Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Background: The public now imposes higher demands on the government than in the past, which has created the role overload faced by low-ranking government employees in China. This research investigates the relationship between role overload and health among low-ranking government employees and explores the mediating effects of burnout. Methods: It draws on a survey of 2064 low-ranking government employees by probability proportionate to size sampling in China's Shandong Province. Structural equation modeling (SEM) methods are used to analyze the data. Results: Both role overload and burnout were found to have negative effects on low-ranking government employees' health; however, the associations varied among the three age groups (less than 36, between 36 and 45, and over 45). Those over 45 reported the highest level of both physical and psychological health, while the youngest age group (less than 36) reported the lowest level of health. Role overload has a direct influence on health among government employees over 45 but not among those below 45. Burnout's mediating effects between role overload and health are significant among all age groups, but most significant among the youngest civil servants below 36. Conclusions The findings evidenced that both role overload and burnout affect low-ranking government employees' self-reported physical and psychological health. In addition, the effect of age differences in coping with role stressors and burnout should be considered.

Objective: To explore the technical characteristics and short-term clinical efficacy of robotic-assisted intersphincteric resection (ISR) for patients with low rectal cancer. Methods: A retrospective cohort study was used. Inclusion criteria: (1) rigid colonoscopy showed lower margin of the tumor ≤5 cm from the anal verge; (2) preoperative rectal MRI or endorectal ultrasound revealed staging T1-2, or T3 patients receiving concurrent chemoradiotherapy; (3) patients less than 70 years old with good function of anal sphincter before surgery; (4) no synchronous multiple primary carcinoma, and no distant metastasis; (5) the method of operation was agreed by the patient. Exclusion criteria: (1) T4 stage tumors; (2) sphincter dysfunction before operation; (3) recurrent tumors; (4) lower edge of tumors beyond the dentate line; (5) death due to non-rectal cancer during follow-up and unsatisfactory follow-up data. The clinical data of 21 patients with low rectal cancer meeting inclusion criteria undergoing robotic-assisted ISR at our department from January 2015 to June 2018 were collected. Parameters during and after operation were observed. Anorectal manometry was performed at 3, 6, and 12 months after the operation, and anal function was evaluated at 3, 6, and 12 months after the closure of the stoma by Kirwan classification and Wexner fecal incontinence score. The key steps of the operation are as follows: according to the principle of total mesorectal excision, the robot continued to enter into the levator ani hiatusdistally, and dissectin the sphincter space; according to the scope of sphincter resection, ISRwas divided into partial ISR, subtotal ISR, and total ISR; subtotal and total ISR usually needed to be combined with transanal pathway. The reconstruction of digestive tract was performed by double stapler anastomosis under laparoscope orhand-sewnanastomosis under direct vision, and preventive ileostomy was completed in the right lower abdomen. Results: Of 21 patients, 13 were male and 8 were female with mean age of (57.5±16.3) years. All the patients successfully completed the operation without conversion to laparotomy. Fourteen cases (66.7%) adopted partial ISR through complete transabdominal approach, 6 cases (28.6%) adopted the subtotal ISR through combined transabdominal and transanal approachs, and 1 case (4.8%) adopted the total ISR through the combined transabdominal and transanal approachs. The total operation time was (213.1±56.3) minutes, including (27.3±5.4) minutes for mechanical arm installation and (175.7±51.6) minutes for robotic operation. The amount of intraoperative hemorrhage was (62.8±23.2) ml, and no blood transfusion was performed in any patient. All patients underwent prophylactic ileostomy, and the stoma was closed 3-6 months after the operation. Except one case of anastomotic leakage, all other stomas were closed successfully. The postoperative hospitalization time was (7.6±2.2) days, and time to fluid intake was (3.3±0.9) days. One case of anastomotic leakage, one case of anastomotic stenosis, one case of inflammatory external hemorrhoids and one case of urinary retention occurred after surgery,and all of them were cured by conservative treatment. The mean diameter of tumors was (2.9±1.2) cm, and the number of harvested lymph node was 12.8 ± 3.3. In the whole group, the circumcision margin was negative, the proximal margin was (12.2 ± 2.1) cm, the distal margin was (1.1 ± 0.4) with all negative, and the R0 resection rate was 100%. The results of anorectal manometry showed that the preoperative rest pressure, rectal maximum squeeze pressure, initial sensory volume and maximum tolerated volume were (45.19±8.46) mmHg, (128.18±18.80) mmHg, (44.33±10.11) ml and (119.00±19.28) ml, respectively;these parameters reduced significantly 3 months after operation and they were (23.44±5.54) mmHg, (93.72±12.15) mmHg, (17.72±5.32) ml and (70.44±10.9) ml, respectively. The differences were statistically significant (all P<0.001). The resting pressure and the rectal maximum squeeze pressure returned to preoperative levels 12 months after operation, which were (39.33±6.64) mmHg and (120.58±16.47) mmHg, respectively (both P>0.05), while the initial sensory volume and the maximum tolerated volume failed to reach the preoperative state, which were (30.67±7.45) ml and (92.25±10.32) ml, respectively (both P<0.05). The patients were followed up for (22.1±10.6) months without local recurrence and distant metastasis. Eighteen patients were evaluated for anal function: Kirwan classification was grade I for 6 cases, grade II for 7 cases, grade III for 4 cases, and grade IV for 1 case; Wexner incontinence score was 8.6±0.8; 14 cases had good defecation control. Conclusion The clinical efficacy of ISR with Da Vinci robot in the treatment of low rectal cancer is satisfactory.

Objective: To understand the epidemiologic features of the rabies in Xishuang banna prefecture of Yunnan province, China in 2008-2017 and the viral molecular-evolution characteristics. Methods: The data of rabies case questionnaire were collected. The brain tissue samples from mad dogs, suspicious sick dogs and human brain tissue, saliva and cerebrospinal fluid samples from rabies patients were collected in Xishuangbanna. Coding region of nucleoprotein and glycoprotein genes were amplified by RT-PCR and sequenced. Homology and phylogenetic analysis were performed using the relevant bioinformatics software. Results: A total of 62 cases of human rabies were occurred in 28 districts of the 3 counties, Xishuangbanna prefecture in 2008-2017. Of them, 37 cases in Jinghong county, 15 in Menghai county and 10 in Mengla county. In which 48 cases were bitten by domestic dogs (77.42%), 11 cases were bitten by wild dogs (17.74%). Rabies case was occurred every year in the past decade. The seasonal incidence was not obvious. The majority of patients were aged from 30 to 59 years-old, with the youngest 1 year-old and the eldest 91 year-old. The male to female ratio was 1.70∶1, most cases were farmers. The nucleotide sequences of nucleoprotein gene of 9 virus strains (7 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from the samples of dogs and patients. Homology and phylogenetic analyses indicated that the 5 strains belonged to clade China-Ⅰ, 3 clade China-Ⅱ and 1 clade China-Ⅵ. The nucleotide sequences of glycoprotein gene of 5 virus strains (3 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from these positive samples, and all were clade China-Ⅰ, it is same with nucleoprotein genes analysis result from these 5 virus strains. These China-Ⅰ and China-Ⅱ strains from Xishuangbanna have a closer genetic relationship with same clade strains isolated from Pu’er and other prefectures of Yunnan province as well as Sichuan, Guizhou and Guangxi. The China-Ⅵ strain from Xishuangbanna share high homology and genetic relationship with China-Ⅵ strains isolated from southwestern Yunnan and neighbouring countries such as Myanmar, Laos and Vietnam in recent years. Conclusions In Xishuangbanna, rabies mainly occurred in rural area and domestic dog was the main source of transmission. These RABV clades China-Ⅰ, China-Ⅱ and China-Ⅵ were found in this region and the China-Ⅰ was principal clade. The transmission source of China-Ⅰ and China-Ⅱ were from adjacent areas in the province and China-Ⅵ was from Myanmar and Laos.

Objective To explore the technical characteristics and short?term clinical efficacy of robotic ? assisted intersphincteric resection (ISR) for patients with low rectal cancer. Methods A retrospective cohort study was used. Inclusion criteria: (1) rigid colonoscopy showed lower margin of the tumor≤5 cm from the anal verge; (2) preoperative rectal MRI or endorectal ultrasound revealed staging T1?2, or T3 patients receiving concurrent chemoradiotherapy; (3) patients less than 70 years old with good function of anal sphincter before surgery; (4) no synchronous multiple primary carcinoma, and no distant metastasis; (5) the method of operation was agreed by the patient. Exclusion criteria: (1) T4 stage tumors;(2) sphincter dysfunction before operation; (3) recurrent tumors; (4) lower edge of tumors beyond the dentate line; (5) death due to non?rectal cancer during follow?up and unsatisfactory follow?up data. The clinical data of 21 patients with low rectal cancer meeting inclusion criteria undergoing robotic?assisted ISR at our department from January 2015 to June 2018 were collected. Parameters during and after operation were observed. Anorectal manometry was performed at 3, 6, and 12 months after the operation, and anal function was evaluated at 3, 6, and 12 months after the closure of the stoma by Kirwan classification and Wexner fecal incontinence score. The key steps of the operation are as follows: according to the principle of total mesorectal excision, the robot continued to enter into the levator ani hiatusdistally, and dissectin the sphincter space; according to the scope of sphincter resection, ISRwas divided into partial ISR, subtotal ISR, and total ISR; subtotal and total ISR usually needed to be combined with transanal pathway. The reconstruction of digestive tract was performed by double stapler anastomosis under laparoscope orhand?sewnanastomosis under direct vision, and preventive ileostomy was completed in the right lower abdomen. Results Of 21 patients, 13 were male and 8 were female with mean age of (57.5 ± 16.3) years. All the patients successfully completed the operation without conversion to laparotomy. Fourteen cases (66.7%) adopted partial ISR through complete transabdominal approach, 6 cases (28.6%) adopted the subtotal ISR through combined transabdominal and transanal approachs, and 1 case (4.8%) adopted the total ISR through the combined transabdominal and transanal approachs. The total operation time was (213.1±56.3) minutes, including (27.3±5.4) minutes for mechanical arm installation and (175.7±51.6) minutes for robotic operation. The amount of intraoperative hemorrhage was (62.8 ± 23.2) ml, and no blood transfusion was performed in any patient. All patients underwent prophylactic ileostomy, and the stoma was closed 3?6 months after the operation. Except one case of anastomotic leakage, all other stomas were closed successfully. The postoperative hospitalization time was (7.6±2.2) days, and time to fluid intake was (3.3± 0.9) days. One case of anastomotic leakage, one case of anastomotic stenosis, one case of inflammatory external hemorrhoids and one case of urinary retention occurred after surgery,and all of them were cured by conservative treatment. The mean diameter of tumors was (2.9±1.2) cm, and the number of harvested lymph node was 12.8 ± 3.3. In the whole group, the circumcision margin was negative, the proximal margin was (12.2 ± 2.1) cm, the distal margin was (1.1 ± 0.4) with all negative, and the R0 resection rate was 100%. The results of anorectal manometry showed that the preoperative rest pressure, rectal maximum squeeze pressure, initial sensory volume and maximum tolerated volume were (45.19±8.46) mmHg, (128.18±18.80) mmHg, (44.33±10.11) ml and (119.00±19.28) ml, respectively;these parameters reduced significantly 3 months after operation and they were (23.44±5.54) mmHg, (93.72±12.15) mmHg, (17.72±5.32) ml and (70.44 ± 10.9) ml, respectively. The differences were statistically significant (all P<0.001). The resting pressure and the rectal maximum squeeze pressure returned to preoperative levels 12 months after operation, which were (39.33±6.64) mmHg and (120.58±16.47) mmHg, respectively (both P>0.05), while the initial sensory volume and the maximum tolerated volume failed to reach the preoperative state, which were (30.67±7.45) ml and (92.25±10.32) ml, respectively (both P<0.05). The patients were followed up for (22.1±10.6) months without local recurrence and distant metastasis. Eighteen patients were evaluated for anal function: Kirwan classification was grade I for 6 cases, grade II for 7 cases, grade III for 4 cases, and grade IV for 1 case; Wexner incontinence score was 8.6 ± 0.8; 14 cases had good defecation control. Conclusion The clinical efficacy of ISR with Da Vinci robot in the treatment of low rectal cancer is satisfactory.

Objective To explore the technical characteristics and short?term clinical efficacy of robotic ? assisted intersphincteric resection (ISR) for patients with low rectal cancer. Methods A retrospective cohort study was used. Inclusion criteria: (1) rigid colonoscopy showed lower margin of the tumor≤5 cm from the anal verge; (2) preoperative rectal MRI or endorectal ultrasound revealed staging T1?2, or T3 patients receiving concurrent chemoradiotherapy; (3) patients less than 70 years old with good function of anal sphincter before surgery; (4) no synchronous multiple primary carcinoma, and no distant metastasis; (5) the method of operation was agreed by the patient. Exclusion criteria: (1) T4 stage tumors;(2) sphincter dysfunction before operation; (3) recurrent tumors; (4) lower edge of tumors beyond the dentate line; (5) death due to non?rectal cancer during follow?up and unsatisfactory follow?up data. The clinical data of 21 patients with low rectal cancer meeting inclusion criteria undergoing robotic?assisted ISR at our department from January 2015 to June 2018 were collected. Parameters during and after operation were observed. Anorectal manometry was performed at 3, 6, and 12 months after the operation, and anal function was evaluated at 3, 6, and 12 months after the closure of the stoma by Kirwan classification and Wexner fecal incontinence score. The key steps of the operation are as follows: according to the principle of total mesorectal excision, the robot continued to enter into the levator ani hiatusdistally, and dissectin the sphincter space; according to the scope of sphincter resection, ISRwas divided into partial ISR, subtotal ISR, and total ISR; subtotal and total ISR usually needed to be combined with transanal pathway. The reconstruction of digestive tract was performed by double stapler anastomosis under laparoscope orhand?sewnanastomosis under direct vision, and preventive ileostomy was completed in the right lower abdomen. Results Of 21 patients, 13 were male and 8 were female with mean age of (57.5 ± 16.3) years. All the patients successfully completed the operation without conversion to laparotomy. Fourteen cases (66.7%) adopted partial ISR through complete transabdominal approach, 6 cases (28.6%) adopted the subtotal ISR through combined transabdominal and transanal approachs, and 1 case (4.8%) adopted the total ISR through the combined transabdominal and transanal approachs. The total operation time was (213.1±56.3) minutes, including (27.3±5.4) minutes for mechanical arm installation and (175.7±51.6) minutes for robotic operation. The amount of intraoperative hemorrhage was (62.8 ± 23.2) ml, and no blood transfusion was performed in any patient. All patients underwent prophylactic ileostomy, and the stoma was closed 3?6 months after the operation. Except one case of anastomotic leakage, all other stomas were closed successfully. The postoperative hospitalization time was (7.6±2.2) days, and time to fluid intake was (3.3± 0.9) days. One case of anastomotic leakage, one case of anastomotic stenosis, one case of inflammatory external hemorrhoids and one case of urinary retention occurred after surgery,and all of them were cured by conservative treatment. The mean diameter of tumors was (2.9±1.2) cm, and the number of harvested lymph node was 12.8 ± 3.3. In the whole group, the circumcision margin was negative, the proximal margin was (12.2 ± 2.1) cm, the distal margin was (1.1 ± 0.4) with all negative, and the R0 resection rate was 100%. The results of anorectal manometry showed that the preoperative rest pressure, rectal maximum squeeze pressure, initial sensory volume and maximum tolerated volume were (45.19±8.46) mmHg, (128.18±18.80) mmHg, (44.33±10.11) ml and (119.00±19.28) ml, respectively;these parameters reduced significantly 3 months after operation and they were (23.44±5.54) mmHg, (93.72±12.15) mmHg, (17.72±5.32) ml and (70.44 ± 10.9) ml, respectively. The differences were statistically significant (all P<0.001). The resting pressure and the rectal maximum squeeze pressure returned to preoperative levels 12 months after operation, which were (39.33±6.64) mmHg and (120.58±16.47) mmHg, respectively (both P>0.05), while the initial sensory volume and the maximum tolerated volume failed to reach the preoperative state, which were (30.67±7.45) ml and (92.25±10.32) ml, respectively (both P<0.05). The patients were followed up for (22.1±10.6) months without local recurrence and distant metastasis. Eighteen patients were evaluated for anal function: Kirwan classification was grade I for 6 cases, grade II for 7 cases, grade III for 4 cases, and grade IV for 1 case; Wexner incontinence score was 8.6 ± 0.8; 14 cases had good defecation control. Conclusion The clinical efficacy of ISR with Da Vinci robot in the treatment of low rectal cancer is satisfactory.

In the process of current clinical efficacy evaluation of traditional Chinese medicine, there are four diagnostic information lack of scientific evidence, patients with individualized information using deficiencies. For example the inadequate efficacy evaluation is rarely mentioned in literature methodology to process syndrome. In order to deal with clinical information more objectively and comprehensively, The clinical curative effect of traditional Chinese medicine should be evaluated reasonably, so as to facilitate the clinical treatment of syndromes. This article describes the background, classifications, advantages and disadvantages of traditional Chinese medicine therapeutic evaluation information of processing method in the real word. Mainly introduced the classifications, include quantification and forecast. The former includes the scaling method, scaling method by TCM diagnosis instrument, Data Envelopment Analysis, Propensity score method, Fuzzy Mathematics Calculation Model and Prescription similarity model. The latter includes the multilevel statistical models, Generalized Linear Model and Markov model. In this paper, we introduce the common information processing methods in clinical practice, and the purpose is to simplify and clarify the evaluation objects so as to facilitate the evaluation of TCM clinical efficacy.

OBJECTIVETo assess the association of interferon gamma gene (IFNγ ) tag single nucleotide polymorphisms (Tag SNPs) with hepatitis B virus (HBV) infection in ethnic Dai and Hani minorities from Xishuangbanna, Yunnan.

METHODSPeripheral blood samples were collected from 300 Dai minorities and 300 Hani minorities, each included 100 healthy controls and 200 HBV infected individuals (including 100 spontaneous recovery subjects and 100 chronic HBV infected patients). Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDITOF-MS) was used to determine the Tag SNPs of IFNγ gene. Haplotypes were constructed.

RESULTSIn Hani and Dai minorities, the frequencies of rs1861494 CC genotype in HBV infected group was significantly higher than the healthy group (Dai: χ2=10.017, P=0.001; Hani: χ2=6.515, P=0.039), and there was a significant difference between the HBV infected group and the control group under the C allele recessive mode (CC/TC+TT) (Dai: P=0.035, OR=9.567, 95%CI: 1.166-78.499; Hani: P=0.027, OR=5.484, 95%CI: 1.216-24.726). In Dai minorities, the frequencies of rs2069705 CC genotype and C allele in chronic HBV infected group was significantly higher than the spontaneous recovery group (genotype: χ2=8.112, P=0.017; allele: χ2=4.066, P=0.044), and there was a significant difference between chronic HBV infected group and spontaneous recovery group under the C allele recessive mode (CC/CT+TT) (P=0.013, OR=0.341, 95%CI: 0.146-0.796).

CONCLUSIONAbove results suggested that the rs1861494 CC genotype of the IFNγ gene has conferred an increased risk for HBV susceptibility in both Dai and Hani minorities. In addition, the rs2069705 CC genotype may be a risky factor for Dai minorities to develop chronic HBV infection.

Adult ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; ethnology ; Genotype ; Hepatitis B ; ethnology ; genetics ; virology ; Hepatitis B virus ; physiology ; Humans ; Interferon-gamma ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; Young Adult

Heat sensitive protein medicines are increasingly exhibiting their critical importance on treatment of various diseases at present. But their popularization and application meet a great challenge because of their heat instability. In the present study, insulin was taken as a heat sensitive protein medicine and amino acid as bio-protective agent in order to investigate if these amino acids can protect the insulin from losing its bioactivity due to desiccation. The experiment was performed by using replica exchange molecular simulation (REMD) method and Gromacs software with Gromos96 (53a6) force field. The REMD results indicated that these amino acids could protect the bioactive structure of insulin during desiccation. The configurations of the protected insulin were preserved very well. Those results proved that amino acid is a kind of good bioactive protective agent for the heat sensitive protein medicines.
Amino Acids ; chemistry ; Desiccation ; Drug Stability ; Insulin ; chemistry ; Molecular Dynamics Simulation ; Software