1.Characterizing tumor nicroenvironment features and identifying potential therapeutic targets in patients with diabetes mellitus and pancreatic cancer based on single-cell transcriptome sequencing
Han PENG ; Yuwei PAN ; Xuesong WANG ; Yixin SUN ; Shuo HUANG ; Houjie LIANG
Journal of Army Medical University 2025;47(10):1069-1080
Objective To investigate the changes in the tumor microenvironment of pancreatic cancer(PDAC)complicated with diabetes mellitus(DM)in a mouse model of hyperglycemia and orthotopic pancreatic cancer by analyzing transcriptome and single-cell transcriptome data in order to identify potential therapeutic targets.Method By integrating single-cell transcriptome and bulk transcriptome data,bioinformatics analysis was conducted to compare the characteristics of tumor cells and tumor immune microenvironment between PDAC patients with DM(DM group)and those without DM(non-DM group).Twenty male C57BL/6 mice(6 weeks old,weighing 18~20 g)were randomly divided into a hyperglycemic group[STZ group,continuous intraperitoneal injection of 50 mg/kg streptozocin(STZ)(final concentration of 1%)dissolved in citrate buffer],and a control group(Control group,an equivalent volume of citrate buffer without STZ at the same time points),with 10 mice in each group.Tail-tip blood glucose level was measured to monitor glycemic status.After orthotopic inoculation of pancreatic cancer cells in both Control and STZ groups,tumor-infiltrating immune cells were harvested.Flow cytometry was employed to determine the effects of hyperglycemia on:total CD8+T cell and Treg cell populations;CD8+T cell subsets expressing Ki67,TNF-α,granzyme B(GZMB)and IFN-γ;surface expression of PD-1,lymphocyte activation gene-3(LAG-3)and T cell immunoglobulin and mucin domain-3(Tim-3)on CD8+T cells;programmed death-ligand 1(PD-L1)expression on tumor cells;and tumor-associated macrophage surface expression of major histocompatibility complex classⅠ(MHC-Ⅰ)and cluster of differentiation 206(CD206).Results Bioinformatics analysis revealed that,compared to the non-DM group,the genes significantly up-regulated in the DM group were associated with poor prognosis(P<0.001).The proportion of type 2 ductal cells was increased in the DM group,exhibiting higher levels of copy number variation(P<0.001).In the tumor immune microenvironment of the DM group,there was an increase in the proportion of Treg cells(P<0.05)and an elevated exhaustion score for CD8+T cells(P<0.001),accompanied by down-regulated expression of effector molecules,up-regulated expression of inhibitory checkpoints,and a significant increase in the M2 score of M2-like macrophages(P<0.001).Animal experiments and flow cytometry found that,compared to the Control group,the STZ group had a shorter survival time(P<0.001),with decreased proportions of total CD8+T cells(P<0.01)and CD8+T cells expressing Ki67,TNF-α,GZMB and IFN-γ(P<0.01),increased proportion of Treg cells(P<0.001),up-regulated expression of PD-1,LAG-3 and Tim-3 on the surface of CD8+T cells(P<0.001),and up-regulation of PD-L1 on tumor cell surface(P<0.001)and enhanced expression of CD206 on the surface of tumor-associated macrophages,while down-regulated expression of MHC-Ⅰ(P<0.001).Conclusion High glucose promotes the formation of an immunosuppressive microenvironment in PDAC,and targeting type 2 ductal cells and immunosuppressive cells in the tumor microenvironment,combined with dual immune checkpoint antibody therapy,may improve patient prognosis.
2.Exploration of the application of vehicle-mounted 5G remote mobile robotic surgical system in thyroid surgery
Meng WANG ; Wen TIAN ; Qingqing HE ; Guolou LI ; Jian ZHU ; Xiaodong MA ; Wei WEI ; Qiongqiong TAN ; Jinzhi HU ; Yingying WANG ; Peng ZHOU ; Gang WANG ; Yixin LIU ; Hejun WANG ; Yu LIU ; Lihu LIU
International Journal of Surgery 2025;52(1):28-32
Objective:To investigate the feasibility and safety of implementing a domestic vehicle-mounted remote mobile robotic surgical system in thyroid surgery applications, integrated with 5G communication technology.Methods:Using the main system located on the vehicle-mounted mobile robot operating platform of the 960th Hospital of PLA Joint Logistics Support Force and the slave system of Weifang Traditional Chinese Hospital, the remote radical thyroidectomy 5G communication technology, and analyze the clinical and information transmission data of two female patients who underwent remote mobile robot thyroid cancer surgery on October 21, 2024 at Weifang Traditional Chinese Medicine Hospital.Results:The remote radical thyroidectomy was conducted by the robosurgeons utilizing a vehicle-mounted mobile robotic surgical system, and the procedure was successfully completed without necessitating intermediate open surgery. The operation durations for patient 1 and patient 2 were 135 minutes and 108 minutes, respectively, with 7 and 13 lymph nodes dissected, respectively. The average delay in surgical data transmission was recorded at 61.9 milliseconds, with no instances of signal interruption or frame loss. The procedure proceeded smoothly, without any jamming, and the audio and video transmissions were consistently clear. Follow up for 21 days after surgery showed no complications such as hoarseness, skin damage, or lymphatic fistula.Conclusion:The implementation of a vehicle-mounted remote mobile robotic surgery system for thyroid surgery has demonstrated safety and feasibility. Furthermore, the utilization of the 5G network offers rapid data transmission and minimal latency, closely approximating the therapeutic efficacy of traditional robotic thyroidectomy.
3.Association between peripheral blood inflammatory markers and the severity of neurological impairment in acute ischemic stroke
Yishan LI ; Yixin LI ; Li PENG ; Yang ZHOU ; Yan MO ; Qin LUO ; Yong ZHAO
Journal of Chongqing Medical University 2025;50(11):1472-1479
Objective:To investigate the association of peripheral blood inflammatory markers and lymphocyte subsets with different severities of acute ischemic stroke(AIS).Methods:A total of 128 AIS patients who were admitted to Department of Neurology,The First Affiliated Hospital of Chongqing Medical University,from January to December 2022 were enrolled as subjects,and according to the National Institutes of Health Stroke Scale(NIHSS)score,the patients were divided into mild AIS group(67 patients with an NIHSS score of<4)and moderate-to-severe AIS group(61 patients with an NIHSS score of≥4).The two groups were compared in terms of baseline clinical data,blood biochemical parameters,and peripheral[MLR],neutrophil-to-lymphocyte ratio[NLR],and platelet-to-lymphocyte ratio[PLR]).Flow cytometry was used to measure the number and percentage of lymphocyte subsets.Results:Compared with the mild AIS group,the moderate-to-severe AIS group had a significantly higher proportion of patients with hyperlipidemia blood inflammatory markers(C-reactive protein[CRP],systemic immune-inflammation index[SII],monocyte-to-lymphocyte ratio(47.761%vs.67.213%,P=0.032),with relatively high values of low-density lipoprotein(LDL)/high-density lipoprotein(HDL)ratio(P=0.025)and total cholesterol(TCHO)/HDL ratio(P=0.020),as well as significantly higher levels of the peripheral blood inflamma-tory markers CRP(P<0.001),platelet count(P=0.001),MLR(P<0.001),and NLR(P<0.001),significantly higher numbers of periph-eral blood CD3 T cells(P=0.006),CD4 T cells(P=0.009),CD8 T cells(P=0.032),and CD3-/CD16+/CD56+NK cells(P=0.002),and a significantly higher proportion of T helper cells(P=0.041).The binary logistic regression analysis showed that platelet count(odds ratio[OR]=1.035,P=0.004),CRP(OR=2.016,P<0.001),NLR(OR=2.585,P=0.030),the proportion of total lymphocytes(OR=1.169,P<0.001),and the number of lymphocytes(OR=1.008,P<0.001)were significantly associated with moderate-to-severe AIS.The receiver operating characteristic(ROC)curve analysis showed that NLR,CRP,and the proportion of total lymphocytes had an area under the ROC curve of 0.760,0.812,and 0.777,respectively.Conclusion:Patients with moderate-to-severe AIS tend to have high levels of the peripheral blood inflammatory markers NLR and CRP,a high lymphocyte count,and a high proportion of lymphocytes.NLR,CRP,and the proportion of lymphocytes are independent risk factors for the development of moderate-to-severe AIS.
4.Clinical efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in refractory autoimmune hemolytic anemia
Gang WANG ; Yixin GAO ; Linyan WU ; Liuyan PAN ; Suying HE ; Lijuan ZHOU ; Yongzheng PENG ; Minghui YANG
Chinese Journal of Blood Transfusion 2025;38(10):1348-1354
Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10
/L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.
5.Parent-of-origin effect and its research progress in cardio-metabolic diseases
Hexiang PENG ; Mengying WANG ; Siyue WANG ; Huangda GUO ; Tianjiao HOU ; Yixin LI ; Hanyu ZHANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Dafang CHEN ; Yonghua HU ; Tao WU
Chinese Journal of Preventive Medicine 2025;59(9):1552-1558
Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.
6.A single-center analysis of the short-term efficacy and safety of RAPN in 45 patients with non-metastatic pT 3a renal cell carcinoma
Xiangpeng ZOU ; Yunhan LUO ; Zhiling ZHANG ; Zhaohui ZHOU ; Longbin XIONG ; Yulu PENG ; Yixin HUANG ; Xin LUO ; Wensu WEI ; Zhenhua LIU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Urology 2025;46(5):369-375
Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy(RAPN)for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was(54.3±10.7)years,and the average clinical tumor diameter was(4.9±1.8)cm. Of all the patients,35(77.8%)were asymptomatic,7(15.6%)presented with hematuria,and 3(6.7%)presented with lumbar pain. Preoperative imaging assessed 34 patients(75.6%)as having clinical stage T 3a,all suspected of involving the collecting system or perirenal fat invasion;the remaining 11 patients(24.4%)were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0(7.0,10.0). A history of hypertension,diabetes,or chronic kidney disease was present in 18 patients(40.0%). The primary endpoint was progression-free survival,and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method,and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients(71.1%),with a median estimated blood loss of 150.0(50.0,300.0)ml. Seven(15.6%)patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0(4.0,6.0)days. Postoperative complications occurred in 6 patients(13.3%),including 5(11.1%)with mild complications and 1(2.2%)with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients(61.5%),while 3 patients(7.7%)developed surgery-related chronic kidney disease 3 to 12 months postoperatively,but none required dialysis. The median follow-up time was 31.8(22.7,50.9)months,12(26.7%)patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up,3 patients experienced tumor recurrence,the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma,RAPN performed by experienced surgeons is a feasible and safe option,providing excellent short-term oncological outcomes,complication control,and renal function recovery. The long-term efficacy remains to be seen.
7.Parent-of-origin effect and its research progress in cardio-metabolic diseases
Hexiang PENG ; Mengying WANG ; Siyue WANG ; Huangda GUO ; Tianjiao HOU ; Yixin LI ; Hanyu ZHANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Dafang CHEN ; Yonghua HU ; Tao WU
Chinese Journal of Preventive Medicine 2025;59(9):1552-1558
Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.
8.Spousal correlations of blood lipid based on a family design
Yixin LI ; Huangda GUO ; Hexiang PENG ; Tianjiao HOU ; Hanyu ZHANG ; Yinxi TAN ; Yi ZHENG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Ying YE ; Tao WU ; Dafang CHEN ; Yonghua HU ; Liming LI
Journal of Peking University(Health Sciences) 2025;57(3):423-429
Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95%CI:0.125-0.327),0.257(95%CI:0.155-0.354),0.179(95%CI:0.074-0.280),and 0.181(95%CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95%CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95%CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.
9.Spousal correlations of blood lipid based on a family design
Yixin LI ; Huangda GUO ; Hexiang PENG ; Tianjiao HOU ; Hanyu ZHANG ; Yinxi TAN ; Yi ZHENG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Ying YE ; Tao WU ; Dafang CHEN ; Yonghua HU ; Liming LI
Journal of Peking University(Health Sciences) 2025;57(3):423-429
Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95%CI:0.125-0.327),0.257(95%CI:0.155-0.354),0.179(95%CI:0.074-0.280),and 0.181(95%CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95%CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95%CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.
10.A single-center analysis of the short-term efficacy and safety of RAPN in 45 patients with non-metastatic pT 3a renal cell carcinoma
Xiangpeng ZOU ; Yunhan LUO ; Zhiling ZHANG ; Zhaohui ZHOU ; Longbin XIONG ; Yulu PENG ; Yixin HUANG ; Xin LUO ; Wensu WEI ; Zhenhua LIU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Urology 2025;46(5):369-375
Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy(RAPN)for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was(54.3±10.7)years,and the average clinical tumor diameter was(4.9±1.8)cm. Of all the patients,35(77.8%)were asymptomatic,7(15.6%)presented with hematuria,and 3(6.7%)presented with lumbar pain. Preoperative imaging assessed 34 patients(75.6%)as having clinical stage T 3a,all suspected of involving the collecting system or perirenal fat invasion;the remaining 11 patients(24.4%)were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0(7.0,10.0). A history of hypertension,diabetes,or chronic kidney disease was present in 18 patients(40.0%). The primary endpoint was progression-free survival,and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method,and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients(71.1%),with a median estimated blood loss of 150.0(50.0,300.0)ml. Seven(15.6%)patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0(4.0,6.0)days. Postoperative complications occurred in 6 patients(13.3%),including 5(11.1%)with mild complications and 1(2.2%)with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients(61.5%),while 3 patients(7.7%)developed surgery-related chronic kidney disease 3 to 12 months postoperatively,but none required dialysis. The median follow-up time was 31.8(22.7,50.9)months,12(26.7%)patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up,3 patients experienced tumor recurrence,the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma,RAPN performed by experienced surgeons is a feasible and safe option,providing excellent short-term oncological outcomes,complication control,and renal function recovery. The long-term efficacy remains to be seen.

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