1.Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway
Minchao FENG ; Baijun QIN ; Fang LUO ; Kai LI ; Ning WANG ; Guozhong CHEN ; Xiping TANG
Journal of Clinical Hepatology 2024;40(2):343-350
ObjectiveTo investigate the therapeutic effect of Qingjie Huagong decoction (QJHGD) on a mouse model of severe acute pancreatitis (SAP) and the mechanism of action of QJHGD against inflammatory response. MethodsA total of 36 male C57BL/6J mice were randomly divided into blank group, model group, Western medicine group (ulinastatin), and low-, middle-, and high-dose QJHGD groups, with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling, the mice in the low-, middle-, and high-dose groups were given QJHGD (1, 2, and 4 g/kg, respectively) by gavage, and those in the Western medicine group were given intraperitoneal injection of ulinastatin (5×104 U/kg), for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas; ELISA was used to measure the levels of α-amylase, lipase, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in mice; RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 (NLRP3), Toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB) in pancreatic tissue; immunohistochemistry was used to measure the positive expression rates of NLRP3, TLR4, and NF-κB in pancreatic tissue; Western blot was used to measure the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group, the model group had diffuse destruction of pancreatic tissue structure, focal dilatation of pancreatic lobular septum, pancreatic acinar atrophy, and massive inflammatory cell infiltration, as well as significant increases in the content of α-amylase, lipase, IL-1β, IL-6, IL-8, IL-18, and TNF-α (all P<0.05), the mRNA expression levels and positive expression rates of NLRP3, TLR4, and NF-κB (all P<0.05), and the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6 (all P<0.05). Compared with the model group, the low-, middle-, and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue, ordered arrangement of pancreatic acinar cells, a small amount of inflammatory cell infiltration, and hemorrhagic foci of pancreatic lobules, as well as significant reductions in the content of α-amylase, lipase, IL-1β, IL-6, IL-8, IL-18, and TNF-α (all P<0.05), the mRNA expression levels and positive expression rates of NLRP3, TLR4, and NF-κB (all P<0.05), and the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6 (all P<0.05). ConclusionQJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins, reducing the release of inflammatory mediators, and preventing the enhancement of inflammatory cascade response.
2.The clinical safety and efficacy of selinexor combined with venetoclax and azactitidine induction therapy in relapsed and refractory acute myeloid leukemia
Li'na LIU ; Yushan CUI ; Yuzhang LIU ; Yaomei WANG ; Pu XIANG ; Lijie LIANG ; Yiran LI ; Baijun FANG
Chinese Journal of Hematology 2024;45(8):772-775
To determine the efficacy and safety of selinexor combined with venetoclax (VEN) and azactitidine (AZA) for patients with relapsed and/or refractory acute myeloid leukemia (R/R AML) . Twelve patients with R/R AML treated with selinexor plus VEN and AZA in the Affiliated Cancer Hospital of Zhengzhou University from May 2022 to May 2023 were included. Their clinical data were retrospectively analyzed. Among the 12 R/R AML patients, 5 (41.7%) achieved complete remission (CR) , 1 (8.3%) achieved CR with incomplete hematological recovery, and 5 (41.7%) achieved partial remission. The median time to reach CR was 28 (16-59) days. The median PFS was 61 (15-300) days. The main adverse event of the regimen was hematological toxicity. No chemotherapy-related deaths were observed. The combination of selinexor plus VEN and AZA is an effective treatment for R/R AML patients.
3.Risk factors of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemia
Yingling ZU ; Jian ZHOU ; Yanli ZHANG ; Yuewen FU ; Baijun FANG ; Fengkuan YU ; Huifang ZHAO ; Ruirui GUI ; Yanyan LIU ; Zhen LI ; Xudong WEI ; Yongping SONG
Chinese Journal of Internal Medicine 2021;60(1):41-44
Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.
4.Daratumumab for the treatment of primary systemic amyloidosis: a multicenter retrospective analysis
Yang LIU ; Xianghua HUANG ; Wenbing DUAN ; Baijun FANG ; Dongping HUANG ; Yuhui ZHANG ; Lei XU ; Hongyu ZHANG ; Hao ZHANG ; Lei WEN ; Xiaojun HUANG ; Jin LU
Chinese Journal of Internal Medicine 2021;60(11):987-992
Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.
5.Primary plasma cell leukemia with complex karyotype: report of one case and review of literature
Juan WANG ; Lijie LIANG ; Yuzhang LIU ; Lina LIU ; Yaomei WANG ; Pu XIANG ; Baijun FANG ; Yongping SONG
Journal of Leukemia & Lymphoma 2020;29(7):419-422
Objective:To observe the efficacy of the serial treatment with autologous hematopoietic stem cell transplantation after bortezomib and dexamethasone-based triple chemotherapy regimen and followed by lenalidomide and intermittent intensive therapy in primary plasma cell leukemia.Methods:A retrospective analysis was made on the clinical data of one patient who was diagnosed as primary plasma cell leukemia with complex karyotype in April 2018 in Henan Cancer Hospital, and the relevant literature was reviewed.Results:The patient received multiple cycles of bortezomib and dexamethasone-based triple chemotherapy regimen, then received autologous hematopoietic stem cell transplantation, lenalidomide and intermittent intensive therapy. The patient eventually achieved complete remission and the progression-free survival time was 18 months until the day before the deadline for this article.Conclusion:The treatment with autologous hematopoietic stem cell transplantation after bortezomib and dexamethasone-based triple chemotherapy regimen and followed by lenalidomide and intermittent intensive therapy may improve the prognosis of patients with primary plasma cell leukemia and prolong the survival time.
6.Analysis of the clinicopathologic features as well as diagnosis and treatment of 59 patients with Castleman disease
Juan WANG ; Lijie LIANG ; Yaomei WANG ; Zhenyang MEI ; Yuzhang LIU ; Li’na LIU ; Baijun FANG ; Yongping SONG
Chinese Journal of Hematology 2020;41(8):666-670
Objective:To investigate the clinicopathologic features, treatment, and prognosis in patients with Castleman disease (CD) .Methods:We retrospectively analyzed the clinicopathologic data of 59 patients for whom a diagnosis of Castleman disease was confirmed using pathological examination from October 2011 to October 2019 at the Henan Cancer Hospital. The patients were divided into the following two groups as per the following clinical classifications: unicentric CD (UCD, n=47) and multicentric CD (MCD, n=12) . Data on clinical manifestations, laboratory findings, treatment, and prognosis were analyzed. Results:There was no significant difference in the median age and the ratio of male to female between the UCD and MCD. UCD was characterized by asymptomatic enlargement of the single lymph node. The main pathological type was hyaline vascular histopathology (83.0%) . Of these, 44 patients chose surgical resection, and their prognosis was good. Treatment. MCD was characterized by multiple enlarged superficial and/or deep lymph nodes with B symptoms, weakness, and hepatosplenomegaly. Anemia, hypoproteinemia, and globulin level were increased on laboratory examinations. Plasmacyte histopathology was the main pathological type and was present in about 50.0% of the subjects. Only chemotherapy was performed for these MCD patients, followed by chemotherapy or chemotherapy followed by radiotherapy, and the efficient was 58.3% (7/12) .Conclusions:UCD, characterized by asymptomatic enlargement of the single lymph node, shows good postoperative prognosis. MCD has relatively complex clinical manifestations and poor prognosis, and optimal treatment is yet to be established.
7.Primary testicular diffuse large B-cell lymphoma: a single center experience
Shiming ZHAO ; Tiejun YANG ; Chaohong HE ; Baijun FANG ; Yanyan LIU ; Zhihua YAO
Chinese Journal of Urology 2019;40(2):132-135
Objective To review the experience of the clinical diagnosis and treatment of primary testicular diffuse large B-cell lymphoma.Methods A review was made who were treated in the Tumor Hospital of Zhengzhou University from January 2011 to November 2018.The average age of the patients was 58 years old,with 4 cases in left side and 8 cases in right side.All patients were admitted to hospital with painless testicle mass.Solid mass of testis were detected by ultrasound with no abnormality in tumor markers.All patients underwent orchiectomy and followed by chemotherapy.Results Twelve primary testicular lymphoma (PTL) were identified by pathology,with 8 cases in phase Ⅰ,2 cases in phase Ⅱ,1 case in phase Ⅲ,and 1 case in phase Ⅳ.The mean follow-up was 31 months.Inguinal orchiectomy was recommended as a diagnositc and initial therapy.All patients underwent R-CHOP/CHOP chemotherapy consisting of cyclophosphamide,doxorubicin,vincristine and prednisone with or without rituximab,including 6 cases with R-CHOP and 6 cases with CHOP.Nine of 12 patients underwent intrathecal prophylatic chemotherapy and 6 of 12 patients underwent contralateral testicle radiotherapy.Relapse occured in 2 patient with CHOP in central nervous system and died of the disease.One case with CHOP relapsed in abdominal cavity.No contralateral testicle relapse was observed.Conclusions PTL is a rare extranodal lymphoma.Painless testicle tumor in men over 50 years old should suspect of this disease.Inguinal orchiectomy is an important part of the treatment,which combines systemic chemotherapy and prophylactic modalities such as radiotherapy of contralateral testis and/or central nervous system (CNS) prophylaxis.
8. Clinical features and management of primary bladder lymphoma
Shiming ZHAO ; Tiejun YANG ; Chaohong HE ; Baijun FANG
Chinese Journal of Urology 2019;40(10):753-756
Objective:
To summarize the clinical experience of primary bladder lymphoma.
Methods:
From September 2012 to May 2019, 8 cases of primary bladder lymphoma treated in our institute were analyzed retrospectively, including 4 males and 4 females. The mean age was 50.5 years old, ranged from 15 to 85. There were 3 cases of localized bladder lymphoma and 5 cases of metastatic bladder lymphoma. Three cases presented with painless gross hematuria primarily and 5 cases suffered from abdominal pain and bloating. Imaging examination showed the bladder tumor or pelvic mass with maximum diameter ranged from 3 to 22 cm, with 11.3 cm on average. Preoperative diagnosis of bladder tumor in 3 cases, and pelvic malignant tumor in 5 cases. Two patients underwent TURBT and 6 cases underwent pelvic mass resection and partial cystectomy.
Results:
Postoperative pathological diagnosis showed 6 cases of diffuse large B-cell lymphoma, 1 case of mucosa-associated lymphoid tissue lymphoma, 1 case of anaplastic large cell lymphoma. Follow-up after surgery ranged 3 to 60 months, with 28.1 months on average. Two patients can not tolerate radiotherapy or chemotherapy for postoperative complications of vesico-vaginal fistula and intestinal fistula, and both were alive at the last follow-up. Six patients underwent CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone), 3 cases were addd with rituximab. Three patients died during the follow-up. One 85-year-old patient died 10 months after surgery. Two cases of metastatic bladder lymphoma died 3 or 6 months after surgery respectively. Three cases were alive after chemotherapy, including 2 young patients undergoing chemotherapy with DICE regime and one patient undergoing pelvic radiotherapy.
Conclusion
The primary bladder lymphoma has no special clinical symptoms, and TURBT and needle biopsy are critical for the diagnosis, based on the pathological and immunohistochemical examination. The most common pathological type is diffuse large B-cell lymphoma. R-CHOP chemotherapy is recommended, which can be followed by DICE regime for young patients. Metastasis and aging predict poor prognosis.
9. The role of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia
Mingyue ZHAO ; Yuewen FU ; Qian WANG ; Hao AI ; Yongqi WANG ; Jian ZHOU ; Baijun FANG ; Xudong WEI ; Yongping SONG
Chinese Journal of Hematology 2019;40(9):726-731
Objective:
To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) .
Method:
The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases.
Results:
There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %.
Conclusion
The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.
10.A comparative study of unrelatedversus matched-sibling donor allogeneic hematopoietic stem cell transplantation for leukemic children
Binglei ZHANG ; Jian ZHOU ; Yanli ZHANG ; Ruirui GUI ; Yuewen FU ; Yingling ZU ; Fengkuan YU ; Huifang ZHAO ; Zhen LI ; Baijun FANG ; Xudong WEI ; Yongping SONG
Chinese Journal of Organ Transplantation 2019;40(2):116-120
Objective To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemic children .Methods Clinical data of 54 leukemic children undergoing allo-HSCT were retrospectively analyzed from May 2006 to March 2018 .According to the source of donor ,they were divided into matched sibling donor allo-HSCT group (MSD ,n = 27 ) and unrelated donor group (URD ,n= 27) .The clinical outcomes of leukemic children receiving URD allo- HSCT were assessed and those in MSD allo-HSCT group were enrolled as control .Results One patient with refractory AML was not implanted in URD group and the remaining 53 cases were successful in hematopoietic reconstitution .The time of neutrophil and platelet ,the incidence of acute graft-versus-host disease (aGVHD ) , chronic GVHD (cGVHD ) , generalized cGVHD and their transplant-related complications including pulmonary complications ,hemorrhagic cystitis between two groups were not statistically different (P> 0 .05) .The incidence of serious aGVHD ,cytomegalovirus (CMV) and EB virus (EBV) infection was significantly higher in URD group than that in MSD group (P< 0 .05) .The proportion of non-recurrent deaths in URD and MSD groups was 80% and 31 .3% respectively and the difference between two groups was statistically significant ( P = 0 .041) .The 3- year disease-free survival rate (DFS) of URD group and MSD group was (52 .9 ± 9 .8 )% ,(38 .5 ± 8 .7 )% and the overall 3-year survival rate (OS) was (57 .9 ± 9 .5)% and (46 .5 ± 9 .7)% respectively . The inter-group difference was not statistically significant ( P > 0 .05 ) .Conclusions In leukemic children ,although the incidence of complications post URD allo-HSCT is significantly increased , the prognosis is comparable to MSD allo-HSCT .It is a good choice when there is no suitable sibling donor .

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