OBJECTIVE To study the osteoprotective effects and possible mechanism of total saponins of Chaenomeles speciosa on rheumatoid arthritis （RA） model mice， and to provide reference for further development of anti-RA drugs. METHODS Seventy male DBA/1 mice were randomly divided into normal group， model group， low-dose and high-dose groups of C. speciose total saponins （60， 240 mg/kg）， Tripterygium wilfordii polyglycoside tablets group （positive control， 30 mg/kg）， with 14 mice in each group. In addition to the normal group， the other groups of mice were induced by glucose-6-phosphate isomerase mixed polypeptide to prepare RA model. The body weight， rear toes thickness and arthritis scores of each group were recorded； the synovial inflammation， bone and cartilage destruction of ankle joint tissues were observed by hematoxylin-eosin staining， tartrate- resistant acid phosphatase staining and safranin O-fast green staining； the contents of interleukin-6 （IL-6） in serum and tumor necrosis factor α （TNF-α）， IL-4 and IL-10 in ankle joint tissues were detected by ELISA； the expression levels of receptor activator of nuclear factor-κB ligand （RANKL）， receptor activator of nuclear factor-κB （RANK）， osteoprotegerin （OPG）， tumor necrosis factor receptor-associated protein 6 （TRAF6） and nuclear factor of activated T cells 1 （NFATC1） protein in ankle joint tissues were detected by Western blot assay. RESULTS At the end of administration， compared with normal group， the body mass of mice in the model group was significantly reduced （P＜0.05）， and the arthritis score and the thickness of the left and right rear toes were significantly increased （P＜0.05）； the ankle joint tissues of mice in the model group showed significant synovial proliferation and inflammatory infiltration， the number of osteoclasts increased significantly and significant destruction of cartilage tissue. The content of IL-6 in serum， the content of TNF-α， the protein expression levels of RANKL， RANK， TRAF6 and NFATC1 in the ankle joint tissues were increased significantly （P＜0.05）， while the contents of IL- 4 and IL-10， the protein expression level of OPG in the ankle joint tissues were decreased significantly （P＜0.05）. Compared with model group， above pathomorphological changes and the content/level of indicators of mice in each administration group were significantly improved （P＜0.05）. CONCLUSIONS Total saponins of C. speciosa may exert osteoprotective effects on RA model mice， the mechanism of which may be associated with reducing the contents of IL-6 and TNF-α， increasing the contents of IL-4 and IL-10， inhibiting the activation of RANKL/RANK/OPG signal pathway， thus inhibiting the proliferation of osteoclasts and promoting the repair of cartilage and bone tissue.

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.
Animals ; Humans ; COVID-19 ; Aedes ; Epidemics ; China/epidemiology* ; Dengue/epidemiology*

Rheumatoid arthritis （RA） is a systemic chronic auto-inflammatory disease， characterized by infiltration of inflammatory cells， pannus formation， articular cartilage destruction， and bone matrix destruction. Therefore， improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components， multiple targets， high activity and low side effects. Based on this， the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors， phosphatidylinositol 3-kinase/protein kinase B， Wnt/β- catenin， nuclear factor-κB， mitogen-activated protein kinase， Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor， microRNAs， fibroblastic synovial cells.

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic or obstetrical events and persistent antiphospholipid antibodies (aPLs). Chemokine-like factor-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system and may closely related to APS. This review aimed to systematically summarize the possible effects of CMTM on APS. Publications were collected from PubMed and Web of Science databases up to August 2020. CKLF, CKLFSF, CMTM, antiphospholipid syndrome, immune cells, and immune molecules were used as search criteria. Immune cells, including neutrophil, dendritic cells (DCs), T-cells, B-cells, and inflammatory cytokines, play an important role in the development of APS. Chemokine-like factor 1 (CKLF1) has a chemotactic effect on many cells and can affect the expression of inflammatory cytokines and adhesion molecules through the nuclear factor- kB (NF- kB) pathway or mitogen-activated protein kinase (MARK) pathway. CKLF1 can participate in the maturation of DCs, T lymphocyte activation, and the activation of neutrophils through the MAPK pathway. CMTM1 may act on Annexin A2 by regulating Ca 2+ signaling. CMTM2 and CMTM6 are up-regulated in neutrophils of APS patients. Some CMTM family members influence the activation and accumulation of platelets. CMTM3 and CMTM7 are binding partners of B-cell linker protein (BLNK), thereby linking B cell receptor (BCR) and activating BLNK-mediated signal transduction in B cells. Moreover, CMTM3 and CMTM7 can act on DCs and B-1a cell development, respectively. CMTM may have potential effects on the development of APS by acting on immune cells and immune molecules. Thus, CMTM may act as a novel prognostic factor or immunomodulatory treatment option of APS.

Objective: Alport syndrome was an inherited kidney disease caused by the mutation of COL4A3, COL4A4, or COL4A5. Whole-exome sequencing was used to detect the mutations on these genes for the molecular diagnosis of Alport syndrome. Methods: A 6-year-old girl found accidentally with microscopic hematuria at the age of 4. The clinical data and blood sample of the family including proband, parents, brothers, and sisters were collected. Whole exome sequencing was conducted using their genomic DNAs. Results: A novel heterozygous frameshift mutation c.1826delC (p.Pro609Glnfs*44) was found in the exon 25 of the COL4A4 (NM_000092) in the proband, the father, and the sister, showing an autosomal dominant inheritance pattern of Alport syndrome. This mutation of COL4A4 was confirmed by mutation analysis, and the mutation of c.1826delC was verified by Sanger sequencing. No mutations on COL4A3 and COL4A5 were detected in this family. And the mother and brother are normal wide-type. Conclusions This novel mutation is a valuable addition to the current genetic profile of Alport syndrome, and provide us a better understanding of the disease. Whole-exome sequencing is a power tool to identify the novel mutations of inherited disease and contribute to the molecular diagnosis of disease.

Objective To compare two different methods to detect the differences of gene mutation rate, sensitivity, specificity and coincidence rate of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) so as to assess the clinical value of qRT-PCR method and its environmental-friendly technologyplatforms.One uses environmental fixative poly hydroxyl acrylic acid and green transparent liquid dewaxing Van-clear alone or in combination to replace the traditional fixative 4％ (volume fraction) neutral buffered formalin and the traditional transparent dewaxing liquid xylene in application of quantitative real-time polymerase chain reaction (qRT-PCR).The other uses traditional reagents in direct sequencing.Methods We selected 91 cases of primary NSCLC specimens resected between May 2013 and March 2016 in Zhongshan Bo`ai Hospital and Zhongshan Hospital of Traditional Chinese Medicine.Five samples were taken from the same tumor lesion.We used a random number table to randomly divide these samples into Groups A, B , C, D, and E.Group A received direct sequencing method in detection of EGFR gene mutations.Besides, during the experiment, 4％ neutral buffered formalin was used for fixing, and xylene transparent dewaxing was used to make slices for DNA extraction dewaxing.Group B received qRT-PCR method to detect EGFR gene mutations.Meanwhile, during the experiment, 4％ neutral buffered formalin was used for fixing, and xylene transparent dewaxing was used to make slices for DNA extraction dewaxing.Group C received qRT-PCR method in detection of EGFR gene mutations.At the same time, during the experiment, polyhydroxy acrylic acid was used for fixing, and xylene transparent dewaxing was used to make slices for DNA extraction dewaxing.Group D received qRT-PCR method to detect EGFR gene mutations.In the meantime, 4％ neutral buffered formalin was used for fixing, Van-clear transparent dewaxing was used to make slices for DNA extraction dewaxing.Group E received qRT-PCR method in detection of EGFR gene mutations.In addition, during the experiment, polyhydroxy acrylic acid was used for fixing, and Van-clear transparent dewaxing was used to make slices for DNA extraction dewaxing.In addition, during the experiment, polyhydroxy acrylic acid was used for fixing, and Van-clear transparent dewaxing was used to make slices for DNA extraction dewaxing.The mutations of Exons 18, 19, 20, and 21 in EGFR genes were respectively determined in the five groups of NSCLC.Results ① Groups B, C, D, E and A did not significantly differ in the percentage of people with mutations or target site mutation rates of EGFR genes in NSCLC (P> 0.05).② The detection results of EGFR target site mutation in Groups B, C, D, E and A had good sensitivity, strong specificity, and high compliance rate.Conclusion The green transparent liquid dewaxing Van-clear alone or in combination to replace the traditional fixative 4％ neutral buffered formalin and the traditional transparent dewaxing liquid xylene in the application of qRT-PCR so as to detect EGFR gene mutations in NSCLC has good consistent results compared with the method that uses traditional reagents in direct sequencing.It has the significance and value in clinical application.

OBJECTIVETo construct a breast cancer gene-drug network model for extracting and predicting the correlations between breast cancer-related genes and drugs.

METHODSWe developed an algorithm based on the ABC principle and the association rules to obtain the correlations between the biological entities. For breast cancer, we constructed 3 different correlations (gene-gene, drug-drug and gene-drug) and used the R language to implement the associated network model. The reliability of the algorithm was verified by ROC curve.

RESULTSWe identified 185 breast cancer-associated genes and 98 associations between them, 97 drugs and 170 associations between them. The breast cancer genes-drugs network contained 127 genes and 77 drugs with 384 associations between them.

CONCLUSIONSWe identified a large number of different correlations between the breast cancer-related genes and drugs and close correlations between some biological entity pairs that have not yet been reported, which may provide a new strategy for experimental design for testing personalized breast cancer treatment.

Algorithms ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; Female ; Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; ROC Curve ; Reproducibility of Results