[摘 要] 树突状细胞（DC）是连接固有免疫与适应性免疫的核心枢纽，其功能稳态是介导肿瘤免疫监视的关键。然而，肿瘤微环境（TME）通过营养竞争及免疫抑制代谢产物的累积，驱动DC发生代谢重编程，进而诱导免疫应答功能缺陷。本文系统综述了TME中DC各亚型在三大代谢层面的重塑机制：糖代谢层面，高乳酸微环境通过GPR81信号抑制MHC-Ⅱ类分子表达，削弱传统树突状细胞（cDC）的抗原提呈能力；脂代谢层面，Wnt5a-β-catenin-PPARγ-CPT1A轴介导的脂肪酸氧化促进cDC向免疫抑制表型极化；氨基酸代谢层面，Arg1-IDO1通路的级联激活诱导DC获得耐受表型。针对上述代谢异常，当前干预策略已由单一靶点调控拓展至多模式联合，包括基于脂质纳米颗粒的原位疫苗与mRNA递送系统、代谢-免疫协同阻断，以及代谢状态优化的DC疫苗等。因此，深化对DC代谢检查点的认知，并靶向干预关键代谢检查点，不仅有望逆转免疫抑制微环境、克服治疗耐药，更为开发新一代代谢-免疫联合疗法提供了重要的科学依据与转化策略。

Objective:To investigate the effect of protein tyrosine phosphatase D(PTPRD)demethylation on the proliferation,migration,and chemoresistance of gastric cancer(GC)cells through the phosphatidyl inositol 3 kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway.Methods:The gastric cancer MKN-74 and MKN-45 cells,as well as human gastric mucosal epithelial GES-1 cells,GES-1 were cultured in vitro and PTPRD expression was detected.MKN-45 cells and their drug-resistant variant MKN-45/5-FU cells were routinely cultured and transfected with various vectors:PTPRD empty vector(NC group,NC/5-FU group),PTPRD overexpressing adenovirus(PTPRD group,PTPRD/5-FU group),shRNA empty vector(sh-NC group,sh-NC/5-FU group),shRNA PTPRD lentivirus(sh-PTPRD group,sh-PTPRD/5-FU group),and PTPRD overexpressing adenovirus+10 μmol/L 740Y-P treatment(PTPRD+740Y-P group,PTPRD+740Y-P/5-FU group).MTT assay and wound healing assay were used to assess cell proliferation and migration.Cell autophagy levels were assessed using autophagy assay,and the expression of epithelial-mesenchymal transition(EMT)and PI3K/Akt/mTOR pathway related proteins was detected using western blot(WB).MKN-45 cells were treated with 0,2.5,5,10,20 and 40 μmol/L 5-aza solutions,and the PTPRD mRNA expression and cell proliferation in MKN-45 cells were detected using qPCR and MTT assays.Results:PTPRD mRNA and protein were significantly downregulated in gastric cancer cells(P<0.05).Compared with the MKN-45 group,the numbers of autophagosomes and autophagosomes,as well as the protein expression of PTPRD,E-cadherin,and BAX significantly increased in the PTPRD group(all P<0.05),while cell proliferation,migration rate,and protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR decreased significantly(all P<0.05);However,in the sh-PTPRD group,cell proliferation activity,migration rate,and protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR increased notably,while the quantity of autophagosomes,autophagosomes,and protein expression of PTPRD,E-cadherin,and BAX decreased(all P<0.05).Compared with the PTPRD group,the PTPRD+740Y-P group showed an increase in cell proliferation activity,migration rate,protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR(all P<0.05),and a decrease in number of autophagosomes,autophagosomes,and protein expression of PTPRD,E-cadherin,and BAX(all P<0.05).With the increase of 5-aza concentration,the mRNA expression of PTPRD in MKN-45 cells increased(P<0.05),while the cell proliferation activity decreased(P<0.05).Compared with the MKN-45/5-FU group,the cell migration rate and proliferation activity decreased in PTPRD/5-FU group,while the sh-PTPRD/5-FU group showed an increase in cell migration rate and proliferation activity(all P<0.05).Compared with the PTPRD/5-FU group,the PTPRD+740Y-P/5-FU group showed an increase in cell migration rate and proliferation activity(all P<0.05).Conclusion:PTPRD is downregulated in GC cells,and its demethylation may inhibit proliferation and migration of GC cells and enhance chemosensitivity by suppressing the PI3K/Akt/mTOR pathway.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

To develop a new type of moxibustion treatment equipment based on moxibustion heat,light and smoke factors.It was composed of three parts:upper cylinder,middle cylinder and lower cylinder,which integrated multiple functions such as temperature control,ash collection,adsorption,and anti-scalding,and all parts could be disassembled.It is convenient to use,convenient for clinical treatment and health care,can overcome the problem of not being able to adjust the temperature of moxibustion therapy and easy to burn in the process of moxibustion,reduce the irritation and pollution of moxa smoke smell and smoke dust on doctors,patients and the diagnosis and treatment environment,and make moxibustion therapy more convenient,efficient and safe.

Objective:To construct the clinical management model of a new type of smoke-purifying temperature-controlled moxibustion device based on the whole life cycle theory,and to explore its management effect on the new type of smoke-purifying temperature-controlled moxibustion device.Methods:The clinical management model of a new type of smoke purification and temperature-controlled moxibustion device was constructed based on the whole life cycle theory with the architecture of the basic layer,access layer,service layer,data layer and application layer.Eighteen new type of smoke purification and temperature-controlled moxibustion devices in clinical use in the Shijiazhuang Pingan Hospital from 2021 to 2022 were selected,and the conventional new smoke-purifying temperature-controlled moxibustion device management scheme(referred to as the conventional management mode)and the new smoke purification and temperature-controlled whole life cycle management model(referred to as the whole life cycle management mode)were adopted respectively according to different management modes.The management effect of the new smoke-purifying temperature-controlled moxibustion therapy device and the satisfaction of the relevant management personnel were compared between the two management modes.Results:The average scores of the management quality,temperature control effect,smoke control effect and moxa smoke purification effect of the new smoke purification moxibustion device using the whole life cycle management mode were(89.37±3.48)points,(93.53±4.26)points,(0.13±0.04)points and(0.11±0.03)points,respectively,the average scores of management quality and temperature control effect were higher those of the conventional management mode,and the average scores of smoke control effect and moxa smoke purification effect were lower than those of the conventional management mode,the difference was statistically significant(t=11.744,14.850,11.266,24.593,P<0.05).The satisfaction scores of engineers,medical staff and patients in the use of the new smoke purification and temperature control moxibustion therapy device adopting the whole life cycle management model were(95.69±6.62)points,(96.82±5.87)points and(95.34±5.14)points,respectively,which were higher than those of conventional management mode,the difference was statistically significant(t=9.334,19.549,33.694,P<0.05).Conclusion:The application of the clinical management model of a new type of smoke-purifying temperature-controlled moxibustion device based on the whole life cycle theory to new type of smoke purification and temperature control moxibustion therapy device can effectively improve the quality of equipment management,improve the temperature control effect of the new smoke and temperature control moxibustion device,and improve the satisfaction of relevant users.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

Objective To analyze the influence of ligaments surrounding sacroiliac joints (SIJs) on stability of SIJs by finite element method. Methods The finite element lumbar spine-pelvis-femur model was established. Based on this normal model, all SIJ ligaments in both sides were removed in turn, to establish models without iliolumbar ligaments, sacroiliac anterior ligaments, sacroiliac posterior ligament, sacrotuberous ligaments, sacrospinous ligaments, sacroiliac interosseous ligaments, respectively. The models were used to simulate physiological motions of the spine. The range of motion (ROM) and average stress on the left and right SIJs were analyzed and compared with the normal models. Results Compared with the normal SIJ model, no significant differences in the ROM of bilateral SIJs were found in the models without sacrotuberous ligaments, sacrospinous ligaments and sacroiliac posterior ligaments; for the model without acroiliacinterosseous ligaments, there was no significant difference in the ROM of the left SIJs under spinal right rotation and ROM of the right SIJs under spinal extension, but the ROM of bilateral SIJs increased significantly under the other spinal physiological activities. Under the physiological activities of the spine, the average stress of the SIJ surface in the left and right sides of the model without acroiliacinterosseous ligaments significantly decreased. Conclusions Of all the sacroiliac ligaments, the sacroiliac interosseous ligaments showed the maximum influences on the stability of SIJs. The research findings are helpful to investigate the mechanism of SIJ subluxation and provide certain theoretical basis for clinical treatment of SIJ subluxation.

Objective: Intraperitoneal chemotherapy is increasingly being used in the treatment of gastric cancer with peritoneal me-tastasis, because the drug can directly act on the metastatic nodules. Repeated treatment can be administered through implanted ports, provided the ports are appropriately managed. Our study aimed to investigate the safety of peritoneal port implantation in pa-tients with gastric cancer with peritoneal metastasis. Methods: We retrospectively reviewed the records of patients undergoing intra-peritoneal port implantation for the administration of chemotherapy between June 2015 and June 2018 to investigate the causes of complications and to discuss their management and prevention. Results: Fifty-five ports were implanted in 54 patients with median us-age time of 8.4 (0.8-32.0) months. Complications occurred at 13 port sites (23.6%), including obstruction (7.3%), severe pain (5.5%), in-fection (3.6%), reflux (3.6%), access difficulty (1.8%), and subcutaneous mass formation (1.8%). The median interval from the time of port implantation to the development of complications was 2.1 months. No factor contributing to the complications was identified (P>0.05). Conclusions: Peritoneal port implantation to systematic chemotherapy in patients with gastric cancer with peritoneal metastasis is safe and feasible if the ports can be carefully managed.

In post-transcriptional mRNA modification, m⁶A has been observed in a wide range of eukaryotes. METTL3, as a component of methyltransferase complex for m⁶A modification, regulates mouse naïve pluripotency and influences mRNA stability, especially affecting the expression level of the key pluripotent transcription factors. To reveal the expression pattern of the porcine METTL3 gene, we analyzed METTL3 expression level in different porcine tissues, somatic cells, and induced pluripotent stem cells (piPSCs) by RT-PCR. To identify the function of METTL3 for regulation of the expression of porcine pluripotent genes, we cloned a 1 859-bp coding sequence of METTL3 and synthesized a shRNA against METTL3. When knocking down METTL3 expression in piPSCs, the cell type of piPSCs became naïve-like morphology, alkaline phosphatase activity was increased, and expression level of pluripotent genes NANOG, OCT4 and LIN28A was significantly elevated. In addition, piPSCs cultured in medium containing 10 mmol/L cycloleucine for 48 h exhibited the similar result as that knocked down METTL3. These findings set the stage for optimization of piPS culture condition and further study on the roles of m6A in piPSCs.