1.Efficacy and immunological mechanisms of pegylated interferon α-2b in treatment-naive patients with chronic hepatitis B
Shufen SONG ; Fengxian JIN ; Yu LAN ; Gongchang ZHANG ; Zhiguo WU ; Yao ZHOU ; Qiong XIE ; Long YANG ; Shuilin SUN
Chinese Journal of Infectious Diseases 2025;43(1):14-23
Objective:To evaluate the efficacy and immunological mechanisms of pegylated interferon α-2b (Peg-IFNα-2b) antiviral therapy in treatment-naive patients with chronic hepatitis B(CHB).Methods:A total of 166 treatment-naive CHB patients, who were treated at Department of Infectious Diseases, the Second Affiliated Hospital of Nanchang University from March 2021 to March 2023, were enrolled in this study. All the patients received Peg-IFNα-2b therapy for 48 weeks. Serum hepatitis B virus (HBV) DNA, HBV serological markers, biochemical parameters, peripheral blood lymphocyte subsets and serum cytokine levels were detected and compared before and after treatment. Chi-square test, Mann-Whitney U test and paired sample t test were used for statistical comparison. Multivariate logistic regression analysis was used to analyze the influencing factors of hepatitis B surface antigen (HBsAg) seroconversion by stepwise regression method, and the receiver operator characteristic curve (ROC curve) was used to evaluate the predictive efficacy of immune indicators on HBsAg seroconversion. Results:Among the 166 treatment-naive CHB patients, the rate of HBV DNA negativity following 48 weeks of Peg-IFNα-2b therapy was 71.08%(118/166), the rate of hepatitis B e antigen (HBeAg) negativity was 32.05%(25/78), and the rate of HBsAg negativity was 20.48%(34/166). HBsAg negativity rate was 52.17%(24/46) in patients with baseline HBsAg<200 IU/mL, 10.26%(4/39) in patients with baseline HBsAg 200 to <1 200 IU/mL, and 7.41%(6/81) in patients with baseline HBsAg≥1 200 IU/mL, and the difference was statistically significant( χ2=39.37, P<0.001). After 48 weeks of treatment, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and alpha-fetoprotein (AFP) were significantly lower than those before treatment ( Z=9.33, 8.58, 5.99, 2.36, respectively, all P<0.05). lmmune indicators were detected in 58 patients, and the proportion of peripheral blood lymphocytes increased significantly post-treatment, with notable increases in CD3 + CD8 + T/CD3 + T, CD3 + CD4 + DR + /CD3 + CD4 + , CD3 + CD8 + DR + /CD3 + CD8 + , CD3 + CD8 + CD38 + /CD3 + CD8 + , CD3 + CD8 + CD28 + /CD3 + CD8 + , and CD19 + B cells, and the differences were all statistically significant ( t=-2.56, t=-8.65, Z=-3.58, t=-3.66, Z=-3.04, t=-3.62, t=-3.87, respectively, all P<0.05). Conversely, the proportion of CD3 + , CD3 + CD4 + T/CD3 + T, CD3 + CD4 + CD45RO + /CD3 + CD4 + , CD3 + CD8 + CD45RO + /CD3 + CD8 + and the CD4 + /CD8 + ratio decreased significantly post-treatment ( t=3.13, t=5.61, t=3.69, Z=3.95, Z=7.33, respectively, all P<0.05). No significant differences were observed in the proportion of CD16 + CD56 + natural killer (NK) cells, CD3 + CD4 + CD28 + /CD3 + CD4 + , CD3 + CD4 + CD38 + /CD3 + CD4 + cells before and after treatment (all P>0.05). Serum levels of interleukin(IL)-8, IL-12P70, and IL-17 significantly decreased post-treatment ( Z=2.85, 3.26, 4.12, respectively, all P<0.05), while IL-2, IL-1β, and interferon(IFN)-α levels were significantly elevated compared to baseline ( Z=-4.92, -4.85, -9.01, respectively, all P<0.001). There were no significant differences in IL-4, IL-6, and IL-10 levels before and after treatment (all P>0.05). Logistic regression analysis identified CD3 + CD8 + T/CD3 + T(odd ratios ( OR)=1.198, 95%confidence interval( CI) 1.003 to 1.432, P=0.046), CD3 + CD4 + DR + /CD3 + CD4 + ( OR=1.185, 95% CI 1.035 to 1.357, P=0.014), CD3 + CD8 + DR + /CD3 + CD8 + ( OR=0.813, 95% CI 0.690 to 0.958, P=0.013), CD3 + CD4 + CD38 + /CD3 + CD4 + ( OR=0.678, 95% CI 0.488 to 0.940, P=0.020), CD3 + CD8 + CD38 + /CD3 + CD8 + ( OR=1.272, 95% CI 1.069 to 1.512, P=0.007), CD19 + B cells( OR=0.752, 95% CI 0.582 to 0.971, P=0.029), IL-2( OR=8.568, 95% CI 1.927 to 38.087, P=0.005), and IL-17( OR=0.728, 95% CI 0.535 to 0.989, P=0.042) as independent factors influencing HBsAg seroconversion. The area under the curve (AUC) of the proportion of dCD19 + B cells (the reciprocal of CD19 + B cells) for predicting HBsAg seroconversion was 0.716, the sensitivity was 0.636, and the specificity was 0.809. The AUC of IL-2 was 0.657, the sensitivity was 0.818, and the specificity was 0.404. The AUC of dIL-17 (the reciprocal of IL-17 levels) was 0.624, the sensitivity was 0.727, and the specificity was 0.489. The AUC of IL-2 and dIL-17 as a combined predictor was 0.830, the sensitivity was 0.909, and the specificity was 0.787. Conclusions:Peg-IFNα-2b demonstrates significant antiviral, biochemical, and serological responses in treatment-naive CHB patients, with enhanced efficacy in patients exhibiting HBsAg levels <200 IU/mL. In patients with HBsAg<200 IU/mL, the rate of HBsAg negativity reached 52.17%.Peg-IFNα-2b can regulate the immune function of patients with CHB by increasing the proportion of activated T lymphocyte subsets and functional subsets. The proportion of CD19 + B cells, IL-2 levels, and IL-17 levels hold predictive value for achieving HBsAg seroconversion.
2.Efficacy and immunological mechanisms of pegylated interferon α-2b in treatment-naive patients with chronic hepatitis B
Shufen SONG ; Fengxian JIN ; Yu LAN ; Gongchang ZHANG ; Zhiguo WU ; Yao ZHOU ; Qiong XIE ; Long YANG ; Shuilin SUN
Chinese Journal of Infectious Diseases 2025;43(1):14-23
Objective:To evaluate the efficacy and immunological mechanisms of pegylated interferon α-2b (Peg-IFNα-2b) antiviral therapy in treatment-naive patients with chronic hepatitis B(CHB).Methods:A total of 166 treatment-naive CHB patients, who were treated at Department of Infectious Diseases, the Second Affiliated Hospital of Nanchang University from March 2021 to March 2023, were enrolled in this study. All the patients received Peg-IFNα-2b therapy for 48 weeks. Serum hepatitis B virus (HBV) DNA, HBV serological markers, biochemical parameters, peripheral blood lymphocyte subsets and serum cytokine levels were detected and compared before and after treatment. Chi-square test, Mann-Whitney U test and paired sample t test were used for statistical comparison. Multivariate logistic regression analysis was used to analyze the influencing factors of hepatitis B surface antigen (HBsAg) seroconversion by stepwise regression method, and the receiver operator characteristic curve (ROC curve) was used to evaluate the predictive efficacy of immune indicators on HBsAg seroconversion. Results:Among the 166 treatment-naive CHB patients, the rate of HBV DNA negativity following 48 weeks of Peg-IFNα-2b therapy was 71.08%(118/166), the rate of hepatitis B e antigen (HBeAg) negativity was 32.05%(25/78), and the rate of HBsAg negativity was 20.48%(34/166). HBsAg negativity rate was 52.17%(24/46) in patients with baseline HBsAg<200 IU/mL, 10.26%(4/39) in patients with baseline HBsAg 200 to <1 200 IU/mL, and 7.41%(6/81) in patients with baseline HBsAg≥1 200 IU/mL, and the difference was statistically significant( χ2=39.37, P<0.001). After 48 weeks of treatment, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and alpha-fetoprotein (AFP) were significantly lower than those before treatment ( Z=9.33, 8.58, 5.99, 2.36, respectively, all P<0.05). lmmune indicators were detected in 58 patients, and the proportion of peripheral blood lymphocytes increased significantly post-treatment, with notable increases in CD3 + CD8 + T/CD3 + T, CD3 + CD4 + DR + /CD3 + CD4 + , CD3 + CD8 + DR + /CD3 + CD8 + , CD3 + CD8 + CD38 + /CD3 + CD8 + , CD3 + CD8 + CD28 + /CD3 + CD8 + , and CD19 + B cells, and the differences were all statistically significant ( t=-2.56, t=-8.65, Z=-3.58, t=-3.66, Z=-3.04, t=-3.62, t=-3.87, respectively, all P<0.05). Conversely, the proportion of CD3 + , CD3 + CD4 + T/CD3 + T, CD3 + CD4 + CD45RO + /CD3 + CD4 + , CD3 + CD8 + CD45RO + /CD3 + CD8 + and the CD4 + /CD8 + ratio decreased significantly post-treatment ( t=3.13, t=5.61, t=3.69, Z=3.95, Z=7.33, respectively, all P<0.05). No significant differences were observed in the proportion of CD16 + CD56 + natural killer (NK) cells, CD3 + CD4 + CD28 + /CD3 + CD4 + , CD3 + CD4 + CD38 + /CD3 + CD4 + cells before and after treatment (all P>0.05). Serum levels of interleukin(IL)-8, IL-12P70, and IL-17 significantly decreased post-treatment ( Z=2.85, 3.26, 4.12, respectively, all P<0.05), while IL-2, IL-1β, and interferon(IFN)-α levels were significantly elevated compared to baseline ( Z=-4.92, -4.85, -9.01, respectively, all P<0.001). There were no significant differences in IL-4, IL-6, and IL-10 levels before and after treatment (all P>0.05). Logistic regression analysis identified CD3 + CD8 + T/CD3 + T(odd ratios ( OR)=1.198, 95%confidence interval( CI) 1.003 to 1.432, P=0.046), CD3 + CD4 + DR + /CD3 + CD4 + ( OR=1.185, 95% CI 1.035 to 1.357, P=0.014), CD3 + CD8 + DR + /CD3 + CD8 + ( OR=0.813, 95% CI 0.690 to 0.958, P=0.013), CD3 + CD4 + CD38 + /CD3 + CD4 + ( OR=0.678, 95% CI 0.488 to 0.940, P=0.020), CD3 + CD8 + CD38 + /CD3 + CD8 + ( OR=1.272, 95% CI 1.069 to 1.512, P=0.007), CD19 + B cells( OR=0.752, 95% CI 0.582 to 0.971, P=0.029), IL-2( OR=8.568, 95% CI 1.927 to 38.087, P=0.005), and IL-17( OR=0.728, 95% CI 0.535 to 0.989, P=0.042) as independent factors influencing HBsAg seroconversion. The area under the curve (AUC) of the proportion of dCD19 + B cells (the reciprocal of CD19 + B cells) for predicting HBsAg seroconversion was 0.716, the sensitivity was 0.636, and the specificity was 0.809. The AUC of IL-2 was 0.657, the sensitivity was 0.818, and the specificity was 0.404. The AUC of dIL-17 (the reciprocal of IL-17 levels) was 0.624, the sensitivity was 0.727, and the specificity was 0.489. The AUC of IL-2 and dIL-17 as a combined predictor was 0.830, the sensitivity was 0.909, and the specificity was 0.787. Conclusions:Peg-IFNα-2b demonstrates significant antiviral, biochemical, and serological responses in treatment-naive CHB patients, with enhanced efficacy in patients exhibiting HBsAg levels <200 IU/mL. In patients with HBsAg<200 IU/mL, the rate of HBsAg negativity reached 52.17%.Peg-IFNα-2b can regulate the immune function of patients with CHB by increasing the proportion of activated T lymphocyte subsets and functional subsets. The proportion of CD19 + B cells, IL-2 levels, and IL-17 levels hold predictive value for achieving HBsAg seroconversion.
3.Progress in the application of 3D printing technology in liver surgery
Yuan SUN ; Fengxian WEI ; Chaofeng GAO ; Zekun ZHAO ; Zhiming ZHOU ; Xiaodong XU
Journal of Clinical Medicine in Practice 2024;28(17):131-136
3D printing, an emerging technology, can assist improving surgical efficiency of liver surgery. 3D-printed organ models facilitate surgeons in surgical planning, enabling the simulation of surgical procedures and guiding interventions through surgical navigation. Furthermore, 3D printing harnesses the potential of utilizing tissue or cells from specific individuals to generate grafts for liver surgeries, thereby addressing the issue of graft shortage and advancing the development of personalized medicine.
4.Preparation and immunological performance identification of ribavirin mono-clonal antibodies
Xiaofei HU ; Fengxian WEI ; Yunrui XING ; Lin WANG ; Yaning SUN
Chinese Journal of Veterinary Science 2024;44(9):2025-2030
This study aims to obtain highly sensitive and specific monoclonal antibodies to ribavirin.Ribavirin was coupled with carrier proteins to synthesize artificial complete antigen by glutaralde-hyde method.UV scanning,gel electrophoresis and animal immunization were employed to identify quality of the synthesized artificial complete antigens.The monoclonal antibody was prepared by cell fusion,positive hybridoma screening and induction of ascites in vivo,and the immunological characteristics of monoclonal antibodies were identified.The results showed that RBV was coupled to carrier proteins,and the artificial antigens were prepared successfully.One cell line that can stably secrete monoclonal antibodies against ribavirin was obtained,and the titers of the mono-clonal antibodies secreted by cell line was above 1∶512 000,with IC50 values of 4.74 μg/L.Fur-thermore,there were no cross-reactivity with other antiviral drugs such as amantadine and carrier proteins.In this study,monoclonal antibodies of ribavirin with high sensitivity and specificity was synthesized successfully,which lays a solid foundation for the establishment of immunoassay methods of ribavirin.
5.Sex Estimation of Han Adults in Western China Based on Three-Dimensional Cranial CT Reconstruction.
Xiao-Tong YANG ; Cheng-Hui SUN ; Yong-Gang MA ; Yong-Jie CAO ; Jian XIONG ; Ji ZHANG ; Ping HUANG
Journal of Forensic Medicine 2023;39(1):27-33
OBJECTIVES:
To examine the reliability and accuracy of Walker's model for estimating the sex of Han adults in western China by using cranium three-dimensional (3D) CT reconstruction, and to study the suitable cranial sex estimation model for Han people in western China.
METHODS:
A total of 576 cranial CT 3D reconstructed images from Hanzhong Hospital in Shaanxi Province from 2017 to 2021 were collected. These images were divided into the experimental group with 486 samples and the validation group with 90 samples. Walker's model was used by observer 1 to estimate the sex of experimental group samples. The logistic function applicable to Han people in western China was corrected by observer 1. The 90 samples in the validation group were scored and substituted into the modified logistic function to complete the back substitution test by observer 1, 2 and 3.
RESULTS:
The accuracy of sex estimation of Han adults in western China was 63.2%-77.2% by applying Walker's model. The accuracy of modified logistic function was 82.9%. The accuracy of sex estimation through back substitution test by 3 observers was 75.6%-91.1%, with a Kappa value of 0.689 (P<0.05) for inter-observer consistency and 0.874 (P<0.05) for intra-observer consistency.
CONCLUSIONS
There are great differences in bone characteristics among people from different regions. The modified logistic function can achieve higher accuracy in Han adults in western China.
Humans
;
Adult
;
Reproducibility of Results
;
Sex Determination by Skeleton/methods*
;
Forensic Anthropology
;
Skull/anatomy & histology*
;
Imaging, Three-Dimensional
;
China
;
Tomography, X-Ray Computed
6.Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer.
Juanjuan FENG ; Zhengke LIAN ; Xinting XIA ; Yue LU ; Kewen HU ; Yunpeng ZHANG ; Yanan LIU ; Longmiao HU ; Kun YUAN ; Zhenliang SUN ; Xiufeng PANG
Acta Pharmaceutica Sinica B 2023;13(3):1145-1163
MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.
7.Research progress on perioperative nutritional management for gastric cancer
Chaofeng GAO ; Zekun ZHAO ; Fengxian WEI ; Yuan SUN ; Zhiming ZHOU ; Xiaodong XU
Practical Oncology Journal 2023;37(6):519-523
Gastric cancer is one of the common tumors in the world and a major cause of cancer death.Although the 5-year survival rate of gastric cancer patients has increased greatly with the improvement levels of diagnosis and treatment,the high malnutri-tion rate of gastric cancer patients still has a significant impact on their overall survival and quality of life.Malnutrition is considered an independent prognostic factor for cancer patients,early detection of malnutrition in gastric cancer patients and more reasonable peri-operative nutritional support play an important role in the survival and prognosis of gastric cancer patients.This article combines exist-ing research at domestic and abroad to review the nutritional risk screening and assessment of gastric cancer patients during periopera-tive period,as well as the research progress of perioperative nutritional support and immunonutrition,in order to provide more compre-hensive nutritional management strategies for patients with gastric cancer during the perioperative period.
8.Expression of CD155/TIGIT in osteosarcoma
Jinrong Liang ; Yawen Zhang ; Yuanjue Sun ; Haiyan Hu
Acta Universitatis Medicinalis Anhui 2023;58(1):37-41
Objective:
To investigate the expression of CD155/TIGIT in patients with osteosarcoma and its significance
Methods :
The expression differences of CD155 and TIGIT in tumor tissues of distant metastatic osteosarcoma patients and non⁃metastatic osteosarcoma patients were analyzed by cancer Genome Atlas ( TCGA)
database.The surgically removed tissues of osteosarcoma patients were collected to prepare pathological sections and tissue chips , and the tumor tissue and cell morphology were observed by HE staining. Immunohistochemical staining was used to detect the expression of CD155 and TIGIT , and the scores were divided into high expression group and low expression group according to the scores. Chi⁃square test was used to analyze the relationship between CD155/TIG⁃IT expression and clinical features and prognosis.
Results :
TCGA database data showed higher expression of CD155 and TIGIT in patients with osteosarcoma accompanied by metastasis. HE staining of pathological sections revealed that tumor tissues with high expression of CD155/TIGIT contained more binuclear or multinucleated , hyperchromatic and obviously heteromorphic tumor cells. Immunohistochemical staining and score analysis of tissue chip showed that the expression of CD155 and TIGIT was correlated with clinical stage and distant metastasis ( P <
0. 05) , but not with age , sex , tumor size , pathological type and tumor necrosis rate.
Conclusion
CD155 and TIGIT may be one of the prognostic indicators of osteosarcoma.
9.Investigation of leprosy survivors in Fengxian District, Shanghai
Qi SUN ; Qun LU ; Yao-zhong QIAN ; Peng LI ; Wei XU ; Lin ZHANG ; Bai-chen LI ; Xiu LI
Shanghai Journal of Preventive Medicine 2021;33(8):762-766
Objective:To understand the current living and health status of leprosy survivors in Fengxian District, Shanghai, and to provide scientific evidence for improving their quality of life. Methods:In January 2018-June 2020, professionally trained CDC staff performed a household investigation on 41 patients with leprosy (case group) and 82 non-leprosy persons (control group) every year. Living and health status, and routine laboratory examinations such as blood pressure, blood glucose, and blood lipids were monitored. Results:Majority of the patients with leprosy had low educational level (68.29% being primary school) and were mostly farmers (51.22%).The patients had abnormal residual Ⅱ level 5 (12.20%) and mostly were tb-like (TT) (53.66%). Moreover, some patients were not incapacitated (46.34%), had no family financial difficulties (29.27%), did not acquire the national subsistence allowance policy (58.54%), and asked for "regular physical examination" (68.29%).Compared to the 82 control persons, the patients with leprosy had significantly different body mass index (BMI) and blood pressure (
10. Perirenal capsule involvement in IgG4-related chronic interstitial nephritis: a case report and literature review
Yagui QIU ; Xi XIA ; Yanyang CHEN ; Qinghua LIU ; Dihua ZHANG ; Haiping MAO ; Fengxian HUANG
Chinese Journal of Nephrology 2019;35(11):822-827
Objective:
To explore the clinicopathological features and the renal biopsy process of a case of IgG4-related chronic interstitial nephritis with perirenal capsule involved and review associated literature to improve the clinician's understanding for this disease and to perform a better renal biopsy.
Methods:
The onset, diagnosis and treatment course of the disease were described and associated literature were reviewed to summary the clinicopathologic features and key points in renal biopsy.
Results:
The data of the patient showed that the urine specific gravity was 1.011, with urine protein ± and urine sugar 3+. The concentration of hemoglobin was 53 g/L, serum creatinine was 1665 μmol/L, and IgG4 was 9.39 g/L. Computed tomography showed that both kidneys enlarged slightly with decreased density and low density shadow around the kidneys. On contrast-enhanced scan, irregular low-density enhancement areas were found in both kidneys, and the edge of the boundary was not clear. For the first renal biopsy, no renal parenchyma was found except mainly hyaline collagen fibrils. At the second time, 3 pieces of tissues were obtained, which showed chronic interstitial glomerulonephritis. The IgG4 positive plasma cells were about 60/HPF and the IgG4+/IgG+cells ratio was more than 40%. The diagnosis of IgG4-related chronic interstitial glomerulonephritis was confirmed. After corticosteroid treatment, the serum creatinine decreased to 502 μmol/L after the patient got rid of dialysis.
Conclusions
There are various manifestations of renal damage caused by IgG4-related disease. It is necessary to pay attention to the involvement of the perirenal capsule, and to balance the risk of bleeding and poor sampling in renal biopsy.


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