Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To compare the prognosis of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV)-associated ICC after radical resection.Methods:The clinicopathological and survival data of 69 patients with ICC undergoing radical resection in the Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital Affiliated to Ningbo University from January 2012 to February 2024 were retrospectively analyzed, including 40 males and 29 females, aged (62.9±10.2) years. Patients were divided into the stone group ( n=40, with hepatolithiasis) and HBV group ( n=29, with HBV). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison. Cox proportional hazard regression model was used for multivariate analysis to analyze the effect of hepatolithiasis and HBV on the prognosis. Results:The median overall survival of ICC patients in the stone group was 16 months, and that in the HBV group was 27 months. The 1-, 3-, and 5-year cumulative survivals of the stone group were 56.6%, 23.2%, and 10.3%, respectively, which were lower than those of the HBV group (72.0%, 50.7%, and 43.4%, respectively, χ2=5.95, P=0.015). The median recurrence-free survivals (RFS) of the stone group and the HBV group were 12 months and 23 months, respectively. The 1-year and 3-year RFS of the stone group were 49.2% and 18.1%, which were lower than those of the HBV group (65.0% and 39.8%, respectively, χ2=3.94, P=0.047). Univariate analysis showed that hepatolithiasis was assciated with prognosis ( χ2=5.95, P=0.015). Multivariate Cox regression analysis showed that hepatolithiasis and hepatitis B virus infection had no effect on the prognosis of ICC patients after surgery (all P>0.05). Conclusion:Compared to HBV infection, ICC patients with hepatolithiasis have a worse prognosis. Hepatolithiasis and HBV infection have no effect on the prognosis of ICC after radical resection.

Objective:To investigate the factors influencing recipient liver regeneration after full-size split liver transplantation (fSLT).Methods:The clinical data of patients undergoing split liver transplantation in the Affiliated Li Huili Hospital of Ningbo University from May 2019 to Sep 2023 were retrospectively collected. Graft volume (GV) and initial graft volume (IGV) at (30±7) days after operation were measured, and postoperative liver regeneration rate (LRR) was calculated. The patients undergoing fSLT were divided into high regeneration group and low regeneration group with LRR=30% as boundary. The differences of donor and recipient data and perioperative data between the two groups were compared.Results:A total of 52 patients were included. The low fSLT regeneration group (16 cases) was compared with the high fSLT regeneration group (36 cases), and in high fSLT regeneration group donor age was lower, the donor liver steatosis was less, GRWR was lower, the incidence of hepatitis B virus-related liver disease was lower, the postoperative diagnosis of malignant liver disease was lower, the intraoperative blood loss was less, and the postoperative platelet count was higher. The levels of liver enzyme and total bilirubin (TBiL) were higher than those in high regeneration group ( P<0.05). Conclusions:Donor age, donor liver steatosis, GRWR, hepatitis B virus associated liver disease, and recipient pathogenesis are important factors affecting liver regeneration after fSLT. Postoperative platelet and liver enzyme levels are important indicators for monitoring liver regeneration after fSLT.

Objective To explore the correlation between thyroid antibody levels and early renal injury in patients with type 2 diabetes mellitus(T2DM)combined with Hashimoto's thyroiditis(HT).Methods A total of 375 T2DM patients hospitalized in The Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022 were selectedas the study subjects,and 197 healthy people were selected as the control subjects.The patients with T2DM were divided into simple T2DM group(n=191)and T2DM combined with HT group(HT,n=184).According to the urinary albumin/creatinine ratio(UACR)level,T2DM patients with HT were divided into microalbuminuria subgroup(MUAlb,30≤UACR≤300 mg/g,n=70)and normal albuminuria subgroup(NUAlb,UACR<30 mg/g,n=114).According to whether the thyroid antibody was positive,they were divided into thyroid peroxides antibody[TPOAb(+)]subgroup(n=56),thyroglobulin antibody[TGAb(+)]subgroup(n=40)and TGAb and TPOAb double antibody positive subgroup(n=88).Results Compared with the NC group,the smoking,drinking,urinary creatinine,alpha 1-microglobulin,UACR,FPG,HbA1c,LDL-C,TC,and TG in the HT and T2DM groups increased(P<0.05),while HDL-C decreased(P<0.05).Compared with the NUAlb subgroup,the MUAlb subgroup showed age,DM duration,FPG,HbA1c,TGAb,TPOAb,thyroid stimulating hormone(TSH)increased(P<0.05),while FT3 and eGFR decreased(P<0.05).Spearman correlation analysis showed that UACR was positively correlated with age,HbA1c,TPOAb,TGAb,TSH(P<0.01),and negatively correlated with FT3(P<0.01).The UACR of the TGAb(+)+TPOAb(+)subgroup was higher than that of the TGAb(+)and TPOAb(+)subgroups(P<0.05).Logistic regression analysis showed that TSH,TGAb,TPOAb,and HbA1c were risk factors for MUAlb,while FT3 was a protective factor for MUAlb.Conclusions In T2DM with HT patients with normal thyroid function,TPOAb and TGAb are closely related to the occurrence of early renal injury.

Objective:To evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.

Objective:To study the safety and efficacy of combining portal vein resection and reconstruction (PVR) with resection of perihilar cholangiocarcinoma (PHC).Methods:A total of 104 patients with PHC who underwent hepatectomies for either biliary resection alone or biliary resection combined with PVR from October 2006 to December 2019 at the Department of Hepatopancreatobiliary, Ningbo Medical Center of Lihuili Hospital entered into this study. There were 63 males and 41 females, with the age of (64.4±10.4) years. The control group consisted of 75 patients who underwent biliary resection alone, while the PVR group consisted 29 patients with biliary resection combined with PVR. The patient characteristics and the follow-up outcomes of the two groups were analyzed and compared. Survival analyses were performed using the Kaplan Meier method with the log-rank test.Results:Wedge resection of portal vein, side to side anastomosis in 2 cases, segmental resection and end to end anastomosis in 27 cases. The time taken for PVR and portal vein resection were (12.7±2.9)(range 8 to 18)min and (20.7±7.3)(range 8 to 38) mm, respectively. The estimated blood loss for the PVR group was significantly more than the control group [ M( Q1, Q3)] 800.0 (600.0, 1 500.0) ml vs. 600.0(500.0, 1 000.0) ml ( P<0.05). Based on postoperative pathological studies, the proportion of lymph node metastasis was significantly higher in the PVR group than the control group (58.6% vs. 32.0%, P<0.05). Clavien-Dindo grade Ⅲ and above complications were 30.7%(23/75) and 34.5%(10/29) in the control and PVR groups, respectively ( P>0.05). The re-operation and postoperative 90 days mortality rates were 9.3%(7/75) and 2.7%(2/75) in the control group, compared with 3.4%(1/29) and 0 in the PVR group, respectively (both P>0.05). The 1-, 3- and 5-year survival rates were 81.1%, 44.8% and 36.4% respectively for the control group and 78.1%, 35.9% and 31.4% for the PVR group (χ 2=0.33, P=0.570). Conclusion:When compared to biliary resection alone, biliary resection combined with PVR did not significantly increase postoperative complication and mortality rates, but with comparable long-term survival outcomes. Combined biliary resection with PVR was safe and improved the resection rate in selected patients with locally advanced PHC.

Objective:To explore the feasibility of technological modification and innovation of full-left/full-right liver splitting in situ for donors and examine the safety of clinical application for liver transplantation (LT).Methods:From March 2021 to June 2022, clinical and surgical data are retrospectively reviewed for 27 donors undergoing full-left/full-right liver splitting in situ and the corresponding 49 recipients undergoing full-left/full-right LT.According to the split liver technique used in donor liver surgery, they are divided into conventional split group(group A, 13 cases)and innovative split group(group B, 14 cases). The corresponding recipients are divided into two groups of recipient C(25 cases)and recipient D(24 cases). General profiles, intraoperative findings, type of vascular allocation and short-term outcomes in two groups are compared.After full-size split liver transplantation(fSLT), follow-ups continued until the end of September 2022.Results:There are 23 males and 4 females in donors.The causes of mortality for donors are traumatic head injury(12 cases)cerebrovascular accident(13 cases)and anoxia encephalopathy(2 cases). Baseline characteristics of two groups indicate that body weight and body mass index(BMI)are higher in group B and blood sodium level is lower than that in group A( P<0.05). No statistical differences exist for the others.Liver splitting time is significantly shorter in group B than that in group A(175 vs.230 min, P=0.022). No significant inter-group difference exists in type of vascular allocation.Retrohepatic inferior vena cava(IVC)is split in one case in group A and 10 cases in group B( P=0.001). Among 20 cases of right hemiliver requiring a reconstruction of segment Ⅴ/Ⅷ venous outflow, 12 cases in group A and 3 cases in group B are reconstructed with conventional independent bridging method(independent type)while another 5 cases in group B reconstruct with innovated technique by bridging Ⅴ/Ⅷ vein for splitting IVC with iliac vessel and molding all outflows as one for anastomosis(combined typ e). There is significant inter-group difference( P=0.004). No significant differences exist in operative duration, anhepatic phase or blood loss between groups C and B, except for T tube retaining in 7 cases of group A and 14 cases of group D( P=0.032). Twelve cases developed a total of 26 instances of≥Clavien-Dindo grade Ⅲ complications.Of which, 7 cases in group C and 5 cases in group D show no significant difference in postoperative morbidity.However, for serious biliary complications(≥Clavien Dindo grade Ⅲ), there are 6 cases in group C versus none in group D( P=0.016). Two cases died from postoperative complication with a postoperative mortality rate of 4.1%.Postoperative hospital stay is similar in two groups.And accumulates 6/12-month survivals were 95.9% and 87.7% for grafts and 95.9% and 92.4% for recipients respectively. Conclusions:Operative duration of full-left/full-right liver splitting in situ tends to shorten with an accumulation of a certain amount of cases.Technological modification and innovation in IVC splitting and segment Ⅴ/Ⅷ vein reconstruction should be further validated as both feasible and safe by short-term outcomes of the corresponding recipients.

Objective:To study the influencing factors in predicting conversion of laparoscopic liver tumor resection to open surgery to provide references for selection of patients for laparoscopic hepatectomy.Methods:The clinical data of 222 patients who were planned to undergo laparoscopic liver tumor resection at Ningbo Medical Center Lihuili Hospital from December 2015 to November 2018 were analyzed retrospectively. There were 146 males and 76 females, with an average age of 58.1 years. These patients were divided into the conversion group ( n=24) and the laparscopic group ( n=198) according to whether intraoperative conversion to open surgery was carried out. Chi-square test was used to evaluate relevant factors of conversion. Logistic regression analysis was used for multivariate analysis and to find out independent risk factors of conversion. Results:The conversion rate was 10.8% (24/222). Univariate analysis showed that hypertension, history of abdominal surgery, liver cirrhosis, tumors located at posterosuperior segments and major liver resection were significantly associated with conversion (all P<0.05). Multivariate analysis showed that the risk factors which were independently associated with conversion were liver cirrhosis ( OR=2.611, 95% CI: 1.018-6.701), tumors located at posterosuperior segments ( OR=6.115, 95% CI: 2.207-16.941), and major liver resection ( OR=3.361, 95% CI: 1.150-9.825)(all P<0.05). Conclusion:Patients who were planned for laparoscopic liver tumor resection with liver cirrhosis, tumors at posterosuperior segments or major liver resection were at higher risks of conversion to open surgery.

Intrahepatic cholangiocarcinoma (ICC) has a high degree malignancy, and its incidence has gradually increased in recent years. Surgery is still the only curative treatment for ICC to achieve long-term survival, but its onset is hidden, and most patients have lost the opportunity of operation when they are diagnosed. ICC shows significant heterogeneity. With the development of the second generation sequencing technology, the tumor patterns of ICC, such as DNA, RNA, epigenetic, protein, microenvironment and so on, have been gradually discovered. The purpose of this article is to review the research progress of molecular typing and clinical application of ICC in recent years.

Objective:To evaluate the feasibility and efficacy of total hilar en bloc resection and reconstruction(THERR) and portal vein resection and reconstruction(PVRR) in treatment of perihilar cholangiocarcinoma(PHC).Methods:Data of a total of 101 consecutive patients with PHC who underwent bile duct resection with various types of hepatectomies from June 2013 to December 2019 at Department of Hepatopancreatobiliary,Lihuili Hospital were retrospectively analyzed. Patients who underwent PHC resection combined with THERR or PVRR were identified and grouped accordingly. Fourteen patients(6 males, 8 females, aged (64.3±9.7)years old) underwent hepatectomy combined with THERR, 19 patients(11 males, 8 females, aged (63.8±8.6)years old) underwent hepatectomy combined with PVRR. Indications and surgical procedures of THERR and PVRR were reported. The clinicopathological characteristics and operation data, as well as the short and long-term outcomes of patients of the two groups were compared by Student′s t-test and the χ 2 test or Fisher exact test, respectively. The actual survivals rates were calculated by using the Kaplan-Meier method, and compared using the Log-rank test. Results:There were no statistically significant differences between the two groups in respect to age,sex and whether they had preoperative biliary drainage or not. The types of combined hepatectomy carried out predominately between the two groups were statistically different with the left side being predominant in the THERR group(10/14, P=0.010) and right side in PVRR group(12/19, P=0.001). There were no significant differences between the two groups in respect to whether they received preoperative portal vein embolization,intraoperative blood loss,curative degree,number of lymph node dissections, and whether there was lymphatic metastasis or not. However, both the times of operation and continuous Pringle maneuver were statistically longer in the THERR group((586±158)minutes and (32.5±7.3)minutes)than those in the PVRR group((453±88)minutes and (12.4±3.8)minutes),respectively( t=3.087, P=0.004; t=10.325, P<0.01). One patient in the THERR group died of liver failure 9 days postoperative, the cumulative 1-, 3- and 5-year survival rates were 84.9%, 57.1% and 37.0% for the THERR group and 81.9%, 37.8% and 30.2% for the PVRR group, respectively. There was no statistically significant differences between the two groups(χ2=0.150, P=0.698). Conclusions:Compared to the role of PVRR in the treatment of PHC, THERR is a novel and technically demanding procedure that is feasible in selected patients for the treatment of advanced PHC with invasion of both the hepatic artery and portal vein. However,due to the small size of this primary study,the value of THERR needs further evaluation.