ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L^-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

BACKGROUND:Research on foot and ankle proprioception is crucial for the rehabilitation of chronic ankle instability and geriatric diseases as well as for the improvement of body posture control and motor performance.Previous studies have often studied the sensory evaluation of the foot and ankle joints separately,which has limitations for a comprehensive understanding of their sensory function. OBJECTIVE:The foot and ankle complex is the only part in direct contact with the support surface,and plays an important role in the collective sensory feedback and regulation and balance control.By combing the existing investigation and research of foot and ankle ontology,the measurement and evaluation methods of the sensation of the foot and ankle complex are combed,in order to pave the way and provide the theoretical basis for future related studies. METHODS:Chinese terms"(foot OR foot ankle OR ankle)AND(sensation OR proprioception)"and English terms"(foot OR ankle)AND(feel OR proprioception)"were used as the keywords for retrieving relevant literature in the Web of Science,PubMed,and CNKI.We understood the basic concepts,current status and scope of research on the foot and ankle,summarized and evaluated the proprioceptive evaluation methods of the foot and ankle,and finally included 57 papers for further review. RESULTS AND CONCLUSION:The evaluation of foot and ankle complex sensation was mainly divided into sensory evaluation of the foot and proprioceptive evaluation of the ankle joint.The sensory evaluation of the foot mainly describes the sensation of the skin and the sensory feedback under the intervention conditions.The methods mainly include the pressure sensory threshold test,the two-point discrimination test of the foot(planar and plantar),and the duration test of skin vibration sensation.Ankle joint proprioception evaluation focuses on the description of joint position,motion range,force value and functional performance.The methods are mainly divided into static joint angle reset test,motion minimum threshold test,force perception reproduction test and dynamic balance,speed and walking ability tests.The report of quantitative results is generally expressed by"an error,"which is generally divided into absolute error,relative error,constant error,etc.To conclude,the foot and ankle complex has specific sensory capabilities,including foot sensation and ankle proprioception,which affect the quality of life and athletic performance of humans.Weakness of both foot sensation and ankle proprioception is associated with reduced human balance,and the combined measurements of the two can comprehensively and effectively evaluate foot and ankle function.The combination of foot and ankle sensory measures is selected according to different research needs and various influencing factors such as environment,emotion and reporting style are fully considered,to improve the validity of measurement and evaluation.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.

Objective:To investigate the correlations of endoscopic evaluation results with laboratory indices and clinical disease activity in Crohn disease (CD) patients with different intestinal involvement.Methods:Data of 147 patients diagnosed as having CD who visited the Department of Gastroenterology, Zhongnan Hospital of Wuhan University from July 1, 2017 to June 30, 2022 were collected retrospectively. According to the involvement of intestinal segment, patients were divided into three groups: the group with isolated small intestinal involvement ( n=55), the group with both small intestinal and large intestinal involvement ( n=48), and the group with isolated large intestinal involvement ( n=44). Correlations of endoscopic evaluation (based on CDEIS) with laboratory indices and clinical disease activity (based on Harvey-Bradshaw index) were analyzed. Results:C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) could be used for the prediction of endoscopic disease activity. The areas under curve (AUC) of receiver operator characteristic (ROC) were 0.677 (0.506-0.849) and 0.744 (0.597-0.890), respectively. In terms of determing clinical disease activity, clinical Harvey-Bradshaw index was consistent with endoscopic CDEIS score in 65.3% (96/147) patients, showing a low positive correlation ( r=0.260, P<0.05). In subgroup analysis for patients with isolated small intestinal involvement, CRP showed no predictive value for clinical disease activity [AUC (95% CI): 0.617 (0.461-0.773), P=0.148], while for endoscopic activity neither CRP nor ESR showed predictive value [AUC (95% CI): 0.537 (0.146-0.929), P=0.829; AUC (95% CI): 0.571 (0.153-0.990), P=0.680]. Furthermore, for patients with isolated small intestinal involvement and both small intestinal and large intestinal involvement, no correlation was found between clinical Harvey-Bradshaw index and endoscopic CDEIS score ( r=0.222, P=0.092; r=0.142, P=0.322). Conclusion:For CD patients with small intestinal involvement, especially isolated small intestinal involvement, laboratory indices and clinical disease activity cannot accurately reflect endoscopic disease activity. Great importance should be attached to evaluation of the extent and activity of intestinal lesions by endoscopy, especially enteroscopy.

Objective    To explore the predictive value of the maximum amplitude (MA) in the thromboelastogram (TEG) in the occurrence of venous thromboembolism (VTE) in patients with lung cancer after surgery. Methods    Forty-one lung cancer patients with postoperative VTE in our hospital from September 2018 to August 2020 were enrolled into a thrombosis group, including 25 males and 16 females, aged 72.17±10.08 years. The 87 lung cancer patients who underwent surgery during the same period but did not suffer postoperative VTE were enrolled into a control group, including 51 males and 36 females, aged 71.06±9.49 years. The MA of thrombus in the TEG before and after the operation was compared between the two groups, and logistic regression analysis was used to test the value of the MA of thrombus at each time point in the TEG to predict the occurrence of VTE in patients with lung cancer surgery. The receiver operating characteristic curve was drawn to test the effectiveness of the MA of thrombus at each time point in the TEG to predict the occurrence of VTE in patients with lung cancer. Results    The MA of thrombus in the two groups after operation was greater than that before operation, and the MA of thrombus in the TEG on the day 3 after operation in the two groups> day 1> day 5 (P<0.05). The logistic regression analysis showed that the MA of thrombus in the TEG increased, which had predictive value for the occurrence of VTE in patients with lung cancer after surgery; the MA of thrombus in the TEG at each postoperative point was used as the test variable. Taking the occurrence of VTE as a state variable, the area under the curve (AUC) of MA of thrombus in the TEG on the 1st postoperative day was 0.82, and its optimal threshold was 75.15 mm; on the 3rd postoperative day, AUC was 0.88, and its optimal threshold was 80.05 mm; on the 5th day afterwards, AUC was 0.78, and its optimal threshold was 66.30 mm. Conclusion    The MA of TEG has a high predictive power for the occurrence of VTE in lung cancer patients after surgery, which suggests that TEG dynamic monitoring should be performed before surgery for lung cancer patients, and a reasonable anticoagulation plan should be formulated accordingly to reduce the occurrence of VTE.

Objective:To investigate the topological alterations of brain functional networks in patients with chronic methamphetamine (MA) dependence.Methods:Resting-state functional magnetic resonance imaging was used to map the brain networks of 46 patients with MA-dependence (MA group) and 46 healthy controls (control group). Statistical methods were used to compare the differences of brain functional connection and topological parameters between the two groups, and the correlations between these topological parameters with significant inter-group differences and clinical measurements were analyzed.Results:(1) Brain functional connection: as compared with the control group, the MA group had significantly enhanced functional connectivity in the subnetworks consisting of several brain regions, including the inferior parietal lobule, posterior central gyrus, lateral occipital cortex, ventromedial occipital cortex, orbital gyrus, anterior central gyrus, fusiform gyrus, superior temporal gyrus and thalamus; as compared with the control group, the MA group had significantly attenuated functional connectivity in the subnetworks consisting of several brain regions, the orbit frontal cortex, precentral gyrus, paracenter lobule, inferior temporal gyrus, fusiform gyrus, parahippocampal gyrus, superior parietal lobule, postcentral gyrus, medioventral occipital cortex, lateral occipital cortex and amygdala. (2) Network topology attributes: the brain functional networks in all subjects from the MA group and control group held worldlet; but attribute of worldlet in the MA group was significantly reduced as compared with that in the control group ( P<0.05); moreover, the MA group had significantly decreased clustering coefficient, local efficiency, and modularity as compared with the control group ( P<0.05). In terms of regional topological attributes, such as betweenness centrality, the MA group presented evident reduction in the left superior frontal gyrus, right orbit frontal cortex, right middle temporal gyrus and right/left lateral occipital cortex as compared with the control group with significant differences ( P<0.05). (3)Correlation analysis: the betweenness centrality of right middle temporal gyrus exhibited a positive correlation with the age of patients using MA for the first time ( r=0.327, P=0.028); a positive correlation was found between the modularity and activating factor scores in Brief Psychiatric Rating Scale (BPRS) in MA group ( r=0.315, P=0.035). Conclusions:Part of the global/local topological attributes of the brain functional network of patients with MA addiction are damaged. The younger the patients are when they take MA for the first time, the lower the betweenness centrality of the right middle temporal gyrus; the more the local attributes are damaged; and furthermore, the deeper the network modularity, the severer the active symptoms in the psychotic symptoms.

OsRhoGDI2 was isolated as a putative partner of Rho protein family member OsRacD from rice panicles by yeast two-hybrid, but its function remains unknown. In order to identify the function of OsRhoGDI2, OsRhoGDI2 knockout mutants were created by CRISPR/Cas9 technology. The results showed that two different homozygous mutants were obtained in T0 generation, and eight kinds homozygous mutants were identified in T1 generation. Sequence analysis revealed that the base substitution or base deletion occurred near the editing targets of the gene in knockout rice, and it could be expected that the truncated OsRhoGDI2 proteins lacking the RhoGDI conserved domain would be generated. Phenotype analysis showed that the OsRhoGDI2 knockout rice plants were significantly lower than the control plants. Statistical analysis confirmed that the significant decrease of plant height was due to the shortening of the second and third internodes, suggesting that OsRhoGDI2 gene may be related with rice height control.
CRISPR-Cas Systems ; Genes, Plant ; genetics ; Oryza ; genetics ; growth & development ; Plants, Genetically Modified ; rho Guanine Nucleotide Dissociation Inhibitor beta ; genetics

OBJECTIVE: To investigate the association of the time of initial diagnosis with the severity of chronic obstructive pulmonary disease (COPD). METHODS: A total of 803 patients who were diagnosed to have COPD for the first time in our hospital between May 2015 to February 2018 were enrolled in this study.The diagnoses of COPD and asthma COPD overlap (ACO) were made according GOLD guidelines and european consensus definition.Lung function of the patients was graded according to the GOLD guidelines. RESULTS: The patients with COPD had a mean age of 61.8±9.9 years,including 726 male and 77 female patients.The course of the patients (defined as the time from symptom onset to the establishment of a diagnosis) was 3(0.5,8) years.Among these patients,85.2% had a moderate disease severity (FEV1%<80%),and 48.3% had severe or very severe conditions (FEV1%<50%);47.0% of them were positive for bronchial dilation test.In the overall patients,295(36.7%) were also diagnosed to have ACO,and the mean disease course of ACO[3(1,9) years]was similar to that of COPD[3(0.5,8) years](>0.05).A significant correlation was found between the disease course and the lung function of the patients.Multiple linear regression analysis showed that an older age and a longer disease course were associated with poorer lung functions and a greater disease severity. CONCLUSIONS The delay of the initial diagnosis is significantly related to the severity of COPD.
Age Factors ; Aged ; Asthma ; diagnosis ; Delayed Diagnosis ; adverse effects ; Disease Progression ; Female ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; physiopathology ; Severity of Illness Index ; Time Factors

Objective To observe the effect of Chaijin-Huayu decoction combined with endoscopic minimally invasive for gallbladder polyposis and its effect on quality of life.Methods A total of 91 patients with gallbladder polyposis were selected from March 2014 to early March 2017 outpatients and wards of Hebei Provincial Traditional Chinese Medicine Hospital.According to the method of random number table,the paitents were randomly divided into the observation group (n=46) and the control group (n=45).After three courses of treatment,the total effective rate,TCM symptom score and quality of life were observed in both groups,and the postoperative complications of the two groups were compared.Results After three courses of treatment,the total effective rate of the observation group was 91.3％ (42/46),while that of the control group was 88.9％ (40/45).There was no significant difference between the two groups (x2=0.149,P=0.592).In the observation group,the scores of subcardiac pycnosis and belching,right flank distended pain and burp were lower than those of the control group (t were 2.431,3.560 and 2.891 respectively,all P＜0.05).In the SF-36 scale,the scores of mental health,social function,physical pain,physiological function,emotional function,vitality,physiological function and overall health of the observation group were higher than those of the control group (t were 2.342,2.831,2.765,2.545,2.485,2.650,2.582,2.325 respectively,all P＜0.05);The incidence of surgical complications of the observation group was 2.2％ (1/46),while that of the control group was 17.8％ (8/45),and the difference between the two groups was statistically significant (x2=0.149,P＞0.05).Conclusions Chaijin-Huayu decoction combined with minimally invasive choledochoplasty could relieve symptoms,improve quality of life and reduce postoperative complications in patients with gallbladder polyposis.