Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Objective:To investigate the grade of varicocele and its impact on semen quality of officers and soldiers stationed in coastal areas.Methods:The research subjects were 146 patients with left-sided varicocele and 32 healthy men selected from the male officers and soldiers who had visited the Beidaihe Sanatorium of PLA Joint Logistics Support Force. They were given physical and ultrasonic examination of spermatic vein and were divided into different groups by ultrasonic grading according to the inner diameter of their spermatic vein. Their semen quality was routinely analyzed.Results:There was no significant difference in semen volume or sperm deformity rate among the groups（ P > 0.05）. As varicocele aggravated，the sperm survival rate，sperm density，and the proportion of Grade A + B sperm all decreased significantly in the groups of clinical type II and III compared with those in the groups of normal type，subclinical type，and clinical type I（ P < 0.05）. Conclusion:The incidence of varicocele in officers and soldiers of coastal garrisons is significantly higher than that in the general population. The varicocele grade is closely related to the semen quality. Varicocele of clinical type I and below has less impact on the semen quality.

Objective:To observe the changes in semen quality before and after operation in the officers and soldiers stationed at coastal areas with clinical varicocele，and to evaluate the outcome of operation.Methods:According to the results of the color Doppler ultrasound，a total of 113 patients with clinical left varicocele who underwent high ligation of the spermatic vein in the Department of Urology of the Beidaihe Rehabilitation and Recuperation Center of PLA Joint Logistics Support Force were divided into three groups：clinical grade Ⅰ（ n=31），clinical grade Ⅱ（ n=36），and clinical grade Ⅲ（ n=46）. The semen qualities of all patients were analyzed before and after operation. Results:There was no significant change in semen quality before and after operation in the clinical grade Ⅰ group（ P>0.05）；the semen quality in the clinical grade Ⅱ group was significantly improved after operation（ P<0.05）；the semen quality in the clinical grade Ⅲ group after operation was generally improved（ P<0.05）. There was no significant difference in semen volumes or sperm deformity rates before and after operation among the three groups（ P>0.05）. Conclusion:The incidence of clinical varicocele in officers and soldiers stationed at coastal areas is significantly higher than that in the general population. The improvement of postoperative semen quality is closely related to the severity of preoperative varicocele. Ultrasound combined with routine semen examination can effectively evaluate the improvement of postoperative semen quality.

Objective:To investigate the grade of varicocele and its impact on semen quality of officers and soldiers stationed in coastal areas.Methods:The research subjects were 146 patients with left-sided varicocele and 32 healthy men selected from the male officers and soldiers who had visited the Beidaihe Sanatorium of PLA Joint Logistics Support Force. They were given physical and ultrasonic examination of spermatic vein and were divided into different groups by ultrasonic grading according to the inner diameter of their spermatic vein. Their semen quality was routinely analyzed.Results:There was no significant difference in semen volume or sperm deformity rate among the groups（ P > 0.05）. As varicocele aggravated，the sperm survival rate，sperm density，and the proportion of Grade A + B sperm all decreased significantly in the groups of clinical type II and III compared with those in the groups of normal type，subclinical type，and clinical type I（ P < 0.05）. Conclusion:The incidence of varicocele in officers and soldiers of coastal garrisons is significantly higher than that in the general population. The varicocele grade is closely related to the semen quality. Varicocele of clinical type I and below has less impact on the semen quality.

Objective:To observe the changes in semen quality before and after operation in the officers and soldiers stationed at coastal areas with clinical varicocele，and to evaluate the outcome of operation.Methods:According to the results of the color Doppler ultrasound，a total of 113 patients with clinical left varicocele who underwent high ligation of the spermatic vein in the Department of Urology of the Beidaihe Rehabilitation and Recuperation Center of PLA Joint Logistics Support Force were divided into three groups：clinical grade Ⅰ（ n=31），clinical grade Ⅱ（ n=36），and clinical grade Ⅲ（ n=46）. The semen qualities of all patients were analyzed before and after operation. Results:There was no significant change in semen quality before and after operation in the clinical grade Ⅰ group（ P>0.05）；the semen quality in the clinical grade Ⅱ group was significantly improved after operation（ P<0.05）；the semen quality in the clinical grade Ⅲ group after operation was generally improved（ P<0.05）. There was no significant difference in semen volumes or sperm deformity rates before and after operation among the three groups（ P>0.05）. Conclusion:The incidence of clinical varicocele in officers and soldiers stationed at coastal areas is significantly higher than that in the general population. The improvement of postoperative semen quality is closely related to the severity of preoperative varicocele. Ultrasound combined with routine semen examination can effectively evaluate the improvement of postoperative semen quality.

Objective:To summarize the technical points of laparoscopic pancreaticoduodenectomy (LPD) carried out in a single center.Methods:The clinical data of 102 patients who underwent laparoscopic pancreaticoduodenectomy in 2018 at the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were retrospectively analyzed, and the general conditions, operation time, intraoperative blood loss, and surgical operation were analyzed. Post-operative complications, hospital stay and other indicators were studied.Results:Of the 102 patients who were included, there were 57 males and 45 females, aged 15.0 to 79.0 (59.9±11.8) years old, with a body mass index (23.6±3.6) kg/m 2. For the 102 patients who underwent LPD, 6 were total pancreatic resection. Three were combined with vascular resection in the form of portal vein-superior mesentery vein segmental resection. The operation time was (376.6±87.2) min, the intraoperative blood loss was 350 (100, 800) ml, and the postoperative hospital stay was (17.0±5.9) days. Postoperative complications occurred in 26 of the 102 patients (25.5%), and more than two complications occurred in 17 patients. B/C grade pancreatic fistula occurred in 9 patients (9.4%), abdominal bleeding in 8 patients (7.8%), gastrointestinal bleeding in 2 patients (2.0%), biliary fistula in 4 patients (3.9%), and gastric emptying disorder in 5 patients (4.9%), 8 patients had pulmonary infection (7.8%). Five patients (4.9%) died during the perioperative period. Conclusion:The main technical points of LPD included en bloc resection, pancreaticojejunostomy, and vascular reconstruction. The basis of LPD is en bloc resection. Combined resection and reconstruction of vascular segments is a sign of maturity of LPD technology and a prerequisite for further development as a routine procedure.

Objective Ginsenoside Rh2 can inhibit the proliferation of a variety of malignant tumor cells.However, little research has been done on the sensitivity of Rh2 in human hepatocellular carcinoma HepG2/ADM cells with multidrug resistance(MDR).This study aimed to explore the reversing effects of ginsenoside Rh2 on the MDR of human hepatocellular carcinoma HepG2/ADM cells and its potential mechanism.Methods MTT assay was applied to detect the effect of Rh2(0-250 μg/mL) on the viability of HepG2/ADM cells and screen out the optimum drug-resistant reversal concentration of Rh2.Cells were divided into 3 groups: HepG2/ADM group (without any medicine treatment), ADM group(ADM treatment for 48 h), ADM+40 μg/mL Rh2 group (pretreatment of 40μg/mL Rh2 for 30 min followed by ADM treatment for 48 h).Flow cytometry was applied to detect the effect of Rh2 on the fluorescence intensity of cellular Rh-123.RT-PCR was used to measure the expression of MDR1 gene.Western blot was used to detect the protein levels of P-gp, Bax, Bcl-2 and cleaved caspase-3.Results 40 μg/mL ginsenoside Rh2 significantly reversed the MDR of HepG2/ADM cells by a 2.55-to-3.70-fold increase in sensitivity.Furthermore, compared with ADM group, the efflux of Rh-123 in HepG2/ADM cells were remarkably inhibited by Rh2 in ADM+40 μg/mL Rh2 group (65.83±1.78 vs 78.21±1.26, P<0.01), along with the down-regulated expressions of MDR1 (0.48±0.02 vs 0.86±0.05, P<0.05), P-gp(0.97±0.04 vs 1.91±0.03,P<0.01), Bcl-2(1.25±0.05 vs 1.86±0.03, P<0.05) and the up-regulated protein level of Bax (1.76±0.04 vs 1.25±0.02,P<0.05) and cleved caspase-3(0.42±0.04 vs 38.26±5.45,P<0.05).Conclusion Ginsenoside Rh2 can effectively reverse the MDR of HepG2/ADM cells, and the potential mechanism is related to the decreased expressions of MDR1 and P-gp, the increasing drug concentration inside the cells and the Bax/Bcl-2 signaling pathway.

Objective To review our experience in laparoscopic pancreaticoduodenectomy combined with major vascular resection and reconstruction.Methods Of 183 patients who underwent laparoscopic pancreaticoduodenectomy in our department from November 2013 to January 2017,major vascular resection and reconstruction using the SMA first approach for total mesopancreas excision was performed in 7 patients.The clinical data of these 7 patients were retrospectively analyzed.Results Total 3D laparoscopic surgery was performed in all these 7 patients.The mean operation time,mean blood loss and blood flow occlusion time were (551.4 ± 83.8) min,(671.3 ± 256.3) ml and (45.8 ± 6.7) min,respectively.Six out of 7 patients were pathologically diagnosed to have pancreatic adenocarcinoma with negative surgical margins.Two patients had lymphatic metastasis (the number of metastatic lymph node was 1 in each patient).The mean number of lymph nodes resected was (12.7 ± 5.8).The portal vein-superior mesenteric vein (PV-SMV) was segmentally resected and reconstructed using an end to end anastomosis following the preoperative plan in 4 patients.These included 2 patients who underwent total pancreatectomy.The portal vein was wedge-resected and reconstructed by venorrhaphy in 2 patients.The remaining 1 patient was histopathologically diagnosed to have a mass-type chronic pancreatitis.Only 1 patient was treated in the ICU for 1 day after surgery.Post-operative complications occurred in 2 patients and they were managed with nonsurgical treatment (PV-SMV thrombosis and gastric emptying disorder in 1 and a pancreatic leakage (level A) in 1).The mean length of post-operative hospital stay was (13.7 ± 3.2) days with no in-hospital mortality.Seven patients were alive by April 2017.The mean follow-up for the 6 patients with pancreatic adenocarcinoma was 4.5 (3.5 ～9) months.Conclusions Based on our experience in skillful and masterly major vascular resection and reconstruction in open surgery and on our experience in standard laparoscopic pancreaticoduodenectomy,laparoscopic pancreatieoduodenectomy combined with major vascular resection and reconstruction was feasible and safe.This surgery requires very mature skills in laparoscopic surgery.

AIM: To investigate the effect of GSTP1 over-expression on the sensitivity of human hepatoma HepG2 cells to oxaliplatin (OXA).METHODS: Adenovirus carrying GSTP1 (Ad-GSTP1) was used to infect HepG2 cells for establishing the cell line over-expressing GSTP1.The cells were randomly divided into 6 groups: control, vehicle, Ad-GSTP1, OXA, OXA +vehicle and OXA +Ad-GSTP1.The cell survival rates were examined by CCK-8 assay, and the apoptotic rates were analyzed by flow cytometry.The protein levels of GSTP1, Akt, mTOR, p-Akt and p-mTOR were deter-mined by Western blot.RESULTS: OXA decreased the cell survival rate in a dose-dependent manner (P <0.05).The protein expression of GSTP1 increased after transfection with adenovirus.At basal level, up-regulation of GSTP1 signifi-cantly decreased the cell survival rate, increased the cell apoptosis, and inhibited the phosphorylation levels of Akt and mTOR (P <0.05).Moreover, GSTP1 over-expression enhanced the effect of OXA on the cell viability, cell apoptosis, and further inhibited the phosphorylation levels of Akt and mTOR ( P <0.05).CONCLUSION: Over-expression of GSTP1 augments the enhanced effect of OXA on HepG2 cell apoptosis, which may be related to the inactivation of Akt/mTOR signaling pathway.

Objective To explore the correlation between hypoglycemia and the increased mortality of patients with acute decompensated liver cirrhosis.Methods A retrospective study was conducted on the clinical data of 120 patients with acute decompensated liver cirrhosis admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from December 2011 to December 2014. The patients were divided into three groups: hypoglycemia group (glucose < 5.0 mmol/L, 21 cases), normoglycemia group (glucose 5.1 - 10.0 mmol/L, 84 cases), and hyperglycemia group (glucose > 10.0 mmol/L, 15 cases). The differences in hepatic carcinoma, decompensation symptoms, the incidence of known glycometabolic disorder, hospitalization situation, indicators of liver function and indexes of blood gas analysis were compared among three groups. The patients' age, hepatic carcinoma, ascites, hepatorenal syndrome, encephalopathy, bleeding, jaundice and glycometabolic disorder, etc were analyzed by the univariate analysis. The resulting risk factors with statistically significant differences were analyzed by multivariate logistic regression method in order to screen out the risk factors of increased mortality.Results The incidences of hepatorenal syndrome [42.9% (9/21) vs. 22.6% (19/84), 33.3% (5/15)] and jaundice [38.1% (7/21) vs. 20.2% (17/84), 13.3% (2/15)], rate of admission into intensive care unit (ICU) [14.3% (3/21) vs. 10.7% (9/84), 13.3% (2/15)] and in-hospital mortality [23.8% (5/21) vs. 10.7% (9/84), 20.0% (3/15)] in the hypoglycemia group were significantly higher than those in the normoglycemia group and hyperglycemia group (P < 0.05 orP < 0.01). The levels of aspartate-aminotransferase (AST), total bilirubin (TBil), serum creatinine (SCr) and international normalized ratio (INR) in hypoglycemia group were obviously higher than those in normoglycemia group and hyperglycemia group [AST (U/L): 628.412±78.625 vs. 170.167±87.035, 156.716±98.047; TBil (μmol/L): 154.122±34.201 vs. 86.712±48.905, 74.313±39.883; SCr (μmol/L): 160.243±56.341 vs. 107.211±59.692, 121.342±84.059; INR: 1.951±0.987 vs. 1.439±0.919, 1.423±0.653,P < 0.05 orP < 0.01]. The levels of HCO3- and base excess (BE) in hypoglycemia group were signicantly lower than those of normoglycemia group and hyperglycemia group [HCO3- (mmol/L): 18.154±10.937 vs. 23.135±11.119, 19.081±12.022; BE (mmol/L): -7.578±2.042 vs. -1.648±0.887, -5.402±2.005, allP < 0.01]. The pH value among three groups showed significant difference (7.352±2.878, 7.461±2.036, 7.219±2.017,P < 0.01). There were no statistically significant differences in alanine transaminase (ALT), blood ammonium, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) and lactate among the three groups (all P > 0.05). Univariate analysis showed that advanced age, hepatic carcinoma, hepatorenal syndrome, bleeding, jaundice and glycometabolic disorder hypoglycemia were the risk factors of the death in patients with acute decompensated liver cirrhosis (P < 0.05 orP < 0.01). Multivariate logistic regression analysis showed that advanced age [odds ratio (OR) = 2.101, 95% confidence interval (95%CI) = 1.297 - 3.403,P = 0.000], hepatorenal syndrome (OR = 3.032, 95%CI = 1.462 - 6.286,P = 0.000) and hypoglycemia (OR = 3.267, 95%CI = 2.135 - 4.999,P = 0.031) were the independent risk factors of the patients' death.Conclusion Hypoglycemia has certain correlation to the increase of mortality in patients with acute decompensated liver cirrhosis.