Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

Non-alcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）， and hepatic stellate cell （HSC） activation is the key link in the progression of NAFLD to liver fibrosis. According to the theory of "Gaozhuo"， spleen deficiency and Qi stagnation， along with Gaozhuo invasion， are the causes of NAFLD progression to liver fibrosis， which reveals the pathogenesis essence of HSC activation in traditional Chinese medicine （TCM）. Among them， spleen deficiency and Qi stagnation are the root causes of the endogenous formation of Gaozhuo. Spleen deficiency indicates the insulin sensitivity decrease and glucose metabolism disorders， and Qi stagnation means the dysregulation of hepatic glucose and lipid metabolism， which creates the preconditions for HSC activation. Gaozhuo invasion is the direct cause of HSC activation， including three stages： Internal retention of Gaozhuo， turbidity and stasis stagnation， and toxic stasis and consolidation. Internal retention of Gaozhuo refers to the abnormal metabolism and deposition of hepatic lipids， as well as the microcirculatory disorders. Turbidity and stasis stagnation is the process by which lipotoxicity stimulates the transformation of HSC into myofibroblast （MFB）， and toxic stasis and consolidation represent the secretion of a large amount of extracellular matrix （ECM） by MFB to promote the fibrosis. According to the theory of Gaozhuo and the activation process of HSC， syndromes for T2DM combined with NAFLD can be classified into spleen deficiency and Qi stagnation with internal retention of Gaozhuo， spleen Qi deficiency with turbidity and stasis stagnation， and spleen Qi deficiency with toxic stasis and consolidation. Clinically， the treatment principle is to strengthen the spleen and promote Qi， resolve turbidity， and eliminate blood stasis. Both TCM compounds and monomers can effectively inhibit the HSC activation. TCM compounds can be classified into categories for regulating spleen and harmonizing liver， resolving turbidity and removing stasis， and detoxifying and removing stasis. They mainly work by improving lipid metabolism， reducing lipid accumulation in the liver， alleviating inflammatory and oxidative stress responses， inhibiting the activation and proliferation of HSC， and reducing ECM deposition， thereby delaying the progression of liver fibrosis.

ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

Objective To establish a method for determining hydrogen sulfide(H2S)in blood and apply it to practical cases.Methods A delute solution was achieved by adding 0.8 mL saturated borax solution into 0.2 mL blood sample was diluted with.1 mL acetonitrile solution containing 0.1％formic acid was then taken in a test tube,followed by adding 0.1 mL dilute solution and 0.1 mL thiozine aqueous solution(1％).After thorough mixing,the mixture was left to stand for 30 minutes.Subsequently,the sample was subjected to liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis after centrifugation and membrane filtration.Results The results showed that H2S exhibited good linearity within the concentration range of 10～2 000 ng/mL,with the R2 value of 0.998 5.The detection limit was 5 ng/mL,and the quantification limit was 10 ng/mL.In three cases of H2S poisoning,sulfur ions were detected in the blood of the deceased individuals,with concentrations ranging from 0.17 to 0.56 μg/mL.Conclusion For the first time,this study established a LC-MS/MS method for determining H2S in blood,which can meet the detection needs of H2S poisoning cases.

Objective To evaluate the clinical efficacy and safety of vitamin D combined with atomoxetine hydrochloride in the treatment of attention deficit hyperactivity disorder(ADHD)in children.Methods A retrospective analysis was performed for the data of children with ADHD admitted to Huzhou First People's Hospital from September 2022 to September 2023,and the children were divided into combination group and control group according to the diagnosis and treatment plan.The efficacy of treatment and cognitive function[Mini-Mental State Examination Scale(MMSE)and Wechsler Intelligence Scale for Children,Fourth Edition(WISC-IV.)],behavioral dysfunction[Conners]and neurofilament markers[neurential-specific enolase(NSE)and neurofilament light chain protein(NFL))before and after 3 months of treatment were observed and compared after treatment.The occurrence of adverse reactions during the treatment period was observed and recorded,and the safety was evaluated.Results A total of 101 children with ADHD were enrolled,including 51 in the combined group and 50 in the control group.After treatment,the total effective rate of the combination group was significantly higher than that of the control group(P<0.05).Before treatment,there were no significant differences in MMSE score,WISC-IV.score,Conners score,serum NSE level and serum NFL level between the two groups(P>0.05).After treatment,the MMSE score,WISC-IV.score,Conners score,serum NSE level and serum NFL level of the two groups were significantly improved compared with those before treatment(P<0.05),and the improvement degree in the combination group was better than that in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups during treatment(P>0.05).Conclusion Compared with atomoxetine hydrochloride monotherapy,vitamin D combined with atomoxetine hydrochloride has better efficacy in children with ADHD,and can improve cognitive function,behavioral dysfunction and neurological impairment,with high safety.

ObjectiveTo investigate the potential active ingredients and targets of Baihu Jia Renshentang（BHJRST） for the treatment of obesity combined with type 2 diabetes mellitus（T2DM） by network pharmacology and in vivo experiments. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify the material basis of BHJRST. Subsequently， potential targets for the action of the active ingredients were queried in databases such as ChEMBL， Therapeutic Target Database（TTD）， YaTCM， DisGeNET and Traditional Chinese Medicine on Immuno-Oncology（TCMIO）， and the shared targets were identified by taking the intersection of these targets with disease targets. The shared targets were imported into the STRING database to construct a protein-protein interaction（PPI） network， the hub genes were identified by cytoHubba plug-in， and molecular docking was used to validate the binding energy of the hub genes to the bioactive ingredients in BHJRST. Meanwhile， the shared targets were imported into the DAVID platform for gene ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis. The predicted results were subsequently verified by animal experiments. Eighteen 8-week-old male skeletal muscle insulin-like growth factor-1 receptor dysfunction（MKR） mice were induced by a high-fat diet for 12 weeks in order to prepare a mouse model of obesity combined with T2DM. The mice were randomly divided into the model group， metformin group（0.2 g·kg^-1） and BHJRST group（27 g·kg^-1 in raw material）， and another 6 male FVB mice of the same age as the normal group. The mice in each group were were given the corresponding drugs by gavage， and the normal and model groups were given the same amount of distilled water by gavage， 1 time/d for 6 consecutive weeks. At the end of administration， the body mass， Lee's index， fasting blood glucose（FBG）， oral glucose tolerance test（OGTT） of mice in each group were examined， and the pathological morphology of the white adipose tissue of the epididymis was observed， and the expression of the mRNA of the hub genes in the white adipose tissue of the epididymis was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultA total of 200 bioactive components of BHJRST were identified， of which 64 bioactive components were reverse-matched to 384 targets， and a total of 308 targets were associated with obesity combined with T2DM. Hub genes included mitogen-activated protein kinase 1（MAPK1）， signal transducer and activator of transcription 3（STAT3）， MAPK3， interleukin（IL）-2， Janus kinase 1（JAK1）， nuclear transcription factor-κB p65（RELA）， estrogen receptor 1（ESR1）， transcription factor AP-1（JUN）， MAPK14 and lymphocyte-specific protein tyrosine kinase（LCK）. GO functional annotation showed that it was mainly enriched in cytoplasm， cell membrane and nucleus， and was closely related to important biological processes such as peptide serine phosphorylation， protein phosphorylation and inflammation. In KEGG enrichment analysis， metabolic pathway， lipid and atherosclerosis， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） and MAPK signal pathways were significantly enriched. The molecular docking results showed that the hub genes had a stable binding relationship with 10 bioactive components， including quercetin， isoliquiritigenin， and morin， in BHJRST. The results of animal experiments showed that BHJRST could significantly reduce body mass， Lee's index and FBG levels（P<0.01） in mice with obesity combined with T2DM， improve the pathological changes of white adipose tissue， and down-regulate the the mRNA expression of the hub genes in white adipose tissue of the epididymis（P<0.01）. ConclusionIn this study， 10 potentially active components such as quercetin， isoliquiritigenin， and morin in BHJRST are identified through network pharmacology and animal experiments， and it is possible to treat obesity combined with T2DM by regulating lipid and atherosclerosis， phosphatidylinositol PI3K/Akt and MAPK signal pathways， which provides important clues and theoretical basis for the study of its mechanism and clinical application.

Objective To evaluate the clinical outcome of kidney transplantation from donation after brain death(DBD)donors complicated with acute kidney injury(AKI).Methods Clinical data of 216 DBD donors were retrospectively analyzed,and they were divided into the AKI group(n=69)and control group(n=147)according to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines.Donors in the AKI group were further divided into the KDIGO stage 1 and stage 2-3 subgroups.One hundred and thirty-five recipients were assigned into the AKI group and 288 recipients in the control group.Postoperative recovery of renal function and clinical outcomes of the recipients were recorded.The risk factors of delayed graft function(DGF)were identified.Results The highest serum creatinine(Scr)level,Scr level before procurement,the highest blood sodium level and blood sodium level before procurement in the AKI group were higher than those in the control group.The application duration of vasopressors in the AKI group was longer than that in the control group.In the AKI group,the amount of fluid resuscitation within 48 h was higher,the HCO3-level at admission was lower,and the incidence of diabetes insipidus and hypotension was higher than those in the control group.The highest Scr level and the Scr level before procurement in KDIGO stage 2-3 donors were significantly higher than those in KDIGO stage 1 counterparts(all P＜0.05).Compared with the control group,the incidence of DGF and acute rejection was higher,the proportion of continuous renal replacement therapy was higher,the Scr level within postoperative 90 d was higher,and the urine amount within postoperative 3 d was less than those of recipients in the AKI group.Compared with KDIGO stage 1 recipients,KDIGO stage 2-3 recipients had higher Scr levels at postoperative 3,4,5 and 15 d,and less urine amount at postoperative 2 d(all P＜0.05).Univariate analysis showed that donor age,the highest Scr level,the highest blood sodium level and the amount of fluid resuscitation within 48 h were the risk factors for DGF in recipients after kidney transplantation.Multivariate analysis showed that donor age was the independent risk factor for DGF in recipients after kidney transplantation(all P＜0.05).Conclusions For the application of DBD donors complicated with AKI,active organ maintenance should be performed to alleviate AKI.It exerts no effect upon graft function and survival rate at postoperative 6 months,which may achieve equivalent efficacy as non-AKI donors and may be used as a source of extended criteria donor kidneys.

Objective:To summarize the experience of brain death determination under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) assisted circulatory support, especially apnea test (AT) precautions, and to provide references for brain death determination in this scenario.Methods:In 78 patients who had VA-ECMO at Organ Transplant Center, Zhengzhou People's Hospital from October 2019 to December 2023, 8 organ donors had brain death determination under VA-ECMO assisted circulatory support. Baseline data, clinical data, and VA-ECMO data during AT trial were collected from these 8 patients to summarize the process of brain death determination.Results:Six of the 8 donors met the criteria of brain death; 10 EEG, 12 evoked potentials and 15 ATs were performed. Complications in ATs, including hypotension, decreased oxygenation and arrhythmia, were alleviated after timely improved VA-ECMO flow and applied cardiotonic and pressor drugs.Conclusion:AT is key for successful brain death determination in organ donors under VA-ECMO assisted circulatory support; therefore, complications should be closely monitored and managed.

Objective To investigate the value of MRI diffusion-weighted imaging (DWI) technique in endocrine therapy for prostate cancer (PCa) based on PI-RADSv2.1. Methods A retrospective analysis of 57 patients with pathologically confirmed PCa was conducted. All patients underwent multi-parametric MRI (mpMRI) according to PI-RADS v2.1 technical specifications before biopsy and six months after endocrine therapy. The apparent diffusion coefficient (ADC) values were measured in cancer and non-cancer areas before biopsy and six months after endocrine therapy. Patients were grouped based on the mRECIST criteria and PSA level into responders (n=45) and non-responders (n=12). ROC curves were obtained to assess the correlation between changes in ADC values and PSA values before and after endocrine therapy. Results In the responder group, the ADC value of the cancer areas was increased significantly after endocrine therapy (P<0.001). No statistically significant difference of the ADC value of the cancer areas was found in the non-responder group before and six months after endocrine therapy (P=0.714). The ADC change of responders and non-responder groups were (0.411±0.178)×10^-3 mm²/s and (-0.014±0.125)×10^-3 mm²/s, respectively (P<0.001); the ADC ratio were (60.603±30.201)% and (-1.096±13.175)%, respectively (P<0.001). The cutoff value of the ADC change was 0.165 (AUC=0.974; sensitivity, 88.89%; specificity, 100.00%; PPV, 100.00%; NPV, 70.59%). The cutoff value of ADC ratio was 16.827% (AUC=0.980; sensitivity, 91.11%; specificity, 100.00%; PPV, 100.00%; NPV, 75.00%). The ADC values were negatively correlated with serum PSA before and after endocrine therapy. Conclusion The ADC change and ADC ratio may be facilitated to monitor the efficacy of endocrine therapy for PCa. The ADC values were negatively correlated with serum PSA.