Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

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.

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

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.

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.

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

Objective To observe the anatomic relationship between the lateral sural artery perforators and the nutrient vessels of the lateral sural cutaneous nerve that were combined to design a compound muscle flap.And to observe the effect of this flap clinical application.Methods Ten adult and fresh cadaver lower limbs were observed the anatomic relationship between the lateral sural artery perforators and the nutrient vessels of the lateral sural cutaneous nerve,and were combined to design a compound muscle flap.Clinically applied in 5 cases,and the flap sizes ranged from 6 cm × 9 cm to 9 cm × 12 cm.Results After into the muscle,the lateral sural artery issued 3-5 perforating branches (OD:0.2-1.8 mm) along the way,which provided nutrition for the lateral head of the gastrocnemius and the surrounding skin and involved in the formation of shallow and deep fascia vascular network with the nutrient vessels of the lateral sural cutaneous nerve.From Feburary 2009 to November 2011,the compound pedicled muscle flap were clinically applied in 5 cases to repair the skin defects of the anterior knee and proximal tibia.Flaps in 4 cases completely survivedand 1 case had partial superficial necrosis on the distal part of the flap,which healed after dressing change.Conclusion The compound pedicled muscle flap has two sets of blood supply that could expand the area of the flap,which could guarantee its feeling.This kind of flap could repair the complicated skin and soft tissue defects around the knee joint.

Objective To investigate the clinical outcomes of sternoclavicular hook plate in treatment of the anterior sternoclavicular joint dislocation. Methods A new device named sternoclavicular hook plate was devised by our team. Between May 2002 and Octorber 2009, 66 patients with sternoclavicular joint anterior dislocation were treated with the new device, among whom there were 47 males and 19 females,aged 21-68 years old (average, 32.6 years old). Twenty-one cases were caused by crush injury, 5 cases by falling and 40 cases by traffic accident. Anterior fracture-dislocation was found in 41 cases. According to the Allman system, there were 35 cases of type Ⅱ and 31 cases of type Ⅲ. Patients were evaluated with serial clinical and radiographic examinations. Rockwood score were used after the operation to assess the curative effect. Results The average operative time was 33 min (range, 20-48 min). The mean blood loss was 60 ml (range, 20-90 ml). There were no vascular or peripheral nerve injuries in the patients. All incisions healed smoothly. The X-ray and CT showed that the reduction of sternoclavicular joint and the location of internal fixation were satisfactory. All the 66 patients were followed up for 12-37 months (average, 17 months). There was no internal fixation failure, redislocation or other complications. The sternoclavicular hook plate was removed 12 months after operation. The mean Rockwood's score was 13.2 (8 to 15). There were excellent in 50cases, good in 15 cases, and fair in 1 case. Conclusion The sternoclavicular hook plate is a new, safe and liable technique for sternoclavicular fracture-dislocation. This new technique is helpful for early functional exercises.

ObjectiveTo investigate the accuracy of percutaneous iliosacral screw fixation in sacroiliac joint fracture-dislocation with minimally invasive guider with CT-guided.MethodsFrom January 2011 to May 2011,8 patients with sacroiliac joint fracture-dislocation were treated using percutaneous iliosacral screw fixation assist with minimally invasive guider in CT-guided,which included 5 males and 3 females,with the average age of 32 years (ranged from 26 to 56 years).All patients suffered with vertically unstable pelvic fractures.Bone traction was used in femoral condyle for 6 cases which displaced more than 2cm in sacroiliac joints.Patients were prone position on the CT bed.First sacroiliac joint CT-scan was performed,then marked the needle position on affected side buttocks after measure the best position and track of needle that expected on CT computer screen.According to the data of CT-scan,the angle of the devices was adjusted,which could control 3D direction of the minimally invasive guider,then insert the Kirschner wire into sacroiliac joint guided with the front end of the sleeve of the minimally invasive guider,confirmed the track of needle was excellent with CT-scan (3D),then the guider was moved out and put the hollow screw (dia 7.3 mm Synthes) into the sacroiliac joint along the Kirschner wire.ResultsAll 8 patients were successfully insert the Kirschner wire.The operation time was from 10 to 20 min(mean,14 min).All screws were in the position expected before surgery,no cut out of bone with the CT-scan immediately after operation,the shape of sacroiliac joint was restored satisfied and the fixation was stable.No numbness and radiation-like pain appeared among the operation in the lower limb for all patients,no case had vascular and neurological complications postoperative.ConclusionThe minimally invasive guider can improve the accuracy,security and simplicity of the percutaneous iliosacral screw fixation with CT-guided,and also avoid the deviation of needle insertion angle that determined by operator himself.