Objective:To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations.Methods:173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data.Results:The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores ( r ?=?0.73, P ?

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.

Self-assembly is the basis of the formation of biological macromolecular structure. Enzyme-instructed self-assembly (EISA) with the help of tool enzymes, realizing the conversion of small molecular compounds to supramolecular nanostructures at specific sites, become a new strategy for drug discovery.In recent years, the exploration of EISA for developing malignant cancer therapy and imaging has made considerable progress, achieving the precise regulation and tumor targeting of nanostructures. This paper reviews the latest progress of EISA in the field of tumor diagnosis and treatment, the functions and characteristics of tool enzymes such as alkaline phosphatase, sirtuin, tyrosinase, γ-glutamyltranspeptidase and caspase-3,summarizes the research status of EISA targeting multiple organelles in tumor therapy, and introduces the application of EISA in tumor imaging, aiming to provide reference forthe research of EISA strategy in tumor diagnosis and treatment.

To ensure proper dosage of a drug,analytical quantification of it in biofluid is necessary.Liquid chro-matography mass spectrometry(LC-MS)is the conventional method of choice as it permits accurate identification and quantification.However,it requires expensive instrumentation and is not appropriate for bedside use.Using soluble epoxide hydrolase(sEH)inhibitors(EC5026 and TPPU)as examples,we report development of a nanobody-based enzyme-linked immunosorbent assay(ELISA)for such small molecules and its use to accurately quantify the drug chemicals in human samples.Under optimized conditions,two nanobody-based ELISAs were successfully established for EC5026 and TPPU with low limits of detection of 0.085 ng/mL and 0.31 ng/mL,respectively,and two order of magnitude linear ranges with high precision and accuracy.The assay was designed to detect parent and two biologically active metabolites in the investigation of a new drug candidate EC5026.In addition,the ELISAs displayed excellent correlation with LC-MS analysis and evaluation of inhibitory potency.The results indicate that nanobody-based ELISA methods can efficiently analyze drug like compounds.These methods could be easily implemented by the bedside,in the field in remote areas or in veterinary practice.This work il-lustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and therapy.At-tributes of nanobody based pharmaceutical assays are discussed.

Objective:To analyze the feasibility and clinical efficacy of reperfusion-expanding-thrombectomy-stenting (RETS) technique in the endovascular treatment of acute carotid artery tandem lesion.Methods:The general clinical data of 88 patients with carotid artery tandem lesion who received emergency endovascular treatment from January 2018 to December 2020 in Department of Neurology, Linyi People′s Hospital were reviewed, the Modified Rankin Scale (mRS) was used as the evaluation standard for the prognosis of patients at 90 days after endovascular treatment, and the clinical data were analyzed, including the recanalization (modified thrombolysis in cerebral infarction ≥2b), perioperative complications and 90-day prognosis, and good prognosis was defined as a mRS score of 0-2.Results:A total of 88 patients with tandem carotid artery disease were included,48 of whom were treated with RETS technique, 40 were treated with anterograde approach. Compared with antegrade recanalization, RETS technique had significant differences in the time from puncture to recanalization [(72.06±17.29) min vs (98.88±26.09) min, t=-5.56, P<0.001] and the primary recanalization rate [35/48(73.0%) vs 21/40(52.5%),χ2=3.93 ,P=0.047], with statistically significant difference. There was no significant difference in clinical prognosis and surgical complications between the two methods (all P>0.05). Conclusions:RETS technique can shorten the operation time and increase the primary recanalization rate. RETS technique is safe and feasible for the treatment of carotid tandem lesions.

Boron neutron capture therapy (BNCT) is a new method for the precise treatment of cancers.By this method, cancer cells can be selectively killed by α particles and recoiling 7Li nuclei generated by the nuclear fission reaction occurring when the 10B isotope atoms in cancer cells capture thermal neutrons.The key to a successful BNCT is to deliver sufficient 10B into the cancer cells.The purpose of this review is to introduce the principles of BNCT and review recent progress in the development of neutron sources and boron delivery agents, as well as the result of BNCT clinical trials.

Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee′s triad syndrome. Methods: The concept of Lee′s triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee′s triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People′s Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee′s triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee′s triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m² to (21.0±1.3) kg/m², total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion When patients with SMACS secondary to chronic constipation have Lee′s triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.

Objective:To observe the long-term efficacy and complication rate of fecal microbiota transplantation (FMT) and the effects of different ways of transplantation and treatment courses on the efficacy of FMT.Methods:From April 2012 to April 2020, the data of 3 932 patients (804 cases of Nanjing General Hospital of Nanjing Military Command and 3 128 cases of Tenth People′s Hospital of Tongji University) who voluntarily received FMT treatment were prospectively collected. After the first course of transplantation, the follow-up rate and efficacy and complications in 5 years were observed at the 1st, 12th, 24th, 36th, 48th and 60th month. According to the different ways of the first transplantation, 3 932 patients were divided into nasointestinal tube group (2 604 cases), capsule group (873 cases), colonoscopy group (268 cases) and enema group (187 cases). One month after transplantation, the effective rate and complication were observed. At the same time, the 1 813 patients with FMT less than four courses were divided into 1 treatment course group (369 cases), 2 treatment courses group (568 cases), 3 treatment courses group (497 cases) and 4 treatment courses group (379 cases). The effective rates of patients in four groups with different treatment courses were observed 6 months after finishing the treatment. Chi square test was used for statistical analysis.Results:Among 3 932 patients, the follow-up rates at 1st, 12th, 24th, 36th, 48th and 60th month after the first course of FMT were 93.67%(3 683/3 932), 82.30%(2 307/2 803), 82.17%(1 825/2 221), 62.41%(978/1 567), 59.85%(559/934) and 60.84%(289/475), respectively. The total effective rates at 1st, 12th, 24th, 36th, 48th and 60th month were 67.23%(2 476/3 683), 64.20%(1 481/2 307), 59.29%(1 082/1 825), 59.71%(584/978), 55.81%(312/559) and 59.17%(171/289), respectively. During FMT period, the total incidence of different complications was 34.49%(1 356/3 932). During follow-up period, the total rate of complication was 4.22%(166/3 932). There were no serious adverse events such as gastrointestinal perforation, multi-drug resistant bacterial infection, organ failure and death. One month after FMT, the effective rates of nasojejunal tube group, capsule group, colonoscopy group, and enema group were 67.18%(1 668/2 483), 68.63%(549/800), 67.23%(158/235), 61.21%(101/165), respectively. There was no significant difference among the four groups ( P>0.05). The effective rates of patients with chronic constipation in nasal jejunal tube group, capsule group and colonoscopy group were all higher than that of enema group (67.82%, 1 043/1 538; 67.98%, 138/203 and 62.96%, 17/27 vs. 26.67%, 8/30), and the differences were statistically significant ( χ2=22.55, 19.07 and 7.60, all P<0.01). During the period of FMT, the total incidence of complications of nasojejunal tube group, capsule group, colonoscopy group and enema group were 35.22%(917/2 604), 30.24%(264/873), 42.54%(114/268) and 32.62%(61/187), respectively. The difference was statistically significant among four groups ( χ2 =18.84, P<0.01). Among nasojejunal tube group, capsule group, colonoscopy group and enema group, there were significant differences in the incidence of diarrhea (4.49%, 117/2 604; 4.58%, 40/873; 7.83%, 21/268 and 5.35%, 10/187, respectively), throat pain (5.30%, 138/2 604; 0.69%, 6/873; 2.99%, 8/268 and 1.07%, 2/187, respectively), gastrointestinal bleeding (0; 0; 1.87%, 5/268 and 0.53%, 1/187, respectively) and enterogenous infection (0; 0; 1.49%, 4/268 and 0.53%, 1/187, respectively) ( χ2 =8.24, 39.24, 63.13 and 49.68, all P<0.05). At the 6th month after treatment, the effective rates of 1 treatment course group, 2 treatment courses group, 3 treatment courses group and 4 treatment courses group were 63.94%(211/330), 61.93%(301/486), 65.75%(286/435) and 72.54%(251/346), respectively. There were statistically significant differences among groups with different treatment courses ( χ2 =10.70, P =0.01). The effective rate of the four treatment courses group was significantly higher than those of the one treatment course group, two treatment courses group and three treatment courses group, and the differences were statistically significant ( χ2=5.78, 10.18 and 4.14, all P<0.05). The effective rates of in chronic constipation and autism in 4 treatment courses group were significantly higher than those in 1 treatment course group and 2 treatment courses group (72.73%(136/187) vs.55.47%(71/128) and 58.71%(155/264), 72.73%(40/55) vs.6/15 and 47.83%(11/23)), the effective rate of autism in 3 treatment courses group was higher than that in 1 treatment course group (69.05%(29/42) vs. 6/15), and the differences were statistically significant ( χ2=10.05, 9.39, 5.60, 4.44 and 3.94, all P<0.05). Conclusions:The long-time efficacy of FMT is definite in the treatment of intestinal flora derangement related intestinal diseases and extraintestinal diseases complicated with intestinal disfunction and there are no serious adverse events. The efficacy of FMT is related to the way of transplantation and treatment. The incidence of complications of FMT is related to the way of transplantation. Different ways of transplantation and treatment courses should be formulated for different diseases.