[摘 要] 树突状细胞（DC）作为抗肿瘤免疫应答的核心启动者与调控者，已成为肿瘤免疫治疗的重要靶点。DC疫苗等靶向DC的免疫治疗策略在抗肿瘤治疗中展现出独特优势，但仍存在抗原提呈效率不足、免疫抑制微环境抵抗、功能特异性调控困难等瓶颈问题。肿瘤微环境（TME）中的DC存在高度异质性，不同DC亚群在分化发育、免疫调控及效应转归方面呈现复杂的多样性。解析DC亚群的精确表型与功能机制对于开发新型DC靶向性免疫治疗策略具有重要意义。TME中募集的经典DC、浆细胞样DC、单核细胞来源DC能与肿瘤浸润免疫细胞和微环境中的非免疫细胞（包括肿瘤细胞、成纤维细胞、内皮细胞等）相互作用激活抗肿瘤免疫应答，而TME还会通过转录调控、表观遗传调控、代谢重塑等多种方式抑制DC招募和抗原提呈能力，甚至诱导其向耐受性DC转化。值得注意的是，新近发现的富含免疫调节分子的成熟DC具有双向免疫调控作用，其起源路径和免疫调控网络仍有待深入研究。随着单细胞分析与空间组学分析等技术的发展，有望在单细胞分辨率下系统解析DC亚群的功能多样性及其与TME的时空相互作用网络，为开发下一代精准免疫治疗策略提供新靶点和新思路。

Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Depressive disorders are common mental illnesses characterized by significant and persistent low mood, with features such as high prevalence, high disability rate, and high suicide rate. The microbiota-gut-brain axis may be one of the potential mechanisms underlying depressive disorders. Gut microbiota metabolites, as important mediators of MGBA signaling, play roles in depressive disorders through multiple pathways. These include short-chain fatty acids, which can regulate the transmission of the vagus nerve, inflammatory responses, and 5-hydroxytryptamine synthesis; secondary bile acids, which can activate farnesoid X receptor and Takeda G protein-compled receptor 5; and choline, which can regulate DNA methylation and trimethylamine N-oxide production. This article reviews the literature on the potential mechanisms of action of gut microbiota metabolites, such as short-chain fatty acids, secondary bile acids, and choline, in depressive disorders. The literature was retrieved from CNKI, PubMed, and Web of Science databases from 2010 to 2025. It aims to provide a theoretical basis for the prevention and treatment of depressive disorders.

Laparoscopic right hemicolectomy is the standard surgical procedure for treating right-sided colon cancer,yet its complex anatomical layers and technically demanding operations pose significant challenges to surgeons'expertise.Currently,surgical skill assessment in clinical practice still predominantly relies on subjective expert evaluation,an approach inherently limited by low efficiency and inconsistent standards.With the rapid advancement of artificial intelligence(AI)technologies(particularly breakthroughs in computer vision and deep learning algorithms),a revolutionary technical foundation has been established for developing objective and precise automated surgical evaluation systems.This article comprehensively reviewed the current clinical application status of right hemicolectomy in China,thoroughly examined the clinical necessity and technical feasibility of constructing an intelligent surgical assessment system,and systematically presented our center's cutting-edge research achievements in this field.Looking ahead,AI-driven intelligent evaluation systems are expected to standardize and quantify surgical skill assessment.Such innovation will not only transform surgical training programs and enhance the quality of multicenter clinical research,but also promote the standardization of precision surgical protocols.This advancement holds significant clinical value and societal importance by improving long-term patient outcomes and fostering more equitable distribution of medical resources.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Laparoscopic right hemicolectomy is the standard surgical procedure for treating right-sided colon cancer,yet its complex anatomical layers and technically demanding operations pose significant challenges to surgeons'expertise.Currently,surgical skill assessment in clinical practice still predominantly relies on subjective expert evaluation,an approach inherently limited by low efficiency and inconsistent standards.With the rapid advancement of artificial intelligence(AI)technologies(particularly breakthroughs in computer vision and deep learning algorithms),a revolutionary technical foundation has been established for developing objective and precise automated surgical evaluation systems.This article comprehensively reviewed the current clinical application status of right hemicolectomy in China,thoroughly examined the clinical necessity and technical feasibility of constructing an intelligent surgical assessment system,and systematically presented our center's cutting-edge research achievements in this field.Looking ahead,AI-driven intelligent evaluation systems are expected to standardize and quantify surgical skill assessment.Such innovation will not only transform surgical training programs and enhance the quality of multicenter clinical research,but also promote the standardization of precision surgical protocols.This advancement holds significant clinical value and societal importance by improving long-term patient outcomes and fostering more equitable distribution of medical resources.

Objective:To report a case of Kufor-Rakeb syndrome caused by novel ATP13A2 mutation, collect the cases related to ATP13A2 gene mutation published in recent years, summarize the clinical manifestations of the disease, and broaden the clinical diagnostic thinking. Methods:The clinical manifestations of a newly diagnosed patient with Kufor-Rakeb syndrome caused by ATP13A2 gene mutation admitted to Zhongda Hospital, Southeast University on November 26, 2021, were summarized. The related cases of ATP13A2 mutation published from January 2000 to December 2021 were searched through the PubMed and CNKI databases using the keywords "ATP13A2" and "Parkinson′s disease". The onset age, clinical symptoms, family history, genetic testing, and levodopa responsiveness results of the patients were collected. Results:The patient is a 52-year-old female with the main clinical symptoms of static tremor and bradykinesia. Physical examination showed a gear like increase in muscle tension in the right upper limb, involuntary shaking of the right hand and slow movement. She had good responsiveness to levodopa, and the magnetic resonance imaging and susceptibility weighted imaging of the head showed a lack of clear observation of bilateral black matter swallowtail sign. Whole exome sequencing showed that mutations c.3010A>G (p.S1004G) and c.1195+5G>A (splice) were found in the ATP13A2 gene, both of which were not reported. The c.3010A>G (p.S1004G) mutation originated from the mother, and the c.1195+5G>A (splice) mutation originated from the father. In the retrospective literature review, a total of 10 cases were collected, with onset ages ranging from 18 months to 24 years. Among them, 4/10 patients′ parents married close relatives, and the clinical manifestations were mainly motor symptoms of Parkinson′s disease. In addition, 5/10 patients had cognitive dysfunction, and 3/10 patients had mental symptoms. And demonstrations of most patients′ magnetic resonance imaging were normal in the early stage of the disease, and as the disease progressed, some patients′ imaging results showed specific changes, such as whole brain atrophy and changes in the corpus callosum. Meanwhile, 8/10 patients showed good responsiveness to levodopa. Conclusions:Kufor-Rakeb syndrome is a special type of adolescent levodopa responsive Parkinson′s disease caused by ATP13A2 mutation, which is an autosomal recessive disorder. In addition to motor symptoms such as static tremor and bradykinesia, its clinical manifestations may also be accompanied by non motor symptoms such as cognitive and psychiatric disorders. The disease responds well to treatment with levodopa.

Objective:To explore the application value of intelligent assembly line in emergency examination.Methods:A retrospective study was carried out by collecting the data from emergency examination in Tongji Hospital affiliated to Tongji University from June 24 to 28, 2019, to July 24 to 28, 2023.The changes of sample size before and after intelligent pipeline application (with pneumatic transmission device), and the median and 90th percentile( P90) of pre-test turnaround time (TAT) were compared to collect and analyze the quality control related data of the same batch of quality control products before and after using intelligent assembly line automatic quality control; The median TAT and the 90th percentile in the laboratory were analyzed and compared before and after the application of the intelligent pipeline automatic audit rules Statistical enabling of intelligent pipeline-based real-time quality control (PBRTQC) function for patient samples and quality control-based indoor quality control mode for out-of-control detection efficacy. The normal distribution data were analyzed by two independent samples t-test, and the skew distribution data were analyzed by Mann-whitney U test. Results:After the operation of the intelligent assembly line pneumatic transmission device, TAT decreased from 27.1(18.0, 47.7) min to 24.3(15.2, 34.9) min, with a significant difference ( Z=-9.173, P<0.001); There was no significant difference in the indoor quality control results of potassium (K), sodium (NA), Alanine transaminase (Alt), glucose (Glu), total protein (TP) and UREA before and after the implementation of automatic quality control (P>0.05), the consumption of dry biochemical quality control products was reduced from 750 μl/time to 600 μl/time, and the use amount was reduced by 20%. The operation time of quality control was reduced from 30 min/time to 20 min/time, the time was saved by 33.3%, the number of quality control personnel and the walking distance of personnel were significantly reduced, and the detection rate of out-of-control was increased from 0.82% to 0.98% after the development of PBRTQC function. After using the intelligent pipeline automatic audit system, the TAT in the laboratory decreased from 37.1(21.3, 49.2) min to 34.4(16.5, 46.3) min before using the automatic audit function, with significant difference ( Z=-10.062, P<0.001); The median TOTAT and TAT decreased from 56.7.45.8, 102.5) min, 37.4(21.5, 49.6) min to 53.3(42.1, 98.3) min, 33.2.16.4, 47.9) min respectively, and the difference was significant ( Z=-7.176 and -8.245, P<0.001); The P90 of ToTAT and TAT decreased by 18.1% and 17.0%, respectively, and the percentage of sample timeout decreased by 65.5% and 92.1%, while the rate of timely notification of critical values increased from 82.5% to 99.3%. Conclusion:The application of an intelligent emergency pipeline can significantly shorten the test sample turnaround time, and effectively improve the quality and efficiency of emergency testing.

Objective:To explore the innovation mode of independent transformation-oriented science and technology research program approval by medical new research & development (R&D) institution.Methods:Through analyzing the program layout, funds, review experts, undertaking units, chief experts and interdisciplinarity to summarize the experiences of the independent transformation-oriented municipal program approval by Haihe laboratory of Cell Ecosystem in 2022.Results:As a new medical R&D institution, which vigorously constructed by Tianjin, Haihe laboratory of Cell Ecosystem has carried out the practice of the independent transformation-oriented municipal program through the measures of layout of full-chain transformation, conducting transformation-oriented review, gathering high-level research talents, and emphasizing interdisciplinarity.Conclusions:The experiences of Haihe laboratory of Cell Ecosystem make significance for medical new R&D institutions to explore and cultivate scientific research program with transformation potential and to promote the transformation of scientific and technological achievements, which are powerful factors for new R&D institutions to play a role of pilot and provide important support to scientific and technological innovation and transformation.