As research delves deeper into the mechanisms of tumor immune responses,studies reveal the importance of microbial com-munities within the tumor microenvironment in tumor progression and their interactions with the host immune system.Intratumoral micro-biota could influence the tumor microenvironment,thereby promoting or inhibiting tumor growth and development.Despite this import-ance,the specific role of intratumoral microbiota impacting cancer immunotherapeutic efficacy remains largely unexplored.A deeper under-standing of the characteristics and biological functions of tumor-specific microbiota heralds a potential revolutionary innovation in cancer treatment.In this review,we introduce the discovery and sources of intratumoral microbiota,also addressing its composition,and discuss tumor tissue characteristics.Moreover,we briefly review the history of cancer immunotherapy development with a particular focus on the research progress concerning the impact of intratumoral microbiota on cancer immunotherapy.Furthermore,we explore emerging strategies that combine targeting intratumoral microbiota with immunotherapy to enhance immune efficacy,inhibit tumor progression,and improve cure rates,anticipating that this approach could represent a new direction for enhancing treatment outcomes and prospects.

Objective: To compare the efficacies of the two techniques of "micro-hemostasis and micro-cutting" with straight bipolar electrocoagulation forceps and traditional clamp-ligation for hemostasia in thyroid surgery. Methods: A total of 228 patients who underwent surgical treatment for thyroid neoplasms in our hospital between January 2015 and December 2018 were retrospectively analyzed, including 50 males and 178 females, aged 23-68 years old. Of those, 150 cases as electric knife group received traditional thyroid surgery between January 2015 and December 2018 and 78 cases as bipolar electrocoagulation group received thyroid surgery by using the technique of bipolar electrocoagulation with meticulous anatomy between January 2018 and December 2018. The total operation time, single operation time, intraoperative hemorrhage, postoperative drainage volume on the first day, postoperative hoarseness and hypocalcemia were compared between the two groups. SPSS 16.0 was used to analyze the data. Results: The total operation time and intraoperative hemorrhage in the bipolar electrocoagulation group were significantly lower than those in the electric knife group ((59.33±18.29)min vs (77.21±25.39)min, (14.83±9.22)ml vs (36.86±11.80)ml, all P<0.01). The single operation time of the bipolar electrocoagulation group was shorter than that of the electric knife group((10.25±6.16) min vs (20.34±7.24)min, (16.25±7.15)min vs (35.68±8.25)min, (12.12±5.25)min vs (20.68±7.26)min, t value was 3.948,16.262,8.238, all P<0.01).There was no significant difference between the two groups in postoperative drainage volume on the first day (P>0.05) and the incidence of postoperative hoarseness (P>0.05), while the incidence of hypocalcemia in the bipolar electrocoagulation group(10.26%) was lower than that in the electric knife group(21.33%,χ²=4.353, P<0.05). Conclusions The fine dissection for thyroid operation can be achieved by using straight bipolar electrocoagulation tweezers. The use of "micro-hemostasis" and "micro-cutting" technique with bipolar electrocoagulation tweezers can greatly reduce intraoperative bleeding, operation time and postoperative complication.

Enzymes have a wide range of applications and great industrial potential. However, large-scale applications of enzymes are restricted by the harsh industrial environment, such as high temperature, strong acid/alkali, high salt, organic solvents, and high substrate concentration. Adaptive modification (such as rational or semi-rational design, directed evolution and immobilization) is the most common strategy to improve the catalysis of enzymes under industrial conditions. Here, we review the catalysis of enzymes in the industrial environment and various methods adopted for the adaptive modifications in recent years, to provide reference for the adaptive modifications of enzymes.
Biocatalysis ; drug effects ; Biotechnology ; Enzymes ; chemistry ; metabolism ; Hot Temperature ; Hydrogen-Ion Concentration ; Protein Engineering ; Solvents ; chemistry ; pharmacology

Objective To study the best formulation and technology of quercetin-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate(PLGA-TPGS) nanoparticles(QPTN) with QT as model drug and PLGA-TPGS as polymer materials by orthogonal tests,and to investigate the in vitro stability of QPTN. Methods To ensure the best formula-tion and technology for preparing QPTN,single-factor test was established to determine the influence of the ratio of quercetin to PLGA-TPGS,the concentration of TPGS as emulsifiers,the ultrasonic power and ultrasonic time to the particle size,drug loading (DL) and entrapment efficiency(EE).According to single-factor test,the factor levels of nanoparticles were set to select the best prescription and technology of QPTN by orthogonal test.The stability of QPTN was examined using the effecting factor test,accel-eration test and long-term test. Results The best formulation and technology of QPTN was that the ratio of quercetin to PLGA-TPGS was 3:10 (W:W) with 0.05% TPGS as emulsifier,the mixed solution was sonicated for 6 min at 200 W.The average particle size,DL and EE of QPTN prepared under the conditions described above were (155.4 ± 2.7) nm,(21.6 ± 1.5)% and (93.7±2.9)% (n=6),respectively.In the in vitro stability test,QPTN showed a good stability at high temperature,high humidity and strong light condition. Conclusion The best formulation and preparation technology of QPTN was selected.QPTN got small particle size,high DL and EE,and good in vitro stability.

Objective: To evaluate the safety and feasibility of laparoscopic radical antegrade modular pancreatosplenectomy(Lap-RAMPS) for left-sided pancreatic adenocarcinoma. Methods: Clinical data of total 12 patients underwent Lap-RAMPS for left-sided pancreatic adenocarcinoma at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital from March 2016 to August 2017 were reviewed retrospectively.There were 7 male patients and 5 female patients, with median age of 60.5 years old(47-68 years old). Abdominal enhanced CT, pancreatic MRI, PET-CT were performed on all patients to evaluate the lesion and exclude metastasis.Follow-up were done with out-patient clinic or telephone consultancy until October 2017. Results: All patients underwent pure Lap-RAMPS.The medium operative time was 250 minutes(180-445 minutes), and the blood loss was 150 ml(50-500 ml). The medium first flatus time and diet resumption time were 3.0 days(1-5 days) and 3.5 days(1-7 days) respectively.The medium postoperative hospital stay was 9 days(4-18 days). Morbidity occurred in 8 patients with gastric empty delay(n=1), bleeding(n=1), fluid collection(n=3). There was no mortality.The medium overall number of retrived lymph nodes was 15.6 and the positive rate was 41.7%. The R0 rate was 100%.The medium follow-up was 10 months.One patient was diagnosed as liver metastasis after 8 months and accepted chemotherapy.One patient died after 14 months for tumor recurrence and metastasis.Others survived without tumor recurrence or metasitasis. Conclusion Lap-RAMPS is safe and feasible with accepted oncological outcomes for selected left side pancreatic adenocarcinoma under skilled hands.

Objective To evaluate the specific antibody-producing capacity of locally infiltrating B lymphocytes in lesions of patients with pemphigus vulgaris (PV).Methods Totally,35 patients with PV and 22 healthy controls were enrolled into this study.Skin tissues were resected from blisters or erosions of the patients with PV,and from normal skin of healthy controls.Then,mononuclear cells were isolated from these skin tissues.Flow cytometry was performed to determine the percentages of lymphocytes,CD 19+ B lymphocytes,and desmoglein (Dsg)1-and Dsg3-specific CD19+ B lymphocytes.B lymphocytes isolated from the lesional skin of patients with PV were cultured in vitro.Enzyme-linked immunosorbent assay (ELISA) was conducted to determine titers of anti-Dsg1 and anti-Dsg3 antibodies in the cell culture supernatant.Receiver operating characteristic (ROC) curve analysis was conducted to calculate positive rates of anti-Dsg1 and anti-Dsg3 antibodies.Results The percentages of lymphocytes (17.95％ ± 3.85％) and CD19+ B lymphocytes (4.27％ ± 1.13％) were significantly higher in the lesional skin of PV patients than in the normal skin of healthy controls (7.83％ ± 1.29％,0.61％ ± 0.31％ respectively;t =2.49,U =13.00 respectively,both P ＜ 0.05).Among the CD19+ B lymphocytes in the lesional skin of PV patients,the percentage of CD19qgG+ B cells was (38.33 ± 5.56)％,and percentages of Dsg1-and Dsg3-specific CD19+ B lymphocytes were 12.87％ ± 1.267％ and 10.42％ ± 1.243％ respectively.After the in vitro culture for 6 days,the titers of anti-Dsg1 and anti-Dsg3 antibodies in the cell culture supematant were (4.89 ± 1.56) U/ml and (35.45 ± 13.03) U/ml respectively,with their positive rates being 85％ (17/20)and 95％ (19/20) respectively.Conclusion There are Dsg1-and Dsg3-specific B lymphocytes aggregating in the lesional skin of patients with PV,which can produce anti-Dsg1 and anti-Dsg3 antibodies after in vitro culture.

Objective To investigate the treatment efficacy,feasibility and safety of laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm.Methods The clinical data of 31 patients who underwent laparoscopic resection of large gastric GISTs between Jan 2010 and Jun 2017 at Sir Run Run Shaw Hospital and People's Hospital of Zhejiang Province were retrospectively analyzed.Results All operations were successful.Two patients were converted to open surgery.The mean tumor size was (7.2 ±0.5) cm.The mean operation time was (127 ± 12) min,intraoperative blood loss was (83 ±25) ml.The first flatus time was (2.2 ±0.8) days,the first diet resumption time was (2.4 ± 1.2) days,and the median postoperative hospital stay was (5.5 ± 1.5) days.The median follow-up time was 25 months.One patient developing liver metastasis 41 months after primary resection received oral mesylate imatinib therapy for 24 months and was still alive at the last follow-up.One patient died of lung cancer 33 months after primary operation without recurrence of gastric GIST.Conclusions Laparoscopic surgery for gastric GIST larger than 5 cm on laparoscopicaly accessible location is feasible and safe.

Objective To evaluate the safety and feasible of adjacent organ resection during laparoscopic pancreaticoduodenectomy(LPD),and summary the surgical strategies.Methods Clinical data of 15 adjacent organ resections combined with LPD from March 2013 to September 2017 were reviewed.There were 10 male and 5 female patients aging from 20 to 86 years,and the body mass index ranged from 19.6 to 34.5 kg/m2.Two patients had previous abdominal surgical history.Two patients underwent preoperative chemotherapy.Results The resected adjacent organs included liver (n =4),stomach (n =3),colon(n =6),right kidney with embolectomy and vasoplastic of inferior vena cava (n =1),and spleen artery aneurysms(n =1).The operative time ranged from 280 to 450 minutes,and the blood loss ranged from 100 to 450 ml.The total complication rate was 5/15 and no one died in 90 days after surgery.The postoperative hospital stay ranged from 10 to 42 days with medium 18 days.The pathology included adenocarcinoma of stomach and duodenum (n =1),gastric cancer invading pancreas or duodenum (n=2),ampullary adenocarcinoma with left hepatolithiasis(n=1),ampullary adenocarcinoma with a benign lesion in left liver (n =1),ampullary adenocarcinoma with single liver metastasis (n =1),ampullary adenocarcinoma(n =1),pancreatic intraductal papillary mucinous neoplasm with splenic artery aneurysms (n=1),pancreatic neuroendocrine neoplasm with colon cancer (n =1),distal common bile duct adenocarcinoma involving righ hepatic duct (n =1),pancreatic neuroendocrine neoplasm invading inferior vena cava and right renal vein(n=1),duodenal adnocarcinoma(n =1),duodenal ewing's sarcoma(n =1),duodenal intesititialoma (n =2).The follow-up was from 3 to 40 months with the medium survival of 17.5 months.Conclusions The oncological outcomes of PD combined with adjacent organ resection is acceptable.Surgical treatment for those patients with periampullary neoplasma and adjacent organ lesions should be aggressive.

Objective To evaluate the safety and feasible of adjacent organ resection during laparoscopic pancreaticoduodenectomy(LPD),and summary the surgical strategies.Methods Clinical data of 15 adjacent organ resections combined with LPD from March 2013 to September 2017 were reviewed.There were 10 male and 5 female patients aging from 20 to 86 years,and the body mass index ranged from 19.6 to 34.5 kg/m2.Two patients had previous abdominal surgical history.Two patients underwent preoperative chemotherapy.Results The resected adjacent organs included liver (n =4),stomach (n =3),colon(n =6),right kidney with embolectomy and vasoplastic of inferior vena cava (n =1),and spleen artery aneurysms(n =1).The operative time ranged from 280 to 450 minutes,and the blood loss ranged from 100 to 450 ml.The total complication rate was 5/15 and no one died in 90 days after surgery.The postoperative hospital stay ranged from 10 to 42 days with medium 18 days.The pathology included adenocarcinoma of stomach and duodenum (n =1),gastric cancer invading pancreas or duodenum (n=2),ampullary adenocarcinoma with left hepatolithiasis(n=1),ampullary adenocarcinoma with a benign lesion in left liver (n =1),ampullary adenocarcinoma with single liver metastasis (n =1),ampullary adenocarcinoma(n =1),pancreatic intraductal papillary mucinous neoplasm with splenic artery aneurysms (n=1),pancreatic neuroendocrine neoplasm with colon cancer (n =1),distal common bile duct adenocarcinoma involving righ hepatic duct (n =1),pancreatic neuroendocrine neoplasm invading inferior vena cava and right renal vein(n=1),duodenal adnocarcinoma(n =1),duodenal ewing's sarcoma(n =1),duodenal intesititialoma (n =2).The follow-up was from 3 to 40 months with the medium survival of 17.5 months.Conclusions The oncological outcomes of PD combined with adjacent organ resection is acceptable.Surgical treatment for those patients with periampullary neoplasma and adjacent organ lesions should be aggressive.

Objective: To summary the experience of 233 cases of laparoscopic pancreaticoduodenectomy (LPD) performed by a single surgical team. Methods: Data of patients undergoing LPD from September 2012 to October 2016 were reviewed. There were 145 males and 88 females with the mean age of(60.3±13.0)years old, ranging from 19 to 92 years old, and the mean body mass index of (22.8±3.5)kg/m^2, ranging from 16.3 to 36.8 kg/m². There were 195 patients with clinical manifestation and 54 patients who had the history of abdominal surgery. Results: LPD were performed on 233 patients by same surgical team consecutively. The mean operative time was(368.0±57.4)minutes. Mean blood loss was(203.8±138.6)ml. The postoperative morbidity rate was 33.5%, with 6.9% of grade B or C pancreatic fistula and 9.9% of bleeding. The reoperation rate was 5.6%. The mortality during 30 days after operation was 0.9%. Mean postoperative hospital stay was (18.1±11.2)days. Mean tumor size was (3.9±2.4)cm, and the mean number of lymph nodes harvested was 21.3±11.9.One hundred and sixty-three patients were diagnosed as malignant tumor, including pancreatic adenocarcinoma(n=84), cholangiocarcinoma(n=17), ampullary adenocarcinoma(n=55), duodenal adenocarcinoma(n=5), gastric cancer(n=1)and duel cancer (n=1) located in distal stomach and duodenum. Conclusion The key point to make laparoscopic pancreaticduodenectomy a routine safe procedure is to operate the procedure under skilled hands in selected patients via suitable surgical approaches.