1.Engineered bacteria modulate tumor-associated macrophages to en-hance immunotherapy
Long WANG ; Yuchen WANG ; Yilin GUO ; Jinhui WU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(3):297-312
The immunosuppressive tumor micro-environment significantly limits the efficacy of im-munotherapy.Tumor-associated macrophages(TAMs),the most abundant immune cells in the tu-mor microenvironment,often exhibit an immuno-suppressive M2 phenotype,contributing to this im-munosuppressive landscape.Modulating TAMs to adopt anti-tumor phenotypes can enhance immu-notherapy outcomes and inhibit tumor progression.In recent years,tumor immunotherapy leveraging engineered bacteria has garnered considerable at-tention.Bacteria possess the ability to target tu-mors,preferentially colonizing tumor regions,and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment.This acti-vation enhances the tumoricidal and clearance ca-pabilities of TAMs.With the rapid advancements in synthetic biology,engineered bacteria have emerged as a potent therapeutic modality for im-munotherapy,leading to increased focus on the regulation of TAMs by engineered bacteria.This pa-per first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor ther-apy.It then reviews recent advancements in bacte-rial regulation of TAMs,detailing how engineered bacteria enhance TAM recruitment,improve TAM phagocytosis,and remodel TAM phenotypes.Mod-ulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.
2.Extent of lymphadenectomy in sigmoid colon cancer
Shengjie MA ; Yuchen GUO ; Liang HE ; Quan WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):999-1005
Complete mesocolic excision in radical colorectal cancer surgery enhances both surgical quality and the accuracy of pathological staging. In the context of sigmoid colon cancer, the optimal extent of lymphadenectomy and the appropriate level of vascular ligation remain controversial. High ligation of the inferior mesenteric artery may facilitate more thorough lymph node dissection and allow for tension-free anastomosis. However, it requires a comprehensive assessment of postoperative complication risks and the preservation of organ function. Para-aortic lymph node dissection has shown potential survival benefits in patients with oligometastatic disease, yet its application should be individualized. Moreover, intraoperative navigation technologies, such as indocyanine green fluorescence imaging, can assist in accurately delineating the dissection field and support the feasibility of personalized surgical strategies. This review synthesizes current evidence and leading domestic and international clinical guidelines to systematically examine the latest developments in lymphadenectomy strategies for sigmoid colon cancer, focusing on mesenteric anatomy, D3 dissection, complete mesocolic excision, vascular ligation levels, para-aortic lymph node dissection, and fluorescence-guided imaging techniques.
3.Analysis of influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region in 2024
Fan ZHAO ; Zhong YANG ; Kaifeng XU ; Fenxia LI ; Shifang ZHANG ; Xinye LI ; Cong LIU ; Mengxin LI ; Yuchen GUO ; Tianrui ZHUANG ; Ke LI ; Zhixian YANG ; Danyu DENG ; Zhongbing ZHANG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(3):232-236
Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.
4.A case of adult-type Sifrim-Hitz-Weiss syndrome
Yuchen WU ; Fangyuan QIAN ; Shiyao ZHANG ; Hui XU ; Xiaojin WEI ; Yuhan XU ; Caiyan WANG ; Ziyue DONG ; Jiale JI ; Yijing GUO
Chinese Journal of Nervous and Mental Diseases 2025;51(1):45-47
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.
5.Expression of keratin 1/sialyl-Tn antigen in primary and metastatic cervical squamous cell carcinomas
Yuchen TAO ; Lingchuan GUO ; Xia GUO ; Renpeng HUANG ; Qianqian YANG
Chinese Journal of Pathology 2025;54(10):1069-1074
Objective:To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism.Methods:Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression.Results:The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium ( P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated ( r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions:The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.
6.Research progress on cAMP signaling pathway in the pathogenesis and intervention strategies of depression
Jingxia LIU ; Xinwang CHEN ; Yajing GUO ; Yongshu DONG ; Yuchen GUO
Acta Laboratorium Animalis Scientia Sinica 2025;33(2):267-274
Depression is a common mental illness that has a negative impact on patient quality of life,as well as representing a serious economic burden to society.The strategy of interfering with depression based on signaling pathways has recently attracted widespread attention.The cAMP pathway is an important cellular signaling pathway that plays a key role in the pathogenesis of and interventions for depression.In this review,we addresses recent studies on cAMP pathway-based interventions in depression,to provide a theoretical basis for regulating the cAMP pathway and its cascade mechanism in depression.
7.Mechanism of Huazhuo Xingxue Decoction on the Treatment of Ischemic Stroke Based on Network Pharmacology
Meng CHEN ; Yuejin DU ; Chunli GUO ; Nana WANG ; Fei HOU ; Yuchen ZHANG ; Zipeng DIAO ; Juaner ZHENG ; Qiang FU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(5):1461-1470
Objective The mechanism of Huazhuo xingxue decoction(HZXXD)in the treatment of ischemic stroke was explored through network pharmacology,molecular docking and cell validation.Methods TCMSP,TCMID,BATMAN-TCM database and literature search were used to get the chemical components and related target proteins of Huazhuo Xingxue Decoction,and the targets of dementia,stroke and amnesia were obtained from Genecards database and OMIM database.The traditional Chinese medicine-active components-target-network and protein interaction map were constructed by using Cytoscape,and the target was enriched by KEGG pathway by David database.Western blot was used to investigate the effect of HZXXD on inflammation-related core targets expression using oxygen and glucose deprivation/reoxygenation cell model.Finally,Autodock was used for molecular docking of key active ingredients and important targets to evaluate their binding activity.Results 76 active molecules and 33 common targets of herb-disease were screened out.KEGG bioaccumulation results involve multiple inflammatory signal pathways such as TNF,chemical carcinogenesis-reactive oxygen species and HIF-1.TNF-α was found to be the core target of HZXXD by oxygen glucose deprivation/reoxygenation cell experiments.Five compounds with the strongest binding ability to TNF-α,kaempferol,apigenin,aloe-emodin,baicalein and stigasterol,were screened by traditional Chinese medicine-active ingredient-target network map and molecular docking.Conclusion Huazhuo Xingxue Decoction may down regulate the expression of core target TNF-α,kaempferol,apigenin,aloe emodin,baicalein and stigasterol may be the main active substances for TNF-α binding.
8.Pathogenesis, risk factors and treatment of low anterior resection syndrome after colon surgery
Yuchen GUO ; Hanxiao ZHAO ; Quan WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(6):633-638
Low anterior resection syndrome (LARS) is a series of symptoms of intestinal dysfunction, and its research is mainly focused on patients with low rectal surgery. However, with the deepening understanding of postoperative LARS, surgeons found that LARS not only exists among patients who have undergone low anterior resection of rectum, but also plagues a considerable number of patients who have undergone non-rectal (mainly colon) surgeries. This article aims to elaborate on the incidence and treatment of LARS after colon surgery. Through a comprehensive analysis of relevant studies, it is found that the incidence of LARS after colon surgery is approximately 20%-30%, and the incidence is relatively higher in patients undergoing right hemicolectomy. Its pathogenesis is related to multiple factors, including surgical methods, resection range, changes in intestinal flora, patient age, gender, and underlying diseases. Treatment methods include conservative treatments such as dietary adjustment, drug therapy, transanal irrigation, and rehabilitation training. Single treatment methods have limited effect, while comprehensive treatment can effectively improve patients' symptoms and quality of life. The current LARS scoring system has not been effectively verified in the application after colon cancer surgery, and it is necessary to develop a more targeted scoring system.
9.The impact of two-stage Turnbull-Cutait pull-through coloanal anastomosis on anal function and surgical safety in the treatment of low rectal cancer
Hanxiao ZHAO ; Yuchen GUO ; Liang HE ; Luyao ZHANG ; Jia'nan SUN ; Xuan SUN ; Yinquan ZHAO ; Yanpeng XING ; Yanjun WANG ; Meiling WANG ; Yang GONG ; Quan WANG
Chinese Journal of General Surgery 2025;40(2):101-107
Objective:To explore the anal function and postoperative complications of 2-stage Turnbull-Cutait pull-through coloanal anastomosis (TCA) for low rectal cancer.Methods:Patients undergoing radical rectal cancer resection from Feb 2023 to Nov 2024 in the First Hospital of Jilin University were divided into the TCA surgery group and the low anterior resection combined with prophylactic stoma (LAR) surgery group.Results:Among the 102 patients, there were 50 cases in the TCA group and 52 cases in the LAR group. In the single-arm analysis of the TCA group, the overall complication rate was 44%. The incidence rates of severe LARS at 1 month, 3 months, and 6 months after surgery were 97%, 77%, and 64% respectively. There was no significant difference in the complication rate within 30 days after surgery between the two groups,(44% vs. 38%, χ2=0.135, P>0.05). There was no significant difference in the incidence rate of severe LARS between the TCA group and the LAR group (77% vs. 69%, χ2=0.202, P>0.05), and there was not significant difference in the incidence rate of severe LARS between the two groups at the 6th month after surgery,(64% vs. 48%, χ2=1.132, P>0.05). Conclusion:In patients who underwent TCA surgery, the LARS symptoms gradually decreased over time. Compared with patients undergoing low anterior resection and stoma reversal, there were no significant differences in complications within 30 days after surgery and LARS symptoms within half a year.
10.Epidemiological characteristics of human metapneumovirus infection among children with acute respiratory infections in Beijing from 2023 to 2024
Xiaoyun LI ; Runan ZHU ; Yu SUN ; Yuchen SUN ; Yutong ZHOU ; Yao YAO ; Qi GUO ; Guoqing ZHANG ; Chunmei ZHU ; Linqing ZHAO
Chinese Journal of Pediatrics 2025;63(8):858-863
Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

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