72°) ( P<0.05). The medial-lateral displacement at the middle support phase [3.69 (0.13, 7.25) mm] of the subjects in the normal group was significantly larger than those in the athlete group and the patient group [-0.59 (-6.65, 5.24) mm, 0.96 (-1.54, 3.89) mm] ( P<0.05). Conclusions:The gait of college athletes is significantly different from that of ordinary college students and that of patients with ACL injury. Indexes like the varus and valgus angles and the medial-lateral displacement may be used as potential indictors for early identification of ACL injury.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

[摘 要] 目的：探讨circFBXL5通过靶向miR-515-5p影响膀胱癌T24细胞的增殖、迁移、侵袭及其分子机制。方法： 收集2020年4月至2020年6月间在苏州市中西医结合医院手术切除的41例膀胱癌组织及其癌旁组织，采用qPCR法检测circFBXL5、miR-515-5p的表达；双荧光素酶报告实验验证circFBXL5与miR-515-5p之间的靶向关系，体外培养人膀胱癌T24细胞，实验分为si-NC组、si-circFBXL5组、anti-miR-NC+si-circFBXL5组和si-circFBXL5+anti-miR-515-5p组；MTT法、细胞克隆形成实验、FCM、Transwell实验和WB法分别检测转染后T24细胞的增殖、细胞克隆形成、迁移、侵袭和凋亡及BAX、Bcl-2蛋白水平。结果：膀胱癌组织中circFBXL5呈高表达，miR-515-5p呈低表达（均P<0.05）；circFBXL5靶向且负向调控miR-515-5p的表达；敲减circFBXL5后T24细胞的增殖抑制率、凋亡率和BAX蛋白水平均显著增高（均P<0.05），细胞克隆形成数和迁移、侵袭细胞数均显著减少（均P<0.05），Bcl-2蛋白水平显著降低（P<0.05）；同时敲减circFBXL5和miR-515-5p可部分逆转敲减circFBXL5对T24细胞增殖的抑制作用。结论：circFBXL5通过调控miR-515-5p表达影响膀胱癌T24细胞的增殖、迁移、侵袭，circFBXL5和miR-515-5p可能膀胱癌治疗的潜在分子靶标。

Objective To investigate the effects of matrine on proliferation and apoptosis of human Tenon capsule fibroblasts (HTFs) in.vitro.Methods After treated with 0,0.3,0.6 and 0.9 g/L matrine in vitro,cell counting kit-8 (CCK-8) method was used to assay the proliferation of HTFs at 24,48 and 72 hours,Western blot and PCR were performed to evaluate the expression of apoptosis-associated factor caspase-3 on both protein and RNA levels.Results The activity of human Tenon capsule fibroblast at 48 hours and 72 hours after treated with 0.3,0.6,0.9 g/L matrine was significantly inhibited when compared with the 0 g/L matrine group,and the inhibitory effect was dose-dependent and time-dependent (F ion =1 019.51,P =0.00;Ftime =5 848.66,P =0.00;Fi ion =147.45,P=0.00).After treated with 0,0.3,0.6 and 0.9 g/L matrine,the early apoptosis rate of HTFs was (2.68±0.30)％,(5.08±0.47)％,(6.97±0.69)％ and (10.30±1.20)％,the grey value ofcaspase-3 protein was 1.00±0.13,1.90±0.19,2.50±0.30 and 2.67±0.30,the relative expression of caspase-3 mRNA was 0.98 ±0.12,2.01 ±0.34,6.15 ± 0.60 and 11.40 ± 1.12,respectively,with significant differences among them (F =55.74,66.01,154.50;all at P＜0.01),the early apoptosis rate of HTFs,the grey value of caspase-3 protein and the relative expression of caspase-3 mRNA were all increased significantly as the concentration of matrine increased,with significant differences between any two groups (all at P＜0.05).Conclusions Matrine can inhibit the proliferation of HTFs and induce the apoptosis of HTFs in a time-and dose-depended manner.

Objective To explore the clinical value of 3.0T nuclear magnetic resonance susceptibility weighted imaging in diagnosis of neonatal hypoxic ischemic encephalopathy,thus to provide guidance for the clinical.Methods From December 10,2015 to December 10,2017,100 cases of neonatal hypoxic ischemic encephalopathy (observation group) and 100 cases of normal newborns in Lishui People's Hospital during the same period accepted health examination (control group) were selected in the research.All the cases received 3.0T magnetic resonance susceptibility weighted imaging,the diagnostic value of 3.0T MR susceptibility weighted imaging was observed.Results The ADC value of the observation group[(0.00 1 13 ± 0.000 01)mm2/s] was significantly lower than that in the control group[(0.001 98 ±0.000 02)mm2/s] (P ＜0.05).The neonatal ADC value of the mild group[(0.001 21 ± 0.000 01)mm2/s] was significantly higher than that in the moderate group[(0.001 12 ± 0.000 02)mm2/s] and the severe group[(0.001 02 ± 0.000 03)mm2/s] (P ＜ 0.05).ADC value was positively correlated with neonatal hypoxic ischemic encephalopathy,namely,the lower the ADC value,the more serious the neonatal hypoxic ischemic encephalopathy.The fractional anisotropy value and relative anisotropy value of newborn babies in the observation group were significantly higher than those in the control group (all P ＜ 0.05).Conclusion For neonatal hypoxic ischemic encephalopathy patients,3.0T nuclear magnetic resonance susceptibility weighted imaging in the diagnosis is feasible,it can help the clinician to analyze the disease,and has positive significance to carry out the treatment.

Objective: To study the mechanism of action of Danggui Shaoyao San (DSS) in the treatment of Alzheimer'sdisease (AD) from a systematic network level using network pharmacology. Methods: The active ingredients of DSS intreating AD was screened from the Traditional Chinese Medicine System Pharmacology Database (TCSMP), and thedrugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichmentanalysis were used for bioinformatics analysis. Results: 51 kinds of DSS active ingredients were screened by networkpharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathwaywas closely related to the reduction of Aβ aggregation and inhibition of tau hyperphosphorylation and biological processessuch as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in theliver, heart, and brain. Conclusion: DSS active compounds interact with multiple targets in multiple ways in a synergisticmanner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancingmetabolism and immune system.

Objective To explore the compliance , success rate of puncture of pediatric intravenous infusion and satisfaction of family .Methods One thousand and eight hundred children with pediatric intravenous infusion from June 2012 to July 2012 were chosen and divided into the control group and the intervention group according to the random number table , each with 900 cases.The control group received the routine nursing , and the observation group received the nursing work of improving pediatric intravenous infusion and the improved the nursing intervention technique .The compliance , puncture success rate and satisfaction of pediatric intravenous infusion were compared between the two groups .Results The rate of compliance was 90.00%in the observation group, and was significantly higher than 62.22% in the control group, and the difference was statistically significant (χ2 =190.99, P<0.05).The success rate of puncture was 93.33% in the observation group , and was significantly higher than 67.78% in the control group, and the difference was statistically significant (χ2 =187.54, P<0.05).The satisfaction of family was 98.89%in the observation group, and was significantly higher than 67.78% in the control group, and the difference was statistically significant (χ2 =194.61, P<0.05).Conclusions The active nursing intervention can effectively improve the compliance , success rate of puncture of pediatric intravenous infusion and satisfaction of family .