Hypercholesterolemia (HCh) represents a prevalent comorbidity in patients with diabetic foot ulcers (DFUs), frequently exacerbating wound recalcitrance, yet the mechanisms linking systemic lipid perturbation to local immune dysregulation remain poorly defined. Here, we applied an integrated transcriptomic and machine learning approach to explore the molecular basis of this comorbidity. Initial analyses identified 70 shared DEGs between DFUs and HCh, primarily enriched in pathways related to lipid homeostasis disruption and inflammatory cascade activation. Subsequently, a four-algorithm machine learning pipeline highlighted AKR1C3 and CLIC3 as candidate diagnostic biomarkers, both consistently downregulated across disease states and supported by independent external validation cohorts (AUC = 0.779 and 0.920). Immune deconvolution further indicated a dysregulated microenvironment featuring sustained innate immune activation alongside adaptive immune impairment, which correlated with reduced AKR1C3 and CLIC3 expression. Drug repurposing analyses proposed that pirfenidone and statins might attenuate this pathological transcriptomic signature, while molecular docking simulations suggested stable binding of exemestane and indomethacin to AKR1C3 (binding energies: -8.0 and -7.3 kcal/mol, respectively). Collectively, these findings suggest that AKR1C3 and CLIC3 act as molecular bridges linking the TGF-β/lipid metabolism axis to local immune dysfunction, offering a rationale for early risk stratification and targeted drug repurposing in DFUs-HCh comorbidity.

目的 系统评价中药溻渍法应用于糖尿病足溃疡的临床疗效.方法 通过计算机系统性检索中国知网、维普、SinoMed、PubMed、the Cochrane Library、Embase等数据库中公开发表的关于中药溻渍法治疗糖尿病足溃疡临床疗效的随机对照研究,检索时限从建库至2021年3月5日,提取相关数据并评价纳入研究的偏倚风险,应用Review Manager 5.3软件进行Meta分析和系统评价.结果 共纳入16篇文献,包括1325例糖尿病足溃疡患者,其中,试验组673例,对照组652例.Meta分析结果显示,试验组患者的伤口显愈率明显高于对照组患者,差异有统计学意义(OR=0.25,95%CI:0.19～0.31,P﹤0.01);有效率明显高于对照组患者,差异有统计学意义(OR=4.27,95%CI:2.94～6.22,P﹤0.01);创面愈合时间明显短于对照组患者,差异有统计学意义(RR=-8.82,95%CI:-13.88～-2.56,P=0.004);C反应蛋白水平明显低于对照组患者,差异有统计学意义(RR=-3.19,95%CI:-4.15～-2.24,P﹤0.01).通过Egger's法检测发表偏倚,结果显示,有效率存在发表偏倚风险.结论 中药溻渍法可以有效提高糖尿病足溃疡创面的有效率和显愈率,缩短创面愈合时间,减轻炎症反应.

Objective:To explore the clinical efficacy of Badu Shengji Powder in the treatment of chronic refractory wounds.Methods:China National Knowledge Infrastructure（CNKI）,China Science Periodical Database（CSPD）,Chinese Citation Database（CCD）,China Biology Medicine（CBM）,American Medicine Database（Medicine）,and the Cochrane Library were searched for clinical randomized controlled trials（RCTs） on the efficacy of Badu Shengji Powder in treating chronic refractory wounds by keywords from database inception to October 2022.After two investigators screened the literature in accordance with inclusion and exclusion criteria, extracted the data, and evaluated the risk of bias of included studies, RevMan5.3 software was used for systematic evaluation and Meta-analysis.Results:Fourteen RCTs were included, with 787 patients involved, i.e.,394 patients in the treatment group and 393 patients in the control group.Meta-analysis showed that the wound healing rate in the treatment group was higher than that in the control group（OR=4.08,95%CI 2.55 to 6.55,P＜0.000 01）.The effective rate of wounds in the treatment group was higher than that in the control group（OR=6.08,95%CI 3.45 to 10.73,P＜0.000 01）.The wound healing time in the treatment group was shorter than that in the control group（MD=-3.07,95%CI-4.12 to-2.03,P＜0.000 01）.The pain score of the treatment group was lower than that of the control group（MD=-1.18,95%CI-2.03 to-0.33,P=0.006）.Conclusion:The current evidence shows that the clinical application of Badu Shengji Powder can improve the healing rate of chronic refractory wounds and the effective rate, shorten the healing time of wounds, and relieve pain.However, due to the limitations of the studies included, the above conclusion still needs more high-quality research validation.

ABSTRACT The gut microbiota is an important risk factor and therapeutic target in atherosclerotic cardiovascular disease (ACVD), a leading cause of morbidity and mortality worldwide. However, alterations in the gut viral community and its contribution to ACVD have rarely been investigated. In this study, we characterized and compared the gut viromes from the fecal metagenomes of 214 patients with ACVD and 171 healthy individuals using a reference-dependent virome approach. We revealed that ACVD patients exhibited a significant increase in viral richness at the family level and a visible alteration in overall virome structure regardless of host sex, age, or body mass index. At the viral operational taxonomic unit (vOTU) level, we identified 105 vOTUs that significantly increased in abundance in ACVD patients and 60 vOTUs that increased in abundance in healthy controls. A majority (43.8%) of the ACVD-enriched vOTUs were predicted to infect Streptococcaceae, Lachnospiraceae, Ruminococcaceae, and Enterobacteriaceae, and Streptococcaceae had tight correlations with the corresponding gut bacterial species, whereas a considerable proportion (35.0%) of the control-enriched vOTUs were Bacteroidaceae, Burkholderiaceae, and Lachnospiraceae phages. Functional analyses revealed five viral auxiliary metabolic genes that differed in frequency between ACVD-enriched and control-enriched vOTUs. Moreover, we identified gut viral signatures for ACVD discrimination and achieved an optimal area under the receiver operator characteristic curve of 0.878 for distinguishing patients from healthy controls. Our results provide a comprehensive view of the ACVD gut virome, which may contribute to the development of novel diagnostic and therapeutic strategies for ACVD and additional relevant cardiovascular diseases. IMPORTANCE Existing studies have found that there is a close relationship between human virome and numerous diseases, and diseases may affect the diversity and composition of the virome; at the same time, changes in the virome will in turn affect the onset and progression of the disease. However, the composition and functional capabilities of the gut virome associated with atherosclerotic cardiovascular disease (ACVD) have not been systematically investigated. To our knowledge, this is the first study investigating the gut virome in patients with ACVD. We characterized the structural changes in the gut virome of ACVD patients, which may facilitate additional mechanistic, diagnostic, and interventional studies of ACVD and related diseases.

Panax notoginseng saponins (PNSs) have been found as the major active ingredient of Panax notoginseng (Burkill) F.H.Chen (PN) leaves, which has the effect of reducing inflammatory response, facilitating fibroblast proliferation, as well as promoting angiogenesis. This study aimed to investigate the molecular basis of PNS combined with bone mesenchymal stem cells (BMSCs) for treating diabetic cutaneous ulcers (DCU) and its mechanism of action. Methods. A total of 75 SD rats were selected to make diabetic cutaneous ulcers model. According random number table method, the rats were randomly divided into a control group, a DCU group, a BMSCs group, a PNS group and BMSCs + PNS group. Five groups of rats were given without treatment. After being treated for 7 days, the rats were anesthetized with pentobarbital, and granulation tissue was collected from the central point of the wound. They were used for pathological analysis, Western blot (WB) and polymerase chain reaction (PCR) assays. Results. The wound healing area was the largest in the BMSCs + PNS group. HE staining results showed that the PNS + BMSCs group could promote the formation of new epidermis and reduce the infiltration of inflammatory cells. Immunohistochemistry (IHC) results showed that the PNS + BMSCs group could up-regulate the expression of Ki67 protein and cell proliferation. In addition, PNS combined with BMSCs up-regulated the expression of miR-146-5p and down-regulated the expression of IL-1β, IL-6 and TNF-α, IRAK1, TRAF6 and p65 in the NF-κB signaling pathway (p < 0.05). Conclusions. PNS combined with bone mesenchymal stem cell transplantation up-regulated miR-146a-5p targeting and binding to IRAK1/TRAF6, inhibiting the activation of NF-κB pathway, which reduced the inflammatory response of DCU and facilitated the skin healing of DCU. Thus, this study provides a theoretical basis and a novel therapeutic option for the treatment of DFU with PNS combined with BMSCs.

周围血管疾病主要包括动脉性、静脉性、淋巴管性疾病.周围血管疾病大部分都有肢体发凉怕冷、疼痛、间歇性跛行、肢体肿胀、肌肤麻木不仁等症状,严重者可发展成溃疡或坏疽.中医认为该类疾病病机多为阳虚、寒凝、血瘀.庞鹤教授认为周围血管疾病即《金匮要略》中的血痹,主张用治疗血痹的黄芪桂枝五物汤治疗周围血管疾病.从根据病情程度分层论治动脉硬化闭塞症、运用对药与角药治疗慢性下肢静脉性水肿、抓住证候特点治疗雷诺氏综合征、运用虫类药与增水行舟法治疗下肢深静脉血栓等方面介绍庞教授应用加减黄芪桂枝五物汤治疗周围血管疾病的经验,并结合临床病案分析庞教授的诊疗和用药思路.

目的:通过研究复方黄柏液对糖基化内皮细胞增殖迁移成管的影响,寻找复方黄柏液治疗糖尿病足溃疡的依据.方法:为说明晚期糖基化终产物受体(RAGE),用晚期糖基化终产物(AGEs)诱发内皮细胞功能障碍的重要受体,本研究设置了RT-PCR实验沉默了RAGE,结果发现沉默RAGE后,经AGEs处理内皮细胞,检测其内皮细胞增殖迁移成管作用出现上升,因此检测RAGE表达水平的变化能作为后续评价复方黄柏液改善内皮细胞功能的重要指标.如果RAGE水平出现下降,就证明内皮细胞功能障碍得到了修复,复方黄柏液治疗糖尿病足溃疡是有效的.为了评估内皮细胞的增殖能力,设置CCK-8实验;用划痕实验检查内皮细胞的迁移水平变化;通过成管实验来测试内皮细胞的成管作用;利用蛋白质印迹法检测RAGE蛋白表达水平.结果:RAGE-3 siRNA沉默效率最好,可用于后续实验.与空白组比较,AGEs处理后内皮细胞增殖活性、迁移水平、成管作用都下降,RAGE蛋白表达水平上升.与AGEs-BSA处理组比较,沉默RAGE或加入复方黄柏液后均较AGEs处理后内皮细胞的增殖迁移成管作用有了提高,RAGE蛋白的表达下降,差异有统计学意义(P<0.05).结论:复方黄柏液可能通过改善AGEs诱发的内皮细胞功能障碍即促进内皮细胞增殖迁移成管来实现对糖尿病足溃疡的愈合.

目的 观察口服参苓白术散加减治疗脾虚湿盛型臁疮的临床分析.方法 以随机数表法将2019年6月—2020年6月北京中医药大学东直门医院收治的臁疮脾虚湿盛型患者76例分为观察组和对照组,各38例.观察组口服参苓白术散加减,对照组口服迈之灵.比较两组治疗前后的溃疡面积、总创面缩小率、中医证候积分、疼痛程度、总有效率.结果 治疗后,观察组的溃疡愈合面积更大,中医证候积分以及疼痛程度评分更低,差异有统计学意义(P<0.05);治疗后观察组总创面缩小率(82.61±3.12)％较对照组总创面缩小率(79.80±4.18)％更高,差异有统计学意义(P<0.05);观察组总有效率(94.73％)与对照组(76.31％)比较,差异有统计学意义(χ2=5.208,P=0.022).结论 口服参苓白术散加减治疗脾虚湿盛型臁疮,疗效满意,且适当延长用药可以提高疗效,值得推广.

目的:探索复方黄柏液对内皮细胞增殖迁移成管影响的机制,为复方黄柏溶液用于治疗糖尿病足溃疡提供依据.方法:用CCK-8法检测药物毒性,探索复方黄柏液使用的最佳药物浓度、CCK-8法检测细胞增殖活力、细胞划痕实验检测细胞迁移率、成管实验检测细胞成管能力、蛋白质印迹法(Western Blotting)实验检测蛋白表达水平的变化.结果:使用复方黄柏液后,高糖组内皮细胞的增殖、迁移、成管能力较前有了提高,并降低了促血管生成素2(Ang-2)蛋白水平,增加血管内皮生长因子(VEGF)和磷酸化酪氨酸激酶受体-2(P-Tie)蛋白水平.结论:复方黄柏液通过促进内皮细胞增殖、迁移、成管以及影响蛋白表达水平,改善内皮功能障碍来实现对糖尿病足溃疡的恢复.

OBJECTIVE In this study, we aimed to evaluate the possible function of miR-130a in atherosclerosis (AS), protection against AS, and its molecular biological mechanism. METHODS Apoe-/- mice were fed a high-fat diet as the AS mice model. Human umbilical vein endothelial cells (HUVECs) were used as in vitro model. Serum samples or cells were used to measure the expression of inflammation. Serum samples or cells were used to determine MiRNA expression profiles using the edgeR tool from Bioconductor. Western Blot analysis was used to assess protein expressions of proliferator-activated receptor γ (PPARγ) and nuclear factor (NF)-κB. RESULTS MiRNA-130a expression was up-regulated in atherosclerotic mice. In addition, over-expression of miRNA-130a promoted inflammation factors [tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, and IL-8] in the in vitro model of AS. However, down-regulation of miRNA-130a reduced inflammation (suppressed TNF-α, IL-1β, IL-6 and IL-8) in the in vitro model. Furthermore, over-expression of miRNA-130a could also suppress the protein expression of PPARγ and induce NF-κB protein expression in the in vitro model. However, suppression of miRNA-130a induced the protein expression of PPARγ and suppressed NF-κB protein expression in the in vitro model of AS. Activation of PPARγ reduced the pro-inflammatory effects of miRNA-130a on the AS-induced in vitro model. CONCLUSION These results strongly support that miRNA-130a suppression can protect against atherosclerosis through inhibiting inflammation by regulating the PPARγ/ NF-κB expression.

臁疮俗称"裤口毒、裙边疮、老烂腿",该病缠绵难愈,治疗极为棘手.中医外科治疗臁疮经验丰富,且疗效较好.《外科正宗》记录大量治疗外科疾病的临床经验,其中就有关于臁疮的记载,包括臁疮的成因、证候特点、治法.本文总结其对于臁疮的诊治思想,旨在为当今臁疮治疗提供思路.

目的:探讨普朗特液体伤口敷料联合负压滴灌治疗糖尿病足创面感染的效果.方法:选取2017年1月-2019年1月于北京中医药大学东直门医院周围血管科收治的糖尿病足患者80例,按照随机数字法分为观察组和对照组各40例,均接受标准化内科基础治疗,创面床准备完善后,观察组采用普朗特液体伤口敷料负压滴灌治疗,对照组采用康复新液负压滴灌治疗,记录两组治疗前、治疗后2周、治疗后4周创面症状积分、创面面积、血清IL-6、ESR及TNF-α水平.结果:治疗2、4周后,两组创面面积均较治疗前缩小,差异有统计学意义(P<0.01);治疗4周后,观察组创面面积及症状积分明显小于对照组(P<0.01).治疗2、4周后,两组血清IL-6、ESR及TNF-α均较治疗前下降,差异有统计学意义(P<0.01).治疗2、4周后,观察组的IL-6、TNF-α及ESR水平均低于对照组,差异有统计学意义(P<0.05).结论:普朗特液体伤口敷料负压滴灌治疗能够减轻糖尿病足创面感染,改善临床症状,促进伤口愈合.

目的 系统评价四妙勇安汤治疗热毒炽盛证糖尿病足的临床效果.方法 计算机检索中国知网、万方、维普、PubMed、Embase、Web of Science和The Cochrane Library数据库,检索时间均从建库至2020年2月15日.检索四妙勇安汤治疗糖尿病足热毒炽盛证的随机对照试验,在严格质量评价的基础上,采用RevMan 5.3软件进行meta分析.结果 最终纳入19篇文献,1380例患者,治疗组694例,对照组686例.结果显示:治疗组总有效率高于对照组[RR=1.26,95％CI(1.20,1.33),P<0.00001],治疗组的踝肱指数(ABI)[MD=0.09,95％CI(0.07,0.12),P<0.00001]、足背动脉血流量[MD=7.46,95％CI(5.48,9.43),P<0.00001]、运动神经传导速度(MCV)[MD=7.44,95％CI(6.32,8.57),P<0.00001]、感觉神经传导速度(SCV)[MD=5.05,95％CI(4.05,6.05),P<0.00001]均显著高于对照组.两组血浆黏度[MD=-0.06,95％CI(-0.16,0.03),P=0.19]、空腹血糖(GLU)[MD=-0.20,95％CI(-0.66,-0.27),P=0.41]比较差异均无统计学意义.结论 当前证据显示,四妙勇安汤可有效改善糖尿病足临床症状,增加ABI、足背动脉血流量、MCV、SCV,受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证.

目的 探讨银芪软膏治疗糖尿病足溃疡的有效成分及干预机制,为新药开发提供新思路和方法.方法 运用中医药整合药理学研究平台2.0获取银芪软膏的化学成分数据库、糖尿病足溃疡的候选疾病靶标、银芪软膏的潜在靶标与糖尿病足溃疡疾病靶标之间的蛋白质-蛋白质相互作用信息,构建银芪软膏治疗糖尿病足溃疡的关键靶标网络,最后利用基因本体数据库与富集分析的结果找到银芪软膏治疗糖尿病足溃疡的关键靶标及其通路.结果 银芪软膏的关键药靶一共有4个,其中HSP90AA1可能是银芪软膏治疗糖尿病足溃疡的最关键靶标.涉及治疗糖尿病足溃疡最主要的通路包括四氢生物蝶呤的合成、再循环、回收和调节,内皮型一氧化氮合成酶激活,血管内皮细胞生长因子受体2介导的血管通透性.结论 本研究虽为银芪软膏及其所含中药成分的进一步研究提供依据,但终究只是基于整合药理学平台的预测,具体机制乃至新药开发还需要具体的实验室研究作支撑.

目的 基于数据挖掘分析庞鹤教授治疗下肢静脉溃疡的用药经验,为治疗提供临床思路.方法 收集庞教授2016年9月-2019年9月于东直门医院周围血管科治疗有效的下肢静脉溃疡门诊处方132首,录入中医传承辅助系统,进行频次统计、关联规则、复杂系统熵聚类以及无监督熵层次聚类提取关联系数、置信度、核心药物组合以及新处方.结果 单味药物频次统计得到出现频次≥30次的药物有27味,频次最高的分别为黄芪、当归、赤芍、川芎、丹参、地龙.应用关联规则挖掘数据,得到置信度≥0.75的药物组合28对;基于熵聚类分析,得到关联系数≥0.06的药物组合30对,核心的组合共17组,新处方9首.结论 数据挖掘分析显示庞鹤治疗下肢静脉溃疡以活血化瘀法贯穿始终,兼以益气、去湿、化浊.

目的:系统评价外敷生肌玉红膏治疗糖尿病足溃疡的临床疗效.方法:检索国家知识基础设施数据库(CNKI)、中国学术期刊数据库(CSPD)、中文科技期刊数据库(CCD)、Web of Science、PubMed、The Cochrane Library、CBN数据库,搜集生肌玉红膏治疗糖尿病足溃疡的随机对照研究,检索时间均从建库至2019年11月31日.由2名研究者筛选符合纳入标准的文献、提取有效资料,应用RevMan5.3软件评价文献偏倚风险并进行系统评价.结果:共纳入9篇随机对照试验(RCT),包括696例患者,纳入文献质量偏低.Meta分析结果显示:外敷生肌玉红膏能够提高糖尿病足溃疡总有效率(MD=4.76,95％CI为2.89～7.85),P<0.0001),缩短创面愈合时间(MD=-4.90,95％CI为-5.77～-4.03),P<0.00001),差异有统计学意义;对降低空腹血糖(MD=-0.08,95％CI为-0.71～0.55),P=0.80)及不良反应发生率(MD=1.01,95％CI为0.33～3.10,P=0.98),差异无统计学意义.结论:当前证据表明,生肌玉红膏治疗糖尿病足溃疡疗效显著.须提高纳入文献数量和质量,增加研究客观性和准确性.

以下肢深静脉血栓形成为首发表现的系统性红斑狼疮(SLE)较为罕见,本文通过分析1例初诊为下肢深静脉血栓形成(DVT)并最终确诊为SLE的病例资料,阐释SLE患者发生DVT的发病机制及诊疗方案,为相关临床工作提供参考.在临床工作中,对无明显诱因的DVT患者,须注意排查SLE等自身免疫性疾病.对已发生DVT的SLE患者,要检测抗磷脂抗体、蛋白C、蛋白S及抗凝血酶水平.

糖尿病足是周围血管疾病动脉系统疾病之一,是临床的常见病和多发病,是糖尿病患者最严重和治疗费用最高的慢性并发症之一,严重者可影响患者工作和生活.庞鹤教授根据多年的临床经验,采用经方辨证论治糖尿病足.庞教授认为该病的病机是气阴两虚,血脉瘀阻为本.治疗中主张中西并重,内外兼治.从健脾益气入手,根据其湿、毒、瘀的偏盛,以及虚实的夹杂拟方用药,采用辨证、辨病、整体与局部辨证相结合,辨证论治,取得了较好的临床效果.

目的:探讨三七总皂苷(PNS)、黄芪总皂苷(TSA)联合自体骨髓干细胞治疗糖尿病溃疡对miRNA-146a的影响.方法:选取SD大鼠60只,在双足背上制成糖尿病足模型,采用全骨髓培养加贴壁法分离、扩增至第4代的骨髓间充质干细胞,按随机数字法将大鼠分为空白组、对照组、干细胞组、黄芪组;三七组干细胞组、黄芪组、三七组创面每日注射自体骨髓干细胞(0.3 mL/cm2),黄芪组每日加注黄芪注射液(0.3 mL/cm2),三七组每日加注血塞通(0.4 mL/cm2),7 d后处死,采用PCR法检测miRNA-146a水平,Western blot法检测TLR4 miRNA、NOD1 miRNA、核因子-κB miRNA的表达.结果:与对照组比较,干细胞组、黄芪组和三七组大鼠创面愈合率极显著增大,差异有统计学意义(P<0.05);与对照组比较,干细胞组、黄芪组和三七组大鼠miRNA-146a、TLR4 miRNA、核因子-κB miRNA、NOD1 miRNA表达量显著增大,差异有统计学意义(P<0.05);与干细胞组比较,三七组miRNA-146a、TLR4 miRNA、核因子-κB miRNA、NOD1 miRNA表达量显著增大,差异有统计学意义(P<0.05).结论:三七总皂苷、黄芪总皂苷联合骨髓干细胞治疗糖尿病足溃疡有效,其愈合机制可能与TLR4/核因子-κB通路上调miRNA-146a的表达有关.