Objective To investigate the epidemiological characteristics of lymphoma mortality and potential years of life lost among Wuhan residents, and to provide a scientific basis for the prevention and control of lymphoma. Methods Data on lymphoma deaths among residents in Wuhan from 2010 to 2019 were collected from the population-based Wuhan Mortality Surveillance System. Joinpoint regression model was used to evaluate the trends in age-standardized mortality rates and potential years of life lost due to lymphoma among the residents of different ages and genders. Potential years of life lost rate was used to assess the disease burden. Results There were 4 055 deaths (2481in male and 1 574 in female) from major kidney diseases in Wuhan residents between 2010 to 2019, with an age-standardized mortality rate of 5.11/100 000. The mortality rate of major kidney diseases showed an upward trend with increasing age. Between 2010 and 2019, the age-standardized mortality rates of the multiple myeloma and non-Hodgkin lymphoma were significantly increased (APC=6.924%, APC=1.407%, P＜0.05), and the potential years of life lost rate of non-Hodgkin lymphoma in female were significantly increased (APC=7.935%，P＜0.05). Conclusion From 2010 to 2019, the mortality rate of lymphoma among residents of Wuhan City shows an upward trend, especially for multiple myeloma and non-Hodgkin lymphoma. The disease burden of multiple myeloma shows an increasing trend in the female population, suggesting the need to take corresponding preventive and control measures.

Objective:To explore the the possibility and potential mechanism of Coptis chinensis in treating caries based on network pharmacology and molecular docking technology.Methods:The active ingredients of Coptis chinensis and the targets of the active in-gredients and caries were obtained through a variety of databases.The intersection targets of Coptis chinensis and caries were obtained by VENNY.Based on the target of the intersection,the protein-protein interaction(PPI)networks relationship diagram was formed on the STRING platform.The core target diagram was formed through the Cytoscape software,and the Coptis chinensis-active ingre-dient-target network diagram was constructed.The intersection targets are analyzed by GO and KEGG.The core targets of Coptis chinensis active ingredients in treating caries was analyzed by molecular docking.Results:The 11 Coptis chinensis active ingredi-ents,465 targets of Coptis chinensis active ingredients and 1 160 targets of caries were obtained from the database.After analysis,71 targets of Coptis chinensis-caries intersection and 12 core targets were obtained.The potential therapeutic effect of Coptis chinensis on caries involved relaxin,phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt),mitogen activated protein kinase(MAPK),ras-re-lated protein 1(RAP1)and other signaling pathways.Berberine,one of the main active components of Coptis chinense,had strong binding activity on epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9)and other core targets.Coptis chinen-sis and its active components can play a role in the treatment of caries through EGFR,MMP9 and PI3K-AKT,MAPK and other path-ways.Conclusion:Coptis chinensis and its active components can regulate several targets and signaling pathways such as EGFR,MMP9,PI3K-AKT and MAPK.Coptis chinensis may play a role in the prevention and treatment of caries through multiple pathways.

Objective:This study investigated the dynamic expression of lipocalin-2(LCN2)and its receptor,brain-type organic cation transporter protein(BOCT),in spinal cords of hSOD1G93A transgenic mice during disease pro-gression,providing potential targets for early anti-inflammatory therapy for ALS.Methods:Utilizing hSOD1G93A trans-genic mice and their wild-type littermates(WT)as animal models,this investigation examined the expression of LCN2 and BOCT at four distinct disease stages:pre-symptomatic stage(60 d),early-symptomatic stage(95 d),symptomatic stage(108 d),and late-symptomatic stage(122 d).Spinal cords were harvested,then RT-qPCR,Western blot,and immunofluorescence double-labeling techniques were employed to assess alteration expressions of LCN2 and BOCT.Ad-ditionally,BV2 cells transfected with the pcDNA3.1-G93A-SOD1 overexpression plasmid served as an in vitro hSOD1G93A BV2 microglial model.After stimulated with LPS for 24 hours,LCN2 mRNA and protein expression in hSOD1G93A BV2 microglial cells and its culture medium were measured by RT-qPCR and ELISA respectively,while BOCT expression was measured by Western blot.Results:Compared with WT mice littermates,increased expression of LCN2 mRNA was detected in the spinal cords of hSOD1G93A transgenic mice at 108 and 122 d.No significant differences were observed in LCN2 or BOCT protein expression in the spinal cords of hSOD1G93A transgenic mice from 60 to 122 d.Double-immunofluorescence labeling revealed co-localization of LCN2 and BOCT with the microglial marker Iba-1 in the ventral horn of lumbar spinal cord of hSOD1G93A transgenic mice from 95 to 122 d.In hSOD1G93A BV2 microglial model,LPS stimulation led to a significantly increased LCN2 mRNA expression and protein secretion.Conversely,there was no significant change in BOCT protein expression after LPS stimulation.Conclusion:Our findings suggest that during ALS progression,there is an enhanced expression and release of LCN2 from activated microglia,potentially exacerbating neuroinflammation and neuronal degeneration.

Objective:To explore the the possibility and potential mechanism of Coptis chinensis in treating caries based on network pharmacology and molecular docking technology.Methods:The active ingredients of Coptis chinensis and the targets of the active in-gredients and caries were obtained through a variety of databases.The intersection targets of Coptis chinensis and caries were obtained by VENNY.Based on the target of the intersection,the protein-protein interaction(PPI)networks relationship diagram was formed on the STRING platform.The core target diagram was formed through the Cytoscape software,and the Coptis chinensis-active ingre-dient-target network diagram was constructed.The intersection targets are analyzed by GO and KEGG.The core targets of Coptis chinensis active ingredients in treating caries was analyzed by molecular docking.Results:The 11 Coptis chinensis active ingredi-ents,465 targets of Coptis chinensis active ingredients and 1 160 targets of caries were obtained from the database.After analysis,71 targets of Coptis chinensis-caries intersection and 12 core targets were obtained.The potential therapeutic effect of Coptis chinensis on caries involved relaxin,phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt),mitogen activated protein kinase(MAPK),ras-re-lated protein 1(RAP1)and other signaling pathways.Berberine,one of the main active components of Coptis chinense,had strong binding activity on epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9)and other core targets.Coptis chinen-sis and its active components can play a role in the treatment of caries through EGFR,MMP9 and PI3K-AKT,MAPK and other path-ways.Conclusion:Coptis chinensis and its active components can regulate several targets and signaling pathways such as EGFR,MMP9,PI3K-AKT and MAPK.Coptis chinensis may play a role in the prevention and treatment of caries through multiple pathways.

Objective:This study investigated the dynamic expression of lipocalin-2(LCN2)and its receptor,brain-type organic cation transporter protein(BOCT),in spinal cords of hSOD1G93A transgenic mice during disease pro-gression,providing potential targets for early anti-inflammatory therapy for ALS.Methods:Utilizing hSOD1G93A trans-genic mice and their wild-type littermates(WT)as animal models,this investigation examined the expression of LCN2 and BOCT at four distinct disease stages:pre-symptomatic stage(60 d),early-symptomatic stage(95 d),symptomatic stage(108 d),and late-symptomatic stage(122 d).Spinal cords were harvested,then RT-qPCR,Western blot,and immunofluorescence double-labeling techniques were employed to assess alteration expressions of LCN2 and BOCT.Ad-ditionally,BV2 cells transfected with the pcDNA3.1-G93A-SOD1 overexpression plasmid served as an in vitro hSOD1G93A BV2 microglial model.After stimulated with LPS for 24 hours,LCN2 mRNA and protein expression in hSOD1G93A BV2 microglial cells and its culture medium were measured by RT-qPCR and ELISA respectively,while BOCT expression was measured by Western blot.Results:Compared with WT mice littermates,increased expression of LCN2 mRNA was detected in the spinal cords of hSOD1G93A transgenic mice at 108 and 122 d.No significant differences were observed in LCN2 or BOCT protein expression in the spinal cords of hSOD1G93A transgenic mice from 60 to 122 d.Double-immunofluorescence labeling revealed co-localization of LCN2 and BOCT with the microglial marker Iba-1 in the ventral horn of lumbar spinal cord of hSOD1G93A transgenic mice from 95 to 122 d.In hSOD1G93A BV2 microglial model,LPS stimulation led to a significantly increased LCN2 mRNA expression and protein secretion.Conversely,there was no significant change in BOCT protein expression after LPS stimulation.Conclusion:Our findings suggest that during ALS progression,there is an enhanced expression and release of LCN2 from activated microglia,potentially exacerbating neuroinflammation and neuronal degeneration.

Objective To explore the mechanism of ginseng in the treatment of periodontitis based on network phar-macology and molecular docking technology.Methods Potential targets of ginseng and periodontitis were obtained through various databases.The intersection targets of ginseng and periodontitis were obtained by using VENNY,the pro-tein-protein interaction network relationship diagram was formed on the STRING platform,the core target diagram was formed by Cytoscape software,and the ginseng-active ingredient-target network diagram was constructed.The selected targets were screened for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway en-richment analysis.The core targets of ginseng's active in-gredients in treating periodontitis were analyzed by mo-lecular docking technique.Results The 22 ginseng's active ingredients,591 potential targets of ginseng's ac-tive ingredients,2 249 periodontitis gene targets,and 145 ginseng-periodontitis intersection targets were analyzed.Ginseng had strong binding activity on core targets such as vas-cular endothelial growth factor A and epidermal growth factor receptor,as well as hypoxia induced-factor 1(HIF-1)sig-naling pathway and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt)signaling pathway.Conclusion Gin-seng and its active components can regulate several signaling pathways such as HIF-1 and PI3K-Akt,thereby indicating that ginseng may play a role in treating periodontitis through multiple pathways.

OBJECTIVE To monitor plasma concentration of anti-tuberculosis drugs in children, and explore the influencing factors and safety of anti-tuberculosis drugs, and promote the rational use of drugs. METHODS The plasma drug concentration monitoring results of isoniazid, rifampicin, pyrazinamide and ethambutol, the adverse drug reactions and the changes of various parameters before and after treatment in 40 children with tuberculosis were analyzed retrospectively in Zhejiang Hospital of Integrated Tradtional Chinese and Western Medicine. RESULTS The compliance rates of plasma drug concentration of isoniazid, rifampicin, pyrazinamide and ethambutol in chlidren with tuberculosis were 48.15%, 34.88%, 73.81%, 18.52%, respectively. Isoniazid(P=0.0250), rifampicin(P=0.0212) concentrations were positively correlated with daily dose. Age was also one of the factors affecting the concentrations of isoniazid(P=0.0430) and rifampicin(P=0.0057). Serum albumin(P=0.0475) and sex(P=0.0087) were correlated with rifampicin and pyrazinamide, respectively. Abnormal liver function(5/40, 12.50%) and rash(4/40, 10%) were the most common adverse drug reaction. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and uric acid levels increased after treatment with anti-tuberculosis drugs. CONCLUSION The plasma drug concentrations of isoniazid, rifampicin and ethambutol in children are low. The anti-tuberculosis drugs maybe related to the increase of AST, ALT and uric acid. Therefore, monitoring of serum drug concentration, renal fuction and liver function during anti-tuberculosis treatment is helpful to improve drug safety and implement individualized treatment.

Objective:To investigate the icariin on cognitive function and astrocytic pyroptosis in hemorrhagic shock resuscitation model mice.Methods:Forty-eight SPF grade C57BL/6 mice (male) were randomly divided into four groups ( n=12 in each group): Sham operation control group (Group C), hemorrhagic shock and resuscitation group (Group H), hemorrhagic shock and resuscitation plus icariin group (Group HI) and hemorrhagic shock resuscitation plus icariin and SSK1 group (Group HIS, SSK1 was a phosphorylation agonist of mitogen-activated protein kinase p38(p38MAPK). The mice in Group H, HI and HIS were subjected to hemorrhagic shock and resuscitation model by bleeding and retransfusion via left femoral vein; the mice in Group HI and HIS were administered with icariin (10 mg/kg) intragastrically for 7 days; the mice in Group C and H were administered with the same amount of normal saline containing dimethyl sulfoxide(DMSO). The mice in Group HIS were administered with SSK1 (0.5 mg/kg) intraperitoneally, but the mice in Group C, H and HI were only administered with the same amount of normal saline containing DMSO.At 15 days after resuscitation, novel objective recognition test and fear conditioning test were used to assess cognitive dysfunction of mice.Microtubule-associated protein 2(MAP2), a specific marker protein of neurons reflecting astrocytic pyroptosis in the hippocampus of mice, were detected by immunofluorescence assay so as to assess neuronal injury and astrocytic pyroptosis.The levels of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the hippocampus were evaluated by Western blot.SPSS 21.0 software was used for data analysis, multiple samples among groups were compared by one-way ANOVA, and SNK- q test was used for further pairwise comparison. Results:The results of new object recognition test showed that the difference of new object recognition index among the four groups was statistically significant ( F=50.75, P<0.05). The new object recognition indexes in H group(22.7±6.9), HI group(40.1±7.0) and HIS group (22.5±7.5) were significantly lower than that in C group (58.5±11.2). The index in HI group was higher than that in H group, while the index in HIS group was lower than that in HI group (all P<0.05). The results of the fear conditioning test showed that there was a statistically significant difference in the percentage of freezing time among the four groups of mice ( F=60.54, P<0.05). And the percentage of freezing time in H group((21.8±5.0)%), HI group ((38.4±7.4) %)and HIS group((21.3±4.2)%)were lower than that in C group((49.1±7.0)%), which in HI group was higher than that in H group ( P<0.05)and which in HIS group was lower than that in HI group(all P<0.05). The results of immunofluorescence showed that there were significant decreases of MAP2 intensity ((35.3±9.3)%, (63.3±6.1)%, (28.7±10.3)%) but increases of pyroptotic astrocytes ((24.5±4.2)%, (9.3±1.5)%, (22.1±3.3)%) in the H, HI and HIS groups compared with those of C group ((106.7±19.7) %, (3.4±2.0)%). There was an increase of MAP2 intensity but a decrease of pyroptotic astrocytes in the HI group compared with those in H group, and there was a decrease of MAP2 intensity but an increase of pyroptotic astrocytes in the HIS group compared with those of HI group (all P<0.05). The Western blot results showed that there were significant increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the H, HI and HIS groups compared with C group, there were decreases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HI group compared with H group, and there were increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HIS group compared with those in HI group (all P<0.05). Conclusion:Icariin alleviates hemorrhage shock and resuscitation-induced cognitive dysfunction and astrocytic pyroptosis in mice, and the mechanism may be associated with inhibition of phosphorylated p38MAPK.

Objective:To explore the effect of Toll-like receptor 9 (TLR9) signaling pathway activation on the transcriptome in the renal tubular cells.Methods:Mouse primary renal tubular epithelial cells were extracted and cultured. When the degree of cell fusion reached 80%, they were divided into two groups, which were added with 10 μL phosphate buffered saline (PBS, PBS control group) and TLR9 activator cytosine phosphate guanidine oligodeoxynucleotide (CpG-ODN) with a final concentration of 5 μmol/L (CpG-ODN treatment group). The RNA sequencing was performed on the Illumina platform after extraction. DEGseq software was used to analyze the differential expression of genes between the two groups. Goatools and KOBAS online software were used to analyze the differential genes involved signal pathways. Homer software was used to predict transcription factors.Results:Compared with the PBS control group, there were a total of 584 differentially expressed genes in the CpG-ODN treatment group, of which 102 were up-regulated and 482 were down-regulated. The most significantly enriched gene ontology (GO) terms of differentially expressed genes included response to interferon-β, defense response to virus and other inflammatory pathway. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways included 2'-5'-oligoadenylate synthase activity, regulation of ribonuclease activity, negative regulation of virus life cycle, cellular response to interferon-βand defense response to protozoan. The results of transcription factor prediction showed that interferon regulatory factor 3 (IRF3) was the most significantly enriched transcription factor in the promoter sequence of differential genes; the most significant transcription factor downstream of TLR9 was IRF3, and other predicted transcription factors such as transcription factor 21 (TCF21), zinc finger protein 135 (ZNF135), and PR domain containing 4 (PRDM4) might be new candidates for TLR9 signaling pathway.Conclusion:CpG-ODN activates TLR9 signaling pathway, and primary renal tubular epithelial cells can directly respond to CpG-ODN stimulation and undergo transcriptome changes, which provides a basis for further research on the molecular mechanism of TLR9 pathway in sepsis induced acute kidney injury.

Objective:To analyze the survival and prognostic factors of adult acute lymphoblastic leukemia (ALL) with different consolidation regimens after complete remission by induction therapy.Methods:A total of 93 adult patients with ALL were enrolled from January 2012 to June 2019 in Peking University Shenzhen Hospital. All the patients achieved complete remission induced by VDLCP regimen, and were divided into the standard group, intensive group and transplantation group according to the consolidation treatment. Thirty-four patients in the standard group received an ALL-like chemotherapy regimen based on VDLCP or Hyper-CVAD consolidation for 4-6 courses. Twenty-nine patients in the intensive group received BFM90/95 consolidation treatment for 2 years. Thirty patients in the transplantation group received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after 2-3 courses of consolidation with the original induction regimen. The median follow-up was 18 (3-96) months, and the main follow-up indicators were overall survival (OS) and disease free survival (DFS). Prognostic factors of adult ALL patients and treatment-related deaths in each group were analyzed.Results:The 3-year OS rates of the standard group, intensive group and transplantation group were 54.0% (95% CI: 35.3%-72.6%), 71.8% (95% CI: 41.0%-94.5%), 62.3% (95% CI: 43.6%-80.9%), with a statistically significant difference ( χ2=6.110, P=0.047). The 3-year DFS rates of the three groups were 31.4% (95% CI: 12.9%-49.8%), 72.1% (95% CI: 52.3%-91.9%), 65.7% (95% CI: 45.3%-86.1%), with a statistically significant difference ( χ2=13.831, P=0.001). There were no significant differences in OS and DFS between the intensive group and the transplantation group ( χ2=0.709, P=0.400; χ2=0.046, P=0.830). OS and DFS of the intensive group were better than those of the standard group ( χ2=5.346, P=0.021; χ2=10.326, P=0.010). Multivariate analysis suggested that bone marrow minimal residual disease (MRD) negative on day 14-21 of chemotherapy was an independent prognostic factor affecting adult ALL ( HR=0.114, 95% CI: 0.015-0.841, P=0.033). The 3-year OS rates of Ph + ALL patients who received and did not receive allo-HSCT were 53.5% (95% CI: 23.1%-83.8%), 52.4% (95% CI: 23.8%-81.0%), the 3-year DFS rates were 77.1% (95% CI: 54.2%-100.0%), 35.0% (95% CI: 4.8%-65.2%), and there were no significant differences between the two groups ( χ2=3.600, P=0.223; χ2=3.824, P=0.050). The treatment-related mortalities of the non-transplantation group (standard group + intensive group) and the transplantation group were 3.2% (2/63) and 20.0% (6/30), and the treatment-related mortality of the non-transplantation group was significantly lower than that of the transplantation group ( χ2=7.318, P=0.007). Conclusion:Adult ALL has a poor prognosis. The 3-year OS rate and 3-year DFS rate of BFM intensive consolidation therapy are better than those of standard consolidation therapy, achieving a similar effect to allo-HSCT, but treatment-related mortality does not increase significantly. Patients with bone marrow MRD negative on the day 14-21 of chemotherapy have the better OS and DFS.