Objective To explore the effects of fecal microbiota transplantation on blood uric acid(UA)metabolism,adverse reactions,and gout control in patients with refractory gout.Methods A total of 102 patients with refractory gout in the First Affiliated Hospital of Medical College of Shantou University from June 2020 to June 2023 were randomly divided into two groups,with 51 cases in each group.Control group received benzbromarone and febuxostat treatment,while the observation group re-ceived fecal microbiota transplantation.The gout control status and occurrence of adverse reactions were observed in both groups;intestinal flora,UA,levels of C-reactive protein(CRP),interleukin-18(IL-18),interleukin-6(IL-6),and scores of joint pain,swelling and limited mobility were compared between the two groups before and after treatment.Results Five patients in each group were lost to follow-up.The total gout control rate in the observation group was 89.13％,which was significantly higher than 69.57％ in the control group(P＜0.05).At 4 and 12 weeks after treatment,the levels of Escherichia coli,UA,CRP,IL-18 and IL-6 as well as the scores of joint swelling,pain and limited mobility in the observation group were significantly lower than those in the control group,while the lev-els of Bifidobacterium,Lactobacillus and Bifidobacterium to Escherichia coli(B/E)ratio were signifi-cantly higher than those in the control group(P＜0.01).The total incidence of adverse reactions was 10.87％ in the observation group and 6.52％ in the control group,with no significant between-group difference(P＞0.05).Conclusion Fecal microbiota transplantation has a definite therapeutic effect for patients with refractory gout,which can significantly reduce UA level and control clinical symptoms,and its mechanism may be related to the correction of intestinal flora imbalance.

Objective To explore the regulatory mechanism of NFE2L2/KEAP1 in alveolar bone repair induced by periodontitis.Methods A rat periodontitis model was established and divided into four groups:Control group(n=6);Periodontitis model group(n=6);Periodontitis+lentivirus empty vector group(n=6);Periodontitis+NFE2L2 overexpression plasmid group(n=6).Histopathological changes in each group were observed using HE staining.TRAP staining was used to detect osteoclast positivity,while ELISA was employed to measure inflammatory cytokine levels in tissues.Immunofluorescence and qPCR were used to detect NFE2L2 expression,and western blot was used to assess the expression of osteogenic proteins ALPL2,RUNX2,and COL1.Primary periodontal ligament cells(hPDLCs)were cultured,and cells were transfected to overexpress NFE2L2 and KEAP1.The cells were divided into six groups:Normal group;Model group;pcDNA-NC group;pcDNA-NFE2L2 group;pc-NFE2L2+pcDNA-NC group;pc-NFE2L2+pcDNA-KEAP1 group.A cellular model was established,and the morphology of primary hPDLCs was observed under a microscope.Cell proliferation was assessed using CCK-8.Osteogenic mineralization was observed using alizarin red staining,and western blot was used to detect osteogenic proteins and autophagy markers.Cell migration was observed using a scratch assay.Results(1)After model induction,redness,swelling of the gums,extensive inflammatory infiltration,and alveolar bone resorption were observed,confirming successful model establishment.Partial tissue recovery occurred after NFE2L2 overexpression via lentivirus.(2)After model induction,osteoclast positivity increased,confirming successful model establishment.Overexpression of NFE2L2 reduced osteoclast positivity(P<0.001).(3)After model induction,levels of IL-1β,IL-10,and TNF-α were significantly higher than in the normal group(P<0.05),confirming successful model establishment.Transfection with NFE2L2 lentivirus reduced inflammatory cytokine levels(P<0.0001).After model induction,osteogenic protein expression decreased compared to the normal group,but overexpression of NFE2L2 increased osteogenic protein expression(P<0.05).(5)LPS treatment significantly reduced cell viability,while NFE2L2 overexpression enhanced it(P<0.0001).(6)LPS treatment reduced calcified nodules,while NFE2L2 overexpression increased them.Addition of pcDNA-KEAP1 reduced mineralized nodules.(7)LPS treatment decreased osteogenic protein expression,while NFE2L2 overexpression increased it.However,addition of pcDNA-KEAP1 reduced osteogenic protein expression(P<0.05).(8)LPS treatment reduced cell migration,whereas NFE2L2 overexpression enhanced it(P<0.0001).(9)Expression of autophagy markers decreased after LPS treatment,but increased after transfection with NFE2L2 plasmid.However,addition of pcDNA-KEAP1 reduced the expression of autophagy markers(P<0.05).Conclusion This study identified the regulatory role of NFE2L2/KEAP1 in periodontitis,providing a scientific basis for the treatment of periodontitis.

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven-tion of neurobehavioral development delays in young children.Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pe-diatric Heart Scale)with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays,and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale,the basic information of the young children and their mothers at the time of birth were investigated,as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected.Results A total of 271 young children were included,196 males and 75 females.Young children had the lowest developmental quotient(DQ)in the language domain among the five domains(P＜0.001).Multiple lin-ear regression models showed:compared with girls,the language domain DQ of boys decreased by 5.321 points(P=0.049,95％CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95％CI:-8.316--0.631).Compared with young children via natural vaginal delivery(NVD),the gross motor domain DQ of young children via caesarean section(CS)decreased by 4.890 points(P=0.008,95％CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95％CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95％CI:-12.826--2.416),per-sonal-social domain DQ decreased by 6.232 points(P=0.001,95％CI:-10.006--2.457).The results of bi-nary logistic regression models showed,compared with young children via NVD,the risk of gross motor domain retar-dation in young children increased(OR=1.763,95％CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95％CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95％CI:1.080-10.124).Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains,boys had lower DQ in language domain and personal-social domain than girls,and the development of young children via CS was slower than that via NVD.Fo-cus should be on the language development of young children especially on the language and personal-social devel-opment of boys.Carefully chose delivery way.Focus should be placed on assessment of young children's comprehen-sive neurobehavioral development in early time.

Objective To analyze the live birth situation after intrauterine adhesions separation opera-tion in the patients with different types of intrauterine adhesions(IUA)and its influencing factors.Methods The medical records data in 188 patients with hysteroscopic electrotomy separation for IUA and pregnancy within postoperative two years in the Affiliated Beijing Obstetrics and Gynecology Hospital of Cap-ital Medical University from January 2010 to January 2022 were analyzed retrospectively.The basic data and pregnancy outcomes of the patients were collected.The main influencing factors of postoperative live birth were analyzed by univariate analysis and multivariate logistics regression.Results Among 188 cases of IUA,there were 163 cases of live births with a live birth rate of 86.7％.There was no statistical difference in the composition situation of conception methods and delivery methods among the patients with different degrees of IUA(P＞0.05),and there was statistical difference in postpartum bleeding volume(P＜0.05).There were significant differences in the composition of placenta implantation,conducting clamp and uterine clearance a-mong the patients with different degrees of IUA(P＜0.05).The univariate analysis results showed that arti-ficial abortion,early pregnant curettage(P=0.008)and labor induction in second trimester(P＜0.001)were the influencing factors of postoperative live birth;the multivariate analysis results showed that induction of la-bor in the second trimester(95％CI:0.02-0.35,P=0.001)was the influencing factor of postoperative live birth.Conclusion Placenta-related diseases and postpartum hemorrhage are prone to occur after IUA opera-tion,and the uterine operation during delivery is increased.The patients with history of previous multiple in-duced abortions and mid-term induced labor should be vigilant against the occurrence of adverse pregnancy outcomes.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

It has been reported that ODB genes play an important role in homologous recombination-directed DNA repair, suggesting their potential applications in plant breeding. To analyze the expression characteristics of tobacco NtODB gene, the cDNA sequence of NtODB was obtained using in silico cloning technique. The physicochemical properties, signal peptide, and advanced structures of the predicted protein were analyzed using bioinformatics tools. The results showed that the NtODB gene has a 579-bp open reading frame which encodes a protein with 192 amino acid residues. The protein NtODB is predicted to be alkaline and hydrophilic. Real-time quantitative PCR showed that NtODB was constitutively expressed in different tissues. Subcellular localization showed that NtODB was mainly expressed in cell membrane and chloroplast. These results may help us to better understand and elucidate the roles of ODB genes in the homologous recombination-directed DNA repair.
Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; Computational Biology ; Computer Simulation ; DNA, Complementary ; Phylogeny ; Plant Breeding ; Tobacco/genetics*

Objective:To explore the clinical value of peripheral blood lymphocyte subsets in the differential diagnosis of BK virus nephropathy (BKVN) in renal transplantation recipients.Methods:From 2014 to 2018, a total of 172 renal transplant recipients were recruited. Their peripheral blood lymphocyte subsets were detected. According to the pathological puncture results of transplanted kidney, they were divided into acute rejection group (AR, n=68), BKVN group ( n=73) and stable graft function group (STA, n=31). The proportion and absolute number of peripheral blood lymphocyte subsets in each group were measured by flow cytometry and the proportion and absolute count of peripheral blood lymphocyte subsets in each group compared. Results:The proportion and absolute number of CD19 + B cells were markedly lower in BKVN group than those in AR group ( P=0.005, 0.003; 8.5% vs 13.2%, 0.094×10 9/L vs 0.202×10 9/L) and STA group ( P=0.005, 0.003; 8.5% vs 14.8%, 0.094×10 9/L vs 0.198×10 9/L); the proportion of CD3 + CD8 + T cells was significantly higher in BKVN group than that in AR group ( P=0.013; 36.9% vs 31.2%). In addition, no obvious difference existed in the proportion and absolute number of lymphocytes, CD3 + T, CD3 + CD4 + T and CD16 + CD56 + natural killer (NK) among three groups ( P>0.05). No obvious difference existed in the proportion of CD3 + CD4 + / CD3 + CD8 + T cells among three groups ( P>0.05). Conclusions:No difference exists in T cell-related lymphocyte subsets between BKVN and acute rejection recipients. However, the number and proportion of CD19 + B cells decrease markedly in BKVN.

Objective: Practice of setting up campus clinics in school,to explore adolescent outpatient service mode to better meet the diversified demands of teenagers,and to promote more effective implementation of adolescent health care. Methods: Campus-based adolescent outpatient clinics were established in 2 universities in Chongqing,a questionnaire survey was conducted among 136 students who participated in the consultation, campus-based outpatient services and adolescents’ satisfaction towards the services were analyzed. Hospital adolescent outpatient services were compared before and after the establishment of campus adolescent clinic. Results: Most of adolescent outpatient clinic in hospitals offered disease-based treatment instead of consultation. The overall satisfaction rate was 94.85%, and the satisfaction towards service ability, communication skills, outpatient time arrangement, and privacy protection was 96.32%, 96.32%, 88.97% and 94.12%, respectively. After the establishment of campus adolescent outpatient clinics, adolescent outpatient services in hospital increased dramatically including consultation. Conclusion It is necessary to offer adolescent outpatient services in schools, which are more helpful for the diversified demands of teenagers.

Objective To investigate the value of high-resolution 3.0T MR in the assessment of local infiltration of preoperative rectal cancer.Methods A total of 168 patients pathologically proved rectal cancer underwent both conventional pelvic and rectal high-resolution before operation, and the imaging findings were reviewed retrospectively.The accuracy of preoperative high-resolution 3.0T MR in prediction of pathological staging was assessed,and the characteristic imaging features of local infiltration in preoperative rectal cancer were discussed.Results The relationship between circumference invasion of colorectal cancer and the pathological T staging was moderately positive (rs=0.530,P=0.003).Compared the staging of colorectal cancer on MRI with pathologic T staging,the overall diagnostic accuracy was 84.52%,and there was a stronger correlation between MRI findings and pathological staging (rs=0.837,P=0.001).The best single parameters for diagnosing T3 stage rectal cancer on MRI were nodular convex of the tumor and muscular signal interruption,with 91.1% specificity and 89.7% sensitively respectively.And the best combination of parameters was the cord appearence of intestinal wall and muscular signal interruption,with 89.3% specificity and 78.0% sensitively respectively.Conclusion High-resolution 3.0T MR can be preferable to evaluating local infiltration of rectal cancer, showing a higher clinical value to asseee T staging of preoperative rectal cancer.