1.assisted clearance of early high-level donor specific antibody after kidney transplantation through splenic radiotherapy: one case report
Wang ZHENG ; Zhiliang GUO ; Rula SA ; Guangyuan ZHAO ; Daqiang ZHAO ; Lan ZHU ; Gang CHEN
Chinese Journal of Organ Transplantation 2024;45(2):122-124
This report described one human leukocyte antigen pre-sensitized recipient undergoing preoperative plasmapheresis (PP), intravenous immunoglobulins (IVIG) desensitization and immune induction therapy before kidney transplantation with a donor kidney. Early postoperative clinical diagnosis was acute antibody-mediated rejection (AMR). A marked elevation of donor-specific antibodies (DSA) was accompanied by a decline of renal function. PP/IVIG dosing failed to lower the level of DSA. After low-dose splenic irradiation, DSA level dropped steadily and transplanted kidney function normalized. Thus adjuvant low-dose splenic irradiation may eliminate DSA immediately without a rebound.
2.Preliminary clinical exploration of anti-CD38 monoclonal antibody in the treatment of late antibody-mediated rejection after kidney transplantation
Zhiliang GUO ; Rula SA ; Daqiang ZHAO ; Hui GUO ; Guangyuan ZHAO ; Yuhao TU ; Songxia LI ; Lan ZHU ; Gang CHEN
Chinese Journal of Organ Transplantation 2024;45(9):622-627
Objective:To explore the efficacy and safety of daratumumab in late antibody-mediated rejection (late AMR) after kidney transplantation (KT).Methods:From December 2020 to December 2021, the relevant clinical data were reviewed for 8 patients with late AMR after receiving daratumumab at Affiliated Tongji Hospital. In intensive phase, the combination of plasma exchange (PP)/intravenous immunoglobulin (IVIG) and daratumumab were dosed once a week; in maintenance phase, once every 2 to 4 weeks. The levels of donor-specific antibody (DSA) and renal function were compared pre-treatment and Month 3/12 post-treatment. The treatment-related toxicities were observed. Independent sample T test was utilized for inter-group comparison.Results:The median treatment course during intensive period was 9(4-17) sessions. Maintenance treatment lasted for 5 to 19 months and 2 cases withdrew after 5 to 6 treatments for achieving antibody clearance. A total of 11 DSAs were detected in 8 recipients. At Month 3/12, mean fluorescent intensity (MFI) of DSA was 6 016±4 775 and 6 438±3 668. Both were significantly lower than 11 944±5 237 pre-treatment and the difference was statistically significant ( P=0.012, 0.004). Seven recipients achieved stable renal function during treatment and one recipient resumed hemodialysis at Month 18 due to acute rejection. Glomerular filtration rate of 7 recipients was (40.6±20.1), (53.6±20.9) and (49.0±17.2) ml·min -1· (1.73 m 2) -1 pre-treatment and Month 3/12 and no significant differences existed among different timepoints. During follow-ups, 2 cases developed mild nasal congestion during an early stage of daratumumab infusion while the remainders had no obvious discomfort during infusion and tolerance was decent. Conclusion:Early combination of daratumumab with PP/IVIG, followed by a course of daratumumab has demonstrated an excellent antibody reduction effect on late AMR. During treatment, renal function remains generally stable.
3.Development and validation of a preoperative nomogram predictive model for proximal gastric cancer with microscopic positive margin
Zhenjiang GUO ; Guangyuan ZHAO ; Liqiang DU ; Fangzhen LIU
Tianjin Medical Journal 2024;52(8):845-849
Objective To explore the preoperative predictive factors influencing microscopic positive proximal margin in upper gastric cancer,and to establish a nomogram prediction model and to validate it internally.Methods Retrospective analysis of 187 patients with upper gastric cancer operated in the Department of Gastrointestinal Surgery of Hengshui People's Hospital from January 2018 to October 2022 were included in this study.Patients were divided into the microscopic positive proximal margin(the R0 group,n=15)and the negative microscopic proximal margin group(the R1 group,n=172)according to histopathological diagnosis.Preoperative factors that may influence positive upper margin of proximal gastric cancer were collected,including patient age,gender,tumor size,tumor location,Borrmann staging,tumor differentiation,Lauren staging,cT stage and cN stage.Receiver operating characteristic(ROC)curve was used to figure out the optimal cut-off value for predicting positive margin of proximal gastric cancer by tumor length.Multivariate Logistic regression was used to analyze the variables with statistical difference between the two groups,and independent risk factors were screened out,and prediction mode was constructed.The prediction accuracy of the model was verified internally using Bootstrap method.Results The best threshold for predicting positive margin of proximal gastric cancer by tumor length was 4.85 cm.Univariate analysis showed that there were significant differences in tumor length,tumor location,Borrmann staging,Lauren staging,cT staging and cN staging between the two groups(all P<0.05).Multivariate Logistic regression analysis showed that tumor length>4.85 cm(OR=4.000,95%CI:1.039-15.399),tumor located in esophagogastric junction(OR=7.108,95%CI:1.604-31.494),Borrmann staging Ⅲ—Ⅳ(OR=6.991,95%CI:1.538-31.782),Lauren staging as diffuse or mixed(OR=7.583,95%CI:1.814-31.701)and cT staging as cT4(OR=8.249,95%CI:1.890-36.007)were independent predictors of microscopic positive proximal margin of advanced upper gastric cancer before surgery,and a prediction model was established based on results of multivariate analysis.The area under ROC curve(AUC)value for subjects with the model was 0.862 after internal validation.The calibration curve showed that the model predicted the probability of microscopic positive proximal margin occurrence in good agreement with the probability of actual microscopic positive proximal margin occurrence(Hosmer-Lemeshow χ2=6.145,P=0.523).Conclusion The established nomogram prediction model can predict the probability of positive upper incisal margin of proximal gastric cancer before operation,and provide clinical guidance for formulating surgical strategy.
4.Application of ARHGAP8 in Predicting the Efficacy of Neoadjuvant Chemotherapy for Locally Advanced Mid-Low Rectal Cancer
Yuning XI ; Jun XUE ; Xueliang WU ; Ming QU ; Guangyuan SUN ; Lei HAN ; Fei GUO ; Chunze ZHANG ; Yifei WANG ; Weizheng LIANG
Acta Academiae Medicinae Sinicae 2024;46(4):528-538
Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P<0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91%(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that(53.33%)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.
5.Research progress on the role of SHP-2 in tumor-associated macrophages
Xueliang WU ; Jianchun FAN ; Fei GUO ; Qi ZHANG ; Jun XUE ; Ximo WANG ; Guangyuan SUN ; Jianling LIU ; Lei HAN ; Shuquan GAO
Chinese Journal of Comparative Medicine 2024;34(1):171-176
Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.
6.Efficacy of ozone combined with low temperature plasma radiofrequency ablation in the treatment of cervical spondylotic radiculopathy
Yansong HUO ; Haiyan SUN ; Jinlei PANG ; Xiangfei GUO ; Yajing LIU ; Guangyuan RAN ; Mingwei HE
Basic & Clinical Medicine 2024;44(6):840-844
Objective To investigate the therapeutic effectiveness of ozone combined with low-temperature plasma coagulation therapy on patients with cervical spondylotic radiculopathy and its influence on inflammatory responses.Methods Ozone in combination with low-temperature plasma radio-frequency coagulation was applied to 75 patients with cervical spondylotic radiculopathy in Pain Medicine Department of Capital Medical University Affiliated Beijing Anzhen Hospital from May 2022 to May 2023.Pain scores were assessed using Visual Analog Scale(VAS)and Neck Disability Index(NDI)before and two weeks after treatment.Enzyme-linked immunosor-bent assay(ELISA)was used to analyze the level of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and interferon-gamma(IFN-γ)before and two weeks after treatment.Results After treatment with ozone plus low-temperature plasma radiofrequency,VAS and NDI scores showed a significant decrease[VAS:5.36(4,7)vs.1.32(1,2),P<0.000 1;NDI:32.72(24,70)vs.7.62(3.55,8.9),P<0.000 1].Two weeks after surgical intervention,there was an effective reduction in the level of IL-6,TNF-αand IFN-γ alleviating the inflammatory re-sponse[IL-6:4.33(2.51,5.04)vs.3.49(2.08,4.43),P<0.05;TNF-α:1.95(1.41,2.21)vs.1.61(1.02,2.03),P<0.05;IFN-γ:1.84(1.18,2.47)vs.1.55(0.76,2.09),P<0.05].Conclusions This Ozone combined with low-temperature plasma radiofrequency ablation is an effective technology for treatment of cer-vical spondylotic radiculopathy.
7.Factors associated with acute rejection after pediatric kidney transplantation: a single-center cohort study
Zhiliang GUO ; Rula SA ; Lan ZHU ; Guangyuan ZHAO ; Daqiang ZHAO ; Hui GUO ; Bin LIU ; Jipin JIANG ; Zhishui CHEN ; Gang CHEN
Chinese Journal of Organ Transplantation 2023;44(2):68-74
Objective:To summarize the incidence of acute rejection (AR) after pediatric kidney transplantation (KT) at a single center and examine its impact on graft/patient survival and risk factors for AR.Methods:This is a retrospective cohort study including pediatric recipients who underwent kidney transplantation in past 8 years.After excluding recipients of graft thrombosis within a week post-transplant and lost to follow-ups, a total of 143 cases were ultimately recruited and assigned into two groups of AR (n=29) and non-AR (n=114).Basic profiles of both donors and recipients and graft/patient survival rate were compared between two groups.Relative risk factors for AR episodes were also examined by Logistic regression.Results:Renal grafts for 130/143 cases (90.9%) were harvested from deceased donors and 120(83.9%) cases from children.Twenty-seven transplants (18.9%) were performed in infants and young recipients aged < 3 years.During a median follow-up of 33 months, 34 AR episodes occurred in 29(20.3%) patients.Rate of re-transplantation (27.6% vs. 7.9%), pediatric donor (96.5% vs. 80.7%) and rabbit anti-human thymocyte globulin (rATG) induction (79.3% vs. 36%) were significantly higher in AR group than non-AR group ( P=0.007, P=0.046, P<0.001).Multivariate regression analysis indicated that basiliximab induction caused a significant reduction in the risk of AR incidence as compared with rATG induction (odds ratio 0.13, 95% confidence interval 0.04-0.43, P<0.001).The median time of AR incidence was 1.3 months post-transplantation and 23 episodes (67.6%) were confirmed by biopsy.After anti-rejection treatment, 52.9%(n=18) of the cases achieved a full recovery and 38.3% (n=13) had improved graft function.However, 3 cases (8.8%) developed irreversible graft failure.The 1/3-year graft survival rates were significantly lower in AR group than those in non-AR group (75.3% vs. 95.2%, 68.4% vs. 90.4%, P=0.01), and there was no significant difference in 1-and 3-year patient survival rates between two groups. Conclusions:The incidence of AR is relatively high in pediatric renal transplantation, which has an impact on graft survival.Basiliximab induction can effectively reduce the risk of AR.
8.Establishment and validation of a predictive nomogram model for advanced gastric cancer with lymphovascular invasion
Zhenjiang GUO ; Guangyuan ZHAO ; Liqiang DU ; Fangzhen LIU
Tianjin Medical Journal 2023;51(12):1382-1386
Objective To explore the preoperative predictors of lymphovascular invasion(LVI)in patients with advanced gastric cancer,and establish the corresponding nomogram prediction model and conduct internal validation.Methods A total of 246 cases of advanced gastric cancer who underwent surgical resection in the Department of Gastrointestinal Surgery of Hengshui People's Hospital from January 2018 to December 2021 were selected.Patients were divided into the LVI positive group and the LVI negative group according to postoperative pathological diagnosis.The age,gender,tumor differentiation,tumor size,tumor site,Borrmann classification,Lauren's classification,cT stage,cN stage and systemic immune-inflammation index(SII)of patients were collected and compared between the two groups.The predictors that were statistically different between the two groups were subjected to multivariate Logistic regression and further developed into a visual prediction model.Bootstrap method was applied for internal validation of the prediction efficiency of the model.Results The differences of tumor size,Borrmann classification,tumor differentiation,Lauren classification,cT staging,cN staging and SII were statistically significant between the two groups(P<0.05).Multivariate Logistic regression analysis showed that tumor size(OR=2.184,95%CI:1.224-3.898),Borrmann classification(OR=2.517,95%CI:1.294-4.896),cT staging(OR=1.860,95%CI:1.045-3.308),cN staging(OR=1.816,95%CI:1.004-3.285)and SII(OR=1.001,95%CI:1.000-1.002)were independent predictors of LVI in advanced gastric cancer.A preoperative nomogram prediction model for advanced gastric cancer LVI was developed based on results of multivariate analysis.By internal validation,the area under curve(AUC)value of the subject operating characteristic(ROC)curve of the nomogram was 0.735,which was higher than that of tumor size(0.599),Borrmann staging(0.564),cT staging(0.604),cN staging(0.582)and SII(0.615),respectively.The calibration curve showed that the probability of predicted LVI by the nomogram was in a good agreement with the probability of actual LVI occurrence.The Hosmer-Lemeshow test showed good model fit(χ2=4.387,P=0.821).Conclusion The established nomogram prediction model can help to predict the probability of LVI in advanced gastric cancer preoperatively,which can provide a guideline for clinical individualized treatment.
9.Renal artery stenosis in children after pediatric donor kidney transplantation: a report of five cases
Zhiliang GUO ; Rula SA ; Guangyuan ZHAO ; Yu ZHANG ; Hesong ZENG ; Lan ZHU ; Gang CHEN
Chinese Journal of Organ Transplantation 2022;43(1):4-8
Objective:To explore the clinical features of transplanted renal artery stenosis after pediatric donor kidneys in children.Methods:We retrospectively summarized the clinical data in five cases of transplanted renal artery stenosis undergoing deceased pediatric donor kidney transplantation from May 1, 2014 to June 30, 2021.Donor/receptor characteristics, diagnosis, treatment and prognosis were recorded.The median follow-up period was 29 months.The median age of five donors and recipients was 9 and 132 months respectively.En bloc renal allograft( n=2)and single kidney transplantation( n=3)were performed.End-to-side anastomosis was performed for renal arteries.The median diagnostic time of renal artery stenosis was 10(3-60)months post-transplantation.Except for one 3-year-old recipient with an earlier onset of stenosis, four stenotic cases during a rapid growth period had a maximal height increase of 30 cm post-transplantation.Three of them had a history of surgery at graft site, including previous kidney transplantation( n=1)and transplant urinary tract reconstruction( n=2). All five cases had hypertension and two showed an elevated serum level of creatinine.Ultrasound indicated a significantly elevated flow rate of >300 cm/s( n=4)and CTA/MRA indicated that the degrees of stenosis varied from 50% to 95%( n=5). Results:After balloon dilatation, stenosis either improved( n=2)or relapsed( n=2). Further stenting succeed( n=1)or failed( n=1). One case of stenosis was relieved partially after 6-month observation without any invasive treatment. Conclusions:As a serious complication, transplant renal artery stenosis is common after pediatric donor kidney transplantation.Too small size in donor kidney and rapid recipient growth may be specific risk factors.After diagnosis, balloon dilation is a preferred treatment.Stent placement should be cautiously employed.
10.Social support status and influencing factors among schizophrenics in remission in Northeast Sichuan
Xin YANG ; Guijun ZHAO ; Qiongying XU ; Pei HE ; Lirong GUO ; Yuanmei XU ; Yanjun CHEN ; Jijun RAN ; Yan HU
Sichuan Mental Health 2022;35(3):234-240
ObjectiveTo investigate the social support status and influencing factors of schizophrenics in remission in Northeast Sichuan, and to provide ideas for improving their social support. MethodsFrom May to September 2020, a total of 533 patients who met the diagnosis criteria of the International Classification of Diseases, tenth edition (ICD-10) for schizophrenics in remission at the mental health institutions in Guangyuan, Bazhong and Dazhou cities were selected for the survey, and patients were assessed by self-made demographic and clinical data inventory and Social Support Rating Scale (SSRS). Then the social support status of schizophrenic in remission and influencing factors were analyzed, meantime, the impact of the second round reimbursement policy of medical insurance benefits on their social support was addressed particularly. Results①The SSRS total score, objective support, subjective support, and utilization of support scores of schizophrenics in remission were lower than those of the national norm (t=5.065~30.382, P<0.01). ②Univariate analysis showed that SSRS score was relatively high among patients with female gender (t=-3.632), retired status (F=5.951), married status (F=5.951), spouse as primary caregiver (F=23.841), annual household income >5 000 yuan (F=15.892), patient's economic income (t=4.083), and outpatient or online follow-up (F=3.954), with statistically significant differences (P<0.05 or 0.01). ③The total and dimensional scores of SSRS in patients with access to the second round medical insurance reimbursement were significantly higher than those without (t=10.195~25.103, P<0.01). ④Multiple linear regression analysis denoted that gender, work status, marital status, primary caregivers, annual family income, economic income, follow-up visits and the second round medical insurance reimbursement were the factors influencing social support status of schizophrenics in remission (β=0.201~2.115, P<0.05 or 0.01). ConclusionThe social support of schizophrenics in remission in Northeast Sichuan is below the national average, furthermore, their social support levels are affected by the gender, work status, marital status, primary caregivers, annual family income, economic income, follow-up visits and the second round medical insurance reimbursement, and the second round medical insurance reimbursement may ameliorate the social support status of patients.

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