Objective:To evaluate the efficacy and adverse effects of 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phel-Tyr3-Thr8-octreotide (DOTA-TATE) in patients with advanced pheochromocytoma and paraganglioma (PPGL). Methods:Sixteen patients with metastatic PPGL, treated with 177Lu-DOTA-TATE in the Affiliated Hospital of Southwest Medical University between April 2020 and December 2023, were retrospectively included. Among these patients, nine were male and seven were female, with an a median age of 44.5(26.5, 51.0) years. Treatment response was assessed based on changes in blood catecholamine level and 68Ga-DOTA-TATE PET/CT imaging. Evaluation criteria included the response evaluation criteria in solid tumors (RECIST) 1.1 and the modified PET response criteria in solid tumors (PERCIST) 1.0. Treatment-related adverse events were graded according to the common terminology criteria for adverse events (CTCAE) 5.0. All patients received long-term follow-up after treatment, with endpoints including disease progression and death. Paired t-test was used to compare laboratory parameters before and after treatment. Results:The median number of treatment cycles of 177Lu-DOTA-TATE was 3(3, 4) per patient, with an average dose of (7.51±0.67) GBq per cycle. Grade 1 hematologic toxicity was observed in 4 patients (4/16), while grade 2 hematologic toxicity occurred in 2 patients (2/16), primarily manifesting as leukopenia and anemia. A slight decrease was noted post-treatment in PLT ( t=4.06, P=0.001) and Hb levels ( t=2.85, P=0.012), while WBC counts showed no statistically significant change ( t=1.57, P=0.137). No grade 3 or 4 hematologic, renal, or hepatic toxicities were observed. The glomerular filtration rate ( t=-0.29, P=0.778), creatinine ( t=0.04, P=0.697), alanine transaminase ( t=0.08, P=0.938), aspartate transaminase ( t=0.08, P=0.463), and total bilirubin ( t=-0.37, P=0.719) after treatment were not significantly different from those before treatment. According to RECIST 1.1, 13 patients achieved stable disease, 2 patients showed partial response and 1 had progression disease. Based on the modified PERCIST 1.0, stable disease was observed in 11 patients, partial response in 3 patients, and progression disease in 2 patients. Among 9 patients with catecholamine-secreting PPGL, 8 showed reduction in blood norepinephrine level. The median follow-up duration was 21.5(21.1, 42.6) months, with a median progression-free survival of 8.6(6.0, 14.6) months, and no mortality reported during the follow-up period. Conclusion:177Lu-DOTA-TATE appears to be a safe and promising therapeutic option for patients with advanced PPGL demonstrating elevated somatostatin receptor expression.

Objective:To evaluate the efficacy and adverse effects of 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phel-Tyr3-Thr8-octreotide (DOTA-TATE) in patients with advanced pheochromocytoma and paraganglioma (PPGL). Methods:Sixteen patients with metastatic PPGL, treated with 177Lu-DOTA-TATE in the Affiliated Hospital of Southwest Medical University between April 2020 and December 2023, were retrospectively included. Among these patients, nine were male and seven were female, with an a median age of 44.5(26.5, 51.0) years. Treatment response was assessed based on changes in blood catecholamine level and 68Ga-DOTA-TATE PET/CT imaging. Evaluation criteria included the response evaluation criteria in solid tumors (RECIST) 1.1 and the modified PET response criteria in solid tumors (PERCIST) 1.0. Treatment-related adverse events were graded according to the common terminology criteria for adverse events (CTCAE) 5.0. All patients received long-term follow-up after treatment, with endpoints including disease progression and death. Paired t-test was used to compare laboratory parameters before and after treatment. Results:The median number of treatment cycles of 177Lu-DOTA-TATE was 3(3, 4) per patient, with an average dose of (7.51±0.67) GBq per cycle. Grade 1 hematologic toxicity was observed in 4 patients (4/16), while grade 2 hematologic toxicity occurred in 2 patients (2/16), primarily manifesting as leukopenia and anemia. A slight decrease was noted post-treatment in PLT ( t=4.06, P=0.001) and Hb levels ( t=2.85, P=0.012), while WBC counts showed no statistically significant change ( t=1.57, P=0.137). No grade 3 or 4 hematologic, renal, or hepatic toxicities were observed. The glomerular filtration rate ( t=-0.29, P=0.778), creatinine ( t=0.04, P=0.697), alanine transaminase ( t=0.08, P=0.938), aspartate transaminase ( t=0.08, P=0.463), and total bilirubin ( t=-0.37, P=0.719) after treatment were not significantly different from those before treatment. According to RECIST 1.1, 13 patients achieved stable disease, 2 patients showed partial response and 1 had progression disease. Based on the modified PERCIST 1.0, stable disease was observed in 11 patients, partial response in 3 patients, and progression disease in 2 patients. Among 9 patients with catecholamine-secreting PPGL, 8 showed reduction in blood norepinephrine level. The median follow-up duration was 21.5(21.1, 42.6) months, with a median progression-free survival of 8.6(6.0, 14.6) months, and no mortality reported during the follow-up period. Conclusion:177Lu-DOTA-TATE appears to be a safe and promising therapeutic option for patients with advanced PPGL demonstrating elevated somatostatin receptor expression.

Objective To evaluate the effect of berberine on fatty liver ischemia-repeffusion (I/R) injury and the relationship with endoplasmic reticulum stress in liver tissues.Methods Thirty-two male Wistar rats,aged 4 weeks,weighing 100-150 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),fatty liver group (group FL),I/R group and berberine group (group BBR).Rats were fed a normal fat diet for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and rats only underwent simple laparotomy in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,and the other treatments were similar to those previously described in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group I/R.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,berberine solution (300 mg/kg) 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group BBR.Hepatic ischemia was induced by clamping the portal vein,hepatic artery,right gastric vein,and supra-and inferior-hepatic vena cava to perform cold perfusion with 4 ℃ lactated Ringer's solution lasting for 30 min,followed by reperfusion.The serum triglyceride (TG) concentrations were determined after 4,8 and 12 weeks of diet.Blood samples were collected at 6 h of reperfusion for measurement of serum aspartate transminase (AST) and alanine transaminase (ALT) concentrations.Livers were removed after blood sampling at 6 h of reperfusion and liver tissues were obtained and stained with oil red O and haematoxylin and eosin for examination of pathological changes and for determination of the expression of Bip,CCAAT/enhancer-binding protein homologous protein (CHOP),protein kinase RNA-like endoplasmic reticulum kinase (PERK) and phosphorylated PERK (p-PERK) (by Western blot).p-PERK/PERK ratio was calculated.Results Compared with group C,the serum TG,ALT and AST concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,p-PERK/PERK ratio was increased (P＜0.05),lipid deposition was increased,and liver steatosis was found in group FL.Compared with group FL,the serum AST and ALT concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,pPERK/PERK ratio was increased (P＜0.05),and the pathological changes of liver tissues were accentuated in group I/R.Compared with group I/R,the serum TG,ALT and AST concentrations were significantly decreased,the expression of Bip and CHOP was down-regulated,p-PERK/PERK ratio was decreased (P＜ 0.05),lipid deposition was reduced,and the pathological changes of liver tissues were significantly attenuated in group BBR.Conclusion Berberine can ameliorate fatty liver I/R injury,and the mechanism may be related to inhibiting endoplasmic reticulum stress in liver tissues of rats.

Objective To evaluate the efficacy of transversus abdominis plane (TAP) block combined with butopenol patient-controlled intravenous analgesia (PCIA) for analgesia after cesarean section under general anesthesia.Methods Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ parturients,aged 18-42 yr,weighing 52-88 kg,at 38-42 weeks of gestation,scheduled for elective cesarean section under general anesthesia,were divided into 3 groups (n=30 each) using a random number table method:TAP block group (group TAP),butopenol PCIA group (group B) and TAP block plus butopenol PCIA group (group TB).In group TAP,bilateral TAP blocks were performed under ultrasound guidance at the end of surgery,and 0.375％ ropivacaine 20 ml was injected into each side.In group B,butopenol 1 mg was intravenously injected at 30 min before the end of operation,PCIA was performed at the end of surgery,PCIA solution contained butopenol 8 mg and ondansetron 8 mg (diluted to 100 ml in sodium chloride injection),and the PCIA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Butopenol 1 mg was intravenously injected at 30 min before the end of operation,and TAP block in combination with butopenol PCIA was performed at the end of operation in group TB.When the postoperative visual analog scale score was greater than or equal to 4 points,morphine 10 mg was intramuscularly injected as rescue analgesic.The requirement for morphine was recorded within 48 h after operation.The occurrence of agitation during emergence from anesthesia and adverse reactions within 48 h after operation were also recorded.Results No adverse reactions such as hematoma at the puncture site or local anesthetic intoxication were observed in TAP group and TB group.Compared with group TAP,the incidence of postoperative shivering and requirement for morphine were significantly decreased in group TB (P＜0.05).The incidence of postoperative nausea and v omiting and requirement for morphine were significantly lower in group TB than in group B (P＜0.05).Conclusion The combination of TAP block and butopenol PCIA exerts better efficacy for analgesia after cesarean section under general anesthesia than either alone.

Objective To explore the effect of berberine (BBR) on steatotic liver ischemia reperfusion injury and analyze the role of endoplasmic reticulum stress and autophagy .Methods Thirty-four Wistar rats were fed with a high-fat diet for 12 weeks and 2 rats were randomly selected after 8 weeks to observe pathological changes and confirm the model of steatotic liver successfully .Then before opening and closing abdominal cavity ,32 rats were divided into I/R group (normal saline was intragastrically 4 weeks before performing cold I/R treatment) ,BBR group (normal saline was replaced by BBR ,BBR was intragastrically at a dose of 300 mg·kg-1 ·d-1 weeks and others were the same as I/R group) and TG group (TG was intraperitoneally at a dose of 0 .2 mg·kg-124h pre-operation and others were the same as BBR group ) .Then the rats were sacrificed at 6h post-reperfusion .Blood samples were collected from inferior vena cava and hepatic tissues harvested .The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected ,histopathologic changes observed by Hematoxylin & Eosin (HE) staining ,oxidative stress and inflammation determined by ELISA kit and the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 detected by Western blot .Results As compared with Sham group ,the serum levels of ALT and AST were significantly higher in I/R ,BBR and TG groups (P < 0 .05) .And hepatic histological changes were severe and oxidative stress increased in parallel with the enhancement of pro-inflammation (P< 0 .05) .In BBR group ,the level of hepatic enzymes declined ,liver injury was milder ,oxidative stress decreased and pro-inflammation was lesser compared with I/R and TG groups (P< 0 .05) .Additionally ,as compared with sham group ,the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 were up-regulated in I/R and BBR groups (P < 0 .05) .TG group increased the levels of LC3 ,Beclin-1 and p62 (P< 0 .05) .Interestingly ,compared with I/R group ,BBR pretreatment down-regulated the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 (P< 0 .05) .TG group had the higher expressions of LC3 ,Beclin-1 and p62 than those of BBR group (P< 0 .05) .Conclusions BBR pretreatment can protect steatotic liver ischemia reperfusion injury .And the mechanisms may be attributed to the inhibitions of endoplasmic reticulum stress and autophagy .

Objective To study the risk factors and prognosis of post-transplant diabetes mellitus (PTDM) in recipients with steatotic donor livers.Method The clinical data of 182 patients who underwent liver transplantation from donors with liver steatosis in Tianjin First Central Hospital from June 2002 to December 2010 were retrospectively analyzed.There were sixteen patients with PTDM and one hundred sixtysix without PTDM.The clinical data of these patients were compared and the risk factors were evaluated by COX regression analysis.The 1-,3-,5-year cumulative survival rates were analyzed after liver transplantation.Result The variables which included sex,pretransplant serum creatinine level,model for end-stage liver disease (MELD) score,intraoperative red blood cell transfusion,and post-transplant biliary complications were significantly different between the two groups.Multivariate Cox regression analysis showed that living-donor,pretransplant fasting blood glucose and post-transplant biliary complications could affect the survival time of patients in PTDM group.The 1-,3-and 5-year cumulative survival rates in the PTDM group were 81.3％,68.8％ and 62.5％,which were significantly lower than those in the non-PTDM group (95.2％,86.1％ and 80.7％ respectively,P ＜ 0.05).Conclusions Living-donation,pretransplant fasting blood glucose and post-transplant biliary complications had a worse prognosis in the PTDM group.A comparatively better long-term survival after liver transplantation can be achieved by reducing the risk factors and the occurrence of PTDM.

Objective To evaluate the effects of fructose-1 ,6-diphosphate (FDP) pretreatment on lung injury induced by hepatic cold liver ischemia-reperfusion in rats .Methods Eighteen healthy male Sprague-Dawley rats were randomly divided into 3 groups (n= 6 each) using a random number table :sham operation group (S group) ,hepatic cold liver ischemia-reperfusion model group (M group) ,and FDP pretreatment group (FP group) . The animals were anesthetized with intraperitoneal chloral hydrate and kept spontaneous breathing .Laparotomy was performed ,and the related blood vessels were only isolated in group S .Hepatic cold ischemia-reperfusion was induced in M and FP groups .In FP group ,FDP 250 mg/kg was injected via the caudal vein at 15 min before skin incision .At 6 h of reperfusion ,the bronchoalveolar lavage fluid (BALF) was collected to detect the levels of tumor necrosis factor-α(TNF-α) ,interleukin-10 (IL-10) and nitric oxide (NO) by ELISA .Lungs were removed for microscopic examination of the pathological changes by light microscopy .Real-time PCR was used to detect the expression of iNOS mRNA .Results Compared with S group , the levels of TNF-α and NO in BALF were significantly increased , the expression of iNOS mRNA was up-regulated , and the level of IL-10 in BALF was decreased in M and FP groups ( P<0.05 ) .Compared with M group ,the levels of TNF-αand NO in BALF were significantly decreased ,the expression of iNOS mRNA was down-regulated ,and the level of IL-10 in BALF was increased in FP group ( P<0.05 ) .The pathological changes of lungs were significantly attenuated in FP group as compared with M group .Conclusion FDP pretreatment can obviously attenuate lung injury induced by hepatic cold ischemia-reperfusion in rats ,and inhibition of iNOS expression ,reduction of NO synthesis ,and decrease in inflammatory responses are involved in the mechanism .