ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

Jiangsu Provincial People's Hospital takes the reform of DRG payment method as an opportunity,based on the theory of incentive behavior,uses literature research,expert consultation,and key performance indicator methods to develop evaluation indicators,and applies PDCA management tools to establish a continuously improving medical insurance service quality evaluation system.It introduces the process of medical insurance service quality evaluation system construction and its application in medical insurance performance management,and analyzes the implementation effect:DRG operation is improving,disease group structure is optimized,medical quality and efficiency continue to improve,and medical service evaluation scores are improving.

Objective To investigate the protective effects and underlying mechanisms of sodium butyrate on rats exposed to hypoxia and cold conditions.Methods Fifty-eight male SD rats (aged 7～8 weeks,weighing 240～260 g ) were randomly divided into normoxia normothermia saline control (NNC ) group (n=10),normoxia normothermia sodium butyrate(NNB)group(n=10),hypoxia cold saline control (HCC) group (n=19),and hypoxia cold sodium butyrate (HCB)group (n=19).The intragastric dose of sodium butyrate was 200 mg/kg for the NNB and HCB groups,while the NNC and HCC groups were given normal saline of 5 mL/kg.①After continuous intragastric administration for 7 d,the rats in the HCC and HCB groups were placed in a low-pressure hypoxic chamber to simulate an altitude of 5000 m and exposed to a temperature of 8 ℃ for 7 d.Subsequently,blood samples were collected from the abdominal aorta for blood gas analysis,blood routine test,and detection for serum biochemical indicators.ELISA was used to determine serum inflammatory cytokines and endocrine hormones.The rats in the NNC and NNB groups(n=10)were fed outside the chamber and underwent the same tests in 7 d later to evaluate the protective effects of sodium butyrate on the body.②Core body temperature monitoring was conducted to assess the impact of sodium butyrate on the rmoregulation in rats exposed to hypoxia and cold(n=3).③Hypoxia exercise tolerance of the HCC group and HCB group in a hypoxic chamber (11％O2 )was evaluated for their hypoxia resistance (n=6).Results Compared to the NNC group,the rats in the HCC group exhibited significant decreases in arterial oxygen saturation (SaO2 )and arterial oxygen partial pressure (PaO2 ),serum levels of IL-4,estradiol (E2)and cortisol (F),core temperature,and exercise duration (P<0.05),and had notably increased levels of red blood cell (RBC)count,hemoglobin (HGB),hematocrit (HCT),cardiac troponin (CRDAC-T),uric acid (UA),alanine aminotransferase (ALT),total cholesterol (TC),low-density lipoprotein (LDL),IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)(P<0.05).Compared to the HCC group,the rats in the HCB group exhibited significant increases in SaO2,PaO2,IL-4,E2,F,corticotropin releasing hormone (CRH)and adrenocorticotropic hormone (ACTH)(P<0.05),remarkably longer exercise duration under hypoxic exposure (P<0.05 ),but decreases in RBC count,serum levels of HGB,HCT,CRDAC-T,UA,ALT,TC,LDL,IL-6,GM-CSF and free thyroxine (FT4 ),and core temperature (P<0.05).Conclusion Sodium butyrate exhibits protective effects on rats exposed to hypoxia and cold conditions,and it is helpful in their adaptation to these hypoxia and cold environments.

Objective:To summarize experience of managing adult Langerhans cell histiocytosis(LCH) in hypothalamic-pituitary region(HPR) from Shanghai Huashan Hospital.Methods:Adult HPR-LCH patients diagnosed at oar endocrinology department from January 2013 to February 2022 were included. Clinical characteristics and treatment response were retrospectively analyzed.Results:A total of 27 adult HPR-LCH patients were included, with 14 cases involving the hypothalamus(H group) and 13 cases without(group NH). The common radiological findings included thickening of the pituitary stalk(25/27, 92.6%). At the time of diagnosis, 14 cases(51.9%) presented with panhypopituitarism, and 19 cases(70.4%) exhibited metabolic abnormalities. The group H had higher proportions of adrenal insufficiency, central hypothyroidism, panhypopituitarism, and diabetes compared to group NH(78.6% vs 23.1%; 78.6% vs 23.1%; 92.9% vs 30.8%, 35.7% vs 0%, respectively, all P<0.05). Hypothalamus syndrome was identified in 71.4%(10/14) of group H. The inital diagnosis rate was 79.2%(19/24), with 48.1% and 51.9% through biopsy of sellar and extrasellar lesions, respectively. Repeated biopsies confirmed the diagnosis in 25.9%(7/27) of cases. The peripheral lesions included bone, thyroid, lung, lymph node, thymus and liver. Out of 20 cases treated with chemotherapy, the objective response rate was 85% at 12 weeks. Four cases received local therapy, one case received traditional Chinese medicine treatment, one case abandoned treatment, and one case was lost to follow-up. The median follow-up time was 28(range 15 to 54) months. During this period, there were 3 deaths in group H and 1 death in group NH. Conclusion:Adult HPR-LCH patients presented with diabetes insipidus and high prevalences of hypopituitarism, hypothalamus syndrome and metabolic abnormalities. Typical imaging features were pituitary stalk thickening. A solitary mass in the HPR was usually very small, posing a great challenge for early diagnosis. Systemic evaluation would help to clarify the diagnosis. Patients with hypothalamus involvement had a higher mortality rate, suggesting the hypothalamus as a risk organ with poor prognosis.

OBJECTIVE: To investigate the protective effects of total saponins from Panax japonicus (TSPJ) against high-fat dietinduced testicular Sertoli cell junction damage in mice. METHODS: Forty male C57BL/6J mice were randomized into normal diet group, high-fat diet group, and low-dose (25 mg/kg) and high-dose (75 mg/kg) TSPJ treatment groups (n=10). The mice in the normal diet group were fed a normal diet, while the mice in the other groups were fed a high-fat diet. After TSPJ treatment via intragastric administration for 5 months, the testes and epididymis of the mice were collected for measurement of weight, testicular and epididymal indices and sperm parameters. HE staining was used for histological evaluation of the testicular tissues and measurement of seminiferous tubule diameter and seminiferous epithelium height. The expression levels of ZO-1, occludin, claudin11, N-cadherin, E-cadherin and β-catenin in Sertoli cells were detected with Western blot, and the localization and expression levels of ZO-1 and β-catenin in the testicular tissues were detected with immunofluorescence assay. The protein expressions of LC3B, p-AKT and p-mTOR in testicular Sertoli cells were detected using double immunofluorescence assay. RESULTS: Treatment with TSPJ significantly improved high-fat diet-induced testicular dysfunction by reducing body weight (P < 0.001), increasing testicular and epididymal indices (P < 0.05), and improving sperm concentration and sperm viability (P < 0.05). TSPJ ameliorated testicular pathologies and increased seminiferous epithelium height of the mice with high-fat diet feeding (P < 0.05) without affecting the seminiferous tubule diameter. TSPJ significantly increased the expression levels of ZO-1, occludin, N-cadherin, E-cadherin and β-catenin (P < 0.05) but did not affect claudin11 expression in the testicular tissues. Immunofluorescence assay showed that TSPJ significantly increased ZO-1 and β-catenin expression in the testicular tissues (P < 0.001), downregulated LC3B expression and upregulated p-AKT and p-mTOR expressions in testicular Sertoli cells. CONCLUSION TSPJ alleviates high-fat diet-induced damages of testicular Sertoli cell junctions and spermatogenesis possibly by activating the AKT/mTOR signaling pathway and inhibiting autophagy of testicular Sertoli cells.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Testis ; Sertoli Cells ; beta Catenin ; Diet, High-Fat ; Occludin ; Proto-Oncogene Proteins c-akt ; Seeds ; Cadherins ; Intercellular Junctions

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6^th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×10⁹/L and PLT≥25×10⁹/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3⁺HLA-DR⁺T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3⁺CD19^-T cells， CD4⁺T cells， CD8⁺T cells， Th1 cells， Th2 cells， and CD3⁺CD25⁺T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×10⁹/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3⁺HLA-DR⁺ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×10⁹/L， PLT≥25×10⁹/L， and higher CD3⁺ HLA-DR⁺T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.
Male ; Humans ; Sertoli Cells ; Leucine/pharmacology* ; Arginine/pharmacology* ; Microcystins/metabolism* ; Immunity

OBJECTIVE To interpret Teacher Training Syllabus for Clinical Pharmacist Training Program （2023 edition） （hereinafter referred as to the “new syllabus”）， and to provide reference and guidance for promoting the implementation of the new syllabus and realizing the quality-improving goal of the reform of the clinical pharmacist teacher training program initiated by China Hospital Association. METHODS From the perspective of the management and based on the position of the designer， the new syllabus was interpreted from four aspects： the background of its compilation and release， the process of its compilation and its characteristics， the key improvements of the program and the points for attention about its subsequent implementation. RESULTS & CONCLUSIONS The development and release of the new syllabus provide a “construction blueprint” for the reform of the clinical pharmacist teacher training program of the China Hospital Association. The whole process of compiling the new syllabus is characterized by four basic features： theory-led， goal-oriented， research-based， and synergistic. Compared with the previous syllabus， in addition to the adjustment of the text structure，the new syllabus presents more complete and clearer competence requirements for clinical teaching competence in terms of training objectives； in terms of training content， it further structures the group of task items， pays attention to the 育。E-mail：zhenjiancun@163.com sequential planning and time arrangement of items， and puts forward both quantitative and qualitative refinement requirements for each specific training task；in terms of training methods， it emphasizes the interaction of lecturing， demonstrating and guiding， and the progression of observation， operation and reflection， with the intention of guiding teacher trainees to “learn how to teach by teaching”. In the subsequent implementation of the new syllabus， it is necessary for the teacher training bases to attach great importance to the guarantee of training conditions and process quality management， and to organize the teacher training team to do a good job in the two training programs of “clinical pharmacist training” and “clinical pharmacist teacher training”. Based on further improving the connection between the two training programs， the teacher training team should continue to explore the scientific model of clinical pharmacist teacher training oriented by clinical teaching competence.

Objective:To establish a multicriteria value assessment index system, so as to provide reference for hospitals access of medical consumables.Methods:In May 2021, based on the paper previously published, the expert consultation method was used to finalize the index structure, index definitions and scoring standards, along with an importance grading of the indexes. And the index weights were calculated using the analytical hierarchy process. Then the assessment scale was designed by way of multi-criteria decision analysis and mini-HTA. With the linear cutting stapler used as an example, six clinicians, three hospital administrators and the medical consumable management committee made an empirical analysis and evaluation of its general value. The coefficient of variation and Kendall coefficient of concordance were used to test the consistency of clinicians′ scores.Results:Three rounds of expert consultations finalized an index structure with 4 level-1 and 11 level-2 indexes, and on such basis a multicriteria value assessment index system for hospital access of medical consumables was established. This system comprised the clinician evaluation scale, hospital administrator evaluation scale and medical consumable management committee evaluation scale. The first two of which were used for preliminary screening, and the third for a full-scale, detailed and quantitative evaluation of those selected, hence a decision was made in the end according to the weighted sum of the three scales. This scale system was used to evaluate a foreign brand and a domestic brand of linear cutting staplers, while the former and the latter scored 90.5 and 75.4 respectively. Statistical analysis of the six clinicians found a coefficient of variation CV<0.25, and the Kendall coefficient of concordance W=0.833, proving good consistency of the evaluation criteria and results. Conclusions:The multicriteria value assessment index system proves highly scientific, comprehensive and practicable, serving a good reference for hospitals to build their value-based mechanism to select medical consumables.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.