Objective To evaluate the renoprotective effects of zinc(Zn)supplementation in diabetes kidney disease(DKD)and to explore its impact on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Methods A total of 12 male OVE26 mice(spontaneous type 1 diabetes mellitus mice)aged 3 months and weighing approximately 24-27 g were selected and randomly assigned to a diabetes mellitus(DM)group and a zinc-treated DM(DM/Zn)group(n=6 each).In addition,12 age-matched male FVB mice weighing approximately 27-30 g were selected and randomly assigned to a non-diabetic control(Ctrl)group and a zinc-treated(Zn)group(n=6 each).Mice in the DM/Zn and Zn groups were given zinc supplementation for 3 months,with each mouse receiving 5 mg/kg of zinc sulfate by gavage every other day.Mice in the DM and Ctrl groups were given the same volume of normal saline.At the end of the experiment,the albumin-to-creatinine ratio(ACR)in urine was used as an indicator to evaluate renal function.Sirius red staining was performed to assess renal fibrosis in each group of mice.Western blotting was performed to determine the expression of fibrotic growth factors,including connective tissue growth factor(CTGF)and transforming growth factor-β1(TGF-β1),in renal tissue,and the protein expression of Nrf2,an antioxidant substance,and the protein expression levels of its downstream targets,including NAD(P)H quinone dehydrogenase 1(NQO1),heme oxygenase 1(HO-1),superoxide dismutase(SOD)-1,SOD-2,and catalase(CAT).Results 1)Compared to the Ctrl group,the urinary protein secretion levels of mice in the DM group exhibited progressive increase.After 3 months of zinc supplementation treatment,the urinary protein secretion levels of mice in the DM/Zn group decreased Compared to that of mice in the DM group,and the difference was statistically significant(P<0.05).2)Compared to that in the Ctrl group,the collagen deposition in the renal tissues of mice in the DM group increased,and the difference was statistically significant(P<0.05),while no obvious change was observed in mice in the DM/Zn group.Compared to the Ctrl group,mice in the DM group exhibited increased expression levels of CTGF and TGF-β1 in the renal tissues,but the expression levels decreased after zinc supplementation treatment,with the differences being statistically significant(P<0.05).3)Compared to that of the Ctrl group,the expression level of Nrf2 in the renal tissues of mice in the Zn and DM groups increased,and the level of Nrf2 in the renal tissues of mice in the DM/Zn group showed a further increase,with the differences being statistically significant(P<0.05).4)Compared to those of the Ctrl group,the protein expression levels of Nrf2 downstream target genes,including NQO1 and HO-1,in the renal tissues of mice in the Zn group increased,and the levels of NQO1 and HO-1 in the renal tissues of mice in the DM/Zn group showed a further increase,with the differences being statistically significant(P<0.05).Compared to those of the mice in the Ctrl group,the protein expressions of Nrf2 downstream target genes,including SOD-1,SOD-2,and CAT of in the renal tissues of the mice in the Zn group increased,while the expression levels of SOD-1,SOD-2,and CAT in the renal tissues of the mice in the DM group decreased,with the differences being statistically significant(P<0.05).Zn supplementation could completely inhibit these changes(P<0.05).Conclusions Zn supplementation has therapeutic effects on DKD and mitigates T1DM-induced renal dysfunction and oxidative injury in mice,which may be associated with the activation of the Nrf2 antioxidant signaling pathway.

To evaluate the effect of bronchoalveolar lavage (BAL) on the clinical prognosis of children with macrolide drug-resistant Mycoplasma pneumoniae pneumonia (MRMPP) in a retrospective cohort study based on propensity score matching (PSM).A retrospective cohort study based on propensity score matching retrospectively collected the clinical data of hospitalized patients diagnosed with mycoplasma macrolide drug-resistant pneumonia (MRMPP) in Respiratory Department of Hunan Children′s Hospital from January 2020 to August 2023. According to whether bronchoalveolar lavage (BAL) was performed during hospitalization, the children were divided into BAL group and non-BAL group, and the baseline information of the two groups was matched by propensity scores, and the clinical prognosis was compared. A total of 302 children were screened, and 150 cases were successfully matched, including 59 cases in the BAL group and 91 cases in the non-BAL group. The results showed that the differences between the non-BAL group and the BAL group before PSM( P<0.05) were significantly different in age [(4.60±2.97)years vs (5.41±3.02) years, t=-2.273, P=0.024], shortness of breath (9.4% vs 22.5%, χ 2=9.864, P=0.002), and radiographic manifestations [lung interstitial changes (29.8% vs 15.3%, χ 2=8.009, P=0.005), lung consolidation (17.3% vs 55.9%, χ 2=48.457, P<0.001), spotted flaky infiltrates (52.4% vs 27.9%, χ 2=17.056, P<0.001)], bacterial infection (3.2% vs 9.2%, χ 2=4.845, P=0.028), duration of azithromycin or doxycycline use [4(2, 5) days vs 5(3, 6) days, Z=-2.374, P=0.018], White Blood Cell Count at admission [7.94 (6.25, 10.34)×10 9/L vs 7.21 (5.65, 9.01)×10 9/L, Z=-2.445, P=0.014], D Dimer [0.58 (0.44, 0.83) μg/ml vs 0.80 (0.52, 1.12) μg/ml, Z=-3.154, P=0.002], but there was no significant difference between the two groups in the above indexes after PSM ( P>0.05). The duration of hospitalization, cough relief, disappearance of rales and fever in the BAL group was shortened in the BAL group compared with that in the non-BAL group [5 (4, 7) days vs 7 (5, 8) days, Z=-2.373, P=0.018], and the difference was statistically significant ( P<0.05). Linear regression analysis of PSM cohort study showed that BAL was negatively correlated with fever time (β=-4.369, 95% CI:-8.600--0.138, P<0.05). In conclusion, BAL can shorten the fever time of MRMPP, and early BAL in addition to conventional treatment has a positive effect on the prognosis of children.

To evaluate the effect of bronchoalveolar lavage (BAL) on the clinical prognosis of children with macrolide drug-resistant Mycoplasma pneumoniae pneumonia (MRMPP) in a retrospective cohort study based on propensity score matching (PSM).A retrospective cohort study based on propensity score matching retrospectively collected the clinical data of hospitalized patients diagnosed with mycoplasma macrolide drug-resistant pneumonia (MRMPP) in Respiratory Department of Hunan Children′s Hospital from January 2020 to August 2023. According to whether bronchoalveolar lavage (BAL) was performed during hospitalization, the children were divided into BAL group and non-BAL group, and the baseline information of the two groups was matched by propensity scores, and the clinical prognosis was compared. A total of 302 children were screened, and 150 cases were successfully matched, including 59 cases in the BAL group and 91 cases in the non-BAL group. The results showed that the differences between the non-BAL group and the BAL group before PSM( P<0.05) were significantly different in age [(4.60±2.97)years vs (5.41±3.02) years, t=-2.273, P=0.024], shortness of breath (9.4% vs 22.5%, χ 2=9.864, P=0.002), and radiographic manifestations [lung interstitial changes (29.8% vs 15.3%, χ 2=8.009, P=0.005), lung consolidation (17.3% vs 55.9%, χ 2=48.457, P<0.001), spotted flaky infiltrates (52.4% vs 27.9%, χ 2=17.056, P<0.001)], bacterial infection (3.2% vs 9.2%, χ 2=4.845, P=0.028), duration of azithromycin or doxycycline use [4(2, 5) days vs 5(3, 6) days, Z=-2.374, P=0.018], White Blood Cell Count at admission [7.94 (6.25, 10.34)×10 9/L vs 7.21 (5.65, 9.01)×10 9/L, Z=-2.445, P=0.014], D Dimer [0.58 (0.44, 0.83) μg/ml vs 0.80 (0.52, 1.12) μg/ml, Z=-3.154, P=0.002], but there was no significant difference between the two groups in the above indexes after PSM ( P>0.05). The duration of hospitalization, cough relief, disappearance of rales and fever in the BAL group was shortened in the BAL group compared with that in the non-BAL group [5 (4, 7) days vs 7 (5, 8) days, Z=-2.373, P=0.018], and the difference was statistically significant ( P<0.05). Linear regression analysis of PSM cohort study showed that BAL was negatively correlated with fever time (β=-4.369, 95% CI:-8.600--0.138, P<0.05). In conclusion, BAL can shorten the fever time of MRMPP, and early BAL in addition to conventional treatment has a positive effect on the prognosis of children.

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of →4)-α-D-GalAp-(1 → and →6)-β-D-Galp-(1 → and the branched structure of →5)-α-L-Araf-(1 →.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akker-mania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia-reperfusion(Ⅱ/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte cluster 1(EC1),enterocyte cluster 3(EC3),and enterocyte cluster 8(EC8)were newly discovered cells in ischemia 45 min/reperfusion 720 min(I 45 min/R 720 min)group.EC1 and EC3 played roles in digestion and absorption,and EC8 played a role in cell junctions.For TA cells,after ischemia 45 min/reperfusion 90 min(I 45 min/R 90 min),many TA cells at the stage of proliferation were identified.For Paneth cells,Paneth cluster 3 was observed in the resting state of normal jejunum.After I45 min/R 90 min,three new subsets were found,in which Paneth cluster 1 had good antigen presentation activity.The main functions of goblet cells were to synthesize and secrete mucus,and a novel subcluster(goblet cluster 5)with highly proliferative ability was discovered in I 45 min/R 90 min group.As a major part of immune system,the changes in T cells with important roles were clarified.Notably,enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells,TA cells,Paneth cells,and goblet cells to elicit intercellular communication.One marker known as glutathione S-transferase mu 3(GSTM3)affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases(MAPK)signaling during Ⅱ/R injury.The data on the heterogeneity of intestinal cells,cellular communication and the mechanism of GSTM3 provide a cellular basis for treating Ⅱ/R injury.

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.How-ever,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hy-drolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and pri-mary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and β-muricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nu-clear factor-kappaB(NF-κB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

Objective:To explore the efficacy and compliance of e-aid cognitive behavioral therapy (eCBTI) in patients with situational insomnia among different age groups.Methods:A total of 194 patients with situational insomnia were recruited via a campaign of the " Prevention and Protection Handbook Against Epidemic" from March to April 2020 in Guangzhou, China.Participants were divided into two groups according to age: under 35 years old ( n=87) and 35 years old and above ( n=107). They all received one-week eCBTI intervention.Insomnia severity index (ISI), Pre-sleep arousal scale (PSAS) and Hospital anxiety and depression scale (HADS) were used to evaluate the severity of insomnia for all participants pre- and post-intervention.The change of each scale within the group and the reduction rate of each scale between groups were compared using t test and one-way ANOVA. Results:(1) Intervention efficacy: in the <35-year-old group, compared with baseline, the scores of ISI scale ((9.2±4.1), (14.8±5.1)), PSAS cognitive arousal subscale ((18.5±8.4), (23.5±6.6)), PSAS((34.3±15.8), (40.3±10.7)), HADS depression subscale ((5.8±3.6), (8.5±4.6)) and HADS anxiety subscale((7.1±3.9), (9.5±4.5) )were statistically significant after eCBTI intervention ( t= 2.88-8.80, all P<0.01), but there was no significant difference in score of PSAS body subscale ((15.8±7.8), (16.8±5.7)). In ≥35-year-old group, compared with baseline, the scores of ISI scale ((9.7±4.2), (14.4±4.3)), HADS depression subscale ((4.6±2.2), (6.6±3.5))and PSAS cognitive arousal subscale ((16.9 ±8.5), (20.0±5.8))were significantly different after intervention ( t= 2.90-6.86, all P<0.01), meanwhile the scores of PSAS body subscale ((14.3±8.0), (13.9±5.2)), PSAS((32.2±16.5), (33.9±9.2)), HADS anxiety subscale((6.1±3.2), (7.0±3.5)) were not statistically significant (all P>0.05). There was no significant difference in the score reduction rate between the two groups before and after intervention (all P>0.05). (2) Compliance: 86 cases dropped out, and the dropout rate was 61.3%.Totally 75 cases (38.7%) completed the 7-day treatment, and 119 cases (61.3%) completed the treatment within 1-6 days.Further study found that there was statistically significant difference in the reduction rate of ISI total score among the three groups with excellent, good and poor compliance ( F=5.655, P=0.004). Conclusion:eCBTI has a good effect on situational insomnia in different age groups, and there is no difference in treatment compliance.

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

Objective:To investigate the difference of vitamin A and E levels in children with different respiratory diseases at different ages.Methods:A total of 671 children in Hunan Children's Hospital from July 2017 to October 2019 were selected as the disease group, including 197 cases of pneumonia, 152 cases of recurrent respiratory tract infection, 91 cases of asthma, 88 cases of cough variant asthma and 143 cases of Mycoplasma pneumoniae pneumonia; At the same time, 245 healthy children were selected as the normal group. The serum vitamin A and vitamin E levels of the two groups were detected by high performance liquid chromatography (HPLC).Results:⑴ The vitamin A level [(0.31±0.09)mg/L] of the disease group was lower than the normal group [(0.35±0.25)mg/L], and the vitamin E level [(8.92±2.57)mg/L] was lower than the normal group [(9.62±2.79)mg/L], with statistically significant difference ( P<0.05); ⑵ The level of vitamin A in the disease group at the age of >1-3 years [(0.32±0.09)mg/L] was lower than that in the normal group of the same age group [(0.35±0.08)mg/L]; the level of vitamin A in the disease group at the age of >3-6 years old [(0.30±0.08)mg/L] was lower than that of the same age group [(0.32±0.07)mg/L], with statistically significant difference ( P<0.05); ⑶ The vitamin E level of the disease group at >1-3 years old [(9.23±2.56)mg/L], >3-6 [(8.02±1.86)mg/L] and >6-14 years old [(8.02±1.82)mg/L] were lower than that of the same age normal group [(9.76±2.81)mg/L, (9.67±2.87)mg/L, (9.19±2.58)mg/L], with statistically significant difference ( P<0.05); ⑷ There were significant differences in vitamin A levels among different age in disease group ( P<0.05). Among them, the children with high risk of subclinical deficiency accounted for the largest proportion (45.78%) in the 6-month-1-year-old group, and the proportion of children with normal vitamin A levels in other age groups was the largest; ⑸ There are significant differences in vitamin E levels in different age groups in the disease group ( P<0.05), the levels in the normal range accounts for the largest proportion of all ages; ⑹ The levels of vitamin A and vitamin E in mycoplasma pneumoniae infection group were increased compared with in recurrent respiratory infection group , asthma group, and cough variant asthma group, and the difference was statistically significant ( P<0.05). Compared with the pneumonia group, the level of vitamin E increased in the recurrent respiratory infection group, and the difference was statistically significant ( P<0.05); The vitamin E levels in the cough variant asthma group were reduced compared with the repeated respiratory infection group, asthma group and pneumonia group ( P<0.05). Conclusions:The Vitamin A and E levels of children suffering from respiratory diseases are lower than those of normal children. The Vitamin A and E levels of different respiratory diseases and different age groups are different. Vitamin A and E supplementation may be significantly targeted according to different ages and different respiratory diseases in clinical practice.

OBJECTIVE: To test the validity and reliability of the Chinese version of Mobile Phone Involvement Questionnaire (MPIQ) in college students. METHODS: We assessed the degree of phone dependence using the MPIQ among 2122 college students. One month later, 60 students were randomly selected for assessment with the MPIQ, and the ROC curve was generated to evaluate the true positive rate (sensitivity) and false positive rate at different cutoff values to determine the optimal cutoff score of the MPIQ. RESULTS: Among 98.9% of the participants who finished all the items, their MPIQ scores show a positive skew distribution and a one-factor structure. The load scores of the items ranged from 0.54 to 0.77. The Cronbach's α coefficient and the Spearman Brown split reliability were 0.84 and 0.83, respectively, the correlation coefficients between the items and total score ranged from 0.54 to 0.76, and the test-retest reliability was 0.48 ( < 0.001). At the optimal cut-off score of 32, the sensitivity and the specificity of the MPIQ were 0.634 and 0.652, respectively. CONCLUSIONS At the optimal cut-off score of 32, the MPIQ has good validity and reliability for assessing phone dependence among college students.
Cell Phone ; Humans ; Reproducibility of Results ; Students ; Surveys and Questionnaires