医疗领域人工智能应用的研究进展＊

人工智能引发了医疗领域的数字革命，在推动行业发展方面具有极大潜力。本研究围绕临床诊疗、医学研究和公共卫生三个基本场景，聚焦人工智能与传统中医药的交叉与融合，并着重介绍人工智能在疾病诊断、决策支持、医学研究以及重大公共卫生事件中的应用。虽然人工智能在诸多方面显示出独特优势，但仍存在透明度不高、缺乏安全性评估和相关法律法规监管等问题需要谨慎解决，以促进人工智能技术在医疗领域的推广。     

基于“肝阳虚”理论探讨化疗所致周围神经病变的病机与治疗＊

化疗所致周围神经病变（Chemotherapy-induced peripheral neuropathy，CIPN）是临床常见的由化疗药物引起的一系列神经毒性症状，易造成神经功能障碍，四肢感觉弱化、缺失等，严重影响肿瘤患者生活质量及临床疗效。CIPN的发病机制尚不十分明确，目前也没有可广泛用于临床的特效药物治疗。中医药治疗CIPN具有特定的优势，取得了一定成绩，但在理论依据和临床疗效方面仍有一定的局限性。本文通过分析CIPN的临床症状特点，深入剖析其与中医肝阳虚理论之间的关系，探讨CIPN的中医病因病机与用药规律，指导临床治疗CIPN，以期更好地发挥中医药在肿瘤治疗中的减毒增效作用。     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.     

Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation.Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up.ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0).ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.     

中毒性表皮坏死松解症导致眼部远期并发症1例

中毒性表皮坏死松解症与Stevens-Johnson综合征是一种由药物反应引起的严重的表皮及黏膜的不良反应。最常发生于成人,与服用磺胺类、巴比妥类、非类固醇抗炎药、苯妥英纳、醋甲唑胺、别嘌呤醇和青霉素等药物有关。约有1/5的患者否认有服药史,约在1/3病例中由于同时患有严重疾病及用药物治疗而病因不明。中毒性表皮坏死松解症为皮肤科少数病情危重的疾病之一,其死亡率达30%~35%。20%~40%的存活者有眼睛受累。少数患者由于泪管阻塞可出现泪眼,多数患者表现为睫毛、眼睑上皮增生,伴鳞状化生、结膜和角膜新生血管形成,引起一种中毒性表皮坏死松解症眼综合征。经及时治疗中毒性表皮坏死松解症可好转。但是部分患者眼部情况可继续发展,可引起畏光、灼痛、视力下降甚至失明。现汇报1例中毒性表皮坏死松解症眼综合征患者眼部远期并发症。     

基于基因表达谱相似性的四物汤重定位及抗乳腺癌有效成分群辨识＊

目的 发现四物汤的新药理作用并辨识其有效成分群。方法 于GEO和Cmap数据库获取四物汤和1309个小分子药物的基因表达谱，计算差异表达基因及四物汤与1309个小分子药物的基因表达谱间的相似性，相似性较高的小分子药物的药理作用为四物汤的新药理作用。相似性较高的小分子药物的靶点作为四物汤发挥新药理作用的靶标，利用分子对接技术辨识四物汤的有效成分群。结果 四物汤具有抗乳腺癌的作用，其有效成分群为荭草苷、芍药苷和半乳糖醛酸等，并通过文献调研验证了辨识结果的可靠性。结论 本研究将为扩大四物汤的临床应用范围及质量控制奠定基础，为乳腺癌的治疗提供新方法。