Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Objective To observe the clinical curative effect of levocarnitine injection combined with mecobalamine injection and hemodialysis in uremic peripheral neuropathy.Methods The patients with uremic peripheral neuropathy were divided into treatment group and control group according to cohort method.The patients in the control group was given mecobalamine injection,0.5 g each time,after each dialysis,3 times a week,intravenous drip.On the basis of the treatment of the control group,the treatment group was given levocarnitine injection,1 g each time,after each dialysis,3 times a week,intravenous drip.Both groups were treated for 12 weeks.Results There were 35 cases in control group and 45 cases in treatment group.After treatment,total response rates of treatment group and control group were 93.33％(42 cases/45 cases)and 77.14％(27 cases/35 cases),the difference was statistically significant(P＜0.05).After treatment,sensory nerve conduction velocity(SCV)of common peroneal nerve in treatment group and control group were(41.73±4.05)and(38.67±3.73)m·s-1;MCV of common peroneal nerve were(46.62±4.41)and(43.51±4.29)m·s-1;levels of serum advanced oxidized protein product were(81.75±14.36)and(109.43±18.57)μmol·L-1;levels of glutathione peroxidase were(73.39±6.05)and(61.83±5.72)U·L-1;levels of superoxide dimutase were(90.68±11.28)and(79.95±9.03)U·L-1,differences were statistically significant(all P＜0.05).The adverse drug reactions in treatment group were mainly on rash,loss of appetite and dizziness,while which in control group were mainly on loss of appetite,diarrhea and vomiting.There were no significant difference in total incidence of adverse drug reactions between treatment group and control group[11.11％(5 cases/45 cases)vs 8.57％(3 cases/35 cases)].Conclusion Curative effect of levocarnitine injection combined with mecobalamine injection and hemedialysis is significant in patients with uremic peripheral neuropathy,which can relieve clinical symptoms and promote the recovery of nerve conduction velocity.

Objective To observe the clinical curative effect of levocarnitine injection combined with mecobalamine injection and hemodialysis in uremic peripheral neuropathy.Methods The patients with uremic peripheral neuropathy were divided into treatment group and control group according to cohort method.The patients in the control group was given mecobalamine injection,0.5 g each time,after each dialysis,3 times a week,intravenous drip.On the basis of the treatment of the control group,the treatment group was given levocarnitine injection,1 g each time,after each dialysis,3 times a week,intravenous drip.Both groups were treated for 12 weeks.Results There were 35 cases in control group and 45 cases in treatment group.After treatment,total response rates of treatment group and control group were 93.33％(42 cases/45 cases)and 77.14％(27 cases/35 cases),the difference was statistically significant(P＜0.05).After treatment,sensory nerve conduction velocity(SCV)of common peroneal nerve in treatment group and control group were(41.73±4.05)and(38.67±3.73)m·s-1;MCV of common peroneal nerve were(46.62±4.41)and(43.51±4.29)m·s-1;levels of serum advanced oxidized protein product were(81.75±14.36)and(109.43±18.57)μmol·L-1;levels of glutathione peroxidase were(73.39±6.05)and(61.83±5.72)U·L-1;levels of superoxide dimutase were(90.68±11.28)and(79.95±9.03)U·L-1,differences were statistically significant(all P＜0.05).The adverse drug reactions in treatment group were mainly on rash,loss of appetite and dizziness,while which in control group were mainly on loss of appetite,diarrhea and vomiting.There were no significant difference in total incidence of adverse drug reactions between treatment group and control group[11.11％(5 cases/45 cases)vs 8.57％(3 cases/35 cases)].Conclusion Curative effect of levocarnitine injection combined with mecobalamine injection and hemedialysis is significant in patients with uremic peripheral neuropathy,which can relieve clinical symptoms and promote the recovery of nerve conduction velocity.

Hoffa fracture is an unstable intra-articular fracture with significant redisplacement tendency. It is easy to be missed diagnosis when accompanied by distal intercondylar or supracondylar fracture of femur. CT scan is the gold standard for the diagnosis of Hoffa fracture. The treatment principles are anatomic reduction of the articular surface, reliable internal fixation, and early functional activity. At present, the main treatment is arthroscopic screw fixation. During screw fixation, the tail cap of screw should be buried, resulting in non-healing iatrogenic injury of articular cartilage. In the early postoperative functional activity of knee joint, fracture block was repeatedly subjected to backward and upward shear force under the action of the tibial plateau, which is the main reason for the failure of internal fixation. Plate assisted screw fixation could increase local mechanical stability, but it still cannot avoid the defects of iatrogenic cartilage injury. At the same time, plate molding is required during the operation due to the absence of special anatomical plates, resulting in increased surgical trauma and time-consuming surgery. The ideal fixation method for Hoffa fracture should include:(1) Avoid iatrogenic injury of articular surface cartilage. (2) With the rear anti-shear barrier plate function.(3) The internal fixator is closer to the load interface, so as to obtain greater load and better fixed strength.
Humans ; Hoffa Fracture ; Femoral Fractures/surgery* ; Tomography, X-Ray Computed ; Fracture Fixation, Internal/methods* ; Bone Plates ; Iatrogenic Disease

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/epidemiology* ; Sucrose/therapeutic use* ; Ferric Compounds/therapeutic use* ; Retrospective Studies ; Iron/therapeutic use* ; Hemoglobins/therapeutic use*

Humans ; Adult ; Mucormycosis ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Antifungal Agents

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Hexokinase/metabolism* ; Humans ; Liver Neoplasms/pathology* ; Protein Phosphatase 2/metabolism* ; RNA, Small Interfering/metabolism*

OBJECTIVE: To investigate the regulation of chronic myelogenous leukemia （CML） imatinib resistant genes, in order to improve the therapeutic effect of CML imatinib resistant patients. METHODS: The human CML cell line K562 and imatinib-resistant K562 cells (K562/G01) were collected, and transcriptome of the cells were achieved by RNA-seq. The sequencing data were analyzed by using standard procedures. RESULTS: Compared with K562 cells, 464 genes were significantly changed in K562/G01 cells, including 163 up-regulated and 301 down-regulated genes. The GO function annotation analysis and KEGG pathway analysis results showed that the differentially expressed genes were mainly involved in biological processes such as oxidative phosphorylation, localization to protein organelle, ribonucleoprotein complex biogenesis and so on. Gene Set Enrichment Analysis (GSEA) plots showed that 5 gene-sets were up-regulated in K562/G01 significantly, including the pathway of TGF-beta, mTOR and CML. CONCLUSION CML imatinib resistance is associated with oxidative phosphorylation, during which the pathway of TGF-beta and mTOR are significantly up-regulated.
Drug Resistance, Neoplasm ; Gene Expression Profiling ; Humans ; Imatinib Mesylate/pharmacology* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*

Objective To analyze the spatial epidemiological characteristics of measles in Taizhou from 2009 to 2017, so as to provide theoretical basis for measles prevention and control. Methods The spatial autocorrelation analysis and trend surface analysis of measles epidemics data from 2009 to 2017 in Taizhou were performed using ArcGIS 10.0 software. The dynamic characteristics of measles epidemics in Taizhou were analyzed. Results Among 2009-2017 years, the incidences of measles in Taizhou ranged from 0.83/1 million to 65.43/1 million. The results of global autocorrelation analysis showed that there were spatial correlations of the incidence of measles among 2012, 2013, 2015, and 2016 in Taizhou with a high-value clustering distribution. Local autocorrelation analysis indicated that the hot spots of measles incidence in Taizhou from 2009 to 2017 were mainly concentrated in the central towns of Taizhou. Trend surface analysis suggested that the measles incidence in the south towns of Taizhou was higher than that in the north in 2010, and the incidence in the central region was higher than those in other regions in 2013 and 2015. Conclusions According to the spatial analysis, autocorrelation was observed for the spatial distribution of measles incidence in Taizhou from 2009 to 2017, and there are hot spots in the central township. Targeted preventive measures should be taken based on these characteristics.