ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

OBJECTIVE To compare the efficacy and safety of new oral anticoagulants （NOACs） and warfarin in the treatment of left ventricular thrombus （LVT）， and to provide evidenced-based reference for rational drug use in clinic. METHODS Retrieved from PubMed， Cochrane Library， Embase， Ovid Medline， CNKI， Wanfang and VIP during the inceptions to March 2022， after screening the literature and extracting data， the quality of randomized controlled trials （RCTs） was evaluated by using bias risk evaluation tool recommended by Cochrane systematic evaluator manual. Newcastle Ottawa Scale was used to evaluate the quality of cohort studies， and RevMan 5.3 software was used for meta-analysis and bias risk analysis. RESULTS A total of 13 studies were included in the analysis， including 2 RCTs， 11 cohort studies and 2 261 patients； results of meta-analysis showed that there was no statistical significance in the incidence of complete LVT resolution [OR＝1.05， 95%CI（0.81，1.37）， P＝0.71]， the incidence of stroke/systemic embolism [OR＝0.89， 95%CI（0.67，1.18）， P＝0.42]， the incidence of massive haemorrhage [OR＝ 0.61， 95%CI（0.19，1.97）， P＝0.41]， the incidence of rehospitalization [OR＝0.84， 95%CI（0.49，1.46）， P＝0.54] or all-cause mortality [OR＝0.93， 95%CI（0.56，1.56）， P＝0.79] between 2 groups. The incidence of any bleeding event in trial group was significantly lower than that control group[OR＝ 025-80863493。0.65， 95%CI（0.45，0.93）， P＝0.02]. Subgroup analysis showed that complete LVT resolution of patients with follow-up ≤6 months in trial group was significantly higher than control group， and the incidence of any bleeding event was significantly lower in patients with follow-up ＞6 months and in the European region than control group （P＜0.05）. There was no statistically significant difference in the rate of complete LVT resolution in patients with follow-up＞6 months， the incidence of any bleeding event in patients from Asia and America， or the incidence of any bleeding event in the two groups included in the RCT or the cohort study （P＞0.05）. The publication bias analysis showed that publication bias was less likely in the rate of complete LVT resolution but more likely in the incidence of any bleeding event. CONCLUSIONS NOACs can eliminate thrombus faster in the early stage， but with the prolongation of anticoagulation time， the efficacy of NOACs is comparable to warfarin， and the safety of NOACs in any bleeding event is better than warfarin.

The new type of coronavirus pneumonia referred to as coronavirus disease 2019 (COVID-19), became pandemic globally, causing tens of millions of infections. The establishment of a sound prevention and control system is particularly important for disease prevention and control. In the process of admission and treatment of COVID-19 patients, we have established an effective rapid prevention and control system for special infections in the hospital. Through the establishment of a hospital-level emergency response and first aid training system, the closed-loop communication between hospitals, departments and medical care is quick to respond. We categorize treatment according to patients’ condition, provide rapid feedback and return, implement the specific responsibility system for special personnel, improve the rapid prevention and control system for special infections, and apply it to the prevention and control of the epidemic of COVID-19 patients in the region, and achieve the effectiveness of the anti-epidemic through comprehensive management measures. The control has achieved zero infection among medical staff and within the hospital, ensuring that the hospital can quickly resume daily work at the end of the epidemic, and has certain promotion and demonstration value.

ObjectiveTo study the change of the pulmonary surfactant protein C, D (SP-C, SP-D) and apoptosis of alveolar epithelium cells in neonatal rats with hyperoxia-induced lung injury.MethodsThe neonatal rats born within 24 hours were divided into the air group (n=50) and the hyperoxia group (n=50). The lung tissue was collected on the ifrst, third, seventh, tenth, fourteenth day after the hyperoxia exposure. The pathological changes were observed by HE staining. The apoptosis rate of lung epithelial cells was detected by TUNEL (terminal deoxyn ucleotidyl transfer-mediated end labeling). The content of SP-C and SP-D in broncho alveolar lavage lfuid (BALF) was detected by enzyme-linked immunosorbent assay.ResultsIn the air group, as age increased, the alveolar were gradually more completely formed with the regular shape and uniform size. Mean-while, in the hyperoxia group, as age increased, the number of alveolar was reduced, the small blood vessels expanded, the alve-olar hemorrhage was increased, the interstitial cells were increased and the lung tissue was swelling. The levels of SP-C, SP-D decreased with the increase of age in the air group. The level of SP-C in hyperoxia group was lower than that in the air group on the ifrst day. It was higher than that in the air group on the third day, peaked on the seventh day, and then it began to decline on the tenth day and decreased more obviously on the fourteenth day. The level of SP-D in hyperoxia group was not signiifcantly dif-ferent from that in the air group on the ifrst day, was higher than that in the air group on the third day and peaked on the seventh day. Then it began to decline on the tenth day and decreased more on the fourteenth day. ConclusionsLong-term inhalation of high concentrations of oxygen inhibits alveolar development. With the prolonged time of oxygen inhalation, the apoptosis of lung epithelial cells is increased, and the level of SP-C and SP-D in BALF was increased ifrst and then decreased.

Objective To investigate the association between body mass index (BMI) and exercise capacity in patients with chronic systolic heart failure.Methods The elderly patients with chronic systolic heart failure were consecutively recruited from 2008 to 2011 in cardiovascular clinic of Zhejiang Hospital.All the participants underwent height and weight measurements and BMI was calculated with these two parameters.Cardiopulmonary exercise test were performed to achieve peak oxygen uptake (PVO2),oxygen uptake to body mass ratio (PKVO2),oxygen uptake to heart ratio (VO2/HR) and ventilation/carbon dioxide production (VO2/VCO2).Results A total of the 273 patients with chronic systolic heart failure included 6 underweight patients (BMI ＜ 18.5 kg/m2),113 normal weight patients (BMI 18.5-＜ 24.0 kg/m2),116 overweight patients (BMI 24.0-＜ 28.0 kg/m2),and 38 obese patients (BMI ≥ 28 kg/m2).In both NYHA Ⅱ and Ⅲ/Ⅳ patients,unadjusted correlation analyses showed that BMI was positively related to PVO2 and VO2/HR,and was inversely related to PKVO2 and VE/VCO2 (P ＜ 0.05),respectively.Multiple stepwise regression analyses showed age,sex,BMI (P ＜ 0.05) and left ventricular ejection fraction (LVEF) were independent determinants of PKVO2,and age and BMI (P ＜ 0.05) were independent determinants of VE/VCO2.Conclusions BMI is significantly associated with exercise capacity in patients with chronic systolic heart failure,and also independent determinant for the PKVO2 and VE/VCO2,respectively.

Tumor cells exhibit two main different migration strategies when invading in 3D environment, i. e. mesenchymal migration and amoeboid migration. This review summarizes the internal reasons and characteristics on various modes of migration adaptation to the microenvironment, and the molecular mechanisms in particular environment where they are mutually interchangeable. A study of the mechanisms that may possibly trigger mesenchymal-amoeboid transition/amoeboid-mesenchymal transition help us to understand the change and the plasticity in the migration strategies of tumor cells. These are important for the development of a cancer treatment, which would efficiently suppress tumor cell invasiveness.
Cell Movement ; physiology ; Extracellular Matrix ; pathology ; Humans ; Integrins ; physiology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; physiopathology

This research project was designed to explore the molecular basis of the loss of contact inhibition in hepatoma cells by regulating the cell growth density of hepatic cells (L02) and hepatoma cells (HepG2) respectively. Analyzing the character of morphology, the change of cytoskeleton, the ability of deformation, the expression and distribution of E-cadherins of hepatic cells and hepatoma cells with different density, we found: Hepatoma cells' E-cadherins increased when compared to the hepatic cells'; Hepatic cells' up-regulated E-cadherins, and with their increased growth density, hepatic cells gathered in the contacted areas; Hepatoma cells, however, tended to down-regulate the expression of E-cadherins, and they kept the fusion distribution. The migration rate and net migration distance of these two kinds of cells were inhibited by growth density. Hepatoma cells kept the strong ability of migration, but the migration trace discretization of hepatic cell decreased with the increase of growth density. Hepatoma cells kept the high discretization of migration trace in different growth density. These different results show that hepatic cells are in positive correlation with E-cadherins distribution, and are in negative correlation with its migration. There is no aggregation tendency seen with respect to hepatoma cells' E-cadherins. The effect of hepatoma cells' growth density on migration is not obvious.
Cadherins ; metabolism ; Cell Count ; Cell Line ; Cell Movement ; Hep G2 Cells ; Humans ; Liver ; cytology ; metabolism