金水宝片联合卡托普利治疗慢性肾功能衰竭的临床研究

目的 分析金水宝片联合卡托普利治疗慢性肾功能衰竭的临床疗效。方法 选取2020年12月—2023年8月南通市中医院收治的116例慢性肾功能衰竭患者,按随机数字表法将所有患者分为对照组和治疗组,每组各58例。对照组口服卡托普利片,25 mg/次,3次/d。治疗组在此基础上口服金水宝片,5片/次,3次/d。两组疗程8周。观察两组临床疗效,比较两组治疗前后主要症状积分、肾功能指标[血肌酐（Scr）、24 h尿蛋白定量（24 h UP）、尿素氮（BUN）、内生肌酐清除率（Ccr）]和血清血管紧张素Ⅱ（AngⅡ）、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶-9（MMP-9）、成纤维细胞生长因子23（FGF-23）水平的变化。结果 治疗后,治疗组总有效率是93.10%,显著高于对照组的79.31%（P＜0.05）。治疗后,两组主要症状（倦怠乏力、腰酸膝软、气短懒言、食少纳呆）积分均较治疗前显著降低（P＜0.05）;治疗后,治疗组主要症状积分低于对照组（P＜0.05）。治疗后,两组Scr、24 h UP、BUN均显著降低,而Ccr均显著增加（P＜0.05）;治疗后,治疗组肾功能指标改善更显著（P＜0.05）。治疗后,两组血清AngⅡ、TNF-α、MMP-9、FGF-23水平均显著下降（P＜0.05）;治疗后,治疗组AngⅡ、TNF-α、MMP-9、FGF-23水平低于对照组（P＜0.05）。结论 金水宝片联合卡托普利治疗慢性肾功能衰竭效果确切,能在较好的用药安全性基础上,有效减轻患者症状,纠正机体炎症和代谢紊乱状态,抑制肾小管纤维化,改善肾功能,值得临床推广应用。     

Pathophysiological Role of Vascular Smooth Muscle Alkaline Phosphatase in Medial Artery Calcification

Medial vascular calcification (MVC) is a pathological phenomenon that causes vascular stiffening and can lead to heart failure; it is common to a variety of conditions, including aging, chronic kidney disease, diabetes, obesity, and a variety of rare genetic diseases. These conditions share the common feature of tissue‐nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. To evaluate the role of TNAP in MVC, we developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells in an X‐linked manner. Hemizygous overexpressor male mice (Tagln‐Cre^+/–; Hprt^ALPL/Y or TNAP‐OE) show extensive vascular calcification, high blood pressure, and cardiac hypertrophy, and have a median age of death of 44 days, whereas the cardiovascular phenotype is much less pronounced and life expectancy is longer in heterozygous (Tagln‐Cre^+/–; Hprt^ALPL/?) female TNAP‐OE mice. Gene expression analysis showed upregulation of osteoblast and chondrocyte markers and decreased expression of vascular smooth muscle markers in the aortas of TNAP‐OE mice. Through medicinal chemistry efforts, we developed inhibitors of TNAP with drug‐like pharmacokinetic characteristics. TNAP‐OE mice were treated with the prototypical TNAP inhibitor SBI‐425 or vehicle to evaluate the feasibility of TNAP inhibition in vivo. Treatment with this inhibitor significantly reduced aortic calcification and cardiac hypertrophy, and extended lifespan over vehicle‐treated controls, in the absence of secondary effects on the skeleton. This study shows that TNAP in the vasculature contributes to the pathology of MVC and that it is a druggable target. © 2015 American Society for Bone and Mineral Research.     

HPLC法测定新型酪氨酸酶抑制剂UP302乳膏的含量及皮肤表面残留量

目的:建立测定UP302乳膏中UP302含量的HPLC方法,并应用于研究UP302乳膏在大鼠皮肤局部给药后的皮肤残留百分率。方法:采用Phenomenex Luna 5u C18(150 mm×4.6 mm,5μm)色谱柱,柱温35℃;流动相为甲醇-水,以1.0 mL·min-1梯度洗脱;检测波长280 nm;检测时间10 min。UP302对照品用甲醇溶解稀释,乳膏和空白乳膏基质中UP302用甲醇提取。结果:UP302在5～100μg·mL-1的浓度范围内线性关系良好(r=0.9999)。本方法日内日间准确度在98.5%～100.6%,日内日间精密度小于2.4%。结论:本方法专属性强,灵敏度高,重现性好,耐用性好,操作简便,结果准确,可用于UP302乳膏的含量测定,以及乳膏皮肤表面残留量的测定和制剂透皮吸收研究。     

Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial

Ethnopharmacological relevance

Stage 3 is the key phase of chronic kidney disease. Traditional Chinese medicine (TCM) has been used for the treatment of chronic kidney disease. But a large sample trial is desirable.

Materials and methods

A total of 578 Chinese patients with primary glomerulonephritis in CKD stage 3 were randomly assigned to three groups: patients received TCM (TCM group), benazepril (Ben group), TCM combined with benazepril (TCM + Ben group). Patients were followed up for 24 weeks. The primary endpoint was the time to the composite of 50% increased of serum creatinine, end stage renal disease or death.

Results

eGFR in the TCM and the TCM + Ben group were improved (week 24 vs. baseline, P < 0.05) while eGFR in the Ben group was decreased (week 24 vs. baseline, P > 0.05). 24 h urinary protein excretion (UP) and urinary albumin/creatinine (UAlb/Cr) were decreased in the TCM + Ben (week 24 vs. baseline, P < 0.05) and the Ben group (week 24 vs. baseline, P > 0.05). UP and UAlb/Cr were increased in the TCM group to week 12, then were stable (week 24 vs. baseline, P < 0.05). The hemoglobin in the TCM group was also improved (week 24 vs. baseline, P < 0.05). The accumulative survival rate in the TCM + Ben group was higher than that in the TCM group and the Ben group (P = 0.044). Side effects in the TCM group were the lowest in these groups (P < 0.05). The patients with dry cough in the TCM + Ben group and the Ben group were increased as compared with the TCM group (P < 0.05). Hyperkalemia happened less frequently in the TCM group as compared with the other two groups (P = 0.052).

Conclusions

For the patients with CKD stage 3, TCM can improve eGFR and hemoglobin with lower side effects. Benazepril significantly decreased the proteinuria. Chinese medicine integrated with benazepril can ameliorate renal function and decrease proteinuria synergistically.     

Establishing a psychiatry clerkship in a clinical teaching unit

Difficulties arising during the establishment of a clinical unit students' clerkship programme are presented. These are reviewed to establish general principles important for the successful introduction of such clerkships. Particular emphasis is laid on continual evaluation, and the results of one such evaluation are discussed.     

Student evaluation: its worth for course tutors

As part of their evaluation of the 9-week 'Medicine in the Community' course, final-year medical students completed a terminal evaluation questionnaire. Items and subject groupings were scored using a scale of 1–5 for 'value', 'interest', and 'presentation', and mean evaluations were calculated for each group of students. The results, summarized in tabular form, were posted to the seventy-three course tutors together with the mean evaluations of the course as a whole. It was hoped that this feedback on the course would help tutors to improve the standard of their contributions.
After 2 years of this evaluation, a questionnaire was sent to the course tutors to examine whether student opinion is useful to them in the planning of teaching. Findings indicate that student opinion is actively sought and the results are useful, but only if tutors can identify their individual contributions from the tabulated summary.     

Inflammatory Markers and the Risk of Hip and Vertebral Fractures in Men: the Osteoporotic Fractures in Men (MrOS)

Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro‐inflammatory markers have a higher risk of fracture. We used a case‐cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non‐spine fractures; average follow‐up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)‐6, C‐reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL‐6 (IL‐6SR) and TNF (TNFαSR1 and TNFαSR2), and IL‐10. The risk of non‐spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable‐adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0–4.2‐fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non‐spine fractures, but associations were smaller. There was no association between CRP and IL‐6SR and fracture. Men in the highest Q of IL‐10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with ≥3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11–3.71) and for vertebral fracture 3.06 (1.66–5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. © 2016 American Society for Bone and Mineral Research.     

Persistent Effect of Vitamin D Supplementation on Musculoskeletal Parameters in Adolescents One Year After Trial Completion

We showed a beneficial effect of vitamin D supplementation on musculoskeletal parameters in adolescent girls in a 1‐year, randomized, double‐blinded placebo‐controlled trial (RCT). Our objective for this study was to investigate the residual effect of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD), at the lumbar spine and hip, lean mass, and height, 1 year after trial completion. We performed post hoc analyses in 167 adolescents, 86 girls and 81 boys, age 13.9 ± 2 years, who received vitamin D or placebo during the trial, and continued into the follow‐up trial. Musculoskeletal parameters were measured at baseline, 12 months (intervention), and 24 months (follow‐up). ANOVA and t tests were used to compare results between the placebo group and the merged vitamin D arms (200 or 2000 IU/day), by gender. Baseline characteristics were comparable between treatment groups at entry into the extension. Girls who had received vitamin D during the trial, had significantly larger hip BMC increments compared to those assigned to placebo, at 24 months compared to study entry, but not 24 compared to 12 months, which persisted in adjusted analyses. There were no significant differences in bone mass changes between treatment groups in boys, at 24 months compared to 12 months or to baseline. The beneficial effect of vitamin D supplementation on hip bone mass, achieved in girls during the trial, persisted 1 year after trial completion. These net cumulative increments, 1 year after discontinuation of supplementation, may have important implications on optimizing peak bone mass accretion in adolescent girls. © 2016 American Society for Bone and Mineral Research.     

The Road to Reproducibility in Animal Research

Reproducibility of research findings is the hallmark of scientific advance. However, the recently noted lack of reproducibility and transparency of published research using animal models of human biology and disease has alarmed funders, scientists, and the public. Improved reporting of methodology and better use of statistical tools are needed to enhance the quality and utility of published research. Reporting guidelines like Animal Research: Reporting In Vivo Experiments (ARRIVE) have been devised to achieve these goals, but most biomedical research journals, including the JBMR, have not been able to obtain high compliance. Cooperative efforts among authors, reviewers and editors—empowered by increased awareness of their responsibilities, and enabled by user‐friendly guidelines—are needed to solve this problem. © 2016 American Society for Bone and Mineral Research.