ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure （CHF） and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction （TAC）. Eight of the 50 SD rats were randomly selected as the sham group， and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model， trimetazidine （6.3 mg·kg^-1）， and Yiqi Wenyang Huoxue Lishui components （60 mg·kg^-1 total saponins of Astragali Radix， 10 mg·kg^-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma， 190 mg·kg^-1 aqueous extract of Lepidii Semen， and 100 mg·kg^-1 cinnamaldehyde） groups. The rats were administrated with corresponding agents by gavage， and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg^-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， hypersensitive troponin（cTnI）， creatine kinase （CK）， lactate dehydrogenase （LD）， free fatty acids （FFA）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The colorimetric assay was employed to measure the levels of adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta （ATP5D）， glucose transporter 4 （GLUT4）， and carnitine palmitoyltransferase-1 （CPT-1）. The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ. ResultsCompared with the sham group， the model group showed a loosening arrangement of cardiac fibers， fracture and necrosis of partial cardiac fibers， inflammatory cells in necrotic areas， massive blue fibrotic tissue in the myocardial interstitium， increased collagen fiber area and myocardial fibrosis， destroyed mitochondria， myofibril disarrangement， sparse myofilaments， and fractured and reduced cristae. In addition， the rats in the model group showed declined ejection fraction （EF） and fractional shortening （FS）， risen left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs）， elevated levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， lowered level of SOD， down-regulated protein levels of GLUT4 and CPT-1， decreased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and declined levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. Compared with the model group， the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue， risen EF and FS， declined LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs， lowered levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， elevated level of SOD， up-regulated protein levels of GLUT4 and CPT-1， increased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and elevated levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function， reduce myocardial injury， regulate glucose and lipid metabolism， optimize the utilization of substrates， and alleviate the damage of mitochondrial structure and function， thus improving the energy metabolism of the myocardium in the rat model of CHF.

Objective:To investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.

Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

Objective To explore the role of serum Irisin,Nesfatin-1 and chitinase like protein 40(YKL-40)levels detection in evaluating the condition of patients with multiple sclerosis(MS).Methods A total of 160 MS patients who visited the First Hospital of Handan City from August 2017 to November 2023 were selected as the study subjects.According to clinical classification,they were separated into a remission group(n=115)and a progression group(n=45),and according to the severity of condition,they were separated into a mild group(n=109)and a severe group(n=51).ELISA method was applied to detect the levels of Irisin,Nesfatin-1 and YKL-40 in serum.Pearson was applied to analyze the correlation between serum Irisin,Nesfatin-1,YKL-40 levels and expanded disability status scale(EDSS)score in MS patients.Multivariate Logistic regression was applied to analyze the influencing factors of Ms Necerity.ROC curve was applied to analyze the evaluation value of serum Irisin,Nesfatin-1 and YKL-40 levels for the progression of MS patients.Results In the advanced stage group,the serum levels of Irisin(8.25±2.17 ng/ml)and Nesfatin-1(5.94±1.76 ng/ml)in MS patients were lower than those in the remission stage group(14.94±3.58 ng/ml,9.92±2.15 ng/ml),while the YKL-40(42.98±10.89 ng/ml)level was higher than that in the remission stage group(22.78±7.95 ng/ml),and the differences were statistically significant(t=11.709,11.048,12.956,all P<0.05).In the severe group,the serum levels of Irisin(8.86±2.21 ng/ml)and Nesfatin-1(6.32±1.91 ng/ml)in MS patients were lower than those in the mild group(15.02±4.42 ng/ml,9.96±2.30 ng/ml),while the disease course(5.84±1.65 years)and YKL-40(37.28±10.15 ng/ml)levels were higher than those in the mild group(3.65±1.45 years,24.34±7.62 ng/ml),and the differences were statistically significant(t=8.514,9.407,9.823,8.971,all P<0.05).Serum Irisin and Nesfatin-1 levels in MS patients were negatively correlated with EDSS scores(r=-0.504,-0.517,all P<0.05),while YKL-40 levels were positively correlated with EDSS scores(r=0.509,P<0.05).Irisin(OR=0.724,95%CI:0.589～0.889)and Nesfatin-1(OR=0.813,95%CI:0.669～0.945)were protective factors for disease progression in MS patients,while YKL-40(OR=2.964,95%CI:1.795～4.894)was a risk factor for disease progression in MS patients(all P<0.05).The AUCs of serum Irisin,Nesfatin-1 and YKL-40 levels in evaluating the progression of MS patients were 0.844,0.849 and 0.823,respectively,which were lower than the AUC(0.957)of their combination(Z=3.158,3.096,3.324,all P<0.05).Conclusion Serum Irisin,Nesfatin-1 and YKL-40 detection levels can effectively evaluate the progression of MS patient condition.

Since the first Drug Administration Law was issued in 1984， the drug regulation of China has undergone a forty- year process. During these four decades， China’s drug regulatory system has gradually transitioned from being extensive to refined， and the concept of supervision has become increasingly scientific. This paper first outlines the historical evolution of China’s drug regulatory laws and regulations since the founding of the People’s Republic of China， with a focus on the historical origins of the revision of the Drug Administration Law during 1984-2001. It also clarifies the new challenges faced by drug regulation as the industry innovates and develops， as well as the corresponding reform of the drug review and approval system. The paper summarizes the reform achievements of drug regulation. By studying and analyzing the challenges faced by drug regulation in terms of regulatory capacity， regulatory resources， and regulatory system in the context of internationalization of the industry， the paper proposes policy suggestions such as establishing a cross-regional regulatory system， reforming the review mechanism， strengthening the construction of the review team， and enhancing transparency in regulatory practices， with the aim of promoting the high-quality development of the pharmaceutical industry.

Objective To explore the safety and efficacy of laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy in the treatment of nutcracker syndrome complicated with varicocele.Methods A retrospective analysis was conducted on the data of 50 patients with nutcracker syndrome complicated with varicocele admitted to our hospital during Nov.2018 and Jul.2023.All patients underwent laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy.Results Altogether 47 patients were followed up after operation,with a mean age of(21.45±3.84)years.All operations were successful,and gross hematuria,proteinuria,abdominal pain and other symptoms relieved within 3-7 days after surgery.Postoperative follow-up showed that no patients had serious complications or recurrence of clinical symptoms.Left renal vein ultrasound and CT showed that the blood flow of the left renal vein was restored,and the stent position was stable.Compared with those before surgery,the angle between the abdominal aorta and the superior mesenteric artery[(44.91±6.59)° vs.(22.58±6.61)°]and the diameter of the left renal vein at the angle[(6.03±0.99)mm vs.(1.87±0.46)mm]were significantly increased,and the blood flow velocity of the left renal vein at the angle[(48.77±14.79)cm/s vs.(102.53±41.15)cm/s]was significantly decreased,with statistically significant differences(P＜0.001).Scrotal ultrasound confirmed that there was no recurrence of varicocele 6 months after surgery,and the diameter of the spermatic vein was significantly reduced,with statistically significant differences(P＜0.001).Semen analysis showed that the sperm concentration[(60.27±48.45)×106/mL vs.(36.57±36.67)×106/mL,P=0.032]and percentage of rapid forward movement of sperm were significantly increased[(22.54±10.70)vs.(15.01±10.77),P=0.005],with statistically significant differences.The increase value of semen concentration[(23.7±41.48)×106/mL vs.(6.12±4.97)×106/mL,P=0.016)]increased after combined operation compared with left renal venous stenting alone,and there was no significant difference in the diameter of spermatic vein,inner diameter of renal vein and flow rate between the two surgical methods(P＞0.05).Conclusion Laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy is a minimally invasive,safe and effective method for the treatment of nutcracker syndrome complicated with varicocele.

BACKGROUND:Total hip and knee arthroplasty is widely used in the elderly population,but there is a lack of accurate prediction methods for unplanned readmission and postoperative complications. OBJECTIVE:To investigate the effect of the Rothman index on unplanned readmission and complications in elderly patients undergoing total hip and knee arthroplasty. METHODS:A total of 153 patients who underwent elective total hip and knee arthroplasty from December 2020 to December 2022 in Ward Area One,Department of Orthopedics,The First People's Hospital of Zunyi were selected as the study subjects.According to whether they were unplanned readmission within 90 days after discharge,they were divided into a readmission group(n=21)and a non-readmission group(n=132).The general data of all patients were collected through the electronic medical record system,including gender,age,body mass index,diabetes mellitus,hypertension,and surgical joint type.The Rothman index was evaluated according to the literature.Postoperative complications were counted. RESULTS AND CONCLUSION:(1)There was no significant difference in gender,body mass index,surgical joint type,and length of hospital stay between the readmission group and the non-readmission group(P>0.05).There were significant differences in the number of comorbidities,age,and Rothman score between the two groups(P<0.05).(2)The results of multivariate Logistics regression analysis showed that the number of comorbidities,age,and Rothman score were independent influencing factors for readmission 90 days after total hip and knee arthroplasty in elderly patients with hip and knee diseases(P<0.05).(3)The results of receiver operating characteristic curve analysis exhibited that the area under the curve of the Rothman index for predicting readmission 90 days after total hip and knee arthroplasty was 0.824;the sensitivity was 80.85%;the specificity was 78.85%;the maximum Youden index was 0.597,and the optimal cutoff value was 46 points.(4)The incidence of total complications in elderly patients with Rothman<46 was higher than that in elderly patients with Rothman≥46(P<0.05).(5)It is concluded that the Rothman index can accurately predict unplanned readmission after total hip and knee arthroplasty in elderly patients with hip and knee joint diseases.Simultaneously,patients with Rothman index of less than 46 points have a higher overall risk of complications and poor joint recovery,which can be used to improve postoperative management of patients in clinical practice.

BACKGROUND:The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss.The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE:To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method. METHODS:Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model.The distal movement amount designed on the bilateral second molars was set to 0.25 mm.First,there were two groups in the study:second premolar bilateral presence and absence groups.Then,four subgroups in each group were created:tapered arch,ovoid arch,square Class Ⅱ Division 1 arch,and Class Ⅱ Division 2 arch groups.The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION:Mesial tipping and extrusion of first molars and premolars,labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners.When the bilateral second premolars were missing,the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups.The square Class Ⅱ Division 1 arch group showed the least anterior labial inclination,while the tapered arch group showed the most.There was no significant difference between the ovoid arch group and the tapered arch group.Moreover,the magnitude of tipping in the square Class Ⅱ Division 2 arch group was slightly higher than that in the Class Ⅱ Division 1 arch group.The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth.And the lowest stress level was detected in the square arch group.Compared with the other groups,the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group.To conclude,the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution.Anterior labial inclination efficiency can be increased in cases of Class Ⅱ Division 2 by designing the anterior labial inclination in conjunction with molar distalization.If the second premolar is missing during molar distalization,it is not conducive to opening up the space in the area of the missing tooth.

Objective:To evaluate the effects of abdomen breathing training combined with electrogalvanic stimulation and biological feedback therapy for postpartum pelvic floor hypertonicity. Method:Ninety-six women with postpartum pelvic floor hypertonicity in Chenghua Women's and Children's Pel-vic Floor Rehabilitation Clinic of West China Second Hospital from January to December 2022 were randomly divided into treatment and control groups.The control group(n=48)was treated with electrogalvanic stimula-tion for 10 minutes and biological feedback for 10 minutes.The treatment group(n=48)received electrogalvan-ic stimulation for 10 minutes,biological feedback for 10 minutes,and abdomen breathing training for 5-10 minutes.Two teams received treatment 2-3 times per week and 10 times in total.The visual analogue scale(VAS)of pelvic floor myofascial pain,pre-baseline rest and post-baseline rest,pelvic floor muscle strength(ac-cording to the 0-5 Oxford scale),phasic(flick)contractions,tonic contractions and the female sexual func-tion index(FSFI)scores of the two groups were evaluated before and after treatment. Result:The VAS score of the pelvic floor myofascial pain,pre-baseline rest,and post-baseline rest were lower than those before the intervention in both groups(P＜0.05).Pelvic floor muscle strength,phasic(flick)contrac-tions,tonic contractions,FSFI scores,were higher than those before the intervention(P＜0.05).After intervention,the VAS score of pelvic floor myofascial palpation tenderness and resting potential of pelvic floor muscles in the treatment group were all lower than those in the control group(P＜0.05),the scores of hand-tested pelvic floor muscle strength and female sexual function index scale were higher than those in the control group(P＜0.05). Conclusion:Abdomen breathing training combined with electrogalvanic stimulation and biological feedback sig-nificantly improved the postpartum pelvic floor hypertonicity and pelvic floor myofascial pain,boosted sexual function in postpartum,which is more advantageous than using the electrical stimulation and biofeedback alone.

Objective To explore the clinical value of shear wave elastic imaging(SWE)for renal cortical elasticity in patients with hypertension.Methods According to the diagnostic criteria of 2020 International Society of Hypertension(ISH)Global Hypertension Practice Guidelines,44 patients with simple hypertension admitted to the Department of Cardiology of our hospital were selected and 46 healthy controls were selected for the same period.The general data and and renal function indicators of blood biochemical were recorded.All subjects were examined by two-dimensional ultrasound and SWE elasticity to obtain the conventional ultrasound parameters and the Young's modulus(YM)value of the right.The above parameters between the two groups were compared.The influence factors were analyzed by multiple linear regression among the YM value of the right renal cortex,the general data,conventional ultrasound indicators and renal function indicators in the simple hypertension group.Results The course,systolic blood pressure(SBP)and diastolic blood pressure(DBP)in the simple hypertension group was higher than those in the control group,and the difference was statistically significant(P＜0.05).The YM value of the right renal cortex in the simple hypertension group was higher than that in the control group,and the difference was statistically significant(P＜0.05).The correlation analysis showed that the YM value of the right renal cortex was positively correlated with the duration of hypertension(P＜0.05),but not with age,blood pressure,right renal volume,right renal cortex thickness,right renal artery trunk peak systolic flow velocity(PSV),right renal artery trunk resistance index(RI),blood urea nitrogen,blood creatinine,or uric acid(P＞0.05).Further simple linear regression analysis showed that the duration of hypertension was an independent factor affecting the YM value of the right renal cortex.Conclusion SWE may be used to find the variation in elasticity of renal cortex in patients with simple hypertension.