ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective To explore the correlation between body fat estimation formula of Navarra University(CUN-BAE)and bone mineral density(BMD)in patients with type 2 diabetes mellitus(T2DM)and its predictive value for osteoporosis(OP).Methods A total of 428 patients with T2DM who were hospitalized in the Department of Endocrinology and Metabolism,Affiliated Hospital of Jiangsu University were enrolled in this study between October 2017 and October 2023.All the patients were divided into simple T2DM group(n=226),osteopenia(OT,n=126)group and OP group(n=76)according to BMD.The general data and biochemical indexes were compared between the two groups.The value of CUN-BAE was calculated,and the BMD value was testedby dual-energy X-ray method.The correlation between CUN-BAE and other indexes was evaluated by Spearman correlation,and the influencing factors for OP was evaluated by Logistic regression in T2DM patients.The diagnostic efficacy of CUN-BAE was explored by receiver operating characteristic(ROC)curve in T2DM patients complicated with OP.Results CUN-BAE was higher in OP group than in T2DM and OT group(P<0.05).Spearman correlation analysis showed that CUN-BAE was negatively correlated with the values of L1,L2,L3,L4,L1～L4,L2～L4,femoral neck BMD,wards triangle BMD,greater trochanter BMD,total hip BMD and L1～L4 BMD T value(P<0.05).Logistic regression analysis showed that CUN-BAE was a influencing factor for OP in T2DM patients.ROC curve analysis showed that the area under the curve predicted by CUN-BAE for T2DM patients complicated with OP was 0.672.Conclusions CUN-BAE value were significantly elevated in T2DM patients with OP.CUN-BAE was valuable for predicting OP in T2DM patients.

Objective To explore the correlation between body fat estimation formula of Navarra University(CUN-BAE)and bone mineral density(BMD)in patients with type 2 diabetes mellitus(T2DM)and its predictive value for osteoporosis(OP).Methods A total of 428 patients with T2DM who were hospitalized in the Department of Endocrinology and Metabolism,Affiliated Hospital of Jiangsu University were enrolled in this study between October 2017 and October 2023.All the patients were divided into simple T2DM group(n=226),osteopenia(OT,n=126)group and OP group(n=76)according to BMD.The general data and biochemical indexes were compared between the two groups.The value of CUN-BAE was calculated,and the BMD value was testedby dual-energy X-ray method.The correlation between CUN-BAE and other indexes was evaluated by Spearman correlation,and the influencing factors for OP was evaluated by Logistic regression in T2DM patients.The diagnostic efficacy of CUN-BAE was explored by receiver operating characteristic(ROC)curve in T2DM patients complicated with OP.Results CUN-BAE was higher in OP group than in T2DM and OT group(P<0.05).Spearman correlation analysis showed that CUN-BAE was negatively correlated with the values of L1,L2,L3,L4,L1～L4,L2～L4,femoral neck BMD,wards triangle BMD,greater trochanter BMD,total hip BMD and L1～L4 BMD T value(P<0.05).Logistic regression analysis showed that CUN-BAE was a influencing factor for OP in T2DM patients.ROC curve analysis showed that the area under the curve predicted by CUN-BAE for T2DM patients complicated with OP was 0.672.Conclusions CUN-BAE value were significantly elevated in T2DM patients with OP.CUN-BAE was valuable for predicting OP in T2DM patients.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

Objective To formulate a pharmaceutical service pathway to standardize the pharmacists'whole process of pharmaceutical services for breast cancer patients in medical institutions,promote the standardization of pharmacists'work and improve the rationality of drug use for breast cancer patients in medical institutions.Methods The editorial committee aimed at several challenging problems in the whole process of pharmaceutical services for breast cancer patients in medical institutions through systematic search,referring to the latest domestic and international guidelines and expert consensus of breast cancer and under the relevant drug administration regulations in China,collected and sorted out the professional opinions of doctors,pharmacists,and methodological experts,developed questionnaires and held two rounds of expert argumentation meetings,and finally screened out the most valuable results.The whole process management pathway of pharmaceutical care for breast cancer patients was formulated,and the referral principles of hospitals at different levels and the contents of pharmacist training and assessment were clarified.Results The whole process management pathway of pharmaceutical services for breast cancer patients was developed,including information collection,analysis,evaluation,development implementation of intervention plans,and follow-up.Conclusion This pharmaceutical service pathway can standardize and guide pharmacists in hospitals at different levels to carry out pharmaceutical services for breast cancer patients,achieve the whole process of monitoring drug use,and ensure rational drug use and treatment effectiveness for patients.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

Heart failure is a group of complex clinical syndromes in the middle and late stages of cardiovascular diseases.Mitochondrial homeostasis imbalance is one of the pathological mechanisms in the occurrence and development of heart failure.This article revolved around the"yin-yang theory"in TCM and explained the pathological mechanism of heart failure through mitochondrial homeostasis.Heart failure is the syndrome of deficiency in nature and excess in superficiality fundamental.Its basic pathogenesis is"yang deficiency and yin excess".Based on the deficiency of heart yang qi and the stagnation of yin pathogens,the combination of deficiency and excess runs through the entire disease.Mitochondrial homeostasis imbalance is a manifestation of yin-yang imbalance at the cellular micro level,mainly manifested as inhibition of mitochondrial biosynthesis,mitochondrial dynamics imbalance,mitophagy disorder,etc.,which affects mitochondrial structure and function and leads to abnormal myocardial energy metabolism.Therefore,based on the"yin-yang theory",the basic treatment method is to"tonify deficiency and damage excess"to regulate mitochondrial biosynthesis,mitochondrial dynamics,and mitophagy,thereby maintaining mitochondrial homeostasis and improving myocardial energy metabolism,which is of great significance for the prevention and treatment of heart failure.