Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Orally inhaled drug products (OIDPs) play a great role in the pharmacological treatment of chronic obstructive pulmonary disease (COPD) and asthma. There is an unmet clinical need for OIDPs. Pharmacodynamics-Bioequivalence studies (PD-BE) are recommended by several national guidelines as important research methods for bioequivalence study of OIDPs. It can effectively bridge the gap between in vitro studies and PK-BE studies in evaluating the efficacy and safety consistency of generic drugs with the original drugs. There are two research methods for PD-BE, using a diastolic model or an excitation model. The different methods use different metrics to evaluate efficacy. The more commonly used metrics include Forced Expiratory Volume in the First Second (FEV1), Specific Airway Conductance (sGaw), Peripheral Airway Resistance (R5-20), and stimulant concentration/dose (PC20/PD20). PD-BE studies using FEV1 as an efficacy metric is also recommended by the FDA (Food and Drug Administration), EMA (European Medicines Agency) and NMPA (National Medical Products Administration) guidelines and is widely accepted by investigators. In such PD-BE studies, the trial protocols for different OIDPs drugs are relatively consistent in terms of trial design, trial data processing, and equivalence evaluation criteria, while there are detailed differences in terms of target population, single/multiple dosing, dose administration, and collection site design. This paper reviews the progress of PD-BE studies in the bioequivalence evaluation of OIDPs by combining national guidelines and PD-BE-related studies of OIDPs published in the last five years, with a view to providing important theoretical information for PD-BE studies of OIDPs.

Objective:To analyze the clinical characteristics and prognostic factors of severe fever with thrombocytopenia syndrome patients with high novel Bunya viral load.Methods:The clinical data of 141 patients with severe fever with thrombocytopenia syndrome whose viral load higher than 1×10 4 copies/mL were retrospectively collected from May 20, 2013 to October 30, 2019 in Weihai Central Hospital. All patients were diagnosed by laboratory tests. According to the prognosis, the cases were divided into survival group and death group. The clinical manifestations, laboratory test results and the influence of viral load on the conditions and the risk factors of prognosis were compared and analyzed. Chi-square test, rank sum test and logistic regression analysis were used for statistical analysis. Results:There were 76 patients in survival group, with a median age of 64 years. There were 65 patients in death group, with a median age of 71 years. There were significant differences in neurological injury, coma, hemorrhage, atrial fibrillation with rapid ventricular rate, and renal injury between the survival group and the death group ( χ2=16.45, 64.06, 11.25, 6.98 and 33.80, respectively, all P<0.01). There were significant differences in activated partial thromboplastin time (APTT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), lactic acid dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatinine, and platelet count between the survival group and the death group ( Z=6.33, 4.51, 2.93, 4.65, 5.00, 4.93, 5.36 and -4.34, respectively, all P<0.01). The RNA quantification of viral load in 138 cases ranged from 1.06×10 4 to 6.53×10 7 copies/mL, and the remaining three cases were higher than 1.00×10 8 copies/mL. The viral load of the two groups were 4.63(4.32, 5.22) and 5.29(4.92, 6.17) lg copies/mL, respectively ( Z=4.91, P<0.01). The mortalities of patients with viral loads of 1.00×10 4-<1.00×10 5 copies/mL, 1.00×10 5-<1.00×10 6 copies/mL and 1.00×10 6-<1.00×10 7 copies/mL were 29.33%(22/75), 51.28%(20/39), 80.95% (17/21), respectively. Six cases with viral loads higher than 1.00×10 7 copies/mL were dead. Logistic regression analysis showed that when age ≥60 years old, viral load >1.00×10 6 copies/mL, platelet count <30.00×10 9/L, LDH ≥5 000.00 U/L, APTT ≥84.00 s, the risk of death increased significantly. Conclusions:The occurrences of coma, hemorrhage, atrial fibrillation with rapid ventricular rate, renal injury suggest that the patients′ conditions are more serious and the risk of death is higher. Age, viral load, platelet count, LDH and APTT can be used as indicators to assess the risk of death.

Objective: To evaluate the association between NLRP2(NLR Family Pyrin Domain Containing 2) gene polymorphisms and classical type 1 diabetes mellitus(T1DM) in Chinese Han population. Methods: A case-control study was conducted in 510 classical T1DM patients from the Department of Metabolism and Endocrinology in the Second Xiangya Hospital affiliated to Central South University and 531 healthy controls in this region. The polymorphisms of rs1043673 in NLRP2 gene were analyzed by MassARRAY. Mann-Whitney U test and χ² test were used to compare the differences between patients and controls. Logistic regression analysis and χ² test were performed to compare the distributions of the alleles and genotypes between T1DM patients and controls. Kruskal-Wallis H test was used to compare the clinical characteristics of different genotypes in T1D patients. Results: The differences of the allele and genotype distributions in rs1043673 of NLRP2 gene were not significant between patients and controls. The polymorphisms of rs1043673 were associated with fasting C-peptide(P=0.029), postprandial 2-h C-peptide(P=0.017), and titer of GADA(P=0.043) in T1DM patients. Conclusion The polymorphisms of NLRP2 gene were associated with the characteristics of T1DM patients.

With the aging of the society, the number of stroke patients has been increasing year by year. Compared with the traditional rehabilitation therapy, the application of upper limb rehabilitation robot has higher efficiency and better rehabilitation effect, and has become an important development direction in the field of rehabilitation. In view of the current development status and the deficiency of upper limb rehabilitation robot system, combined with the development trend of all kinds of products of the upper limb rehabilitation robot, this paper designed a center-driven upper limb rehabilitation training robot for cable transmission which can help the patients complete 6 degrees of freedom (3 are driven, 3 are underactuated) training. Combined the structure of robot with more joints rehabilitation training, the paper choosed a cubic polynomial trajectory planning method in the joint space planning to design two trajectories of eating and lifting arm. According to the trajectory equation, the movement trajectory of each joint of the robot was drawn in MATLAB. It laid a foundation for scientific and effective rehabilitation training. Finally, the experimental prototype is built, and the mechanical structure and design trajectories are verified.

Objective To explore the severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) existence time in the body,and the correlation between viral load and the severity and prognosis of disease.Methods The clinical data of 125 SFTS patients from May 2015 to October 2016 in Weihai Central Hospital in Shandong province were analyzed retrospectively.Patients were divided into low viral load group and high viral load group according to the SFTSV RNA levels.Neurological symptoms,bleeding tendency,the incidence of myocardial damage and severe pneumonia,laboratory biochemical index and prognosis of two groups were compared.SFTSV RNA of 46 cases were detected dynamically.Data with homogeneity of variance were tested by t test,and data with heterogeneity of variance was tested by rank sum test.Results Among the 125 cases,64 were male and 61 were female.The mean age was (59.0±3.6) years old.One hundred and one cases were cured,and 24 died.SFTSV RNA loads in low viral load group(81 cases) were (3.08± 1.01) copies/mL,and those in high viral load group (44 cases) were (5.69 ± 0.99) copies/mL,with statically significant difference (t =11.78,P＜0.05).By the dynamic detection of SFTSV RNA load in 46 patients,viral loads in most patients were gradually declined after 1 week of onset,and cleared after 23 days.The incidence of neurological symptoms,bleeding tendency,severe myocardial damage and pneumonia of two groups showed significant difference (x2 =92.987,38.711,75.889 and 54.680,respectively,all P＜0.05).The viral loads of patients who died varied from 1.06× 104 copies/mL to 5.78 × 107 copies/mL.White blood counts of two groups showed no significant difference (t =0.181,P＞ 0.05).The platelet counts of two groups had significant difference (t =2.869,P＜0.05).AST and γ-GT of two groups also had significant difference (P＜0.01 and 0.05,respectively).creatine kinase,creatine kinase isoenzyme,lactic dehydrogenase and hydroxybutyrate dehydrogenase of two groups all had significant difference (P＜0.01 or 0.05).Serum sodium,blood calcium and glucose of the two groups had significant difference (P＜0.01 or 0.05).activated partial thromboplastin time of the two groups showed significant difference as well (t=5.623,P＜0.01).Conclusions After the onset of SFTSV infection,the virus existence in the body may less than 4 weeks.Viral loads are closely associated with disease severity and prognosis.The higher the viral loads are,the heavier organ dysfunction could be and the higher mortality is.

OBJECTIVE:To study improvement effect of modified mahuang chanyi decoction on allergic rhinitis(AR)model guinea pigs and its mechanism. METHODS:32 guinea pigs were randomly divided into normal group (0.9% Sodium chloride in-jection),model group (0.9% Sodium chloride injection),experimental [Modified mahuang chanyi decoction,5.18 g (medicinal materials)/kg] group and control [Fluticasone propionate nasal spray,50 μg/(guinea pig·d)] group. Except for normal group,other groups received ovalbumin 30 mg and calmogastrin 30 mg intraperitoneally to induce AR model. Except for control group,other groups were given relevant medicine intragastrically,twice a day for consecutive 15 d. Nasal symptoms of guinea pigs were ob-served and recorded,and then analyzed and scored. The protein expression of nasal mucosa SHP-1 was detected by immunohisto-chemistry,the serum contents of IL-4 and IFN-γ were determined by enzyme-linked immunosorbent assay. RESULTS:Compared with normal group,model group suffered from AR symptom,and nasal symptoms score was increased;and the protein expression of nasal mucosa SHP-1 and the serum content of IL-4 increased,while the content of IFN-γ decreased(P<0.05). Compared with model group,AR symptom of experimental group and control group were improved;nasal symptoms score,the protein expression of nasal mucosa SHP-1 and the serum content of IL-4 decreased while the content of IFN-γ increased(P<0.05). CONCLUSIONS:Modified mahuang chanyi decoction shows certain improvement effect on AR,and its mechanism is associated the decrease of IL-4 content and the increase of IFN-γcontent in serum.