Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The study investigated the intrinsic changes in material basis of Angelicae Sinensis Radix during wine processing by headspace-gas chromatography-ion mobility spectrometry(HS-GC-IMS), headspace-solid phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS), and ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS) combined with chemometrics. HS-GC-IMS fingerprints of Angelicae Sinensis Radix before and after wine processing were established to analyze the variation trends of volatile components and characterize volatile small-molecule substances before and after processing. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed for differentiation and difference analysis. A total of 89 volatile components in Angelicae Sinensis Radix were identified by HS-GC-IMS, including 14 unsaturated hydrocarbons, 16 aldehydes, 13 ketones, 9 alcohols, 16 esters, 6 organic acids, and 15 other compounds. HS-SPME-GC-MS detected 118 volatile components, comprising 42 unsaturated hydrocarbons, 11 aromatic compounds, 30 alcohols, 8 alkanes, 6 organic acids, 4 ketones, 7 aldehydes, 5 esters, and 5 other volatile compounds. UPLC-Q-Orbitrap-MS identified 76 non-volatile compounds. PCA revealed distinct clusters of raw and wine-processed Angelicae Sinensis Radix samples across the three detection methods. Both PCA and OPLS-DA effectively discriminated between the two groups, and 145 compounds(VIP>1) were identified as critical markers for evaluating processing quality, including 4-methyl-3-penten-2-one, ethyl 2-methylpentanoate, and 2,4-dimethyl-1,3-dioxolane detected by HS-GC-IMS, angelic acid, β-pinene, and germacrene B detected by HS-SPME-GC-MS, and L-tryptophan, licoricone, and angenomalin detected by UPLC-Q-Orbitrap-MS. In conclusion, the integration of the three detection methods with chemometrics elucidates the differences in the chemical material basis between raw and wine-processed Angelicae Sinensis Radix, providing a scientific foundation for understanding the processing mechanisms and clinical applications of wine-processed Angelicae Sinensis Radix.
Wine/analysis* ; Gas Chromatography-Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Angelica sinensis/chemistry* ; Solid Phase Microextraction/methods* ; Drugs, Chinese Herbal/isolation & purification* ; Chemometrics ; Volatile Organic Compounds/chemistry* ; Principal Component Analysis ; Ion Mobility Spectrometry/methods*

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Objective To explore the construction and visualization for knowledge graph of Ling Shu(Spiritual Pivot),with a view to providing ideas for the structured storage and display of the theoretical knowledge of the ancient Chinese medical books.Methods Using the professional idea of constructing knowledge graphs for reference,text mining technology was applied to construct the thesaurus,and then word division,entity recognition,and relationship extraction for the original text of Ling Shu were performed to get the elements of knowledge graph construction.The graph database Neo4j was used for the storage and query of the knowledge graph,and then the visual display of the knowledge graph was achieved.Results The 1 216 high-quality words consisting of the thesaurus of Ling Shu were obtained,and the construction of the knowledge graph of the theory of Ling Shu was realized.The constructed knowledge graph basically displayed the traditional Chinese medicine theories such as the correlation of visceral manifestations with essence qi,and the relationship between emotions and the five-zang organs described in Ling Shu,which made the retrieval and utilization of the related entities and relationships possible,and provided ideas for the structured storage and display of the theoretical knowledge of the ancient books of Chinese medicine.Conclusion The knowledge graph construction technology can be used to obtain the Chinese medicine theoretical knowledge graph of Ling Shu,and to display the knowledge connections of yin-yang and the five elements,and the internal organs and meridians expressed in the Ling Shu.The construction of the knowledge graph and its storage in the graph database enable the knowledge graph involved in the text of Ling Shu to be displayed in the form of visualized semantic network graph,and also make the embedding of other search systems such as the semantic search and semantic wiki possible,which will be helpful for the development of Chinese medicine intelligent medical services.

Objective To evaluate the safety and efficacy of splenectomy with distal pancreatectomy during cytoreductive surgery in epithelial ovarian cancer(EOC).Methods A total of 17 patients from Zhongshan Hospital,Fudan University and the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)received splenectomy with distal pancreatectomy during cytoreductive surgery in EOC were recruited.Their clinicopathological characteristics,postoperative complications and survival situation were retrospective analyzed.Results Of the 17 patients,there were 13 primary cases and 4 recurrent cases.Eleven cases(64.7%)had preoperative imaging finding with metastatic lesions in the splenic hilum,among whom 6 cases had distal pancreas metastasis during the operation.The drainage was placed in the splenic fossa for the measurement of amylase levels in drain fluid and was removed after 8(3-12)days.There were 4 patients had postoperative pancreatic fistula(POPF)of grade A,3 patients had POPF of grade B and no POPF of grade C occurred.The 2 patients with POPF of grade B improved after percutaneous drainage,and the rest recovered with somatostatin,antibiotic drugs and medicines without perioperative mortality.The interval between surgery to chemotherapy was 17.5(13-37)days.The median follow-up time was 14(4-64)months and the median progression-free survival was 10(5-32)months.Conclusion Splenectomy with distal pancreatectomy as part of cytoreduction surgery in EOC is needed for optimal resection,and the complication of pancreatic fistula could be managed conservatively.

Objective To screen the key characteristic genes of metastatic nasopharyngeal carcinoma(mNPC)and analyze the immune cell infiltration in tumor microenvironment using machine learning algorithm.Methods Firstly,the training set GSE103611 was downloaded from the GEO database,and the data were subjected to differential expression gene(DEGs)screening,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genome(KEGG)and immune cell infiltration analysis.Second,the predicted genes in DEGs were screened by least absolute shrinkage and selector operation(LASSO)regression,and the characteristic genes were screened by using the expression level of the predicted genes and receiver operating characteristic(ROC).Third,the correlation between characteristic genes and immune cells was further analyzed to determine the key characteristic genes.Finally,the expression levels of key characteristic genes and ROC were verified using the reverse validation set GSE1245 data.Results A total of 136 DEGs were obtained,and their KEGG were mainly enriched in cytochrome P450,tumor necrosis factor(TNF)signaling pathway,prion disease,EB virus infection,and other pathways.GO was mainly enriched in the negative regulatory processes of peptide-based tyrosine phosphorylation modification,viral gene expression,and B cell and leukocyte activation.The difference in the degree of infiltration of the 22 immune cells in nasopharyngeal carcinoma(NPC)and mNPC was not significant.Two key characteristic genes(DAZ1 and SCCPDH)of mNPC were finally obtained by LASSO regression,and they were significantly correlated with immune cells in the mNPC microenvironment(P＜0.05).In the reverse validation data set,the differential expressions of DAZ1 and SCCPDH between non-NPC(nNPC)and NPC groups were not significant(P＞0.05),and the AUC values of ROC of both were less than 0.6.Conclusion DAZ1 and SCCPDH are the key characteristic genes of mNPC and can be used as important markers for mNPC and immunotherapy.

Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR-insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.