Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To create a mouse model of colorectal polyps with Apc-Kras-Cre gene mutations using the tamoxifen induction method.Methods Mice with Apc-Kras-Cre mutations were divided into four groups and injected intraperitoneally with different concentrations and dosages of tamoxifen for different durations,with group 1 injected with low dosage tamoxifen(5 mg/kg)for 1 day,group 2 injected with low dosage tamoxifen(5 mg/kg)for 3 days,group 3 injected with high dosage tamoxifen(50 mg/kg)for 1 day,group 4 injected with high dosage tamoxifen(50 mg/kg)for 3 days.C57BL/6J mice were used as a healthy control group and survival and changes in body weight were observed.All mice were euthanized 4 weeks post-tamoxifen induction and the colon length and number and size of intestinal polyps were observed.Histological changes in the intestinal tissue and polyps were detected by hematoxylin and eosin staining.Results The survival rate of male mice was higher(P＜0.001)and the morbidity rate of male mice was lower compared with female mice(P＜0.05).The survival rate differed significantly among the four groups(P＜0.01).All groups showed significant changes in body weight compared with the healthy control group(P＜0.001).There were also significant differences in weight changes between tamoxifen-induced groups 1 and 2,between groups 2 and 3,and between groups 1 and 4(P＜0.001,P＜0.01,P＜0.05,respectively).There were no significant differences in colon length between any treated group and the healthy control group(P＞0.05),but colon length did differ between tamoxifen-induced groups 1 and 3(P＜0.05).Polyp size varied in each group of tamoxifen-treated mice,with most polyps occuring at the distal end of the colon,while mice in groups 3 and 4 had more and larger polyps.Histopathological examination showed intestinal polyps with uneven and misaligned glandular and epithelial arrangements,a loosely-packed intestinal mucosal barrier,and irregularly-distributed crypts in tamoxifen-induced mice compared with the healthy control group,while mice in tamoxifen-induced groups 3 and 4 showed signs of inflammation and mice in group 4 showed necrosis of cells in some regions.Conclusions Tamoxifen-induced Apc-Kras-Cre model mice were successfully established,with the group 3 induction method being the most suitable.

OBJECTIVE To establish a comprehensive and rapid m ethod for the a nalysis of chemical constituents as phthalides and organic acids in Angelica sinensis ，and to provide scientific reference for the quality evaluation and pharmacodynamic substance research of A. sinensis . METHODS The 70％ ethanol extract of A. sinensis was analyzed by ultra high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF/MS）. The determination was performed on ACQUITY UPLC BEH-C 18 column with mobile phase consisted of 0.1％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃，and sample size was 2 µL. The ion source was an electrospray ion source ，using positive ion scanning mode ，and the mass scanning range was m/z 50-1 000. Capillary voltage was 4 000 V； atomizer pressure was 35 psi；cracking voltage was 135 V and the taper hole voltage was 65 V；the temperature of dry gas was 320 ℃；the flow of dry gas was 10 L/min and the flow of sheath gas was 11 L/min；collision energy were 20 and 40 V. Qualitative Analysis 10.0 software was used to obtain the retention time of compounds ，the accurate mass number of excimer ion peaks and secondary fragments. The compounds were analyzed by comparing with the mass spectra of the reference substance ，combined with relevant literature ，mass spectrometry cleavage law and database such as Chemspider ，MassBank，PubChem. RESULTS A total of 72 compounds were identified or deduced from A. sinensis ，including 55 phthalides，13 organic acids and 4 other constituents. CONCLUSIONS The established method is rapid and accurate for the identification of chemical constituents from A. sinensis ，such as organic acids and phthalides ，which provides an efficient and rapid analytical method for the comprehensive characterization of its chemical constituents.

Objective To study and the succession of sarcosaphagous insects and their regular activity on carcass in Xinxiang area. Methods Six rats and five rabbits were sacrificed and placed at the remote grassland of Xinxiang Medical University in July 2015. The main insect species and the decomposition process were observed. The different decomposition stages and the community succession of insects were recorded. Results Seven main species could be identified belonging to 3 families from Diptera, main including Musca domestica, Chrysomya megacephala, Lucilia sericata, Boettcherisca peregrina, Helicophagella melanura. Muscina stabulans and Fannia prisca. And showed regulations of the succession of sarcosaphagous flies community. Conclusion It may be used for estimating postmortem interval in Xinxiang area.

Objective To study the effect of dampness-eliminating and spleen-strengthening Prescription (ESP) on expression levels of adiponectin (APN) , tumor necrosis factor alpha (TNF-α) , and hepatic fat content in type 2 diabetes mellitus ( T2DM) patients complicated with non-alcoholic fatty liver disease ( NAFLD) . Methods One hundred and twenty T2DM patients complicated with NAFLD were randomized into ESP group and pioglitazone group, 60 cases in each group. Based on the fundamental treatment for decreasing glucose, ESP group and pioglitazone group were given oral use of ESP and pioglitazone respectively. Twenty-four weeks constituted one treatment course. Before and after treatment, we observed the hepatic fat content, serum concentrations of APN and TNF-α, blood glucose, blood lipid, and hepatic function with the virtual touch tissue quantification technique ( VTQ) , enzyme-linked immunosorbent assay ( ELISA) , biochemical analysator respeetively in the two groups. Results After treatment, the levels of fasting plasma glucose ( FPG) , 2-hour postprandial plasma glucose ( 2hPG) , glycosylated hemoglobin ( HbA1c) fasting insulin ( FINS) , total cholesterol ( TC) , triglyceride ( TG) , low density lipoprotein cholesterol ( LDL-C) and TNF-α, and hepatic acoustic radiation force impulse ( ARFI) scores in the two groups were significantly lower than those before treatment (P<0.05) . On the other hand, the serum levels of high density lipoprotein cholesterol (HDL-C) and APN in both groups were significantly higher than those before treatment ( P<0.05) . The difference values of FINS and NF-α before and after treatneat in ESP group were higher than those in pioglitazone group ( P<0.05) . Conclusion ESP can significantly ameliorate the metabolic disorders of glucose and lipid , protect the pancreatic function and reduce hepatic fat, which is possibly related with the increase of APN level and the de-crease TNF-αlevel.