Tyrosol is a natural polyphenolic product that is widely used in chemical, pharmaceutical and food industries. Currently, the de novo synthesis of tyrosol by Escherichia coli suffers from issues such as low cell density and poor yield. Therefore, the phenylpyruvate decarboxylase mutant ARO10^F138L/D218G obtained in our previous study was fused with an alcohol dehydrogenase from different microorganisms for fusion expression, and the optimal ARO^{10F138L/D218G}-L-YahK produced 1.09 g/L tyrosol in shake flasks. In order to further improve tyrosol production, feaB, a key gene in the competing pathway of 4-hydroxyphenylacetic acid, was knocked out, and the resulted strain produced 1.26 g/L tyrosol with an increase of 21.15% compared to that of the control. To overcome the low cell density in tyrosol fermentation, the quorum-sensing circuit was used to dynamically regulate the tyrosol synthesis pathway, so as to alleviate the toxic effect of tyrosol on chassis cells and relieve the growth inhibition. Using this strategy, the yield of tyrosol was increased to 1.74 g/L, a 33.82% increase. In a 2 L fermenter, the production of tyrosol in the engineered strain TRFQ5 dynamically regulated by quorum-sensing reached 4.22 g/L with an OD₆₀₀ of 42.88. Compared with those in the engineered strain TRF5 statically regulated by induced expression, the yield was increased by 38.58% and the OD₆₀₀ was enhanced by 43.62%. The combination of blocking the competing pathway using gene knockout technology, and reducing the inhibitory effect of tyrosol toxicity on chassis cells through quorum-sensing dynamic regulation increased the production of tyrosol. This study may facilitate the biosynthesis of other chemicals with high toxicity.
Escherichia coli/genetics* ; Biological Products ; Bioreactors ; Fermentation

Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.

OBJECTIVE: To explore the genetic etiology of a patient with epilepsy and provide genetic counseling. METHODS: A patient who had visited the Center for Reproductive Medicine of Shandong University on November 11, 2020 was selected as the study subject, and her clinic information was collected. Candidate variant was identified through whole exome sequencing (WES), and Sanger sequencing was used for validation. Possible transcriptional changes caused by the variant was detected by reverse transcription-PCR and Sanger sequencing. RESULTS: The patient was a 35-year-old female with no fever at the onset, loss of consciousness and abnormal firing in the temporal lobe, manifesting predominantly as convulsions and fainting. WES revealed that she had harbored a heterozygous c.2841+5G>A variant of the SCN9A gene, which was verified by Sanger sequencing. cDNA sequencing confirmed that 154 bases were inserted between exons 16 and 17 of the SCN9A gene, which probably produced a truncated protein and affected the normal function of the SCN9A protein. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.2841+5G>A variant was classified as likely pathogenic (PVS1_Strong+PM2_Supporting). CONCLUSION The c.2841+5G>A variant of the SCN9A gene probably underlay the epilepsy in this patient. Above finding has enriched the variant spectrum of the SCN9A gene and provided a basis for the prenatal diagnosis and preimplantation genetic testing for this patient.
Humans ; Female ; Pregnancy ; Adult ; Epilepsy/genetics* ; Seizures ; Exons ; DNA, Complementary ; Genetic Counseling ; NAV1.7 Voltage-Gated Sodium Channel

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective:To explore the value of Caprini risk assessment scale and serum D-dimer in early prediction of postoperative lower extremities deep vein thrombosis (DVT) in patients with gastrointestinal malignant tumor.Methods:A total of 240 patients with gastrointestinal malignant tumors treated in Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from Jan to Oct 2020 were analyzed retrospectively.Results:Caprini score was 4 in 8 cases, 5-7 in 217 cases, and 8 in 15 cases. Sixty-seven patients developed lower extremity DVT after operation. No patients with Caprini score of 4 had DVT, 57 cases (26.3%) with a score of 5-7 had DVT; 10 cases whose score were ≥8 points (66.7%) developed DVT. There was a higher incidence of lower extremity DVT in patients ≥8 points than those of 5-7 points after surgery ( P<0.01). The postoperative Caprini score of the DVT group was higher than that of the non-DVT group (6.37±1.01 vs. 5.80±0.94, t=4.108, P<0.001). D-dimer on the first day after operation in DVT group (4.08±2.27 vs. 2.01±1.04, t=7.715, P<0.001) and the level of serum D-dimer (2.93±1.81 vs. 2.30±1.21, t=2.631, P<0.001) on day 3 was higher than that in the non-DVT group. According to the ROC curve, the best cut-off value for serum D-dimer to predict lower extremity DVT on the first postoperative day was 2.84 mg/L, the sensitivity was 70.1%, the specificity was 87.3%, and the area under the curve (AUC) was 0.815. The best cut-off value of D-dimer for predicting lower limb DVT on day 3 after surgery was 1.67 mg/L, sensitivity was 85.1%, specificity was 34.7%, and AUC was 0.611. Conclusions:Patients with gastrointestinal malignant tumors have a high incidence of postoperative lower extremity DVT. When the serum D-dimer exceeds 2.84 mg/L on the first postoperative day, the likelihood of postoperative lower extremity DVT is higher.

Objective:To evaluate the clinical outcomes of additional surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Sixty-nine patients with early gastric cancer who underwent ESD and were diagnosed as having non-curative resection by postoperative pathology at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2020 were included in the retrospective observation. Patients were divided into the additional surgery group ( n=12) and the follow-up group ( n=57). The differences in clinical and pathological data of the two groups, the surgical outcomes of the additional surgery group, three-year recurrence-free survival and tumor-specific survival of the two groups, and the independent risk factors affecting three-year recurrence-free survival in the follow-up group were analyzed. Results:Compared with the follow-up group, the rates of submucosal infiltration [66.7% (8/12) VS 21.1% (12/57), χ 2=7.927, P=0.005], vascular invasion [33.3% (4/12) VS 1.8% (1/57), P=0.003] and nerve invasion [16.7% (2/12) VS 0.0% (0/57), P=0.028] in the additional surgery group were significantly higher. In the additional surgery group, the interval between the additional surgery and ESD was 18.5 d (7-55 d), the surgical time was 286.4±85.9 min, and the number of dissected lymph nodes was 25.6±7.4. Four patients (33.3%) had residual tumor. Postoperative complications occurred in 4 patients (33.3%) (all were discharged after conservative treatment), and there was no perioperative death. One patient developed liver metastases 17 months after the surgery, and died 22 months after surgery due to liver metastases. One patient died 22 months after surgery due to non-tumor causes. The three-year recurrence-free survival and three-year tumor-specific survival in additional surgery group were 91.7% (11/12) and 91.7% (11/12), respectively, and those in the follow-up group were 87.7% (50/57) and 100.0% (57/57), respectively. Multivariate Cox regression analysis showed that tumor size ≥2 cm was an independent risk factor for three-year recurrence-free survival in the follow-up group ( P=0.037, HR=15.595, 95% CI: 1.181-205.952). Conclusion:Additional surgery and close follow-up are safe and feasible therapeutic strategies for early gastric cancer patients who underwent non-curative ESD. Clinicians should make reasonable choice based on the pathological results, patients' physical condition and surgery intention. But for patients with primary tumor size ≥2 cm, additional surgery is recommended.

Gastric cancer has high morbidity and mortality, and limited treatment options for advanced cancer. In recent years, with the advent of targeted drugs (including VEGFR-2 antagonists, anti-HER-2 antibodies) and immunotherapeutics (such as anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies), the efficacy of advanced gastric cancer has been increased. Currently, the clinical data of PD-1 and its ligand PD-L1 inhibitors have achieved phased success, but which factors affect the efficacy of PD-1/PD-L1 immune checkpoint inhibitors immunotherapy, and how to select the benefited patient population and establish the prognosis evaluation system are the urgent problems to be solved. Therefore, this review elaborated the factors affecting the immunotherapy effects of PD-1/PD-L1 inhibitors from the aspects of systemic chemotherapy, intestinal microbiota, MSI, Hp infection, Epstein-Barr virus, TMB, and tumor infiltrating lymphocytes, in order to provide new ideas for clinical work.

Objective:To investigate the short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-programmed death-1 (PD-1) antibody therapy for locally advanced rectal cancer.Methods:The prospective study was conducted. The clinicopathological data of 30 locally advanced rectal cancer patients who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from November 2019 to September 2020 were selected. Patients underwent laparos-copic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Observation indicators: (1) situations of the enrolled patients; (2) situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events; (3) preoperative evaluation and surgical situations; (4) postoperative situations and pathological examinations; (5) postoperative adjuvant chemo-therapy and follow-up. Follow-up was conducted using outpatient examination and telephone interview up to March 2022. Patients were followed up once every 3 weeks during the period of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy to detect the adverse events and patients were followed up once every 3 months during the first postoperative 2 years and once every 6 months thereafter to detect tumor recurrence and survival of patients. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:(1) Situations of the enrolled patients. A total of 30 patients were selected for eligibility. There were 17 males and 13 females, aged (57±16)years. Cases with preoperative primary tumor in stage cT3 and cT4 were 22 and 8, respectively. Cases with preoperative clinical lymph node metastasis in stage cN0, cN1, cN2 were 4, 16, 10, respectively. Cases in preoperative clinical stage Ⅱ and Ⅲ were 4 and 26, respectively. Of the 30 patients, there were 21 cases with positive circumferential margin and 12 cases with vascular invasion in extramural of rectum in the preoperative imaging evaluation. Distance from the distal margin of tumor to anal margin and tumor diameter of the 30 patients were 4.7(range, 1.9?9.0)cm and 5.4(range, 2.1?10.0)cm, respectively. There were 28 cases with mismatch repair proficient and 1 case with mismatch repair deficiency in tumor tissues. There was 1 case missing the data of mismatch repair in tumor tissues as failed in biopsy of pathological examination before the treatment. (2) Situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events. All the 30 patients completed preoperative short-course radiotherapy successfully. Of the 30 patients, there were 3 cases not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy and there were 24 cases undergoing 2 courses of the sequential chemotherapy combined with anti-PD-1 antibody therapy and 3 cases undergoing 1 course of the sequential chemotherapy combined with anti-PD-1 antibody therapy. The time interval between ending of radiotherapy and starting of chemotherapy combined with anti-PD-1 antibody therapy of the 27 patients was 12(range, 4?18) days. Cases with leukopenia, cases with endothelial hyperplasia of skin capillaries, cases with radiation proctitis, cases with anemia, cases with peripheral neurotoxicity, cases with neutropenia, cases with thrombocytopenia, cases with fatigue, cases with anorexia, cases with abnormal liver function, cases with hypothyroidism were 24, 22, 21,20, 18, 16, 16, 13, 10, 9, 2 in the 30 patients during the preoperative short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Cases with the above adverse events were improved after symptomatic treatment. (3) Preoperative evaluation and surgical situations. Seven of the 30 patients were in clinical complete remission after preoperative multidisciplinary evaluation and the other 23 patients were not in clinical complete remission. Twenty-seven of the 30 patients underwent laparoscopic radical resection of rectal cancer and 3 patients not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy did not undergo surgery. The time interval between ending of chemotherapy combined with anti-PD-1 antibody therapy and the surgery of the 27 patients were 14(range, 5?141)days. Of the 27 cases, there were 13 cases and 14 cases with 0 and 1 of the preoperative Eastern Cooperative Oncology Group score, respectively, and there were 24 cases undergoing low anterior proctectomy and 3 cases undergoing abdominoperineal excision. The operation time and volume of intra-operative blood loss of the 27 cases were (182±36)minutes and 30(range, 10?150)mL, respectively. Of the 27 cases, there were 16 cases with protective ileostomy and 24 cases with anal preservation. (4) Postoperative situations and pathological examinations. The time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay of the 27 patients undergoing surgery were 2(range, 1?4)days, 3(range, 2?5)days and 8(range, 7?16)days, respectively. Five of the 27 patients had postoperative grade Ⅰ?Ⅱ complications, including 2 cases with incision infection, 1 case with abdominal infection, 1 case with incision hemorrhage and 1 case with venous thrombosis in left lower limb intermuscular. Cases with postoperative complica-tions were improved after symptomatic treatment. Results of postoperative pathological examina-tion showed that the rate of pathologic complete response in 27 patients was 48.1%(13/27). Of the 27 cases, cases in grade 0, grade 1, grade 2, grade 3 of the tumor regression grading were 13, 5, 7, 2, respectively, cases in stage T0, stage Tis, stage T2, stage T3 of the tumor T staging were 13, 1, 5, 8, respectively, cases in stage N0, stage N1, stage N2 of the tumor N staging were 19, 6, 2, respectively, cases in stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ of the tumor TNM staging were 14, 0, 5, 8, respectively. The number of lymph node dissected of the 27 patients was 15(range, 3?29). Of the 27 patients, there was 1 case with positive circumferential margin and 26 cases achieving R 0 resection. None of the 27 patients underwent secondary operation or perioperative death. (5) Postoperative adjuvant chemotherapy and follow-up. Of the 27 patients undergoing surgery, 21 cases underwent post-operative adjuvant chemotherapy, with the cycles of 4(range, 1?6). All the 27 patients were followed up for 20(range, 20?29)months. During the follow-up, 3 cases not achieving pathological complete response had tumor recurrence and no patient died. The disease free survival rate of the 27 patients was 88.9%. Conclusion:Laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with immunotherapy for locally advanced rectal cancer is safe and feasible, with satisfied short-term efficacy.

Objective:To investigate the clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastrointestinal stromal tumor (GIST).Methods:The retrospective cohort study was conducted. The clinicopathological data of 741 duodenal GIST patients who under-went radical surgery in 17 medical centers, including 121 cases in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 121 cases in Chinese PLA General Hospital, 116 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 77 cases in Fudan University Shanghai Cancer Center, 77 cases in West China Hospital, Sichuan University, 31 cases in Guangdong Provincial People′s Hospital, 24 cases in Fujian Cancer Hospital, 22 cases in Fujian Medical University Union Hospital, 25 cases in Shengjing Hospital of China Medical University, 19 cases in Xiangya Hospital, Central South University, 23 cases in Zhejiang Cancer Hospital, 17 cases in Liaoning Cancer Hospital＆Institute, 17 cases in the First Affiliated Hospital of Xiamen University, 15 cases in Sun Yat-sen University Cancer Center, 14 cases in the First Affiliated Hospital of Nanjing Medical University, 14 cases in Zhongshan Hospital Affiliated to Xiamen University and 8 cases in General Hospital of Chinese People′s Liberation Army Air Force, from January 2010 to April 2020 were collected. There were 346 males and 395 females, aged 55(range, 17?86)years. Observation indicators: (1) neoadjuvant treatment; (2) surgical and postoperative situations; (3) follow-up; (4) stratified analysis. Follow-up was conducted using outpatient examination or telephone interview. Patients were followed up once every 3?6 months during neoadjuvant therapy and once every 6?12 months after radical surgery to detect tumor recurrence and survival of patient up to April 2022. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, and the matching tolerance was 0.02. Results:(1) Neoadjuvant therapy. Of the 741 patients, 34 cases received neoadjuvant therapy for 8(range, 3?44)months. Cases assessed as partial response, stable disease and progressive disease before the radical surgery of the 34 cases were 21, 9, 4, respectively. The tumor diameter of the 34 patients before the neoadjuvant therapy and before the radical surgery were 8.0(range, 3.0?26.0)cm and 5.3(range, 3.0?18.0)cm, with the regression rate as 31.9%(range, ?166.7% to 58.3%). (2) Surgical and postoperative situations. Of the 741 patients, 34 cases underwent radical surgery after receiving neoadjuvant therapy, and 707 cases underwent radical surgery directly. All the 741 patients underwent radical surgery successfully, in which 633, 102 and 6 cases received open surgery, laparoscopic surgery and endoscopic treatment, respectively. Of the 633 cases receiving open surgery and the 102 cases receiving laparoscopic surgery, cases with surgical resection range as pancreatoduodenectomy (PD) was 238, and cases with surgical resection range as duodenal limited resection, including duodenal wedge resection, distal gastrectomy, segmental duodenal resection, local resection of duodenal tumor or segmental duodenum combined with subtotal gastrectomy, was 497, 226, 55, 204, 12. Of the 741 patients, 131 cases had post-operative complications including 113 cases with grade Ⅰ?Ⅱ complications and 18 cases with ≥ grade Ⅲ complications of the Clavien-Dindo classification. The duration of postoperative hospital stay of the 741 patients was 13(range, 4?120)days. Of the 707 patients receiving direct radical surgery, 371 cases were evaluated as extremely low risk, low risk, medium risk of the modified National Institutes of Health (NIH) risk classification after surgery, and 336 cases were evaluated as high risk in which 205 cases receive postoperative adjuvant imatinib therapy with the treatment time as 24(range, 6?110)months. (3) Follow-up. All the 741 patients were followed up for 58(range, 7?150)months. During the follow-up, 110 patients had tumor recurrence and metastasis. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 741 patients were 100.0%, 98.6%, 94.5% and 98.4%, 90.9%, 84.9%, respectively. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 707 patients receiving direct radical surgery were 100.0%, 98.5%, 94.3% and 98.4%, 91.1%, 85.4%, respectively. (4) Stratified analysis. ① Analysis of prognostic factors in patients undergoing radical surgery directly. Results of univariate analysis showed that primary tumor location, tumor diameter, mitotic count, modified NIH risk classification and tumor gene information were related factors affecting the overall survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.43, 0.18, 0.22, 0.06, 0.29, 95% confidence intervals as 0.20?0.93, 0.09?0.35, 0.10?0.50, 0.03?0.12, 0.09?0.95, P<0.05). The primary tumor location, tumor diameter, mitotic count, modified NIH risk classification were related factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.65, 0.25, 0.25, 0.10, 95% confidence intervals as 0.41?1.03, 0.17?0.37, 0.15?0.42, 0.07?0.15, P<0.05). Results of multivariate analysis showed that primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation were independent risk factors affecting the overall survival of 365 patients with primary duodenal GIST after removing 342 patients without tumor gene information who underwent direct radical surgery ( hazard ratio=2.85, 2.73, 3.13, 95% confidence intervals as 1.12?7.20, 1.07?6.94, 1.23?7.93, P<0.05). Tumor diameter >5 cm and mitotic count >5/50 high power field were independent risk factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=3.19, 2.98, 95% confidence intervals as 2.05?4.97, 1.99?4.45, P<0.05). ② Effect of postoperative adjuvant therapy on prognosis of high-risk patients of modified NIH risk classification. Of the 336 patients evaluated as high risk of the modified NIH risk classification, the 5-year overall survival rate and 5-year disease-free survival rate were 94.6% and 77.3% in the 205 cases with postoperative adjuvant therapy, versus 83.2% and 64.4% in the 131 cases without postoperative adjuvant therapy, showing significant differences between them ( χ2=8.39, 4.44, P<0.05). Of the 205 patients evaluated as high risk of the modified NIH risk classification who received postoperative adjuvant therapy, there were 106 cases receiving postoperative adjuvant therapy <36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 87.1% and 58.7%, and there were 99 cases receiving post-operative adjuvant therapy ≥36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 100.0% and 91.5%. There were significant differences in the 5-year overall survival rate and 5-year disease-free survival rate between the 106 patients and the 99 patients ( χ2=13.92, 29.61, P<0.05). ③ Comparison of clinical efficacy of patients with different surgical methods. Before propensity score matching, cases with primary tumor located at bulb, descending, horizontal, ascending segment of duodenum, cases with tumor diameter ≤5 cm and >5 cm were 95, 307, 147, 34, 331, 252, in the 583 patients receiving open surgery with complete clinical data, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery with complete clinical data, showing no significant difference in the primary tumor location ( χ2=0.94, P>0.05), and a significant difference in the tumor diameter ( χ2=17.33, P<0.05) between them. After propensity score matching, the above indicator were 16, 39, 20, 8, 67, 16 in the 83 patients receiving open surgery, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery, showing no significant difference between them ( χ2=1.54, 0.00, P>0.05). Cases with postoperative complications, cases with grade Ⅰ?Ⅱ complica-tions and ≥grade Ⅲ complications of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 17, 12, 5, 11(range, 5?120)days, 92.0%, 100.0% in the 83 patients receiving open surgery, versus 9, 7, 2, 11(range, 5?41)days, 91.6%, 97.3% in the 83 patients receiving laparoscopic surgery, showing no signi-ficant difference in postoperative complications, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=2.91, Z=3 365.50, χ2=3.02, 1.49, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification between them ( P>0.05). ④ Comparison of clinical efficacy of patients with primary tumor located at the descending segment of duodenum who underwent surgery with different surgical resection scopes. Before propensity score matching, cases with tumor diameter ≤5 cm and >5 cm, cases with tumor located at opposite side of mesangium and mesangium were 71, 85, 28, 128 in the 156 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 92, 41, 120, 13 in the 133 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing significant differences between them ( χ2=16.34, 150.10, P<0.05). After propensity score matching, the above indicator were 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference between them ( χ2=0.00, 0.00, P>0.05). Cases with postopera-tive complications, cases with grade Ⅰ?Ⅱ complications and ≥grade Ⅲ compli-cations of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 13, 11, 2, 15(range, 9?62)days, 94.2%, 64.3% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 9, 8, 0, 15(range, 7?40)days, 100.0%, 78.8% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference in post-operative complica-tions, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=0.99, 0.34, 1.86, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification ( P>0.05) and there was a significant difference in duration of postopera-tive hospital stay ( Z=614.50, P<0.05) between them. Conclusions:The clinical efficacy of radical surgery for duodenal GIST are ideal. Primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation are independent risk factors affec-ting the overall survival of patients undergoing direct radical surgery and tumor diameter >5 cm and mitotic count >5/50 high power field are independent risk factors affecting the disease-free survival of patients. There is no significant difference in the short-term efficacy and long-term prognosis between patients undergoing open surgery and laparoscopic surgery. For patients with primary tumor located at the descending segment of duodenum, the duration of postoperative hospital stay is longer in patients undergoing PD compared with patients undergoing duodenal limited resection. For patients evaluated as high risk of the modified NIH risk classification, posto-perative adjuvant therapy and treatment time ≥36 months are conducive to improving the prognosis of patients.

Objective:Comparison of conventional chemotherapy and immunotargeted therapy efficacy in patients with relapsed/refractory (R/R) acute B cell leukemia (B-ALL) .Methods:The clinical data of 212 patients with R/R B-ALL in the Affiliaed Cancer Hospital of Zhengzhou University from January 2008 to July 2020 were analyzed retrospectively to compare the response rate and survival time difference between conventional chemotherapy and immunotargeted therapies (antiCD19 CAR-T and CD3CD19 bi-specific antibody blinatumomab) , and to explore the related factors affecting prognosis.Results:The CR rate of patients with R/R B-ALL treated with anti-CD19 CAR-T cells was 80.4% , patients treated with blinatumomab was 62.5% , and patients treated with chemotherapy was 38.6% . There was significant difference in the CR rate among the three therapies ( P<0.001) . CAR-T cells 1-year OS rate was 41.5% , which was significantly higher than that of the chemotherapy group (10.3% ) ( P<0.001) . The 1-year PFS rate of CAR-T cells (30.1% ) was also significantly higher than that of the chemotherapy group (9.7% ) ( P<0.001) . The median OS of patients with bridging allo-HSCT after CR treatment by CAR-T cells was 18.5 months, which was higher than that of patients without allo-HSCT (8 months) ( P=0.027) . The median PFS of patients with allo-HSCT was 17 months, which was higher than that of patients without allo-HSCT (4 months) ( P=0.001) . The 1-year OS rate of patients treated with blinatumomab was 14.3% , which was higher than that of the chemotherapy group (10.3% ) ( P=0.018) . The 1-year PFS rate (14.6% ) was also higher than that of the chemotherapy group (9.7% ) ( P=0.046) . The median OS and median PFS of patients with bridging allo-HSCT were 13 and 11 months, respectively, which was higher than that of patients without allo-HSCT (9.5 and 6 months) . The cytokine release syndrome (CRS) incidence in patients with R/R B-ALL treated with anti-CAR-T cells was 89.8% . Grades 3-4, grade 2, and grade 1 CRS were experienced by 30.2% , 11.3% and 58.5% patients, respectively. Only three patients (37.5% ) with blinatumomab developed CRS, all of which were grade 1. Conclusion:The response rate and survival rate of patients with R/R B-ALL treated with CD19 CAR-T cells and blinatumomab were significantly better than those treated with conventional chemotherapy.