Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective To observe the value of spectral CT for predicting regional lymph node metastasis of colorectal cancer(CRC).Methods Totally 73 patients with CRC confirmed by postoperative pathology were retrospectively enrolled and divided into positive group(n=29)and negative group(n=44)based on the presence or absence of regional lymph node metastasis.The lymph node short diameter,CT value of 120 kV conventional image(CT value120 kV),CT values of 40 keV and 70 keV virtual single energy images(CT value40 keV and CT value70keV),iodine density(ID),effective atomic number(Zeff)and spectral curve slope(λHU).The above parameters and clinical indicators were compared between groups.After excluding those with variance inflation factor greater than 10,model 1 was constructed based on carbohydrate antigen 19-9(CA19-9)and carcinoembryonic antigen(CEA),model 2 based on conventional CT parameters(lymph node short diameter,CT value120 kV),model 3 based on spectral CT parameters(CT value70 keV,ID,Zeff,λHU),and model 4 based on conventional CT parameters and spectral CT parameters.The efficacy of 4 models for predicting regional lymph node metastasis of CRC were analyzed.Results Significant differences in patients'gender,carbohydrate antigen 19-9(CA1 9-9),carcinoembryonic antigen(CEA),lymph node short diameter,CT value120 kV,CT value40 keV,CT value70 keV,ID,Zeff and λHU were found between 2 groups(all P＜0.05).The area under the curve(AUC)of model 1-4 for predicting regional lymph node metastasis of CRC was 0.734,0.752,0.996 and 0.995,respectively,and significant differences were found between model 1 and 3,model 1 and 4,model 2 and 3,as well as model 2 and 4(all P＜0.001).Conclusion Enhanced venous phase spectral CT could effectively predict regional lymph node metastasis of CRC.

Objective This study aims to determine whether electroacupuncture regulates the phospholipase C(PLC)/inositol-1,4,5-trisphosphate(PLC/IP3)pathway in platelet-derived growth factor receptor α-positive(PDGFRα+)cells,thereby improving gastrointestinal motility disorders in functional dyspepsia(FD).Methods 40 SD rats were randomly divided into blank group,model group,electroacupuncture group,U73122(PLC inhibitor)group,and U73122+electroacupuncture group,with 8 rats in each group.Except for the blank group,all rats were subjected to multi-factor stress intervention to establish the FD model.After successful modeling,the U73122 group was given intraperitoneal injection of inhibitor,the electroacupuncture group was acupunctured at Zusanli and Taichong points,and the U73122+electroacupuncture group was injected with inhibitor 2 hours before acupunc-ture.Ten days later,gastrointestinal motility was tested;immunoblotting was used to detect the protein expression levels of PDGFRα,PLC,P-PLC,IP3;immunofluorescence was used to detect the average fluorescence density and co-localization expression of PDGFRα and PLC,IP3;electron microscope was used to observe the gap junction(GJ)situation in the gastric antrum area.Results After modeling,the gastrointestinal motility of rats was weakened,the protein expression levels of PDGFRα,PLC,and IP3 were significantly reduced,GJ widened,and cell morphol-ogy changed;compared with the model group,the gastrointestinal motility of rats in the electroacupuncture group,U73122 group,and U73122+electroacupuncture group was significantly improved,the expression levels of PDGFRα,PLC,P-PLC,IP3 increased,GJ was slightly tight,and cell morphology recovered;there was no significant difference in the expression levels of PDGFRα,PLC,P-PLC,IP3 in the gastric antrum of U73122 group and U73122+electroacupuncture group;PDGFRα,PLC,and IP3 had fluorescence co-localization.Conclusion Electroacupuncture can improve gastrointestinal dyskinesia in FD rats by activating the PLC/IP3 pathway in PDGFRα+cells.

ObjectiveTo explore the effect and possible mechanism of electroacupuncture （EA） at Fenglong （ST40） on liver lipid synthesis and insulin resistance （IR） in hyperlipidemic （HLP） rats. MethodEighteen rats were randomly divided into three groups， blank group， model group， and EA group， each consisting of six rats. The blank group rats were with fed a basic diet， while those in the model group and EA group were fed high-fat diet for 8 weeks. After modeling， the rats in the EA group received bilateral EA treatment at “Fenglong” （ST 40）. The rats in the model group underwent daily binding treatment， once a day， continuously 5 days a week， for a total of 4 weeks. Following the intervention， the levels of triglycerides （TG） and free fatty acids （FFA） in liver tissue was determined using ELISA. Serum TG， FFA， fasting insulin （FINS）， alanine transaminase （ALT）， aspartate Transaminase （AST）， tumor necrosis factor-ɑ （TNF-ɑ）and interleukin 6 （IL-6） were also measured. The fasting plasma glucose （FBG） assessed using a glucose meter and the homeostatic model assessment of insulin resistance （HOMA-IR） was calculated. Liver pathology was examined through HE staining and oil red O staining. The expression of hepatic sterol regulator binding protein 1c （SREBP1c）， recombinant fatty acid synthase （FASN） and stearoyl-CoA desaturase 1 （SCD1） were detected through immunofluorescence. The protein expression levels of liver insulin receptor substrate 1 （IRS1） and tyrosine-phosphorylated insulin receptor substrate 1 （p-IRS1-Tyr） were determined via Western blot. ResultsWhen compared to the blank group， the model group of rats exhibited elevated serum and liver tissue levels of TG and FFA， as well as increased serum levels of AST， ALT， TNF-α， IL-6， FBG， FINS， and HOMA-IR （P＜0.05）. HE staining revealed disordered arrangements of liver cells， indicating widespread fatty degeneration. Oil red O staining showed abundant bright red lipid droplets within liver cell cytoplasm， indicating severe lipid accumulation. The average fluorescence intensity of SREBP1c， FASN， and SCD1 in liver tissue significantly increased （P＜0.05）， while p-IRS1-Tyr protein expression levels significantly decreased （P＜0.05）. In comparison to the model group， the EA group of rats showed significantly reduced serum and liver tissue levels of TG and FFA， along with decreased serum levels of AST， ALT， TNF-α， IL-6， FBG， FINS， and HOMA-IR （P＜0.05）. HE staining indicated more regular arrangements of liver cells， and oil red O staining revealed a significant reduction in liver cell lipid droplets， indicating a less severe degree of lipid accumulation. The average fluorescence intensity of SREBP1c， FASN， and SCD1 in liver tissue significantly decreased （P＜0.05）， while p-IRS1-Tyr protein expression levels significantly increased （P＜0.05）， with no significant difference in IRS1 protein expression （P＞0.05）. ConclusionEA at “Fenglong” （ST 40） can significantly decrease serum lipid in HLP rats， improves liver fat accumulation， and also ameliorate insulin resistance. The mechanism may be related to the inhibition of hepatic lipid synthesis molecule expression， reduced serum inflammatory factors， and an increase in insulin substrate receptor phosphorylation levels.

Objective:To evaluate the short-term efficacy of dual biologics combination therapy in the treatment of refractory Crohn′s disease (CD) .Methods:The clinical features, diagnosis and treatment of 5 cases of refractory CD treated with biologics dual-target therapy in the Seventh Medical Center of Chinese PLA General Hospital between January 26, 2020 and August 15, 2021 were retrospectively analyzed. The relevant literatures were reviewed and summarized by searching the articles on biologics dual-target therapy published in MEDLINE, EMBASE and Cochrane Library until August 2021.Results:Five patients with refractory CD were all male, aged 40.8 (23.0, 56.0) years, with disease course of 10.4 (6.0, 17.0) years, including 2 patients treated with infliximab (IFX) in combination with ustekinumab (UST) . Two patients treated with IFX in combination with vedolizumab (VDZ) and 1 patient treated with UST in combination with VDZ. Laboratory and colonoscopy examinations were performed 14 weeks after combination therapy in the VDZ containing group and 16 weeks after combination therapy in the VDZ free group. Results of examinations after treatment indicated that 1 case presented clinical remission, 3 cases presented clinical response and 3 cases presented endoscopic response. Combination therapy group with UST had better efficacy. None of the 5 patients had special adverse drug reactions during follow-up for six months after combined treatment. A total of 17 relevant reports were retrieved.Conclusion:Biologic dual-target therapy may be a short-term effective and safe treatment for refractory CD.

Objective:To explore any effect of electroacupuncture (EA) at the Zusanli point on the scorch death of duodenal cells in rats with functional dyspepsia (FD) and possible mechanisms.Methods:Twenty-four 7-day-old Sprague-Dawley rats were randomly divided into a blank group, a model group and an EA group, each of 8. FD was induced in both the model and EA group rats using iodoacetamide gavage with tail-clip stimulation. After successful modeling the EA group was given acupuncture at the Zusanli point and then connected with a Korean acupuncture point nerve stimulator for 2 weeks. The other 2 groups were not given any intervention. The rats′ body weight was recorded before and after the modeling, as well as 7 and 14 days later. The gastric emptying rate and the small intestine propulsion rate of the three groups were detected right after the EA intervention, and the serum expression levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) were measured using enzyme-linked immunoassays. Real-time fluorescence quantitative polymerase chain reactions were used to detect the transcription levels of IL-1β and IL-6 in the rats′ duodenums, while western blotting was employed to assess the expression of caspase-1 P20 and dermatin D (GSDMD) in their duodenums.Results:After successful modeling, the average body weight of the rats in the model and EA groups was significantly different from that in blank group, and after 7 and 14 days the average body weight of the former groups was significantly different from that of the blank group, with significant differences between the two groups as well. After the EA intervention significant differences were observed in gastric reside and small intestine propulsion rate between the EA group and the model group, as well as between the model and the blank group. After the intervention, there were significant differences between the blank group and the other two groups in the average expression of IL-1β and IL-6 in serum, IL-1β and IL-6 mRNA in the duodenum, as well as the GSDMD and caspase-1 p20 proteins in the duodenum. There were significant differences between the model and EA groups in all of the above measurements.Conclusions:EA at the Zusanli point can significantly reduce the level of scorch death in the duodenum of FD rats, as well as relieve low-grade duodenal inflammation and the clinical symptoms of FD. Its mechanism may be related to the down-regulation of the expression of caspase-1 P20 and GSDMD-N protein, and of inflammatory factors such as IL-1β and IL-6, relieving low-grade duodenal inflammation.

Objective:To evaluate the short-term efficacy of dual biologics combination therapy in the treatment of refractory Crohn′s disease (CD) .Methods:The clinical features, diagnosis and treatment of 5 cases of refractory CD treated with biologics dual-target therapy in the Seventh Medical Center of Chinese PLA General Hospital between January 26, 2020 and August 15, 2021 were retrospectively analyzed. The relevant literatures were reviewed and summarized by searching the articles on biologics dual-target therapy published in MEDLINE, EMBASE and Cochrane Library until August 2021.Results:Five patients with refractory CD were all male, aged 40.8 (23.0, 56.0) years, with disease course of 10.4 (6.0, 17.0) years, including 2 patients treated with infliximab (IFX) in combination with ustekinumab (UST) . Two patients treated with IFX in combination with vedolizumab (VDZ) and 1 patient treated with UST in combination with VDZ. Laboratory and colonoscopy examinations were performed 14 weeks after combination therapy in the VDZ containing group and 16 weeks after combination therapy in the VDZ free group. Results of examinations after treatment indicated that 1 case presented clinical remission, 3 cases presented clinical response and 3 cases presented endoscopic response. Combination therapy group with UST had better efficacy. None of the 5 patients had special adverse drug reactions during follow-up for six months after combined treatment. A total of 17 relevant reports were retrieved.Conclusion:Biologic dual-target therapy may be a short-term effective and safe treatment for refractory CD.

Objective:To investigate the risk factors of Crohn′s disease (CD)-related gastrointestinal stenosis, and to summarize and analyze the corresponding treatments.Methods:From January 2010 to December 2018, 122 patients diagnosed with CD and hospitalized in the Seventh Medical Center, PLA General Hospital were selected including 72 patients in gastrointestinal stenosis group and 50 patients in non-gastrointestinal stenosis group. The gender, age of onset, course of disease, location of lesions involved (Montreal classification), disease activity, extraintestinal manifestations, application of therapeutic drugs, and complications were compared between the two groups. The treatment of CD patients with gastrointestinal stenosis was analyzed. Multivariate logistic regression was used to analyze the risk factors of CD patients with gastrointestinal stenosis. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The age of onset of patients in gastrointestinal stenosis group was older than that in non-gastrointestinal stenosis group ((37.6±15.1) years old vs. (30.8±14.7) years old), and course of disease was longer than that of non-gastrointestinal stenosis group (72 months, 11 to 492 months vs. 45 months, 3 to 240 months); and the differences were statistically significant ( t=-2.044, Z=-2.770; P=0.018, 0.006). The proportion of patients with ileum involvement of the gastrointestinal stenosis group was lower than that of the non-gastrointestinal stenosis group (69.4%, 50/72 vs. 86.0%, 43/50), and the proportion of severe patients was higher than that of the non-gastrointestinal stenosis group (15.3%, 11/72 vs. 4.0%, 2/50); and the differences were statistically significant ( χ2=4.463 and 3.942, P=0.035 and 0.047). There were no significant differences in gender, use of therapeutic drugs, extraintestinal manifestations, application of therapeutic drugs or the incidence of complications between the patients of two groups (all P>0.05). The results of multivariate logistic regression showed that the age of onset and course of disease were risk factors of CD-related gastrointestinal stenosis ( β=0.028, odds ratio ( OR)=1.028, 95% confidence interval ( CI) 1.000 to 1.056, P=0.046; β=0.008, OR=1.008, 95% CI 1.002 to 1.015, P=0.013). Further stratified analysis revealed that the incidence rates of CD-related gastrointestinal stenosis in patients with age of onset over 40 years old and course of disease more than five years were higher than those of patients with age of onset less than 40 years old and course of disease less than five years (76.3%, 29/38 vs. 51.2%, 43/84; 68.4%, 39/57 vs. 50.8%, 33/65), and the differences were statistically significant ( OR=3.072, 95% CI 1.298 to 7.272, P=0.009; OR=2.101, 95% CI 1.002 to 4.406, P=0.048). Among the 72 CD patients with gastrointestinal stenosis, 15 cases (20.8%) were treated with medicine and nutrition, without endoscopic or surgical treatment. Fifty-two patients (72.2%) underwent surgical treatment, among them six patients (11.5%) received twice surgery, the interval between the two operations was 46 months (1 to 204 months), and eight patients (15.4%) had postoperative complications. Twenty-one patients (29.2%) were treated with endoscopic dilatation, and no complications occurred after surgery. Five patients (23.8%) underwent surgical treatment during the follow-up period. Conclusions:The age of onset over 40 years old and the course of disease more than five years are the risk factors of CD-related gastrointestinal stenosis. Individualized medical treatment is the basis for the treatment of CD-related gastrointestinal stenosis. Surgery is still the main treatment. The endoscopic treatment is safety and can delay or avoid surgery to a certain extent.

Objective: To investigate the risk factors of prolonged postoperative length of stay (LOS) in patients with gastric cancer. Methods: A retrospective study was performed on 2033 patients who underwent curative surgery in Department of Pancreatic-gastric, Cancer Hospital, Chinese Academy of Medical Sciences. Eightieth percentile of postoperative hospital stay for all patients was taken as the cutoff, the patients were divided into the normal group (1 532 patients) and the extended group (501 patients). Logistic regression model was used to determine the risk factors related to prolonged postoperative LOS in gastric cancer. Results: A total of 417 cases with postoperative complications were recruited in extended group. The five highest complications accounting for prolonged LOS were: abdominal infection in 69 cases (13.77%), pleural effusion in 60 cases (11.98%), anastomotic leakage in 43 cases (8.58%), poor wound healing in 34 cases (6.79%), and bleeding in 25 cases (4.99%). Logistic regression analysis showed that age (OR=1.348, P=0.013), surgical procedure (OR=2.712, P<0.001), extent of resection (OR=2.035, P<0.001), degree of incision healing(OR=4.867, P<0.001), and perioperative blood transfusion (OR=1.711, P<0.001) were independent risk factors for prolonged postoperative LOS. Conclusions The most common complication associated with prolonged postoperative LOS for gastric cancer patients is abdominal infection. Age, surgical procedure, extent of resection, degree of incision healing, and perioperative blood transfusion are the independent risk factors for prolonged postoperative LOS.

Objective To analyze the incidence and predictors of chronic subdural hematoma (CSDH) after surgical clipping between unruptured intracranial aneurysms (UIAs) and ruptured intracranial aneurysms (RIAs).Methods A retrospective cohort study was adopted to collect 486 cases of aneurysm patients (102 cases of UIAs patients and 384 RIAs patients) closed by aneurysm surgery who were admitted to the department of neurosurgery of The Fifth People's Hospital of Chengdu from October 2009 to December 2017.The clinical data,preoperative and postoperative imaging data and postoperative follow-up results were collected.The incidence of CSDH after operation in UIAs patients and RIAs patients was compared.The risk factors of CSDH after UIAs and RIAs patients were analyzed by multivariate Logistic regression model.Results The incidence of CSDH in UIAs and RIAs patients (10.78％ vs 3.13％,x2 =10.487,P =0.001) and the reoperation rate after CSDH (3.92％ vs 0.78％;x2 =5.599,P =0.018) were all statistically different,all of which showed that the patients with UIAs were higher than those of the patients with RIAs.Brain atrophy of grade 3-4 (OR =1.978,95％ CI:1.939-2.030,P ＜ 0.001),subdural effusion CT value ≥40 (OR =3.394,95％ CI:2.908-3.867,P ＜ 0.001) and subdural effusion (OR =2.872,95％ CI:2.648-3.019,P ＜0.001 grade) of Ⅰ B are independent risk factors of CSDH in patients with UIAs after aneurysm clipping (P ＜0.05).Subdural effusion CT value ≥ 40 (OR =3.442,95％ CI:2.918-3.8769,P ＜ 0.001) and grade Ⅰ B subdural effusion (OR =2.329,95％ CI:2.011-2.564,P ＜ 0.001) are independent risk factors for CSDH in patients with RIAs after aneurysm clipping (P ＜0.05).Conclusions The incidence of CSDH after aneurysm clipping in UIAs patients was significantly higher than that of RIAs patients.The risk factors for CSDH in the two groups were not the same.