OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

Objective:To explore the clinical characteristics, diagnosis and treatment of secondary adrenocortical insufficiency(SACI)after kidney transplantation.Methods:Retrospective analysis was conducted for clinical data of 12 recipients with SACI after transplantation from March 2018 to November 2019(observation group). Meanwhile, 10 healthy subjects(control group)were randomly selected for in-hospital physical reexaminations during the same period. General data and morning cortisol levels of adrenocorticotropic hormone(ACTH)and aldosterone were compared between two groups.Results:In observation group, there were 8 male and 4 female with an average age of (43.67±8.81) years. Six cases(50.0%)of SACI occurred during recovery period within 30 days and 3 cases(25.0%)within 30 to 90 days post-transplantation. Deceased citizen donation(DCD)was performed in 9 cases(75.0%)and re-transplanted in 3 cases(25.0%). Oral immunosuppressive regiments were administered in a low-dose prednisone-based triple/quadruple regimen. The mean eGFR of observation group was(54.08±20.03)ml/min. The first patient had adrenal crisis, the fourth had sole symptom of fatigue and the remainder stayed asymptomatic. All of them had persistent hyperkalemia and hyponatremia. The average level of plasma cortisol was(62.24±24.16)mmol/L and it was much lower than normal in all patients at 8 am. The determination of plasma ACTH at 8 am showed that 7 patients(58.33%)were lower than normal and the remaining 5 slightly surpassed the low limit of normal. The average level of plasma cortisol at 8 am was significantly lower in observation group than that in control group(141.34±26.28)nmol/L( t=-7.349, P<0.001). The average ACTH level of observation group at 8 am was(1.08±0.515)pmol/l and it was significantly lower than that of control group(2.53±1.06)pmol/L( t=-4.178, P<0.001). The level of aldosterone was normal in both groups and showed no significant difference. All patients in observation group received an intravenous injection of hydrocortisone with satisfactory outcomes. Conclusions:Transplant surgeons should be on a high alert for an occurrence of SACI in renal transplant recipients. Serum potassium and sodium levels may be the predictors of SACI.

Objective To explore whether therapeutic dosing timing of proteasome inhibitor bortezomib(BZ) would impact its clinical efficacy .Methods From 2012 to 2018 ,35 biopsy-confirmed cases of acute antibody-mediated kidney transplant rejection (AMR) were collected .They received intravenous immunoglobulin (IVIG) plus sirolimus (Sir) plus bortezomib (BZ) .Three groups were assigned according to dosing timing of BZ .After a diagnosis of AMR ,ET (early treatment ) group began BZ dosing within 7 days (n=16) while DT (delayed treatment) group within 8-14 days (n=11) and LT (late treatment) group > 14 days (n= 8).Their clinical parameters and incidence of complications were analyzed .Results DSA reversal rate of ET ,DT and LT groups was 87 .5％ , 45 .5％ and 25 .0％ (P=0 .006) while DSA declining rate 93 .8％ ,90 .9％ and 50％ respectively (P=0 .019);recurrent rate of AMR was lower in ET/DT group than LT group (6 .6％ vs 10％ vs 75％ , P=0 .042) .No significant differences existed in blood perfusion score of allograft at 1 month post-dosing among three groups .In three groups ,creatinine (Cr) of ET group was lower than DT group at month 1/3/12 while DT group was lower than LT group .No significant difference existed in the incidence of adverse reactions among 3 groups .Conclusions More likely to enter the window period , early dosing of BZ is more effective for treating acute AMR .An earlier intervention yields a better efficacy .

Objective To investigate the effect of preoperative hyperbaric oxygen therapy upon the incidence of hypoxemia in patients after renal transplantation. Methods In the experimental group, 55 patients received hyperbaric oxygen therapy prior to renal transplantation, and 66 counterparts in the control group underwent conventional renal transplantation. Postoperatively, the incidence of hypoxemia, pulmonary infection, time of in-bed oxygen inhalation and length of hospital stay were statistically compared between two groups. Results In the experimental group, 12 among 55 patients (22%) presented with hypoxemia after renal transplantation, and 20 of 66 (30%) in the control group. In the experimental group, 4 cases suffered from pulmonary infection with an incidence of b7%, and 14 (21%) in the control group. In the experimental group, the incidences of hypoxemia and pulmonary infection were lower than those in the control group (both P<0.05). Inthe experimental group, the time of in-bed oxygen inhalation and length of hospital stay were (5.9±2.0) d and (17.7±3.7) d, significantly shorter compared with (6.8±2.6) d and (20.5±4.2) d in the control group (both P<0.05). Conclusions Prior to renal transplantation, hyperbaric oxygen therapy can significantly reduce the risk of hypoxemia and pulmonary infection after renal transplantation, which can be served as a conventional preventive measure against the incidence of hypoxemia following renal transplantation.

Objective To describe the experiences when different methods were used to treat early-onset antibody-mediated rejection (AMR) after kidney transplantation.Methods The clinical data of 42 recipients who experienced early-onset acute AMR after kidney transplantation in our department from Jan.2010 to Apr.2016 were retrospectively analyzed.The recipients were divided into 3 groups based on different strategies against AMR:group A (plasma exchange with intravenous immunoglobin);group B (bortezomib solo),and group C (combination of bortezomib and sirolimus).Results All the AMR episodes were diagnosed by kidney biopsy 9-27 days after transplantation.The AMR reversal rate in groups B and C was significantly higher than that in group A (100％ versus 60.00％,P=0.034;100％ versus 60.00％,P=0.007).The AMR recurrence rate in groups B and C was significantly lower than that in group A (0 versus 41.67％,P =0.035;0 versus 41.67％,P =0.007).The recipient survival rate was 100％ in all the three groups.There were 11 graft losses in group A,and none in group B or C.The graft survival rate in group B at 6 months,1 year and 3 years was significantly higher than in group A (100％ versus 60.00％,P =0.034;100％ versus 55.00％,P =0.021;100％ versus 50.00％,P =0.013).The graft survival rate in group C at 6 months and 1 year was significantly higher than in group A (100％ versus 60.00％,P =0.007;100％ versus 55.00％,P =0.003).There was no significant difference in AMR reversal rate,AMR recurrence rate and graft survival rate between groups B and C.There was no significant difference in incidences of infection,hyperlipidemia and bone marrow suppression among the three groups.The incidence of diarrhea in groups B and C was significantly higher than in group A (50.00％ versus 0,P =0.001;42.86％ versus 0,P =0.001).The incidence of peripheral neuritis in group B was significantly higher than in group A (25.00％ versus 0,P =0.02),but similar to group C.There was no significant difference in average serum creatinine level among three groups within 1 year after treatment (P＞ 0.05).Antibodies against human leukocyte antigen (HLA) and donor specific antibodies were detected in all the 42 recipients before treatment.The negative conversion ratio of panel reactive antibody (PRA) in group A was significantly lower than in groups B and C (10.00％ versus 87.50％,P＜ 0.001;10.00％ versus 92.86％,P ＜ 0.001).The PRA recurrence rate in group A was significantly higher than in groups B and C (85.00％ versus 37.50％,P＜0.001;85.00％ versus 0,P＜0.001),while that in group B was significantly higher than in group C (37.50％ versus 0,P =0.014).The ratio of Treg in peripheral blood at 3-12 month after treatment in group C was significantly higher than in groups A and B (P＜0.05).Conclusion Treatment for early-onset AMR after kidney transplantation based on bortezomib might be an effective and safe strategy.Graft longterm survival might benefit from the combination of bortezomib and sirolimus.

Objective To evaluate the efficacy and safety of retroperitoneal laparoscopic pyelolithotomy ( RLP) combined with holmium laser lithotripsy under flexible cystoscopy in the treatment of complicated nephrolithiasis. Methods The retrospective analysis was made on the clinical data of 37 patients who underwent RLP and holmium laser lithotripsy under flexible cystoscopy for complicated nephrolithiasis from January 2013 to January 2014. The clinic parameters involved basic data of patients,operational time,blood loss,post-operative hospital stay,the status of stone-free,perioperative complications,and the follow-up data of patients were observed. Results No patient was converted to open surgery. The mean stone size was (2. 8 ± 0. 9) cm in diameter,operational time was (89 ± 24) min,blood loss was (21. 3 ± 7. 7) mL,post-operative hospital stay was (6. 8 ± 1. 7) d,the stone removal rate in one session was 94. 6%. One case occurred urinary leakage,1 case occurred fever after operation,who were all recovered through conservative treatment. All cases were followed up at the sixth months after operation. Conclusion RLP combined with holmium laser lithotripsy under flexible cystoscopy is effective and safe for the treatment of com-plicated nephrolithiasis.

Objective To discuss the efficiency and safety of conversion from tacrolimus(Tac)to cyclosporine A(CsA) in patients with new onset diabetes after transplantation (NODAT).Methods The glucose metabolism parameters and related clinical indicators in 45 Tac treated renal transplantation recipients who developed NODAT were retrospectively analyzed.The oral immunosuppressive strategy was Tac + mycophenolate mofetil (MMF) + prednisone(Pred).Results 32 cases were converted to CsA whereas 13 patients stuck to Tac.After conversion,fasting plasma glucose (FPG)decreased from(8.2 ± 2.7)mmol/L to(5.9 ± 1.2)mmol/L(P ＜ 0.01)and HbA1c level decreased from (7.0 ± 0.9) ％ to (6.1 ± 0.7) ％ (P ＜ 0.05).The level of FPG and HbA1c was lower in the conversion group than in the control group(P ＜ 0.05).During the 1-year follow-up,the curative rate of NODAT was 53.1％ (17/32) in the conversion group while it was 0％ in the control group.No acute rejection happened after the conversion.There was no obvious change in renal function.The 1-year survival rate of patient and the transplanted kidney was 100％.Blood pressure and lipid levels were stable after the conversion.Conclusion Conversion from Tac to CsA is a simple and effective strategy to improve glucose metabolism in renal transplantation recipients with NODAT.

Objective To explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells (DCs) in renal allograft recipients. Methods Donor bone marrow monocytes (BMMCs) were isolated and cryopreserved in liquid nitrogen before kidney transplantation. At 0 day, 1month,3 month, 6 month and 9 month post-operation, CD34+ cells which were isolated from frozen BMMCs and cultured into DCs as well as the peripheral blood lymphocytes (PBLs) of donors were used as the stimulating cells to the PBLs of recipients and healthy volunteers. The number of viable DCs from frozen- and room temperature-preserved BMMCs was counted and the reactions of recipients'and healthy volunteers' lymphocytes to DCs and donor PBLs were measured. Results 6. 8 × 107BMMCs were isolated from each 10 ml of donor bone marrow on average while (4. 10 ± 0. 58) × 105CD34+ cells were isolated by magnetic active cell sorting (MACS). There was no significant difference in the isolating rate of recovered CD34+ cells at each observation point postoperatively. The percentage of viable BMMCs and CD34+ was decreased significantly at 1 month after surgery, then, decreased slowly and progressively. The decreasing rate of BMMCs was higher than CD34+. The rate of viable DCs was maintained stable (93. 2%-94. 8% ) in each group. The reactions of recipients' and healthy volunteers' lymphocytes to DCs were stronger than those to donor PBLs (P＜0. 05). The reactions of healthy volunteers' lymphocytes to DCs were maintained stable while those of recipients' were fluctuating. Conclusion Bone marrow-derived DCs are superior to PBLs in mediating long-term lymphocyte reaction after kidney transplantation due to their stable viability and stimulating ability to lymphocytes. Only once collection of a small quality of bone marrow of donors is needed to meet the demand of immune monitoring at any time after transplantation.

ObjectiveTo explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells (DCs) in renal allograft recipients to guide individualized inmunosuppressive therapy. Methods From Jan. 2008 to Jan. 2010, 30 recipients received living related kidney transplantation were successively and divided into 2 groups according to the strategies of the correction of the dosage of immunosuppressant, 15 in each group. The strategy of immunosuppressive therapy in both groups was Tac + MMF + Pred. The correction of the dosage of immunosuppressant in experimental group was conducted by recipient lymphocyte reaction with donor DC (LR) combined with Tac and MPA blood concentration monitoring. Only blood concentration monitoring of drugs was applied in control group. Examinations of liver and renal function, blood and urine routine as well as blood sugar were done monthly for 1 year. ResultsDuring the follow-up period, the rate of acute rejection in experimental group and control group was 13. 3 ％ and 46. 7 ％ respectively (P＜0. 05) ;the rate of infection in experimental group and control group was 6. 7％ and 40. 0％ (P＜0. 05)respectively; the adverse reaction rate in experimental group and control group was 13. 3％ and 46. 7％(P＜0. 05). There was no significant difference in the serum creatinine level between the two groups at each observation point. ConclusionThe application of combined recipient LR with donor DC and blood concentration monitoring of drugs in individualized irnmunosuppressive therapy is more comprehensive and accurate.

AIM: To explore the protective effect of curcumin on high glucose-induced decrease in contraction of isolated rat aortic rings, and to elucidate its underlying mechanism. METHODS: The thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured. HO activity was also evaluated. RESULTS: (1)Four hours after incubated with 44 mmol/L of glucose (high glucose),the vascular contraction responses to phenylephrine (PE) decreased compared to control group (containing 11 mmol/L of glucose). (2)Coincubation with curcumin (3×10~(-11)-3×10~(-10) mol/L) and high glucose,the high glucose-induced decrease in contraction responses to PE of arteries was partly inhibited. (3)Four hours after incubation with curcumin,the HO activity in thoracic aorta increased. ZnPP,an inhibitor of HO-1,completely abrogated the protection effect of curcumin. (4)Methylene blue,an inhibitor of guanylate cyclase (GC),partly abolished the protective effect of curcumin. CONCLUSION: Curcumin prevents the high glucose-induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be mainly involved in the activation of HO-1 and GC.