渴络欣胶囊联合培哚普利治疗早期糖尿病肾病的临床研究

目的 探讨渴络欣胶囊联合培哚普利治疗早期糖尿病肾病的临床疗效。方法 选取2021年6月—2023年1月郑州大学第五附属医院收治的168例早期糖尿病肾病患者,按随机数字表法将患者分为对照组和治疗组,每组各84例。对照组晨服培哚普利叔丁胺片,4 mg/d,1次/d。治疗组在对照组基础上口服渴络欣胶囊,4粒/次,3次/d。两组疗程12周。比较两组临床疗效,治疗前后中医症状积分、肾功能指标[24 h尿蛋白定量（24 h UP）等]、相关量表[肾脏病生活质量量表1.3（KDQOL-SF 1.3）、简式抑郁-焦虑-压力量表（DASS-21）]评分及血清血管生成抑制蛋白1（VASH-1）、高迁移率族蛋白B1（HMGB1）、CXC趋化因子配体10（CXCL10）水平。结果 治疗后,治疗组总有效率是94.05%,显著高于对照组的84.52%（P＜0.05）。治疗后,两组气短乏力积分、咽干口渴积分、肢体麻木积分、肢体麻木积分、腰膝酸软积分、畏寒肢冷积分均较治疗前显著降低（P＜0.05）;治疗后,治疗组中医症状积分低于对照组（P＜0.05）。治疗后,两组血肌酐（Scr）、24 h UP、尿蛋白排泄率（UAER）低于同组治疗前（P＜0.05）;治疗后,治疗组肾功能指标改善优于对照组（P＜0.05）。治疗后,两组KDQOL-SF 1.3评分均显著增高,而DASS-21评分均显著降低（P＜0.05）;治疗后,治疗组KDQOL-SF 1.3评分和DASS-21评分改善优于对照组（P＜0.05）。治疗后,两组血清VASH-1、HMGB1、CXCL10水平均显著降低（P＜0.05）;治疗后,治疗组血清VASH-1、HMGB1、CXCL10水平低于对照组（P＜0.05）。结论 渴络欣胶囊联合培哚普利治疗早期糖尿病肾病具有良好的疗效,能有效缓解机体炎症反应、控制肾组织纤维化,在患者症状和负面情绪减轻、肾功能和生活质量改善方面获得更佳效果,值得临床推广应用。     

胃癌的综合治疗

目的 评价胃癌综合治疗的效果。方法 回顾性分析１９８４年１０月～１９９９年１０月接受治疗的２０４例胃癌病人的临床资料。结果 综合治疗组５年生存率为４１．２％,单纯手术组５年生存率为２０．６％（Ｐ〈０．０１）。结论 以手术为主,辅以腹腔灌注化疗、全身化疗、免疫治疗的综合治疗能显著改善胃癌病人的预后。     

Relationship of Height to Site‐Specific Fracture Risk in Postmenopausal Women

Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (p_{heterogeneity} < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (p_{heterogeneity} = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Bisphosphonate Withdrawal: Effects on Bone Formation and Bone Resorption in Maturing Male Mice

Bisphosphonates are being increasingly used to treat pediatric patients with skeletal disorders. However, the effects of long‐term bisphosphonate therapy and cessation of therapy during growth are unclear. Thus, studies were undertaken to determine the effects of alendronate discontinuation after treatment of C57Bl/6 mice during the period of rapid skeletal growth. Compared with vehicle‐treated mice, 16 weeks of alendronate treatment starting at age 18 days resulted in a 3.7‐fold increase in trabecular bone in the setting of suppressed bone formation. Alendronate therapy for 8 weeks followed by 8 weeks of vehicle treatment resulted in a more pronounced increase in trabecular bone compared with mice treated with alendronate for 16 weeks (1.7‐fold) and to vehicle‐treated controls (6.5‐fold). Mice that received alendronate for 8 weeks followed by 8 weeks of vehicle exhibited increased osteoblast surface (2.5‐fold), mineralizing surface (5.7‐fold), and bone formation rate (5.1‐fold) compared with mice treated continuously with alendronate. However, these parameters were not restored to the levels observed in the vehicle‐treated mice. Thus, partial resumption of bone formation upon cessation of bisphosphonate therapy leads to a greater increase in trabecular bone than that found when bisphosphonates are administered continuously to growing mice. These data suggest that intermittent administration of bisphosphonates may optimize their beneficial effects on the growing skeleton. © 2017 American Society for Bone and Mineral Research.     

Sclerostin-Neutralizing Antibody Treatment Rescues Negative Effects of Rosiglitazone on Mouse Bone Parameters

Obesity, a growing pandemic, is a risk factor for many cancers and causes increased bone marrow adipose tissue (BMAT). in vitro studies and obese animal models suggest that BMAT contributes to cancer progression, but there is a lack of preclinical models to directly test BMAT's role in cancer. Overactivation of peroxisome-proliferator-activated receptor-γ (PPARγ) can skew bone formation and resorption rates, resulting in increased BMAT and trabecular bone loss. Thiazolidinediones (eg, rosiglitazone) are anti-diabetic therapies that promote adipogenesis through PPARγ activation. We investigated if rosiglitazone increases BMAT in an immunocompromised model, commonly used in cancer research, and if these effects could be reversed by co-administering a bone anabolic agent (sclerostin-neutralizing antibody [Scl-Ab]), which has been shown to inhibit adipogenesis, using DXA, μCT, OsO4 μCT, and dynamic histomorphometry. Four weeks of rosiglitazone in female SCID Beige mice (cohort 1) significantly decreased trabecular bone volume (BV/TV) by about one-half, through increased osteoclast and suppressed osteoblast activity, and significantly increased BMAT. In cohort 2, mice were administered rosiglitazone ± Scl-Ab for 4 weeks, and then rosiglitazone was discontinued and Scl-Ab or vehicle were continued for 6 weeks. Scl-Ab significantly increased bone parameters (eg, BV/TV, N.Ob/B.Pm, and MS/BS) in both groups. Scl-Ab also overcame many negative effects of rosiglitazone (eg, effects on trabecular bone parameters, increased mineralization lag time [MLT], and decreased bone formation rate [BFR]). Interestingly, Scl-Ab significantly decreased rosiglitazone-induced BMAT in the femur, mostly due to a reduction in adipocyte size, but had a much weaker effect on tibial BMAT. These data suggest targeting sclerostin can prevent rosiglitazone-induced bone loss and reduce BM adiposity, in some, but not all BMAT locations. Collectively, our data demonstrate that rosiglitazone increases BMAT in SCID Beige mice, but concomitant changes in bone may confound its use to specifically determine BMAT's role in tumor models. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Objectively‐Verified Parental Non‐Hip Major Osteoporotic Fractures and Offspring Osteoporotic Fracture Risk: A Population‐Based Familial Linkage Study

Parental hip fracture (HF) is associated with increased risk of offspring major osteoporotic fractures (MOFs; comprising hip, forearm, clinical spine or humerus fracture). Whether other sites of parental fracture should be used for fracture risk assessment is uncertain. The current study tested the association between objectively‐verified parental non‐hip MOF and offspring incident MOF. Using population‐based administrative healthcare data for the province of Manitoba, Canada, we identified 255,512 offspring with linkage to at least one parent (238,054 mothers and 209,423 fathers). Parental non‐hip MOF (1984–2014) and offspring MOF (1997–2014) were ascertained with validated case definitions. Time‐dependent multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). During a median of 12 years of offspring follow‐up, we identified 7045 incident MOF among offspring (3.7% and 2.5% for offspring with and without a parental non‐hip MOF, p < 0.001). Maternal non‐hip MOF (HR 1.27; 95% CI, 1.19 to 1.35), paternal non‐hip MOF (HR 1.33; 95% CI, 1.20 to 1.48), and any parental non‐hip MOF (HR 1.28; 95% CI, 1.21 to 1.36) were significantly associated with offspring MOF after adjusting for covariates. The risk of MOF was even greater for offspring with both maternal and paternal non‐hip MOF (adjusted HR 1.61; 95% CI, 1.27 to 2.02). All HRs were similar for male and female offspring (all p_interaction >0.1). Risks associated with parental HF only (adjusted HR 1.26; 95% CI, 1.13 to 1.40) and non‐hip MOF only (adjusted HR 1.26; 95% CI, 1.18 to 1.34) were the same. The strength of association between any parental non‐hip MOF and offspring MOF decreased with older parental age at non‐hip MOF (p_trend = 0.028). In summary, parental non‐hip MOF confers an increased risk for offspring MOF, but the strength of the relationship decreases with older parental age at fracture. © 2016 American Society for Bone and Mineral Research.     

Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts

Sclerostin antibody (Scl‐Ab) increases osteoblast activity, in part through increasing modeling‐based bone formation on previously quiescent surfaces. Histomorphometric studies have suggested that this might occur through conversion of bone lining cells into active osteoblasts. However, direct data demonstrating Scl‐Ab‐induced conversion of lining cells into active osteoblasts are lacking. Here, we used in vivo lineage tracing to determine if Scl‐Ab promotes the conversion of lining cells into osteoblasts on periosteal and endocortical bone surfaces in mice. Two independent, tamoxifen‐inducible lineage‐tracing strategies were used to label mature osteoblasts and their progeny using the DMP1 and osteocalcin promoters. After a prolonged “chase” period, the majority of labeled cells on bone surfaces assumed a thin, quiescent morphology. Then, mice were treated with either vehicle or Scl‐Ab (25 mg/kg) twice over the course of the subsequent week. After euthanization, marked cells were enumerated, their thickness quantified, and proliferation and apoptosis examined. Scl‐Ab led to a significant increase in the average thickness of labeled cells on periosteal and endocortical bone surfaces, consistent with osteoblast activation. Scl‐Ab did not induce proliferation of labeled cells, and Scl‐Ab did not regulate apoptosis of labeled cells. Therefore, direct reactivation of quiescent bone lining cells contributes to the acute increase in osteoblast numbers after Scl‐Ab treatment in mice. © 2016 American Society for Bone and Mineral Research.     

A Meta‐Analysis of the Association of Fracture Risk and Body Mass Index in Women

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m²) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m², the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m² was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.