Cytomegalovirus colitis in a patient with Behcet’s disease receiving tumor necrosis factor alpha inhibitory treatment

Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.

Chronic Urticaria Due to Allergy to Wheat Alpha-Amylase Inhibitor Proteins

Chronic spontaneous urticaria (CSU) is defined as the spontaneous appearance of wheals, angioedema, or both, for at least 6 weeks, due to known or unknown causes [1]. In some patients who present a CSU with daily or almost daily symptoms a type I allergy could be the underlying cause. We present one adult patient with chronic urticaria who was finally diagnosed as a non-occupational case of IgE-mediated wheat allergy manifested following exposure by 3 different routes: inhalation (rhinitis and bronchial asthma), dermal absorption (contact urticaria) and ingestion (systemic chronic urticaria). We were able to detect the culprit proteins by immunoblotting. Serum IgE binds mainly to alpha-amylase/trypsin inhibitors and, to a lesser extent, to other proteins associated with food allergy to grains (e.g. beta-glucanase, serpin, peroxidase). In our opinion, skin prick tests with a food standard battery could help in the etiological diagnosis of chronic urticaria. The identification of responsible allergens could be difficult because only a few complex in vitro techniques allow detecting the allergy to several proteins.

Pre-Androgen Ablation Prostate Cancer Patients Who Bleed Do Well with 5 Alpha Reductase Inhibitors

Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like dutasteride has been found helpful in bleeding prostate cancer patients if they have not undergone hormonal manipulation before they developed haematuria. Patients and Method: 26 patients with gross haematuria of prostatic origin who had histologic confirmation of adenocarcinoma of the prostate but who have not had chemical or surgical castration were randomized to receive daily dutasteride in addition to vigorous saline irrigation and antibiotics on one arm and vigorous saline irrigation and antibiotics only as control on the other arm. The time taken before haematuria resolved and the amount of irrigation fluid used were noted. Statistical analysis was done using SPSS. Student’s t-test and Kaplan Meier survival analysis were used to test various variables at 0.5 significant levels. Results: Of the 26 patients 12(46.2%) received 0.5 mg oral dutasteride in addition to saline irrigation while 14 (53.8%) received saline irrigation only. Haematuria stopped in all of 12 (100%) patients on dutasteride arm but on 12 (85.7%) of the 14 patients on the control arm. It took significantly shorter time and lesser volume of irrigation fluid before haematuria resolved in those treated with dutasteride than in those on the control arm. Conclusion: Dutasteride is effective in the control of acute haematuria in pre-androgen ablation prostate cancer patients.

On the Activities of Pancreatic Proteases and Alpha-1 Proteinase Inhibitor in Meat-Type Chicken

The study was aimed at the evaluation of the effects of breed, age, different digestion stimulators, and dietary crude protein (CP) level on the activities of proteolytic enzymes in pancreatic tissue and duodenal chymus (in vivo), serum trypsin and α1-proteinase inhibitor (A1PI) concentrations in meat-type chicks. The study of age dynamics of trypsin and A1PI concentrations was performed on the chicks of hybrid cross “Smena-8”and two parental lines (Plymouth Rock and Cornish) fed standard commercial corn-wheat-SBM diets. Twenty birds per breed were euthanized at 1, 7, 14, 21, 28 and 35 days of age to obtain blood samples and pancreatic homogenate. Experiments on the effects of different digestion promotors (probiotic, acidifier, phytobiotic, enzymatic preparation) and different CP levels (finisher diet, CP 20%, vs. ground corn, CP 8.5%) were performed on 12 hybrid chicks with fistulated duodenum from 14 to 50 days of age. The following conclusions were made: 1) At 1 day of age high proteolytic activity in pancreatic tissue and maximal serum concentrations of trypsin and A1PI were found in both hybrid and parental lines. Since 7 to 35 days of age A1PI concentration was nearly constant, serum trypsin concentration decreased while proteolytic activity in pancreatic tissue exhibited undulate increase;2) Proteolytic activity in pancreatic tissue was higher in hybrids compared to the parental lines from 7 to 35 days of age (p 0.05);3) Supplementation of diet with exogenous enzymes stimulated the digestion due to the increase in protease activity in duodenal chymus by 9.1% compared to unsupplemented control (p 0.05);4) Proteolytic activity in duodenal chymus significantly responded to the substitution of ground corn for the complete diet by 2-fold decrease while serum trypsin concentration responded by 2.5-fold increase (p 0.001). This fact can indicate that physiological functions of digestive proteases are not confined to the digestive processes.

一种用微孔板筛选alpha-葡萄糖苷酶抑制剂的方法(英文)

目的：建立敏感的微孔板方法检测alpha-葡萄糖苷酶抑制活性，以进行抑制剂体外高通量筛选。方法：调整酶和底物适当配比，通过标准曲线、波长扫描、动力学分析以及最佳反应条件的研究，用阿卡波糖验证所建方法。结果：确定反应步骤，96孔板，160μl体系含2．5mmol·L^(-1)PNPG和0．2U·ml^(-1)alpha-葡萄糖苷酶，37℃，pH7．0反应15min，400 nm检测，此法正确、可靠。结论：本文所述用小体积样品筛选得到大量抑制剂的方法，利于从天然产物中开发改善餐后血糖的糖尿病及其并发症治疗药物。

Alpha-黑素细胞刺激素及其新型类似物对小鼠脑微血管内皮细胞产生组织因子的抑制作用

目的：研究Alpha-黑素细胞刺激素（α-MSH）及其新型类似物（STY39）对原代小鼠脑微血管内皮细胞（ MBMEC）在脂多糖（ LPS）刺激下产生组织因子（ TF）和组织因子途径抑制物（ TFPI）的影响。方法选用雌性BALB/c小鼠,纯化并原代培养MBMEC,培养至57 d,采用免疫荧光法检测Ⅷ因子相关抗原,鉴定MBMEC模型。将MBMEC分为PBS对照组,LPS刺激组,LPS刺激后1、2、3 h加入10-7mol/L的α-MSH或STY39组（LPS＋α-MSH,LPS＋STY39）,共8组,每组4孔。分别在LPS刺激后6 h和8 h收集细胞培养上清液和细胞,应用酶联免疫吸附法检测细胞上清液的TF和TFPI浓度,RT-PCR检测细胞TF mRNA表达水平。结果（1） LPS 可诱导 MBMEC 产生 TF 和TFPI蛋白,细胞培养上清液中TF水平于6 h达到高峰, TFPI水平于8 h达到高峰。（2） LPS刺激 MBMEC后1、2、3 h给予10-7mol/L的α-MSH或 STY39,均可显著降低细胞上清液中 TF蛋白含量（P〈0.01）,尤其在 LPS刺激后1 h给予α-MSH 或 STY39的效果最显著（P 〈0.05）, STY39降低TF含量的作用较α-MSH明显（P〈0.05）；但α-MSH和STY39对LPS诱导MBMEC产生TFPI均没有显著的上调作用。（3）在LPS刺激后不同时间点给予10-7mol/L的α-MSH 或STY39,均可显著下调MBMEC TF mRNA的表达水平（P〈0.01）,其中1 h时间点作用最显著（P〈0.05）,但α-MSH与STY39的作用差异无统计学意义。结论α-MSH和 STY39均能抑制LPS诱导原代 MBMEC 产生 TF 蛋白和表达 TF mRNA,且 LPS 刺激1 h 后给药效果较好；STY39对MBMEC产生TF蛋白的抑制作用优于α-MSH。

Differential expression of 5-alpha reductase sozymes in the prostate and its clinical implications

The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone （T） and dihydrotestosterone （DHT）. T is converted to DHT by 5-alpha reductase （5-AR） isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors （5-ARI） are commonly used for the treatment of benign prostatic hyperplasia （BPH） and were once promoted as chemopreventive agents for prostate cancer （PCa）. This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.

Urinary trypsin inhibitor attenuates hepatic ischemia-reperfusion injury by reducing nuclear factor-kappa B activation

BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P < 0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappa B activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group I showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappa B activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.

Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors(Anti-TNFα)

AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) inhibitors.METHODS A meta-analysis of randomized, double-blind, placebocontrolled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction(EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds.RESULTS Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028(95%CI: 0.0011-0.055). The odds ratio was 4.85(95%CI: 1.02-22.99) with EBC and 5.85(95%CI: 1.13-30.38) without EBC.CONCLUSION The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.

I_κB kinase-beta inhibitor attenuates hepatic fibrosis in mice

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.

Design and synthesis of DPP-4 inhibitor for the treatment of type 2 diabetes

An efficient stereoselective synthesis of the rigid aza-bicyclo[3.2.0]heptane scaffold has been developed to provide 2-cyano-pyrrolidine alpha-amino amide 1 as DPP-4 inhibitor.

自身免疫疾病应用肿瘤坏死因子-α抑制剂后并发结核病33例临床特征分析

目的探讨自身免疫疾病患者应用肿瘤坏死因子-α抑制剂后并发结核病的临床特点、治疗及预后。方法收集2019年1月至2023年3月期间广州市胸科医院收治的33例应用生物制剂(肿瘤坏死因子-α抑制剂)后并发结核病患者的临床资料,其中男性25例,女性8例,中位年龄32岁,回顾性分析其临床症状、实验室检查结果、影像学及气管镜特征、病理特点、治疗及转归进行综合分析。结果常见临床表现为咳嗽(26/33)、咳痰(23/33)、发热(17/33)。发病多见于肺结核(32/33)、支气管结核(15/33)、纵隔及肺门淋巴结结核(11/33)。结核菌双侧全肺播散(21/33),结核菌肺内组织(支气管、纵隔肺门淋巴结、胸膜)播散(19/33),肺外结核(18/33),肺结核伴肺内组织或肺外结核(26/33)。血CD4+T淋巴细胞检测正常(23/33),血IGRA检测阳性(27/33)。肺部影像学粟粒性结节(8/33)。淋巴结组织病理为不典型肉芽肿结节。抗结核治疗疗程8~32个月。死亡1例。结论自身免疫疾病应用肿瘤坏死因子-α抑制剂后并发结核病患者以双肺病灶多见,易播散到肺内组织及全身多个器官,免疫功能下降,多需延长治疗疗程,经综合治疗多预后良好。

血清LncRNA FAF、ITIH4在慢性心力衰竭患者中的表达意义及对预后的预测价值

目的探讨血清长链非编码RNA(LncRNA)FAF、间α胰蛋白酶抑制因子重链4(ITIH4)在慢性心力衰竭(CHF)患者中的表达意义及对预后的预测价值。方法选择2020年1月—2022年1月安徽医科大学第二附属医院急诊内科收治的CHF患者187例为CHF组,再根据NYHA心功能分级分为Ⅱ级亚组65例,Ⅲ级亚组77例,Ⅳ级亚组45例。于同期招募健康志愿者103例为健康对照组。2组受试者均检测血清LncRNA FAF表达和ITIH4水平,CHF患者出院后随访12个月,统计随访期间主要不良心血管事件(MACE)发生率;多因素Logistic回归分析影响CHF患者发生MACE的因素;受试者工作特征(ROC)曲线分析LncRNA FAF、ITIH4预测CHF患者发生MACE的价值。结果CHF组血清LncRNA FAF表达、ITIH4水平低于健康对照组(t/P=24.469/<0.001、35.196/<0.001)。血清LncRNA FAF表达、ITIH4水平Ⅳ级亚组低于Ⅲ级亚组低于Ⅱ级亚组(F/P=91.653/<0.001、102.345/<0.001)。MACE亚组血清LncRNA FAF表达,ITIH4水平低于非MACE亚组(t/P=13.556/<0.001、6.293/<0.001)。NYHAⅣ级、高水平NT-proBNP是CHF患者发生MACE的危险因素[OR(95%CI)=4.627(2.245~9.538)、2.284(1.505~3.468)],高表达LncRNA FAF、高水平ITIH4是保护因素[OR(95%CI)=0.599(0.425~0.844)、0.666(0.478~0.928)]。LncRNA FAF、ITIH4及二者联合预测CHF患者发生MACE的曲线下面积为0.796、0.801、0.896,二者联合预测曲线下面积高于单独预测(Z=2.453、2.404,均P<0.001)。结论CHF患者血清LncRNA FAF表达和ITIH4水平均降低,且与不良预后有关,联合LncRNA FAF和ITIH4可预测CHF患者预后不良风险。

山甲白花汤联合吉西他滨抗胰腺癌耐药机制研究

目的:探讨山甲白花汤联合吉西他滨抗胰腺癌耐药的作用机制。方法:将30只小鼠按随机数表法分为模型组、吉西他滨组和联合组,构建皮下移植瘤小鼠模型,分别使用山甲白花汤、吉西他滨及联合处理小鼠,观察肿瘤的体积、重量变化和类固醇受体辅激活因子/分化抑制蛋白1(Src/Id1)信号通路蛋白。将人胰腺癌细胞系1(PANC-1)细胞分为对照组、吉西他滨处理组、联合处理组、联合+微小核糖核酸-124-3p抑制剂(miR-124-3p inhibitor)组和联合+过表达信号转导蛋白2样1(oe-SDF2L1)组,比较各组细胞增殖与迁移能力、微核糖核酸-124-3p(miR-124-3p)、信号转导蛋白2样1(SDF2L1)及信使核糖核酸(mRNA)水平。结果:与吉西他滨组比较,联合组中肿瘤体积与重量降低、Id1和磷酸化非受体酪氨酸激酶/非受体酪氨酸激酶(p-Src/Src)、SDF2L1水平降低。与对照组比较,吉西他滨处理组细胞增殖与迁移率明显降低,微小核糖核酸-124-3p(miR-124-3p)水平升高且SDF2L1水平明显降低,与吉西他滨处理组比较,联合处理组细胞增殖与迁移率明显降低,miR-124-3p水平升高且SDF2L1水平明显降低,与联合处理组比较,联合+miR-124-3p inhibitor组和联合+oe-SDF2L1组细胞增殖与迁移率均明显升高,SDF2L1水平均明显升高。结论:山甲白花汤联合吉西他滨通过上调miR-124-3p抑制SDF2L1发挥抗胰腺癌耐药作用。

肿瘤坏死因子α抑制药的围手术期管理

肿瘤坏死因子α抑制药(TNFαi)作为抑制免疫系统、降低炎症水平的一类生物制剂,在自身免疫性疾病中的应用越来越广泛。但TNFαi理论上具有增加感染、肿瘤及其他并发症风险的可能,因此对于接受手术的患者,需权衡继续用药引起并发症发生率升高和暂停用药导致症状加重的相对风险,以提高围手术期用药安全性。目前中国尚无明确的临床指南指导TNFαi的围手术期管理,该文以类风湿关节炎、强直性脊柱炎、炎症性肠病、银屑病等适应证为出发点,系统梳理TNFαi在患者围手术期药物治疗中的使用建议与注意事项,以期为TNFαi的围手术期管理提供参考。

动态增强MRI联合血清SPINK1水平诊断原发性肝癌价值研究

目的探讨动态增强磁共振(MRI)联合血清丝氨酸蛋白酶抑制剂因子Kazal 1型(SPTINK1)水平诊断原发性肝癌(PLC)的价值。方法2020年4月~2023年4月我院收治的乙型肝炎肝硬化患者204例,均接受动态增强MRI扫描检查,对肝内占位性病变者行细针穿刺病理学检查。采用ELISA法检测血清SPTINK1和甲胎蛋白水平。应用二元多因素Logistic回归分析诊断HCC的血清指标,应用受试者工作特征曲线(ROC)分析血清指标的诊断效能。结果在204例乙型肝炎肝硬化患者中,发现肝内占位性病变并经穿刺病理学检查诊断肝细胞癌(HCC)30例(14.7%);HCC组血清SPTINK1和AFP水平分别为(23.9±5.2)ng/mL和(426.5±67.0)ng/mL,显著高于肝硬化组【分别为(7.4±2.1)ng/mL和(14.4±4.3)ng/mL,P<0.05】;血清SPTINK1(OR:3.69,95%CI:1.08~12.49)和甲胎蛋白(AFP,OR:3.54,95%CI:1.04~11.98)均与HCC高度相关;以血清AFP水平大于等于360.1 ng/mL为截断点,其诊断HCC的AUC为0.80(95%CI:0.72~0.89),灵敏度和特异度分别为71%和73%,以血清SPTINK1水平等于或大于15.6 ng/mL为截断点,其诊断HCC的AUC为0.82(95%CI:0.74~0.91),灵敏度和特异度分别为82%和79%。结论在肝硬化患者,经影像学检查发现肝内占位性病变时,血清SPINK1和AFP水平升高可以帮助初步判断病变性质,应尽早进行穿刺病理学检查。

HIF-1α和HIF-PHI在慢性肾脏病血管钙化中的研究进展

慢性肾脏病已成为全球公共卫生的重大挑战,心血管疾病是其首要致死原因。血管钙化表现为钙和磷酸盐矿物质在动脉壁的病理性沉积,可导致血管硬化、管腔狭窄,不仅影响肾脏的血流供应,还增加心血管疾病的风险。在慢性肾脏病的病理环境下,肾脏持续处于低氧状态,低氧诱导因子-1α(HIF-1α)作为关键的转录因子,对细胞适应低氧环境至关重要。HIF-1α通过促进血管平滑肌细胞成骨样分化等多条途径,影响慢性肾脏病血管钙化的进展。低氧诱导因子脯氨酸羟化酶抑制剂(HIFPHI)是肾性贫血的新型口服治疗药物,可以通过激活人体对缺氧的自然生理反应,抑制HIF的降解以促进红细胞生成,增加内源性促红细胞生成素的产生。HIF-PHI有促进血管钙化的可能,其促钙化作用与HIF-1α的稳定性密切相关。因此,充分了解HIF-PHI在血管钙化中潜在的危害性并加以重视意义重大。

Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients

Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.

凝血酶-抗凝血酶复合物、纤溶酶-α2-纤溶酶抑制剂复合物和血栓弹力图评估肿瘤患者凝血功能的价值

目的 分析凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2-纤溶酶抑制剂复合物(PIC)和血栓弹力图(TEG)评估肿瘤患者凝血功能的价值。方法 选取2022年1月—2023年8月中国医学科学院肿瘤医院深圳医院120例肿瘤患者(病例组),以同期体检健康者30名作为对照组。比较2组TAT、PIC、TEG各参数的差异。基于Caprini评分将肿瘤患者细分为不同血栓风险组,比较各组TAT、PIC、TEG各参数的差异。比较不同肿瘤类型患者3项指标的差异。采用受试者工作特征(ROC)曲线分析TAT、PIC、TEG各参数诊断肿瘤患者凝血功能的效能。结果 病例组TAT、PIC高于对照组(P<0.05)。血栓极高风险组TAT、PIC高于中/低风险组(P<0.05);肝癌、肺癌、肠癌、胃癌患者TAT、PIC水平均升高,但差异无统计学意义(P>0.05);TAT、PIC、TEG评价肿瘤患者血液高凝状态的敏感性分别为85.0%、55.0%、56.70%,特异性分别为93.3%、81.7%、70.0%,ROC曲线下面积分别为0.94、0.72、0.63。结论 TAT、PIC可早于TEG提示肿瘤患者凝血功能异常,能更好地提示肿瘤患者血液高凝状态。

血清ITIH4和MCL-1水平与急性缺血性脑卒中患者病情程度及预后的关系

目的探究急性缺血性脑卒中(AIS)患者血清间α胰蛋白酶抑制因子重链4(ITIH4)、髓样细胞白血病因子-1(MCL-1)表达与病情程度及预后的关系。方法纳入2019年7月—2022年7月河南科技大学附属黄河医院神经内科诊治AIS患者128例为AIS组。根据入院时美国国立卫生研究院卒中量表(NIHSS)评分,分为轻度亚组(NIHSS<6分,n=42)、中度亚组(NIHSS 6~<14分,n=52)和重度亚组(NIHSS≥14分,n=34)。根据出院3个月时AIS患者改良Rankins评分,分为预后不良亚组(mRS评分>2分,30例)和预后良好亚组(mRS评分≤2分,98例)。另选取同期医院体检的健康人70例为健康对照组。酶联免疫吸附试验检测血清ITIH4、MCL-1水平。Pearson相关分析血清ITIH4、MCL-1水平与病情程度及预后的相关性;多因素Logistic回归分析影响AIS患者预后的因素;受试者工作特征曲线分析血清ITIH4、MCL-1对AIS患者预后的预测价值。结果AIS组患者血清ITIH4、MCL-1水平显著低于健康对照组(t/P=43.211/<0.001,43.191/<0.001);病情程度越重,AIS患者血清ITIH4/MCL-1水平越低(F/P=107.796/<0.001,297.976/<0.001);预后不良亚组梗死面积、入院24 h NIHSS评分高于预后良好亚组(t/P=9.637/<0.001,9.752/<0.001),血清ITIH4、MCL-1水平及出院3个月简易智能状态量表(MMSE)评分、蒙特利尔认知评估量表(MoCA)评分低于预后良好亚组(t/P=26.723/<0.001,11.709/<0.001,13.674/<0.001,10.782/<0.001);AIS患者血清ITIH4、MCL-1与梗死面积、入院24 h NIHSS评分呈负相关(r/P=-0.705/<0.001,-0.685/<0.001;-0.761/<0.001,-0.619/<0.001),与出院3个月MMSE评分、MoCA评分呈正相关(r/P=0.656/<0.001,0.632/<0.001;0.751/<0.001,0.789/<0.001);出院3个月MMSE评分高、出院3个月MoCA评分高是影响AIS患者预后不良的独立保护因素[0.622(0.446~0.868),0.606(0.427~0.861)],血清ITIH4低、MCL-1低、梗死面积大、入院24 h NIHSS评分高是危险因素[OR(95%CI)=1.467(1.150~1.870),1.415(1.094~1.829),1.605(1.168~2.205),1.765(1.233~2.526)];血清ITIH4、MCL-1及两项联合预测AIS预后不良的AUC分别为0.811、0.835、0.923,两项联合预测AIS预后不良的AUC大于单一指标,差异具有统计学意义(Z=4.258、4.119,P均<0.001)。结论AIS患者血清ITIH4、MCL-1表达下调,两者表达水平与病情严重程度有关,两者联合对AIS患者预后具有较高的预测价值。