OBJECTIVE To study the way in which hypidone hydrochloride(code:YL-0919)improves motor function after ischemic stroke(IS)and explore the related mechanism.METHODS Adult male SD rats were used to establish a middle cerebral artery occlusion(MCAO)model that simulated acute IS.All animals were randomly divided into four groups:sham group,MCAO group,MCAO+YL-0919 group,and MCAO+YL-0919+erastin(Era,ferroptosis inducer)group.The drug administration groups received the first ip injection 6 h after operation,followed by continuous ip injection once per day.After 7-10 d of drug administration,the effect of YL-0919 on motor function after IS were evaluated via neu-rological function test,adhesive-removal test,rotarod test,balance beam test and open field test.After 7 d of drug administration,TTC staining was used to detect the cerebral infarction area while the colo-rimetry method was used to measure the contents of glutathione(GSH),malondialdehyde(MDA),and ferrous ions(Fe2+)in the penumbra of the cerebral cortex.Western blotting was used to detect the expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(xCT),acyl-CoA synthetase long-chain family member 4(ACSL4),and transferrin receptor 1(TFR1)in the cortical penumbra.RESULTS Compared with the sham group,the MCAO group showed higher neurological function scores(P<0.01),with notably prolonged time for tape removal and first contact with the right forepaw(P<0.01),spent significantly more time crossing the balance beam(P<0.01)but endured a notably shorter duration on the rotarod(P<0.01),reduced the movement distance in the open field(P<0.01),had a remarkably increased infarct area(P<0.01)but significantly level of GSH in the cortical penumbra region decreased(P<0.01),while MDA and Fe2+levels were markedly increased(P<0.01).Protein expression levels of GPX4 and xCT were reduced(P<0.05),while those of ACSL4 and TFR1 were elevated(P<0.05).Compared with the MCAO group,these changes were significantly reversed after YL-0919 administration.However,when Era and YL-0919 were administered simultaneously,the reversal effect of YL-0919 was significantly weakened.CONCLUSION YL-0919 can improve motor function impairment and reduce cerebral infarction areas in rats after IS,and the mechanism may be related to the inhibition of ferroptosis.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective:To evaluate the feasibility, safety and efficacy of a domestic novel endoscopic clip for the treatment of gastrointestinal perforation in an animal model, and discuss its potential clinical adoption.Methods:Eight experimental pigs were randomly assigned to either an experimental group receiving the domestic novel endoscopic clip or a control group receiving an over-the-scope clip system (OTSC) using the random number table. Each animal underwent the creation of 2 cm perforations in the stomach and rectum, which were immediately sealed with clips. The performance, safety, and immediate closure rate of the clips during surgery were evaluated. Endoscopic examinations were conducted on days 3, 7, 14, 21, and 35 post-surgery to assess clip retention and wound healing. At the end of the observation period, animals were euthanized to evaluate wound healing, and histological examinations of the wound sites were conducted.Results:Both groups, consisting of 4 pigs each, successfully created and closed artificial perforations in both the stomach and rectum without intraoperative adverse events in either group such as accidental activation, device failure, or malfunctions in the delivery system. Endoscopic clip performance in the stomach were uniformly rated as 3 in all 4 pigs in the control group, while in the experimental group, 3 pigs were scored as 3 and 1 as 2. For rectal clip performance, 3 pigs were scored as 3 in both groups. One pig were scored as 1 in the experimental group, and the remaining pig in the control group were 2. All pigs survived the observation period without any postoperative complications. One clip (in the control group, rectal site) naturally dislodged during the observation period, while the other clips remained in place. Gross pathological examination revealed that the gastric surgical sites in all 8 pigs and the rectal sites in 7 pigs had healed, with wound healing scores of 3. However, 1 pig (control group) exhibited poor healing of the rectal mucosal incision, with persistent redness and swelling, and a wound healing score of 2. Histopathological examination showed similar levels of inflammation, cell necrosis, and vascular proliferation between the two groups, without ulcer formation observed.Conclusion:The domestically produced novel endoscopic clip exhibits simplicity in operation and demonstrates comparable technical feasibility, safety, and efficacy to OTSC. Its promising clinical application warrants further investigation and promotion through additional clinical research.

Objective To investigate the effect of Osteoporosis Self-Assessment Tool for Asia(OSTA)index on brachial ankle pulse wave velocity(baPWV)and its predictive value for peripheral atherosclerosis in menopausal women.Methods A total of 1 138 menopausal women who underwent physical examination at our hospital from January 2022 to December 2022 were enrolled in the study.General clinical data were collected,the OSTA index was calculated,and baPWV was measured.Patients were divided into the control group(n=539)and the peripheral atherosclerosis group(n=599)according to the baPWV values(peripheral atherosclerosis occurs with baPWV≥1 400 cm/s).Linear regression and Logistic regression were used to analyze the effect of OSTA index on baPWV in menopausal women.The predictive value of peripheral atherosclerosis was evaluated using the receiver operating characteristic(ROC)curve.Results The OSTA index was lower in the peripheral atherosclerosis group than that in the control group[-0.40(-2.20,1.00)vs.0.40(-0.60,1.40),P＜0.05].Univariate linear regression analysis was used to conclude that the OSTA index was an influencing factor of baPWV,and after correcting for risk factors,multivariate linear regression analysis indicated that OSTA index still affected the value of baPWV(P＜0.05).The linear regression equation was baPWV=-27.911-39.752×OSTA+6.444×SBP+7.008×DBP+11.506×HCY+27.942×Hs-CRP.Logistic regression analysis suggested that increased OSTA index was a protective factor for peripheral atherosclerosis(OR=0.664,95%CI:0.535-0.823,P＜0.001).ROC curve analysis suggested that OSTA index was-1.25 as the optimal cutoff point,which predicted peripheral atherosclerosis with an area under the curve of 0.619,a sensitivity of 36.2%and a specificity of 86.3%.Conclusion In menopausal women,OSTA index is an influential factor for baPWV,and increased OSTA index is a protective factor against peripheral atherosclerosis,which can be used to predict baPWV value.

Objective:To explore the effects of posterior malleolar fracture fixation on the rotational stability of the ankle joint.Methods:A total of 20 fresh cadaveric specimens of lower limbs were anatomized to measure the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia. One healthy volunteer was selected to construct a finite element model for the intact tibiofibular and ankle joints and finite element models for posterior malleolar fracture with different posterior projection areas. A load of 600 N was vertically applied to the inferior calcaneus along the tibial mechanical axis. The contact area and maximum Von Mises stress of the distal tibial articular surface were analyzed to verify the validity of the model for the intact tibiofibular and ankle joints. In the finite element models for the posterior malleolar fracture (S, 1/2S, 1/4S, 1/8S and 1/16S model groups, with S standing for the complete projection area of the ligament complex on the posterior surface of the tibia), the width increase in the tibiofibular clear space was measured when a vertical load of 600 N and external rotation load of 5 N·m were applied to the ankle joint after the reduction and fixation of posterior malleolar fracture. The cutoff value of the posterior projection area of posterior malleolar fracture that could maintain the rotational stability of the ankle joint was assessed.Results:The measurement results of the cadaveric specimens showed that the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia was relatively large. It was attached to the posterolateral area of the distal tibia with the highest point located at (45.2±5.6)mm from the articular surface. With the increase in the distance from the joint line, the width of the posterior attachment area of the ligament complex was decreased. Results of the finite element analysis showed that in the finite element model for the intact tibiofibular and ankle joints, the tibiotalar joint contact area was 324.02 mm 2 and the maximum Von Mises stress was 4.495 1 MPa with a vertical load of 600 N. In the finite element models for the posterior malleolar fracture, the distal tibiofibular clear spaces of the S, 1/2S, 1/4S and 1/8S model groups increased by less than 2 mm following loading, while it was increased by 3.445 8 mm in the 1/16S model group. The cutoff value of the posterior tibial projection area that could maintain the rotational stability of the ankle joint was 1/8S. Conclusions:The attachment area of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia is large. Both the axial stability and rotational stability of the ankle joint should be considered in the treatment selection for posterior malleolar fracture. Simple posterior malleolar fixation is recommended to restore the rotational stability and axial stability of the ankle joint when tibiofibular syndesmosis is unstable and the cutoff value is larger than or equal to 1/8, while tibiofibular syndesmosis screws must be implanted when tibiofibular syndesmosis is unstable and the cutoff value is less than 1/8.

Objective To investigate the status and the influencing factors of thyroid volume of children aged 8-10 years in Tianjin. Methods Among the 1-2 primary schools were randomly selected from 12 districts in Tianjin. A total of 1 090 children were selected by class cluster sampling method (half male and half female, with a balanced age distribution). A questionnaire survey was conducted. Children’s height, weight and thyroid volume were measured, and their salt iodine content and urinary iodine content were detected. Results I n this study, the median urinary iodine in children was 161.35 µg/L, the mean thyroid volume was 2.56 mL, and the goiter rate was 3.58%. Univariate analysis showed that age, BSA, salt iodine content, urinary iodine content, eating habits, food taste, eating lunch at school, father's work, anxiety and depression, pressure, and different regional grouping were the influencing factors of thyroid volume (P<0.05). Multivariate linear regression showed that BSA, age, food taste, and urinary iodine content had significant independent effects on thyroid volume (P<0.05). Conclusion In Tianjin, the iodine nutrition level of children aged 8-10 years is at an appropriate level. When evaluating the thyroid volume of children, in addition to age factors, other factors such as physical development level and iodine intake should also be considered.

OBJECTIVE To compare the effects of roxadustat and recombination human erythropoietin （rHuEPO） on coronary artery calcification in maintenance hemodialysis （MHD） patients. METHODS In retrospective analysis， MHD patients prescribed roxadustat in the Blood Purification Center of the First Affiliated Hospital of Chongqing Medical University from April 2019 to June 2021 were selected as the ROX group （56 patients）， and MHD patients prescribed rHuEPO during the same period were selected as the EPO group （60 patients）， and follow-up observation was conducted for 12 months. The differences in laboratory index， coronary artery calcification score （CACS）， and cardiac ultrasound parameters before and after treatment as well as the occurrence of cardiac and cerebrovascular adverse events during follow-up period were compared between the two groups. RESULTS There was no statistical difference in CACS between the two groups before and after treatment （P＞0.05）； but the difference of CACS in the ROX group was significantly lower than the EPO group （P＜0.05）. There was no statistically significant difference in cardiac ultrasound parameters and laboratory indexes between the two groups before and after treatment （P＜0.05）. The incidence of apoplexy and myocardial infarction in the ROX group was lower than that in the EPO group （P＜0.05）， and there was no statistically significant difference in the incidence of hospitalization due to heart failure between the two groups （P＞0.05）. CONCLUSIONS Compared with rHuEPO， roxadustat may have a positive effect on delaying coronary artery calcification in MHD patients and may be beneficial in reducing the incidence of myocardial infarction and apoplexy in MHD patients.

Objective To construct an in vitro"metabolic memory"cell model of HT-22 mouse hippocampal neurons induced by high glucose,and to investigate the effect of"metabolic memory"on apoptosis and histone acetylation in HT-22 cells.Methods HT-22 cells were cultured in high glucose medium(glucose concentration was 55 mmol/L)and conventional glucose medium(glucose concentration was 25 mmol/L),and cells were divided into the control group(NG 4,6 and 8 groups,25 mmol/L glucose was cultured for 4,6 and 8 days,respectively),the high glucose group(HG 4,6 and 8 groups,respectively)and the metabolic memory group(HG2NG2,HG2NG4,HG2NG6,HG4NG2 and HG4NG4 groups,high glucose culture for 2 days to 25 mmol/L glucose culture for 2,4 or 6 days,high glucose culture for 4 days to 25 mmol/L glucose culture for 2 or 4 days).Cell viability was detected by CCK-8 method.The release of lactate dehydrogenase(LDH)in cell culture supernatant was detected,and the optimal time to establish a"metabolic memory"model was selected.Subsequently,cells were divided into the NG4 group,the NG8 group,the HG4 group,the HG4NG4 group and the HG8 group,and the cell morphology of each group was observed by optical microscope.The apoptosis rate was detected by flow cytometry.The activities of deacetylase(HDAC)and histone acetyltransferase(HAT)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot assay was used to detect expression levels of histone deacetylase 4(HDAC4),B lymphocyte tumor 2(Bcl-2),Bcl-2 related X protein(Bax)and Caspase-3 protein.Results The HG4NG4 group was the ideal cell model with high glucose metabolic memory.Cells of the NG4 group and the NG8 group were interwoven into a dense network,growing well,with spindle shaped cells and distinct synaptic structures.However,in the HG4 group and the HG8 group,the cell body became round,synaptic structure disappeared and growth was inhibited.In the HG4NG4 group,the number of cells increased but their morphology was damaged.Results of flow cytometry showed that compared with the NG8 group,the apoptosis rates were significantly increased in the HG8 group and the HG4NG4 group(P＜0.05).ELISA results showed that compared with the NG8 group,the expression levels of HDAC4,Bax,and Caspase-3 proteins increased in the HG8 group and the HG4NG4 group,while the expression level of Bcl-2 protein significantly decreased(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels of HAT and HDAC in the HG4NG4 group.Western blot reslts showed that compared with the NG8 group,the levels of HDAC4,Bax and Caspase-3 protein increased in the HG8 group and the HG4NG4 group(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels in the HG4NG4 group.Conclusion HT-22 mouse hippocampal neurons cultured with 55mmol/L high glucose for 4 days,and then cultured with 25 mmol/L glucose for 4 days are the ideal"metabolic memory"cell model.The mechanism may be related to the increased activity of HDAC,HAT and HDAC4 expression in the hyperglycemic model.

Objective To establish a method for the determination of mercury, methylmercury (MeHg) and ethylmercury (EtHg) in the hair of mercury-exposed individuals using high performance liquid chromatography-atomic fluorescence spectrometry. Methods About 0.20 g of hair was mixed with 5.0 mL of hydrochloric acid to a concentration of 5.00 mol/L. After standing for 12 hours, ultrasonic extraction was carried out for 30 minutes at room temperature. Ammonia solution was added dropwise into 2.0 mL supernatant after centrifuge to adjust the pH to 4-5. The solution was diluted to 10.0 mL with pure water after mixed with 0.2 mL of L-cysteine with a mass concentration of 10.0 g/L. The mobile phase consisted of 5.0% methanol + a mass concentration of 0.06 mol/L ammonium acetate + a 0.1% L-cysteine, and was used for separation by a C₁₈ liquid chromatography column, followed by detection using atomic fluorescence spectrometry after UV digestion. Results The linear relationship of mercury, MeHg and EtHg in human hair was good at mass concentrations of 0.0-10.0 μg/L, with all correlation coefficients >0.999 0. The detection limit of mercury, MeHg and EtHg was 0.008, 0.008, and 0.010 μg/g, respectively. The within- and between- run relative standard deviations of the three forms of mercury were 1.6%-4.3% and 2.0%-5.6%, respectively, and the recovery rates were 94.0%-101.2%. Conclusion This method is simple, with low detection limit, high sensitivity, and good accuracy, and is suitable for the simultaneous determination of mercury, MeHg and EtHg in the hair of mercury-exposed individuals.

Toxoplasma gondii(T.gondii or Tg),is an obligatory intracellular parasite with humans as its intermediate hosts.In recent years,significant correlations between T.gondii infection and schizophrenia have been reported,including the possible mediating mechanisms.Currently,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain unclear.In this article,we review the studies related to T.gondii infection and schizophrenia,particularly the latest research progress.Research on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also discussed.In addition,we also summarized the results of some new epidemiological investigations.