[摘 要] 目的：探究外周血1型辅助性T细胞（Th1）/Th2/Th17细胞相关细胞因子IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α、IL-17A对Ⅲ~Ⅳ期肺鳞状细胞癌（LSCC）患者一线免疫治疗联合化疗疗效和预后的预测价值及其动态变化的意义。方法：回顾性分析2020年1月至2023年12月在内蒙古医科大学附属医院接受一线免疫治疗联合化疗的58例Ⅲ~Ⅳ期LSCC患者的临床资料，采集基线及治疗2、4、6周期后和疾病进展时的外周血，用流式细胞术检测Th1/Th2/Th17细胞分泌的细胞因子水平，用受试者工作特性曲线（ROC）确定各细胞因子基线的最佳截断值，据此将患者分为高、低表达组；根据RECIST 1.1标准，将患者分为客观缓解（ORR）[完全缓解（CR） + 部分缓解（PR）]组、非ORR[（疾病稳定（SD） + 疾病进展（PD）]组、疾病控制（DCR）（CR + PR + SD）组和非DCR（即PD）组；根据PD-L1表达评分将患者分为PD-L1 ≥ 1%组和PD-L1 < 1%或未知组。比较组间疗效的差异；分析临床病理特征与疗效的相关性；用广义估计方程（GEE）评估细胞因子动态变化与疗效的关系；用Kaplan-Meier法绘制生存曲线，Log-Rank检验比较组间差异，COX比例风险回归模型进行单因素及多因素预后分析。结果：IL-2和IFN-γ高表达组患者的客观缓解率（ORR）显著高于低表达组患者（P < 0.001）。IL-2、IFN-γ高表达组和IL-10、TNF-α低表达组患者的疾病控制率（DCR）均显著高于对应低/高表达组（P < 0.001）。PD-L1 ≥ 1%组DCR显著高于PD-L1 < 1%或未知组（P < 0.001）。动态分析显示，在4周期及6周期时，有效组患者血清中IL-6表达水平显著低于无效组（P < 0.05），控制组IL-6表达水平显著低于未控制组（P < 0.001）；治疗前及6周期时有效组IFN-γ表达水平显著高于无效组（P < 0.05），治疗前控制组IFN-γ表达水平显著高于未控制组（P < 0.05）。生存分析显示，IL-2低表达组、IL-10高表达组、TNF-α高表达组和IFN-γ低表达组患者的中位PFS显著缩短（均P < 0.05）。COX多因素分析证实，治疗前IL-2 < 2.45 pg/mL和IL-10 ≥ 3.52 pg/mL 是PFS的独立危险因素。结论：外周血Th1/Th2/Th17细胞相关细胞因子的基线水平及动态变化对Ⅲ~Ⅳ期LSCC患者一线免疫治疗联合化疗的疗效和预后具有预测价值。

Hungary, as the first European country to legislate TCM, its legislation experience has significant implications for the international development of TCM. This article reviewed the historical process of TCM legislation in Hungary, summarized its legislative achievements, and analyzed the problems encountered during the implementation process. It was found that the current challenges faced by TCM legislation in Hungary mainly include constraints from the dominance of modern medicine, restrictions from strict qualification requirements, insufficient public awareness, difficulties in TCM registration, and challenges in policy coordination and cooperation. Based on these findings, the article proposed countermeasures such as improving the legal framework, strengthening educational cooperation, enhancing public awareness, promoting the mutual recognition of standards between China and Europe, and deepening China-Hungary collaboration. These measures aim to further improve the legislation and implementation of TCM in Hungary, thereby promoting the healthy development of TCM in Hungary and the global service trade of TCM.

The clinical manifestations of Japanese encephalitis virus infection are often acute encephalitis, and etiological diagnosis is a common diagnostic method. It is difficult to detect and isolate viruses clinically, and the types of pathogens detected are relatively limited. Metagenomics second-generation sequencing (mNGS) is a rapid and accurate molecular diagnostic method, which can improve the detection rate and types of pathogenic microorganisms. Pathogens uncommon in central nervous system infections can be detected. This paper reports a 27-year-old male patient with nausea and vomiting, high fever, disturbance of consciousness, and multiple organ failure as the main clinical manifestations. Japanese encephalitis virus was considered clinically, but etiological evidence was lacking. Japanese encephalitis virus was detected by cerebrospinal fluid mNGS, which greatly improved the accuracy of diagnosis of Japanese encephalitis virus infection.

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K _D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

Objective: To investigate the application value of augmented reality (AR) technology in pancreatoduodenectomy (PD). Methods: The retrospective and descriptive study was conducted. The clinicopathological data of 3 male patients who underwent PD in Tsinghua University Affiliated Beijing Tsinghua Changgung Hospital from June 2018 to February 2019 were collected. The 3 patients were aged from 52 to 63 years, with a median age of 57 years. Digital imaging and communication standard format data of enhanced computed tomography (CT) scan were collected, the three-dimensional (3D) images of abdominal arteries, portal vein, descending duodenum, pancreatic body and tail, pancreatic head, common bile duct, and pancreatic duct were reconstructed. The results were imported into the AR software. Optical tracking based on two-dimensional codes and manual interactive rigid registration were adopted for intraoperative navigation. Observation indicators: (1) surgical and postoperative conditions; (2) postoperative pathological examination; (3) follow-up. Follow-up using outpatient examination or telephone interview was conducted to detect survival of patients and tumor metastasis and recurrence up to June 2019. The measurement data with skewed distribution were expressed as M (range). Count data were expressed as absolute numbers. Results: (1) Surgical and postoperative conditions: all the 3 patients underwent PD with AR technology as intraoperative navigation successfully. The operation time, volume of intraoperative blood loss, and duration of postoperative hospital stay were 6 hours (range, 5-8 hours), 700 mL (range, 300-900 mL), 11 days (range, 9-12 days). There was no perioperative death or complication occured. After surgery, the patients who underwent PD combined with superior mesenteric vein (SMV) resection and reconstruction had patent SMV on the enhanced computed tomography examination. (2) Postoperative pathological examination: results of pathological examination showed 1 case of intraductal papillary mucinous neoplasm (IPMN) of the pancreas with invasive adenocarcinoma (neoplasm invading SMV), 1 case of insulinoma, and 1 case of periampullary neuroendocrine carcinoma, respectively. (3) Follow-up: 3 patients were followed up for 4-12 months, with a median follow-up time of 6 months. During the follow-up, the patient with IPMN of the pancreas and invasive adenocarcinoma had liver metastasis at 3 months after surgery, and received chemotherapy at other hospital. After 4 cycles of chemotherapy, the metastatic nodule shrank, and the patient was still in follow-up up to deadline of follow-up. Other 2 patients had no recurrence or metastasis. Conclusion AR technique assisted PD is safe and feasible, which is helpful to indentify vascular branches and tracks.

Objective To investigate the mental states of the community-dwelling elderly in Beijing ,and to explore their relationship with depression using multivariate analysis ,in order to provide evidence for strategies to prevent depression in the elderly. Methods A total of 400 community elderly residents in Chaoyang District of Beijing were recruited in this cross-sectional study. The mental states of older adults were assessed by using the Zung Self-Rating Depression Scale(SDS) ,the Medical Outcomes Study(Mos)36-item Short Form Health Survey (SF-36) ,and the Social Support Rating Scale(SSRS).The correlations of the mental state with demographic data ,quality of life and social support were examined via multivariate analysis. Results Of 400 questionnaires ,364 were valid.Depression occurred in 64 older adults ,and the detection rate was 17.6% (64/364).Multivariate linear regression analysis showed that depression was closely correlated with age ( P = 0.049 ) , physiological function(P=0.009) ,vitality(P=0.028) ,mental health(P＜0.001) ,self-reported health transition(P=0.003) ,objective support(P=0.001)and subjective support(P=0.001)in community-dwelling elderly residents in Beijing.Bivariate Logistic regression analysis showed that five factors , including vitality (OR = 0.595 ,P= 0.036 ) ,mental health (OR = 0.548 ,P = 0.021 ) ,self-reported health transition(OR=1.597 ,P= 0.048) ,objective support (OR= 0.524 ,P= 0.018)and subjective support(OR=1.787 ,P=0.027) ,were influencing factors for depression in the elderly.Self-reported health transition and subjective support had the greatest impact on depression in the elderly . Conclusions Critical approaches to preventing depression in the elderly include a focus on the mental health and social needs as well as measures to enhance self-confidence in the health of these individuals.

Objective To study the feature of MIG and IFN-γ obtained from PBMCs stimulated with Mtb specific antigens and the potential value in the differential diagnosis of active pulmonary tuberculosis from bacterial pneumonia and primary lung cancer. Methods 90 patients with active pulmonary tuberculosis and 31 patients with bacterial pneumonia and primary lung cancer were enrolled. MIG and IFN-γin supernatants from PBMCs stimulated with Mycobacterium tuberculosis-specific antigens were analyzed with Bender Flowcytomix on flow cytometry. The diagnostic values were established based on receiver operating characteristic curve analysis. Results PBMCs stimulated with Mtb-specific antigens produced significantly higher levels of MIG compared with IFN-γ The level of MIG in active pulmonary TB patients was significantly higher than in controls(3023.0 pg/ml vs 112.5 pg/ml, P ＜0.0001). The MIG and IFN-γtests were positive in 96. 8 and 86. 7% of the TB patients, the specificity was up to 94. 4 and 87. 1%. With combination of MIG and IFN-γtests, the positive rate increased among TB patients to 97. 8% without a significant decrease in specificity. Conclusions The responses of the MIG and IFN-γagainst to Mtb-specific antigens could be used to discriminate newly-treated active pulmonary tuberculosis fiom bacterial pneumonia and primary lung cancer. Combination of MIG and IFN-γ might be a simple and quick approach to diagnosis newly-treated active pulmonary tuberculosis.