1.Mechanisms of Intestinal Microecology in Hyperuricemia and Traditional Chinese Medicine Intervention:A Review
Mingyuan FAN ; Jiuzhu YUAN ; Hongyan XIE ; Sai ZHANG ; Qiyuan YAO ; Luqi HE ; Qingqing FU ; Hong GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):329-338
In recent years, hyperuricemia (HUA) has shown a rapidly increasing incidence and tends to occur in increasingly young people, with a wide range of cardiac, renal, joint, and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage, medication restriction, and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid (UA), and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology, which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine (TCM) can treat HUA via multiple targets and multiple pathways from a holistic view, with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However, its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA, this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora, intestinal metabolites, intestinal UA transporters, and intestinal barriers. Furthermore, we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology, with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.
2.The effect of wza gene deletion in Klebsiella pneumoniae on capsule formation and bacteriophage sensitivity
Zheng FAN ; Hongbo LIU ; Yuchen CHEN ; Xiaohu CUI ; Zhoufei LI ; Tongtong FU ; Jing YUAN
Chinese Journal of Preventive Medicine 2024;58(7):992-997
Objective:To investigate the effects of wza gene deletion in Klebsiella pneumoniae on capsule formation ability and bacteriophage sensitivity. Methods:The wza deletion mutant strain was constructed through a temperature-sensitive plasmid-mediated homologous recombination. The growth curves of W14 and Δ wza were detected by measuring the optical density OD 600. In order to analyze the effect of gene wza on bacterial capsule formation, wild-type strain W14 and Δ wza mutant strain were detected by transmission electron microscope, and their capsule contents were measured by quantifying the uronic acid contents. The plaque assay was used to detect bacterial sensitivity to bacteriophage in wild-type strain W14 and Δ wza mutant strain. The t test was used to compare whether there were differences in the contents of uronic acid in the capsules of wild-type strain W14 and Δ wza mutant strain. Results:The PCR results revealed that the Δ wza mutant strain was successfully constructed. Compared with wild-type strain W14, the growth curves of Δ wza on the solid plates demonstrated a slightly slower growth. However, no difference in growth was observed among wild-type strain W14 and Δ wza mutant strains in LB broth. The transmission electron microscope results showed that wza gene deletion resulted in the loss of capsule in bacteria. The uronic acid content assay suggested that the capsule content was significantly decreased in Δ wza mutant strain (45.963±2.795) μg/ml compared with wild-type strain W14 (138.800±5.201) μg/ml. There was a statistical difference between the two groups ( t=27.233, P<0.001). The plaque assay indicated that bacteria lost its sensitivity to bacteriophage when gene wza was deleted. Conclusion:Deletion of the wza gene impairs bacterial capsule formation ability and can affect bacterial sensitivity to bacteriophage phiW14.
3.Expression, purification and functional validation of phage depolymerase from hypervirulent Klebsiella pneumoniae serotype K1
Zheng FAN ; Yuchen CHEN ; Hongbo LIU ; Xiaohu CUI ; Zhoufei LI ; Tongtong FU ; Jing YUAN
Chinese Journal of Preventive Medicine 2024;58(9):1348-1353
Objective:To express and purify the phage depolymerase from hypervirulent Klebsiella pneumoniae (hv Kp) serotype K1 and validate its function. Methods:Phage that infected serotype K1-type hv Kp was isolated from hospital sewage. The biology and morphology of the phage were determined by plaque assay and transmission electron microscopy. The whole genome of the phage was sequenced by the Illumina HiSeq 2500 platform. The presence of depolymerase was determined by observing the plaque halo. Bioinformatic analysis and prokaryotic protein expression system were further used to predict and identify phage depolymerase. The depolymerase gene fragment was obtained by PCR and cloned into the pET28a expression vector, and the expression and purification of the depolymerase were completed in strain BL21. The depolymerase activities on the capsular polysaccharide of serotype K1-type hv Kp clinical isolates were detected by plaque assay and low-speed centrifugation assay. Results:A lytic phage (phiA2) that infected serotype K1-type hv Kp clinical isolate was isolated from hospital sewage. It was typical of the Caudovirales order and Autographiviridae family, and its whole genome was 43 526 bp in length and contained 51 coding domain sequences. The phage phiA2-derived depolymerase phiA2-dep was predicted, expressed and purified. The plaque assay and low-speed centrifugation assay indicated that the depolymerase phiA2-dep had good lytic activity on the capsular polysaccharide of serotype K1-type hv Kp clinical isolates. Conclusion:Depolymerase phiA2-dep can specifically degrade the capsular polysaccharide of serotype K1-type hv Kp, which has potential application value in treating bacterial infection.
4.The effect of wza gene deletion in Klebsiella pneumoniae on capsule formation and bacteriophage sensitivity
Zheng FAN ; Hongbo LIU ; Yuchen CHEN ; Xiaohu CUI ; Zhoufei LI ; Tongtong FU ; Jing YUAN
Chinese Journal of Preventive Medicine 2024;58(7):992-997
Objective:To investigate the effects of wza gene deletion in Klebsiella pneumoniae on capsule formation ability and bacteriophage sensitivity. Methods:The wza deletion mutant strain was constructed through a temperature-sensitive plasmid-mediated homologous recombination. The growth curves of W14 and Δ wza were detected by measuring the optical density OD 600. In order to analyze the effect of gene wza on bacterial capsule formation, wild-type strain W14 and Δ wza mutant strain were detected by transmission electron microscope, and their capsule contents were measured by quantifying the uronic acid contents. The plaque assay was used to detect bacterial sensitivity to bacteriophage in wild-type strain W14 and Δ wza mutant strain. The t test was used to compare whether there were differences in the contents of uronic acid in the capsules of wild-type strain W14 and Δ wza mutant strain. Results:The PCR results revealed that the Δ wza mutant strain was successfully constructed. Compared with wild-type strain W14, the growth curves of Δ wza on the solid plates demonstrated a slightly slower growth. However, no difference in growth was observed among wild-type strain W14 and Δ wza mutant strains in LB broth. The transmission electron microscope results showed that wza gene deletion resulted in the loss of capsule in bacteria. The uronic acid content assay suggested that the capsule content was significantly decreased in Δ wza mutant strain (45.963±2.795) μg/ml compared with wild-type strain W14 (138.800±5.201) μg/ml. There was a statistical difference between the two groups ( t=27.233, P<0.001). The plaque assay indicated that bacteria lost its sensitivity to bacteriophage when gene wza was deleted. Conclusion:Deletion of the wza gene impairs bacterial capsule formation ability and can affect bacterial sensitivity to bacteriophage phiW14.
5.Expression, purification and functional validation of phage depolymerase from hypervirulent Klebsiella pneumoniae serotype K1
Zheng FAN ; Yuchen CHEN ; Hongbo LIU ; Xiaohu CUI ; Zhoufei LI ; Tongtong FU ; Jing YUAN
Chinese Journal of Preventive Medicine 2024;58(9):1348-1353
Objective:To express and purify the phage depolymerase from hypervirulent Klebsiella pneumoniae (hv Kp) serotype K1 and validate its function. Methods:Phage that infected serotype K1-type hv Kp was isolated from hospital sewage. The biology and morphology of the phage were determined by plaque assay and transmission electron microscopy. The whole genome of the phage was sequenced by the Illumina HiSeq 2500 platform. The presence of depolymerase was determined by observing the plaque halo. Bioinformatic analysis and prokaryotic protein expression system were further used to predict and identify phage depolymerase. The depolymerase gene fragment was obtained by PCR and cloned into the pET28a expression vector, and the expression and purification of the depolymerase were completed in strain BL21. The depolymerase activities on the capsular polysaccharide of serotype K1-type hv Kp clinical isolates were detected by plaque assay and low-speed centrifugation assay. Results:A lytic phage (phiA2) that infected serotype K1-type hv Kp clinical isolate was isolated from hospital sewage. It was typical of the Caudovirales order and Autographiviridae family, and its whole genome was 43 526 bp in length and contained 51 coding domain sequences. The phage phiA2-derived depolymerase phiA2-dep was predicted, expressed and purified. The plaque assay and low-speed centrifugation assay indicated that the depolymerase phiA2-dep had good lytic activity on the capsular polysaccharide of serotype K1-type hv Kp clinical isolates. Conclusion:Depolymerase phiA2-dep can specifically degrade the capsular polysaccharide of serotype K1-type hv Kp, which has potential application value in treating bacterial infection.
6.Design of new type of acupressure wrist-ankle strap and its value for treating mild anxiety insomnia
Ying YUAN ; Wei-Hong LI ; Yan-Li YOU ; Qian-Xi DAI ; Fan-Fu FANG
Chinese Medical Equipment Journal 2024;45(4):78-82
Objective To design a new type of acupressure wrist-ankle strap and evaluate its clinical effect on the treatment of patients with mild anxiety insomnia.Methods The acupressure wrist-ankle strap was composed of a fixation band and an acupressure part.Totally 94 insomnia patients with mild anxiety at some hospital from October 2020 to January 2023 were selected as the subjects and divided into an observation group(n=48)and a control group(n=46)with the random number table method.The observation group was treated with the acupressure wrist-ankle strap,and the control group was given with placebos.The two groups were compared before and after treatment in terms of Pittsburgh sleep quality index(PSQI)and Hamilton anxiety scale(HAMA)with two-way repeated measures ANOVA.SPSS 21.0 software was used for data analysis.Results The PSQI and HAMA scores of the two groups were enhanced significantly after treatment(P<0.05).The two groups had statistically significant difference in the effect of the time factor on PSQI and HAMA scores(P<0.05),and also in the effect of the time x group interaction on PSQI and HAMA scores(P<0.05).Condusion The acupressure wrist-ankle strap contributes to improving the sleep and anxiety of mild anxiety insomnia patients in a self-administered,non-invasive,painless,and non-adverse manner.[Chinese Medical Equipment Journal,2024,45(4):78-82]
7.Clinical Features and Prognostic Analysis of Newly Diagnosed Diffuse Large B-cell Lymphoma Combined with Hemophagocytic Syndrome
Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Fei LIU ; Qiao-Lin CHEN ; Qi-Ke ZHANG
Journal of Experimental Hematology 2024;32(2):466-469
Objective:To compare the clinical features and prognosis between newly diagnosed diffuse large B-cell lymphoma(DLBCL)patients with and without hemophagocytic syndrome(HPS).Methods:The clinical data of 45 DLBCL patients in Gansu Provincial Hospital from January 2012 to December 2021 were retrospectively analyzed.The patients were divided into HPS group(15 cases)and non-HPS group(30 cases).The clinical features and prognosis of the two groups were compared,and survival analysis was performed using Kaplan-Meier method.Results:Patients with HSP were mostly characterized by fever,cytopenia and splenomegaly.The levels of ferritin and soluble CD25 increased in all patients.The level of fibrinogen decreased in 66.67%patients,while triglyceride increased in 53.33%patients,and bone marrow hemophagocytosis occurred in 80.00%patients.Compared with non-HSP group,the proportions of patients with advanced stage(Ann Arbor stage Ⅲ/Ⅳ)and lactate dehydrogenase(LDH)≥ 240 U/L were higher in HSP group(both P<0.05).The median survival time of HSP group was 8.0 months,which was significantly shorter than 45.5 months of non-HSP group(P<0.001).Conclusion:The DLBCL patients with HPS have later Ann Arbor stage,higher LDH and shorter overall survival time compared with patients without HPS.
8.Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma
Qing-Fen LI ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Yang-Yang ZHAO ; Xiu-Juan HUANG
Journal of Experimental Hematology 2024;32(2):499-504
Objective:To analyze the prognostic nutritional index(PNI),controlling nutritional status(CONUT)and fibrinogen/albumin ratio(FAR)levels in elderly patients with multiple myeloma(MM)and their prognostic impact.Methods:The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed.The optimal cut-off values for PNI,CONUT score and FAR were obtained by receiver operating characteristic(ROC)curve,which were used for grouping patients.The correlation of above three indexes with clinical parameters such as sex,serum calcium(Ca),β2-microglobulin(β2-MG),serum creatinine(Cr)in elderly MM patients were analyzed.The survival rates of patients with different levels of each index were compared.Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed.Results:The optimal cut-off values for PNI,CONUT score and FAR were 39.775,3.5 and 0.175,respectively,according to which the patients were divided into high and low group.Statistical analysis showed that there were significant differences in albumin level among different groups(all P<0.05).In addition,there was a significant difference in hemoglobin between high-PNI group and low-PNI group(P<0.05),while in sex distribution between high-FAR and low-FAR group(P<0.05).The survival rate of elderly MM patients with increased PNI,decreased CONUT score and FAR was higher(all P<0.05).Univariate and multivariate analysis showed that β2-MG,Cr,PNI,CONUT score and FAR were independent prognostic factors for elderly MM patients.Conclusion:PNI,CONUT score and FAR are related to some clinical indicators of elderly MM patients,and have an impact on the prognosis.
9.Clinical Features and Prognosis of Patients with CD5+Diffuse Large B-Cell Lymphoma
Xiu-Juan HUANG ; Jian YANG ; Xiao-Fang WEI ; Yuan FU ; Yang-Yang ZHAO ; Ming-Xia CHENG ; Qing-Fen LI ; Hai-Long YAN ; You-Fan FENG
Journal of Experimental Hematology 2024;32(3):750-755
Objective:To analyze the clinical characteristics and prognosis of patients with CD5+diffuse large B-cell lymphoma(DLBCL).Methods:The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed.According to CD5 expression,the patients were divided into CD5+group and CD5-group.The clinical characteristics and prognosis of the two groups were statistically analyzed.Results:The median age of patients in CD5+group was 62 years,which was higher than 56 years in CD5-group(P=0.048).The proportion of women in CD5+group was 62.96%,which was significantly higher than 41.79%in CD5-group(P=0.043).The proportion of patients with IPI score>2 in CD5+group was 62.96%,which was higher than 40.30%in CD5-group(P=0.031).Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+group were 27(3-77)and 31(3-76)months,respectively,which were both shorter than 30(5-84)and 32.5(4-83)months in CD5-group(P=0.047,P=0.026).Univariate analysis showed that advanced age,positive CD5 expression,triple or double hit at initial diagnosis,high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients.Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age.Conclusion:CD5+DLBCL patients have a worse prognosis than CD5-DLBCL patients.Such patients are more common in females,with advanced age and high IPI score,which is a special subtype of DLBCL.
10.Clinical Characteristics and Prognosis of Patients with Primary Bone Marrow Lymphoma
Qiao-Lin CHEN ; You-Fan FENG ; Yuan FU ; Fei LIU ; Wen-Jie ZHANG ; Yang CHEN ; Xiao-Fang WEI ; Qi-Ke ZHANG
Journal of Experimental Hematology 2024;32(4):1117-1120
Objective:To investigate the clinical characteristics and prognosis of primary bone marrow lymphoma.Methods:The clinical data of 6 patients with primary bone marrow lymphoma admitted to Gansu Provincial People's Hospital from February 2011 to March 2023 were collected,and their clinical characteristics and prognosis were retrospectively analyzed and summarized.Results:The median age of 6 patients was 61(52-74)years old.There were 2 males and 4 females.All patients had fever and abnormal blood routine examination.Physical examination and imaging examination showed no lymphadenopathy,no extranodal lesions in lung,gastrointestinal,liver and spleen,skin,etc.After strict exclusion of systemic lymphoma involvement in the bone marrow,the diagnosis was confirmed by bone marrow examination,5 cases were primary myeloid diffuse large B-cell lymphoma and 1 case was primary myeloid peripheral T-cell lymphoma(NOS).1 case abandoned treatment,5 cases received CHOP-like or combined R regimen,including 1 case of autologous stem cell transplantation.4 cases died and 2 case survived.The median OS was 5.5(1-36)months.Conclusion:The prognosis of primary marrow lymphoma is poor,and bone marrow-related examination is an important means of diagnosis.Diffuse large B-cell lymphoma is the most common histomorphologic and immune subtype,and autologous hematopoietic stem cell transplantation may improve the prognosis.

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