Background With economic development and globalization, shift work has become prevalent across industries. Its relationship with type 2 diabetes mellitus (T2DM) attracts increasing attention. Objective To thoroughly explore the relationship between shift work and T2DM, and analyze the impacts of specific shift patterns on T2DM, so as to provide a basis for formulating reasonable shift schedules. Methods We conducted a 1:2 matched case-control study among adults (20-60 years) who ordered occupational health examinations at the Wuxi No.8 People's Hospital from November to December 2023. The case group comprised 200 T2DM patients, while the controls were 400 age-stratified matched non-diabetic individuals. General demographic characteristics, behavioral habits, medical history, and shift work exposure data (including shift patterns, frequency, and length of service) 5 years prior to diagnosis were collected through standardized questionnaires. Logistic regression adjusted for selected confounders was employed to evaluate the association between shift work and T2DM. Results The logistic regression analysis demonstrated that shift work was associated with an increased risk of T2DM. After adjusting for confounding factors, shift workers had a 3.55 times higher risk of being diagnosed T2DM compared to non-shift workers (OR=3.55, 95%CI: 1.026, 12.263). The risk varied across different shift patterns, and the three-shift two-rotation system showed the highest risk (OR=4.17, 95%CI: 1.921, 9.035), followed by the two-shift system (OR=2.94, 95%CI: 2.016, 4.281) and four-shift three-rotation system (OR=2.66, 95%CI: 1.611, 6.093). Workers with more than 3 monthly shift days had a 2.74-fold increased risk (95%CI: 1.658, 4.512) compared to non-shift workers. Additionally, working more than 8 h daily (OR=1.74, 95%CI: 1.185, 2.562) and having more than 20 years of service (OR=2.51, 95%CI: 1.581, 3.976) were both significantly associated with a higher T2DM risk. The trend tests revealed that each incremental increase in monthly shift days and length of service elevated T2DM risk by 2.61 times (95%CI: 1.813, 3.765) and 1.49 times (95%CI: 1.147, 1.931), respectively (P<0.05). Conclusion Shift work is an independent risk factor for T2DM, with three-shift two-rotation system posing the highest risk. Shift frequency, daily working hours, and length of service are all significant factors affecting the risk of T2DM. These findings support industry-specific shift policy reform and targeted glucose monitoring and health interventions are recommended for workers engaged in high-risk shift patterns (e.g., three-shift two-rotation system, frequent shifts) and those with prolonged shift work history (>20 years).

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Objective To investigate the effect of indigo on inflammatory factors and the aryl hydrocarbon receptor(AhR)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in lipopolysaccharide(LPS)-induced keratinocytes(HaCaT cells).Methods An LPS-induced HaCaT cell model was established,and experimental groups were set as follows:blank group,model group,indigo group,AhR agonist(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)group,AhR inhibitor(CH-223191)group,and indigo+AhR inhibitor group.The Cell Counting Kit-8(CCK-8)assay was used to detect the effects of different concentrations of indigo,TCDD,and CH-223191 on HaCaT cell viability after 24 hours of intervention.Quantitative real-time PCR(qPCR)was employed to measure the mRNA expression levels of interleukin-1β(IL-1β),nuclear factor kappa B(NF-κB),tumor necrosis factor-α(TNF-α),AhR,cytochrome P450 family 1 subfamily A member 1(CYP1A1),NLRP3,Caspase-1,and apoptosis-associated speck-like protein(ASC)in each group.Western Blot analysis was used to assess changes in the cellular localization of AhR protein expression.Results(1)The IC50 of indigo intervention in HaCaT cells was 118.7 μmol·L-1.Treatment with different concentrations of CH-223191 and TCDD for 24 hours had no significant effect on HaCaT cell viability.(2)Compared with the model group,the indigo group showed decreased mRNA expression levels of IL-1β,NF-κB,NLRP3,and Caspase-1(P＜0.05 or P＜0.000 1),while the mRNA expression levels of AhR and CYP1A1 were significantly increased(P＜0.05 or P＜0.000 1).(3)Compared with the blank group,the indigo group reduced cytoplasmic AhR protein expression and increased nuclear AhR protein expression(P＜0.001 or P＜0.000 1).(4)Compared with the model group,both the indigo group and the AhR agonist group significantly increased AhR mRNA expression levels(P＜0.05),while the AhR inhibitor group decreased AhR and CYP1A1 mRNA expression levels(P＜0.05)and increased IL-1β and NLRP3 mRNA expression levels(P＜0.05).(5)Compared with the AhR inhibitor group,the indigo+AhR inhibitor group showed increased mRNA expression levels of AhR and CYP1A1(P＜0.05)and decreased mRNA expression levels of NLRP3,Caspase-1,and IL-1β(P＜0.05).Conclusion Indigo reduces inflammatory factors in LPS-induced HaCaT cells and participates in inhibiting the occurrence and development of psoriasis by activating AhR to negatively regulate the NLRP3 inflammasome.

Objective : To construct a humanized mouse model of the interleukin-9 receptor(IL-9R) coding DNA sequence(CDS) gene and to verify the genotype and IL-9R expression in mice. Methods : The CRISPR/Cas9 genome editing technology was used to replace the exon 2-7 fragment of the il-9r gene in mouse embryonic stem cells with the corresponding human IL-9R sequence. After verifying the completion of the gene fragment replacement, tetraploid embryos were constructed and microinjected back into the oviducts of surrogate mice. Through surrogacy by female mice, homozygous humanized mice were obtained. DNA was extracted from the homozygous humanized mice IL-9R CDS gene, and their genotypes were identified by agarose gel electrophoresis after PCR amplification. Western blot was used to detect the expression of IL-9R in the spleen and thymus of homozygous humanized mice with either wild-type(WT) or IL-9R gene humanization. Results : Gel electrophoresis after PCR amplification showed that mice with only a 1 805 bp band amplified using WT primers were wild-type, while mice with 2 553 bp and 2 340 bp bands amplified using 5KI and 3KI primers, respectively, were homozygous humanized mice with IL-9R CDS gene. Western blot results indicated that the tissues of homozygous humanized mice model with IL-9R CDS gene expressed IL-9R significantly. Conclusion The humanized mouse model with IL-9R CDS gene has been successfully constructed and characterized.

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Objective To examine the precise function of influenza A virus target genes(IATGs)in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for IATGs.IATG expression in cancer cells was analyzed using transcriptome analysis.Copy number variation(CNV)was assessed using GISTICS 2.0.Spearman's analysis was used to correlate mRNA expression with methylation levels.GSEA was used for the enrichment analysis.Pearson's correlation analysis was used to examine the association between IATG mRNA expression and IC50.The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. Results In 13 solid tumors,IATG mRNA levels were atypically expressed.Except for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG mutations.The main types of CNVs in IATGs are heterozygous amplifications and deletions.In most tumors,IATG mRNA expression is adversely associated with methylation.RT-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.

Objective:To investigate the relationship between protein-energy wasting (PEW) and parathyroid hormone (PTH) levels in patients undergoing maintenance hemodialysis.Methods:A cross-sectional study was conducted to enroll 150 adult patients undergoing maintenance hemodialysis at The Third Affiliated Hospital of Anhui Medical University from January 2022 to May 2023. These patients were categorized into four groups based on their PTH levels: low PTH group (< 150 ng/L), standard PTH group (150-300 ng/L), very high PTH group (300-600 ng/L), and extreme high PTH group (> 600 ng/L). The diagnosis of PEW was determined using the diagnostic criteria proposed by the International Society of Renal Nutrition and Metabolism (ISRNM). Logistic regression analysis was performed to investigate the association between PEW and PTH levels.Results:Among the 150 patients undergoing maintenance dialysis, 52 (34.7%) were diagnosed with PEW. The prevalence of PEW was significantly higher in the low PTH group compared with the standard, very high, and extreme high PTH groups ( χ2 = 20.64, all P < 0.05). Univariate logistic regression analysis revealed a strong association between low PTH levels ( OR = 13.810, 95% CI: 2.907-65.603, P = 0.001) and an increased risk of PEW. The risk of PEW in the low PTH group was 13.810 times higher than that in the extreme high PTH group. Multivariate logistic regression analysis further confirmed that low PTH levels ( OR = 19.891, 95% CI: 1.810-218.620, P = 0.014) and low C-reactive protein levels ( OR = 1.056, 95% CI: 1.015-1.099, P = 0.007) were independently associated with an increased risk of PEW. Higher hemoglobin levels ( OR = 0.959, 95% CI: 0.931-0.988, P = 0.005) and a larger middle upper arm circumference ( OR = 0.544, 95% CI: 0.338-0.875, P = 0.012) were independently associated with a reduced risk of PEW. The risk of PEW in the low PTH group was 19.891 times higher than that in the extreme high PTH group. However, there was no significant difference in the risk of PEW in the standard and very high PTH groups compared with the extreme high PTH group (both P > 0.05). Conclusion:The risk of PEW is markedly elevated in patients with low PTH levels, emphasizing the importance of clinical attention to the prevention and treatment of low PTH levels. Addressing this issue may hold great value in reducing the risk of PEW.

Objective To investigate the job burnout of medical staff during long voyage in a navy warship troop and its influencing factors.Methods A total of 141 medical staff,who participated in a long voyage between January 2021 and December 2021,were consecutively included for surveys about basic information,job burnout,sleep quality,and regulation mode.Univariate and multivariate analyses were used to explore influencing factors for job burnout.Results The proportion of mild and below job burnout and moderate to severe job burnout in the cohort was 45.39%and 54.61%,respectively.Univariate analysis showed that married status,Master's or Doctor's degree,moderate to heavy workload,no psychological training experience,sleep disorder and low-exercise regulation mode were significant influencing factors for job burnout(P<0.05).Multivariate analysis showed that married status,Master's or Doctor's degree,sleep disorder and low-exercise and high-evaluation regulation mode were independent risk factors for job burnout(P<0.05).However,psychological training experience was considered to be a significant protective factor(P= 0.021).Conclusion Medical staff in a navy warship troop experiences severe job burnout during long voyage.The people who are married,have a Master's or Doctor's degree,have sleep disorder and low-exercise and high-evaluation regulation mode are more likely to experience job burnout,which should be paid more attention to.

Objective:To evaluate the efficacy of arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique for the treatment of tibial avulsion fracture of posterior cruciate ligament (PCL).Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with tibial avulsion fracture of PCL, who were admitted to First People′s Hospital of Huizhou from January 2018 to October 2022. There were 19 males and 13 females, with age range of 18-65 years [(42.8±15.0)years]. By the Meyers-Mckeever classicfication, 27 patients were type II, and 5 type III. All the patients were treated with arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique to fix PCL tibial avulsion fracture at the insertion point. The fracture reduction was observed by X-ray films before discharge. Three months postoperatively, the fracture healing was observed by CT imaging, and the stability of knee joint was evaluated by posterior drawer test. The knee active range of motion, visual analogue score (VAS), Lysholm score, and International Knee Documentation Committee (IKDC) score were used to evaluate the pain and knee function before operation, at 3 months after operation, and at the last follow-up. Intraoperative and postoperative complications were observed.Results:All the patients were followed up for 6-36 months [(19.7±8.7)months]. The X-ray films showed satisfactory reduction of the fracture before discharge, and the CT showed that the fracture line was blurred to various degrees at 3 months after operation. Two patients had degree I positive posterior drawer test at 3 months after operation, and the rest were negative. The knee active range of motion was improved from 54.2°(45.0°, 70.0°) preoperatively to 124.8°(120.0°, 130.0°) at 3 months postoperatively and to 130.6°(125.0°, 135.0°) at the last follow-up (all P<0.01). The VAS was decreased from 5.1(3.0, 7.0)points preoperatively to 1.2(1.0, 2.0)points at 3 months postoperatively and to 0.1(0.0, 0.0)points at the last follow-up (all P<0.01). The Lysholm score was improved from 31.2(24.3, 37.0)points preoperatively to 73.6(69.3, 78.8)points at 3 months postoperatively and 92.6(91.0, 95.0)points at the last follow-up (all P<0.01). The IKDC score was increased from (20.9±7.1)points preoperatively to (59.2±8.9)points at 3 months postoperatively and to (77.5±7.0)points at the last follow-up (all P<0.01). Compared with 3 months after operation, the last follow-up showed significantly improved knee active range of motion, significantly decreased VAS, and significantly increased Lysholm score and IKDC score (all P<0.05). No intraoperative nerve vascular injury, postoperative incision infection, or lower limb venous thrombosis was observed. Conclusion:Arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique can achieve good reduction and high healing rate in patients with tibial avulsion fracture of PCL, with improved joint mobility, relieved pain, good recovery of knee joint function, and few complications.

Background Studies on the association between greenness exposure and allergic rhinitis (AR) in children are mostly conducted in developed countries, and the conclusion is not consistent. Objective Using street view data to explore the association between greenness exposure and allergic rhinitis (AR) prevalence in Chinese children. Methods A cross-sectional study was conducted among 40868 children aged 2-17 years in three cities of Northeast China from 2012 to 2013, which consisted of 20886 (51.1%) boys and 19982 (48.9%) girls. The information of AR prevalence was obtained through questionnaire. Based on downloaded street view images from Tencent Maps, a green view index (GVI) of green vegetation (trees and grass) within 800 m and 1000 m buffer of the participants' schools was calculated by using artificial intelligence, and it was used as a surrogate of the greenness exposure. A mixed-effect logistic regression model was used to estimate the odds ratio (OR) of AR prevalence in children for per increase of inter-quartile range (IQR) of GVI. In addition, according to ambient PM_2.5 concentration, the participants were divided into a low PM_2.5 exposure group (≤56.23 μg·m⁻³) and a high exposure group (>56.23 μg·m⁻³) to investigate whether PM_2.5 was a modifier on the association between GVI and AR. Results The average age of the subjects was (10.40±3.68) years and 3 963 (9.7%) subjects reported diagnosed AR. Within 800 m buffer, an IQR increase in GVI for trees (IQR=0.031, OR=0.85, 95%CI: 0.81-0.90) and overall greenness (IQR=0.029, OR=0.86, 95%CI: 0.81-0.90) was associated with lower adjusted odds ratio of AR. The interaction between PM_2.5 and GVI was statistically significant (P< 0.1), that is, the negative associations of trees and overall greenness with AR were observed only at low PM_2.5 exposure levels. The sensitivity analysis results of GVI within 1000 m buffer was consistent with that within 800 m buffer. Conclusion Exposure to green vegetation, especially trees, may be associated with decreased risks of AR in children, and such associations may be more obvious in areas with a low PM_2.5 concentration.