Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus(T2DM) patients with different disease durations. Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected. They were divided into three groups,short duration group (≤10 years group,n=95),medium duration group (10～20 years group,n=96) and long duration group (≥20 years group,n=97). Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months. Clinical efficacy,blood glucose indices,pancreatic β-cell function and complications during the treatment period were compared among the three groups. Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<0.05). Meanwhile,HDL-C,C-P,HOMA-β and HOMA-IS values showed a significant increase(P<0.05). After treatment,WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<0.05),while HDL-C,C-P,HOMA-β and HOMA-IS decreased in turn in ≤10 years group,10～20 years group,≥20 years group(P<0.05). The BMI of 10～20 years group was lower than that of ≤10 years group and ≥20 years group (P<0.05),while the BMI of ≥20 years group was higher than that of ≤10 years group (P<0.05). Conclusions In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreatic β-cell function,especially for patients with a shorter disease duration.

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus(T2DM) patients with different disease durations. Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected. They were divided into three groups,short duration group (≤10 years group,n=95),medium duration group (10～20 years group,n=96) and long duration group (≥20 years group,n=97). Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months. Clinical efficacy,blood glucose indices,pancreatic β-cell function and complications during the treatment period were compared among the three groups. Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<0.05). Meanwhile,HDL-C,C-P,HOMA-β and HOMA-IS values showed a significant increase(P<0.05). After treatment,WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<0.05),while HDL-C,C-P,HOMA-β and HOMA-IS decreased in turn in ≤10 years group,10～20 years group,≥20 years group(P<0.05). The BMI of 10～20 years group was lower than that of ≤10 years group and ≥20 years group (P<0.05),while the BMI of ≥20 years group was higher than that of ≤10 years group (P<0.05). Conclusions In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreatic β-cell function,especially for patients with a shorter disease duration.

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

Objective: To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) containing cladribine sequential busulfan regimen for refractory/relapsed acute myeloid leukemia (AML) . Methods: The clinical data of 12 refractory/relapsed AML patients received allo-HSCT with cladribine sequential busulfan regimen. Results: ① Of the 12 patients, 9 were males and 3 females, with a median age of 36 (27-50) years. The donors were identical sibling (3) , matched unrelated (1) and haploidentical family member (9) respectively. Nine patients reached partial remission and other remained no remission after chemotherapy before allo-HSCT. The median previous chemotherapy courses before allo-HSCT were 6 (2-13) . ② Conditioning regimen: Smostine 250 mg·m^-2·d^-1, d-7; Cladribine 5 mg·m^-2·d^-1, d-6 to d-2; Cytarabine Arabinoside 2 g·m^-2·d^-1, d-6 to d-2; Busulfan 3.2 mg·m^-2·d^-1, d-6 to d-3; Rabbit anti-human thymocyte immunoglobulin (ATG) 1.5 mg·m^-2·d^-1 (unrelated donor transplantation) or 2.0-2.5 mg·m^-2·d^-1 (haplo-HSCT) , d-4 to d-1. ③ Of the 12 patients, 11 patients attained complete haploidentical engraftment, one case occurred primary graft failure. The median durations for neutrophils and platelet implantations were 15 (15-21) and 19 (17-30) days respectively. ④After conditioning, no hepatic veno-occlusive diseases were observed, hemorrhagic cystitis occurred in 2 patients, 8 patients had fever, 3 cases experienced acute GVHD grade II, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 8 (4-12) months. Leukemia relapse occurred in 2 patients at time of 6, 12 months after allo-HSCT. The estimated 1-year OS and DFS were (71.1±1.8) % and (62.2±1.8) %, respectively. Conclusions allo-HSCT with cladribine sequential busulfan regimen was a feasible choice with favorable outcome for refractory/relapsed AML.

Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.

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.

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.

Objective To investigate the clinical manifestations of early postoperative internal hernia. Methods Patients who were diagnosed with early postoperative small bowel obstruction(EPSBO)within 30 days after operation and underwent laparotomy between 1994 and 2006 were included for study.Clinical and radiological findings were analyzed. Results Totally 38 EPSBO patients were identined.among those,9 patients(23.7%)had an internal hera ag the cause of the howel obstruction.Other causes included intestinal adhesions in 27 patients(71.1%),gallstone ileus in 1 patient(2.6%)and stoma obstruction in 1 patient(2.6%).In the internal hernia group,6 cases were male and 3 cases were female witIl a mean age of 53.6 years.The mean time from the primary operation to symptom development was 7.8 d(range,2～17 d)and the mean time of conservative treatment Was 3.4 d(range,1～8 d).The main clinical features included:complete mechanical obstruction with symptoms rapidly progressing and early bowel strangulation.Specific radiologic abnormalities misht be identified,especially by contrast-enhanced CT.In this series,intestinal strangulation was found in 6 patients with bowel necrosis in 4 eases,necessitating howel resection in 5 patients.Wound infection developed in one cage and there was no perioperative death.Conclusion Internal hernia can occur early postoperatively and it bears a high risk of strangulation and bowel necrosis.Prompt operative intervention should be carried out in highly suspicious patients in order to avoid complications and achieve good outcome.