Ferroptosis is a form of programmed cell death,which plays a crucial driving role in the onset and progression of diabetic nephropathy(DN).Ferroptosis is closely related to the damage of renal intrinsic cells in patients with diabetes.Chinese materia medica can improve DN by regulating the ferroptosis of renal intrinsic cells,with a good research and application prospect.This article reviewed the key regulatory factors and regulatory pathways of ferroptosis in DN,explained the"imbalance between yin and yang"of ferroptosis in DN based on TCM theories,and combed the research status of targeted inhibition of ferroptosis by active components of Chinese materia medica.The regulation of active components of Chinese materia medica on ferroptosis in DN has the characteristics of multiple targets,multiple links and integrity,which can provide a reference for the mechanism research and drug development of Chinese materia medica in treating DN.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective To investigate the effect of ring finger protein 130(RNF130)on myocardial ischemia-reperfusion injury(MI/RI)and its potential mechanism.Methods Male C57BL/6J mice were divided into four groups(n=6):Sham,MI/RI,MI/RI+Vector,and MI/RI+RNF130 overexpression(MI/RI+RNF130OE).Cardiac function was evaluated by echocardiography 24 hours after ischemia-reperfusion.Pathological changes,oxidative damage,and apoptosis in myocardial tissues were observed via IHC,DHE,and TUNEL staining.Protein expression was detected using Western blot,immunofluorescence,and immunohistochemistry.Proteomic analysis was performed to identify downstream proteins regulated by RNF130,and protein-protein interactions were validated by immunoprecipitation(IP)assay.Results Compared with the MI/RI+Vector group,RNF130 overexpression significantly improved cardiac function,as indicated by increased left ventricular ejection fraction(EF)and fractional shortening(FS),reduced myocardial infarction area,and decreased expression of NOX-2 and BAX proteins(P＜0.05).DHE and TUNEL staining showed that RNF130 overexpression alleviated myocardial oxidative damage and apoptosis(P＜0.05).Proteomic analysis and IP assays revealed a significant interaction between RNF130 and PARP1,with PARP1 expression inversely correlated with RNF130.Conclusions RNF130 may mitigate MI/RI injury by regulating the PARP1 ubiquitination pathway,providing a new target for therapeutic intervention.

Objective To examine the effect and mechanism of Duhuo Jisheng Decoction on lumbar intervertebral disc degeneration.Methods In total,105 Sprague-Dawley(SD)rats were randomly assigned to seven groups:sham operation group,model group,Duhuo Jisheng Decoction 1,rapamycin group,rapamycin+Duhuo Jisheng Decoction group,MHY1485 group,and MHY1485+Duhuo Jisheng Decoction group.Except for the sham operation group,the other groups underwent annulus fibrosus puncture to establish a lumbar intervertebral disc degeneration(IDD)animal model.After successful model establishment,a six-week drug intervention was performed,followed by MRI evaluation of the degree of disc degeneration.Samples of the L5-6 intervertebral disc were collected for HE and Alcian blue-nuclear fast red staining,and the degeneration of the nucleus pulposus and changes in the extracellular matrix were observed using light microscopy.Simultaneously,the expression levels of the downstream proteins of the mTOR pathway,p70S6K and 4E-BP1,along with the autophagy-related genes Beclin-1 and LC3,were assessed at both the protein and mRNA levels.Autolysosomes in nucleus pulposus cells were visualized using transmission electron microscopy(TEM).Results ①MRI showed disc Pfirrmann grade I in the sham group,and disc Pfirrmann grade Ⅲ-Ⅳ in the remaining 6 groups in L5-6 segments.②The degree of lumbar disc degeneration with histomorphological observation:MHY1485 group>model group>MHY1485 group+Duhuo Jisheng Decoction group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group.Allan-nuclear red staining extracellular matrix proteoglycan content:sham group>rapamycin+Duhuo Jisheng Decoction group>rapamycin group>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485 group.③Relative expression of p-mTOR,p70S6K and 4E-BP1 downstream of mTOR signaling pathway:MHY1485 group>MHY1485 group+Duhuo Jisheng Decoction group>model group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group,each experimental group varied significantly from the model group(P<0.01).④Autophagy-related protein Beclin-1 and LC3 expression levels:rapamycin+Duhuo Jisheng Decoction group>Duhuo Jisheng Decoction group>rapamycin>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485>sham group,and the content of each group was significantly(P<0.01).⑤TEM observation of autophagy levels in the cells of each group showed the formation of autolysosomes in Duhuo Jisheng Decoction group,rapamycin group andrapamycin+Duhuo Jisheng Decoction group.Conclusion Duhuo Jisheng Decoction can slow down the degenerative process of lumbar intervertebral discs in rats,and its effect may be linked to the suppression of the mTOR signaling pathway and the promotion of autophagy in nucleus pulposus cells.

Objective To investigate the effect of ring finger protein 130(RNF130)on myocardial ischemia-reperfusion injury(MI/RI)and its potential mechanism.Methods Male C57BL/6J mice were divided into four groups(n=6):Sham,MI/RI,MI/RI+Vector,and MI/RI+RNF130 overexpression(MI/RI+RNF130OE).Cardiac function was evaluated by echocardiography 24 hours after ischemia-reperfusion.Pathological changes,oxidative damage,and apoptosis in myocardial tissues were observed via IHC,DHE,and TUNEL staining.Protein expression was detected using Western blot,immunofluorescence,and immunohistochemistry.Proteomic analysis was performed to identify downstream proteins regulated by RNF130,and protein-protein interactions were validated by immunoprecipitation(IP)assay.Results Compared with the MI/RI+Vector group,RNF130 overexpression significantly improved cardiac function,as indicated by increased left ventricular ejection fraction(EF)and fractional shortening(FS),reduced myocardial infarction area,and decreased expression of NOX-2 and BAX proteins(P＜0.05).DHE and TUNEL staining showed that RNF130 overexpression alleviated myocardial oxidative damage and apoptosis(P＜0.05).Proteomic analysis and IP assays revealed a significant interaction between RNF130 and PARP1,with PARP1 expression inversely correlated with RNF130.Conclusions RNF130 may mitigate MI/RI injury by regulating the PARP1 ubiquitination pathway,providing a new target for therapeutic intervention.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective To examine the effect and mechanism of Duhuo Jisheng Decoction on lumbar intervertebral disc degeneration.Methods In total,105 Sprague-Dawley(SD)rats were randomly assigned to seven groups:sham operation group,model group,Duhuo Jisheng Decoction 1,rapamycin group,rapamycin+Duhuo Jisheng Decoction group,MHY1485 group,and MHY1485+Duhuo Jisheng Decoction group.Except for the sham operation group,the other groups underwent annulus fibrosus puncture to establish a lumbar intervertebral disc degeneration(IDD)animal model.After successful model establishment,a six-week drug intervention was performed,followed by MRI evaluation of the degree of disc degeneration.Samples of the L5-6 intervertebral disc were collected for HE and Alcian blue-nuclear fast red staining,and the degeneration of the nucleus pulposus and changes in the extracellular matrix were observed using light microscopy.Simultaneously,the expression levels of the downstream proteins of the mTOR pathway,p70S6K and 4E-BP1,along with the autophagy-related genes Beclin-1 and LC3,were assessed at both the protein and mRNA levels.Autolysosomes in nucleus pulposus cells were visualized using transmission electron microscopy(TEM).Results ①MRI showed disc Pfirrmann grade I in the sham group,and disc Pfirrmann grade Ⅲ-Ⅳ in the remaining 6 groups in L5-6 segments.②The degree of lumbar disc degeneration with histomorphological observation:MHY1485 group>model group>MHY1485 group+Duhuo Jisheng Decoction group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group.Allan-nuclear red staining extracellular matrix proteoglycan content:sham group>rapamycin+Duhuo Jisheng Decoction group>rapamycin group>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485 group.③Relative expression of p-mTOR,p70S6K and 4E-BP1 downstream of mTOR signaling pathway:MHY1485 group>MHY1485 group+Duhuo Jisheng Decoction group>model group>rapamycin group>Duhuo Jisheng Decoction group>rapamycin+Duhuo Jisheng Decoction group>sham group,each experimental group varied significantly from the model group(P<0.01).④Autophagy-related protein Beclin-1 and LC3 expression levels:rapamycin+Duhuo Jisheng Decoction group>Duhuo Jisheng Decoction group>rapamycin>MHY1485 group+Duhuo Jisheng Decoction group>model group>MHY1485>sham group,and the content of each group was significantly(P<0.01).⑤TEM observation of autophagy levels in the cells of each group showed the formation of autolysosomes in Duhuo Jisheng Decoction group,rapamycin group andrapamycin+Duhuo Jisheng Decoction group.Conclusion Duhuo Jisheng Decoction can slow down the degenerative process of lumbar intervertebral discs in rats,and its effect may be linked to the suppression of the mTOR signaling pathway and the promotion of autophagy in nucleus pulposus cells.

Ferroptosis is a form of programmed cell death,which plays a crucial driving role in the onset and progression of diabetic nephropathy(DN).Ferroptosis is closely related to the damage of renal intrinsic cells in patients with diabetes.Chinese materia medica can improve DN by regulating the ferroptosis of renal intrinsic cells,with a good research and application prospect.This article reviewed the key regulatory factors and regulatory pathways of ferroptosis in DN,explained the"imbalance between yin and yang"of ferroptosis in DN based on TCM theories,and combed the research status of targeted inhibition of ferroptosis by active components of Chinese materia medica.The regulation of active components of Chinese materia medica on ferroptosis in DN has the characteristics of multiple targets,multiple links and integrity,which can provide a reference for the mechanism research and drug development of Chinese materia medica in treating DN.

Objective:To evaluate the predictive value of preoperative frailty combined with nutritional status for prolonged postoperative ileus (PPOI) in the patients with gynecological malignancies.Methods:Patients undergoing elective surgery for gynecological malignancies in the Affiliated Hospital of Jiangnan University from April 2022 to February 2023 were selected. The Frail scale was used to evaluate the frailty within 24 h of admission, and the nutritional status was evaluated by the Controlling Nutritional Status score. The general characteristics of patients and occurrence of PPOI were recorded, and the risk factors for PPOI were analyzed by multivariate logistic regression. The ability of frailty, nutritional status and their combination to predict PPOI was assessed by the receiver operating characteristic curve.Results:Two hundred and fourteen patients were finally included, 52 cases developed of PPOI, and 98 cases were frail patients. Preoperative frailty combined with moderate to severe malnutrition was an independent risk factor for PPOI in the patients with gynecological malignancies ( P<0.05), and the area under the curve in predicting the occurrence of PPOI was 0.796 (95% confidence interval 0.736-0.857) in the patients with gynecological malignancies. Conclusions:Preoperative frailty combined with moderate to severe malnutrition has a higher accuracy in predicting PPOI in the patients with gynecological malignancies.

Screening for diabetes and its complications contributes to slowing the progression of diabetes mellitus. Based on the setting of grass-roots diabetes complication screening workstation with the concept of two stages of screening and three levels of prevention, we proposed a hospital-community-family integrated diabetes management strategy. This article discusses the background, organization structure, operation mechanism and implementation process of this strategy, aiming to provide reference for constructing a suitable and practical grass-roots diabetes management model.