Foot-and-mouth disease (FMD) is one of the major animal infectious diseases in the world. All cloven-hoofed animals are susceptible to FMD. Vaccination is still the first choice for the prevention and control of FMD. mRNA vaccines can be rapidly designed, synthesized, and produced on a large scale in vitro, and they can induce effective protective immune responses, demonstrating the advantages of rapid development, easy preparation, and low biosafety risks. The design of untranslated regions is a key to enhancing the expression and efficacy of mRNA vaccines. In order to generate an efficient FMD mRNA vaccine, we designed three FMD P12A3C expression vectors with different untranslated regions and synthesized corresponding mRNAs. By comparing expression efficiency of these vectors and their mRNAs at different time points and in different cell lines, we found that the mRNA P12A3C-UTR3 had the best expression and universality. This study laid a foundation for the development of mRNA vaccines against FMD and provided a theoretical basis for the optimal sequence design of efficient mRNA.
Foot-and-Mouth Disease Virus/genetics* ; Animals ; RNA, Messenger/biosynthesis* ; Foot-and-Mouth Disease/immunology* ; Antigens, Viral/biosynthesis* ; Viral Vaccines/biosynthesis* ; Genetic Vectors/genetics* ; Cell Line ; Vaccines, DNA/immunology*

Objective:To investigate the relationship between serum osteopontin (OPN), bone morphogenetic protein 2 (BMP2), retinol binding protein 4 (RBP4) and renal function and bone mineral density in patients with diabetes nephropathy (DN).Methods:A total of 120 patients with DN diagnosed in the Affiliated Hospital of Jining Medical University from January 2020 to December 2021 were selected as the DN group, 60 patients with simple diabetes as the type 2 diabetes mellitus (T2DM) group, and 60 subjects with normal glucose tolerance test as the control group. The serum OPN, BMP2, RBP4, low bone mineral density (LBMD), femoral neck bone density (FNBMD) and renal function indicators of the three groups were compared. According to the urinary albumin excretion rate (UAER) of DN patients, the patients were divided into microalbuminuria DN group (71 cases) and massive albuminuria DN group (49 cases), and stratified comparison was made. The simple linear correlation analysis was used to analyze the OPN of DN patients. BMP2, RBP4, renal function and bone mineral density.Results:The fasting blood glucose (FPG), glycated hemoglobin (HbA 1c), serum creatinine (Scr), UAER, and cystatin (CysC) levels of DN group patients were significantly higher than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The FPG and HbA 1c in the T2DM group were higher than those in the control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of DN group patients were higher than those of T2DM group and control group, while the RBP4, LBMD, FNBMD of DN group were lower than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of the T2DM group were higher than those of the control group, while RBP4 was lower than that of the control group, and the differences were statistically significant (all P<0.05); The levels of FPG, HbA 1c, Scr, UAER, and CysC in patients with macroalbuminuria DN were significantly higher than those in patients with microalbuminuria DN, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of patients in the large albuminuria DN group were higher than those in the microalbuminuria DN group, while the RBP4, LBMD, and FNBMD of patients in the large albuminuria DN group were lower than those in the microalbuminuria DN group, and the differences were statistically significant (all P<0.05). The OPN of DN group patients was positively correlated with Scr, UAER, and CysC (all P<0.05), while BMP2 was positively correlated with UAER and CysC (all P<0.05); The OPN and BMP2 of DN group patients were negatively correlated with LBMD and FNBMD (all P<0.05), while RBP4 was positively correlated with LBMD and FNBMD (all P<0.05). Conclusions:OPN, BMP2, RBP4 are closely related to the degree of renal function impairment and bone loss in DN patients, and can to some extent reflect the degree of bone metabolism and osteoporosis in T2DM patients.

Background/Aims: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. Methods: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. Results: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. Conclusions The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

Lipid nanoparticles serve as a promising drug delivery system due to the good biocompatibility, non-immunogenicity, and high drug loading efficiency. However, unmodified lipid nanoparticles have limitations such as poor stability, easy hydrolysis, and rapid removal. To overcome these shortcomings, researchers have developed peptide modification, antibody modification, ligand modification, nucleic acid aptamer modification, and polysaccharide modification for lipid nanoparticles. Polysaccharides are a class of natural polymers, and the polysaccharide-modified lipid nanoparticles exhibit good biocompatibility, precise targeting, and low toxicity. Therefore, polysaccharide-modified lipid nanoparticles demonstrate great potential in clinical treatment. This review summarizes the preparation and application of polysaccharide-modified lipid nanoparticles, aiming to provide a reference for further research and development of new lipid nanoparticles.
Polysaccharides/chemistry* ; Nanoparticles/chemistry* ; Lipids/chemistry* ; Drug Delivery Systems ; Humans ; Drug Carriers/chemistry*

Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

Clinical cases treated by magnetic compression anastomosis (MCA) for different causes and types of intestinal stenosis/ atresia to successfully achieve intestinal recanalization were reviewed, so as to explore the clinical application of MCA. From May 2019 to August 2022, 4 patients underwent colorectal MCA for intestinal recanalization in the First Affiliated Hospital of Xi'an Jiaotong University and Northwest Women and Children's Hospital. All operations went well, and the intestinal anastomosis was recanalized. The magnetic ring was discharged in 7-15 days, and the postoperative colonoscopy or radiography showed that the anastomosis was intact. MCA can be used to treat different types of colorectal stenosis and atresia due to different reasons, and can also be used to assist intestinal anastomosis in colorectal surgery.

Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Objective:To investigate the relationship between triglyceride glucos (TyG), C-reaction protein/albumin (CRP/Alb), 25-hydroxy vitamin D[25(OH)D] and the prognosis of patients with continous ambulatory peritoneal dialysis (CAPD).Methods:A total of 220 CAPD patients in the Affiliated Hospital of Jining Medical University from January 2017 to March 2020 were prospectively selected and divided into death group and survival group according to the 6-month prognosis. The peritoneal urea clearance index (Kt/V urea), TyG, CRP/Alb, 25(OH)D were compared between the two groups. Logistic regression was used to analyze the prognostic factors of CAPD patients. The predictive value of TyG, CRP/Alb and 25(OH)D on the prognosis of CAPD patients was analyzed by receiver operating characteristic (ROC) curve. Results:After 3 months and 6 months of dialysis, the peritoneal Kt/V urea in the death group [(1.21±0.18)ml/(s·1.73 m 2), (1.02±0.14)ml/(s·1.73 m 2)] was significantly lower than that in the survival group [(1.57±0.40)ml/(s·1.73 m 2), (1.49±0.42)ml/(s·1.73 m 2)] (all P<0.05). After 3 months and 6 months of dialysis, the TyG [(8.79±0.86), (9.24±1.03)] and CRP/Alb [(4.98±0.94)×10 -4, (5.14±1.39)×10 -4] in the death group were higher than those in the survival group [(8.03±0.60), (7.26±0.93), (3.57±1.19)×10 -4, (3.07±0.88)×10 -4], while the 25(OH)D [(19.14±2.29)ng/ml, (17.79±3.17)ng/ml] was lower than that of survival group [(22.67±3.03)ng/ml, (24.31±2.51)ng/ml] (all P<0.05). TyG and CRP/Alb at 3 months and 6 months of dialysis were negatively correlated with Kt/V urea, while the 25(OH)D was positively correlated with Kt/V urea (all P<0.05). Logistic regression analysis showed that Kt/Vurea, TyG, CRP/Alb and 25(OH)D were associated with prognosis in the two groups after 3 and 6 months of dialysis (all P<0.05). The AUC of TyG, CRP/Alb and 25(OH)D at 6 months of dialysis combined to predict the prognosis of CAPD patients was the highest, which was 0.911. Conclusions:TyG, CRP/Alb and 25(OH)D are associated with all-cause mortality in CAPD patients. High TyG and CRP/Alb and low 25(OH)D suggest a higher risk of all-cause mortality. Combined detection of all indicators can effectively predict the prognosis of CAPD, which is convenient for early clinical intervention.