Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly. The development of foot ulcer in a diabetic patient has been estimated to be 19%-34% through their lifetime. The pathophysiology of diabetic foot ulcer consist of neuropathy, trauma and, in many patients, additional peripheral arterial disease. In particular, diabetic neuropathy leads to foot deformity, callus formation, and insensitivity to trauma or pressure. The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification, surgical debridement, dressing to facilitate wound healing, off-loading, vascular assessment (status and presence of a chance for interventional vascular correction), and infection and glycemic control. Although especially surgical procedures are sometimes inevitable, they are poor predictive factors for the prognosis of diabetic foot ulcer. Different novel treatment modalities such as nonsurgical debridement agents, oxygen therapies, and negative pressure wound therapy, topical drugs, cellular bioproducts, human growth factors, energy-based therapies, and systematic therapies have been available for patients with diabetic foot ulcer. However, it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials. This review aims at evaluating diabetic foot ulcer with regard to all aspects. We will also focus on conventional and novel adjunctive therapy in diabetic foot management.     

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.     

Effect of Yinqi Ointment on Wound Morphology and Growth Factor in Treating Diabetic Foot Ulcer

Objective: To investigate the effect of Yinqi ointment on wound morphology and growth factor in treating diabetic foot ulcer(DFU).Methods: From December 2016 to December 2017, 92 cases of DFU with deficiency of both Qi and Yin syndrome were randomly divided into treatment group and control group(44 cases in each group). The treatment group was treated with Yinqi ointment, while the control group was treated with mupirocin ointment. After 4 weeks of treatment, the ulcer healing effect, ulcer area, granulation tissue, epithelial tissue coverage,pain score, and dynamic analysis of vascular endothelial growth factor(VEGF), epidermis growth factor(EGF), and basic fibroblast growth factor(bFGF) in local granulation tissue were statistically analyzed before and after treatment in both groups. Results: The total effective rate was 88.37% in the treatment group and 74.42% in the control group. The wound reduction rate, epithelial tissue coverage rate, granulation tissue growth rate, and local pain relief rate in the treatment group were significantly superior to those in the control group(P 0.05). Through the local granulation detection, the treatment group and the control group have increased VEGF, EGF, and bFGF, but the treatment group increased the role of growth factor than the control group. Conclusion: Yinqi ointment can promote the healing of DFU, and its mechanism may be related to the increase of the content of growth factor in granulation tissue.     

糖尿病患者饥饿感中医病机浅识

糖尿病患者饥饿感病机有胃火炽盛、胃强脾弱、脾胃虚弱、瘀热消谷、痰热消谷等。糖尿病初期,痰热、火热之证常见,患者出现多食易饥表现,应考虑痰热消谷、火热消谷,选用白虎汤、玉女煎、消渴方等加减治疗;病程日久,火热伤阴,壮火食气,出现气阴两虚等表现,此时出现多食易饥症状,则需考虑胃强脾弱、脾胃虚弱等病机,采用半夏泻心汤、附子理中丸、参苓白术散等治疗;瘀血贯穿糖尿病始终,故在使用以上方法治疗糖尿病患者消谷易饥效果欠佳时,可考虑瘀热消谷的因素,采用桃核承气汤、白虎汤合桂枝茯苓丸治疗。糖尿病与痰湿关系密切,针对该病机引起的饥饿感,在清热的同时,还应化痰除湿。糖尿病病程日久患者,饥饿感病机复杂,宜"观其脉证,知犯何逆,随证治之"。     

基于数据挖掘对治疗口疮的成方制剂的用药规律分析*

目的分析治疗口疮的成方制剂的剂型、功能主治、组方用药规律及核心组合，为临床治疗口疮的辨证用药及新药研发提供参考。方法 收集《中华人民共和国卫生部药品标准·中药成方制剂》(以下简称《中药成方制剂》)、《中华人民共和国药典：2015年版》(以下简称2015年版《中国药典》)中治疗口疮的成方制剂的名称、处方、剂型、功能与主治，录入Microsoft Excel及中医传承辅助平台(V2.5)，统计用药频次；运用Apriori算法及关联规则对处方核心组合进行统计分析(支持度为10%，置信度100%)；采用熵聚类算法统计2-3个不同成分间的关联系数(支持度为8，惩罚度为2)；根据无监督的熵层次聚类法提取内在核心组合和新方组合。结果 挖掘得出86种成方制剂及其处方，以丸剂、散剂、片剂等多见，包含药物148味，使用频次较高为冰片、甘草、大黄、黄芩等，药物四气五味以苦寒为主，主要归肺胃心脾经，治疗证型较多为热毒炽盛证、热毒攻喉证等，常用核心配伍包括“黄芩-大黄”“黄连-甘草”等，挖掘得出新方组合“珍珠-川贝母-灯心草-天花粉-没药”等4首。结论 利用数据挖掘分析治疗口疮的成方制剂的组方规律，由核心药物组合成新方，可为临床辨证使用及研发治疗口疮成方制剂、新药提供依据和参考。     

良附丸对寒邪客胃证大鼠胃排空及小肠推进度的影响

目的研究良附丸对寒邪客胃证大鼠胃排空和小肠推进度的影响。方法采用冰水灌胃(内寒)、冰敷胃部(外寒)复制寒邪客胃证大鼠动物模型,边给药边造模,实验7 d后,大鼠予以半固体糊灌胃,30 min后水合氯醛麻醉,解剖检测指标。结果良附丸对治内大鼠饮食、体质量的改善无显著作用(P> 0.05),但能增加饮水量(P <0.01),对治外和治混大鼠的饮食、饮水、体质量均有明显的改善作用(P <0.05);治疗组胃残留率和排空率虽有改善趋势,但无统计学差异(P> 0.05);治疗组小肠推进率显著增加(P <0.05),差异具有统计学意义。结论内寒对大鼠饮食、体质量,外寒对大鼠小肠推进度影响均不大。良附丸不能显著改善胃实寒大鼠胃排空状态,但有改善的趋势;良附丸能显著改善寒邪客胃证(内、混)大鼠小肠推进率,促进胃肠蠕动。     

重灸中脘穴对脾胃虚寒型糖尿病胃轻瘫患者胃肠激素、胃动力学的影响

目的观察重灸中脘穴对脾胃虚寒型2型糖尿病胃轻瘫患者胃肠激素、胃动力学的影响。方法选取符合纳入标准的88例脾胃虚寒型糖尿病胃轻瘫患者,按随机数字表法分为治疗组和对照组,每组44例。对照组采用常规药物治疗,治疗组采用重灸中脘穴治疗。疗程结束后记录并对比分析两组临床疗效、胃肠激素[胃泌素(GAS)、胃动素(MTL)]、胃动力学(胃收缩频率、胃排空时间、胃排空率)、主要临床症状评分等变化。结果治疗组临床疗效明显优于对照组,差异具有统计学意义(P<0.05);两组治疗后GAS、MTL均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05);两组治疗后胃收缩频率、胃排空时间、胃排空率均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05);两组治疗后主要临床症状评分均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05)。结论在常规药物治疗基础上重灸中脘穴治疗脾胃虚寒型2型糖尿病胃轻瘫,可调节胃肠激素,改善胃肠动力,促进胃肠功能恢复。