Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective To compare the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulphonate in the treatment of hyperkalemia in chronic kidney disease(CKD).Methods Hospitalized patients with CKD hyperkalemia admitted to Qingyuan People's Hospital from January 2022 to November 2023 were retrospectively selected as study objects,and were divided into sodium zirconium cyclosilicate group and calcium polystyrene sulphonate group according to different drug use.The two groups of patients were matched with 1:1 propensity score,and finally 43 pairs of data were successfully matched.The efficacy and incidence of adverse reactions were compared between two groups of patients after matching.Results After treatment,the serum potassium level in both groups was significantly lower than that before treatment(P<0.05),but there was no significant difference in serum potassium level between two groups(P>0.05).There was no significant difference in the total effective rate between two groups(χ2=1.242,P=0.537).After treatment,the blood sodium level in sodium zirconium cyclosilicate group was significantly higher than that before treatment(P<0.05),there was no significant difference in blood calcium level before and after treatment(P>0.05).There was no significant difference in serum sodium and serum calcium before and after treatment in calcium polystyrene sulphonate group(P>0.05).There was one patient with hypokalemia in each group,and no treatment related adverse reactions such as nausea,edema,constipation,abdominal bloating and diarrhea were observed,and no abnormal laboratory test results were found.Conclusion The clinical efficacy of sodium zirconium cyclosilicate and calcium polystyrene sulphonate in treatment of hyperkalemia in CKD patients is comparable,and the safety is good.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective To compare the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulphonate in the treatment of hyperkalemia in chronic kidney disease(CKD).Methods Hospitalized patients with CKD hyperkalemia admitted to Qingyuan People's Hospital from January 2022 to November 2023 were retrospectively selected as study objects,and were divided into sodium zirconium cyclosilicate group and calcium polystyrene sulphonate group according to different drug use.The two groups of patients were matched with 1:1 propensity score,and finally 43 pairs of data were successfully matched.The efficacy and incidence of adverse reactions were compared between two groups of patients after matching.Results After treatment,the serum potassium level in both groups was significantly lower than that before treatment(P<0.05),but there was no significant difference in serum potassium level between two groups(P>0.05).There was no significant difference in the total effective rate between two groups(χ2=1.242,P=0.537).After treatment,the blood sodium level in sodium zirconium cyclosilicate group was significantly higher than that before treatment(P<0.05),there was no significant difference in blood calcium level before and after treatment(P>0.05).There was no significant difference in serum sodium and serum calcium before and after treatment in calcium polystyrene sulphonate group(P>0.05).There was one patient with hypokalemia in each group,and no treatment related adverse reactions such as nausea,edema,constipation,abdominal bloating and diarrhea were observed,and no abnormal laboratory test results were found.Conclusion The clinical efficacy of sodium zirconium cyclosilicate and calcium polystyrene sulphonate in treatment of hyperkalemia in CKD patients is comparable,and the safety is good.

Carotenoid cleavage dioxygenase (CCD) family is important for production of volatile aromatic compounds and synthesis of plant hormones. To explore the biological functions and gene expression patterns of CsCCD gene family in tea plant, genome-wide identification of CsCCD gene family was performed. The gene structures, conserved motifs, chromosome locations, protein physicochemical properties, evolutionary characteristics, interaction network and cis-acting regulatory elements were predicted and analyzed. Real time-quantitative reverse transcription PCR (RT-qPCR) was used to detect the relative expression level of CsCCD gene family members under different leaf positions and light treatments during processing. A total of 11 CsCCD gene family members, each containing exons ranging from 1 to 11 and introns ranging from 0 to 10, were identified. The average number of amino acids and molecular weight were 519 aa and 57 643.35 Da, respectively. Phylogenetic analysis showed the CsCCD gene family was clustered into 5 major groups (CCD1, CCD4, CCD7, CCD8 and NCED). The CsCCD gene family mainly contained stress response elements, hormone response elements, light response elements and multi-factor response elements, and light response elements was the most abundant (142 elements). Expression analysis showed that the expression levels of CsCCD1 and CsCCD4 in elder leaves were higher than those in younger leaves and stems. With the increase of turning over times, the expression levels of CsCCD1 and CsCCD4 decreased, while supplementary LED light strongly promoted their expression levels in the early stage. The expression level of NCED in younger leaves was higher than that in elder leaves and stems on average, and the expression trend varied in the process of turning over. NCED3 first increased and then decreased, with an expression level 15 times higher than that in fresh leaves. In the late stage of turning over, supplementary LED light significantly promoted its gene expression. In conclusion, CsCCD gene family member expressions were regulated by mechanical force and light. These understandings may help to optimize tea processing techniques and improve tea quality.
Camellia sinensis/genetics* ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Leaves/genetics* ; Plant Proteins/metabolism* ; Tea

Xanthomonas albilineans (Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. X. albilineans produces a potent phytotoxin/antibiotic called albicidin. As a pathogenic factor, albicidin causes typical white leaf stripes by inhibiting plastid DNA gyrase and disturbing chloroplast differentiation. Meanwhile, the antibacterial activity of albicidin gives X. albilineans a competitive advantage against rival bacteria during their colonization. Furthermore, albicidin has a rapid bactericidal activity against a variety of Gram-positive and Gram-negative pathogenic bacteria of human species at nanomolar concentrations, making it a potential antimicrobial drug for clinical application. This article reviews the advances of albicidin from the aspects of its molecular structure, traditional extraction methods, mechanism of action, biosynthetic genes and processes, chemical synthesis method and improvement, in order to provide insights into the prevention and treatment of the sugarcane leaf scald disease, and the development of new antibiotics.
Anti-Bacterial Agents/pharmacology* ; China ; Humans ; Organic Chemicals ; Xanthomonas/genetics*

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted. Clinical data of 45 patients with active CD at the Sixth Affiliated Hospital of Sun Yat-sen University from November 2020 to May 2022 were analyzed. All of the patients received VDZ at the dose of 300 mg per time at 0, 2th, 6th weeks and subsequently once every 8 weeks. The clinical response and remission were evaluated by Crohn′s disease activity index (CDAI) . The endoscopic response and remission were evaluated by simple endoscopic score for Crohn′s disease (SES-CD) . All of the adverse effects occurred during the treatment of VDZ were recorded in order to evaluate the safety. The primary endpoint was the clinical remission rate at 22 weeks after treatment. The secondary endpoints included the clinical response rate at 22 weeks after treatment, the clinical response rate and clinical remission rate at 52 weeks after treatment, the endoscopic response rate and remission rate at (22 ± 8) weeks after treatment. Thirty-one patients who had previously used infliximab (IFX) and adalimumab (ADA) were set as non-Bio-Na?ve group, and 14 patients who had not previously used biologics were set as Bio-Na?ve group. The differences of the primary endpoint and some secondary endpoints between the two groups were compared.Results:At 22 weeks after treatment, the CDAI score of 45 patients decreased from baseline (261.4 ± 98.3) points to (166.6 ± 93.5) points, the difference was statistically significant ( t = 4.6, P<0.01) . Among them, 64.4% (29/45) patients achieved clinical response and 46.7% (21/45) patients achieved clinical remission. There were no significant difference in clinical response rate [71.4% (10/14) vs. 61.3% (19/31) , χ 2 = 0.4, P = 0.4] and clinical remission rate [42.9% (6/14) vs. 48.4% (15/31) , χ 2 = 0.1, P = 0.8] between the Bio-Na?ve group and non-Bio-Na?ve group at 22 weeks after treatment. At 52 weeks after treatment, the CDAI score of 33 patients decreased from baseline (306.9 ± 130.7) points to (126.6 ± 92.7) points, the difference was statistically significant ( t = 8.5, P<0.01) . Among them, 39.4% (13/33) of the patients achieved clinical response, 33.3% (11/33) of the patients achieved clinical remission, but 41.4% (12/29) of the patients had secondary loss of response. At (22 ± 8) weeks after treatment, the SES-CD score of 25 patients in active phase under endoscopy at baseline decreased from baseline 13.0 (7.0, 19.0) points to 8.0 (2.5, 18.5) points, the difference was statistically significant ( Z = -2.6, P<0.05) . Among them, 40.0% (10/25) patients achieved endoscopic response and 20.0% (5/25) patients achieved endoscopic remission. The new facial rash occurred in 1 patient (2.2%) , new joint pain in 2 (4.4%) and there was no new active tuberculosis and hepatitis B virus infection during the treatment of VDZ for 45 patients. Conclusions:Single drug of VDZ has a good effect on inducing remission in patients with mild to moderate CD and has a good safety. The previous use of IFX or ADA does not affect the efficacy of VDZ, but part of patients still have secondary loss of response.

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted. Clinical data of 45 patients with active CD at the Sixth Affiliated Hospital of Sun Yat-sen University from November 2020 to May 2022 were analyzed. All of the patients received VDZ at the dose of 300 mg per time at 0, 2th, 6th weeks and subsequently once every 8 weeks. The clinical response and remission were evaluated by Crohn′s disease activity index (CDAI) . The endoscopic response and remission were evaluated by simple endoscopic score for Crohn′s disease (SES-CD) . All of the adverse effects occurred during the treatment of VDZ were recorded in order to evaluate the safety. The primary endpoint was the clinical remission rate at 22 weeks after treatment. The secondary endpoints included the clinical response rate at 22 weeks after treatment, the clinical response rate and clinical remission rate at 52 weeks after treatment, the endoscopic response rate and remission rate at (22 ± 8) weeks after treatment. Thirty-one patients who had previously used infliximab (IFX) and adalimumab (ADA) were set as non-Bio-Na?ve group, and 14 patients who had not previously used biologics were set as Bio-Na?ve group. The differences of the primary endpoint and some secondary endpoints between the two groups were compared.Results:At 22 weeks after treatment, the CDAI score of 45 patients decreased from baseline (261.4 ± 98.3) points to (166.6 ± 93.5) points, the difference was statistically significant ( t = 4.6, P<0.01) . Among them, 64.4% (29/45) patients achieved clinical response and 46.7% (21/45) patients achieved clinical remission. There were no significant difference in clinical response rate [71.4% (10/14) vs. 61.3% (19/31) , χ 2 = 0.4, P = 0.4] and clinical remission rate [42.9% (6/14) vs. 48.4% (15/31) , χ 2 = 0.1, P = 0.8] between the Bio-Na?ve group and non-Bio-Na?ve group at 22 weeks after treatment. At 52 weeks after treatment, the CDAI score of 33 patients decreased from baseline (306.9 ± 130.7) points to (126.6 ± 92.7) points, the difference was statistically significant ( t = 8.5, P<0.01) . Among them, 39.4% (13/33) of the patients achieved clinical response, 33.3% (11/33) of the patients achieved clinical remission, but 41.4% (12/29) of the patients had secondary loss of response. At (22 ± 8) weeks after treatment, the SES-CD score of 25 patients in active phase under endoscopy at baseline decreased from baseline 13.0 (7.0, 19.0) points to 8.0 (2.5, 18.5) points, the difference was statistically significant ( Z = -2.6, P<0.05) . Among them, 40.0% (10/25) patients achieved endoscopic response and 20.0% (5/25) patients achieved endoscopic remission. The new facial rash occurred in 1 patient (2.2%) , new joint pain in 2 (4.4%) and there was no new active tuberculosis and hepatitis B virus infection during the treatment of VDZ for 45 patients. Conclusions:Single drug of VDZ has a good effect on inducing remission in patients with mild to moderate CD and has a good safety. The previous use of IFX or ADA does not affect the efficacy of VDZ, but part of patients still have secondary loss of response.

Objective: To summarize the clinical characteristics, virological and histopathological features, clinical outcome of Epstein-Barr virus-positive lymphoproliferative disease (EBV⁺LPD) in children. Methods: The clinical and follow-up data of 13 children histopathologically diagnosed as EBV⁺LPD in the Department of Infectious Disease of Beijing Children's Hospital between January 2011 and December 2016 were summarized. Results: Of the 13 patients, 5 were males and 8 females. The median age of disease onset was 6.0 years (range 1.3 to 15.0 years). The median duration between disease onset and diagnosis was 3 months (range 1 to 24 months). All the 13 patients had fever, 9 cases had hepatosplenomegaly and lymphoadenopathy, 4 cases had only lymphoadenopathy, 7 cases had reduced peripheral blood cells, 7 cases had lung involvement, 3 cases had central nervous system involvement, 3 cases had cardiac involvement, 3 cases had intestinal involvement, 2 cases had skin involvement and 1 case had abdominal mass. All the 13 patients underwent whole blood EBV-DNA PCR examination and the copies ranged from 1×10⁸/L to 1×10¹¹/L. Pathology of lymph node confirmed 6 cases, skin pathology confirmed 2 cases, lung pathology, ileum mucosa pathology, liver pathology, abdominal mass pathology and bone marrow pathology confirmed 1 case each. Among 13 patients, 9 cases presented with EBV-positive T cell lymphoproliferative disease(EBV⁺ T-LPD), 2 cases with hydroa vacciniforme (HV) and 2 cases with EBV-positive diffuse large B-cell lymphoma (EBV⁺ DLBCL) . All the patients were followed up for 2 days to 65 months after discharge. Among 9 cases of EBV⁺T-LPD, 1 case died in a short time, 1 case died after evolved to T-cell lymphoma, 2 cases recovered after hematopoietic stem cell transplantation, 1 case recovered after the chemotherapy of hemophagocytic lymphohistiocytosis(HLH) 2004 protocol and 4 cases were stable now. Of 2 cases of HV patients, 1 case died after evolved to HV like lymphoma and the other still have symptoms. Among 2 cases of EBV⁺ DLBCL, 1 case died shortly after discharge and the other was still stable after chemotherapy. Conclusions Chronic recurrent fever, lymphadenopathy and hepatosplenomegaly are the most common clinical manifestations in children with EBV⁺LPD. Involvement of lung, central nervous system, intestinal tract, skin and other organs are also involved frequently. For children with chronic fever of unknown cause and accompanied by lymphadenopathy and (or) hepatosplenomegaly, EBV ⁺ LPD should be considered highly when the whole blood EBV-DNA load continues to increase significantly, early biopsy of the proliferative lesion should be performed to make a definite diagnosis. The prognosis of EBV ⁺ LPD is poor, and some evolve to lymphoma, hematopoietic stem cell transplantation is an effective way to treat this disease.

Objective To explore the relationship between the women menopausal period and metabolic syndrome (MS) .Meth-ods The female residents of Chongqing urban areas above 40 years were selected as the investigation group ,all the subjects were performed the questionnaire survey and the physical examination ,at the same time the biochemical indexes were detected .Finally , 1402 women of natural menopause were included in this study .The study subjects were divided into different groups according to the menopausal period of <5 years ,5- <10 years ,10- <15 years and ≥15 years .The Logistic regression analysis was adopted to analyze the relationship between the menopausal period with MS and its components .Results The MS prevalence in this group was 40 .87% ,and the menopausal period of the women with MS was significantly higher than that without MS (P<0 .05) .The MS prevalences of postmenopausal women in the menopause period of <5 years ,5 - <10 years ,10 - <15 years and ≥15 years were 29 .37% ,34 .29% ,45 .30% and 49 .13% respectively (P<0 .05) .After adjustment for age and BMI (except central obesity ) ,the MS risk in the menopausal period of 10- <15 years and was 1 .54 times of that in the menopausal period of <5 years .The Logis-tic regression analysis showed that BMI and menopausal period were the influence factors of MS .Conclusion Post-menopausal women are the high-risk group of MS and the menopausal period is correlated to MS .