Kidney is a highly energy-demanding organ rich in mitochondria. Numerous studies have indicated that mitochondria play a crucial role in maintaining normal kidney function and in the pathogenesis of various kidney diseases. Mitochondrial DNA is the exclusive genome of mitochondria. Damage to mtDNA not only leads to mitochondrial dysfunction and degradation of mitochondrial quality, but also acts as an endogenous inflammatory molecule, activating various inflammatory pathways, which contribute to cellular damage and the progression of kidney diseases. This article reviews the mechanisms of mitochondrial DNA damage and its significant role in triggering inflammatory injury in kidney diseases. Additionally, it summarizes the current research progress on various intervention strategies targeting this type of damage.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective:To investigate the effects of regulation of GATA6 expression by long non-coding RNA(lncRNA)GATA6 antisense RNA 1(GATA6-AS1)on the proliferation,apoptosis,and metastasis of 5-fluorouracil(5-FU)resistant gastric cancer(GC)cells SGC7901/5-FU,and to explore the underlying mechanisms. Methods:Parental SGC7901 cells and SGC7901/5-FU cells were used as controls(treated with blank culture medium).Empty vector pcDNA3.1(control for GATA6-AS1 overexpression),recombinant vector pcDNA3.1-GATA6-AS1(for GATA6-AS1 overexpression),shNC(negative control for GATA6-AS1 silencing)or shGATA6-AS1(for GATA6-AS1 silencing)were transfected into SGC7901/5-FU cells by Lipofectamine 2000 to overexpress or silent GATA-AS1.The mRNA expression of GATA6-AS1 and GATA6 in cells of different treatment groups were examined by real-time fluorescence quantitative PCR.After 5-FU treatment,the proliferation,migration,invasion and apoptosis were analyzed by CCK-8 assay,wound-healing assay,Transwell assay,and flow cytometry(FCM)assay,respectively.The protein expression levels of Bax,Bcl-2,Caspase 3 and GATA6 in different treatment groups were examined by Western blotting.The stability of GATA6 mRNA was evaluated after α-amanitin treatment.The relationship between GATA6-AS1 and GATA6 was studied by RNA pull-down experiment.Furthermore,the SGC7901 cell transplantation tumor model was established using Balb/c nude mice,and the grouping was the same as in vitro experiments with 12 mice in each group.The tumor growth was recored and the tumor inhibition rate was calculated after 5-FU treatment.The histopathological changes of tumor tissue in each group was assessed by HE staining.The protein expression of proliferating cell nuclear antigen(PCNA)in tumor tissues of nude mice in each group was detected by Western blotting. Results:Compared with parental SGC7901 cells(control group),the expression of GATA6-AS1 and GATA6 mRNA was significantly downregulated in SGC7901/5-FU cells(P＜0.05);the proliferation,migration and invasion of SGC7901/5-FU cells was significantly decreased while the apoptosis of SGC7901/5-FU cells was significantly decreased(P＜0.05);the protein expression levels of GATA6,Bax and Caspase 3 were significantly decreased while that of Bcl-2 was significantly increased(P＜0.05).Compared with SGC7901/5-FU-pcDNA group,the above changes showed opposite trends in SGC7901/5-FU cells overexpressing GATA6-AS1.Compared with SGC7901/5-FU-shNC group,the expression of GATA6-AS1 and GATA6 mRNA was significantly downregulated in GATA6-AS1-silencing SGC7901/5-FU cells(P＜0.05);the proliferation,migration and invasion of GATA6-AS1-silencing SGC7901/5-FU cells was significantly decreased while apoptosis of GATA6-AS1-silencing SGC7901/5-FU cells was significantly decreased(P＜0.05);the protein expression levels of GATA6,Bax and Caspase 3 were significantly decreased while that of Bcl-2 was significantly increased(P＜0.05).GATA6-AS1 can increase the stability of GATA6 mRNA and positively regulate the expression of GATA6.In vivo characterization showed that,compared with mice transplanted with parental SGC7901 cells,the tumor volume and PCNA protein expression in tumor tissues were significantly increased in mice transplanted with drug resistant SGC7901/5-FU cells after 5-FU treatment(P＜0.05).Mice in SGC7901/5-FU-GATA6-AS1 group showed significantly reduced tumor volume and PCNA protein expression compared with the SGC7901/5-FU-pcDNA group(P＜0.05),and pathological analysis of the tumor tissues revealed milder development of GC in SGC7901/5-FU-GATA6-AS1 group.Whereas,mice in SGC7901/5-FU-shGATA6-AS1 group showed significantly increased tumor volume and PCNA protein expression compared with the SGC7901/5-FU-shNC group(P＜0.05),and histopathological analysis of the tumor tissues revealed severer development of GC in SGC7901/5-FU-shGATA6-ASl group. Conclusion:Overexpression of GATA6-AS1 can promote the expression of GATA6,inhibit the growth of GC cells,and thus reverse the resistance of SGC7901/5-FU cells to 5-FU.

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Objective To investigate the consistency between Shengxiang (S) and Xinbo (X) real-time PCR methods in the quantification of HBV RNA. Methods In the prospective follow-up cohort of 108 chronic hepatitis B (CHB) patients established from July 2007 to August 2008, 20 patients with HBeAg seroconversion were selected, and 20 patients without seroconversion were selected by propensity score matching at a ratio of 1∶ 1. The two quantification methods from S and X companies were used, and a retrospective analysis was performed for HBV RNA in serum samples at baseline and weeks 12, 24, and 48. The paired t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data. The Pearson correlation coefficient, intraclass correlation coefficient (ICC), and the Bland-Altman method were used to evaluate the consistency of the two quantification methods. Results A total of 132 serum samples were tested by S reagent, and 154 were tested by X reagent; the detection rate of HBV RNA was 100% by both reagents. A total of 131 serum samples were tested by both reagents, with 34 samples at baseline and 29, 35, and 33 samples, respectively, at weeks 12, 24, and 48 of follow-up; at these four time points, the HBV RNA quantification data detected by X reagent were significantly higher than those detected by S reagent (5.75±1.64/5.43±1.73/5.13±1.54/4.76±1.55 log 10 copies/mL vs 4.80±1.48/4.52±1.53/4.10±1.50/3.92± 1.43 log 10 copies/mL, t =8.348, t =5.341, Z =-5.086, Z =-4.762, all P < 0.001). The correlation analysis of the two methods showed a Pearson correlation coefficient of 0.915 (95% confidence interval [ CI ]: 0.836-0.957) and an ICC of 0.771(95% CI : -0.021 to 0.931) at baseline, a Pearson correlation coefficient of 0.849(95% CI : 0.701-0.927) and an ICC of 0.733(95% CI : 0.138-0.902) at week 12, a Pearson correlation coefficient of 0.951(95% CI : 0.905-0.975) and an ICC of 0.776(95% CI : -0.058 to 0.942) at week 24, and a Pearson correlation coefficient of 0.933(95% CI : 0.867-0.967) and an ICC of 0.804(95% CI : -0.014 to 0.944) at week 48 (all P < 0.05). The Bland-Altman analysis showed that the difference of 96.18%(126/131) samples tested by the two methods was within the mean difference±1.96 standard deviation. Conclusion HBV RNA quantification by X reagent is higher than that by S reagent, while the two real-time PCR quantification methods show a good consistency in CHB patients with HBeAg seroconversion and those without seroconversion.

Objective:To evaluate the effect of deep learning based on DWI and fluid attenuated inversion recovery (FLAIR) to construct a prediction model of the onset time in acute stroke.Methods:A total of 324 cases of acute stroke with clear onset time, from January 2017 to May 2020 in Nanjing First Hospital, were retrospectively enrolled and analyzed. The patients were divided into a training set of 226 patients and a test set of 98 patients according to the complete randomization method using a 7∶3 ratio, and the patients were divided into ≤ 4.5 h and >4.5 h according to symptom onset time in each group. The acute infarction areas on DWI and the corresponding high signal area on FLAIR were manually outlined by physician. Using the InceptionV3 model as the basic model for image features extraction, the deep learning prediction model based on single sequence (DWI, FLAIR) and multi sequences (DWI+FLAIR) were established and verified. Then the area under curve (AUC), accuracy of human readings, single sequence model and multi sequence model in predicting the acute stroke onset time from imaging were compared.Results:DWI-FLAIR mismatch was found in 94 cases (94/207) of patients with symptom onset time from imaging ≤ 4.5 h, while in 28 cases (28/117) of patients with symptom onset time from imaging >4.5 h. ROC analysis showed that the AUC of DWI-FLAIR mismatch in predicting acute stroke onset time from imaging was 0.607, and the accuracy was 60.2%. The prediction model of deep learning based on single sequence showed that the AUC of FLAIR was 0.761 and the accuracy was 71.4%; the AUC of DWI was 0.836 and the accuracy was 81.6%. The AUC of predicting stroke onset time based on the multi-sequence (DWI+FLAIR) deep learning model was 0.852, which was significantly better than that of manual identification ( Z = 0.617, P = 0.002), FLAIR sequence deep learning model ( Z = 2.133, P = 0.006) and DWI sequence deep learning model ( Z = 1.846, P = 0.012). Conclusion:The deep learning model based on DWI and FLAIR is superior to human readings in predicting acute stroke onset time from imaging, which could provide guidance for intravenous thrombolytic therapy for acute stroke patients with unknown onset time.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To investigate the relationship between the composition of vaginal microbiota and the course of cervical precancerous lesion.Methods A total of 64 vaginal swabs were collected from 22 healthy women, 18 CINⅠ patients and 24 CINⅡ/Ⅲ patients who visited Obstetrics and Gynecology of the Second Xiangya Hospital of Central South University during July 2014 and July 2015.The Bacterial genomic DNA was extracted and the V3 and V4 hypervariable regions of 16S rRNA were amplified and high-throughput sequenced.The abundance and composition of vaginal microbiota were analyzed by Uparse, Mothur and LefSe statistical software.Results There was no significant difference in Alpha diversity index between CINⅡ/Ⅲ group(Chao:63±32;ACE:72±38;Simpson:0.70±0.27;Shannon:0.70±0.63) and control group ( Chao:48±24;ACE:54±25;Simpson:0.71±0.27;Shannon:0.65±0.58)(W=192,P=0.11;W=189,P=0.10;W=281,P=0.72;W=241,P=0.62).The ACE(85±37) and Chao(66±25) values of CINⅠgroup were significantly different from those of the control group (ACE:54±25;Chao:48±24)(W=99,P=0.006;W=113,P=0.02).At the phylum level, 78.69%(309 020/392 722) of the vaginal microbiota in the control group was Firmicutes, 16%(62 846/392 722) was Actinobacteria.Firmicutes was reduced to 64.86%(208 422/321 318) and Actinobacteria increased to 27.71%(89 040/321 318) in CINⅠgroup.The composition of vaginal microbiotain in CINⅡ/Ⅲ group was similar to those of control group.At the genus level, the composition of vaginal microbiota were similar between CINⅡ/Ⅲ group and control group, with Lactobacillus as predominant genus[71.81%(307 658/418 424)], Gardnerella[12.91%(55 299/428 424)], others such as Prevotella, atopobium were less.In the CINⅠ group, the abundance of Lactobacillus was decreased to 56.26%(180 787/321 318), Gardnerella was increased to 19.62%(63 057/321 318), and Listeria was increased to 7.7%(24 746/321 318).The composition of vaginal microbiota in the most samples was classified as CSTⅢ and CSTⅠ, with Lactobacillus inersand and Lactobacillus crispatus were dominant respectively.There was no significant difference in the composition of vaginal microbiota between the three groups(χ2=2.72, P=0.949).LEfSe analysis showed that the abundance of bacteria in CIN group and control group were varied.At the genus level, there were significant differences in the abundance of Geobacter, Atopobium and Ureaplasma (P<0.05, P<0.05, P<0.01, respectively).At the species level, there was significant difference in the abundance of Ureaplasma urealyticum serotype 9 (P<0.01).Conclusion The diversity and the composition of vaginal microbiota were similar between CIN patients and healthy women, but the abundances of some bacteria were varied, with Ureaplasma increased in patients with CIN.

Objective To evaluate the clinical value of medical thoracoscopy in the diagnosis of exudative pleural effusions with unknown etiology.Methods We analyzed retrospectively the clinical data of 180 patients with undiagnosed pleural effusions who underwent medical thoracoscopy and appraised clinical value regarding validity,effectivity and applicability of thoracoscopy.Result In 180 cases of pleural effusion,there were 178 cases of patients with a clear diagnosis,including 87 cases of tuberculous pleurisy,28 cases of malignant tumor,malignant breast bildes mesothelioma in 2,lung cancer in 24,bile duct carcinoma in 1,cercival cancer in 1),pneumonia 58 case fo pyothorax,5 caseso of pyothorax,and 2 cases withou clear diagnosis.No check failure and terminate,the 95％CI was 5 cases of 97.78％-99.98％.Conclusions Medical thoracoscopy is a safe and effective method in the diagnosis of exudative pleural effusions with unknown aetiology.The early application of this method is very helpful for the management of the pleural diseases in suitable patients.