This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

Objective To investigate the effects of human milk on serum bilirubin levels and gut microbiota in neonatal rats with hyperbilirubinemia.Methods A total of 24 7-day-old specific-pathogen-free Sprague-Dawley rats were injected with bilirubin or normal saline,respectively,and human milk or formula milk was administered 24 hours later for intervention.The rats were divided randomly into four groups:human milk-normal saline group(HN),human milk-bilirubin group(HB),formula milk-normal saline group(FN),and formula milk-bilirubin group(FB).Samples were taken 72 hours later,and serum bilirubin values were detected by enzyme-linked immunosorbent assay.The intestinal microbiota were analyzed using 16S rDNA high-throughput sequencing.Results There was no significant difference in bilirubin values among the groups.Pseudomonas was negatively correlated with indirect bilirubin value(P＜0.05).The composition of the intestinal microbiota differed significantly between human milk and formula milk after gastric administration,with Firmicutes(P＜0.01),Enterococci(P＜0.05),being the main microbiota in the HN and HB groups,and Proteobacteria(P＜0.001),Escherichia Shigella(P＜0.01)and Acinetobacter(P＜0.01)being the main in the FN and FB groups.Conclusions Pseudomonas may be negatively associated with bilirubin,and the structure of the intestinal microbiota may differ in relation to human milk and formula feeding.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective:To learn about the genotyping of human Brucella isolated from Sichuan Province. Methods:BCSP31-PCR and AMOS-PCR were used to identify the genus and biotype of the 66 strains isolated from confirmed human brucellosis cases in Sichuan Province from 2014 to 2020, respectively. The isolated strains were genotyped by multi-locus sequence typing (MLST)-9. The sequence type (ST) was compared trough the online MLST database. A minimum spanning tree (MST) was constructed to cluster the newly discovered and known ST using the BioNumerics software version 7.6.Results:The 66 strains isolated from human cases of brucellosis in Sichuan Province from 2014 to 2020 were Brucella, and 65 of them were Brucella melitensis while one strain was Brucella abortus. The MLST method identified three known STs (ST-8, ST-39 and ST-2) and one newly type (ST-101). Among them, ST-8 was the main ST in Sichuan Province (90.91%, 60/66), another 4 strains of Brucella melitensis were ST-39, and 1 strain of Brucella abortus was ST-2. The newly type ST-101 was isolated from Leshan City in 2019, belonging to the Brucella melitensis and closely related to the evolution of ST-8. Conclusion:Brucella melitensis is the main epidemic Brucella strain in Sichuan Province, ST-8 is predominant genotype, with a small amount of ST-39, ST-101 and ST-2.

Objective:To study the protective effect of alendronate combined with Lactobacillus rhamnosus on bone loss in ovariectomized mice.Methods:Fifty female C57BL/6 mice were divided into 5 equal groups ( n=10). Ovariotomy was performed in groups A, B, C and D while a sham operation was performed in group E. Group A was subjected to combined administration of alendronate and Lactobacillus rhamnosus, group B to administration of alendronate, group C to administration of Lactobacillus rhamnosus, and groups D and E to administration of physiological saline only. At 3 months after operation, all the mice were sacrificed to harvest their femurs. Micro CT scanning was performed to detect the bone mineral density (BMD), trabecular relative volume, bone surface area/bone volume, and trabecular thickness and number of trabecular bone. Three-point bending test was used to detect the maximum load, stiffness, ultimate load, Young＇s modulus, and fracture energy. Osteocalcin and alkaline phosphatase levels were measured using blood samples from the mice eyeballs. The 2 groups were compared in terms of all the above indexes. Results:The BMD [(669.87±67.87) mg/cm 3], maximum load [(14.35±0.75) N] and fracture energy [(1,497.43±38.29) J/m 2] in group A were significantly higher than those in group B [(520.07±9.01) mg/cm 3, (11.94±0.82) N and(1,277.61±35.12) J/m 2] and group C [(388.15±25.61) mg/cm 3, (11.10±0.93) N and (1,115.27±63.24) J/m 2] (all P<0.05). The osteocalcin level in group A [(22.25±1.78) ng/mL] was significantly higher than that in group B [(19.08±1.45) ng/mL] and group D [(19.33±1.66) ng/mL] (both P<0.05). The alkaline phosphatase level in group A [(83.21±9.69) ng/mL] was significantly lower than that in group C [(113.16±14.44) ng/mL] and group D [(137.96±14.01) g/mL] (both P<0.05). Conclusion:Alendronate combined with Lactobacillus rhamnosus may play a synergistic role in prevention of bone loss in ovariectomized mice, because combined administration of the two is more effective than administration of either of the two.

Objective:To analyze the clinical data of 203 discharged patients with corona virus disease 2019(COVID-19), and to investigate the predictors for the severe cases.Methods:Confirmed COVID-19 cases hospitalized at Zhongnan Hospital of Wuhan University from January 1 to February 1, 2020 were consecutively enrolled, who were divided into severe group and non-severe group.The clinical data of enrolled patients were collected and the clinical manifestations, laboratory results, imaging, treatments and prognosis of patients in the two groups were analyzed. Mann-Whitney U rank sum test and chi-square test were used for statistical analysis. Results:A total of 203 discharged patients with COVID-19 were enrolled. The common clinical manifestations included fever (89.2%, 181/203), dry cough (60.1%, 122/203), chest distress (35.5%, 72/203), shortness of breath(29.1%, 59/203)and myalgia or arthralgia (26.6%, 54/203). The time from disease onset to hospital admission was 5.8 days (1.0 to 20.0 days). Among 203 enrolled patients, 107(52.7%) were divided into severe group and 96(47.3%) were non-severe group. The age in severe group was 60 years (23 to 91 years), which was significantly older than non-severe group (47 years (20 to 86 years)), the difference was statistically significant ( Z=-6.12, P<0.01). There were 63.6%(68/107) patients in severe group with at least one underlying disease, which was significantly more than non-severe group (20.8% (20/96)), the difference was statistically significant ( χ2=37.60, P<0.01). The proportions of patients with increased white blood cells, decreased lymphocytes and albumin, elevated alanine aminotransferase, aspartate aminotransferase, creatinine, lactic acid dehydrogenase, creatine kinase, fasting blood glucose, D-dimer, erythrocyte sedimentation rate, C-reactive protein, interleukin-6, and procalcitonin in severe group were all higher. On admission, 172 patients (84.7%) had bilateral patchy shadows or ground glass opacity in the lungs on chest imaging study, 20(9.9%) presented pleural effusion. Fifty-five cases (27.1%) showed progressions of lung lesions on computed tomography (CT) rescan at an average interval of five days. Among 203 patients, 123(60.6%) were given oxygen therapy upon admission, 107(52.7%) were given short-term glucocorticoid therapy, and 131(64.5%) received antiviral therapy; and 26(12.8%) died. The hospital stay was 11.0 days (1.0 to 45.0 days). Conclusions:Fever is the most common symptoms in COVID-19 patients.Elderly and patients with underlying diseases are risk factors for progression to severe cases. The elderly patients should be strengthened early monitoring, paid attention to the control of underlying diseases, and reduce the occurrence of critical diseases.

Hepatocellular carcinoma (HCC) is highly heterogeneous in nature and has been one of the most common cancer types worldwide. To ensure repeatability of identified gene expression patterns and comprehensively annotate the transcriptomes of HCC, we carefully curated 15 public HCC expression datasets that cover around 4000 clinical samples and developed the database HCCDB to serve as a one-stop online resource for exploring HCC gene expression with user-friendly interfaces. The global differential gene expression landscape of HCC was established by analyzing the consistently differentially expressed genes across multiple datasets. Moreover, a 4D metric was proposed to fully characterize the expression pattern of each gene by integrating data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). To facilitate a comprehensive understanding of gene expression patterns in HCC, HCCDB also provides links to third-party databases on drug, proteomics, and literatures, and graphically displays the results from computational analyses, including differential expression analysis, tissue-specific and tumor-specific expression analysis, survival analysis, and co-expression analysis. HCCDB is freely accessible at http://lifeome.net/database/hccdb.
Carcinoma, Hepatocellular ; genetics ; Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; genetics

BACKGROUND: Bone tissue engineering based on pluripotent stem cells (PSCs) is a new approach to deal with bone defects. Protocols have been developed to generate osteoblasts from PSCs. However, the low efficiency of this process is still an important issue that needs to be resolved. Many studies have aimed to improve efficiency, but developing accurate methods to determine efficacy is also critical. Studies using pluripotency to estimate efficacy are rare. Telomerase is highly associated with pluripotency. METHODS: We have described a quantitative method to measure telomerase activity, telomeric repeat elongation assay based on quartz crystal microbalance (QCM). To investigate whether this method could be used to determine the efficiency of in vitro osteogenic differentiation based on pluripotency, we measured the pluripotency pattern of cultures through stemness gene expression, proliferation ability and telomerase activity, measured by QCM. RESULTS: We showed that the pluripotency pattern determined by QCM was similar to the patterns of proliferation ability and gene expression, which showed a slight upregulation at the late stages, within the context of the general downregulation tendency during differentiation. Additionally, a comprehensive gene expression pattern covering nearly every stage of differentiation was identified. CONCLUSION: Therefore, this assay may be powerful tools for determining the efficiency of differentiation systems based on pluripotency. In this study, we not only introduce a new method for determining efficiency based on pluripotency, but also provide more information about the characteristics of osteogenic differentiation which help facilitate future development of more efficient protocols.
Bone and Bones ; Down-Regulation ; Gene Expression ; In Vitro Techniques ; Methods ; Mouse Embryonic Stem Cells ; Osteoblasts ; Pluripotent Stem Cells* ; Quartz Crystal Microbalance Techniques ; Telomerase* ; Up-Regulation

Objective To develop novel polyetheretherketone(PEEK) based nanocomposites which possess the favorable antibacterial property,and to investigate the oral microbial adhesion and biofilm formation on the surfaces of PEEK,nano-fluorohydroxyapatite(n-FHA)-PEEK and nano-hydroxyaptite (n-HA)-PEEK.Methods The bacterial adhesion and biofilm formation on the surfaces of n-FHA-PEEK,n-HA-PEEK were investigated via microbial viability assay kit and laser scanning confocal microscope (LSCM),respectively,with pure PEEK as control group.Results No significantly statistical difference were found in the bacterial adhesion amounts on the surfaces of n-FHA-PEEK,n-HA-PEEK and PEEK at 1 h and 4 h.However,the number of bacteria on the n-FHA-PEEK surface decreased dramatically at 2 h(0.496±0.008) compared with n-HA-PEEK groups(0.543± 0.015,P＜0.01).Although the biofilms formation on surfaces observed by LSCM had similar morphology and thickness at 3,7,14 d,that on the n-FHA-PEEK surface showed the highest dead-to-live bacteria ratio among the three materials at 14 d.Conclusions The combination of n-HA,especially for the n-FHA could inhibit the bacteria adhesion and accelerate the bacterial death,eventually may have an influence on the structure of biofilms and reduce the risk of periimplantitis.Therefore,n-FHA-PEEK nanocomposites presented a good prospect for clinical applications as dental implant materials.