Objective:To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method.Methods:Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. Results:A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. ① MR analysis showed that TMAO may increase the risk of AP [odds ratio ( OR) = 1.100, 95% confidence interval (95% CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95% CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. ② There was a positive causal relationship between plasma TMAO level and circulating monocyte count ( OR = 1.017, 95% CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. Conclusion:TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

YABBY proteins are important transcription factors that regulate morphogenesis and organ development in plants. In order to study the YABBY of strawberry, bioinformatic technique were used to identify the YABBY gene families in Fragaria vesca (diploid) and Fragaria×ananassa (octoploid), and then analyze the sequence characters, phylogeny and collinearity of the family members. The RNA-seq data and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique were used to assay the expression patterns of the family members. A green fluorescent protein (GFP) was fused with FvYABBYs and transiently expressed in tobacco leaf cells for the subcellular localization. As the results, six FvYABBY genes and 26 FxaYABBY genes were identified from F. vesca and F.×ananassa, respectively. The FvYABBY genes were grouped into five clades, and five family members were orthologous with AtYABBY genes of Arabidopsis. In F. vesca, all of the FvYABBYs were basically not expressed not expressed in root and receptacle, while FvYABBY1, FvYABBY2, FvYABBY5 and FvYABBY6 were highly expressed in leaf, shoot, flower and achene. In F.×ananassa, FxaYABBY1, FxaYABBY2, FxaYABBY5 and FxaYABBY6 were expressed in achene, and all FxaYABBY were poorly or not expressed in receptacle. Additionally, under the abiotic stresses of low temperature, high salt and drought, the expression of FvYABBY1, FvYABBY3, FvYABBY4 and FvYABBY6 were down-regulated, FvYABBY5 was up-regulated, and FvYABBY2 was up-regulated and then down-regulated. In tobacco leaf cells, the subcellular localization of FvYABBY proteins were in the nucleus. These results provides a foundation for the functional researches of YABBY gene in strawberry.
Fragaria/genetics* ; Arabidopsis ; Biological Assay ; Cold Temperature ; Computational Biology

OBJECTIVE To evaluate the post-marketing safety of Compound porcine cerebroside and ganglioside injection in patients with ischemic stroke. METHODS A drug-induced， prospective， non-controlled clinical study design was conducted. Using the patients with ischemic stroke who received Compound porcine cerebroside and ganglioside injection at least once in 46 secondary class A and above medical institutions across the country from April 2020 to May 2021 as the monitoring objects， and their basic data， medication information and the occurrence of adverse drug reactions were analyzed. RESULTS Among 13 514 patients with ischemic stroke， the incidence of adverse events was 10.01%， and the incidence of adverse reactions related to Compound porcine cerebroside and ganglioside injection was 0.33%. Drug-related adverse drug reactions were mild or moderate， concentrated in the gastrointestinal system （18 cases）， skin and subcutaneous tissue （10 cases）， nervous system （7 cases） and other systems/organs， mainly including constipation， abdominal pain， diarrhea， rash， pruritus， dizziness and other symptoms. Most of the patients （91.03%） recovered or improved after treatment， and 2 patients died. Among the 45 patients with adverse drug reactions， 84.44% were cured or improved after drug withdrawal or symptomatic treatment， and 15.56% had no significant change. The incidence of adverse drug reactions in tertiary hospitals was significantly higher than that in secondary hospitals， and the incidence of adverse drug reactions in patients with allergic history was significantly higher than that in patients without allergic history （P＜0.05）. Irrational drug use was found in 2.76% of patients， and the incidence of adverse drug reactions（2.95%） was significantly higher than that in patients without irrational drug use（0.26%，P＜0.05）. CONCLUSIONS The adverse drug reaction symptoms of ischemic stroke patients treated with Compound porcine cerebroside and ganglioside injection are relatively common， the incidence rate is generally low， and it is related to the patients’ physique and whether the drug use is standardized.

GLKs (GOLDEN 2-LIKEs) are a group of plant-specific transcription factors regulating the chloroplast biogenesis, differentiation and function maintains by triggering the expression of the photosynthesis-associated nuclear genes (PhANGs). The GLKs also play important roles in nutrient's accumulation in fruits, leaf senescence, immunity and abiotic stress response. The expression of GLK genes were affected by multiple hormones or environmental factors. Therefore, GLKs were considered as the key nodes of regulatory network in plant cells, and potential candidates to improve the photosynthetic capacity of crops. Since numerous researches of GLKs have been reported in plants, the biological function, molecular mechanism of GLKs genes and its applications in breeding were summarized and a GLK-mediated signaling network model was developed. This review may facilitate future research and application of GLKs.
Chloroplasts/genetics* ; Gene Expression Regulation, Plant ; Photosynthesis/genetics* ; Plant Breeding ; Transcription Factors/metabolism*

The gut microbiota plays an important role in regulating the pharmacokinetics and pharmacodynamics of many drugs. FLZ, a novel squamosamide derivative, has been shown to have neuroprotective effects on experimental Parkinson's disease (PD) models. FLZ is under phase Ⅰ clinical trial now, while the underlying mechanisms contributing to the absorption of FLZ are still not fully elucidated. Due to the main metabolite of FLZ was abundant in feces but rare in urine and bile of mice, we focused on the gut microbiota to address how FLZ was metabolized and absorbed.

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. , , , , and other conditional pathogens increased significantly in the model group, while and , the short-chain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, , urease, could assist the treatment and prevention of this disease.

Objective:To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma.Methods:Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ 2) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results:A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy ( P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion:TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.

Objective:The present study was aimed to evaluate the nutritional risk using nutritional risk screening 2002 (NRS2002) score and to investigate the impact of nutrition support on clinical outcome in hospitalized patients.Methods:Six hundred and ninety four hospitalized patients were recruited.NRS 2002 was applied to evaluate the nutritional risk of patients.Meanwhile,the effect of nutrition support on complication rate was evaluated between different types of patients.Results:14.0％ of patients had malnutrition and the incidence of nutritional risk was 27.5％.Patients with nutritional risk had a higher complication rate (P ＜0.01).Totally,22.0％ (153/694) patients received nutrition support,including 81.7％ patients with nutritional risk and 18.3％ patients without nutritional risk.Patients with nutritional risk benefited from nutrition support,as shown by lower complication rate and shorter length of hospital stay.In patients with nutritional risk,complication rate was lower in enteral fed patients compared to parenteral fed patients.Conclusion:With nutritional risk screening,patients' nutritional status can be evaluated and appropriate nutrition support can be performed.Compared to those without nutritional risk,patients with nutritional risk will benefit more from nutrition support,as indicated by lower complication rate and reduced length of hospital stay.

Non-coding RNAs ( ncRNA ), including ribosomal RNA( rRNA), transfer RNA( tRNA), MicroRNA ( miRNA), long noncoding RNA(lncRNA) and small nucleolar RNA(snoR-NA), are a class of RNA that have multiple functions and are not translated to proteins. MicroRNA and lncRNA are involved in the injury, remodeling and aging of blood vessels, and it is necessary to understand the regulatory roles of MicroRNA and lncRNA in these processes. It is reported that MicroRNA and lncRNA are not only participated in the regulation of oxidative response, inflammation, cell proliferation and migration, and phenotype transition, they are also involved in the regulation of gene expression by conducting different mechanisms, including transcriptional regulation, post-transcriptional modification and chromatin remodeling. These aspects of regulation by MicroRNA and lncRNA are related to cardiovascular diseases, such as ath-erosclerosis, hypertension, myocardial infarction, stroke, pul-monary hypertension and diabetes, and thus provide a new way for genetic diagnosis and therapy of cardiovascular diseases.

OBJECTIVE:To investigate the characteristics and regularity of lornoxicam related ADR,and to provide reference for rational and safe use of lornoxicam. METHODS:From Jan. 1,2006 to Dec. 31,2013,lornoxicam related ADR reports collect-ed by National ADR Monitoring System in Beijing were analyzed retrospectively about their characteristics and related factors. RE-SULTS:In the statistical period,there were 48 ADR reports related to lornoxicam. The people over 40 years age accounted for 62.5%. 38 patients used lornoxicam by intravenous infusion or intramuscular injection ,accounting for 79.17%. The clinical mani-festations were diverse and complex,in which skin(32.96%)and gastrointestinal damage(25.00%)were more common ADR oc-curred within 30 min,accounting for 35.42%,and it would be better after stopping drug or 1-3 days symptomatic treatment. CON-CLUSIONS:The rational use of lornoxicam can reduce the occurrence of ADR. Suggestion on the use of the drug,is that the pa-tient should be monitored for security,in order to reduce the risk of ADR.