1.Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient
Rui ZOU ; Xiao ZHOU ; Hailing LIU ; Peng WANG ; Fan XIA ; Liqing KANG ; Lei YU ; Depei WU ; Zhengming JIN ; Changju QU
Cancer Research and Treatment 2023;55(4):1363-1368
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.
2.Research progress of interleukin-6 in pancreatic diseases
Rong LI ; Hao SHI ; Hao CHEN ; Ankang WANG ; Zhengming LEI ; Wenguang FU
Chinese Journal of Hepatobiliary Surgery 2020;26(6):476-480
Acute pancreatitis, chronic pancreatitis and pancreatic ductal adenocarcinoma are common pancreatic diseases. Interleukin-6 (IL-6) is a multipotent cytokine, which plays an important role in the differentiation of the severity of pancreatic diseases, prognosis and treatment of pancreatic diseases. This article reviews recent studies on the role of IL-6 in pancreatic diseases.
3.Application of APRI score and FIB-4 index in prognostic evaluation of patients with chronic liver failure
Zhengming GE ; 浙江省台州恩泽医疗中心(集团)恩泽医院公共卫生中心 ; Zerun DENG ; Lei YAO ; Lihua SUN ; Yuexin ZHANG ; Xiaobo LU ; Xiuhang ZHANG
Chinese Journal of Clinical Infectious Diseases 2017;10(5):341-346
Objective To assess the prognostic value of APRI score and FIB-4 index for patients with chronic liver failure.Methods Clinical data of 426 patients with chronic liver failure admitted in the First Affiliated Hospital of Xinjiang Medical University from March 2005 to September 2014 were retrospectively analyzed.The MELD score,APRI score and FIB-4 index were calculated.Patients were divided into survival group and fatal group according to survival situation within 3 month after admission.Logistic regression was used to analyze the differences in all the indexes between the survival group and fatal group.Receiver operating characteristic (ROC) curve was used to assess the value of the above indexes in predicting the 3-month survival.Results Among 426 patients 244 died within three months after admission.Univariate analysis and multivariate Logistic regression showed that MELD score and FIB-4 index were statistically significant between the survival and fatal groups (Z =-4.783 and-4.104,x2 =26.31 and 11.34,both P < 0.01).The area under the ROC curve of MELD score,APRI score and FIB-4 index was 0.635,0.511 and 0.616 for predicting 3-month survival,respectively.Compared with the APRI score,MELD score and FIB4 index were statistically different (x2 =13.669 and 6.341,P < 0.05 or P < 0.01).When MELD score > 28,FIB-4 index > 11.27,the patient has a high fatality rate and poor prognosis within three months.Conclusion FIB-4 index can be used to evaluate the short-term prognosis of patients with chronic liver failure,and the higher score of FIB-4 index predicts the worse prognosis.
4.An analyses of 104 cases spontaneous rupture of hepatocellular carcinoma
Jin LI ; Zhengming LEI ; Wenguang FU
Chongqing Medicine 2016;45(27):3783-3784,3787
Objective To investigate the clinical management of Spontaneous rupture of hepatocellular carcinoma(SRHCC) . Methods This was a retrospective review of the clinical data of patients with SRHCC who underwent treated in the affiliate hospi‐tal of Luzhou medical college from January 2001 to December 2014 .Results Among 104 patients ,small hepatocellular carcinoma (<5 cm) were found in 11 cases ,and large hepatocellular carcinoma(>5 cm) in 93 cases .Thirty‐one cases which underwent surgi‐cal treatment ,were cured;44 underwent transcatheter arterial embolization (TAE) ,5 cases died of liver function failure;29 cases were treated conservatively ,11 cases died of huge bleeding ,18 cases gave up discharged .Twenty‐two small and medium‐sized SRH‐CC cases underwent hepatectomy survived 1to‐10 years ;8 huge sized SRHCC cases survived 5to‐13 months;one case who under‐went partial filling pressure hemostasis and hepatic artery ligation ,but died of tumor rupture again after 34 days .Sixteen cases un‐derwent TAE were followed up ,14 cases survived 3to‐10 moths ,the survival time of two cases were 3 years and 5 years ,respective‐ly .Conservative treatment group has not been followed up .Conclusion The tumours should be surgical resection as soon as possi‐ble in those whose lesions confined to the liver and may be removed ,systemic condition is good;TAE should be used for other pa‐tients .
5.Treatment of massive variceal bleeding secondary to localized pancreatitis-associated portal hypertension
Zhengming LEI ; Jiaqi DENG ; Wenguang FU ; Jing LI
Chinese Journal of Hepatobiliary Surgery 2016;22(12):819-821
Objective To study treatment of massive variceal bleeding secondary to localized pancreatitis-associated portal hypertension (MVBPAPH).Methods A retrospective study on the clinical data of patients with MVBPAPH was carried out.Of 24 patients with MVBPAPH,20 had pancreatic pseudocysts.12 were operated after failure of treatment with endovascular intervention for variceal bleeding (including 10 patients with splenectomy and gastric fundus-body peripheral vessels amputation and 2 patients with pancreatic pseudocystogastrostomy).8 patients underwent partial splenic embolization and left gastroepiploic artery embolization.4 patients directly underwent splenectomy and gastric fundus-body peripheral vessels amputation for variceal bleeding.Results Left pleural effusion developed in 5 patients who underwent arterial embolization.Left pleural effusion and lung infection occurred in 2 patients who underwent operation.All patients recovered well and were discharged home.During the follow-up period of 2 to 72 months,no rebleeding occurred in these patients (including 2 patients had passed little interval melena).Gastroscopy re-examination showed that variceal veins were not found in 18 patients.Variceal veins which were detected in the remaining 6 patients were obviously less severe.Conclusion Individualized treatment should be given to patients with MVBPAPH and according to the specific type of pancreatitis and the onset time of any accompanying pseudocyst.
6.Clinical application of modified skin soft tissue expansion in early repair of devastating wound on the head due to electrical burn.
Jin LEI ; Chunsheng HOU ; Peng DUAN ; Zhengming HAO ; Yanbin ZHAI ; Yanbin MENG ; Email: M64225@163.COM.
Chinese Journal of Burns 2015;31(6):406-409
OBJECTIVETo observe the clinical effect of modified skin soft tissue expansion in repair of devastating wound on the head due to electrical burn in the early stage.
METHODSTwenty-one patients with partial scalp soft tissue defect accompanying skull exposure and necrosis in different degree due to high-voltage electrical burn were hospitalized from April 2009 to October 2014, with wound area ranging from 7 cm × 5 cm to 15 cm × 13 cm. The wounds were debrided as early as possible, and necrotic skulls were kept in situ and covered with porcine ADM and silver-containing dressing. Bacterial culture of exudate from the residual soft tissue was carried out 3 days after hospitalization. Pertinent antibiotics were applied topically to control infection, and autologous split-thickness skin grafts were transplanted. Two to three weeks after injury when the skin grafts survived, modified skin soft tissue expansion was carried out. The crossbow-form incision was made on the normal scalp 2 cm away from the edge of transplanted skin; a capsule cavity was formed by ladder-like dissection. An expander was inserted with the injection port laying outside. The expander was stretched by inflation and deflation. The incisions were sutured layer by layer. The time of continuing negative pressure drainage in the interval of expansion was extended. Volume of water reaching 2 to 3 times of the capacity of expander was injected for excessive expanding. The expanded skin flap was rotated to repair the wound after expansion was ended.
RESULTSWithin 1 week after debridement, 4 kinds of bacteria were detected in the bacterial culture of wound exudate, including 4 cases of Staphylococcus aureus, 5 cases of Staphylococcus epidermidis, 5 cases of Pseudomonas aeruginosa, and 3 cases of Acinetobacter baumannii. A total of 26 expanders were imbedded. No infection or incision dehiscence in the expanding area or cracking and leakage of expander was observed during expanding period. Two to three months after injury, expanded skin flap transplantation was completed, and the wound was repaired. Raw wounds were seen in 4 expanded skin flaps after transfer, and they healed after dressing change. Punctiform ulceration at the seams of 2 flaps was observed one month after the operation, which healed after removing few pieces of sequestra by themselves. The other expanded skin flaps survived well. During the postoperative follow-up for 3 to 12 months, satisfactory appearance and hair growth was observed in the operation area.
CONCLUSIONSRepair of the devastating wound on the head due to electrical burn with modified skin soft tissue expansion could achieve the result of early wound covering and cosmetic repair without alopecia in one time.
Animals ; Bandages ; Burns, Electric ; surgery ; Craniocerebral Trauma ; surgery ; Debridement ; Female ; Head ; Humans ; Male ; Middle Aged ; Necrosis ; Postoperative Complications ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Skull ; Soft Tissue Injuries ; surgery ; Staphylococcus aureus ; Surgical Flaps ; Swine ; Tissue Expansion ; Treatment Outcome ; Wound Healing
7.Effects of leptin on BSEP protein expression and signaling pathway in HepG2 cells
Jingyu HE ; Zhengming LEI ; Jian WEN ; Wenguang FU
Chinese Journal of Pathophysiology 2015;(5):877-881
AIM:To investigate the effects of leptin on the expression of bile salt export pump ( BSEP) and signaling pathway in human hepatocellular carcinoma cell line HepG2.METHODS: HepG2 cells were cultured in vitro. Leptin at concentrations of 10 -8 , 10 -7 and 10 -6 mol/L was used as a stimulating factor.The protein levels of adenosine monophosphate-activated protein kinase alpha subunit (AMPKa), phosphorylated AMPKa (p-AMPKa) and BSEP in the HepG2 cells at 24 h, 48 h and 72 h were detected by Western blotting.The optimal culture time and leptin concentration were selected, and compound C at concentration of 10 μmol/L was added to this group.The protein expression of BSEP was detected by Western blotting.RESULTS:Intervention of HepG2 cells with leptin for 72 h increased the protein ex-pression of AMPKa gradually in a concentration-dependent manner, and leptin at concentration of 10 -6 mol/L induced the strongest AMPKa expression ( P<0.01 ) .Intervention of HepG2 cells with leptin for 24 h increased the phosphorylation level of AMPKa gradually in a dose-dependent manner (P<0.01).The effect of leptin on the increase in the protein ex-pression of p-AMPKa was also in a time-dependent manner ( P<0.01) .After intervention with different concentrations of leptin for 24 h, the protein expression of BSEP in the HepG2 cells was gradually increased by the stimulation of leptin in a concentration-and time-dependent manner (P<0.01).Compared with NC group, the protein expression of BSEP in 10 -6 mol/L leptin group and 10 -6 mol/L leptin+10μmol/L compound C group was increased at 72 h (P<0.01), and that in 10-6 mol/L leptin+10 μmol/L compound C group was lower than that in 10 -6 mol/L leptin group at 72 h ( P<0.01 ) . CONCLUSION:Leptin promotes the protein expression of BSEP in HepG2 cells by leptin-AMPK-BSEP signaling path-way.Leptin promotes the increases in AMPKa protein and the level of phosphorylation of AMPKa in HepG2 cells.
8.To evaluate hepatic functional reserve and operational risks of primary hepatic carcinoma in Child A using functional CT
Yunchuan XIE ; Zhengming LEI ; Guangcai TANG ; Yongshu LAN ; Guidong DAI ; Jianfei HU
Journal of Practical Radiology 2014;(10):1670-1673
Objective To evaluate hepatic functional reserve and operational risks of primary hepatic carcinoma in Child A using functional CT.Methods In 128 cases of primary hepatic carcinoma of Child A undergoing hepatoectomy and identified by pathology, CT perfusion scanning and measurement of remannent hepatic volume were done before operation and whole patients were divided in-to acute hepatic failure group(AHF group,33 cases)and non-acute hepatic failure(non-AHF group,95 cases).All variables were ana-lyzed by one way analysis of variance(one-way ANOVA)firstly.The variables with significance (P<0.05)were analyzed with Step-wise Logistic regression further.Results One-way ANOVA result:There were significant difference between two groups in RHVS measured by CT,PVP,HBF,HBV,serum creatinine,thrombinogen activity,total bilirubin and intraoperative blood loss (P<0.05).The StepwiseLogistic regression analysis demonstrated that decreased RHVS and the lowed PVP were the independent risk factors of AHF complicated to hepatoectomy of primary hepatic carcinoma(P<0.01).Conclusion Hepatic functional reserve and operational risks of primary hepatic carcinoma could be j udged with functional CT before operation .
9.The change in clinical presentation of patients with hepatobiliary stones: an analysis of 2 359 patients treated in a single hospital
Zhengming LEI ; Jian WEN ; Wenguang FU ; Jing LI
Chinese Journal of Hepatobiliary Surgery 2014;20(2):86-88
Objective To review the clinical presentation of patients with hepatobiliary stones (HS).Method 2 359 patients with HS were divided into group A and B according to the presentation of these patients before or after 2002.Their clinical data were retrospectively analyzed.Results The age,the percentage of patients with a case history > 10 years,the admission rate for relapse,the intrahepatic to extrahepatic stone ratio,the number of patients complicated with liver cirrhosis/portal hypertension,the elective operation rate,the ratio of biliary drainage operation,or the ratio of biliary drainage combined with hepatic resection in group B were 54.02 ± 13.54 years,68.99%,53.07%,73.18%,13.41%,80.80%,83.81%,44.74%,respectively.The corresponding figures for group A were 48.65 ± 14.47 years,46.25%,32.0%,62.02%,4.63%,63.92%,41.45%,19.05%,all P <0.01.However,the rates of biliary ascariasis,acute cholangitis of severe type (ACST),hepatic abscess,bleeding or perforation of the biliary tract,non-operative mortality,emergency operation rate and stone residual rate in group B were 6.56%,6.15%,0.84%,0,0,1.71%,5.18%,18.70%,respectively.All these were significantly lower than those in group A (12.11%,33.72%,1.95%,0.37%,0.67%,25.62%,respectively,all P < 0.01).Conclusions The popularization of medical insurance and the increase in hospital admission rate,but not the actual increase in HS,led to the increase in hospitalization of patients.There was a tendency of less patients presenting with severe disease due to delay in treatment.Routine choledochoscopic stone extraction intraoperatively or postoperatively and the increased liver resection rate had decreased the residual stone rate.There should be a strict restriction on the use of choledochojejunostomy.
10.Adult liver hemangioma: natural course and treatment
Zhengming LEI ; Mingxing LI ; Wenguang FU ; Jian WEN ; Jingyu HE ; Tingyu CHEN
Chinese Journal of Hepatobiliary Surgery 2013;(1):4-7
Objective To investigate the natural course and treatment of adult liver hemangioma (ALH).Methods The records of ultrasonography of 2422 patients with ALH were retrospectively reviewed.Results The patients were between 16 and 69 years of age (mean age 42,9± 11.4) with a male to female ratio of 1 ∶ 1.02 (1197/1225).The prevalence rate gradually increased with age after 30 years old.The highest prevalence rate occurred between 40-69 years.ALH was most commonly 1.1-3 cm in size,located in right liver with a solitary lesion.ALHs were bigger and were seen earlier in females than males.Concurrent illness was also more common in females than males.1427 patients had 3 to 8 repeat sonographies.At a follow-up of 42.7±9.5 months,1351 patients had no change in the ultrasonographic pattern or number of haemangiomas.Increasing in size of the lesions was demonstrated in 76 patients.154 patients received operation or interventional treatment.Conclusions The prevalence rate of ALH rose with age.Female sex hormones might accelerate ALH enlargement but they did not induce the formation of ALH.Most ALH remained stable in size and in patterns.Attention should be paid to rule out other illnesses in patients with ALH and with symptoms.

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