1.Role and mechanism of T helper 17 cells/regulatory T cells immune balance regulated by the TGF-β1/Smad signaling pathway mediated in nonalcoholic steatohepatitis
Qian WANG ; Kaiyang LI ; Mei YANG ; Hang ZHANG ; Shengjin ZHU ; Qi ZHAO ; Jing HUANG
Journal of Clinical Hepatology 2025;41(5):942-947
Nonalcoholic steatohepatitis (NASH) is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration, and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 (Th17) and regulatory T (Treg) cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 (TGF-β1) is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells, and TGF-β1 binds to its receptor and activates the Smad signaling pathway, thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells, in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.
2.Efficacy and safety of obinutuzumab combined with short-course dexamethasone for relapsed immune thrombocytopenia after treatment with rituximab
Xiaotong CHEN ; Yanqiu ZHAO ; Qi LI ; Shengjin FAN
Journal of Leukemia & Lymphoma 2025;34(10):597-600
Objective:To investigate the efficacy and safety of obinutuzumab combined with short-course dexamethasone in patients with relapsed immune thrombocytopenia (ITP) who had previously been treated with rituximab.Methods:A retrospective case series study was conducted. A total of 8 patients with relapsed ITP after treatment with rituximab who received obinutuzumab combined with short-course dexamethasone between January 2023 and January 2024 in the First Affiliated Hospital of Harbin Medical University were collected. The clinical characteristics, changes in platelet counts, changes in peripheral blood B-lymphocyte counts, treatment outcome and treatment-related adverse events were analyzed.Results:There were 1 male and 7 females in 8 patients with relapsed ITP after treatment with rituximab. The median age [ M ( Q1, Q3)] of the 8 enrolled patients was 52.5 (40.5, 56.0) years. The median relapsed times was 2.0 (2.0, 2.5) times and the median course of disease was 16.0 (13.0, 18.5) months. The platelet count increased from 8.73 (5.79, 11.65)×10 9/L pre-treatment to 180.00 (83.40, 255.00)×10 9/L post-treatment, and the difference was statistically significant ( Z = -2.37, P = 0.018); conversely, peripheral blood B-lymphocyte count decreased from 322.59 (148.29, 403.07) × 10 9/L pre-treatment to 1.23 (0.57, 1.76) ×10 9/L post-treatment, and the difference was statistically significant ( Z = -2.52, P = 0.012). After obinutuzumab and short-course dexamethasone treatment, 6 patients achieved complete remission, 1 case showed response, and 1 case had no response. No severe adverse events were observed during treatment and follow-up in all patients. Conclusions:Obinutuzumab combined with short-course dexamethasone appears to be effective in treating relapsed ITP patients after treatment with rituximab, and its safety is good.
3.Role of mitophagy induced by the PTEN-induced kinase 1/Parkin signaling pathway in metabolic associated fatty liver disease and related advances in targeted therapies
Shengjin ZHU ; Xiaodeng ZHU ; Kaiyang LI ; Mei YANG ; Xian WU
Journal of Clinical Hepatology 2025;41(8):1655-1661
Metabolic associated fatty liver disease(MAFLD)has a complex pathogenesis,and mitophagy is involved in the development and progression of MAFLD and plays a key role in liver metabolic pathways and signaling networks.Mitophagy is regulated by a variety of pathways,and the PTEN-induced kinase 1(PINK1)/Parkin pathway is considered the main pathway for regulating mitophagy.Mitophagy mediated by the PINK1/Parkin pathway can regulate lipid metabolism,inflammation,and fibrosis and delay the progression of MAFLD.This article reviews the role of mitophagy mediated by the PINK1/Parkin pathway in MAFLD and the research advances in targeted therapy,in order to provide theoretical bases and ideas for the prevention and treatment of MAFLD.
4.Analysis of key prognostic factors for postoperative radiotherapy for adenoid cystic carcinoma of the head and neck
Ying XIAO ; Wen JIANG ; Shengjin DOU ; Lulu YE ; Lin ZHANG ; Jiang LI ; Shengwen LIU ; Guopei ZHU
Chinese Journal of Radiation Oncology 2025;34(4):326-333
Objective:To evaluate the impact of surgical margin status and pathological subtypes on the prognosis of patients with adenoid cystic carcinoma of the head and neck (ACCHN) who underwent postoperative radiotherapy.Methods:A retrospective analysis was conducted on 309 patients with initially treated, non-metastatic ACCHN who completed postoperative radiotherapy at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. All patients underwent curative (non-palliative) surgery followed by postoperative radiotherapy, with a median dose of 66 Gy (range: 54-70 Gy). The Kaplan-Meier method was used to compare 5-year local recurrence-free survival (LRFS) between R0 (negative margin) and non-R0 resections in patients with initially resectable (T 1-T 4a stage) and initially unresectable (T 4b stage) disease. Univariate and multivariate Cox proportional hazards models were employed to analyze risk factors for local recurrence, with a focus on surgical margin status and pathological subtypes. Results:The median follow-up was 48 months. Of the 309 patients included in the study, 133 were males and 176 were females, with a median age of 51 years (range: 18-77 years). Primary tumors were located in the major salivary glands in 135 cases (including 42 in the parotid gland, 65 in the submandibular gland, and 28 in the sublingual gland) and in the minor salivary glands in 174 cases. The 5-year overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and progression-free survival rates were 91.5%, 90.8%, 66.1%, and 63.9%, respectively. Non-R0 resection was achieved in 177 patients (57.3%). Among initially resectable patients ( n=253), the non-R0 resection rate was 49.0% ( n=124), with only 6 cases (2.4%) experiencing local recurrence (all non-R0 resections). In initially unresectable patients ( n=56), the non-R0 resection rate was as high as 95% ( n=53), with 13 cases (23%) experiencing local recurrence (2 cases in non-R0 resection and 1 case in R0 resection). For initially resectable patients, non-R0 resection significantly reduced the 5-year LRFS rate to 95.2%, compared to 100% in R0 resection patients ( P=0.014). However, multivariate analysis revealed that the solid pathological subtype was an independent risk factor for 5-year LRFS ( HR=7.40, 95% CI: 2.81-19.52, P<0.001), while the surgical margin status was not an independent factor. Conclusions:The combined strategy of surgery and postoperative radiotherapy provides high local control rates for ACCHN patients. Achieving R0 resection is crucial for initially resectable patients, while a comprehensive treatment strategy involving surgery and postoperative radiotherapy remains essential for initially unresectable patients. The solid pathological subtype is the most significant risk factor for local recurrence.
5.Clinical characteristics and prognostic evaluation of patients with hematological disease and sepsis in the Hematological intensive care unit
Haitao LI ; Dongxue LU ; Dandan LI ; Dongyang ZHANG ; Jinyue FU ; Qian ZHANG ; Shengjin FAN
Chinese Journal of Hematology 2025;46(1):58-63
Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.
6.Advancing the development of hematology care units to enhance hematology-specific critical care capacity
Shengjin FAN ; Haitao LI ; Xi ZHANG
Chinese Journal of Hematology 2025;46(11):985-990
Establishing hematology care units (HCU) is essential for strengthening hematology-specific critical care capacity. This article outlines two HCU operational models in China—the ICU model and the pre-ICU model—and discusses practical insights from their implementation. It recommends establishing HCU within hematology wards, equipped for respiratory and hemodynamic monitoring and blood purification, and led by hematologists trained in critical care or by teams collaborating efficiently with general ICU through standardized workflows. For units not yet meeting these standards, establishing a resuscitation room and strengthening critical care training are advised. HCU primarily admit patients with severe or life-threatening bleeding due to hematologic diseases, severe infections or septic shock, early complications of newly diagnosed acute myeloid leukemia or acute promyelocytic leukemia (AML/APL), treatment-related complications, rapidly progressive or highly lethal conditions, and those requiring organ support or blood purification. Emphasis is placed on quantitative assessment of disease severity and timely transfer to the HCU, using tools such as the National Early Warning Score, quick Sequential Organ Failure Assessment (qSOFA), SOFA/ΔSOFA, and the Multinational Association of Supportive Care in Cancer risk index for patient stratification. Early implementation of sepsis bundles is emphasized. For organ support, high-flow nasal cannula oxygen therapy is prioritized to improve oxygenation. Continuous renal replacement therapy is performed when there are indications such as renal failure with oliguria or anuria, congestive heart failure, or drug overdose, etc. Treatment of the underlying hematologic disease follows a "three-tier stratification" and "watch-and-adjust" strategy, while respecting patient preferences. We encourage eligible hematology centers to actively establish HCU, explore new care models, and strengthen hematology-specific critical care capacity.
7.Role and mechanism of T helper 17 cells/regulatory T cells immune balance regulated by the TGF-β1/Smad signaling pathway mediated in nonalcoholic steatohepatitis
Qian WANG ; Kaiyang LI ; Mei YANG ; Hang ZHANG ; Shengjin ZHU ; Qi ZHAO ; Jing HUANG
Journal of Clinical Hepatology 2025;42(5):942-947
Nonalcoholic steatohepatitis(NASH)is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration,and it plays an important role in the progression of hepatic steatosis.Recent studies have shown that immune homeostasis imbalance between T helper 17(Th17)and regulatory T(Treg)cells are closely associated with the pathological process of NASH.Transforming growth factor-β1(TGF-β1)is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells,and TGF-β1 binds to its receptor and activates the Smad signaling pathway,thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation.This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells,in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.
8.Clinical characteristics and prognostic evaluation of patients with hematological disease and sepsis in the Hematological intensive care unit
Haitao LI ; Dongxue LU ; Dandan LI ; Dongyang ZHANG ; Jinyue FU ; Qian ZHANG ; Shengjin FAN
Chinese Journal of Hematology 2025;46(1):58-63
Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.
9.Advancing the development of hematology care units to enhance hematology-specific critical care capacity
Shengjin FAN ; Haitao LI ; Xi ZHANG
Chinese Journal of Hematology 2025;46(11):985-990
Establishing hematology care units (HCU) is essential for strengthening hematology-specific critical care capacity. This article outlines two HCU operational models in China—the ICU model and the pre-ICU model—and discusses practical insights from their implementation. It recommends establishing HCU within hematology wards, equipped for respiratory and hemodynamic monitoring and blood purification, and led by hematologists trained in critical care or by teams collaborating efficiently with general ICU through standardized workflows. For units not yet meeting these standards, establishing a resuscitation room and strengthening critical care training are advised. HCU primarily admit patients with severe or life-threatening bleeding due to hematologic diseases, severe infections or septic shock, early complications of newly diagnosed acute myeloid leukemia or acute promyelocytic leukemia (AML/APL), treatment-related complications, rapidly progressive or highly lethal conditions, and those requiring organ support or blood purification. Emphasis is placed on quantitative assessment of disease severity and timely transfer to the HCU, using tools such as the National Early Warning Score, quick Sequential Organ Failure Assessment (qSOFA), SOFA/ΔSOFA, and the Multinational Association of Supportive Care in Cancer risk index for patient stratification. Early implementation of sepsis bundles is emphasized. For organ support, high-flow nasal cannula oxygen therapy is prioritized to improve oxygenation. Continuous renal replacement therapy is performed when there are indications such as renal failure with oliguria or anuria, congestive heart failure, or drug overdose, etc. Treatment of the underlying hematologic disease follows a "three-tier stratification" and "watch-and-adjust" strategy, while respecting patient preferences. We encourage eligible hematology centers to actively establish HCU, explore new care models, and strengthen hematology-specific critical care capacity.
10.Role of mitophagy induced by the PTEN-induced kinase 1/Parkin signaling pathway in metabolic associated fatty liver disease and related advances in targeted therapies
Shengjin ZHU ; Xiaodeng ZHU ; Kaiyang LI ; Mei YANG ; Xian WU
Journal of Clinical Hepatology 2025;41(8):1655-1661
Metabolic associated fatty liver disease(MAFLD)has a complex pathogenesis,and mitophagy is involved in the development and progression of MAFLD and plays a key role in liver metabolic pathways and signaling networks.Mitophagy is regulated by a variety of pathways,and the PTEN-induced kinase 1(PINK1)/Parkin pathway is considered the main pathway for regulating mitophagy.Mitophagy mediated by the PINK1/Parkin pathway can regulate lipid metabolism,inflammation,and fibrosis and delay the progression of MAFLD.This article reviews the role of mitophagy mediated by the PINK1/Parkin pathway in MAFLD and the research advances in targeted therapy,in order to provide theoretical bases and ideas for the prevention and treatment of MAFLD.

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