Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

OBJECTIVE: To explore effectiveness of musculoskeletal ultrasound combined with Wide-Awake technique in extensor indicis proprius tendon (EIP) transfer for repairing extensor pollicis longus tendon (EPL) rupture. METHODS: A clinical data of 20 patients with EPL spontaneous rupture, who were admitted between January 2019 and June 2024 and met the selective criteria, was retrospectively analyzed. During EIP transfer surgery, the musculoskeletal ultrasound-guided incision marking combined with Wide-Awake technique was used in combination group (n=10) and the tourniquet-assisted surgery under brachial plexus block anesthesia in the control group. There was no significant difference in the baseline data between groups (P>0.05), including gender, age, affected side, cause and location of tendon rupture, and time from injury to hospitalization. The accuracy of preoperative musculoskeletal ultrasound in predicting the actual tendon rupture site was evaluated in the combination group. The operation time, intraoperative blood loss, visual analogue scale (VAS) scores during operation and at 6 hours after operation, total incision length, and postoperative complications were recorded. Surgical outcomes were assessed at 12 months after operation using the specific EIP-EPL evaluation method (SEEM), which included measurements of thumb elevation loss, thumb flexion loss, index finger dorsiflexion loss, and total score. RESULTS: In the combination group, the incision position marked by preoperative musculoskeletal ultrasound positioning was consistent with the actual tendon rupture position. Compared with the control group, the operation time and total incision length in the combination group were significantly shorter and the VAS score at 6 hours after operation was significantly higher (P<0.05). There was no significant difference in intraoperative blood loss or intraoperative VAS score between groups (P>0.05). All incisions in both groups healed by first intention. Two patients in the control group developed swelling and blisters in the tourniquet area, which subsided spontaneously without special treatment. All patients were followed up 12-14 months, with an average of 12.5 months. The thumb dorsiflexion function of all patients recovered to varying degrees. At last follow-up, the thumb elevation loss in combination group was significantly lower than that in control group, and the total score was significantly higher (P<0.05); there was no significant difference in thumb flexion loss or index finger dorsiflexion loss between groups (P>0.05). CONCLUSION Musculoskeletal ultrasound can accurately locate the site of tendon rupture, assist the Wide-Awake technique in implementing precise anesthesia, and adjust tendon tension while reducing tissue trauma, with satisfactory effectiveness.
Humans ; Male ; Tendon Injuries/diagnostic imaging* ; Tendon Transfer/methods* ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Ultrasonography/methods* ; Rupture/surgery* ; Treatment Outcome ; Operative Time ; Tendons/surgery* ; Young Adult

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Non-alcoholic fatty liver disease(NAFLD)is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes.If not intervened in time,NAFLD may develop into liver fibrosis or liver cancer,and ultimately threatening life.NAFLD has complicated etiology and pathogenesis,and there are no effective therapeutic means and specific drugs.Currently,insulin sensitizers,lipid-lowering agents and hep-atoprotective agents are often used for clinical intervention,but these drugs have obvious side effects,and their effectiveness and safety need to be further confirmed.Adenosine monophosphate(AMP)-activated protein kinase(AMPK)plays a central role in maintaining energy homeostasis.Activated AMPK can enhance lipid degradation,alleviate insulin resistance(IR),suppress oxidative stress and inflammatory response,and regulate autophagy,thereby alleviating NAFLD.Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects.In this article,we reviewed the biologically active natural herbal medicines(such as natural herbal medicine formulas,extracts,polysaccharides,and monomers)that reported in recent years to treat NAFLD via regulating AMPK,which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.

Objectives:To explore the causal relationship between body mass index,uric acid and congestive heart failure(CHF),and provide genetic evidence to support the association between uric acid-mediated body mass index and the risk of CHF. Methods:Using the published data set of genome-wide association studies(GWAS)in East Asia,inverse variance weighting(IVW)method was used as the main analysis method,and MR-Egger method,weighted median model(WME),simple model and weighted model were used to analyze the causal relationship between body mass index,uric acid and CHF.MR-Egger regression was used to detect pleiotropy,Cochran Q test was used to detect heterogeneity,leave-one-out sensitivity was used to detect bias,funnel plot was drawn to detect bias,and MR-PRESSO package was used to remove outlier single nucleotide polymorphism(SNP).After Mendelian analysis,the mediating effect ratio was calculated,and the reverse Mendelian randomization study results between body mass index,uric acid and CHF were analyzed. Results:IVW method showed that body mass index(OR=1.685,95%CI:1.417-2.003,P<0.001)and uric acid(OR=1.225,95%CI:1.087-1.380,P<0.001)were risk factors of CHF in two-sample Mendelian analysis.Body mass index(OR=1.204,95%CI:1.139-1.273,P<0.001)was a risk factor for uric acid.The mediating effect of uric acid was 7.23%.The P values of MR-Egger regression intercept terms were all>0.05,that is,there was no pleiotropy of the selected SNP,and the causal inference method was valid.The Cochran Q test P values of body mass index and uric acid,and body mass index and CHF were<0.01,indicating heterogeneity.IVW analysis of CHF and body mass index in reverse Mendelian analysis was OR=0.977,95%CI:0.947-1.008,P>0.05 and CHF and uric acid was OR=1.000,95%CI:0.963-1.038,P>0.05,so the reverse causal inference was not valid.However,the analysis of uric acid and body mass index showed pleiotropy,so the causal inference method was invalid. Conclusions:There is a causal and positive correlation between body mass index and CHF.There is a causal relationship and positive correlation between uric acid and CHF.However,uric acid is an incomplete mediator between body mass index and CHF.