This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

In order to investigate the effect of SIRT2 on tight junctions and endoplasmic reticulum stress in liver tissues of cold-treated mice,10 each of 5-week-old male C57BL/6 mice and SIRT2 knockout mice were selected and randomly divided into the wild-type room-temperature control group(WT Control),the wild-type cold-treated group(WT Cold),the SIRT2 knockout+room-temperature control group(KO Control)and SIRT2 knockout+cold treatment group(KO Cold).Mice in the room-temperature control group were kept at a temperature of(24+2)℃,and the cold-treatment group was placed in a(4+2)℃ artificial climate chamber for 3 h of random stimu-lation per day for 3 weeks.H&E staining,Masson staining,and transmission electron microscopy were employed to examine the microscopic and ultrastructural changes in mouse liver;AST and ALT concentrations in mouse serum were detected by biochemical analyzers;Western blot analysis was used to detect the expressions of tight junction-related proteins(Claudin1,Occludin),endo-plasmic reticulum stress-related proteins(GRP78,CHOP,XBP1,p-eIF2α,eIF2α),and pro-inflam-matory cytokines(TNF-α,IL-1β,IL-6).The results showed that compared with WT Control,the liver lobular structure of WT Cold and KO Control mice was unclear,hepatic cord arrangement was disordered,cytoplasm was loose,white vacuoles appeared,a small amount of collagen deposi-tion and fibroplasia,mitochondria were slightly swollen in hepatocytes,and endoplasmic reticulum was unevenly distributed,while the serum concentrations of AST and ALT were increased(P＜0.050,P＜0.010),and the liver tissues showed decreased protein expression of Occludin and Clau-din1(P＜0.050,P＜0.010,P＜0.001),and increased protein expression of GRP78,CHOP,XBP1,p-eIF2α/eIF2α,TNF-α,IL-6,and IL-1β(P＜0.050,P＜0.010,P＜0.001);compared with the KO Control,KO Cold mice showed a large number of white vacuoles,a small number of balloon-like lesions,inflammatory cell infiltration,obvious collagen deposition and fibroplasia,mitochondrial swelling in hepatocytes,mitochondrial ridge reduction,endoplasmic reticulum thickening,and ser-um AST and ALT concentrations increased(P＜0.010),and in liver tissue,the protein expression of Occludin and Claudinl decreased(P＜0.010),while the protein expression of GRP78,CHOP,XBP1,p-eIF2α/eIF2α,TNF-α,IL-6 and IL-1β increased(P＜0.050,P＜0.010,P＜0.001).The re-sults showed that SIRT2 knockdown could aggravate the liver tissue tight junction damage caused by cold treatment,induce endoplasmic reticulum stress,and further promotes the inflammatory re-sponse.

This research aimed to comprehensively understand the prevalence of mutation in drug-resistant molecular markers of imported Plasmodium vivax in Chongqing,the Pvmdr1,Pvdhps,Pvdhfr,Pvcrt-o and Pvk12 genes of Plasmodium vivax were systematically analyzed.Blood samples were collected from imported Plasmodium vivax-infected patients in Chongqing between 2011 and 2022.The Pvmdr1,Pvdhps,Pvdhfr,Pvcrt-o,and Pvk12 genes were amplified and then sequenced to precisely evaluate gene mutations.Bioinformatics methods were employed to conduct in depth analysis of the mutation prevalence.Regarding the Pvdhfr gene,mutations at codons 50,57,58,61,99,117,and 199 were detected in 2.9%,23.5%,76.4%,23.53%,2.9%,82.3%,and 5.88%of the samples,respectively.The double-mutant haplotype S58R/S117N was the most prevalent,accounting for 50%,followed by the quadruple-mutant haplotype F57L/S58R/T61M/S117T,which accounted for 11.76%.Among the four types of tandem-repeat variations of Pvdhfr,the wild-type was the most common,and the insertion type was a novel discovery in this study.For the Pvdhps gene,the prevalence among mutation genotypes was relatively low.The single-mutant genotype was dominant,constituting 27.03%.The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100%and 89.19%,respectively.Among the 37 successfully sequenced samples,K10 insertion was detected in only 8 cases(22.22%).Notably,no non-synonymous mutations of Pvk12 were identified in this study.The cases in this study were imported from various countries of origin.Novel tandem-repeat variation tyres of Pvdhfr and new mutation sites of Pvdhps were identifide,thus enriching the mutation information of imported Plasmodium vivax resistance molecular markers in China.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Spectral computed tomography (CT) has triggered a technological revolution in radiodiagnosis while demonstrating its increasing application value in radiotherapy. Employing dual-energy techniques for material decomposition, spectral CT provides optimized solutions for several critical aspects of radiotherapy. Based on a review of the application situation of spectral CT in radiotherapy, this study delved into spectral CT′s significant advantages in image quality improvement, precise dose calculation, and comprehensive quantitative assessment. Furthermore, this study envisioned the development orientations and application prospects of spectral CT.

Objective To analyze the dynamic changes and influencing factors of Mycobacterium tuberculosis(TB)infection in grade-1 students in senior high school at the time of enrollment and one year after enrollment.Methods In 2022,TB screening was carried out among grade-2 students in 4 senior high schools in Binhai and Xiqing Districts of Tianjin.Basic information of students was collected,and TB infection detection results of grade-1 students in senior high school at the time of enrollment were collected retrospectively.Positive rate,strong positive rate and positive conversion rate from tuberculin skin test(TST)results of students were compared.Univariate and multiva-riate logistic regression models were used to analyze the relevant influencing factors for positive conversion of TST results.Results The overall positive rate of 1 839 students one year after enrollment was higher than that at the enrollment(46.82％vs 33.12％),while strong positive rate was lower(12.51％vs 13.00％),both with statisti-cally significant differences(both P＜0.001).One year after enrollment,64 out of 1 230 students who were origi-nally negative for TST in their first year of senior high school turned positive,with a positive conversion rate of 5.20％(95％CI:3.93％-6.48％).One year after enrollment,TST results showed that the average diameter of induration was 5(2,8)mm,diameter was 2(0,5)mm at the enrollment of the first year of senior high school,but the difference was not statistically significant(P=0.478).The difference range of average diameter of induration was±21 mm,39.70％of students being within±2 mm.Students with increased and decreased average diameter of induration accounted for 65.09％and 28.49％,respectively.Multivariate logistic regression analysis result showed that students in boarding school had a higher risk of positive conversion compared with non-boarding school students(OR=4.842,95％CI:2.794-8.392).Conclusion The screening of TB infection among grade-2 students in senior high school should be strengthened,with a focus on boarding school students.Early detection of tuberculosis patients and newly infected individuals can provide reference for implementing precise prevention and control.

Objective::This study aimed to explore the causal link between olive intake and the occurrence of coronary heart disease (CHD) using Mendelian randomization (MR).Methods::In this study, genome-wide association study data from IEU OpenGWAS were employed. A 2-sample MR analysis was used to determine the causal association of olive intake with CHD and cardiovascular outcomes (myocardial infarction, heart failure, stroke, and death due to cardiac causes). The data for olive intake included 64,949 samples and 9,851,867 single nucleotide polymorphisms (SNPs), the data for CHD included 361,194 samples and 13,295,130 SNPs; The data for myocardial infarction included 361,194 samples and 12,640,541 SNPs, the heart failure include 208,178 samples and 16,380,422 SNPs, the data for stroke included 361,194 samples and 12,404,026 SNPs, and the data for death due to cardiac causes included 361,194 samples and 10,071,648 SNPs. Additionally, a 2-step, 2-sample MR approach was used for mediation analysis to determine whether lipid traits mediate the causal association between olive intake and CHD. The data for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein A1 included 115,078 samples and 12,321,875 SNPs, while the data for triglycerides included 21,545 samples and 11,871,391 SNPs. Cochran’s Q test was applied to examine potential heterogeneity, and the MR-Egger method was used to assess horizontal pleiotropy among SNPs. Leave-one-out analysis was performed as a sensitivity analysis to evaluate the robustness of the results. Results::For each standard deviation increase in olive intake, the risk of CHD decreased by a substantial 1.9% (odds ratio (OR) = 0.981, 95% confidence interval (CI): 0.963 to 0.998, P = 0.031), the risk of myocardial infarction was significantly reduced by 1.6% (OR = 0.984, 95% CI: 0.969 to 0.999, P = 0.032), and the risk of heart failure declined by 62.1% (OR = 0.379, 95% CI: 0.192 to 0.746, P = 0.005). Furthermore, mediation analysis with MR indicated that lipid traits did not mediate the causal relationship between olive intake and CHD. Conclusion::There is a negative correlation between olive intake and the incidence of CHD, and this relationship is not mediated by lipid traits. Olive intake was also negatively associated with some cardiovascular outcomes, suggesting that increasing olive intake holds significant value in preventing the onset and progression of CHD.

Standardized research reporting is crucial for the translation of pharmacoepidemiology research findings,and visual reporting can significantly enhance the clarity,understandability,and transparency of research results.Based on the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition),this article systematically explains the key points for writing each component of a research report(including title,abstract,introduction,research methods,research results,discussion and conclusions,acknowledgments,conflict of interest statement,and references).This article also summarizes recognized international and domestic standards for pharmacoepidemiology research reporting,providing a reference for researchers.Furthermore,real-world cases will be used to demonstrate common forms of visualized reports and their interpretation methods.Finally,it further explores strategies for communicating research results.This study aims to provide pharmacoepidemiology researchers with detailed guidance on visually presenting research results and writing high-quality research reports,thereby enhancing the integrity and impact of their research.

Objective:To explore the influence of human induced pluripotent stem cell (iPSC) derived skin organoid-conditioned culture medium (SO-CM) on the function of human dermal fibroblasts (Fbs) induced by high glucose, with the aim of providing treatment ideas for diabetic wounds.Methods:This study was an experimental research. Human iPSCs were induced into skin organoids. Human iPSC-derived skin organoids and human dermal Fbs were seeded into skin organoid culture medium (SOM) and cultured for three days, respectively. Then the cell culture supernatants were collected as SO-CM and Fb-conditioned culture medium (Fb-CM), respectively. The content of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-18, C-C motif chemokine ligand 2 (CCL-2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), epidermal growth factor (EGF), and VEGF-β in SOM, Fb-CM, and SO-CM was detected by enzyme-linked immunosorbent assay. Human Fbs of passage 8 and 9 induced by high glucose were divided into SOM group, Fb-CM group, and SO-CM group according to the random number table method, and were cultured with SOM, Fb-CM, and SO-CM all containing glucose at final molarity of 35 mmol/L, respectively. After 24 hours of culture, the Ki67 positive ratio of cells was calculated after immunofluorescence staining, and the cell absorbance value was detected by using cell counting kit-8, representing cell proliferation activity. The cell scratch test was performed to calculate the cell migration rate at 13 hours after scratching. After 48 hours of culture, the expression of reactive oxygen species in cells was detected by fluorescent probe method, and the rate of β-galactosidase-positive staining of cells was detected by β-galactosidase staining kit, representing cellular senescence. The sample size was three.Results:There was no statistically significant difference in the content of TNF-α, PDGF, and TGF-β among the three culture media ( P>0.05). Compared with that in SOM, the content of IL-10 and EGF in Fb-CM and SO-CM was significantly decreased ( P<0.05), while the content of CCL-2 in FB-CM and VEGF in SO-CM was significantly increased ( P<0.05). After 24 hours of culture, the Ki67 positive ratio ((45.2±6.0)% and (57.4±4.0)%) and absorbance values (124±5 and 158±12) of cells in the Fb-CM group and the SO-CM group were significantly higher than those in the SOM group ((29.6±2.1)% and 100±6, P<0.05), and the Ki67 positive ratio and absorbance value of cells in the SO-CM group were significantly higher than those in the Fb-CM group ( P<0.05). At 13 hours after scratching, the cell migration rates in the Fb-CM group and the SO-CM group were significantly higher than that in the SOM group ( P<0.05). After 48 hours of culture, the level of reactive oxygen species in the SO-CM group was significantly higher than that in the SOM group and the Fb-CM group (with both P values <0.05). After 48 hours of culture, there was no statistically significant difference in the rate of β-galactosidase-positive staining of cells among the three groups ( P>0.05). Conclusions:The SO-CM has high content of VEGF and can significantly promote the proliferation, migration, and expression of reactive oxygen species in human dermal Fbs induced by high glucose, but has no significant effect on cell senescence.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.