Objective To evaluate the efficacy and drug resistance profiles of nucleosides (NA) retreatment in NA experienced chronic hepatitis B (CHB) patients. Methods Totally 104 NA experienced CHB subjects were enrolled in this study.All these subjects had received at least 3 months NA monotherapy and stopped the treatment,and then received NA retreatment for at least one year.The subjects were divided into three groups according to the following criteria:reached the therapy endpoint of China guideline when they stopped NA-naive treatment (group A,n =39); did not reach the therapy endpoint when they stopped NA-naive treatment but hepatitis B virus (HBV) DNA＜1.0× 103 copy/mL (group B,n=33); and with HBV DNA＞1.0× 103 copy/mL (group C,n=32).The efficacy and drug resistance profiles of retreatment were compared among three groups. The effects of baseline alanine aminotransferase (ALT) levels,HBV DNA levels and HBeAg titers on the retreatment efficacies were analyzed. The mutations of HBV P gene were detected by nested polymerase chain reaction (PCR) and direct sequencing.The data were analyzd by Wilcoxon test and x2 test.Results The time to ALT normalization in patients with baseline ALT＜ 1.3 × upper limit normal (ULN) was shorter than that in patients with ALT≥1.3×ULN (2 months vs 4 months; Z=2.281,P=0.023).The time to virological response in patients with baseline HBV DNA＜5 lg copy/mL was shorter than that in patients with HBV DNA≥5 lg copy/mL (1 month vs 2 months; Z=2.054,P =0.040). The time to virological response and ALT normalization in baseline HBeAg negative were both shorter than those in patients with baseline HBeAg positive patents ( 1 month vs 3 months and 2 months vs 4.5 months,respectively; Z=2.580 and 2.304,respectively; both P＜0.05). The subjects in group A achieved virological response and HBeAg seroconversion after retreatment earlier compared to previous NA-naive therapy ([1.61 ± 1.76] months vs [3.48±4.066]months and [3.38 ± 3.34] months vs [9.92-11.22] months,respectively; Z=-2.854 and-1.094,respectively; both P＜0.05).The cumulative HBeAg seroconversion rate in group A was higher compared to those in group B and group C (80.0％ vs 36.8％ and 37.5％,respectively; x2 =4.368 and 5.100,respectively; both P＜0.05).Thirteen patients developed clinical resistance and four of them developed genotypic resistance proved by PCR direct sequencing.Among the patients retreated with the same regimen as previous in the C group,the cumulative resistance rate was highest compared to group A and B (44％ vs 9％ and 0,respectively; x2 =5.019 and 6.588,respectively;both P＜0.05).No resistance was detected in the 14 patients retreated with combined NA treatment without cross resistance.Conclusions For NA experienced CHB patients who fulfill the indication of antiviral therapy,the retreatment should be started as earlier as possible. Retreatment with NA combination without cross resistance can prevent (reduce) the risk of developing drug resistance.

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.

Objective: To understand the symptoms of depression and anxiety among rural returning adolescents and to analyze their association with physical activity related factors, so as to provide reference for interventions targeting depression and anxiety symtoms in the population. Methods: From April to June 2020, 3 495 middle school students were selected from 6 counties and districts of Shangrao City by random cluster stratified sampling sampling. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to evaluate the depressive and anxiety symptoms among middle school students. The International Physical Activity Questionnaire was used to assess their physical activity levels during the past week. Chi square test and Logistic regression analysis were used to determine the strength of the association between depression and anxiety symptoms and physical activity related factors in returning and non returning adolescents as well as the overall population. Results: Univariate analysis showed significant differences in the prevalence of depressive and anxiety symptoms between rural returning and non returning adolescents and the overall population in terms of "type of school" "family economic situation" "parental occupation" "number of sports classes per week" and "level of physical activity per week" ( χ 2=78.21, 16.56, 135.44, 107.75, 7.10, 8.62; 97.94, 24.26 , 124.07, 90.36, 9.60, 8.34, P <0.05). Multivariate regression analysis showed a correlation between the occurrence of depression and the number of sports classes per week for rural returning and non returning adolescents and the overall population (number of sports classes per week for non returning was 2 times, OR=1.22, 95%CI =1.01-1.49; returning adolescents for 1 time, OR=1.85, 95%CI =1.06-3.23; the overall population for 1 time, OR=1.34, 95%CI =1.01-1.77 and 2 times, OR=1.20, 95%CI =1.01-1.43, P <0.05). There was a correlation between anxiety symptoms and the number of sports classes per week for returning adolescents (number of sports classes per week for returning adolescents was 1 time, OR=2.10, 95%CI=1.21-3.63, P < 0.05 ). Conclusion A low frequency of weekly sports classes may be a risk factor for depressive or anxiety symptoms in rural and returning adolescents. Rural primary and secondary schools should appropriately increase the number of physical education courses or arrange sports extended classes to promote the development of adolescent mental health.

Objective:To explore the correlation of serum adiponectin (APN) , D-dimer (D-D) and neutrophil-to-lymphocyte ratio (NLR) levels with disease severity and prognosis in patients with diabetic foot ulcer infection.Methods:92 patients with diabetic foot ulcer infection in the Nantong Third Hospital Affiliated to Nantong University from Feb. 2020 to Feb. 2021 were selected, and they were divided into mild ( n=30) , moderate ( n=44) and severe ( n=18) patients according to the severity of the disease. The serum APN, D-D and NLR levels in patients with different severity were compared, the relationship between serum APN, D-D and NLR levels and disease severity in patients with diabetic foot ulcer infection were analyzed. Patients were followed up for 1 year, and the prognosis of the patients was counted. Factors affecting serum APN, D-D and NLR levels in patients with diabetic foot ulcer infection were analyzed, and the receiver operating curve (ROC) was used to analyze the value of serum APN, D-D and NLR levels in predicting poor prognosis of patients. Results:There were significant differences in serum APN, D-D and NLR levels in patients with different severity ( P<0.05) . APN level in severe patients was 5.35±0.98, in moderate patients was 7.64±1.25, both lower than that of the mild patients 9.19±1.73 ( P<0.05) . Serum APN level in severe patients was lower than that in moderate patients ( P<0.05) . Serum D-D and NLR levels were 3.49±0.72 and 2.86±0.58 in severe patients, respectively; and they were 3.02±0.63 and 2.24±0.46 in moderate patients, higher than that of mild patients 2.43±0.51; 1.71±0.33 ( P<0.05) . The levels of serum D-D and NLR in severe patients were higher than those in moderate patients ( P<0.05) . Spearman correlation analysis showed that the severity of the disease was negatively correlated with serum APN levels ( r=-0.414, P<0.001) , and positively correlated with serum D-D and NLR levels in patients with diabetic foot ulcer infection ( r=0.387, P<0.001; r=0.461, P<0.001) . Univariate analysis showed that the proportion of severe disease, serum fasting blood glucose, glycosylated hemoglobin, fibrinogen, D-D and NLR levels in patients with poor prognosis were higher than those in patients with good prognosis ( P<0.05) , and the APN level in patients with poor prognosis was lower than that in patients with good prognosis ( P<0.05) . Logistic multivariate regression analysis showed that severe disease, serum glycosylated hemoglobin, APN, D-D, and NLR levels were independent risk factors for poor prognosis in patients with diabetic foot ulcer infection ( P<0.05) . ROC analysis showed that the optimal cut-off points of serum APN, D-D and NLR levels for predicting poor prognosis of patients were 5.73 mg/L, 3.06 mg/L, 2.12, the sensitivity was 78.57%, 82.14%, 85.71%, the specificity was 76.56%, 67.19%, 73.44%, the area under the curve (AUC) was 0.793, 0.784, 0.818, the specificity and AUC of the three were 98.44 %, 0.918, respectively. Conclusions:Serum APN, D-D and NLR levels are related to the severity of the disease in patients with diabetic foot ulcer infection. Clinical detection of serum APN, D-D and NLR levels can be used as sensitive indicators to predict poor prognosis.

Objective : To investigate whether Mitochondria-targeted antioxidant peptide SS-31 can inhibit the ozone ( O3 ) -induced mice lung airway hyperresponsiveness and mucus hypersecretion． Methods : Eight-week C57BL /6 mice were randomized into four groups，including phosphate buffer saline (PBS) + Air group，SS-31 + Air group， PBS + O3 group and SS-31 + O3 group．C57BL /6 mice were injected intraperitoneally with SS-31 ( 10 mg / kg) one hour before ozone exposure ，and then single-exposed to ozone at a concentration of 5. 01 × 10 －6 mol / m3 for 3 hours．After 24 hours，airway hyperresponsiveness(AHR) and bronchoalveolar lavage fluid (BALF) cells numbers were measured．Lung tissue schiff periodic acid shiff (PAS) staining，malondialdehyde (MDA) ，inflammatory factors ( interleukin，IL ) -1 β , IL-6 ，IL-18 and monocyte chemoattractant protein-1 ( MCP-1 ) ) and mucin factor (MUC5B) were detected，and the protein expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) ，pro-Caspase 1 / Caspase 1 (p20) ，Gasdermin D ( GSDMD) and Cleaved GSDMD were determined by Western blot. Results: O3 exposure caused both mice lung airway hyperresponsiveness and mucus hypersecretion．However，SS-31 could inhibit the O3 -induced airway hyperresponsiveness and mucus secretion，reduce the levels of oxidative stress and inflammatory factor mRNA expression ，and downregulate the protein expression level of NLRP3 and the activated forms of Caspase 1 and GSDMD． Conclusion SS-31 could suppress O3 -induced mice airway hyperresponsiveness and mucus hypersecretion by inhibiting the NLRP3 / Caspase 1 / GSDMD signaling pathway.