Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

Protective effect of Liangxue Huayu decoction on human retinal pigment epithelial cell(ARPE-19)injury induced by hypoxia through autophagy pathway

Background:Exploring the protective mechanism of the Liangxue Huayu(LXHY)decoction on human retinal pigment epithelial(RPE)cells induced by hypoxia through the autophagy pathway.Methods:The appropriate LXHY decoction concentration was determined by CCK-8.ARPE-19 cells were divided into the normal control group(A group),CoCl_(2)group(B group),3-Methyladenine(3-MA)group(treated with 3-MA(the inhibition of autophagy pathway))(C group),blank serum(BS)group(D group),LXHY drug-contained serum(DCS)group(E group),and Rapamycin(RAP)group[treated with LXHY drug-contained serum combined with rapamycin group(the activation of autophagy pathway)](F group).Counting the number of autophagosomes and autolysosomes in each group of cells under transmission electron microscopy.After infection of cells in each group by mRFP-GFP-LC3 fusion protein adenovirus,the strength of autophagic flux was detected.The mRNA expression levels of LC3 and Beclin-1 were detected by Q-PCR.Results:CCK-8 assay results showed that LXHY DCS could inhibit the cell proliferation of ARPE-19 under hypoxia(all P<0.05).As the transmission electron microscopy assay result showed,compared with the normal control group,the number of autolysosomes was significantly increased in the CoCl_(2)group(P<0.05).Compared with CoCl_(2)group,the number of autolysosomes was significantly reduced the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).As autophagic flux assay result showed,compared with the normal control group,the level of autophagosomes and autolysosomes were significantly risen in CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the level of autophagosomes and autolysosomes were significantly fell down in 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.05).The level of autolysosomes in the LXHY drug-contained serum group was lower than in the blank serum group(P<0.05).Compared with the LXHY drug-contained serum group,the levels of autophagosomes and autolysosomes were significantly risen in the LXHY drug-contained serum combined with the rapamycin group(all P<0.05).As the Q-PCR result showed,compared with the normal control group,the expression of LC3 and Beclin-1 mRNA were significantly reduced in the CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the expression of LC3 mRNA were significantly increased in the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).Beclin-1 mRNA expression was increased significantly(all P<0.001)in the blank serum group and the LXHY drug-contained serum group.And Beclin-1 mRNA expression in the LXHY drug-contained serum group was statistically significant increased than blank serum group(P<0.001).In the LXHY drug-contained serum combined with the rapamycin group,the LC3 and Beclin-1 mRNA expression was reduced significantly compared with the LXHY drug-contained serum group(all P<0.001).Conclusion:The LXHY DCS has the ability to protect the human retinal pigment epithelial cell(ARPE-19)damage under hypoxia through the autophagy pathway.

Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer:protocol for a prospective,double-arm,randomized controlled clinical trial

Background:Neoadjuvant chemotherapy plays a vital role in the treatment of advanced gastric cancer(GC),however,optimizing its effectiveness remains an important research focus.Traditional Chinese medicine(TCM),a promising adjunctive therapy,has shown enhanced clinical outcomes when combined with postoperative adjuvant chemotherapy.Therefore,this study is designed to evaluate the clinical efficacy of Yiqi Huayu Jiedu decoction combined with neoadjuvant chemotherapy FLOT in the treatment of advanced GC.Methods:This study is a prospective,double-arm,randomized controlled trial.It involves a total of 260 patients diagnosed with advanced GC,who will be randomly assigned to two groups-a TCM treatment group and a control group,each comprising 130 patients.All patients will receive standard FLOT chemotherapy,and patients in the TCM treatment group will additionally receive TCM treatment with Yiqi Huayu Jiedu decoction.After four cycles of chemotherapy,GC D2 radical surgery will be performed.The primary objective is to evaluate the postoperative pathological response rate of the tumor.The secondary objectives include evaluating the perioperative nutritional status,the efficacy of TCM syndrome,and adverse events associated with both chemotherapy and surgery.Discussion:Currently,no trials have investigated the impact of TCM in combination with neoadjuvant chemotherapy on the preoperative treatment in patients with advanced GC.Accordingly,it is imperative to conduct this prospective study to evaluate the clinical efficacy and safety of this regimen,meanwhile providing high-level clinical evidence for TCM combined with neoadjuvant chemotherapy and introducing an innovative regimen for preoperative comprehensive treatment of GC.

Intervention of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma

Objective:To study the intervention effect of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma (ASDH).Methods: 160 SD rats were randomly divided into four groups, and the ASDH model rats were made by stereotactic autoblood injection, and sham operation group received craniotomy without blood injection. Sham operation group and model group were normally bred after model establishment, and 6 h after model establishment, the treatment group received intragastric administration of Peiyuan Huayu Decoction, and control group received intragastric administration of Piracetam Tablets, 1 time a day. On the 1d, 3d, 5d and 7d after model establishment, the general conditions of rats (activity, food intake and mental state) were observed, blood was collected via auricula dextra, ELISA method was used to determine peripheral plasma NSE and S100β protein contents, routine HE staining was conducted after perfusion fixation, the neurons in blood injection side of brain tissue were counted, and the neuron damage was observed.Results: 26 rats were dead in the experiment. The general conditions of sham operation group were significantly better than those of other groups, treatment group was significantly better than model group and control group on the 5d group (P<0.05), and there was no significant difference on the 1d, 3d and 7d (P>0.05);neuron count of sham operation group was basically stable, treatment group was not different from model group and control group on the 1d (P>0.05), treatment group was better than model group (P<0.05), and not different from control group (P>0.05) on the 3d, and treatment group was better than model group and control group on the 5d and 7d (P<0.05);peripheral plasma S100β protein and NSE contents of sham operation group were at lower levels, treatment group was not significantly different from model group and control group on the 1d (P>0.05), S100β protein and NSE contents decreased significantly on the 3d, and treatment group was significantly different from model group and control group (P<0.05), S100β protein and NSE contents increased on the 5d and 7d, the increase in treatment group was slower than that in model group and control group, and there was significant difference (P<0.05).Conclusion:Peiyuan Huayu Decoction has obvious protective effect on the neurons in ASDH model rats, and this effect may be based on the inhibition of secondary neuron damage.

Effect of Huoxue Huayu Lishui Decoction on P65 and TAK1 of acute soft tissue injury in rats

Objective:To explore the mechanism of the action of Huoxue Huayu Lishui prescription on acute ankle joint injury.Methods:Forty-eight SPF rats were randomly divided into blank group,model group,Shujin Huoluo capsule group,low,medium and high dose groups for promoting blood circulation and removing blood stasis.The blank group was not modeled,and the other groups were modeled.Each group of 8 animals,the Shujin Huoluo capsule group was given 0.2g/ml mixed liquid by gavage,and the low,medium and high blood circulation and blood stasis Lishui prescription group was given 1.03g/ml,2.06g/ml,4.12g/ml decoction For the stomach,the normal group was given 1.5ml/100g,once a day for 1 week.The expression of NF-κB P65 and transforming growth factor kinase 1(TAK1)protein in the soft tissue around the ankle joint of rats was detected by sports protein immunoblotting method,and the mRNA expression of NF-κB P65 and TAK1 was detected by PCR technology.Results:One day after modeling,the expressions of P65 and TAK1 mRNA and protein in the model group,the positive drug group,and low,medium and high doses of Huoxue Huayu Lishui Recipe were significantly different from those of the blank control group(P<0.05).After taking the medicine for 7 days,compared with the model group,the expressions of P65 and TAK1 mRNA and protein in the Shujin Huoluo capsule group and the low,medium and high dose Huoxue Huayu Lishui Recipe group were all decreased(P<0.05).After 7 days of taking the medicine,compared with the Shujin Huoxue Capsule group,there was no difference in P65 protein in the low-dose Huoxue Huayu Lishui Recipe group.The expression of P65 protein in the middle and high groups and the Shujin Huoxue Capsule group were all decreased(P<0.05).Compared with the Shujin Huoxue Capsule group,the expressions of TAK1 protein,P65 and TAK1 mRNA in the low,medium,and high groups and the Shujin Huoxue Capsule group were all decreased(P<0.05).The results suggest that Huoxue Huayu Lishui Recipe can inhibit the expression of NF-κB P65 and TAK1 protein in ankle joint injury.Conclusion:Huoxue Huayu Lishui prescription may regulate the expression of NF-κB P65 and TAK1 in ankle joint injury of NF-κB rats,so as to improve the clinical symptoms of local swelling and pain in the ankle joint.

Mechanism of Liangxue Huayu decoction in treatment of age-related macular degeneration based on network pharmacology and clinical validation

Background:This paper investigates the mechanism of Liangxue Huayu decoction treating age-related macular degeneration through network pharmacology and clinical verification.Methods:The potential targets of Liangxue Huayu decoction were retrieved by the BATMAN-TCM database,and age-related macular degeneration-related disease targets were collected using the OMIM,GeneCards,and CTD databases.The intersection of targets for Liangxue Huayu decoction for age-related macular degeneration was performed using the online tool Venny2.1.0.Protein-protein interaction network was drawn using the String database.And core targets were obtained with the CytoNCA plugin.The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape database.Finally,targets of Liangxue Huayu decoction for age-related macular degeneration were identified in clinical research.Results:In this study,832 potential action targets and 9,475 age-related macular degeneration-related disease targets were screened,and 575 intersection targets of Liangxue Huayu decoction and age-related macular degeneration were obtained.Protein-protein interaction network analysis showed that 15 core targets include chemokine 8,interleukin 1,histone deacetylase 2,estrogen receptor 2,and glutamate ionotropic receptor NMDA type subunit 1,et al.Gene ontology enrichment analysis included 2,727 biological processes,434 molecular functions,and 206 cellular components.Kyoto Encyclopedia of Genes and Genomes enrichment analysis selected 107 signaling pathways.Clinical validation showed that peripheral blood chemokine 8 and interleukin 1 levels were significantly lower after age-related macular degeneration patients compared with before treatment,and the difference was statistically significant(t chemokine 8=12.684,t interleukin 1=11.405,all P<0.001).Conclusion:By treating age-related macular degeneration with multiple targets and multiple pathways,Liangxue Huayu decoction can down-regulate the expression of inflammatory factors and treat age-related macular degeneration,which provides a basis for further studying the action mechanism of regulating age-related macular degeneration.

麻杏化瘀汤联合穴位贴敷对支气管肺炎患者的临床疗效

目的考察麻杏化瘀汤联合穴位贴敷对支气管肺炎患者的临床疗效。方法120例患者随机分为对照组和观察组,每组60例,对照组给予常规治疗,观察组在对照组基础上加用麻杏化瘀汤联合穴位贴敷,疗程10 d。检测症状体征改善时间、CRP、SAA、PCT、IL-4、IL-6、TNF-α、IFN-γ、肺功能指标(TPTEF、TPTEF/TE、TEF25、TEF25/PTEF)、生活质量评分、CPIS评分、中医证候评分、不良反应发生率变化。结果观察组症状体征改善时间短于对照组(P<0.05)。治疗后,2组CRP、SAA、PCT、IL-6、TNF-α、IFN-γ、CPIS评分、中医证候评分降低(P<0.05),肺功能指标、生活质量评分升高(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论麻杏化瘀汤联合穴位贴敷可安全有效地促进支气管肺炎患者症状消退,改善肺功能,抑制炎症反应,提高生活质量。

Effect of Qingre Huayu Decoction on Autophagy and Apoptosis of Neurons in Rats with Ischemic Brain Injury by Regulating Ca^(2+)/CaMKKβ-AMPK-mTOR Pathway

[Objectives]To explore the neuroprotective mechanism of Qingre Huayu Decoction on rats with acute cerebral ischemia injury.[Methods]SD rats were divided into sham operation group,ischemia model group,low,medium and high dose groups of Qingre Huayu De-coction,with 10 rats in each group.Referring to the MCAO operation model,both the sham operation group and the model group were given normal saline by gavage,and the Qingre Huayu Decoction group was given different doses of Qingre Huayu Decoction by gavage.After the op-eration,the rats were scored for neurological deficit,neurons were stained with HE,apoptotic cells were detected with TUNEL,and the levels of autophagy and apoptotic proteins in the Ca^(2+)/CaMKKβ-AMPK-mTORpathway in brain tissue were detected with Western-blot.[Results]Compared with the model group,the neurological function score of Qingre Huayu Decoction Group decreased significantly(P<0.05),the pathological damage of neurons in Qingre Huavu Decoction Group decreased.the proportion of apoptosis-positive cells detected by TUNEL de-creased(P<0.05),and the expression of CaMKKβand AMPK increased,expression of mTOR decreased,expression of Beclin-1 and LC3 increased,and expression of Caspase-3decreased in Qingre Huayu Decoction Group(P<0.05).[Conclusions]Qingre Huayu Decoction may play a neuroprotective role by activating Ca^(2+)/CaMKKβ-AMPK-mTOR pathway and regulating the level of apoptosis and autophagy.

健脾固肾化瘀方治疗脾肾两虚夹瘀型糖尿病肾脏病的疗效及对相关生物标志物的影响

[目的]探讨健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型糖尿病肾脏病(DKD)的临床疗效以及其对患者血清基质金属蛋白酶-9(MMP-9)、单核细胞趋化因子-1(MCP-1)和血管内皮生长因子(VEGF)水平的影响。[方法]选择沧州中西医结合医院2019年1月—2021年5月纳入80例脾肾两虚夹瘀型DKD患者作为研究对象,采用随机数字表法分成观察组与对照组各40例。观察组给予健脾固肾化瘀方联合氯沙坦钾片治疗,对照组单用氯沙坦钾片治疗,连续治疗12周后观察两组临床疗效。治疗前后检测受试者血糖[空腹血糖(FPG)、餐后2 h血糖(2 h PG)和糖化血红蛋白(HbA1c)]、血脂[总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白胆固醇(LDL-C)]及肾功能指标[尿微量白蛋白/尿肌酐比值(UACR)、肌酐(SCr)和尿素氮(BUN)]。选用酶联免疫吸附法测定血清MMP-9、MCP-1和VEGF水平。并统计两组不良反应情况。[结果]观察组总有效率为92.50%(37/40),较对照组72.50%(29/40)有所提高(P<0.05)。两组治疗后FPG、2 h PG和HbA1c均较治疗前降低(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后血清TC、TG和LDL-C浓度均较治疗前下降(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后UAER和血清SCr、BUN水平均较治疗前降低(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后血清MMP-9水平均较治疗前升高(P<0.05),血清MCP-1、VEGF浓度均较治疗前下降(P<0.05);且治疗后,观察组对血清MMP-9水平的升高作用及对血清MCP-1、VEGF水平的降低作用较对照组更显著(P<0.01)。所有患者均无明显不良反应发生。[结论]应用健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型DKD能安全有效地上调患者MMP-9表达水平,下调MCP-1、VEGF表达水平,改善肾功能,整体疗效确切。

化瘀去疣汤内服外用治疗对扁平疣患者中医证候、血清免疫球蛋白及复发的影响

目的:探讨化瘀去疣汤内服外用治疗对扁平疣患者中医证候、血清免疫球蛋白及复发的影响。方法:选取2021年8月~2023年8月收治的132例扁平疣患者,按照随机数表法分为观察组和对照组各66例,对照组采用常规药物治疗,观察组在对照组的基础上采用化瘀去疣汤内服外用治疗,比较两组临床疗效、中医证候积分(皮疹颜色、瘙痒感、身热口干、便干尿黄)、血清免疫球蛋白[IgG、IgA、IgM]、免疫细胞因子[IL-2、IL-10、IFN-γ]及复发率。结果:观察组总有效率高于对照组(P<0.05);治疗后,观察组的中医症候积分(皮疹颜色、瘙痒感、身热口干、便干尿黄)低于对照组(t=6.114;t=5.552;t=6.705;t=5.435,P<0.05);治疗后,观察组血清IgG、IgA、IgM水平高于对照组(t=4.056;t=3.630;t=5.918,P<0.05);治疗后,观察组血清IFN-γ、IL-2高于对照组,IL-10低于对照组(t=9.462;t=5.429;t=8.314,P<0.05);随访6个月,观察组复发率低于对照组(4.55%vs 16.67%,χ2=5.114,P<0.05)。结论:化瘀去疣汤内服外用治疗扁平疣患者的效果显著,可有效提高免疫球蛋白水平,改善免疫细胞因子,降低复发率。

通窍化瘀汤辅助治疗缺血性脑卒中的疗效及对神经功能的影响

目的 观察通窍化瘀汤辅助治疗缺血性脑卒中的疗效及对神经功能的影响。方法 选取2021年1—12月泉州市中医院收治的缺血性脑卒中患者60例,按照随机数字表法分为中西联合组30例和丁苯酞组30例。在常规治疗基础上,丁苯酞组予丁苯酞软胶囊治疗,中西联合组在丁苯酞组基础上联合通窍化瘀汤治疗,2组均连续治疗30 d。比较2组临床疗效,治疗前后血清学指标[神经元特异性烯醇化酶(NSE)、血管内皮生长因子(VEGF)、同型半胱氨酸(Hcy)、超敏C反应蛋白(hs-CRP)]、血液流变学指标[纤维蛋白原(Fib)、血浆黏度(PV)、血小板聚集率]、美国国立卫生院卒中量表(NIHSS)评分、日常生活活动能力(ADL)评分及不良反应。结果 中西联合组总有效率为93.33%,高于丁苯酞组的70.00%(χ^(2)=5.455,P=0.020)。治疗30 d后,2组血清NSE、Hcy、hs-CRP水平较治疗前降低,血清VEGF水平较治疗前升高,且中西联合组降低或升高的幅度大于丁苯酞组(P<0.05或P<0.01);2组Fib、PV、血小板聚集率较治疗前降低,且中西联合组低于丁苯酞组(P<0.01);2组NIHSS评分较治疗前降低,ADL评分较治疗前升高,且中西联合组降低或升高的幅度大于丁苯酞组(P<0.01);中西联合组与丁苯酞组不良反应总发生率比较差异无统计学意义(3.33%vs.13.33%,χ^(2)=0.873,P=0.350)。结论 通窍化瘀汤在缺血性脑卒中的辅助治疗中具有显著临床效果,可明显改善血管内皮功能和血流动力学,改善患者神经功能和日常活动能力,且安全性较高。

化瘀杀胚汤联合甲氨蝶呤治疗异位妊娠的疗效及对TGF-β/Smad2/3蛋白水平和microRNA-30d-5p表达量的影响

【目的】探讨化瘀杀胚汤(由丹参、赤芍、桃仁、蜈蚣、紫草、天花粉、三七等中药组成)联合甲氨蝶呤治疗异位妊娠疗效及对患者TGF-β/Smad2/3蛋白水平和microRNA-30d-5p表达量的影响。【方法】将104例异位妊娠患者随机分为观察组和对照组,每组各52例。对照组给予甲氨蝶呤联合米非司酮治疗,观察组在对照组的基础上加用化瘀杀胚汤治疗,连续用药3 d并随访观察1个月。比较2组患者保守治疗成功率、血β人绒毛膜促性腺激素(β-HCG)水平恢复正常时间以及异位妊娠包块吸收时间、治疗后输卵管完全通畅率与不通畅率,观察2组保守治疗成功患者治疗前后血清TGF-β/Smad2/3蛋白水平和microRNA-30d-5p相对表达量的变化情况。【结果】(1)观察组的保守治疗成功率为94.23%(49/52),明显高于对照组的71.15%(37/52),差异有统计学意义(P<0.05)。(2)与对照组比较,观察组的血β-HCG恢复正常时间及包块吸收时间均明显缩短,差异均有统计学意义(P<0.01)。(3)观察组治疗后的输卵管完全通畅率为55.77%(29/52),明显高于对照组的21.15%(11/52);不通畅率为19.23%(10/52),明显低于对照组的59.62%(31/52),差异均有统计学意义(P<0.05或P<0.01)。(4)与治疗前比较,2组保守治疗成功患者治疗结束1个月后的TGF-β/Smad2/3蛋白水平和microRNA-30d-5p相对表达量均明显降低(P<0.05或P<0.01);与对照组比较,观察组治疗结束1个月后的TGF-β/Smad2/3蛋白水平和microRNA-30d-5p相对表达量均明显降低,差异均有统计学意义(P<0.01)。(5)2组患者的不良反应均以胃肠道不适为主,观察组的不良反应发生率为25.00%(13/52),明显低于对照组的46.15%(24/52),组间比较,差异有统计学意义(P<0.05)。【结论】化瘀杀胚汤联合甲氨蝶呤治疗异位妊娠,可有效提高药物保守治疗的成功率,有助于包块的吸收以及输卵管通畅,能有效降低患者的TGF-β/Smad2/3蛋白水平及microRNA-30d-5p的相对表达量,且药物安全性较高。

益气化瘀汤联合羟苯磺酸钙治疗糖尿病肾病气虚血瘀证的疗效及对VEGF,IGF-1表达水平的影响研究

【目的】观察益气化瘀汤(由黄芪、山药、茯苓、炒芡实、旱莲草、金樱子、焦山楂、女贞子、丹参、益母草等组成)联合羟苯磺酸钙治疗糖尿病肾病(DN)气虚血瘀证的临床疗效及对血管内皮生长因子(VEGF)、胰岛素样生长因子1(IGF-1)的影响。【方法】将90例DN气虚血瘀证患者随机分为观察组和对照组,每组各45例。所有患者均接受基础降糖治疗和控制血压、调节脂代谢紊乱等治疗。在此基础上,对照组患者给予羟苯磺酸钙治疗,观察组患者在对照组的基础上联合益气化瘀汤治疗,疗程为3个月。观察2组患者治疗前后中医证候积分、肾功能指标及血清VEGF、IGF-1水平的变化情况,并评价2组患者的临床疗效。【结果】(1)疗效方面,治疗3个月后,观察组的总有效率为91.11%(41/45),对照组为75.56%(34/45),组间比较(χ2检验),观察组的疗效明显优于对照组(P<0.05)。(2)中医证候积分方面,治疗1个月和3个月后,2组患者的中医证候积分均较治疗前明显降低(P<0.05),且治疗3个月后又均较治疗1个月后明显降低(P<0.05);组间比较,观察组在治疗1个月和3个月后对中医证候积分的降低作用均明显优于对照组(P<0.01)。(3)肾功能指标方面,治疗后,2组患者的血肌酐(Scr)、尿素氮(BUN)、肾小球滤过率(GFR)等肾功能指标均较治疗前明显改善(P<0.05),且观察组对各项肾功能指标的改善作用均明显优于对照组(P<0.01)。(4)血清VEGF、IGF-1水平方面,治疗后,2组患者的血清VEGF、IGF-1水平均较治疗前明显降低(P<0.05),且观察组对血清VEGF、IGF-1水平的降低作用均明显优于对照组(P<0.01)。(5)治疗过程中,2组患者均无明显不良反应发生,具有较高的安全性。【结论】益气化瘀汤联合羟苯磺酸钙治疗DN气虚血瘀证患者疗效确切,可有效下调血清VEGF、IGF-1水平,明显改善患者肾功能,显著减轻患者临床症状,且具有较高的安全性。

活血化瘀通络汤对输卵管阻塞性不孕症临床疗效及对盆腔局部微环境、卵巢血流动力学参数的影响

目的评估活血化瘀通络汤对输卵管阻塞性不孕症的临床疗效及对盆腔局部微环境、卵巢血流动力学参数的影响。方法选取2020年10月—2022年10月医院收治输卵管阻塞性不孕症患者104例,使用随机数字表法将患者分为对照组和观察组,每组52例。对照组患者行输卵管通液术,术后口服头孢克肟分散片,观察组在对照组基础上给予活血化瘀通络汤,两组均治疗3个月经周期,治疗结束后对比两组患者临床治疗效果、月经血细胞因子、卵巢血流动力学、炎性因子水平、妊娠情况。结果两组患者治疗后,对照组总有效率为76.92%(40/52),显著低于观察组(92.31%,48/52)的总有效率(P<0.05);两组患者治疗后月经血趋化因子1(CXC chemokine ligand-1,CXCL1)、趋化因子13(CXC chemokine ligand-13,CXCL13)水平较治疗前显著降低(P<0.05),且观察组低于对照组(P<0.05);两组患者治疗后卵巢血流动力学参数均明显改善,差异具有统计学意义(P<0.05);观察组收缩期峰值流速(Peak systolic velocity, PSV)及子宫动脉搏动指数(Pulse index, PI)均显著高于对照组(P<0.05),阻力指数(Resistance index, RI)显著低于对照组(P<0.05);两组患者治疗后,两组炎症因子水平均显著低于治疗前(P<0.05);观察组显著低于对照组(P<0.05);两组患者治疗后,对照组妊娠率为40.38%(21/52),显著低于观察组(73.08%,38/52)的妊娠率(P<0.05)。结论活血化瘀通络汤显著提升治疗输卵管阻塞临床疗效,改善盆腔局部微环境及卵巢血流动力学,降低炎性因子水平,并最终提高患者妊娠率。

孙克伟教授运用温法治疗慢加急性肝衰竭的经验

总结孙克伟教授治疗慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)的临床经验。孙克伟教授认为,ACLF以湿热瘀毒互结为标,脾阳虚损为本,脾虚可贯穿ACLF疾病全程,故治疗时多使用炮附子、白术、干姜等温药,全病程重视应用温法,并创制自拟温阳解毒化瘀汤,攻补兼施,逆转肝功能急性失代偿,临床效果显著,为ACLF的临床治疗提供参考与借鉴。

气血瘀滞型非小细胞肺癌患者“瘀毒”病机临床特征及补肺化瘀汤辅助治疗干预机制

【目的】探讨气血瘀滞型非小细胞肺癌(non-small cell lung cancer,NSCLC)患者“瘀毒”病机的临床特征以及补肺化瘀汤辅助治疗的干预机制。【方法】选取六安市中医院呼吸内科2021年1月至2022年9月收治的78例气血瘀滞型NSCLC患者作为NSCLC组,另选取71例同期健康体检志愿者为健康对照组,观察NSCLC组“瘀毒”病机的临床特征,比较2组凝血功能指标的差异。根据治疗方式的不同将NSCLC组患者分为补肺化瘀组40例和常规治疗组38例,常规治疗组采用常规化疗方案治疗,补肺化瘀组在常规治疗组的基础上加用补肺化瘀汤治疗,以3周为1个疗程,共治疗2个疗程。观察2组患者治疗前后中医证候积分、生活质量Karnofsky功能状态(KPS)评分、凝血功能、免疫功能、血清一氧化氮(NO)、血管内皮生长因子(VEGF)水平的变化情况,比较2组患者的临床疗效和治疗期间不良反应发生情况。【结果】(1)临床特征方面,NSCLC组患者临床分期为Ⅲ、Ⅳ期,病理类型为鳞癌、腺癌,KPS评分低于70分患者比例较高,中医证候积分较高,提示NSCLC患者病情较为严重;与健康对照组相比,NSCLC组患者的凝血酶原时间(PT)、凝血酶时间(TT)明显缩短,纤维蛋白原(FIB)、D-二聚体(D-D)水平明显升高,差异均有统计学意义(P<0.01)。(2)疗效方面,治疗6周后,补肺化瘀组的总有效率和总稳定率分别为32.50%(13/40)、85.00%(34/40),明显优于常规治疗组的13.16%(5/38)、60.53%(23/38),差异均有统计学意义(P<0.05)。(3)证候积分方面,治疗3周后,补肺化瘀组的各项中医证候积分(包括神疲乏力、胸闷气短、胸部刺痛、脉络瘀血等)和常规治疗组的神疲乏力、胸闷气短积分均较治疗前改善(P<0.05);治疗6周后,2组NSCLC患者的各项中医证候积分均较治疗前和治疗3周后改善(P<0.05);组间比较,除治疗3周后的胸闷气短外,补肺化瘀组在治疗3周和6周后对各项中医证候积分的改善作用均明显优于常规治疗组(P<0.05或P<0.01)。(4)凝血功能方面,治疗6周后,补肺化瘀组的PT、TT、FIB、D-D水平均较治疗前明显改善(P<0.05),而常规治疗组仅FIB、D-D水平较治疗前改善(P<0.05);组间比较,补肺化瘀组对PT、FIB、D-D水平的改善作用均明显优于常规治疗组(P<0.05)。(5)血清NO、VEGF水平方面,治疗6周后,2组患者的血清NO、VEGF水平均较治疗前明显降低(P<0.05),且补肺化瘀组的降低作用均明显优于常规治疗组(P<0.01)。(6)免疫功能方面,治疗6周后,补肺化瘀组的T细胞亚群CD3^(+)、CD4^(+)水平和CD4^(+)/CD8^(+)比值较治疗前升高(P<0.05)、CD8^(+)水平较治疗前降低(P<0.05),而常规治疗组的CD3^(+)、CD4^(+)水平及CD4^(+)/CD8^(+)比值较治疗前降低(P<0.05)、CD8^(+)水平较治疗前升高(P<0.05);组间比较,补肺化瘀组对CD3^(+)、CD4^(+)水平和CD4^(+)/CD8^(+)比值的升高作用及对CD8^(+)水平的降低作用均明显优于常规治疗组(P<0.01)。(7)生活质量方面,治疗6周后,2组患者的KPS评分均较治疗前明显升高(P<0.05),且补肺化瘀组的升高作用明显优于常规治疗组(P<0.01)。(8)不良反应方面,治疗过程中,2组患者的胃肠道反应、脱发的发生率比较,差异无统计学意义(P>0.05),而补肺化瘀组的肝肾功能损伤、骨髓抑制、口腔黏膜毒性的不良反应发生率均明显低于常规治疗组(P<0.05或P<0.01),表明补肺化瘀汤可一定程度上降低化疗所引起的不良反应。【结论】气血瘀滞型NSCLC患者普遍病情进展程度深,血液凝滞性高,契合中医“瘀毒”病机;针对“瘀毒”病机使用补肺化瘀汤治疗可明显改善患者中医证候积分和凝血功能,下调血清NO、VEGF水平,改善患者免疫功能,可提高患者临床疗效及生活质量,减少化疗所带来的不良反应,具有较高的安全性。

清金化痰益肺汤合保和丸在支气管肺炎治疗中作用及对肺功能、免疫功能、FeNO、EOS、PCT、CRP水平的影响

目的清金化痰益肺汤合保和丸对支气管肺炎的应用价值以及对肺功能、免疫功能、一氧化氮(Fractional ex-haled nitric oxide,FeNO)、血清嗜酸粒细胞(Eosinophil,EOS)、降钙素原(Procalcitonin,PCT)及C反应蛋白(C-reactive protein,CRP)水平的影响。方法选取医院收治的支气管肺炎患儿100例,并将患儿随机分为对照组和观察组,每组50例。对照组均给予常规西药对症治疗,观察组在对照组方案的基础上给予清金化痰益肺汤合保和丸,两组疗程均为1周,对比两组临床治疗效果、肺功能、免疫功能、呼出气FeNO、EOS、PCT及CRP水平。结果两组患者治疗后,观察组总有效率为94.00%(47/50),显著高于对照组(76.00%,38/50)(P<0.05);对照组及观察组经治疗后一秒呼气最大容积(Forced expiratory volume in one second,FEV_(1))、用力肺活量(Forced vital capacity,FVC)及FEV_(1)/FVC水平均显著提升(P<0.05),同时观察组改善显著优于对照组(P<0.05);对照组及观察组经治疗后免疫球蛋白G(Immunoglobulin G,IgG)、免疫球蛋白A(Immunoglobulin A,IgA)、免疫球蛋白M(Immunoglobulin A,IgM)水平均较治疗前提升显著(P<0.05),同时观察组改善显著优于对照组(P<0.05);对照组及观察组经治疗后FeNO、EOS、PCT及CRP水平均较治疗前降低显著(P<0.05),同时观察组改善显著优于对照组(P<0.05)。结论清金化痰益肺汤合保和丸能显著提高小儿支气管肺炎的临床治疗效果,改善患儿的肺功能及免疫功能,减轻相关炎性反应,具有临床研究意义。

扶正透邪解毒化瘀方对多重耐药铜绿假单胞菌肺炎老年大鼠炎症损伤的影响

目的探讨扶正透邪解毒化瘀方对多重耐药铜绿假单胞菌(MDRPA)肺炎老年大鼠不同时相炎症损伤的影响。方法将老年SD大鼠分为空白组、模型组、西药组、中药组、中药提前给药组、中西医结合治疗组,除空白组外使用经口气管插管法进行MDRPA肺炎造模,观察各组大鼠死亡保护率、生命延长率;在感染后不同时间点取大鼠血清及肺组织标本,应用ELISA试剂盒测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)水平,光镜下观察肺组织支气管、肺泡等结构;在感染后第3日取肺组织标本,电镜下观察各组肺组织超微结构。结果中药提前给药组和中西医结合治疗组可提高死亡保护率和生命延长率。中西医结合治疗组可明显降低MDRPA肺炎老年大鼠血清中促炎因子TNF-α水平,升高抑炎因子IL-10水平,其作用强度明显优于西药组,且可明显减少肺组织炎症细胞浸润和充血水肿,明显减轻肺泡结构的破坏。中药提前给药组可在炎症反应早期升高血清抑炎因子IL-10水平,降低促炎因子TNF-α水平。结论扶正透邪解毒化瘀方对老年MDRPA肺炎大鼠有着较高的死亡保护率和生命延长率,与头孢他啶联合治疗可纠正MDRPA感染后紊乱的炎症状态,减轻炎症损伤。中药提前给药可对MDRPA感染后造成的炎症损伤起到保护与治疗作用,对维持机体免疫稳态具有重要意义。

补肾化瘀方对PCOS患者血清半乳糖凝集素-3、IL-6及CRP水平的影响

目的 探讨补肾化瘀方治疗肾虚血瘀型多囊卵巢综合征(PCOS)患者的临床疗效及可能的作用机制。方法 将2020年9月至2021年9月期间,首次就诊于浙江省中西医结合医院生殖医学科门诊的60例肾虚血瘀型PCOS患者按照随机数字表法分为对照组和治疗组,各30例。对照组给予二甲双胍治疗,治疗组给予补肾化瘀方治疗,两组均治疗3个月经周期。观察治疗前后中医证候积分、性激素、糖脂代谢相关指标及半乳糖凝集素-3(Galectin-3)、白介素6(IL-6)、C反应蛋白(CRP)水平的变化情况。结果 治疗前,两组患者性激素、糖代谢相关指标、脂代谢相关指标、炎症因子水平比较,差异无统计学意义(P>0.05)。治疗后,治疗组PCOS患者排卵率较对照组高(76.83%比49.43%,P<0.01)。与治疗前相比,两组患者中医证候积分[(4.18±2.58)分比(12.50±2.17)分,(6.07±2.94)分比(11.97±2.44)分,P<0.01]、空腹血糖[(5.05±0.45)mmol/L比(5.27±0.70)mmol/L,(4.92±0.56)mmol/L比(5.44±0.37)mmol/L,P<0.05]、空腹胰岛素[(9.66±4.54)mU/L比(13.48±4.73)mU/L,(8.44±2.81)mU/L比(12.20±5.19)mU/L,P<0.05]及胰岛素抵抗指数[(2.18±1.05)比(3.17±1.24),(1.89±0.76)比(2.99±1.42),P<0.05]降低。与对照组比较,治疗组中医证候积分降低[(4.18±2.58)分比(6.07±2.94)分,P<0.05],黄体生成素[(10.12±1.72)mIU/mL比(12.54±2.56)mIU/mL,P<0.05]、黄体生成素/卵泡刺激素[(1.65±0.32)比(1.95±0.40),P<0.05]、睾酮[(0.47±0.12)ng/mL比(0.57±0.16)ng/mL,P<0.05]水平降低,三酰甘油[(1.31±0.62)mmol/L比(1.66±0.56)mmol/L,P<0.05]、总胆固醇[(3.91±0.98)mmol/L比(4.40±0.70)mmol/L,P<0.05]、低密度脂蛋白[(2.60±0.61)mmol/L比(3.05±0.79)mmol/L,P<0.05]水平降低,高密度脂蛋白水平升高[(1.41±0.17)mmol/L比(1.31±0.17)mmol/L,P<0.05]。与对照组比较,治疗组Galectin-3 [(8.71±1.67)ng/mL比(9.91±2.23)ng/mL,P<0.05]、IL-6 [(30.24±3.85)pg/mL比(32.62±4.97)pg/mL,P<0.05]、CRP[(2.80±0.91)mg/L比(3.32±0.64)mg/L,P<0.05]水平降低。结论 补肾化瘀方可有效缓解肾虚血瘀型PCOS临床症状,降低血清炎症指标Galectin-3、IL-6及CRP水平,改善糖脂代谢紊乱,调节性激素水平,促进排卵。

基于网络药理学-分子对接技术及体内实验探讨化瘀消痞汤干预萎缩性胃炎癌前病变的作用机制

目的基于网络药理学和分子对接技术预测化瘀消痞汤干预萎缩性胃炎癌前病变(Precancerous lesions of gastric cancer,PLGC)作用靶点和分子机制,并进行实验验证。方法60只SPF级SD雄性大鼠,随机选取10只为空白对照,其余大鼠进行PLGC模型复制,造模成功后随机分为模型组,叶酸组(2 mg·kg^(-1)·d^(-1)),化瘀消痞汤高、中、低剂量组(24.8、12.4、6.2 g·kg^(-1)·d^(-1)),连续给药干预90天,记录大鼠体质量和3 h进食量,HE染色观察大鼠胃组织病理形态;采用网络药理学和分子对接技术预测化瘀消痞汤干预PLGC的潜在靶点,采取Western blot技术对核心靶点进行验证。结果与空白组比较,模型组大鼠体质量和3 h进食量明显降低(P<0.05),镜下见大鼠胃黏膜明显变薄,腺体明显减少并且排列紊乱,部分区域可见肠上皮化生的杯状细胞及大量炎性细胞浸润,与模型组相比较,各给药组大鼠体质量和3 h进食量不同程度改善,化瘀消痞汤中、高剂量改善明显(P<0.05),大鼠胃黏膜不同程度的修复,腺体排列趋于整齐,间质炎性细胞逐渐减少。网络药理学及分子对接结果表明TP53、JUN、MAPK3/1(ERK1/2)是化瘀消痞汤干预PLGC的核心靶点。分子生物学检测结果显示:与空白组相比较,模型组大鼠胃组织中TP53、c-Jun、ERK1/2蛋白磷酸化水平显著升高(P<0.05);与模型组相比较,各给药组大鼠胃组织中TP53、c-Jun、ERK1/2蛋白磷酸化水平不同程度降低,其中化瘀消痞汤高、中剂量组显著降低(P<0.05)。结论化瘀消痞汤可明显改善PLGC大鼠生存状况,促进胃黏膜修复,其具体机制可能与化瘀消痞汤降低PLGC大鼠胃组织中ERK1/2、c-Jun、TP53蛋白磷酸化水平,进而调节下游信号分子响应有关。