Aim To investigate the regulatory effects of coenzyme Q10(CoQ10)on blood lipid level and intesti-nal flora abundance in atherosclerotic(As)rats.Methods 24 rats were randomly divided into control group,As group and CoQ10 intervention group.Rats in the As group and CoQ10 intervention group were fed with high-fat chow for 2 weeks,combined with abdominal aortic balloon injury to replicate the As model.CoQ10 was administered by gavage start-ing on the next day of modeling,once daily for 4 weeks.Aortic Movat's staining and lipid levels were used to verify the effect of CoQ10 intervention in As,and the abundance of intestinal flora in intestinal contents was analyzed using met-agenomics.Results Compared with the control group,rat aortic tissues in the As group showed endothelial damage,structural disorganization of the internal elastic plate and inflammatory infiltration,serum triglyceride(TG),total cholester-ol(TC)and low density lipoprotein cholesterol(LDLC)levels were increased,and high density lipoprotein cholesterol(HDLC)levels were decreased.Compared with the As group,the structure of the endothelial cells of the aorta and the structure of the endothelial cells,the internal elastic plates and the smooth muscle cell morphology were relatively regular,serum TC,TG and LDLC levels were decreased,and HDLC levels were increased in the CoQ10 intervention group.Com-pared with the control group,the intestinal bacterial biodiversity in the As group was reduced.At the phylum level,the abundance of the Firmicutes and the Bacteroidetes were down-regulated,whereas that of Proteobacteria was up-regulated.At the genus level,the relative abundance of Lactobacillus,Bacteroides,Akkermansia,Limosilactobacillus,Parabacteroides and Ligilactobacillus was down-regulated,and the relative abundance of Muribaculum was up-regulated.Compared with the As group,CoQ10 intervention restored the biodiversity of the intestinal microbiota in As rats and increased the relative abundance of Firmicutes,Bacteroidetes,Lactobacillus,Bacteroides,Akkermansia,Limosilactobacillus,Parabacteroides and Ligilactobacillus,while reducing the relative abundance of Proteobacteria and Muribaculum(all P＜0.05).Conclusion CoQ10 can regulate blood lipid levels in As rats,upregulate the abundance of beneficial microbiota,downregulate the abun-dance of harmful microbiota,and modulate the diversity of the gut microbiota.

Objective To explore the effect of compound centella asiatica on diabetic kidney disease(DKD)by regulating intestinal microflora metabolism.Methods Sixty DKD patients who visited Hangzhou Ninth People's Hospital from January to December 2022 were randomly divided into experimental group and control group,with 30 patients in each group.Patients in control group received basic treatment guided by lifestyle and diet,while patients in experimental group received treatment with compound centella asiatica on the basis of control group.Both groups of patients were followed up for 6 months to measure gut microbiota metabolite levels,urinary protein,and other indicators.Results After treatment,the levels of short-chain fatty acid(SCFA)in experimental group increased,while the levels of trimethylamine oxide(TMAO),indophenol sulfate(IS),microalbuminuria/creatinine(ACR),and 24-hour urinary protein quantification(24hPro)decreased;24hPro and ACR of experimental group patients were lower than those of control group.ACR in DKD patients is positively correlated with TMAO and negatively correlated with SCFA(P＜0.05).Conclusion ACR in DKD patients is positively correlated with TMAO and negatively correlated with SCFA;Compound centella asiatica can increase the levels of SCFA in DKD patients,reduce the levels of TMAO,IS,and ACR,indicating that compound centella asiatica can regulate the metabolic levels of gut microbiota in DKD patients and reduce proteinuria.

Aim To investigate the regulatory effects of coenzyme Q10(CoQ10)on blood lipid level and intesti-nal flora abundance in atherosclerotic(As)rats.Methods 24 rats were randomly divided into control group,As group and CoQ10 intervention group.Rats in the As group and CoQ10 intervention group were fed with high-fat chow for 2 weeks,combined with abdominal aortic balloon injury to replicate the As model.CoQ10 was administered by gavage start-ing on the next day of modeling,once daily for 4 weeks.Aortic Movat's staining and lipid levels were used to verify the effect of CoQ10 intervention in As,and the abundance of intestinal flora in intestinal contents was analyzed using met-agenomics.Results Compared with the control group,rat aortic tissues in the As group showed endothelial damage,structural disorganization of the internal elastic plate and inflammatory infiltration,serum triglyceride(TG),total cholester-ol(TC)and low density lipoprotein cholesterol(LDLC)levels were increased,and high density lipoprotein cholesterol(HDLC)levels were decreased.Compared with the As group,the structure of the endothelial cells of the aorta and the structure of the endothelial cells,the internal elastic plates and the smooth muscle cell morphology were relatively regular,serum TC,TG and LDLC levels were decreased,and HDLC levels were increased in the CoQ10 intervention group.Com-pared with the control group,the intestinal bacterial biodiversity in the As group was reduced.At the phylum level,the abundance of the Firmicutes and the Bacteroidetes were down-regulated,whereas that of Proteobacteria was up-regulated.At the genus level,the relative abundance of Lactobacillus,Bacteroides,Akkermansia,Limosilactobacillus,Parabacteroides and Ligilactobacillus was down-regulated,and the relative abundance of Muribaculum was up-regulated.Compared with the As group,CoQ10 intervention restored the biodiversity of the intestinal microbiota in As rats and increased the relative abundance of Firmicutes,Bacteroidetes,Lactobacillus,Bacteroides,Akkermansia,Limosilactobacillus,Parabacteroides and Ligilactobacillus,while reducing the relative abundance of Proteobacteria and Muribaculum(all P＜0.05).Conclusion CoQ10 can regulate blood lipid levels in As rats,upregulate the abundance of beneficial microbiota,downregulate the abun-dance of harmful microbiota,and modulate the diversity of the gut microbiota.

Objective To explore the effect of compound centella asiatica on diabetic kidney disease(DKD)by regulating intestinal microflora metabolism.Methods Sixty DKD patients who visited Hangzhou Ninth People's Hospital from January to December 2022 were randomly divided into experimental group and control group,with 30 patients in each group.Patients in control group received basic treatment guided by lifestyle and diet,while patients in experimental group received treatment with compound centella asiatica on the basis of control group.Both groups of patients were followed up for 6 months to measure gut microbiota metabolite levels,urinary protein,and other indicators.Results After treatment,the levels of short-chain fatty acid(SCFA)in experimental group increased,while the levels of trimethylamine oxide(TMAO),indophenol sulfate(IS),microalbuminuria/creatinine(ACR),and 24-hour urinary protein quantification(24hPro)decreased;24hPro and ACR of experimental group patients were lower than those of control group.ACR in DKD patients is positively correlated with TMAO and negatively correlated with SCFA(P＜0.05).Conclusion ACR in DKD patients is positively correlated with TMAO and negatively correlated with SCFA;Compound centella asiatica can increase the levels of SCFA in DKD patients,reduce the levels of TMAO,IS,and ACR,indicating that compound centella asiatica can regulate the metabolic levels of gut microbiota in DKD patients and reduce proteinuria.

Objective:To observe the clinical efficacy of Xiaosheng Powder ultrasonic nebulization combined with meibomian gland massage in treating liver depression and Yin deficiency pattern of meibomian gland dysfunction dry eye.Methods:Randomized controlled trial. From March 2021 to September 2021, a total of 50 patients (100 eyes) diagnosed with meibomian gland dysfunction dry eye of the liver depression and Yin deficiency pattern at the Ophthalmology Hospital of China Academy of Chinese Medical Sciences were selected. They were randomly divided into two groups using a random number table, with 25 patients (50 eyes) in each group. The control group received 0.1% sodium hyaluronate eye drops combined with meibomian gland massage, while the treatment group received Xiaosheng Powder nebulization combined with meibomian gland massage. Both groups were treated for 4 weeks. Before and after treatment, the tear film break-up time (BUT), Schirmer I test (SIT), corneal fluorescein staining (FL) scores, TCM symptom scores, and meibomian gland function scores were observed and evaluated. Adverse reactions were recorded.Results:After treatment, the treatment group exhibited statistically significant improvements compared to the control group in the following aspects: BUT was significantly longer in the treatment group (t=8.76, P<0.01); SIT values were significantly higher in the treatment group ( t=6.18, P<0.01); FL scores, TCM symptom scores and meibomian gland function scores were significantly lower than in the treatment group ( t values were 2.19, 5.36 and 12.09, P<0.01). The total effective rate in the treatment group was 96.0% (24/25), while in the control group, it was 68.0% (17/25), and the difference between the two groups was statistically significant ( χ2=4.88, P=0.027). Conclusion:The combination of Xiaosheng Powder ultrasonic nebulization and meibomian gland massage is effective in improving the clinical symptoms of patients with meibomian gland dysfunction dry eye of the liver depression and Yin deficiency pattern. Furthermore, this approach is considered safe and efficient.

Objective:To screen the host interaction proteins of the severe fever with thrombocytopenia syndrome virus(SFTSV)nonstructural protein(NSs)by immunoprecipitation combined with mass spectrometry analysis,to discuss the functions,subcellular localization,and biological pathways of these interaction proteins,and to provide the basis for clarifying the replication and pathogenic mechanism of SFTSV.Methods:The eukaryotic expression vectors pSFTSV-NSs-Flag(experimental group)and Flag-CMV-3(negative group)were transfected into the human embryonic kidney 293T cells,and contorl group(no treatment)was set up.The lysates of the cells in various groups were collected,and the expression and localization of SFTSV NSs in the host cells were verified by indirect immunofluorescence and Western blotting methods.The protein lysates were treated with protein A/G and immunoprecipitation was used to enrich host proteins binding to NSs.The captured interaction proteins were initially analyzed by silver staining and Coomassie brilliant blue staining to observe the differential protein bands in various groups;liquid chromatography-tandem mass spectrometry was used to obtain the information of protein sequences;the reliable proteins were retained and searched by UniProt database;Gene Ontology(GO)functional enrichment analysis,IPR,eukaryotic orthologous groups(KOGs)functional annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis,subcellular localization,and transcription factor(TF)functional annotation were used to determine the subcellular structure,gene functions,and biological processes of the interaction proteins.Results:The immunofluorescence results showed that the SFTSV NSs expressed a single specific band at relative molecular mass 33 000 and was localized in the cytoplasm in a granular inclusion body-like manner.The silver staining and Coomassie brilliant blue staining results showed there were significant differential protein bands between experimental group and negative group.The mass spectrometry results identified 46 potential interaction proteins.The GO functional enrichment analysis,KOGs functional annotation,and KEGG signaling pathway enrichment analysis results showed that the biological pathways related to viral translation,cellular metabolism,and protein transport were enriched with a considerable number of proteins.Eight annotated proteins had intermediate filament domains.The highest percentage of subcellular localization was cytoplasmic proteins,consistent with the NSs localization site.The TF functional annotation analysis results showed one protein from the NF-Y family.Conclusion:The interaction proteins play roles in assisting the proper protein folding,participating in the cribosome translation,and forming the cytoskeleton,which may be involved in antiviral replication.These proteins can be used as candidate proteins for further study on the replication mechanism of SFTSV.

Third space fluid(TSF) is a common complication of advanced malignancies, including malignant pleural effusion, malignant ascites, intracranial effusion, and pelvic effusion, etc. The pharmacokinetics(PK) of anti-tumor drugs in vivo are influenced by various factors, and TSF is one of the potential factors that contributes to PK variations, which may consequently affect the efficacy and safety of anti-tumor drugs. This paper aimed to comprehensively investigate PK studies related to anti-tumor drugs in patients with malignant tumors accompanied by TSF. The paper summarized the PK characteristics of common cytotoxic drugs, small molecule targeted drugs, and monoclonal antibodies in both blood and TSF.

Objective:To investigate the roles of N6-methyladenosine (m 6A) modification in regulating RP11-426A6.5 in the development of laryngeal squamous cell carcinoma (LSCC). Methods:The methylation and expression levels of lncRNAs were identified and important lncRNAs were screened utilizing long non-coding RNA (lncRNA) m 6A methylation microarray. Cancer and para cancer tissue samples were taken from 48 LSCC patients hospitalized to the Department of Otolaryngology-Head and Neck Surgery of the Second Affiliated Hospital of Harbin Medical University between January and September 2017. Expression profiling microarray was performed in 3 of 48 LSCC samples, and methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR) and quantitative real-time fluorescent PCR (qRT-PCR) were performed in the remaining 45 LSCC samples to verify the m 6A modification and expression levels of RP11-426A6.5. Correlations between RP11-426A6.5 and clinical factors were anlysed. Laryngeal cancer cell line with low expression of RP11-426A6.5 was created in vitro using RNA interference (RNAi) technology. The 5-Ethynyl-2′-deoxyuridine (EdU) cell proliferation experiment, wound healing experiment, and transwell invasion experiment were used respectively to measure the proliferation, migration, and invasion of LSCC cells. The effect of RP11-426A6.5 down-regulation on the growth of transplanted tumors in vivo was verified by nude mice tumorigenesis assay. The Cancer Genome Atlas (TCGA) database and sequence-based RNA adenosine methylation site predictor (SRAMP) website were used to predict the enzymes and corresponding methylation sites. MazF digestion was chosen to validate the binding sites. RNAi technology was used to observe the changes in cell function after interfering with the expression of the corresponding genes of the modified enzymes. MeRIP-qPCR was used to detect the level of RP11-426A6.5 m 6A cell line treated with actinomycin D was used to observe the stability of RP11-426A6.5. Results:RP11-426A6.5 methylation and expression levels were significantly higher in LSCC tissues than those in paracancerous tissues (methylation levels: 23.828±4.975 vs 20.280±3.607; expression levels: 1.197±0.314 vs 1.015±0.170, all P values<0.05). RP11-426A6.5 expression levels were closely correlated with T stage (T1-2: 1.081±0.298 vs T3-4: 1.306±0.292, χ 2=5.35, P<0.05). The postoperative survival of patients with high RP11-426A6.5 expressions was significantly lower than that of patients with low RP11-426A6.5 expression ( P=0.046). Assays in vitro and in vivo showed that the downregulation of RP11-426A6.5 significantly decreased the proliferation, migration, and invasion abilities of LSCC cells and the growth of transplanted tumors. The binding of methyltransferase-like 3 (METTL3), an m 6A-modified enzyme, to the corresponding methylation site of RP11-426A6.5 enhanced its stability and mediated its regulation of malignant behaviors of LSCC cells. Conclusions:RP11-426A6.5 can regulate the malignant behaviors of LSCC cells, which is mediated by the m 6A modification process involving in the methyltransferase METTL3.

Objective:To study the clinical characteristics and compliance of early-onset gout patients by case-control analysis.Methods:A total of 111 early-onset patients (onset age ≤35 years old) were included as Group A, and 111 non-early-onset patients (onset age >35 years old) with matched disease durationwere included as Group B. The differences ofclinical characteristics, causes of acute gout attack, dairy diet habits, compliance, and misunderstanding of the disease were compared.Results:Compared with the non-early-onsetgoutpatients, the early-onset patients had a higher proportion of obesity (63 cases vs 28 cases), family history (36 cases vs 20 cases) and tophus (39 cases vs 23 cases) and higher level of VAS scores (8.5±1.3 vs 7.6±1.7; χ2=22.988, P<0.01; χ2=5.749, P=0.016; χ2=5.729, P=0.017; t=4.639, P<0.01), lowerproportionof the first metatarsophalangeal joint involvement as the initial joint involvement (45.9%, 51 cases vs 59.4%, 66 cases; χ2=4.066, P=0.044), higher proportion of the ankle involvement as the initial joint involvement (34.2%, 38 cases vs 21.6%, 24 cases; χ2=4.386, P=0.036), higher proportion of alcohol drinkers and high fructose drinkers, which was more likely to relate to alcohol intake, strenuous exercise and high fructose intakeas trigger of the flare ( χ2=6.513, P=0.011; χ2=7.126, P=0.008; χ2=1.978, P=0.160), while the proportion of regular exercisers and on diet in the family was lower ( χ2=22.887, P<0.01; t=-4.917, P<0.01). The proportion of poor diet and medication compliance in Group A was higher than that in Group B(57.7%, 64 cases vs 38.7%, 43 cases; χ2=5.207, P=0.022; χ2=5.867, P=0.015). As for the reason for poor treatment compliance, early-onset gout patients were more worry about the side-effects of drugs than non-early onset patients ( χ2=4.190, P=0.041). There was no significant difference between the two groups in the main misunderstanding of gout. Conclusion:Although early onset gout patients are young, their condition is more serious, and compliance is poorer, this group of patients should be highly valued in clinical diagnosis and treatment.

Objective: To assess the health risk associated with drinking water in Hangzhou from 2016 to 2017,and to provide evidence for the safety of drinking water . Methods: The monitoring data of 5 genetic toxic substances（arsenic,hexavalent chromium,cadmium,chloroform,tetrachloromethane）and 13 body toxic substances（lead,mercury,selenium,cyanide,fluoride,nitrate,iron,ammonia nitrogen,manganese,copper,zinc,aluminum,volatile phenol）from 36 source water samples,36 finished water samples and 288 tap water samples in the main urban areas of Hangzhou were collected from 2016 to 2017. The health risk of drinking water containing the chemical pollutants mentioned above were assessed based on the evaluation models recommended by United States Environmental Protection Agency . Results: The concentrations of 5 genetic toxic substances and 13 body toxic substances in source water,finished water and tap water were all within the reference limits issued by Standards for Drinking Water Quality（GB 5749—2006）. The carcinogenic risk,non-carcinogenic risk and total health risk caused by the chemical pollutants in the source water were 2.18×10-5/a,7.75×10-9/a and 2.18×10-5/a. The carcinogenic risk,non-carcinogenic risk and the total health risk caused by the chemical pollutants in the finished water were 1.08×10-5/a,3.70×10-9/a and 1.08×10-5/a. The carcinogenic risk,non-carcinogenic risk and total health risk caused by the chemical pollutants in the tap water were 1.96×10-5/a,3.61×10-9/a and 1.96×10-5/a. The carcinogenic risk and total health risk caused by chemical pollutants ranged from high to low in the source water,tap water and finished water. The non-carcinogenic risks ranged from high to low in the source water,finished water and tap water . Conclusion The health risks of 18 chemical pollutants in drinking water in Hangzhou were at a low level,with the greater carcinogenic risk than the non-carcinogenic risk. Hexavalent chromium had the highest carcinogenic risk,while fluoride and aluminum had the highest non-carcinogenic risk.