Objective The objective of this study was to investigate the effects of propofol on glycolysis of lung cancer,and to further explore its potential mechanism of inhibiting glycolysis in lung cancer through glucose transporter 4(GLUT4).Methods Human lung cancer A549 cells and mouse lung cancer LLC cells were cultured,and the experimental groups were set as the blank control group(Control group)and propofol(10μmol/L)group(Propofol group).The CCK-8 assay was used to detect cell viability;Immunofluorescence(IF)was used to detect the expression of Ki-67 in lung cancer cells and A549 cell xenografts.Extracellular acidi-fication rate(ECAR)and mitochondrial oxygen consumption(OCR)assays were used to detect the cellular metabolic levels;ELISA was used to detect the cell lactate and pyruvate content;Molecular docking experiments were used to detect the binding ability of GLUT4 with propofol using CB-Dock online tool;The glucose uptake kit was used to detect glucose uptake;Western blot was used to detect the expression of GLUT4,HK2,and PFK1 proteins in lung cancer cells.Results The cell viability of A549 cells(0.661±0.052)and LLC cells(0.632±0.033)in the propofol group was significantly inhibited by 10 μmol/L of propofol in lung cancer cells(P＜0.001).Compared with the control group,the average fluorescence intensity of Ki-67 in A549 and LLC positive cells(0.663±0.064 and 0.540±0.070)was significantly suppressed(P＜0.001).The ELISA results showed that compared with the control group,the levels of lactate and pyruvate in the propofol group decreased(P＜0.001),and under the action of propofol,the glucose uptake ability of cells decreased(P＜0.001).Molecular docking experiments using the CB-Dock online tool showed that GLUT4 had the strongest binding force with propofol.The results of Western blot showed a decrease in the expression of GLUT4 and its downstream HK2 and PFK1 pro-teins.After transient transfection and knockdown of GLUT4,cellular lactate(P＜0.001)and pyruvate content(P＜0.01)decreased,glu-cose uptake capacity reduced,and the inhibitory effect of propofol on glycolysis disappeared.In A549 cell xenografts,the weight of xenografts in the propofol group was significantly smaller than that of the model group(P＜0.001).Compared with the model group,the lactate content and pyruvate content decreased in the propofol group(P＜0.001).Conclusion Propofol can inhibit the proliferation of lung cancer cells and the progression of A549 cell xenografts in bearing mice by inhibiting the glycolysis of lung cancer cells,and its mechanism may be related to the targeted effect of GLUT4 on the glycolysis of lung cancer cells.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.
Humans ; Transcription Factors/metabolism* ; Nuclear Proteins/metabolism* ; Histones ; Cell Cycle Proteins/metabolism* ; Neoplasms/metabolism* ; Protein Domains

Objective:To investigate the effect of tumor deposits on the prognosis and lymph node staging in patients with gastric cancer.Methods:The clinicopathological data of 907 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from Jan to Dec 2016 were retrospectively analyzed. According to the pathological diagnosis, the patients were divided into tumor deposits positive group (121 cases) and tumor deposits negative group (786 cases), and the relationship between tumor deposits and clinicopathological features and prognosis was analyzed.Results:Tumor deposits were found in 121 patients among 907 cases. Univariate analysis showed that tumor deposits were correlated with pT stage, pN stage, pTNM stage, tumor diameter, nerve invasion and vascular invasion (all P<0.05). Multivariate analysis showed that pT stage ( P<0.001), pN stage ( P=0.002), pTNM stage ( P=0.001), tumor diameter ( P=0.033),nerve invasion ( P=0.017), vascular invasion ( P=0.011) were the independent influencing factors of positive tumor deposits. The prognosis of patients with tumor deposits was worse than those without ( χ2=77.869, P<0.001). By univariate analysis, age, tumor location, size, pT stage, pN stage, pTNM stage, tumor thrombus, nerve invasion, tumor deposits and number affected prognosis (all P<0.05). Multivariate analysis showed that age, pT stage, pN stage, pTNM stage, nerve invasion, vascular invasion and the number of tumor deposits were independent prognostic factors (all P<0.05). By stratified analysis tumor deposits were found to have statistical difference in N0~N3a stage (all P<0.05). Conclusion:Tumor deposits is an independent risk factor affecting the prognosis of gastric cancer patients.

Objective: To compare the clinical value of ultrasonic elastography (UE) and three common ultrasonic features in diagnosing papillary thyroid carcinoma (PTC). Methods: From January 2012 to December 2017, the clinical data of 105 cases with PTC which were confirmed by postoperative pathologic examination and 20 cases with benign thyroid nodules (BTN) in the Integration of Chinese and Western Medicine Hospital Affiliated to Nanjing University of Traditional Chinese Medicine were analyzed retrospectively.The UE and common ultrasonic features comprising a taller-than-wide shape, irregular margins and microcalcifications were analyzed.The sensitivity, specificity and area under curve (AUC) of PCT dingnosis with two different ultrasonic parameters are calculated. Results: Based on surgical pathology, the diagnostic sensitivity of irregular boundary is the highest amony the three paraneters of ordinary ultrasound.Although an irregular margin showed higher sensitivity than taller-than-wide shape and microcalcifications with 71.42% vs.59.04% vs.60.00%, but there was no statistically significant difference (χ²=4.3, P=0.116). There was also no statistically significant difference in specificity (χ²=0.134, P=0.935). The diagnostic efficiency of UE was higher than taller-than-wide shape (Z=3.046, P=0.002), irregular margin(Z=2.962, P=0.003) as well as microcalcifications(Z=3.942, P=0.000), the difference was statistically significant(P<0.05). The diagnostic efficiency of UE was higher than the combined three common ultrasonic features together (Z=3.125, P=0.001). Conclusion UE score shows a higher diagnostic efficiency, easy to perform, indicating the important application value in preoperative diagnosis of PTC, and is worthy of promoting in clinic.

Objective: To summarize the experience of treatment for blunt pancreatic trauma. Methods: The clinical data of 52 patients with blunt pancreatic trauma admitted to the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2018 were analyzed retrospectively.There were 40 male and 12 female patients, aging from 12 to 112 years with a median age of 35.5 years.According to the organ injury scale by American Association for the Surgery of Trauma(AAST) for pancreatic injury severity, 15 cases were in grade Ⅰ(28.8%), 20 cases were in grade Ⅱ(38.5%), 10 cases were in grade Ⅲ(19.2%),5 cases were in grade Ⅳ(9.6%) and 2 cases were in grade Ⅴ(3.8%). Isolated blunt pancreatic trauma occurred in 11(21.2%) patients including 5 cases of grade Ⅰ,5 cases of grade Ⅱ and 1 case of grade Ⅲ, and associated injuries existed in 41 patients(78.8%). Results: Among 52 patients, 36 patients(69.2%) were transferred from other hospitals and 16(30.8%) patients were admitted through the emergency department. Finally, 49 patients(94.2%) were cured and 3 patients (5.8%) died.For the 15 cases of grade Ⅰ,9 patients were managed non-operatively, 5 cases underwent peritoneal lavage and drainage after surgery for the other injured abdominal organs, and 1 patient received percutaneous catheter drainage(PCD) with non-operative treatment. For the 20 cases of grade Ⅱ,4 cases only received non-operative treatment and 2 cases also received PCD. Besides, 2 cases underwent debridement and drainage for peripancreatic necrotic tissue and external drainage for pancreatic pseudocyst retrospectively after about 25 days of getting injured. As for patients who received exploratory laparotomy, 5 patients underwent suture repair associated with external drainage, and 7 patients were managed only with external drainage. For the 10 cases of grade Ⅲ,6 patients were cured through distal pancreatectomy and splenectomy with external drainage, while 2 patients underwent endoscopic retrograde cholangiopancreatography and ductal stenting, and the other 2 patients just received debridement and drainage for peripancreatic necrotic tissue.For the 5 cases of grade Ⅳ,2 patients underwent jejunostomy and abdominal cavity drainage, 1 patient had a pancreaticoduodenectomy with drainage,1 patient received suture repair of the pancreas and pancreaticojejunostomy, and 1 patient was managed with suture repair of the head of pancreas and external drainage.For the 2 patients of grade Ⅴ,1 patient received exploratory laparotomy and gauze compression packing hemostasis, and the other patient underwent pancreaticoduodenal repair, gastrointestinal anastomosis, duodenal exclusion surgery and external drainage. Conclusion According to the AAST classifications, associated injuries, physiological status and intraoperative situation, it could be better to make a comprehensive judgment, achieve early diagnosis and take appropriate individualized treatment strategy, and to improve the overall therapeutic effect for blunt pancreatic trauma.

Objective To summarize the experience of treatment for blunt pancreatic trauma. Methods The clinical data of 52 patients with blunt pancreatic trauma admitted to the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2018 were analyzed retrospectively.There were 40 male and 12 female patients,aging from 12 to 112 years with a median age of 35.5 years.According to the organ injury scale by American Association for the Surgery of Trauma(AAST) for pancreatic injury severity,15 cases were in grade Ⅰ(28.8%), 20 cases were in grade Ⅱ(38.5%),10 cases were in grade Ⅲ(19.2%),5 cases were in grade Ⅳ(9.6%) and 2 cases were in grade Ⅴ(3.8%). Isolated blunt pancreatic trauma occurred in 11(21.2%) patients including 5 cases of grade Ⅰ,5 cases of gradeⅡand 1 case of gradeⅢ,and associated injuries existed in 41 patients(78.8%). Results Among 52 patients, 36 patients(69.2%) were transferred from other hospitals and 16(30.8%) patients were admitted through the emergency department. Finally, 49 patients(94.2%) were cured and 3 patients (5.8%) died.For the 15 cases of grade Ⅰ,9 patients were managed non?operatively, 5 cases underwent peritoneal lavage and drainage after surgery for the other injured abdominal organs,and 1 patient received percutaneous catheter drainage(PCD) with non?operative treatment. For the 20 cases of grade Ⅱ, 4 cases only received non?operative treatment and 2 cases also received PCD. Besides, 2 cases underwent debridement and drainage for peripancreatic necrotic tissue and external drainage for pancreatic pseudocyst retrospectively after about 25 days of getting injured. As for patients who received exploratory laparotomy, 5 patients underwent suture repair associated with external drainage, and 7 patients were managed only with external drainage. For the 10 cases of grade Ⅲ, 6 patients were cured through distal pancreatectomy and splenectomy with external drainage, while 2 patients underwent endoscopic retrograde cholangiopancreatography and ductal stenting, and the other 2 patients just received debridement and drainage for peripancreatic necrotic tissue.For the 5 cases of gradeⅣ,2 patients underwent jejunostomy and abdominal cavity drainage, 1 patient had a pancreaticoduodenectomy with drainage,1 patient received suture repair of the pancreas and pancreaticojejunostomy,and 1 patient was managed with suture repair of the head of pancreas and external drainage.For the 2 patients of gradeⅤ,1 patient received exploratory laparotomy and gauze compression packing hemostasis, and the other patient underwent pancreaticoduodenal repair, gastrointestinal anastomosis, duodenal exclusion surgery and external drainage. Conclusion According to the AAST classifications, associated injuries, physiological status and intraoperative situation, it could be better to make a comprehensive judgment, achieve early diagnosis and take appropriate individualized treatment strategy,and to improve the overall therapeutic effect for blunt pancreatic trauma.

Objective To summarize the experience of treatment for blunt pancreatic trauma. Methods The clinical data of 52 patients with blunt pancreatic trauma admitted to the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2018 were analyzed retrospectively.There were 40 male and 12 female patients,aging from 12 to 112 years with a median age of 35.5 years.According to the organ injury scale by American Association for the Surgery of Trauma(AAST) for pancreatic injury severity,15 cases were in grade Ⅰ(28.8%), 20 cases were in grade Ⅱ(38.5%),10 cases were in grade Ⅲ(19.2%),5 cases were in grade Ⅳ(9.6%) and 2 cases were in grade Ⅴ(3.8%). Isolated blunt pancreatic trauma occurred in 11(21.2%) patients including 5 cases of grade Ⅰ,5 cases of gradeⅡand 1 case of gradeⅢ,and associated injuries existed in 41 patients(78.8%). Results Among 52 patients, 36 patients(69.2%) were transferred from other hospitals and 16(30.8%) patients were admitted through the emergency department. Finally, 49 patients(94.2%) were cured and 3 patients (5.8%) died.For the 15 cases of grade Ⅰ,9 patients were managed non?operatively, 5 cases underwent peritoneal lavage and drainage after surgery for the other injured abdominal organs,and 1 patient received percutaneous catheter drainage(PCD) with non?operative treatment. For the 20 cases of grade Ⅱ, 4 cases only received non?operative treatment and 2 cases also received PCD. Besides, 2 cases underwent debridement and drainage for peripancreatic necrotic tissue and external drainage for pancreatic pseudocyst retrospectively after about 25 days of getting injured. As for patients who received exploratory laparotomy, 5 patients underwent suture repair associated with external drainage, and 7 patients were managed only with external drainage. For the 10 cases of grade Ⅲ, 6 patients were cured through distal pancreatectomy and splenectomy with external drainage, while 2 patients underwent endoscopic retrograde cholangiopancreatography and ductal stenting, and the other 2 patients just received debridement and drainage for peripancreatic necrotic tissue.For the 5 cases of gradeⅣ,2 patients underwent jejunostomy and abdominal cavity drainage, 1 patient had a pancreaticoduodenectomy with drainage,1 patient received suture repair of the pancreas and pancreaticojejunostomy,and 1 patient was managed with suture repair of the head of pancreas and external drainage.For the 2 patients of gradeⅤ,1 patient received exploratory laparotomy and gauze compression packing hemostasis, and the other patient underwent pancreaticoduodenal repair, gastrointestinal anastomosis, duodenal exclusion surgery and external drainage. Conclusion According to the AAST classifications, associated injuries, physiological status and intraoperative situation, it could be better to make a comprehensive judgment, achieve early diagnosis and take appropriate individualized treatment strategy,and to improve the overall therapeutic effect for blunt pancreatic trauma.

OBJECTIVE:To establish a method for the residual simultaneous determination of methanol,alcohol,dichlorometh-ane,n-hexane,tetrahydrofuran and benzene in tosufloxacin tosylat. METHODS:Headspace GC was performed on the capillary col-umn with 6%cyanopropylphenyl-94%dimethylpolysiloxane(DB-624)as fixative lipid,temperature programmed,the inlet temper-ature was 180 ℃,detector was flame ionization detector with temperature of 300 ℃,carrier gas was high purity N2 at a flow rate of 1.5 mL/min,split ratio was 10:1,headspace equilibrium temperature was 100℃,equilibrium time was 40 min,headspace sam-ple volume was 10 mL,and the headspace sample volume was 1 mL. RESULTS:The linear range was 178.3-1782.7 μg/mL for methanol (r=0.9991),301.2-3012.1 μg/mL for alcohol(r=0.9997),33.81-338.10 μg/mL for dichloromethane(r=0.9993), 18.02-180.22 μg/mL for n-hexane(r=0.9991),43.26-432.58 μg/mL for tetrahydrofuran(r=0.9991)and 0.1268-1.2681 μg/mL for benzene(r=0.9991);limits of quantification were 0.31,3.00,0.67,0.02,0.005,0.10 μg/mL,limits of detection were 0.15, 1.51,0.22,0.01,0.001,0.05 μg/mL;RSD of precision test was no higher than 3.1%;RSDs of methanol and n-hexane in stabili-ty and reproducibility tests were no higher than 5%;recoveries were 93.72%-102.20%(RSD=3.1%,n=9),90.10%-101.79%(RSD=4.0%,n=9),97.07%-103.11%(RSD=2.0%,n=9),92.38%-103.83%(RSD=3.9%,n=9),95.44%-103.62%(RSD=2.8%,n=9),and 94.00%-104.73%(RSD=4.1%,n=9). CONCLUSIONS:The method is rapid,sensitive,accurate,and suitable for the residual determination of methanol,alcohol,dichloromethane,n-hexane,tetrahydrofuran and benzene in tosufloxacin tosylat.