1.Mechanism of action of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Wei LI ; Tinghui JIANG ; Yongqiang ZHU ; Yan LIU
Journal of Clinical Hepatology 2025;41(3):588-593
Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis, and its pathogenesis is complex and remains unclear. In recent years, more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota, including bile salt metabolism, dynamic changes of microbiota, inflammatory response, and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma, especially gut microbiota dysbiosis, abnormal bile salt metabolism, chronic inflammatory response, and immune system interaction, this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.
2.Analysis of the current status of red blood cell transfusion in very preterm infants from Chinese Neonatal Network in 2022
Yan MO ; Aimin QIAN ; Ruimiao BAI ; Shujuan LI ; Xiaoqing YU ; Jin WANG ; K. Shoo LEE ; Siyuan JIANG ; Qiufen WEI ; Wenhao ZHOU
Chinese Journal of Pediatrics 2025;63(1):55-61
Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.
3.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
4.Outcome after spleen-preserving distal pancreatectomy by Warshaw technique for pancreatic body cancer
Endi ZHOU ; Guodong SHI ; Hongyuan SHI ; Kai ZHANG ; Jishu WEI ; Min TU ; Zipeng LU ; Feng GUO ; Jianmin CHEN ; Kuirong JIANG ; Wentao GAO
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):177-186
Background:
s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer.
Methods:
We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R.
Results:
Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices.
Conclusions
SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.
5.Outcome after spleen-preserving distal pancreatectomy by Warshaw technique for pancreatic body cancer
Endi ZHOU ; Guodong SHI ; Hongyuan SHI ; Kai ZHANG ; Jishu WEI ; Min TU ; Zipeng LU ; Feng GUO ; Jianmin CHEN ; Kuirong JIANG ; Wentao GAO
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):177-186
Background:
s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer.
Methods:
We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R.
Results:
Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices.
Conclusions
SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.
6.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
7.Outcome after spleen-preserving distal pancreatectomy by Warshaw technique for pancreatic body cancer
Endi ZHOU ; Guodong SHI ; Hongyuan SHI ; Kai ZHANG ; Jishu WEI ; Min TU ; Zipeng LU ; Feng GUO ; Jianmin CHEN ; Kuirong JIANG ; Wentao GAO
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):177-186
Background:
s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer.
Methods:
We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R.
Results:
Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices.
Conclusions
SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.
8.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
9.Analysis of prognostic risk factors for chronic active antibody-mediated rejection after kidney transplantation
Yu HUI ; Hao JIANG ; Zheng ZHOU ; Linkun HU ; Liangliang WANG ; Hao PAN ; Xuedong WEI ; Yuhua HUANG ; Jianquan HOU
Organ Transplantation 2025;16(4):565-573
Objective To investigate the independent risk factors affecting the prognosis of chronic active antibody-mediated rejection (caAMR) after kidney transplantation. Methods A retrospective analysis was conducted on 61 patients who underwent renal biopsy and were diagnosed with caAMR. The patients were divided into caAMR group (n=41) and caAMR+TCMR group (n=20) based on the presence or absence of concurrent acute T cell-mediated rejection (TCMR). The patients were followed up for 3 years. The value of 24-hour urinary protein and estimated glomerular filtration rate (eGFR) at the time of biopsy in predicting graft loss was assessed using receiver operating characteristic (ROC) curves. The independent risk factors affecting caAMR prognosis were analyzed using the LASSO-Cox regression model. The correlation between grouping, outcomes, and Banff scores was compared using Spearman rank correlation matrix analysis. Kaplan-Meier analysis was used to evaluate the renal allograft survival rates of each subgroup. Results The 3-year renal allograft survival rates for the caAMR group and the caAMR+TCMR group were 83% and 79%, respectively. The area under the ROC curve (AUC) for predicting 3-year renal allograft loss was 0.83 [95% confidence interval (CI) 0.70-0.97] for eGFR and 0.78 (95% CI 0.61-0.96) for 24-hour urinary protein at the time of biopsy. LASSO-Cox regression analysis and Kaplan-Meier analysis showed that eGFR≤25.23 mL/(min·1.73 m²) and the presence of donor-specific antibody (DSA) against human leukocyte antigen (HLA) class I might be independent risk factors affecting renal allograft prognosis, with hazard ratios of 7.67 (95% CI 2.18-27.02) and 5.13 (95% CI 1.33-19.80), respectively. A strong correlation was found between the Banff chronic lesion indicators of renal interstitial fibrosis and tubular atrophy (P<0.05). Conclusions The presence of HLA class I DSA and eGFR≤25.23 mL/(min·1.73 m²) at the time of biopsy may be independent risk factors affecting the prognosis of caAMR.
10.Research progress in antibody drug therapy for relapsed/refractory diffuse large B-cell lymphoma
Yanyan SUN ; Weichen ZHAO ; Chunyuan HE ; Yimiao XIA ; Wei ZHOU ; Yuanyuan ZHEN ; Junjie JIANG ; Facai WANG
China Pharmacy 2025;36(13):1677-1682
Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease. Although standard first-line regimens can cure >50% of patients, approximately one-third of them develop relapsed/refractory DLBCL (r/r DLBCL). Consequently, immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment, antibody-based therapies have evolved rapidly, progressing from monoclonal antibodies (e.g., rituximab, tafasitamab) to bispecific antibodies(e.g., odronextamab,glofitamab, epcoritamab) and antibody-drug conjugate (e.g., polatuzumab vedotin, loncastuximab tesirine). These engineered agents enhance immune cytotoxicity and tumor-specific targeting, providing novel therapeutic options for r/r DLBCL patients.

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