Objective To summarize a case of latent autoimmune diabetes in adults(LADA)who received medication therapy management(MTM)of pharmaceutical outpatient service,and to provide reference for the treatment of similar diseases.Methods The physician recommended a 61-year-old male patient with LADA to the pharmacy clinic on March 27,2023.The pharmacists provided MTM services for the patient through pharmacy inquiry,medication evaluation,medication reconciliation,medication education,and pharmacy follow-up,return visit or pharmacy follow-up for the patient once a week,and established the patient MTM archives.Results Through fifteen MTM services for over three months,including eight visits to the pharmaceuti-cal outpatient clinic and follow-up seven times.On July 10,2023,the atherosclerotic cardiovascular disease(ASCVD)monitoring indicators,such as fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),blood pressure,heart rate,low density lipo-protein cholesterol(LDL-C),and homocysteine(HCY),reduced from 7.17 mmol·L-1,6.8％,140-150/90-100 mmHg,80-90 times·min-1,2.15 mmol·L-1,16.30 μmol·L-1 to 6.06 mmol·L-1,6.1％,120-130/70-80 mmHg,60-70 times·min-1,1.63 mmol·L-1,8.67 μmol·L-1 after MTM services.The ASCVD monitoring indicators were effectively controlled.After thirty-two weeks,the re-examination of the patient's fasting C-P level remained stable,there was no significant decline in pancreas islet function,and cardiac ultrasound showed that cardiac function had a certain improvement.Conclusion By providing MTM serv-ices and reconciliation the medication regimen for the patient with LADA,the ASCVD monitoring indicators such as blood glu-cose,blood pressure,blood lipids,heart rate,and homocysteine were controlled to meet the standards,effectively protecting the pancreatic β-cell and target organs functions of the patient,and significantly improving his health management level.

Objective To summarize a case of latent autoimmune diabetes in adults(LADA)who received medication therapy management(MTM)of pharmaceutical outpatient service,and to provide reference for the treatment of similar diseases.Methods The physician recommended a 61-year-old male patient with LADA to the pharmacy clinic on March 27,2023.The pharmacists provided MTM services for the patient through pharmacy inquiry,medication evaluation,medication reconciliation,medication education,and pharmacy follow-up,return visit or pharmacy follow-up for the patient once a week,and established the patient MTM archives.Results Through fifteen MTM services for over three months,including eight visits to the pharmaceuti-cal outpatient clinic and follow-up seven times.On July 10,2023,the atherosclerotic cardiovascular disease(ASCVD)monitoring indicators,such as fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),blood pressure,heart rate,low density lipo-protein cholesterol(LDL-C),and homocysteine(HCY),reduced from 7.17 mmol·L-1,6.8％,140-150/90-100 mmHg,80-90 times·min-1,2.15 mmol·L-1,16.30 μmol·L-1 to 6.06 mmol·L-1,6.1％,120-130/70-80 mmHg,60-70 times·min-1,1.63 mmol·L-1,8.67 μmol·L-1 after MTM services.The ASCVD monitoring indicators were effectively controlled.After thirty-two weeks,the re-examination of the patient's fasting C-P level remained stable,there was no significant decline in pancreas islet function,and cardiac ultrasound showed that cardiac function had a certain improvement.Conclusion By providing MTM serv-ices and reconciliation the medication regimen for the patient with LADA,the ASCVD monitoring indicators such as blood glu-cose,blood pressure,blood lipids,heart rate,and homocysteine were controlled to meet the standards,effectively protecting the pancreatic β-cell and target organs functions of the patient,and significantly improving his health management level.

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.

AIM To study the chemical constituents from Euphorbia humifusa Willd.and their in vitro anti-hepatoma activity.METHODS Silica gel,D101 macroporous adsorption resin and semi-preparative RP-HPLC were used for isolated and purified,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-hepatocellular carcinoma activity was determined by MTT mothod.RESULTS Eighteen compounds were isolated and identified as 22-O-angeloyl-R1-barrigenol(1),dimethyl 3,3'-[oxybis(4,1-phenylene)](2E,2'E)-diacrylate(2),N-(3-methoxy-1,3-dioxopropyl)-D-tryptophan methyl ester(3),N-acetyltryptophan methyl ester(4),N-(methoxycarbonyl)-tryptophan methyl ester(5),(3β,5α,17β)-4,4,8,14-tetramethyl-18-norandrostane-3,17-diol(6),3β,18,19β-trihydroxylupane(7),pregnenolone(8),3-hydroxy-5,6-epoxy-7-megastigmen-9-one(9),dehydrovomifoliol(10),loliolide(11),2,2'-oxybis(1,4-di-tert-butylbenzene)(12),dibutyl phthalate(13),4-methoxycinnamic acid(14),3,4-dimethoxycinnamic acid(15),methyl 4-hydroxybenzoate(16),kaempferol(17),quercetin(18).The IC50 values of compounds 1,7 and 8 on HepG2 cells were(17.27±0.92),(19.11±2.14)and(7.53±1.09)μmol/L,respectively.CONCLUSION Compounds 1-16 are first isolated from this plant.Compounds 1,7 and 8 have anti-hepatoma activity.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

Objective:This study aimed to analyze the expression of B-cell maturation antigen (CD269) on myeloma cells in patients with newly diagnosed multiple myeloma (NDMM) and evaluate its prognostic value.Methods:The retrospective analysis was conducted on the clinical data of 154 NDMM patients admitted to the outpatient clinics and wards of Beijing Chaoyang Hospital, Capital Medical University from October 23, 2018 to December 25, 2023, including 90 males and 64 females, aged 60(55,66) years old. CD269 phenotype was analyzed using flow cytometry (FCM). Specifically, patients were divided into CD269 positive group (expression>20%, n=103) and CD269 negative group (expression≤20%, n=51) based on the flow cytometry prior to treatment. Initially, we assessed the effect of CD269 expression on progression-free survival (PFS) in patients with NDMM and compared the two groups. Through a cross-sectional analysis, we examined the basic clinical characteristics, 32 laboratory indicators, and 5 cytogenetic indicators. We identified differences between the two groups and analyzed the impact of various indicators on the PFS of patients in both the CD269 positive and negative groups. Furthermore, we employed the Cox proportional hazards regression model to evaluate the influence of CD269 expression and other disease-related indicators on patients′ PFS. Results:Among 154 NDMM patients, 103 were identified as CD269 positive (66.9%), while 51 were CD269 negative (33.1%). No statistically significant differences in clinical indicators were observed between the two groups. The PFS for CD269 positive group was significantly lower than it in the CD269 negative group [28.0(18.0,41.0) months vs 35.0 (27.0, -) months, HR=2.012, 95% CI 1.059-3.824, χ 2=4.554, P=0.033]. Cox proportional hazards regression analysis indicated that CD269 positivity and non-IgG subtypes were independent risk factors influencing PFS in NDMM patients( HR=2.395,95% CI 1.152-4.979, P=0.019; HR=0.425,95% CI 0.223-0.810, P=0.009). In the CD269 positive group, progression-free survival (PFS) was significantly shortened in patients with>65 years, non-IgG subtypes, International Staging System (ISS) stage Ⅲ, β2-microglobulin (β2-MG) levels≥5.5 mg/L, abnormal t(11;14) or ≥3 cytogenetic abnormalities. Conclusion:CD269 positivity serves as an independent risk factor influencing PFS in NDMM patients. Among the factors examined, older age, non-IgG subtype, ISS stage Ⅲ, elevated serum β2-MG, the presence of an abnormal t(11;14) translocation and≥3cytogenetic abnormalities, significantly impact the PFS of CD269 positive patients.

Objective To investigate the effect of programmed death-1(PD-1)on cell infiltration in muscle tissue and immune response types in mice infected with Trichinella spiralis.Methods C57BL/6J wild-type(WT)and PD-1 deficient(PD-1-/-)mice were infected with T.spiralis(400 muscle larvae per mouse),and samples were collected on day 35 after infection.The proportions of infiltrating inflammatory cells and fibroblasts around encapsulated larvae were assessed by immunohistochemistry.The expression levels of interferon-γ(IFN-γ),interleukin(IL)-4,IL-5,IL-13,and eotaxin in muscle tissue were measured using enzyme-linked immunosorbent assay.Peripheral blood and spleen were collected at different time points after infection.The percentages of CD4+IFN-γ+Th1 and CD4+IL-4+Th2 within CD4+T cells population in peripheral blood and spleen of mice were analyzed using flow cytometry.Results The proportions of eosinophils and fibroblasts among total infiltrating cells around the encapsulated larvae in the muscle of PD-1-/-mice were significantly lower than those in WT mice after T.spiralis infection(P＜0.01).The infected PD-1-/-mice exhibited higher proportions of macrophages,T cells and B cells in total infiltrating cells than the infected WT mice(P＜0.01).The levels of IL-4,IL-5,IL-13,and eotaxin in the muscle tissue of infected PD-1-/-mice were significantly lower than those in infected WT mice(P＜0.05).However,IFN-γ levels were not significantly different between the infected WT and PD-1-/-mice.The proportions of Th2 cells in CD4+T cells from peripheral blood and spleen of infected PD-1-/-mice were significantly lower than those in infected WT mice,whereas the proportion of Th1 cells showed no difference among the infected groups.Conclusions PD-1 deletion results in decreased expression of key chemokines of eosinophils and key cytokines of fibroblast formation,and a corresponding decrease in inflammatory cells in muscle in T.spiralis-infected mice.This effect may be associated with a diminished Th2 immune response caused by PD-1 deletion.