ObjectiveTo investigate the principle and scientific connotation of Euodiae Fructus（EF） processed with Glycyrrhizae Radix et Rhizoma（Gly） by comparing the effects of unprocessed products of EF（UEF） and processed products of EF with the different proportions of Gly（GEFs） at toxic doses on oxidative stress and autophagy in the liver of mice. MethodSeventy mice were randomly divided into 7 groups， namely the control group， the UEF group， the group of the processed products of EF without Gly（PEF） and 4 groups of GEFs（the mass ratios of EF to Gly were 100∶3， 100∶6， 100∶12 and 100∶24， respectively， hereinafter referred to as the processed products of EF with the mass ratios of 100∶3， 100∶6， 100∶12 and 100∶24 of Gly）. The mice were given purified water， the decoction of UEF， PEF and GEFs by gavage at a dose of 30 g·kg^-1. PEF and GEFs were prepared according to the method under EF in the 2020 edition of Chinese Pharmacopoeia. Levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were determined by ultraviolet-visible spectrophotometry， hematoxylin-eosin（HE） staining was used to evaluate the pathological changes of liver tissue， the level of reactive oxygen species（ROS） was detected by fluorescence method， the mRNA expression of heme oxygenase-1（HO-1）， quinone oxidoreductase-1（NQO1）， glutathione-S-transferase 1（GSTA1）， Kelch-like epichlorohydrin-associated protein 1（Keap1） and p62 were measured by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， western blot was used to detect the protein expression of phosphorylated mammal target of rapamycin（p-mTOR）， phosphorylated ribosomal p70 S6 protein kinase（p-p70S6K）， p62， microtubule-associated protein 1 light chain 3Ⅰ（LC3Ⅰ） and LC3Ⅱ. ResultCompared with the control group， after 7 d of administration， the increase in body mass of mice in the UEF group began to slow down and the difference gradually increased， and the liver body index significantly increased（P<0.01）， pathomorphological observation showed that the structure of hepatic lobules was disordered， and local hepatic sinuses were narrowed or disappeared， and there were inflammatory infiltration and local bleeding， the levels of ALT and AST in serum and ROS in liver tissue were significantly increased（P<0.01）， and the expressions of Keap1， HO-1， NQO1， GSTA1， p62 mRNA and p-mTOR， p-p70S6K， p62 protein in liver tissue were significantly decreased（P<0.01）， and LC3Ⅱ/LC3Ⅰ was significantly increased（P<0.01）. Compared with the UEF group， the body mass of mice increased， and the liver body index， the levels of ALT and AST in serum， and the level of ROS in liver tissue all decreased in the groups of PEF and GEFs. Among these groups， only the liver lobules in GEF（100∶6） group were intact， and the size of liver sinuses was close to that in the control group. The mRNA expressions of Keap1， HO-1， NQO1， GSTA1 and p62 in liver tissue showed an overall upward trend in the groups of PEF and GEFs. Among these groups， only the ones of the above mRNA in the GEF（100∶6） group had a significant increase（P<0.05， P<0.01）. The protein expressions of p-mTOR， p-p70S6K， p62 and LC3Ⅱ/LC3Ⅰ had a callback in the groups of PEF and GEFs， of which the protein expressions of p-mTOR， p-p70S6K and LC3Ⅱ/LC3Ⅰ in the GEF（100∶6） group and the expression of p62 protein in the GEF（100∶24） group had the largest callback. Except for p-mTOR protein， other protein expressions were statistically significant（P<0.05， P<0.01）. ConclusionThe hepatotoxicity of EF is closely related to its ability to induce oxidative stress， which leads to pathological autophagy and hepatocyte damage. This ability can be reduced by the processing with different proportions of Gly， especially the ratio of 100∶6.

ObjectiveTo explain the scientific connotation of Morindae Officinalis Radix （MOR） processed by Glycyrrhizae Radix et Rhizoma （Gly） by comparing the effect of raw products of MOR and processed products of MOR with different proportions of Gly （GMOs） on the improvement of renal function and hypothalamic-pituitary-gonadal （HPG） axis， the protein expression of Wnt/β-catenin and transforming growth factor-β₁ （TGF-β₁）/Smad signal pathways in kidney Yang deficiency model rats induced by adenine. MethodGMOs were prepared according to method under MOR in 2020 edition of Chinese Pharmacopoeia. Rat model of kidney Yang deficiency was established by intragastrical administration of adenine， levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂） and testosterone （T） were measured by enzyme-linked immunosorbent assay （ELISA）. Levels of urea nitrogen （BUN） and serum creatinine （SCr） were measured by spectrophotometry， hematoxylin-eosin （HE） staining was used to evaluate the pathological changes of kidney， testis and epididymis. Immunohistochemistry （IHC） was used to analyze the protein expression of E-cadherin， α-smooth muscle actin （α-SMA）， Wnt2b， β-catenin， Smad1 and Smad4. ResultMOR processed with 100∶6 and 100∶12 proportions of Gly （short for GMO/100∶6 and GMO/100∶12） had the most obvious improvement on the body posture of kidney Yang deficiency model rats. GMO/100∶12 had the best effect on reducing the levels of BUN， SCr， FSH， LH and the ratio of E₂/T. GMO/100∶6 and GMO/100∶12 had the best effect on regulating the protein expression of E-cadherin， α-SMA， Wnt2b， β-catenin， Smad1 and Smad4. ConclusionGMO/100∶6 and GMO/100∶12 have the a good effect on the improvement of renal function and HPG axis in kidney Yang deficiency model rats induced by adenine， which is related with the fact that they can regulate Wnt/β-catenin pathway in renal and testicular tissue and TGF-β₁/Smads pathway in testicular tissue.

Animals ; Glycyrrhiza/adverse effects* ; Plant Extracts/toxicity* ; Rats ; Rats, Sprague-Dawley ; Sargassum

Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.

BACKGROUND/AIMS: Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. METHODS: A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. RESULTS: The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson's capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities. CONCLUSIONS: These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.
Calibration ; Carcinoma, Hepatocellular ; Cohort Studies ; Disease-Free Survival ; Hepatectomy ; Humans ; Multivariate Analysis ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate

Objective To observe the anesthesia related effect of dexmedetomidine conscious sedation on Laryngeal mask airway general anesthesia in Parkinson patients with deep brain electric stimulus implantation.Methods Forty patients (72 males, 8 females, aged 18-75 years, ASA physical status Ⅰ or Ⅱ) of Parkinson disease with selective operated bilateral subthalamic nucleus deep brain electric stimulus implantation were selected and randomly divided into dexmedetomidine group (group D) and contrast group (group C), 20 cases in each group.The operation divided into two stages: in the first stage, the electrode was put under the local anesthesia, CT examination proof of electrode placement satisfaction was the end of the first stage.The second stage needed to bury the pulse generator under of the chest skin under general anesthesia.For group D, dexmedetomidine 0.5 μg/kg was pumped venously within 15 min after entering the operating room, the speed of 0.1-0.3 μg·kg-1·h-1 was kept subsequently until the end of the first period.For group C, the same dosage of normal saline was pumped.The times of micro-electrode interference, tremor relief were recorded.Ramsay scores of two groups of patients were recorded at the entry of operating room (T0), partial infiltration anesthesia (T1), unilateral electrode implantation (T2), contralateral electrode implantation (T3), the end of the first period (T4);the time needed to vanish consciousness, implant laryngeal mask airway, recover the spontaneous breathing and extubation were recorded;the propofol, remifentanil dosage from the beginning of general anesthesia induction to the end of the surgery were recorded.Results The micro-electrode was intervened and tremble was relieved in both two groups.Compared with group C, the ramsay scores of T1-T4 were obviously increased in group D (P<0.05), the time needed to vanish consciousness, implant laryngeal mask airway, recover the autonomous respiration, extubation were significantly shortened in group D (P<0.05), the dosage of propofol, remifentanil from the beginning of the general anesthesia starts to the end of the surgery were significantly reduced in group D (P<0.05).Conclusion Dexmedetomidine provided the excellent sedation to the first period of Parkinson patients with deep brain electric stimulus implantation;it can shorten the time of the anesthesia induction and awakening time, as well as decreases propofol and remifentanil dosage.

Objective To assess the efficacy and safety of morinidazole combined with appendectomy in treating purulent or gangrenous appendicitis.Methods Double-blind randomized controlled multicenter clinical trial was designed and conducted.Totally 437 patients were included,219 in the control group and 218 in the experimental group.Cases of purulent or gangrenous appendicitis were enrolled and assigned to each of the two groups.The control group received ornidazole injection for 5 to 7 days while the experimental group received morinidazole injection.Both groups underwent appendectomy.Clinical response,micrombiological outcomes,overall response were evaluated.Adverse events and side effects were recorded.Results No significant difference was observed between the two groups regarding the clinical healing rate at 5-10 days after medicine withdrawal,anaerobia clearance and overall healing rates.Adverse events occurred in 140 patients (32.1％).Incidence of adverse events in the control group and the experimental group was 34.7％ and 29.4％,respectively (P ＞ 0.05).The overall incidence of side effects was 15.1％ (66 cases).Side effects were less seen in the experimental group compared with that in the control group (11.5％ vs.18.7％,P ＜ 0.05).The most frequent side effects were aminotransferase rising,thrombocytosis,nausea,vomiting and electrocardiographic abnormality.Conclusions The effect of morinidazole plus operation was comparable with ornidazole in treating purulent or gangrenous appendicitis.The safety of morinidazole is better than ornidazole.

Objective To explore the effect of the unilateral lumbar anesthesia by hypobaric bupivacaine and general anesthe‐sia in elderly hip replacement and their influence on the stress response .Methods Forty elderly patients undergoing hip replace‐ment in our hospital from December 2013 to November 2014 were selected and randomly divided into the unilateral lumbar anesthe‐sia group and general anesthesia group according to the random number table ,20 cases in each group .Venous blood was collected to determine the levels of blood sugar ,serum catecholamine(CA) and cortisol(CORT ) at 10 min before anesthesia(T0 ) ,end of surgery (T1 ) and at postoperative 24 h(T2 ) .MAP ,HR ,SpO2 ,intraoperative adverse reactions and postoperative related complications were recorded at each time point ,and the comparative analysis was performed .Results All patients successfully completed surgery and the anesthetic effect was satisfied .The occurrence rates of intraoperative hypotension ,hypertension and bradycardia in the unilateral lumbar anesthesia group were lower than those in the general anesthesia group ,the differences had statistical significances (P>0 .05) .HR and MAP at T1 in the two groups were reduced ,but the differences between the two groups were no statistical signifi‐cance(P>0 .05);the levels of GLU ,CORT and CA were increased ,moreover the differences between the two groups were statisti‐cally significant(P<0 .05) .SpO2 at T2 in the general anesthesia group was obviously lower than that in the unilateral lumbar anes‐thesia group ,while CORT was higher than that in the unilateral lumbar anesthesia group ,the differences were statistically signifi‐cant(P<0 .05) .The occurrence rates of postoperative nausea and vomiting ,sore throat ,dizziness ,drowsiness and pulmonary infec‐tion in the unilateral lumbar anesthesia group were lower than those in the general anesthesia group ,the differences were statistical‐ly significant(P<0 .05) .Conclusion The unilateral lumbar anesthesia by using hypobaric bupivacaine and general anesthesia all could offer better anesthetic effect .The unilateral lumbar anesthesia by using hypobaric bupivacaine can effectively regulate the stress response in elderly patients with hip replacement .

Objective To investigate activated nano carbon in prophylactic central lymph node dissection of T1 papillary thyroid non-microcarcinoma.Methods Patients with T1 papillary thyroid non-microcarcinoma in Thyroid Surgery Department of Sun Yat-sen Memorial Hospital of Sun Yat-sen University undergoing surgery from Jan.2012 to Jun.2013 were divided into 2 groups:odd numbers were the experimental group,and even numbers were the control group.Activated nano carbon was injected in the affected side of the thyroid in the experimental group.The lymph node metastasis,parathyroid function,and the rate of recurrent laryngeal nerve (RLN) injury were compared between the 2 groups.Results The total number of resected lymph nodes in the experimental group and the control group were 327 and 238 respectively.The positive lymph nodes in the experimental group and the control group were 120 (36.7％)and 56 (23.5 ％)respectively.The difference had statistical significance (P =0.000 85).The number of patients with lymphatic metastasis in the experimental group and the control group was 42 (56％) and 30 (40％) respectively.The difference had statistical significance (P =0.049 9).The average number of positive lymph node for patients in the experimental group and the control group was (2.86 ± 0.13) and(1.87 ± 0.09) respectively.The difference had statistical significance(P =0.009).The rate of transient hypoparathyroidism in the experimental group and the control group was 34.7％ and 60％ respectively.The difference had statistical significance (P =0.002).The incidence of hoarseness caused by RLN injury was 2.7％ and 4％ respectively in the experimental group and the control group.The difference had no statistical significance(P =1.000).Conclusions Activated nano carbon plays an important role in prophylactic central lymph node dissection of T1 papillary thyroid non-microcarcinoma phase.It not only contributes to lymph node dissection,but also protects parathyroid.However,it can't reduce the incidence of RLN injury.

ObjectiveTo evaluate the mid- and long-term efficacy of subfascial endoscopic perforator surgery (SEPS)in the treatment CEAP classification C4 - C6 of primary chronic venous insufficiency(CVI). MethodsClinical data of 82 cases of chronic venous insufficiency were analysed retrospectively. According to operative method adopted,patients were divided into group A in which perforator veins were ligated under subfascial endoscopic surgery (SEPS group ),and group B in which perforator veins were not ligated (non-SEPS group).Diagnosis was established by clinical symptoms,color Doppler or ascending venography in all patients.Postoperatively patients were followed up regularly.The clinical outcomes between different surgicalmethods in two groups were assessed byCEAP clinical classification,CEAP clinical symptom scores,cumulative ulcer healing rate and cumulative ulcer recurrence rate.ResultsNo significant differences were found in CEAP clinical classification,CEAP clinical symptom scores between the two groups preoperatively ( P ＞ 0.05 ). There were significant differences in CEAP clinical classification such as edema,lipodermatosclerosis,venous ulceration between the two groups on 2 years postoperatively (P ＜ 0.05 ).The amount of swelling limbs,healed ulceration,active ulceration in group A was less than group B (P ＜ 0.05 ) on 3' and 5' years postoperatively.Significant differences were found postoperatively in total clinical symptom scores between group A and B.Clinical symptoms such as swelling,lipodermatosclerosis,ulcer healing in group A relieved more markedly than group B ( P ＜ 0.05 ).The median healing time of ulcers was 2.3 and 3.7 months respectively in group A and B.Log-rank test on group differences was sensitive to long-term cumulative ulcer healing rate ( x2 =4.063,P =0.044).But Breslow test on group differences was sensitive to early cumulative ulcer healing rate ( x2 =5.471,P =0.019).Cumulative ulcer healing rate in group A was significantly higher than in group B postoperatively (P ＜ 0.05 ).The cumulative ulcer recurrence rate in group A was significantly lower than group B (P ＜ 0.05).ConclusionsSuperficial vein resection combined with perforator vein ligation significantly enhanced clinical efficacy,accelerated ulcer healing and decreased mid- and long-term ulcer recurrence rate.