Objective:To explore the relationship between spondin 2(SPON2)and metastasis associated in colon cancer-1(MACC1)proteins expression in hepatocellular carcinoma cancer(HCC)tissues and clinicopathological features and transcatheter arterial chemoembolization(TACE)efficacy.Methods:140 patients who were diagnosed with HCC and underwent TACE from March 2022 to September 2024 in our hospital were collected as research subjects,and the SPON2,MACC1 protein expression in the cancer tissue and paracancer tissue of HCC patients were detected and compared.The correlation between SPON2 and MACC1 protein expression in HCC tissues was analyzed.SPON2 and MACC1 proteins expression in cancer tissues of different clinicopathological features were compared.After 3 months of follow-up,HCC patients were divided into ineffective group and effective group according to the TACE efficacy.Multivariate logistic regression was used to analyze the influencing factors of TACE efficacy,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of SPON2 and MACC1 protein expression of TACE efficacy.Results:SPON2 and MACC1 proteins positive expression rates in HCC cancer tissues were significantly higher than those in paracancer tissues(P＜0.05).There was a positive correlation between SPON2 and MACC1 protein expression in HCC cancer tissues(P＜0.05).SPON2 and MACC1 proteins positive expression rates in HCC cancer tissues were significantly correlated with Child-Pugh grade,tumor diameter,differentiation degree,Chinese liver cancer(CNLC)staging,microvascular invasion,lymph node metastasis,portal vein cancer thrombolus and alpha-fetoprotein(AFP)level(P＜0.05).Multivariate logistic regression analysis showed that Child-Pugh grade B,low differentiation degree,microvascular invasion,lymph node metastasis,AFP level＞400 μg/L,SPON2 and MACC1 protein positive expression were risk factors for poor TACE efficacy in HCC patients(P＜0.05).ROC curve analysis showed that,the area under curve(AUC)of SPON2 and MACC1 protein expression combined to predict TACE efficacy in HCC patients was 0.882,which was significantly higher than that of 0.807 and 0.786 by single detection(P＜0.05).Conclusion:SPON2 and MACC1 positive protein expression in HCC tissues are closely related to clinicopathological features of patients,and they are risk factors for poor TACE efficacy,which can be used as predictors for TACE efficacy in patient with HCC.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.

Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.

Objective:To explore the relationship between spondin 2(SPON2)and metastasis associated in colon cancer-1(MACC1)proteins expression in hepatocellular carcinoma cancer(HCC)tissues and clinicopathological features and transcatheter arterial chemoembolization(TACE)efficacy.Methods:140 patients who were diagnosed with HCC and underwent TACE from March 2022 to September 2024 in our hospital were collected as research subjects,and the SPON2,MACC1 protein expression in the cancer tissue and paracancer tissue of HCC patients were detected and compared.The correlation between SPON2 and MACC1 protein expression in HCC tissues was analyzed.SPON2 and MACC1 proteins expression in cancer tissues of different clinicopathological features were compared.After 3 months of follow-up,HCC patients were divided into ineffective group and effective group according to the TACE efficacy.Multivariate logistic regression was used to analyze the influencing factors of TACE efficacy,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of SPON2 and MACC1 protein expression of TACE efficacy.Results:SPON2 and MACC1 proteins positive expression rates in HCC cancer tissues were significantly higher than those in paracancer tissues(P＜0.05).There was a positive correlation between SPON2 and MACC1 protein expression in HCC cancer tissues(P＜0.05).SPON2 and MACC1 proteins positive expression rates in HCC cancer tissues were significantly correlated with Child-Pugh grade,tumor diameter,differentiation degree,Chinese liver cancer(CNLC)staging,microvascular invasion,lymph node metastasis,portal vein cancer thrombolus and alpha-fetoprotein(AFP)level(P＜0.05).Multivariate logistic regression analysis showed that Child-Pugh grade B,low differentiation degree,microvascular invasion,lymph node metastasis,AFP level＞400 μg/L,SPON2 and MACC1 protein positive expression were risk factors for poor TACE efficacy in HCC patients(P＜0.05).ROC curve analysis showed that,the area under curve(AUC)of SPON2 and MACC1 protein expression combined to predict TACE efficacy in HCC patients was 0.882,which was significantly higher than that of 0.807 and 0.786 by single detection(P＜0.05).Conclusion:SPON2 and MACC1 positive protein expression in HCC tissues are closely related to clinicopathological features of patients,and they are risk factors for poor TACE efficacy,which can be used as predictors for TACE efficacy in patient with HCC.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn³⁺SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn²⁺SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn²⁺SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn²⁺SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn²⁺ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O₂^• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O₂^• into the inner sphere, and avoid O₂^•/Mn²⁺ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH^-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Child ; Humans ; Mpox (monkeypox)/prevention & control* ; Disease Outbreaks

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Interleukin-35(IL-35)is an important immunosuppressive cytokine that has been shown to play a role in the immune response of various diseases.In this study,we cloned the coding sequence of human IL-35 gene,constructed single subunit expression vectors pXC17.4-p35 and pcDNA3.1(+)-EBI3,and co-transfected CHO-K1 cells to express IL-35 in vitro.No binding was found between subunits of p35 and EBI3.Knobs-into-Holes(KIH)can solve the problem of heavy chain mismatch of heterolo-gous antibodies.Therefore,expression vectors pXC17.4-p35-Fch and pcDNA3.1(+)-EBI3-Fck were constructed by fusing KIH structures on the basis of the original sequences to express the recombinant fu-sion protein of KIH-IL-35.The expression vectors of two subunits were exchanged at the same time to verify the influence of different vectors on the expression level of KIH-IL-35.The analysis of various pro-tein detection methods showed that the correct expression rate of KIH-IL-35 structure was significantly im-proved.Affinity purification of KIH-IL-35 was performed after large amount of expression,and the bind-ing activity of KIH-IL-35 to glycoprotein 130(gp130)was detected by ELISA.The results showed that the binding of KIH-IL-35 to gp130 was concentration dependent.The indirect activity of KIH-IL-35 and M1 cells was detected by cell activity assay.Further results showed that the inhibition rate of M1 cells in-creased in a dose-dependent manner with the concentration of KIH-IL-35.In addition,a method for de-termining IL-35 activity by activated human peripheral blood mononuclear cells was successfully estab-lished.Activated PBMCs increased in a dose-dependent manner with KIH-IL-35 concentration.In sum-mary,this study utilized the KIH-IL-35 model to enhance the expression of recombinant human IL-35 and validated its high activity in vitro,providing new ideas for the study of IL-35 and the recombinant expres-sion of similar heterodimeric cytokines.