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关键词： 肺肠同治   通腑泻肺方   慢性阻塞性肺疾病急性加重期   肺功能   炎症反应  

摘要： 【目的】基于肺肠同治理论探讨通腑泻肺方对慢性阻塞性肺疾病急性加重期(AECOPD)患者临床疗效及血清炎症细胞因子的影响。【方法】选取2020年12月至2022年12月期间在唐山市中医医院中医肺病科就诊的134例AECOPD患者展开回顾性研究,根据治疗方案的不同将患者分为观察组和西药组,每组各67例。西药组给予常规西医治疗,观察组在西药组治疗的基础上给予通腑泻肺方治疗,疗程为2周。观察2组患者治疗前后改良呼吸困难量表(mMRC)评分、慢阻肺评估测试(CAT)评分、肺功能指标、动脉血气分析指标、血清炎症细胞因子水平的变化情况,比较2组患者的临床疗效、不良反应总发生率和住院时间。【结果】(1)疗效方面,治疗2周后,观察组的总有效率为95.52%(64/67),西药组为79.10%(53/67),组间比较(χ^(2)检验),观察组的疗效明显优于西药组(P<0.01)。(2)相关量表评分方面,治疗后,2组患者的mMRC评分、CAT评分均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于西药组(P<0.01)。(3)肺功能指标方面,治疗后,2组患者的第一秒用力呼气量(FEV1)、用力肺活量(FVC)及其比值(FEV1/FVC)均较治疗前升高(P<0.05),且观察组的升高幅度均明显优于西药组(P<0.01)。(4)动脉血气分析指标方面,治疗后,2组患者的血氧饱和度(SaO_(2))、动脉血氧分压(PaO_(2))水平均较治疗前升高(P<0.05),动脉血二氧化碳分压(PaCO_(2))水平均较治疗前降低(P<0.05),且观察组治疗后对SaO_(2)、PaO_(2)水平的升高幅度及对PaCO_(2)水平的降低幅度均明显优于西药组(P<0.01)。(5)血清炎症细胞因子方面,治疗后,2组患者的血清肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、白细胞介素6(IL-6)水平均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于西药组(P<0.01)。(6)安全性方面,观察组的不良反应总发生率为2.99%(2/67),西药组为5.97%(4/67),组间比较,差异无统计学意义(P>0.05)。(7)住院时间方面,观察组的住院时间较西药组明显缩短,差异有统计学意义(P<0.05)。【结论】基于肺肠同治理论的通腑泻肺方可有效缓解AECOPD患者呼吸困难等症状,改善患者肺功能,纠正动脉血气紊乱,抑制炎症因子释放,缩短治疗时间,且未引发严重不良反应,安全有效。

关键词： 干燥综合征   T淋巴细胞亚群   免疫调节   免疫失衡   中医治疗   炎症通路  

摘要： 干燥综合征(SS)是以外分泌腺功能障碍为核心的自身免疫病,其发病机制涉及遗传易感性、表观遗传调控异常及感染触发等多因素交互作用,免疫失衡核心聚焦于T淋巴细胞亚群动态紊乱。Th17/Treg比例失调及Tfh细胞异常活化通过细胞因子网络加剧腺体炎症浸润,其中白介素(IL-17)、B细胞激活因子(BAFF)等分子介导的免疫-上皮细胞交互作用尤为突出。当前西医治疗虽能控制病情进展,但存在靶向性不足、长期用药安全性等问题。中医学通过多靶点调控改善SS患者免疫稳态,内治法以滋阴润燥方药调节Th1/Th2平衡,外治法通过雾化给药、穴位刺激等改善局部微环境,临床观察显示中西医结合治疗可显著延缓腺体功能退化。本文系统综述SS免疫病理机制、T细胞亚群动态变化规律及中医药干预策略,为优化、改进SS患者中医治疗方案提供新思路。

关键词： 细菌性肝脓肿   超声引导   穿刺置管引流   细胞因子   治疗  

摘要： 目的观察在超声引导下穿刺引流治疗细菌性肝脓肿患者的疗效。方法2020年10月~2023年10月我院收治的96例细菌性肝脓肿患者,被随机分为观察组48例和对照组48例,分别给予超声引导下穿刺置管引流或超声引导下穿刺抽吸治疗。采用ELISA法检测血清丙二醇(MDA)、超氧化物歧化酶(SOD)和皮质醇(COR)水平,采用ELISA法检测血清白细胞介素-6(IL-6)、IL-8和IL-12水平。结果经1~3周治疗,两组均治愈,脓腔闭合,随访3月,经超声检查未发现脓肿复发病例;治疗后观察组血清TBIL、ALT、ALB和GGT水平分别为(15.3±2.4)μmol/L、(72.4±7.5)U/L、(39.3±2.8)g/L和(79.3±19.4)U/L,与对照组【分别为(16.5±2.3)μmol/L、(73.2±10.3)U/L、(36.6±2.9)g/L和(73.1±22.3)U/L】比,差异无统计学意义(P>0.05);观察组血清SOD、COR和MDA水平分别为(73.3±7.5)U/mL、(117.8±8.4)nmol/L和(5.1±0.8)μmol/mL,与对照组【分别为(75.4±7.1)U/mL、(118.8±8.5)nmol/L和(5.5±0.9)μmol/mL】比,差异无统计学意义(P>0.05);观察组血清IL-6、IL-8和IL-12水平分别为(0.2±0.1)ng/mL、(0.3±0.1)ng/mL和(81.3±16.5)ng/mL,均显著低于对照组【分别为(0.3±0.1)ng/mL、0.4±0.1)ng/mL和(95.2±17.1)ng/mL,P<0.05】。结论采取在超声引导下穿刺置管引流治疗肝脓肿患者效果肯定,可减少穿刺次数,缩短治疗时间,减少抗生素用量。

关键词： 疱疹性咽峡炎   小儿柴桂退热口服液   磷酸奥司他韦颗粒   炎性因子   体液免疫  

摘要： 目的观察小儿柴桂退热口服液联合磷酸奥司他韦颗粒治疗疱疹性咽峡炎的临床效果。方法选取2021年1月—2023年2月鹰潭市妇幼保健院收治的疱疹性咽峡炎患儿80例,采用随机数字表法分为观察组和对照组,每组40例。对照组在常规治疗基础上予以磷酸奥司他韦颗粒治疗,观察组在对照组基础上予以小儿柴桂退热口服液治疗,2组均治疗5 d。比较2组临床疗效,症状缓解时间,治疗前后血清炎性因子[白介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)]、体液免疫指标[免疫球蛋白A(IgA)、免疫球蛋白M(IgM)]及不良反应。结果观察组总有效率为95.00%,高于对照组的80.00%(χ^(2)=4.114,P=0.043);观察组疱疹消退、食欲恢复及退热时间均短于对照组(P<0.01)。治疗5 d后,2组IL-6、CRP、TNF-α水平较治疗前降低,且观察组低于对照组(P<0.01);2组IgA、IgM水平较治疗前升高,且观察组高于对照组(P<0.01)。观察组不良反应总发生率为7.50%,与对照组的5.00%比较差异无统计学意义(χ^(2)=0.213,P=0.644)。结论小儿柴桂退热口服液联合磷酸奥司他韦颗粒治疗疱疹性咽峡炎临床效果较好,可缩短症状缓解时间,降低炎性因子表达水平,提高免疫功能,且安全性较高。

关键词： 肺癌   癌胚抗原   神经元特异性烯醇化酶   鳞状细胞癌抗原  

摘要： 目的探讨血清癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)和鳞状细胞癌抗原(SCCA)与肺癌患者病情和预后的关系。方法选取57例肺癌患者作为观察组,并选取同期体检健康人员57例为A组,同期肺部良性肿瘤患者57例为B组。比较3组受试者和不同TNM分期肺癌患者的CEA、NSE及SCC水平,分析肺癌患者预后的影响因素。结果B组患者血清CEA、NSE和SCCA水平均高于A组,观察组患者血清CEA、NSE和SCCA水平均高于A组及B组,差异均有统计学意义(P﹤0.05)。Ⅱ期患者血清CEA、NSE和SCCA水平均高于Ⅰ期,Ⅲ期患者血清CEA、NSE和SCCA水平均高于Ⅰ期及Ⅱ期,差异均有统计学意义(P﹤0.05)。多因素Cox回归分析结果显示,TNM分期为Ⅲ期、CEA水平≥14.01 ng/ml、NSE水平≥27.17 ng/ml均是肺癌患者预后不良的独立危险因素(P﹤0.05)。结论肺癌患者血清CEA、NSE以及SCCA水平与疾病严重程度密切相关,且TNM分期、CEA水平以及NSE水平均是肺癌患者预后的独立影响因素。

关键词： Mitochondria   AAV8   GAN diet   White adipose tissue   Lipopolysaccharide   TGF beta  

摘要： ATAD3A deficiency in hepatocytes has been shown to promote simple steatosis (SS). ATAD3 is upregulated in MCD diet-induced MASH. Since the MCD diet is commonly used to induce liver fibrosis, which is related to HSCs activation, we are prompted to investigate the functions of ATAD3 in these two cell types and their mediated transition from SS to MASH. To investigate the role of ATAD3A in HSCs, human LX-2 cells were treated with TGF beta. The results showed that ATAD3A expression was linked to the fibrotic markers ACTA2 and COL1A1. Knockdown of ATAD3A reversed TGF beta-induced HSC activation by downregulating both canonical (SMAD2/3) and non-canonical (ERK1/2 and p38 MAPK) TGF beta signaling pathways. To examine the effect of ATAD3 on the transition from SS to MASH, MASH was induced in mice using the GAN diet for 24 weeks. After 12 weeks, AAV8conjugated Atad3 shRNA was administered to knock down Atad3 in the liver. This intervention suppressed steatosis and fibrosis while enhancing insulin sensitivity. Further analysis using conditioned medium (CM) from WT and ATAD3A KO Huh7 cells treated with LPS and PA revealed that IL-6 secretion from Huh7 hepatocytes activated HSCs. However, IL-6 secretion was diminished in ATAD3A KO CM. CM from ATAD3A KO cells also suppressed expression of fibrotic markers ACTA2, P-P38, and P-SMAD3 compared to WT cells under MASH conditions. These data suggest that AAV8-mediated Atad3 silencing in hepatocytes prevents the transition from SS to MASH, at least in part, by downregulating IL-6 secretion to suppress HSC activation in MASH.

关键词： Antimicrobial peptides   Atopic dermatitis   Barrier function   Innate immunity   Keratinocyte biology  

摘要： Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis. At high concentrations, the nonreducing disaccharide trehalose (a-d-glucopyranosyl a-d-glucopyranoside) induces a transient senescence-like state in fibroblasts and promotes wound repair. In this study, we investigated the effect of trehalose on normal human keratinocytes and demonstrated its specific role in the skin barrier. RNA-sequencing analysis revealed that trehalose regulates the expression of many skin barrier-associated genes. T helper 2 cytokines IL-4/IL-13 were observed to downregulate several differentiation markers (FLG, loricrin, keratin 1, and keratin 10) and epidermal antimicrobial proteins in monolayer-cultured keratinocytes and living skin equivalents and impaired skin barrier function in living skin equivalents, all of which were significantly upregulated or restored by trehalose. Trehalose inhibited IL-33 expression and reduced nuclear IL-33 levels by activating MAPK/extracellular signal-regulated kinase kinase 5-extracellular signal-regulated kinase 5 and suppressing extracellular signal-regulated kinase kinase 1/2-extracellular signal-regulated kinase pathway. It also increased NRF2 activation to trigger antioxidant enzyme production through JNK, thus neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription 3/signal transducer and activator of transcription 6 activation and restored IL-4/IL-13-suppressed skin barrier molecules through IL-33 downregulation and NRF2 activation. This study demonstrated that trehalose may play a role in skin barrier repair in atopic dermatitis.

关键词： Chronic Obstructive Pulmonary Disease (COPD)   Small airway disease   Biomass smoke   IL-17a   IL-17a   NR1D1  

摘要： Introduction: Biomass smoke (BS) exposure is a critical environmental risk factor for Chronic Obstructive Pulmonary Disease (COPD). In this study, mechanisms of biomass smoke (BS)-induced small airway disease are explored, with a focus on the roles of Interleukin-17a (IL-17a) and Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1). Methods: This study included 20 BS exposure COPD (BS-COPD) patients and 13 controls, who underwent chest high-resolution computed tomography (HRCT) scans to assess emphysema and small airway disease. The control group was divided into a low- and high BS exposure control group. Serum IL-17a levels were measured. Wild-type and IL-17a-/- B6/C57 mice were exposed to wood smoke to establish a COPD model in mice. Airway pathology was evaluated by histological analysis. The effects of IL-17a and NR1D1 on cell proliferation of BEAS-2b cells exposed to wood smoke particulate matter 2.5 were assessed in vitro using flow cytometry and Western blotting. Results: HRCT revealed significantly higher small airway disease and emphysema in BS-COPD patients compared to controls (p < 0.01). Small airway disease exhibited the strongest negative correlation with FEV1%predicted (r = -0.61, p = 0.004). High-exposure control group showed significant BS Index correlations with small airway disease (r = 0.81, p = 0.049) and emphysema (r = 0.87, p = 0.025). Serum IL-17a levels correlated with small airway disease in BS-COPD (r = 0.48, p = 0.033). The mouse model demonstrated higher airway wall thickness and small airway disease in IL-17a-/- mice exposed to wood smoke. In vitro, IL-17a promoted BEAS-2b cell proliferation, an effect enhanced by NR1D1 downregulation. Conclusions: BS exposure drives emphysema and small airway disease in non-COPD individuals. NR1D1 downregulation exacerbates IL-17a-mediated remodeling in vitro, suggesting therapeutic potential. Trial registration: ChiCTR-OOC-16008692

关键词： Interleukin-6   gp130   BACE1   Long-term potentiation   Neuronal activity   Verubecestat   AZD3839  

摘要： The pleiotropic cytokine IL-6 regulates numerous processes in the body, including neuronal functions. IL-6 either binds to membrane-bound receptor (mIL-6R) and triggers signaling via heteromerization with the signal transducer gp130 (classical signaling), or binds to its soluble form (sIL-6R) to act on cells that do not express mIL-6R (trans-signaling). The ss-secretase BACE1 can cleave gp130 as well as IL-6R and we hypothesized that BACE1 may alter neuron activity and synaptic transmission via modulation of IL-6 signaling. We used multielectrode array (MEA) recordings to monitor electrical activity of neuronal networks in acute cerebellar slices as well as long-term potentiation (LTP) induced by high-frequency stimulation in the hippocampus and to assess how exposure to IL-6 affects these processes. A pharmacological approach was applied to elucidate the contribution of trans-signaling involving BACE1. Spontaneous neuronal activity in cerebellar slices significantly decreased upon perfusion with IL-6 but not LIF and recovered during wash out. BACE1 inhibitors verubecestat or AZD3839 abolished the inhibitory effects of IL6. Furthermore, IL-6 and LIF reversibly inhibited LTP in hippocampal slices, and in contrast to cerebellar neurons, BACE1 inhibitors verubecestat or AZD3839 did not abolish the inhibitory effect of IL-6 on LTP. Interestingly, a dramatic rebound effect on excitatory postsynaptic potentials was observed with BACE1 inhibitor AZD3839 but not verubecestat during wash out. Our results support relevant and differential roles of IL-6, LIF and BACE1 in pathways modulating neuronal discharge activity in the cerebellum and the synaptic plasticity in the hippocampus, and a possible involvement of this interaction in deficits of memory and learning.

关键词： Syringomyelia   TNF-alpha   Necroptosis   Reactive astrocytes   Infliximab   Sensory dysfunction  

摘要： Syringomyelia is a severe and progressive disease characterized by fluid-filled cavities that form within the spinal cord, leading to progressive neurological deterioration. However, the molecular mechanisms that cause neuronal death and subsequent dysfunction remain incompletely understood. This study demonstrates that tumor necrosis factor-alpha (TNF-alpha)-mediated necroptosis plays a crucial role in neuronal death during syringomyelia progression. RNA-seq analysis revealed significantly elevated necroptosis scores at both 14 and 28 days after syrinx formation, with identified disease-related differentially expressed necroptosis genes primarily enriched in TNF-alpha-related signaling pathways. Through establishing a rat model of syringomyelia with central canal dilation, significant activation of necroptosis markers, phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL), was observed in the area surrounding the syrinx, with their expression predominantly localized to neurons. Concurrently, we found markedly elevated TNF-alpha levels around the syrinx, and primarily originating from reactive astrocytes (70.29 %). Upregulation of TNF receptor 1 (TNFR1) in perilesional neurons suggested enhanced sensitivity to TNF-alpha-mediated death signals. Subsequently, administration of the TNF-alpha inhibitor infliximab at day 14 post-modeling significantly alleviated the expression of necroptosis markers and attenuated the progression of sensory dysfunction at day 28, even in the presence of persistent syrinx. This study is the first to reveal TNF-alpha-mediated neuronal necroptosis as a crucial mechanism in neurological deterioration in syringomyelia, providing novel molecular targets for treatment. These findings suggest that targeting this pathway, particularly in combination with conventional surgical approaches, may offer therapeutic benefits for patients with syringomyelia.