Objective To investigate the active ingredients of Zizyphi Spinosae Semen(ZSS)in relieving benzodiazepine(BDZ)dependence and its molecular mechanism based on the integrated Traditional Chinese Medicine and chemical drugs idea of"enhancing effect and reducing toxicity"via the approach of network pharmacology and the technique of molecular dynamics simulation.Methods First,literature search was undertaken to find the main components of ZSS.Then,the major effective constituents of ZSS in relieving BDZ dependence and its target of action were explored on the basis of network pharmacology and molecular docking.Finally,the relationship between core components of ZSS and key proteins was further verified through the technique of molecular dynamics simulation.Results After literature search,a total of 24 chemical components in ZSS were found to act on 731 targets.Through establishing the network of"ingredients-targets-pathways",topology analysis was performed to obtain nine core components such as linoleic acid,palmitic acid,oleic acid,tetradecanoic acid,spinosin,oleanolic acid and jujuboside A,as well as five key targets including AR,PTGS2,PPARG,RXRA and CYP19A1.Bioinformation enrichment analysis was made to obtain critical pathways such as calcium signaling pathway,cAMP signaling pathway,IL-17 signaling pathway and TNF signaling pathway.The results of molecular docking revealed that there was a good combination between core components of ZSS and key targets,and it was mainly dominated by hydrogen bonding.Furthermore,the molecular dynamics simulation experiments indicated that the combinations between jujuboside A and RXRA,oleanolic acid and RXRA,spinosin and PPARG were stable,and these three active ingredients played an important role in improving BDZ dependence.Conclusion The active components in ZSS may exert multi-target and multi-pathway intervention effects on BDZ dependence by means of processes such as immunoregulation,anti-anxiety,and anti-insomnia.

Objective:To investigate the clinical efficacy of laparoscopic radical resection of hilar cholangiocarcinoma (LRHCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of 211 patients who under LRHCCA in the Second Hospital of Hebei Medical University from May 2014 to June 2022 were collected. There were 135 males and 76 females, aged (63±8)years. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. Results:(1) Surgical situations. All 211 patients underwent LRHCCA successfully, with the operation time as 350 (300,390)minutes, volume of intraoperative blood loss as 400(200,800)mL, and intraoperative red blood cell transfusion as 2.0(range, 0-15.0)U, respectively. As partial portal vein invasion, 10 of 211 patients underwent portal vein resection and reconstruction. Results of intraoperative histopathology examination showed negative margin of portal vein. The operation time, volume of intraoperative blood loss, intraopera-tive red blood cell transfusion of the 10 patients was (400±53)minutes, 1 200(range, 800-3 000)mL, 5.5(range, 4.0-15.0)U, respectively. (2) Postoperative situations. Of the 211 patients, there were 63 cases of the Bismuth type Ⅰ, 65 cases of the Bismuth type Ⅱ, 22 cases of the Bismuth type Ⅲa, 26 cases of the Bismuth type Ⅲb, 35 cases of the Bismuth type Ⅳ. The R 0 resection rate was 95.73%(202/211). There were 202 patients identified as adenocarcinoma of the bile duct, including 7 cases with poorly differentiated tumor, 189 cases with moderate to poorly differentiated tumor, 3 cases with moderate to well differentiated tumor, 3 cases with well differentiated tumor. There were 8 patients with poorly differentiated biliary mucinous adenocarcinoma, 1 patient with intraductal papillary neoplasm with high-grade epithelial dysplasia. There were 24 cases of stage Ⅰ, 98 cases of stage Ⅱ, 30 cases of stage ⅢA, 34 cases of stage ⅢB, 19 cases of stage ⅢC, 6 cases of stage ⅣA. Of the 211 patients, there were 25 cases with postoperative biliary fistula, 11 cases with postoperative abdominal infection, 3 cases with postoperative bleeding as anastomotic bleeding after biliary fistula, 2 cases with postoperative gastric emptying disability, 1 case with postoperative acute liver failure. There were 7 patients undergoing postoperative unplanned reoperation, including 3 cases with emergency operation for hemostasis, 4 cases with abdominal exploration debridement and drainage for severe abdominal infection. There were 3 cases dead during perioperative period, including 1 case of acute liver failure, 1 case of systemic infection and multiple organ failure, 1 case of exfoliated deep venous thrombosis of lower extremities and acute pulmonary embolism. The postoperative duration of hospital stay was (15±5)days of the 211 patients and (17±4)days of patients undergoing portal vein resection and reconstruction. The cost of hospital stay of the 211 patients was (11.7±1.7)ten thousand yuan. (3) Follow-up. Of the 211 patients, 188 patients were followed up for 21(range, 4?36)months. The median survival time of 188 patients was 22 months, and the postoperative 1-, 2- and 3-year survival rate was 90.9%, 43.1% and 18.7%, respectively. Conclusion:LRHCCA is safe and feasible, with satisfactory short-term effect, under the coditions of clinicians with rich experience in laparoscopic surgery and patients with strict surgical evaluation.

To investigate the effects of cigarette smoking in different manners on acute lung injury in rats.The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels.In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels.Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Acute Lung Injury ; etiology ; pathology ; physiopathology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemotaxis, Leukocyte ; drug effects ; Glutathione ; analysis ; drug effects ; Interleukin-1beta ; analysis ; drug effects ; Lung ; chemistry ; pathology ; Lymphocytes ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; pathology ; Peroxidase ; analysis ; drug effects ; Rats ; Reactive Oxygen Species ; analysis ; Smoking ; adverse effects ; Superoxide Dismutase ; analysis ; drug effects ; Tobacco Products ; adverse effects ; classification ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Weight Loss ; drug effects

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats .Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking ( health canada method , HCM) manner , and those with tar of 11 mg were also smoked in international standard ( ISO) smoking manner .Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure .After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro -inflammatory cytokines IL-1βand TNF-α.The right lungs were subjected to histological examination and determination of myeloperoxidase ( MPO ) and superoxide dismutase (SOD) activities and glutathione , reactive oxygen species (ROS) and malondialdehyde (MDA) levels.Results:In both HCM and ISO manners , the degree of lung injury was closely related to the tar content of cigarettes , and significant decrease in the body weight of rats was observed after smoking for one week .In a HCM manner , smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages , lymphocytes and neutrophils into lungs , significant increase in IL-1βand TNF-αlevels and MPO activities , and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels ( all P <0.05 ) .Smoking with cigarette of 5 mg tar led to moderate increase in IL-1βand TNF-αlevels, and MPO activities (all P<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels ( all P<0.05).However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1βand TNF-αlevels.Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes .

Aged ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Vertigo ; genetics

Objective To compare the characteristics of remifentanil and sufentanil for tracheal intubation general anesthesia in gyneco-logical laparoscopic operation. Methods 80 patients received gynecological laparoscopic operation were randomly divided into the remifen-tanil group and the sufentanil group with 40 patients in each group, and they were performed total intravenous anesthesia with remifentanil or sufentanil respectively. Compare the changes of heart rate, mean arterial pressure in the two groups before and after induction, at the time of intubation, pneumoperitoneum, and after the operation. And differences in two groups were recorded in the recovery time, extubation time, postoperative pain in 24 hours, exhaust time and postoperative complications. Results Change trend and magnitude in heart rate, mean ar-terial pressure had no significant difference in the two groups (P>0. 05). The recovery time, extubation time in remifentanil group was shor-ter (P<0. 01), postoperative pain in 24 hours in sufentanil group was more mild (P<0. 01). Exhaust time and postoperative complications of the two groups had no significant difference (P>0. 05). Conclusion Remifentanil and sufentanil used in gynecological laparoscopic op-eration can achieve good effect. and effects of the two drugs on hemodynamics were similar. Remifentanil can recieve better effect in terms of recovery time, while sufentanil has better postoperative analgesia effect.

OBJECTIVE: To analyze the clinical characters, surgical treatments and prognosis of differentiated thyroid carcinoma (DTC) with laryngeal or tracheal invasion. METHOD: Forty-six cases including 33 papillary and 13 follicular were retrospectively reviewed. Thirty-four cases with tracheal invasion received conservative resection (17), window resection (11) and sleeve resection (6). One case with subglottic invasion was performed subglottic partial laryngectomy. Eleven cases with trachea-laryngeal invasion received total laryngectomy(4), 3 shave technique and 4 preservative laryngectomy. RESULT Complications included infections and hypocalcaemia, 15 patients got permanent fistula. 5-year survival rate in cases of tracheal shave resection was 88.2%, while 63.6% in those of window resection and 83.3% in those of sleeve resection. Survival rate within 5 years of patients received preservative laryngectomy was 62. 5%. Conclusion: With meticulous preoperative examination and positive surgical treatment, both survival rate and quality of life could be improved in patients of DTC with laryngeal or tracheal invasion.
Adenocarcinoma ; Humans ; Laryngectomy ; Larynx ; pathology ; Larynx, Artificial ; Neoplasm Invasiveness ; Prognosis ; Quality of Life ; Retrospective Studies ; Survival Rate ; Thyroid Neoplasms ; pathology ; surgery ; Trachea ; pathology

OBJECTIVE To investigate the antimicrobial susceptibility of Streptococcus pneumoniae isolated in Yantai and their mechanisms of resistance to macrolides.METHODS Antimicrobial susceptibility of S.pneumoniae was determined by agar dilution method.Phenotypes of macrolide-resistant S.pneumoniae were determined using double disk test with erythromycin and clindamycin disks.ermB And mefE genes were amplified by PCR.RESULTS Among 42 strains of S.pneumoniae,65.0% were intermediate to and no strain was resistant to penicillin.The resistance rates to erythromycin and clindamycin were 93.0%,respectively.Of 41 erythromycin resistantstrains,93.0% were constitutive resistant.ermB Was detected in 40 strains and mefE in 1 strain,both ermB and mefE genes were found in 9 strains.CONCLUSIONS The resistance rate of S.pneumoniae to penicillin is high in Yantai area,the resistance rates to erythromycin and clindamycin are very high.Target modification by ermB methylase is the predominant mechanism in macrolide-resistant S.pneumoniae in Yantai.

Objective To investigate the selective killing effect of MDA/IL-24 on human hepatocellular carcinoma line HepG2 in vitro and provide a theoretical basis for gene therapy of hepatocellular carcinoma.Methods The MDA-7/IL-24 gene was transfected into human hepatocullular carcinoma cell line HepG2 and normal liver cell line L02 with a replication-incompetent adenovirus vector.The mRNA and protein expression of MDA7/IL-24 in HepG2 and L02 cells was examined by RT-PCR and ELISA assay respectively.MTT assay and flow cytometry were used to study tumor cell proliferation and cell cycle in vitro.Hoechst and Annexin-V and PI staining were studied to indicate the apoptosis.Results RT-PCR confirmed that the exogenous MDA-7/IL-24 gene was expressed in HepG2 and L02 cells.The protein product was confirmed by assay of the supernatant with ELISA.MTT and apoptosis test indicated MDA-7/IL-24 induced growth suppression and cell apoptosis of the HepG2 cell in vitro but not in cell line L02,and cell cycle test revealed MDA-7/IL-24 could block HepG2 cell in G2/M but not in L02.Conclusions MDA-7/IL-24 selectively induces growth suppression and apoptosis in lines HepG2 in vitro but not in L02 cell,which indicates that adenovirus mediated MDA-7/IL-24 can be an excellent tool for gene therapy in hepatocellular carcinoma.

Objective To evaluate the biocompatibility and antibacterial activities of the Ornidazole Slow-Release Membrane.Methods 1.The lower lips of 12 rats were sewed into 12 pockets and the pockets were immited with extracting solution of the ornidazole membrane, formaldehyde and normal saline respectively once per day.The specimens were examined histologically 7 days later.2.The dorsal muscles of 16 rats were implanted with the membranes or silk threads,and examined histologically 1 week and 2,4,6 weeks later respectively.3. The antibacterial activity against Streptococcus mutans and Fusobacterium nucleatum was observed on solid culture medium in vitro.Results The animal experiments showed the membranes were not irritative to the oral mucosa.It was found that the tissue reaction of the membranes was similar to that of the silk threads after implanted into dorsal muscles and the membranes had been degraded in the second week.And the membranes had effective antibacterial action against Streptococcus mutans and Fusobacterium nucleatum.Conclusion The Ornidazole Slow-Release Membrane possesses favorable biocompatibility and antibacterial activities.