Objective To investigate the effect of Pirfenidone(PFN)on respiratory syncytial virus(RSV)infection-induced damage to bronchial epithelial cells by regulating the high mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway.Methods Human bronchial epithelial cells(HBE)were divided into Control group(cultured for 24 h under normal conditions),RSV group(inoculated with 4.65×106/mL RSV at 33℃for 2 h);low PFN(L-PFN)group(treated with 0.05 mg/mL PFN for 24 h),moderate PFN(M-PFN)group(treated with 0.10 mg/mL PFN for 24 h),high PFN(H-PFN)group(treated with 0.20 mg/mL PFN for 24 h)and recombinant HMGB1(rHMGB1)group(treated with 1 μg/mL rHMGB1+0.20 mg/mL PFN for 24 h).EdU method was applied to detect the proliferation rate of cells in each group,Hochest33258 staining method was applied to detect apoptosis status of cells in each group,and the migration of cells in each group was evaluated by the scratch experiment.Enzyme linked immunosorbent assay(ELISA)was applied to measure the levels of interferon(IFN)-α,IFN-γ,tumor necrosis factor-α(TNF-α),interleukin(IL)-1α,IL-6 and IL-4 in each group of cells,and Western blot was applied to detect the protein expression of HMGB1,RAGE,B lymphoblastoma-2-associated X protein(Bax),cysteine aspartic protease-3(Caspase-3),and B lymphoblastoma-2(Bcl-2).Results Compared with the RSV group,the cell proliferation rate,scratch closure rate,IL-4 levels,and expression of Bcl-2 in L-,M-,and H-PFN groups increased,while the apoptosis rate,the levels of IFN-α,IFN-γ,TNF-α,IL-1α,IL-6,and the expression of HMGB1,RAGE,Bax,and Caspase-3 reduced(P<0.05);rHMGB1 weakened the effect of H-PFN on the above-mentioned indicators(P<0.05).Conclusion PFN may suppress the apoptosis and inflammatory damage of RSV-infected bronchial epithelial cells by inhibiting the HMGB1/RAGE pathway.Conclusion PFN may suppress the apoptosis and inflammatory damage of RSV-infected bronchial epithelial cells by inhibiting the HMGB1/RAGE pathway.

Objective:To investigate the detection status of serological markers for hepatitis B virus (HBV) among Tibetan college students and their relationship with HBV- deoxyribonucleic acid (DNA) load.Methods:A cross-sectional study was carried out to retrospectively analyze data from 1 514 Tibetan college students who visited the Affiliated Hospital of Xizang Minzu University for consultations or health examinations between June 1, 2021 and June 1, 2022. The prevalence of HBV infection among these students was analyzed, the primary epidemiological patterns of HBV markers were identified, and their relationship with HBV-DNA load was determined.Results:The positive rate of hepatitis B surface antigen (HBsAg) among the 1 514 Tibetan college students was 6.7% (101/1 514), while the positive rate for Hepatitis B surface antibody (HBsAb) was 42.2% (639/1 514). The primary serological pattern of HBV infection consisted of positive results for HBsAg, HBeAg, and HBcAb, which accounted for 48.5% of cases. This pattern showed significantly higher rates of HBV-DNA positivity and elevated viral load compared with other serological patterns ( χ2 = 8.70, P < 0.05). Conclusions:The HBV infection rate among Tibetan college students is 6.7%. The primary infection pattern is characterized by positive tests for HBsAg, HBeAg, and HBcAb, with an HBV-DNA positivity rate as high as 87.0% and elevated viral loads.

Objective To investigate the effect of Pirfenidone(PFN)on respiratory syncytial virus(RSV)infection-induced damage to bronchial epithelial cells by regulating the high mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway.Methods Human bronchial epithelial cells(HBE)were divided into Control group(cultured for 24 h under normal conditions),RSV group(inoculated with 4.65×106/mL RSV at 33℃for 2 h);low PFN(L-PFN)group(treated with 0.05 mg/mL PFN for 24 h),moderate PFN(M-PFN)group(treated with 0.10 mg/mL PFN for 24 h),high PFN(H-PFN)group(treated with 0.20 mg/mL PFN for 24 h)and recombinant HMGB1(rHMGB1)group(treated with 1 μg/mL rHMGB1+0.20 mg/mL PFN for 24 h).EdU method was applied to detect the proliferation rate of cells in each group,Hochest33258 staining method was applied to detect apoptosis status of cells in each group,and the migration of cells in each group was evaluated by the scratch experiment.Enzyme linked immunosorbent assay(ELISA)was applied to measure the levels of interferon(IFN)-α,IFN-γ,tumor necrosis factor-α(TNF-α),interleukin(IL)-1α,IL-6 and IL-4 in each group of cells,and Western blot was applied to detect the protein expression of HMGB1,RAGE,B lymphoblastoma-2-associated X protein(Bax),cysteine aspartic protease-3(Caspase-3),and B lymphoblastoma-2(Bcl-2).Results Compared with the RSV group,the cell proliferation rate,scratch closure rate,IL-4 levels,and expression of Bcl-2 in L-,M-,and H-PFN groups increased,while the apoptosis rate,the levels of IFN-α,IFN-γ,TNF-α,IL-1α,IL-6,and the expression of HMGB1,RAGE,Bax,and Caspase-3 reduced(P<0.05);rHMGB1 weakened the effect of H-PFN on the above-mentioned indicators(P<0.05).Conclusion PFN may suppress the apoptosis and inflammatory damage of RSV-infected bronchial epithelial cells by inhibiting the HMGB1/RAGE pathway.Conclusion PFN may suppress the apoptosis and inflammatory damage of RSV-infected bronchial epithelial cells by inhibiting the HMGB1/RAGE pathway.

Objective:To investigate the detection status of serological markers for hepatitis B virus (HBV) among Tibetan college students and their relationship with HBV- deoxyribonucleic acid (DNA) load.Methods:A cross-sectional study was carried out to retrospectively analyze data from 1 514 Tibetan college students who visited the Affiliated Hospital of Xizang Minzu University for consultations or health examinations between June 1, 2021 and June 1, 2022. The prevalence of HBV infection among these students was analyzed, the primary epidemiological patterns of HBV markers were identified, and their relationship with HBV-DNA load was determined.Results:The positive rate of hepatitis B surface antigen (HBsAg) among the 1 514 Tibetan college students was 6.7% (101/1 514), while the positive rate for Hepatitis B surface antibody (HBsAb) was 42.2% (639/1 514). The primary serological pattern of HBV infection consisted of positive results for HBsAg, HBeAg, and HBcAb, which accounted for 48.5% of cases. This pattern showed significantly higher rates of HBV-DNA positivity and elevated viral load compared with other serological patterns ( χ2 = 8.70, P < 0.05). Conclusions:The HBV infection rate among Tibetan college students is 6.7%. The primary infection pattern is characterized by positive tests for HBsAg, HBeAg, and HBcAb, with an HBV-DNA positivity rate as high as 87.0% and elevated viral loads.

Objective: To analyse the expression of differential mRNA in the plasma exosomes in patients with latent tuberculosis infection (LTBI) and active tuberculosis (ATB) using high-throughput sequencing, so as to provide insights into differential diagnosis of LTBI and ATB. Methods: The plasma samples were collected from the patients treated at The Affiliated Hospital of Hangzhou Normal University, including 16 cases of LTBI and 21 cases of ATB. The exosomes were extracted by Invitrogen extracellular extracts purification kit, and the size and morphology of exosomes were observed by transmission electron microscope (TEM). The exosomes were identified by Western blotting. Total RNA was extracted from plasma exosomes using high-throughput sequencing, differential expression mRNA was identified, and gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Two differential mRNAs with the highest differential expression fold were selected, and five patients with ATB and three patients with LTBI were recruited for verification using real-time quantitative PCR. Results: The sequencing results of plasma exosomes showed that compared with ATB patients, 2 875 differentially expressed mRNAs were detected in exosomes of LTBI patients, of which 1 002 mRNAs were up-regulated and 1 873 mRNAs were down-regulated. The most significant differentially expressed downregulated and upregulated mRNA were M6PR and RGPD5, respectively. GO analysis and KEGG pathway analysis showed that differential mRNAs were enriched in protein serine kinase activity, rRNA binding molecular function, human cytomegalovirus infection, pancreatic cancer, endometrial cancer, insulin signaling pathway and FoxO signaling pathway. The real-time quantitative PCR showed that the expression of differential mRNA was consistent with sequencing. Compared with ATB patients, the relative expression level of M6PR in plasma exosomes in LTBI patients (0.954±0.212) was downregulated compared with that of ATB patients (2.168±0.226), while the relative expression level of RGPD5 (2.126±0.200) was upregulated compared with that of ATB patients (0.588±0.129) (both P<0.05). Conclusions There is a difference in mRNA expression of plasma exosomes between patients with LTBI and ATB. M6PR and RGPD5 may become markers for distinguishing plasma exosomes between LTBI and ATB.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Objective:To construct a diabetic foot classification prediction model based on radiomics features of fundus photographs.Methods:A total of 2 035 fundus photographs of patients with type 2 diabetes diagnosed at Nanfang Hospital between December 2011 and December 2018 were retrospectively collected [282 photographs from patients with diabetic foot(DF), and 1 753 from patients with diabetes mellitus(DM)]. All fundus photographs were randomly divided into a training set(1 424 photos) and a test set(611 photos) using a computer generated random number at 7∶3. After pre-processing the fundus photographs, a total of 4 128 texture features based on the gray matrix were extracted by the Radiomic toolkit, and 11 339 other features were extracted using the ToolboxDESC toolkit. The LASSO algorithm was used to select the 30 features most relevant to DF, and then the Bootstrap + 0.632 self-sampling method was used to further select the 7 best combinations. Logistic regression analysis was used to obtain the regression coefficients and establish the final diabetic foot classification prediction model. ROC curve was drawn, and AUC, sensitivity, specificity, and accuracy of the training and test sets were calculated to verify its prediction performance. Results:We screened 7 fundus radiomics markers for diabetic foot patients, and based on this established a DF/DM classification prediction model. The AUC, sensitivity, specificity, and accuracy of the model were 0.958 6, 0.984 0, 0.920 0, and 0.928 0 in the training set, and 0.927 1, 0.988 9, 0.881 0, and 0.896 9 in the test set, respectively.Conclusion:In this study, seven DF fundus markers were screened using radiomics technology. Based on this, a highly accurate and easy-to-use DF/DM classification model was constructed. This technology has the potential to increase the efficiency of DF screening programs.

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.

Objective: To compare the short-term and long-term results of thoracoscopic and open pneumonectomy for non-small cell lung cancer. Methods: The clinical data of patients with non-small cell lung cancer who underwent pneumonectomy in the Department of Thoracic Surgery, Qingdao University Hospital from January 2008 to December 2016 were collected. Totally 142 patients (55 in the thoracoscopic group and 87 in the open group) were included in the study. A total of 29 pairs of patients were successfully matched by propensity score matching (PSM). Perioperative outcomes and overall survival were compared between the two groups using t test, χ² test, Kaplan-Meier curve and Log-rank test, respectively. Results: Camparion with open group, the thoracoscopic group had longer operative time ((209.7±70.2) minutes vs. (171.3±43.5) minutes, t=2.50, P=0.02), more mediastinal lymph node dissection (M(Q_R): 17(9) vs. 11(10), W=388, P=0.02) and shorter postoperative hospital stay (7.0(3.5) vs. 9.0(3.0), W=285, P=0.03). There was no significant difference in estimated blood loss, postoperative drainage time, dissected lymph node number, dissected lymph node station and perioperative complications. After PSM, there were no signifificant differences found in 3-year survival (71.4% vs. 48.1%, P=0.10) and 3-year disease-free survival (67.4% vs. 47.2%, P=0.13) between the two groups. Conclusion Thoracoscopic pneumonectomy is safe and feasible for the treatment of non-small cell lung cancer with more mediastinal lymph node dissection and accelerating recovery, and equivalent long-term prognosis when compared with open approach.

Objective To investigate the characteristics of phenylalanine hydroxylase (PAH) gene mutations in Han ethnic children with phenylketonuria of Xinjiang region.Methods The mutations in the promoter,exons 1-13 and flanking introns of PAH genes from 71 Han ethnic PKU children and their parents of Xinjiang region were detected by PCR,DNA sequencing and high-throughput targeted sequencing,and the obtained results were compared with those from other four provinces in northwest of China,Japan and Europe.Re suits A total of 37 kinds of mutations,including missense mutation,splice site mutation,nonsense mutation,deletion mutation and frameshift mutation,were detected in 90.1％ (128/142) of PAH alleles from 71 Han ethnic PKU children of Xinjiang region.Most mutations existed in exons 7,6,3,12,2 and 11 and intron 4 of PAH gene.The most common missense mutations were R243Q (21.8％) and R53H (7.7％).The most common splicing sites were EX6-96A ＞ G(6.3％),IVS4-1G ＞ A(4.9％) and V399V (4.2％).Moreover,The most common nonsense mutations were R111X(4.9％) and Y356X(4.9％).The detection rate of R53H mutation (7.7％) in Han ethnic PKU children of Xinjiang region was significantly higher than that in other 4 provinces of northwest of China,and a novel PAH gene nutation P225S(c.673C ＞ T) was found.Conclusion The mutation spectrum of PAH gene in Han ethnic PKU children of Xinjiang region is similar to that in other 4 provinces of northwest of China,but significantly different from that of Japanese and European population,which displays a distinct and conservative characteristic.