Application of silk fibroin coatings for biomaterial surface modification: a silk road for biomedicine / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Silk fibroin (SF) as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity, tunable biodegradability, and high biocompatibility. Nowadays, various techniques have been developed for the applications of SF in bioengineering. Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films, hydrogels, and scaffolds. SF is also valuable as a coating on other substrate materials for biomedicine; however, there are few reviews related to SF-coated biomaterials. Thus, in this review, we focused on the surface modification of biomaterials using SF coatings, demonstrated their various preparation methods on substrate materials, and introduced the latest procedures. The diverse applications of SF coatings for biomedicine are discussed, including bone, ligament, skin, mucosa, and nerve regeneration, and dental implant surface modification. SF coating is conducive to inducing cell adhesion and migration, promoting hydroxyapatite (HA) deposition and matrix mineralization, and inhibiting the Notch signaling pathway, making it a promising strategy for bone regeneration. In addition, SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury. SF coating has been proven to enhance the mechanical properties of the substrate material, and render integral stability to the dressing material during the regeneration of skin and mucosa. Moreover, SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties, mechanical flexibility, and angiogenesis promotion effect. In addition, SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials. Thus, this review can be of great benefit for further improvements in SF-coated biomaterials, and will undoubtedly contribute to clinical transformation in the future.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

The 10-year outcome and prognostic factors of laparoscopic D 2 radical distal gastrectomy for locally advanced gastric cancer: a CLASS multicenter study / 中华消化外科杂志

Objective:To investigate the 10-year outcome and prognostic factors of laparo-scopic D 2 radical distal gastrectomy for locally advanced gastric cancer. Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 652 patients with locally advanced gastric cancer who were admitted to 16 hospitals from the multicenter database of laparoscopic gastric cancer surgery in the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group, including 214 cases in the First Affiliated Hospital of Army Medical University, 191 cases in Fujian Medical University Union Hospital, 52 cases in Nanfang Hospital of Southern Medical University, 49 cases in West China Hospital of Sichuan University, 43 cases in Xijing Hospital of Air Force Medical University, 25 cases in Jiangsu Province Hospital of Chinese Medicine, 14 cases in the First Medical Center of the Chinese PLA General Hospital, 12 cases in No.989 Hospital of PLA, 12 cases in the Third Affiliated Hospital of Sun Yat-Sen University, 10 cases in the First Affiliated Hospital of Nanchang University, 9 cases in the First People's Hospital of Foshan, 7 cases in Zhujiang Hospital of Southern Medical University, 7 cases in Fujian Medical University Cancer Hospital, 3 cases in Zhongshan Hospital of Fudan University, 2 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2 cases in Peking University Cancer Hospital & Institute, from February 2004 to December 2010 were collected. There were 442 males and 210 females, aged (57±12)years. All patients underwent laparoscopic D 2 radical distal gastrectomy. Observation indicators: (1) surgical situations; (2) postoperative pathological examination; (3) postoperative recovery and complications; (4) follow-up; (5) prognostic factors analysis. Follow-up was conducted by outpatient examination and telephone interview to detect the tumor recurrence and metastasis, postoperative survival of patients up to March 2020. 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 percen-tages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-Rank test was used for survival analysis. Univariate and multivariate analyses were analyzed using the COX hazard regression model. Results:(1) Surgical situations: among 652 patients, 617 cases underwent D 2 lymph node dissection and 35 cases underwent D 2+ lymph node dissection. There were 348 cases with Billroth Ⅱ anastomosis, 218 cases with Billroth Ⅰ anastomosis, 25 cases with Roux-en-Y anastomosis and 61 cases with other digestive tract reconstruction methods. Twelve patients had combined visceral resection. There were 569 patients with intraoperative blood transfusion and 83 cases without blood transfusion. The operation time of 652 patients was 187(155,240)minutes and volume of intraoperative blood loss was 100(50,150)mL. (2) Postoperative pathological examina-tion: the maximum diameter of tumor was (4.5±2.0)cm of 652 patients. The number of lymph node dissected of 652 patients was 26(19,35), in which the number of lymph node dissected was >15 of 570 cases and ≤15 of 82 cases. The number of metastatic lymph node was 4(1,9). The proximal tumor margin was (4.8±1.6)cm and the distal tumor margin was (4.5±1.5)cm. Among 652 patients, 255 cases were classified as Borrmann type Ⅰ-Ⅱ, 334 cases were classified as Borrmann type Ⅲ-Ⅳ, and 63 cases had missing Borrmann classification data. The degree of tumor differentiation was high or medium in 171 cases, low or undifferentiated in 430 cases, and the tumor differentiation data was missing in 51 cases. There were 123, 253 and 276 cases in pathological stage T2, T3 and T4a, respectively. There were 116, 131, 214 and 191 cases in pathological stage N0, N1, N2 and N3, respectively. There were 260 and 392 cases in pathological TNM stage Ⅱ and Ⅲ, respectively. (3) Postoperative recovery and complications: the time to postoperative first out-of-bed activities, time to postoperative first flatus, time to the initial liquid food intake, duration of postoperative hospital stay of 652 patients were 3(2,4)days, 4(3,5)days, 5(4,6)days, 10(9,13)days, respectively. Among 652 patients, 69 cases had postoperative complications. Clavien-Dindo grade Ⅰ-Ⅱ, grade Ⅲa, grade Ⅲb, and grade Ⅳa complications occurred in 60, 3, 5 and 1 cases, respectively (some patients could have multiple complications). The duodenal stump leakage was the most common surgical complication, with the incidence of 3.07%(20/652). Respiratory complication was the most common systemic complication, with the incidence of 2.91%(19/652). All the 69 patients were recovered and discharged successfully after treatment. (4) Follow-up: 652 patients were followed up for 110-193 months, with a median follow-up time of 124 months. There were 298 cases with postoperative recurrence and metastasis. Of the 255 patients with the time to postoperative recurrence and metastasis ≤5 years, there were 21 cases with distant metastasis, 69 cases with peritoneal metastasis, 37 cases with local recurrence, 52 cases with multiple recurrence and metastasis, 76 cases with recurrence and metastasis at other locations. The above indicators were 5, 9, 10, 4, 15 of the 43 patients with the time to postoperative recurrence and metastasis >5 years. There was no significant difference in the type of recurrence and metastasis between them ( χ2=5.52, P>0.05). Cases in pathological TNM stage Ⅱ and Ⅲ were 62 and 193 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 23 and 20 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological TNM staging between them ( χ2=15.36, P<0.05). Cases in pathological stage T2, T3, T4a were 42, 95, 118 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 9, 21, 13 of the patients with the time to postoperative recurrence and metastasis >5 years, showing no significant difference in pathological T staging between them ( Z=-1.80, P>0.05). Further analysis showed no significant difference in cases in pathological stage T2 or T3 ( χ2=0.52, 2.08, P>0.05) but a significant difference in cases in pathological stage T4a between them ( χ2=3.84, P<0.05). Cases in pathological stage N0, N1, N2, N3 were 19, 44, 85, 107 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 12, 5, 18, 8 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological N staging between them ( Z=-3.34, P<0.05). Further analysis showed significant differences in cases in pathological stage N0 and N3 ( χ2=16.52, 8.47, P<0.05) but no significant difference in cases in pathological stage N1 or N2 ( χ2=0.85, 1.18, P>0.05). The median overall survival time was 81 months after surgery and 10-year overall survival rate was 46.1% of 652 patients. The 10-year overall survival rates of patients in TNM stage Ⅱ and Ⅲ were 59.6% and 37.5%, respectively, showing a significant difference between them ( χ2=35.29, P<0.05). In further analysis, the 10-year overall survival rates of patients in pathological TNM stage ⅡA, ⅡB, ⅢA, ⅢB and ⅢC were 65.6%, 55.8%, 46.9%, 37.1% and 24.0%, respectively, showing a significant difference between them ( χ2=55.06, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage T2, T3 and T4a were 55.2%, 46.5% and 41.5%, respectively, showing a significant difference between them ( χ2=8.39, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage N0, N1, N2 and N3 were 63.7%, 56.2%, 48.5% and 26.4%, respectively, showing a signifi-cant difference between them ( χ2=54.89, P<0.05). (5) Prognostic factors analysis: results of univariate analysis showed that age, maximum diameter of tumor, degree of tumor differentiation as low or undifferentiated, pathological TNM staging, pathological T staging, pathological stage N2 or N3, post-operative chemotherapy were related factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrectomy ( hazard ratio=1.45, 1.64, 1.37, 2.05, 1.30, 1.68, 3.08, 0.56, 95% confidence interval as 1.15-1.84, 1.32-2.03, 1.05-1.77, 1.62-2.59, 1.05-1.61, 1.17-2.42, 2.15-4.41, 0.44-0.70, P<0.05). Results of multivariate analysis showed that maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ were independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrectomy ( hazard ratio=1.48,1.44, 1.81, 95% confidence interval as 1.19-1.84, 1.11-1.88, 1.42-2.30, P<0.05) and postoperative chemotherapy was a independent protective factor for the 10-year overall survi-val rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrec-tomy ( hazard ratio=0.57, 95% confidence interval as 045-0.73, P<0.05). Conclusions:Laparoscopic assisted D 2 radical distal gastrectomy for locally advanced gastric cancer has satisfactory 10-year oncologic outcomes. A high proportion of patients in pathological TNM stage Ⅲ, pathological stage T4a, pathological stage N3 have the time to postoperative recurrence and metastasis ≤5 years, whereas a high proportion of patients in pathological TNM stage Ⅱ or pathological stage N0 have the time to postoperative recurrence and metastasis >5 years. Maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ are independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D 2 radical distal gastrectomy. Postoperative chemotherapy is a independent protective factor for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D 2 radical distal gastrectomy.

“Internet+Pharmaceutical Care ”Mode：Practices and Reflection / 中国药房

OBJECTIVE：To explore n ew ideas for the intell igent development of pharmaceutical care under the background of “Internet + ”. METHODS ：Through the exploration and practice of “Internet + pharmaceutical care ”mode in Jiangsu Provincial Hospital of TCM ，the management and experience of “Internet + pharmaceutical care ”were combed out ，the results were summarized，and new thinking was put forward. RESULTS & CONCLUSIONS ：After conducting “Internet+pharmaceutical care ” practice for more than three years ，the hospital had shifted from offline services to “offline + online ”services，and drugs were delivered on line ；the mode had improved patient satisfaction ，closely connected doctors ，pharmacies and patients ，and explored new pharmaceutical care pattern of oversea anti-epidemic ，full played the advantages of pharmaceutical care in Internet healthcare ； embodies the value of pharmaceutical care ，and promoted new ecosystem of pharmaceutical care. Under the background of “Internet+”，it is necessary to let the three pronged approach （management of prescription ，drug quality and logistics enterprises ） become the key point of “Internet+pharmaceutical care ”，let data enhance the competitiveness of pharmaceutical services ，enable independent innovation to promote pharmaceutical development ，and make intelligent medicine become an innovative entry point for promoting pharmaceutical development ，constantly explore a new prospect of integrated development of medical health and information technology.

Comparison of Functional Outcomes between Functional Jejunal Interposition and Conventional Roux-en-Y Esophagojejunostomy after Total Gastrectomy for Gastric Cancer.

BACKGROUND: The reconstruction of digestive tract after total gastrectomy is associated with various postoperative complications. We aimed to investigate the differences in functional outcomes of 2 reconstruction techniques following total gastrectomy: functional jejunal interposition (FJI) versus Roux-en-Y esophagojejunostomy. METHODS: Sixty patients were enrolled and divided into FJI and Roux-en-Y groups. Nutritional parameters and incidences of reconstruction-related symptoms were evaluated. Oral glucose tolerance test and endoscopy examination were carried out. RESULTS: The postoperative prognostic nutritional index scores and postoperative/preoperative body weight, meal intake, serum albumin level ratio were significantly higher in the FJI group than in the Roux-en-Y group. At 3, 6, and 12 months postoperatively, the elevations of plasma glucose level after glucose intake were more significant in the FJI group than in the Roux-en-Y group. The incidence of postoperative stasis symptoms in the Roux-en-Y group was significantly higher than in the FJI group, but no obvious difference was observed regarding dumping and reflux symptoms. The incidence rates of severe esophageal mucosa injury and severe anastomotic stricture were also similar between the 2 groups. CONCLUSION: FJI reconstruction might accelerate the recovery of nutritional status and reduce the occurrence of stasis symptoms postoperatively as compared with Roux-en-Y esophagojejunostomy, which may have an advantage over FJI in stabilizing body glycometabolism after surgery. These 2 types of reconstruction may have a similar anti-reflux function to prevent severe reflux esophagitis and anastomotic stenosis.

Perioperative weight loss and its influencing factors in patients with colorectal cancer / 中华临床营养杂志

Objective To investigate the perioperative weight loss and its influencing factors in patients with colorectal cancer, and to provide evidence for the development and management of perioperative nutritional support strategies. Methods Ninety-one patients with colorectal cancer were enrolled and divided into observation group (n =61) with the degree of weight loss less than 5％ of preoperative weight and control group (n = 30) with the degree of weight loss more than 5％ of preoperative weight. Change of body composition and factors of weight loss in patients with colorectal cancer were compared between the two groups by single factor and multivariate analysis. Results Ninety-one patients with colorectal cancer had the average weight loss of 2. 0 kg. Of perioperative changes in body composition, the degree of body fat, muscle mass and protein group decreased statistically (P<0. 05). Univariate analysis showed that the age, intraoperative blood loss and postoperative oral nutrition intake compliance were the risk factors for the degree of weight loss in patients with colorectal cancer after the operation. Multivariate logistic regression analysis showed that the intraoperative blood loss was an independent influencing factor for the degree of postoperative weight loss in patients with colorectal cancer (P< 0. 05). Conclusion Age, intraoperative blood loss and postoperative oral nutritional intake compliance may affect the degree of weight loss during perioperative period. Intraoperative blood loss is an independent risk factor affecting the degree of weight loss during perioperative period. In future clinical research and practice, minimally invasive and accurate surgical treatment should be strengthened, the amount of intraoperative blood loss and surgical trauma should be reduced, and the postoperative oral nutrition intake of patients should be paid attention, especially for elderly patients. Personalized dietary guidance and management for different groups should be conducted, and perioperative nutritional status of patients should be improved.

Perioperative weight loss and its influencing factors in patients with colorectal cancer / 中华临床营养杂志

Objective@#To investigate the perioperative weight loss and its influencing factors in patients with colorectal cancer, and to provide evidence for the development and management of perioperative nutritional support strategies.@*Methods@#Ninety-one patients with colorectal cancer were enrolled and divided into observation group (n=61) with the degree of weight loss less than 5% of preoperative weight and control group (n=30) with the degree of weight loss more than 5% of preoperative weight. Change of body composition and factors of weight loss in patients with colorectal cancer were compared between the two groups by single factor and multivariate analysis.@*Results@#Ninety-one patients with colorectal cancer had the average weight loss of 2.0 kg. Of perioperative changes in body composition, the degree of body fat, muscle mass and protein group decreased statistically (P<0.05). Univariate analysis showed that the age, intraoperative blood loss and postoperative oral nutrition intake compliance were the risk factors for the degree of weight loss in patients with colorectal cancer after the operation. Multivariate logistic regression analysis showed that the intraoperative blood loss was an independent influencing factor for the degree of postoperative weight loss in patients with colorectal cancer (P<0.05).@*Conclusion@#Age, intraoperative blood loss and postoperative oral nutritional intake compliance may affect the degree of weight loss during perioperative period. Intraoperative blood loss is an independent risk factor affecting the degree of weight loss during perioperative period. In future clinical research and practice, minimally invasive and accurate surgical treatment should be strengthened, the amount of intraoperative blood loss and surgical trauma should be reduced, and the postoperative oral nutrition intake of patients should be paid attention, especially for elderly patients. Personalized dietary guidance and management for different groups should be conducted, and perioperative nutritional status of patients should be improved.

Current Status of Enhanced Recovery After Surgery in China / 中华胃肠外科杂志

ERAS (enhanced recovery after surgery) has made significant progress since it was first introduced into China a decade ago. Series of studies on ERAS has been carried out in Jinling Hospital, Nanjing University, and brought out many exciting achievements for gastrointestinal cancer surgery. Merely in the year of 2015, advance in ERAS has been achieved in China. The first ERAS Group in China was founded. The first China ERAS Congress was inaugurated in 2015, publishing several Chinese Experts consensuses on ERAS clinical practice. All these show that ERAS are gradually brought to the attention of the Chinese surgeons and their active participation. It is believed that ERAS will have a promising future in China.

Effect of the intra-abdominal infection on peritoneal lymphatic stomata and regulatory mechanism of PD123319 on peritoneal lymphatic stomata / 中华消化外科杂志

Objective To investigate the effect of the peritoneal lymphatic stomata on intra-abdominal infection and the regulatory mechanism of angiotensin Ⅱ receptor specific inhibitor PD123319 on peritoneal lymphatic stomata.Methods The experimental study was adopted.Forty rats were divided into the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group by the random number table,every group had 10 rats.The classic appendix perforation (CLP) intraabdominal infection model was established in the abdominal infection group.After establishing the model of abdominal infection,PD123319 solution was injected intraperitoneally immediately (0.2 g/kg) in the abdominal infection drug intervention group.Abdominal cavity of the rats in the sham operation group was opened,and then was shut after flipping the intestine.The rats in the control group,sham operation group and intra-abdominal infection group were treated with intraperitoneal injection of 1ml stroke-physiological saline solution.After 2 hours,the rats were sacrificed,and peritoneal tissue was taken for the following tests.(1) The aperture size and distribution density of peritoneal lymphatic stomata were observed by scanning electron microscope (SEM).(2) The nitric oxide (NO) concentration in the peritoneal tissues was detected using nitric oxide nitric acid reduction method.(3) The expressions of endothelial nitric oxide synthase (eNOS) and Phospho-eNOS (P-eNOS) were detected by the Western blot.(4) The intracellular Ca2+ concentration were detect by flow cytometry.Measurement data with normal distribution were presented as-x ± s.The comparison among groups was analyzed using the ANOVA and pairwise comparison was analyzed by the LSD test.Results (1) The aperture size and distribution density of the peritoneal lymphatic stomata in the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group were respectively (2.3 ± 0.4) μm,(2.5 ± 0.5)μm,(4.7 ±0.5)pm,(3.8 ±0.5)pm and (2.0 ±0.8) × 108/m2,(2.1 ±0.7) × 108/m2,(6.2 ± 1.3) × 108/m2,(4.6 ± 1.4) × 108/m2,with statistically significant differences among the 4 groups (F =98.130,56.780,P ＜ 0.05).There were statistically significant differences in the aperture size and distribution density of the peritoneal lymphatic stomata between the intra-abdominal infection group and control group or intra-abdominal infection drug intervention group (t =11.586,8.573,3.854,3.098,P ＜ 0.05) and no statistically significant differences between the control group and sham operation group (t =1.281,0.514,P ＞0.05).(2) The concentrations of NO in the peritoneal tissues in the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group were respectively (0.380 ± 0.024) μmol/gprot,(0.450 ±0.020) μmol/gprot,(1.253 ±0.033) μmol/gprot and (0.579 ±0.035) μmol/gprot,with a statistically significant difference among the 4 groups (F =52.725,P ＜ 0.05).There were statistically significant differences in the concentration of NO between the intra-abdominal infection group and control group or intra-abdominal infection drug intervention group (t =10.536,67.798,P ＜ 0.05) and no statistically significant difference in the concentration of NO between the control group and sham operation group (t =2.007,P ＞ 0.05).(3) The results of Western blot showed that the expressions of eNOS and P-eNOS in the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group were respectively (0.591 ± 0.028)U/mg,(0.603 ± 0.007) U/mg,(0.615 ± 0.027) U/mg,(0.626 ±0.026) U/mg and (0.578 ±0.003)U/mg,(0.603 ± 0.071) U/mg,(0.773 ± 0.033) U/mg,(0.710 ± 0.012) U/mg,with no statistically significant difference in the expression of eNOS among the 4 groups (F =0.902,P ＞ 0.05) and with a statistically significant difference in the expression of P-eNOS among the 4 groups (F =205.062,P ＜ 0.05).There were statistically significant differences in the expression of P-eNOS between the control group and sham operation group or intra-abdominal infection group (t =7.678,13.322,P ＜ 0.05) and between the intra-abdominal infection group and intraabdominal infection drug intervention group (t =4.035,P ＜0.05).(4) The results of flow cytometry showed that Ca2+ concentration in the control group,sham operation group,intra-abdominal infection group and intraabdominal infection drug intervention group were respectively 82.200％ ± 0.060％,81.730％ ± 0.052％,21.980％ ± 0.010％,29.500％ ± 0.004％,showing a statistically significant difference between the 4 groups (F =21 271.030,P ＜ 0.05).There were statistically significant differences in the Ca2+ concentration between the intra-abdominal infection group and control group (t =164.750,P ＜ 0.05) and between the intra-abdominal infection group and intra-abdominal infection drug intervention group (t =21.338,P ＜ 0.05),and no statistically significant difference between the control group and sham operation group (t =1.861,P ＞ 0.05).Conclusion The intra-abdominal infection could increase aperture size and distribution density of peritoneal lymphatic stomata,and PD123319 may be through inhibiting the activation of NO synthase to decrease the concentration of NO,enhance the concentration of Ca2+ in peritoneal mesothelial cells and reduce the opening of peritoneal lymphatic stomata.

Quantitative research and nursing effect of early ambulation in patients with gastrointestinal tumor after operation / 医学研究生学报

Objective There is no quantization scheme for the early ambulation in patients with gastrointestinal tumor after operation of enhanced recovery .The aim of this study was to explore a suitable objective method of postoperative ambulation for gastro -intestinal tumor patients . Methods Sixty six gastrointestinal tumor postoperative patients were randomly assigned to two groups :ex-perimental group ( 33 cases ) and control group ( 33 cases ) .Enhanced recovery was adopted in the both groups afterthe operation . Wireless smart bracelets ( fitbit flex) were used in the experimental group , and the ambulation of patients was monitored by the hand of synchronous real time computer digital panel .At the same time, the patients was supervised for positive ambulation . Traditional quantitative methods of electronic pedometer were used in the control group.The postoperative ambulation , effect and compliance were compared between the two groups . Results Postoperative ambula-tion steps in the experimental group were increased compared with the control group on the days 1, 2, and 3postoperative, and the data were (208.70 ±45.76) vs (144.36 ±47.68), (560.73 ±148.67) vs (407.00 ±85.92), and (894.70 ±91.68) vs (674.00 ±73.06) steps (P<0.05).The first time of early ambulation, flatus, ca-tharsis, and compliance of ambulation showed significant difference in the two groups (P<0.05). Conclusion Wireless intelligent monitoring bracelet is objective and effective for monitoring and quantifying postoperative ambulation .It is superior to the traditional quantitative methods , and can improve the effect and compliance of the ambulation .Moreover , it can promote postoperative recovery in patient with enhanced recovery surgery .

Current status and prospect of enhanced recovery after surgery / 中华外科杂志

Since the concept of fast track surgery (also known as enhanced recovery after surgery (ERAS)) was first introduced by Professor Kehlet in 1997, it has been 18 years of clinical practice. Significant progressions have been made in different fields of surgery, generally, in reducing the surgical stress, reducing the postoperative complications, and shortening the length of hospital stay. It has also been over ten years since the first research of ERAS in China. However, there are still some difficulties and obstacles in clinical applications, especially from the traditional habit. Thus, future studies of surgical stress and the regularity of metabolism are needed. The existing evidence of researches on ERAS should be translated into clinical application. Therefore, the aim of free-pain and no risk surgery will be achieved.

Clinical significance of enhanced recovery after surgery is not only to shorten the duration of hospital stay / 中华消化外科杂志

Enhanced recovery after surgery (ERAS) has developed continuously in China for 10 years,including optimizing step by step the perioperative analgesia regimens and goal-oriented fluid therapy.The ERAS principle has been accepted and expanded extensively in the surgery field,meanwhile,ERAS for perioperative care have been proved valueble in shortening hospital stay,reducing complications,improving organ function,reducing surgical stress reaction,accelerating recovery and increasing survival rate.ERAS is in the ascendant,and promotes development of multidisciplinary training and education program,supples of high-quality research evidences and translational clinical applications seem to be the direction of ERAS.And therefore,the content that this paper talks about is of great significance to deepen the research and understanding of ERAS.

Understanding of the 2014 guidelines for enhanced recovery after gastrectomy published by European Enhanced Recovery After Surgery Society / 中华消化外科杂志

Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway designed to achieve early recovery for patients undergoing major surgery.The ERAS programs aim to reduce traumatic stress and postoperative complications,improve full recovery of patients or combine and coordinate evidence-based perioperative care interventions that support standardizing and optimizing surgical care.The international working group assembled by the ERAS Society composed the 2014 Consensus guidelines for enhanced recovery after gastrectomy Enhanced Recovery After Surgery (ERAS(@)) Society recommendations in July 2014.This guideline is designed for optimal perioperative care for patients undergoing gastrectomy.This paper presented the understanding of hot issues of the guidelines in order to provide the clinical evidence of evidence-based medicine for the surgical field in China.

Importance of data management with statistical analysis set division / 药学学报

Testing of hypothesis was affected by statistical analysis set division which was an important data management work before data base lock-in. Objective division of statistical analysis set under blinding was the guarantee of scientific trial conclusion. All the subjects having accepted at least once trial treatment after randomization should be concluded in safety set. Full analysis set should be close to the intention-to-treat as far as possible. Per protocol set division was the most difficult to control in blinded examination because of more subjectivity than the other two. The objectivity of statistical analysis set division must be guaranteed by the accurate raw data, the comprehensive data check and the scientific discussion, all of which were the strict requirement of data management. Proper division of statistical analysis set objectively and scientifically is an important approach to improve the data management quality.

Prevention and handling of missing data in clinical trials / 药学学报

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.

Clinical application of veno-arteriolization of finger lateral vein for repairing severed finger tips / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate effect of veno-arteriolization of finger lateral vein for repairing severed finger tips.</p><p><b>METHODS</b>From March 2007 to April 2012, 20 patients with severed finger tips were treated with veno-arteriolization of finger lateral vein after failure in anastomosing artery of finger over times. During operation, the dominant digital artery at proximal end and the dominant finger lateral vein at distal end was anastomosed as the blood supply, the non-superiorty finger lateral vein was anastomosed as the blood drainage.</p><p><b>RESULTS</b>All flaps survived completely and achieved primary healing. 18 patients were successfully followed up for 6 to 12 months with satisfactory appearance and nail growth. Finger pulp was plump with good flexibility. The average length of nail was (15.6 +/- 2.7) mm and the average motion of DIP joint was (62 +/- 4) degrees. The average two point discrimination was (4.6 +/- 0.3) mm and the average sensation measurement was S3+.</p><p><b>CONCLUSION</b>The veno-arteriolization of finger lateral vein is a valuable method for repairing severed finger tips, which can promote nail growth, and restore fingers motion and sensation.</p>

Comparative study on da Vince robotic and laparoscopic radical gastrectomy for gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the short-term clinical outcomes of laparoscopic and da Vince robotic radical gastrectomy for gastric cancer and evaluate the safety and efficacy of robotic system.</p><p><b>METHODS</b>Clinical data of 200 consecutive gastric cancer patients undergoing radical gastrectomy, including 100 cases of robotic (RRG group) and 100 cases of laparoscopic (LRG group), in our department from January 2012 to May 2013 were retrospectively analyzed. Reconstruction of the alimentary tract was achieved using extracorporeal method through a minilaparotomy in LRG group, and intracorporeal robot-sewn anastomosis in RRG group. Comparative analysis between the two groups for intraoperative factors (conversion, blood loss, operative time, incision length), oncologic outcomes (TMN stage, lymph node dissection, margin) and postoperative parameters (ventilation time, hospital stay, complications, mortality) was performed.</p><p><b>RESULT</b>There was only 1 conversion in LRG group. As compared to LRG group, RRG group was associated with less blood loss[(60±16) vs. (98±17) ml, P=0.005], longer operative time [(215±46) vs. (188±52) min, P=0.001], shorter incision length [(4.2±1.7) vs. (8.9±2.6) cm, P=0.028], and shorter postoperative hospital stay [(4.5±2.6) vs. (5.7±3.1) d, P=0.018] in RRG group. While there were no significant differences in other aspects between the two groups, such as number of harvested lymph nodes, distance to upper or lower margin of tumor, postoperative bowel function recovery, and postoperative complication morbidity.</p><p><b>CONCLUSION</b>Robotic radical gastrectomy is feasible and safe for gastric cancer, and has better short-term and oncologic outcomes compared with laparoscopic radical gastrectomy.</p>

Clinical research on finger lateral veins anastomosis for restoring venous return of severed fingertip / 中华骨科杂志

Objective To investigate effect of finger lateral veins anastomosis for restoring venous return of severed fingertip.Methods From March 2008 to December 2012,36 patients underwent finger lateral veins anastomosis,including 21 males and 15 females,aged from 15 to 52 years (average,29.5±6.6 years).The thumb was involved in 3 cases,the index finger in 9 cases,the middle finger in 9 cases,the ring finger in 7 cases,and the little finger in 8 cases.The causes of injury included crush injury in 12 cases,electric saw injury in 8 cases,and incised injury in 16 cases.According to type of fingertip injury,there were 14 cases of type Ⅰ,5 cases of type Ⅱ,10 cases of type Ⅲ,and 7 cases of type Ⅴ.The ratios of anastomotic artery and veins were 1∶1,1∶2 or 2∶2 (average,1∶2).Results Thirty-six fingertips survived completely and no venous return obstruction happened,arterial crisis occurred in 3 cases after operation,which were cured after operative and medication treatment.Thirty patients were successfully followed up for 6 to 24 months (average,12.4±2.8 months).The fingers' appearances were satisfactory,finger pulps were plump with good flexibility,and no obvious atrophy of finger was found.The nails were nearly smooth,and the length of nails ranged from 10.5 to 18.9 mm (average,14.4±3.2 mm).The motion of distal interphalangeal joints,the two point discrimination,and the results of sensation measurement ranged from 0° to 70° (average,63°±5°),4.2 to 6.0 mm (average,4.6±0.4 mm),and S3 to S4,respectively.According to Tamai's classification,Tamai score increased from 68 to 100 at final follow-up,the results were excellent in 28 cases,good in 2 cases,with an excellent and good rate of 100％.Conclusion The finger lateral veins anastomosis is an effective method for restoring venous return of severed fingertip,which can avoid venous return obstruction,promote growth of nail,and restore motion and sensation of fingers.