ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.

Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

Objective:To determine the prevalence and risk factors of constipation in Hangzhou urban areas by analyzing data from a recent epidemiological survey.Methods:From August 2022 to June 2023, a cross-sectional survey was conducted on 43 communities on eight streets in suburbs of Hangzhou, including Wangjiang, Sijiqing, Puyan, Changhe, Ziyang, Xiaoshanchengxiang, Zhuantang, and Banshan. Written questionnaires were filled out face to face by community doctors. The prevalence of constipation was investigated using a combination of the Bristol stool typing method and the Rome IV criteria. The risk factors for constipation were analyzed using multivariate logistic regression analysis.Results:The study cohort comprised 10,479 participants, 5551 of whom were male (53.0%) and 4928 female (47.0%). The overall prevalence of constipation was 10.6% (1107/10,479). The prevalence was 11.0% (613/5551) for male and 10.0% (494/4928) for female participants; this difference is not statistically significant ( P>0.05).There were no significant differences in the prevalence of constipation between different categories of body mass index ( P>0.05). The prevalence of constipation was highest in individuals aged 70 years and above, accounting for 15.4% (264/1717) of all cases. There were significant differences in the prevalence of constipation between different occupations, marital statuses, and educational levels ( P<0.001). Patients with hypertension or diabetes mellitus had a higher prevalence of constipation than those without these conditions, those who had been taking long-term medication had a higher prevalence of constipation than those who did not, parents of children with constipation had a higher prevalence of constipation than those with children who did not have constipation, and there were other significant differences in various variables ( P<0.001). Multivariate logistic regression analysis of modifiable factors revealed that eating less fruit (OR=1.284, 95%CI: 1.061–1.553, P=0.010), liking spicy and salty food (OR=1.234, 95%CI: 1.039–1.466, P=0.016), sleeping for too long (OR=1.644, 95%CI: 1.260–2.144, P<0.001), irregular sleep patterns (OR=1.370, 95%CI: 1.127–1.665, P=0.002) and minimal exercise (OR=1.388, 95% CI: 1.168–1.649, P<0.001) were all risk factors for constipation; whereas mix diets (OR=0.709,95%CI:0.608–0.826, P<0.001), meat diets (OR=0.604,95%CI: 0.495–0.736, P<0.001), moderate alcohol consumption (OR=0.659, 95% CI: 0.534–0.812, P<0.001), less or no drinking (OR=0.523, 95% CI: 0.428–0.638, P<0.001), and non-smoking (OR=0.819, 95%CI:0.674–0.995, P<0.001) protected against constipation. We found no association between dietary preferences and the risk of constipation (refined grains: OR=1.147, 95%CI:0.944–1.393, P=0.167; no specific preference: OR=0.935, 95%CI:0.783–1.117, P=0.459). The rate of agreement between self-evaluation of constipation by the respondents and objective criteria was higher for negatives (95.8%) than for positives (38.0%). Conclusion:The prevalence of constipation is relatively high in the urban population of Hangzhou. A good lifestyle and diet can significantly reduce its incidence. There should be more emphasis on preventive education, promotion of prevention of constipation, and advocacy for a healthy lifestyle.

Objective:To determine the prevalence and risk factors of constipation in Hangzhou urban areas by analyzing data from a recent epidemiological survey.Methods:From August 2022 to June 2023, a cross-sectional survey was conducted on 43 communities on eight streets in suburbs of Hangzhou, including Wangjiang, Sijiqing, Puyan, Changhe, Ziyang, Xiaoshanchengxiang, Zhuantang, and Banshan. Written questionnaires were filled out face to face by community doctors. The prevalence of constipation was investigated using a combination of the Bristol stool typing method and the Rome IV criteria. The risk factors for constipation were analyzed using multivariate logistic regression analysis.Results:The study cohort comprised 10,479 participants, 5551 of whom were male (53.0%) and 4928 female (47.0%). The overall prevalence of constipation was 10.6% (1107/10,479). The prevalence was 11.0% (613/5551) for male and 10.0% (494/4928) for female participants; this difference is not statistically significant ( P>0.05).There were no significant differences in the prevalence of constipation between different categories of body mass index ( P>0.05). The prevalence of constipation was highest in individuals aged 70 years and above, accounting for 15.4% (264/1717) of all cases. There were significant differences in the prevalence of constipation between different occupations, marital statuses, and educational levels ( P<0.001). Patients with hypertension or diabetes mellitus had a higher prevalence of constipation than those without these conditions, those who had been taking long-term medication had a higher prevalence of constipation than those who did not, parents of children with constipation had a higher prevalence of constipation than those with children who did not have constipation, and there were other significant differences in various variables ( P<0.001). Multivariate logistic regression analysis of modifiable factors revealed that eating less fruit (OR=1.284, 95%CI: 1.061–1.553, P=0.010), liking spicy and salty food (OR=1.234, 95%CI: 1.039–1.466, P=0.016), sleeping for too long (OR=1.644, 95%CI: 1.260–2.144, P<0.001), irregular sleep patterns (OR=1.370, 95%CI: 1.127–1.665, P=0.002) and minimal exercise (OR=1.388, 95% CI: 1.168–1.649, P<0.001) were all risk factors for constipation; whereas mix diets (OR=0.709,95%CI:0.608–0.826, P<0.001), meat diets (OR=0.604,95%CI: 0.495–0.736, P<0.001), moderate alcohol consumption (OR=0.659, 95% CI: 0.534–0.812, P<0.001), less or no drinking (OR=0.523, 95% CI: 0.428–0.638, P<0.001), and non-smoking (OR=0.819, 95%CI:0.674–0.995, P<0.001) protected against constipation. We found no association between dietary preferences and the risk of constipation (refined grains: OR=1.147, 95%CI:0.944–1.393, P=0.167; no specific preference: OR=0.935, 95%CI:0.783–1.117, P=0.459). The rate of agreement between self-evaluation of constipation by the respondents and objective criteria was higher for negatives (95.8%) than for positives (38.0%). Conclusion:The prevalence of constipation is relatively high in the urban population of Hangzhou. A good lifestyle and diet can significantly reduce its incidence. There should be more emphasis on preventive education, promotion of prevention of constipation, and advocacy for a healthy lifestyle.

As a new therapeutic method, music therapy has a good clinical effect on improving the motor dysfunction of patients with stroke. This article reviews the concept, main forms of music therapy and its role in motor function recovery of patients with stroke.

Objective: To understand the concern of freshmen with different characteristics on sexual knowledge in Sichuan province and to provide evidence for comprenensive sex education in colleges. Methods: A survey was conducted among 2 532 freshmen from 13 universities in Sichuan Province in September 2018. Attention to specific sexual knowledge among students with different characteristics was analyzed. Results: Sexual knowledge that the freshmen concerned included partner communication (39.25%~55.10%), STD and AIDS (37.78%~44.85%) and gender equality (33.33%~43.34%). Logistic regression results showed that male students payed more attention to partner communication(OR=0.77,95%CI=0.65-0.91), masturbation (OR=0.36，95%CI=0.27-0.47) and sexual minorities (OR=0.61,95%CI=0.41-0.90), while female students payed more attention to gender equality (OR=1.31,95%CI=1.10-1.57), sexual harassment and violence (OR=1.65,95%CI=1.37-1.98). Rural students pay. more attention to partner communication (OR=0.79,95%CI=0.65-0.94), while urban students pay. more attention to masturbation (OR=1.50,95%CI=1.08-2.08), sexual harassment and sexual violence (OR=1.30,95%CI=1.07-1.58). Students who had sex were more concerned about contraception and unwanted pregnancy than those who had not (OR=0.53,95%CI=0.39-0.72). Sexual minority students were more concerned about topic of sexual minorities than heterosexual students (OR=3.50,95%CI=2.30-5.33). Conclusion College freshmen with different characteristics varied in their concern on sexual knowledge, which is related to their needs. It is suggested that schools set up comprehensive education courses according to the needs of students, the content of sex education knowledge can be focused, and carry out comprehensive and targeted sex education.

Objective To investigate the effects of mild hypothermia on post-resuscitation neurological outcome after ventricular fibrillation (VF) in rabbits.Methods Forty-five adult New Zealand rabbits were induced VF by direct current of electricity.The rabbits were randomly(random number) divided into following groups:normothermic resuscitation group (NR),mild hypothermia prearrest group (HP),mild hypothermia resuscitation 30 min group (HRe30),mild hypothermia resuscitation 90 min group (HRe90),normothermic sham group (NS),and hypothermia sham group (HS).The rabbits of NR group were observed for 600 min in room temperature after restoration of spontaneous circulation (ROSC).The mild hypothermia was induced by surface cooling,and maintained for 600 min after the aimed low temperature reached.The arterial blood samples were collected for determining neuron-specific enolase (NSE) and thioredoxin (Trx) and the mean arterial pressure (MAP),left ventricular end-diastolic pressure (LVEDP) and left ventricular pressure raise and fall rate (±dp/dtmax) were observed at 15 min before CA,and 30 min,60 min,120 min,360 min and 600 min after ROSC.After the animals were sacrificed at 600 min after ROSC,the whole brain of animals was harvested and observed under light microscope to calculate the apoptotic index of the hippocampal CA1 neurons by using TUNEL method.One-way ANOVA was used to determine the statistical significance between two groups,a two-tailed value of P＜0.05 was considered statistically significant.Results (1) Hemodynamically compared with normal temperature groups,HR was lower in hypothermia groups.Compared with NR,HRe30,and HRe90 group,LVEDP was higher in HP group at 30 min after ROSC(3.4±0.8 vs.4.6±1.0,4.1±0.5,4.3±0.2,F=9.85,P=0.019).In Hp group,the level of +dp/dtmax was higher than that in NR,HRe30 and HRe90 groups at 30 min and 120 min after ROSC.In HP group,the level of-dp/dtmax was higher than that of NR group at 30 min,60 min,120 min,360 min and 600 min after ROSC.(2) Serologically compared with HP,HRe30 and HRe90 group,NSE levels were higher in NR group at 60 min,120 min and 360 min after ROSC.Compared with NR,HRe30,and HRe90 group,Trx levels in NR group were lower at 60 min,120 min,360 min and 600 min after ROSC.Compared with HP group,Trx levels in HRe30 and HRe90 groups were higher at 60 min,120 min,360 min and 600 min after ROSC.(3) Pathologically compared with NR group,histopathological changes in hippocampus CA1 area were milder found in HP,HRe30 and HRe90 groups.AI (％) was lower in HP,HRe30 and HRe90 groups than that in NR group[(62.25±10.43)％ vs.(20.61±5.02)％,(25.08±3.92)％,(30.33±7.15)％,P=0.001].Concusions This study shows that hypothermia should be initiated as soon as possible,and especially early intra-arrest cooling appears to be significantly better than post-ROSC cooling and normothermia.

Objective To compare the effects of different stent configurations on shunt failure,hepatic encephalopathy,and hepatic myelopathy after transjugular intrahepatic portosystemic shunt (TIPS).Methods From March 2014 to June 2015,the clinical data of 73 hospitalized,patients who met the inclusion and exclusion criteria,and underwent TIPS for upper gastrointestinal hemorrhage caused by cirrhotic portal hypertension were retrospectively analyzed.According to the stent configuration during operation,patients were divided into simple coated stent group (hepatic vein,portal vein and hepatic parenchyma coated stent,23 cases),simulated Viatorr stent group (hepatic vein and hepatic parenchyma coated stent plus portal vein bare stent,27 cases) and combined stent group (hepatic vein and portal vein hare stent plus hepatic parenchyma coated stent,23 cases).Patients were followed up for one year,the incidences of shunt failure,hepatic encephalopathy and hepatic myelopathy within one year after TIPS of three groups were compared.Chi-square test,Fisher exact probability method and variance analysis were performed for comparison among groups.Cox regression analysis was used for difference analysis in imbalance of variables and incidence of outcome events among the three groups.Results The portal vein pressure gradient of simple coated stent group,simulated Viatorr stent group and combined stent group decreased from (22.15±4.52),(23.01±5.48) and (21.13±4.49) mmHg (1 mmHg=0.133 kPa) to (9.15±2.94),(11.20±3.27) and (8.75+4.06) mmHg after operation,respectively.Before and after operation,the differences in portal venous pressure gradient were statistically significant of three groups (t=10.488,7.188 and 7.850,all P＜0.05).The shunt failure rates of simple coated stent group,simulated Viatorr stent group and combined stent group were 13.0％ (3/23),18.5％ (5/27) and 30.4％ (7/23),respectively.The results of Cox regression analysis indicated that there was no statistically significant difference in shunt failure rates among different stent configurations after TIPS (P=0.339).The incidences of hepatic encephalopathy of simple coated stent group,simulated Viatorr stent group and combined stent group postoperative were 69.6％ (16/23),33.3％ (9/27) and 30.4％ (7/23),respectively,the difference was not statistically significant among the three groups (P＞ 0.05).The results of Cox regression analysis showed that the relative ratio values (95％ confidence interval) of incidence of postoperative hepatic encephalopathy of simple coated stent group compared with simulated Viatorr stent group and combined stent group were 2.901 (1.279 to 6.584) and 2.735 (1.123 to 6.658),and the differences were statistically significant (both P＜0.05).The incidences of hepatic myelopathy of simple coated stent group,simulated Viatorr stent group and combined stent group were 8.7％ (2/23),3.7％ (1/27) and 4.3％ (1/23),respectively,and there was no statistically significant difference in the incidence of hepatic myelopathy among three groups after operation (P＞0.05).During one-year follow-up,among 73 patients,two patients died,one in simple coated stent group and the other in combined stent group.The one-year survival rate after TIPS was 97.3％.Conclusions One year after operation,the incidences of shunt failure are similar between simple coated stent group,simulated Viatorr stent group and combined stent group.One year after operation,the incidence of hepatic encephalopathy is similar between simulated Viatorr stent group and combined stent group which are both lower than that of simple coated stent.The incidence of hepatic myelopathy is low,and its association with TIPS remains to be further investigated.