Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

Objective:To investigate the clinical profile of primary bilateral macronodular adrenal hyperplasia(PBMAH) and sex difference.Methods:One hundred and forty cases of PBMAH were recruited in our center from 2014, and all patients were evaluated for hormone secretion, adrenal imaging, and metabolic parameters.Results:Overt Cushing′s syndrome accounted for 76.4% of PBMAH cohort and 47.9% were female. The overt group had higher serum cortisol and 24 h urinary free cortisol levels, lower adrenocorticotropic hormone, higher serum cortisol after low-dose dexamethasone suppression tests, larger total adrenal size, and a higher percentage of obesity, hypertension, diabetes mellitus, and hypokalemia than the subclinical group(all P<0.05). When compared with the male group, the female group had smaller adrenal size( P<0.001), lower HbA 1C( P=0.003), higher total cholesterol( P=0.005), and lower density lipoprotein-cholesterol levels( P=0.035). Further, 24 h urinary free cortisol in the male group was found to be positively correlated with diastolic blood pressure, fasting glucose, 2 h postprandial glucose after oral glucose tolerance test(OGTT), and HbA 1C after adjusted for age, body mass index, and onset duration, and was negatively correlated with body mass index and potassium levels. While 24 h urinary free cortisol in the female group was positively correlated only with diastolic blood pressure, fasting glucose, and 2 h postprandial glucose after OGTT(all P<0.05). During follow-up, 80.0% of patients achieved remission after unilateral adrenalectomy, with a recurrence rate of 17.9%. Conclusion:PBMAH related metabolic disorder is more pronounced in overt Cushing′s syndrome and males. Unilateral adrenalectomy as an effective treatment can benefit the majority of patients.

Objective:To analyse the risk factors of biliary leakage after surgical resection in patients with perihilar cholangiocarcinoma (PHCC).Methods:The medical data on 179 patients who underwent surgical resection for PHCC at the Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University from April 2000 to April 2020 were collected, and 160 patients were finally enrolled into this study. There were 86 males and 74 females, aged (63.4±10.8) years. The 44 patients with class B biliary leakage and the 5 patients with class C biliary leakage were classified into the biliary leakage group, while the remaining 111 patients were classified into the control group. Risk factors of biliary leakage were analysed by univariate and multivariate logistic regression analyses.Results:Operation time ≥360 min, resection and reconstruction of hepatic hilar vessels on the preserved side of liver and number of bile duct openings of >3 in remnant liver were significantly higher in the biliary leakage than the control group (all P<0.05). Multivariate analysis showed that resection and reconstruction of hepatic hilar vessels on the preserved side ( OR=2.322, 95% CI: 1.078-5.002, P=0.028) and 3 or more bile duct openings in the remnant liver ( OR=2.656, 95% CI: 1.198-5.892, P=0.016) were significantly associated with biliary leakage. Conclusion:Resection and reconstruction of hepatic hilar vessels on the preserved side of liver and 3 or more bile duct openings in remnant liver were independent risk factors for biliary leakage after PHCC resection.

OBJECTIVE：To provide reference for the selection of more economical programmed death- 1（PD-1）/programmed death-ligand 1（PD-L1）inhibitors for National Medical Insurance List and the quality improvement of related economic evaluation. METHODS：Retrieved from CNKI ，VIP，Wanfang database ，PubMed，Web of Science and Ovid Embase ，economic evaluation studies including listed PD- 1/PD-L1 inhibitors of China were collected during the inception to Oct. 2020. CHEERS checklist was used to evaluate the quality of the included literatures ，and the methodological characteristics and economic evaluation results of the included studies were analyzed systematically. RESULTS ：A total of 14 literatures were included ，all of which were model-based and with moderate or high quality. However ，there were still some deficiencies in the included literatures ，mainly manifesting as the insufficient reports on the reasons for setting or selecting model parameters ，as well as the great uncertainty of clinical effect data and utility value. Only 3 of the 8 PD-1/PD-L1 inhibitors listed in China were involved in the included literatures. Compared with chemotherapy or targeted therapy plan ，9 literatures（64.29％）showed that the therapy plan containing PD- 1/PD-L1 inhibitors was not cost-effective. CONCLUSIONS ：The economic evidence of domestic PD- 1/PD-L1 inhibitors is lacking ，the higher price of imported PD- 1/PD-L1 inhibitors lead to poor economic performance. The existing economic evaluations has some shortcomings in methodological application and parameter selection. Pharmaceutical enterprises should fill in the data gaps and adjust the pricing strategy，researchers should improve the standardization of research ，and medical insurance decision-making departments should improve the judgment on the quality of economic evidences ，so as to promote more economical drugs to be included in the National Medical Insurance List.

Objective:To evaluate clinical and pathological factors related to the actual 5-year survival of patients with hilar cholangiocarcinoma (HCC).Methods:A total of 94 HCC patients who underwent radical surgery at the Department of Hepatobiliary and Pancreatic Surgery, Li Huili Hospital of Ningbo Medical Center from Jan 2000 to Jun 2015 were enrolled in this study.Patients were divided into two groups: postoperative survival group beyond 5 years and death group within 5 years. The clinical and pathological features of the two groups were analyzed.Results:Of the 94 patients, 19 (20.2%) had a postoperative survival time of more than 5 years. The actual 5-year overall survival rate of HCC patients (20.2%) was lower than that estimated by Kaplan-Meier survival analysis (22.2%). Gender, age, CEA value, CA199 value, total bilirubin, Child-Pugh classification, Bismuth classification and preoperative jaundice reduction were not significantly different between the two groups nor there were significant difference between two groups in operation time, blood loss, surgical procedure, combined caudate lobectomy, combined pancreaticoduodenectomy, combined resection of surrounding organs, vascular reconstruction and number of bile duct orifices in remnant liver surface. There were significant differences between two groups in the variables of pathological phenotype ( P=0.012), lymph node metastasis ( P=0.001) and resection level ( P=0.048). Conclusion:Non-papillary type, lymph node metastasis and R 1 resection are the independent risk factors of the actual 5-year survival.

Objective:To investigate the efficacy and nephrotoxicity of high-dosepolymyxin B (PMB) in treatment of patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) infections.Methods:Clinical data of 90 patients with MDR-GNB infections who admitted to the Affiliated Huaian First People′s Hospital from January 2018 to December 2020 were retrospectively analyzed. Thirty one patients receivedhigh-dose PMB(≥25 000 U·kg?1·d?1) for treatment (high-dose group) and 59 patients received standard-dose PMB(<25 000 U·kg?1·d?1) for treatment (control group). The curative effect and renal function of the two groups were compared. The factors related toacute kidney injury (AKI) were analyzed with logistic regression.Results:The daily PMB dose and treatment course in high-dose group were (29 800±4 500) U/kg and (9.16±4.15) d, while those of the control group were (17 300±3 500)U/kg and (7.32±3.87) d ( P<0.01). The effective rate of the high-dose group was higher than that of control group (83.9% vs. 61.0%, χ2=4.95, P<0.05).The creatinine levels in high-dose group were increased significantly from 69.40(47.00, 94.70)μmol/L before treatment to 116.20(59.20, 213.20)μmol/L after treatment ( Z=-2.99, P<0.01); while there were no significant changesin control group before and after treatment [55.00(37.00, 92.47)μmol/L vs. 50.10(34.00, 156.00)μmol/L, Z=-1.78, P=0.78]. The 30-day mortality rate in the high-dose group was 32.3% (10/31), that in the standard-dose group was 49.2% (29/59)(χ2=2.36, P=0.12). The AKI incidence rate in high-dose group was higher than that in standard-dose group [ 67.7% (21/31) vs. 45.8% (27/59), χ2=3.94, P=0.04]. There were 4 and 10 deaths due to AKI in the high-dose and standard-dose groups, respectively (χ2=0.25, P=0.61). Logistic regression analysis showed that daily high-dose PMB was independently associated with AKI( OR=2.662, 95% CI:1.082-6.549, P=0.03). Conclusion:Thehigh-dose PMB is effective in treatment of patients with multidrug-resistant Gram-negative bacteriainfections, but the incidence of AKI is also significantly increased. Therefore, when using daily high-dose PMB, the pros and cons must be weighed to avoid increasing the risk of AKI.

Objective To explore the clinical effect of traditional Chinese medicine on lipid metabolism dis-orders in hemodialysis patients.Methods 70 patients with hemodialysis received in the hospital from Novem-ber 2015 to April 2017 were enrolled in the study.They were randomly divided into control group and treat-ment group with 35 cases in each group.The control group was treated with simvastatin and and the treatment group was treated with self-made fat recipe combined with simvastatin.The levels of serum lipid ,serum in-flammatory cytokines ,renal function and liver function ,the total effective rate of treatment and the incidence of adverse reactions were compared between the two groups before and after treatment.Results There were no statistical significances in serum lipid indexes such as triglyceride (TG) ,total cholesterol (TC) ,high densi-ty lipoprotein cholesterol (HDL-C) ,low density lipoprotein cholesterol (LDL-C) ,C reactive protein (CRP) , interleukin 6 (IL-6) ,tumor necrosis factor α(TNF-α) and other serum inflammatory factors ,and renal func-tion indexes ,including urea nitrogen (BUN) ,creatinine (Scr) ,liver function indexes ,including alanine amin-otransferase (ALT) ,aspartate aminotransferase (AST) between two groups before treatment (P＞0.05) ;af-ter treatment ,the TG ,TC ,LDL-C ,CRP ,IL-6 ,TNF-α ,BUN ,Scr ,ALT and AST levels of the patients in the treatment group were significantly lower than those in the control group ;the HDL-C level of the patients in the treatment group was significantly higher than that in the control group ;the total effective rate of the treat-ment group was significantly higher than that in the control group ;the incidence of adverse reactions was sig-nificantly lower than that of the control group ,and the differences were statistically significant (P＞0.05). Conclusion The lipid-lowering effect of treatment of hemodialysis patients with traditional Chinese medicine lipid-lowering treatment is remarkable ,and worthy of promotion.

Objective To explore the protective effects of cannabinoid analogues WIN55212-2 on paraquat poisoned mice. Methods Totally 35 healthy male C57BL/6 mice were randomly(random number) divided into four groups: PQ group (paraquat poisoned, n=10), WIN 1 mg group (PQ+WIN55212-21 mg n=10), WIN 2 mg group (PQ+WIN55212-22 mg, n=10), control group (n=5).The PQ poisoned animal models were established in the PQ group, WIN 1 mg group and WIN 2 mg group by intraperitoneally injection of paraquat with a concentration of 20 mg/kg. Intraperitoneal injection of WIN55212-2 (containing Tween 80 cosolvent) at the concentration of 1 mg/kg and 2 mg/kg was performed 1 h before PQ exposure in the two interfered groups. Equivalent volume of saline was given to the control group. WIN55212-2 was injected twice a week from the second week. In the acute phase (14 d), 5 mice were randomly sacrificed in the PQ group, WIN 1 mg group and WIN 2 mg group, and 3 mice were sacrificed in the control group to obtain blood sample, bronchoalveolar lavage fluid (BALF) and lung tissue. All the remaining mice were executed on day 28, and the tissue samples were collected as mentioned above. HE staining and Masson staining were performed to observe the changes of lung tissues after PQ poisoning. Changes of TNF-α, IL-6 and TGF-β in plasma and BALF were measured by ELISA. Results In the acute phase, the pathological sections of lung tissues in the PQ group, WIN 1 mg group and WIN 2 mg group showed diffuse inflammation, which was improved after the intervention of WIN5522-2, especially in the WIN 1 mg group. IL-6 levels of BALF in the PQ group, WIN 1 mg group, WIN 2 mg group and the control group were (1024.77±124.74)U/L, (620.48±99.76)U/L, (823.29±157.88) U/L, and (180.42±20.22)U/L, respectively. IL-6 levels in the WIN 1 mg group and the WIN 2 mg group were statistically lower than those in the PQ group (P=0.021, P=0.016). However, no difference was found between the two intervention groups(P=0.114). The similar condition was also found in TNF-α in BALF and plasma. In the chronic phase, mice in the PQ group, WIN 1 mg group and WIN 2 mg group showed fibrosis in tissue by HE and Masson staining, and the inflammatory condition was improved after the intervention of WIN5522-2, which was more obvious in the WIN 1 mg group. In BALF, TNF-α level was (321.64±50.54)U/L, (260.23±48.19)U/L, (278.89±29.40)U/L, (89.76 ± 10.87)U/L in the PQ group, WIN 1 mg group, WIN 2 mg group and the control group. Differences were found between the WIN 1 mg group and the control group and the WIN 2 mg group. Similar differences were also observed in plasma TNF-α, but not in TGF-β. Conclusions A small dose of WIN55212-2 can improve the general condition of PQ poisoning mice, and reduce the inflammatory and fibrosis-related cytokines levels in PQ poisoning mice.

Objective To discuss the treatment experience of adrenocorticotropic hormone independent macronodular adrenal hyperplasia (AIMAH).Methods The clinical data of 24 cases of AIMAH from August 1972 to December 2016 were retrospectively analyzed.The cases included 10 males and 14 females with a mean age of 43 (range 26 to 59) years.16 patients presented with typical Cushing syndrome (CS) and 8 patients had weight gain, hypertension or diabetes mellitus without any sign of CS.The circadian rhythm of serum cortisol was abnormal.Low and high dose dexamethasone suppression tests failed to suppress cortisol secretion.The preoperative CT scan showed bilateral enlargement of the adrenal glands with multiple macmnodules.14 patients underwent open surgery, including 5 cases of unilateral adrenalectomy, 6 cases of adrenalectomy combined with contralateral subtotal adrenalectomy and 3 cases of bilateral adrenalectomy simuhaneously.6 patients underwent conventional laparoscopic adrenalectomy,including 2 cases of unilateral adrenalectomy, 2 cases of adrenalectomy combined with contralateral subtotal adrenalectomy and 2 cases of bilateral adrenalectomy.4 patients underwent robot-assisted laparoscopic bilateral adrenalectomy.Results The postoperative pathological examination showed that all patients had bilateral adrenal macronodular or adenomatoid hyperplasia.During the mean follow-up of 68 months (range 3 to 192 months), the clinical symptoms of CS disappeared after surgery in all cases.7 patients who received unilateral adrenalectomy had urinary free cortisol and serum cortisol within normal ranges and no further enlargement of the contralateral gland was noticed.Among the 3 patients who received bilateral adrenalectomy simultaneously, 1 case died of adrenal crisis on the seventh day post-operation.The remaining 2 cases presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy.Nelson's syndrome was not observed in other patients.Conclusions The use of bilateral adrenalectomy to treat AIMAH may involve risk.Unilateral adrenalectomy is recommended for an alternative treatment for AIMAH.Controlateral adrenalectomy with lifelong corticosteroid replacement or contralateral subtotal adrenalectomy may be performed if the symptoms have not improved or recurred after unilateral adrenalectomy.

Objective To explore the efficacy and safety of minimal invasive adrenal sparing surgery for the treatment of Cushing syndrome caused by adrenocortical adenoma.Methods Patients who underwent minimal invasive adrenal surgery for adrenocortical adenoma in our institution from January 2010 to December 2015 were retrospectively analyzed.Preoperative, intraoperative, and postoperative variables were reviewed from the database.The mean patient age at diagnosis was 39 years and male:female ratio was 10:111.Of the 121 adenomas, 50 were located in the right adrenal and 71 in the left.The mean tumor size was 2.6 cm.84 cases had hypertension (69.4％), 36 cases had diabetes mellitus (29.8％), and 45 cases had obesity (37.2％).Postoperative follow-up was performed by evaluating adrenal gland function and imaging.Results Mininal invasive partial adrenalectomy was performed in 121 cases and the success rate of operation was 99.2％ (120/121).Sixty-two cases received operation through retroperitoneal approach,and 59 cases were through transperitoneal approach.The median operative time was 50 min with a median blood loss of 50 ml.The mean postoperative hospital stay were (5.0 ± 3.2) days.The vascular injury occurred in 2 cases (1 case in each surgical approach), while the abdominal organ injury occurred in 2 cases with 1 case of spleen injury and 1 case of liver injury (both in transperitoneal approach).Postoperative complications were observed in 6 cases:1 case of deep venous thrombosis, 1 case of wound hematoma, 4 cases of wound infection.Cortisol substitution was given in 2 to 12 months (mean 6.2 months)postoperatively.One year after operation, the remission rate of hypertension, diabetes and obesity was 58.3％ (49/84), 30.6％ (11/36) and 60.0％ (30/45), respectively.Conclusions Minimal invasive adrenal surgery using retroperitoneal and transperitoneal laparoscopic technique can be performed with low morbidity and achieve an excellent outcome.The perioperative hormone therapy may also play an important role.