Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.

OBJECTIVE: To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back. METHODS: Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage. RESULTS: All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site. CONCLUSION The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Plastic Surgery Procedures ; Myocutaneous Flap/surgery* ; Shoulder/surgery* ; Skin Transplantation ; Superficial Back Muscles/transplantation* ; Soft Tissue Injuries/surgery* ; Wound Healing ; Treatment Outcome ; Perforator Flap

Postoperative pain, a common problem in perioperative management, has negative impact on patients' experience and functional recovery. The development of postoperative pain is not only related to direct surgical trauma, but also a series of preventable perioperative risk factors, among which perioperative sleep quality should not be neglected. In recent years, more and more researches have indicated that poor perioperative sleep quality is a risk factor for both acute and chronic postoperative pain, and some researches have even pointed out that sleep quality can directly influence patients' pain threshold. Therefore, this review aims to summarize current research progress on the influence of perioperative sleep quality on postoperative pain, hoping to provide reference for improving the perioperative pain management for patients.

Objective To analyze the efficacy of bevacizumab combined with paclitaxel+carboplatin in the treatment of recurrent/metastatic cervical cancer,and to explore the influence on survival prognosis of patients.Methods Patients with recurrent/metastatic cervical cancer were divided into control group and treatment group according to different treatment methods.The control group received paclitaxel combined with carboplatin chemotherapy regimen(intravenous infusion of 170 mg·m-2 paclitaxel and carboplatin(AUC=5 mg·mL-1·min)for 3 weeks as a course of chemotherapy),and the treatment group was given bevacizumab on the basis of control group,intravenous infusion of 15 mg·kg-1 bevacizumab,once every 3 weeks.Both groups were treated for 3 cycles of treatment by taking 3 weeks as 1 treatment cycle.The clinical efficacy,levels of serum tumor markers,quality of life,survival prognosis and occurrence of drug-related adverse reactions during treatment were compared between the two groups.Results There were 41 cases in treatment group and 48 cases in control group.After treatment,the overall response rate(ORR)of treatment group and control group were 31.71％(13 cases/41 cases)and 14.58％(7 cases/48 cases),with no statistical significance(P＞0.05).After treatment,the disease control rate(DCR)in control group and treatment group were 62.50％(30 cases/48 cases)and 82.93％(34 cases/41 cases);the squamous cell carcinoma antigen(SCCA)levels were(3.58±0.73)and(2.52±0.57)ng·mL-1;carbohydrate antigen 19-9(CA19-9)levels were(23.60±4.29)and(19.19±3.72)U·mL-1;carbohydrate antigen 15-3(CA15-3)levels were(27.13±5.36)and(22.86±3.94)U·mL-1;carbohydrate antigen 125(CA125)levels were(39.24±6.88)and(26.47±5.09)U·mL-1;the overall improvement rates of quality of life were 41.67％(20 cases/48 cases)and 73.17％(30 cases/41 cases),the progression-free survival times were 8.67 months(95％CI:7.82-9.53)and 10.25 months(95％CI:9.68-10.81),the total survival times were 9.96 months(95％CI:9.13-10.79)and 11.47 months(95％CI:11.00-11.93),all with significant difference(all P＜0.05).There were no statistically significant differences in the incidence of nausea and vomiting,leukopenia,thrombocytopenia and liver-kidney function impairment between both groups(all P＞0.05).Conclusion Bevacizumab combined with chemotherapy has significant efficacy in the treatment of recurrent/metastatic cervical cancer,and it can reduce the levels of serum tumor markers,enhance the quality of life,and improve the survival prognosis,and it has good safety.

Objective To investigate the effect of propanaxanediol on proliferation and apoptosis of human ovarian cancer cell HO-8910 and analyze the mechanism.Methods Human ovarian cancer cell HO-8910 were randomly divided into blank group(0.9％NaCl)and experimental-L,-M,-H groups(25,50,100 mg·kg-1 propanaxanadiol treated cells,respectively).Cell counting kit-8(CCK-8)was used to detect the proliferation inhibition;the apoptosis was detected by flow cytometry;the migration was detected by cell scratch test;the invasion was detected by Transwell assay;the expression levels of phosphatidylinositol 3 kinase(PI3K),phosphorylated protein kinase B(p-AKT),proliferating cell nuclear antigen(PCNA),B cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)were detected by Western blot.Results The proliferation inhibition rates of blank group and experimental-L,-M,-H groups were(16.89±4.15)％,(28.43±3.66)％,(37.96±4.98)％and(50.11±5.24)％;the apoptosis rates were(4.23±1.07)％,(12.36±2.79)％,(24.32±2.93)％and(42.40±3.28)％;the expression levels of PCNA protein were 0.85±0.08,0.69±0.06,0.43±0.06 and 0.25±0.03;the expression levels of Bax protein were 0.18±0.03,0.33±0.04,0.50±0.05 and 0.69±0.05;the expression levels of Bcl-2 protein were 0.82±0.07,0.63±0.04,0.47±0.05 and 0.30±0.03;the mobility were(52.33±4.25)％,(40.16±4.03)％,(29.63±3.25)％and(20.15±2.12)％;the invasion rates were(60.26±5.88)％,(49.33±4.28)％,(30.15±3.68)％and(22.15±1.96)％;the expression levels of PI3K protein were 0.48±0.04,0.34±0.04,0.26±0.03 and 0.15±0.01;the expression levels of p-AKT protein were 0.45±0.03,0.35±0.02,0.23±0.03 and 0.13±0.02,respectively.There were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the blank group(all P＜0.05).Conclusion Protopanaxadiol may inhibit the proliferation,migration and invasion of human ovarian cancer cell HO-8910 by blocking the activation of PI3K/AKT signaling pathway,regulating the expression of PCNA,Bax and Bcl-2 proteins and promoting their apoptosis,thus achieving anti-ovarian cancer effects.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective:Screening factors that might influence rheumatoid arthritis (RA) complicating interstitial lung diseases (ILD) by constructing and validating a model for early diagnostic.Methods:The study subjects were composed of 712 RA patients in the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University during December 2019 to October 2022. Fifty-two variables such as their demographic data, clinical symptoms, and laboratory indexes were collected. Patients were categorized into RA-only group and RA-ILD group with or without the occurrence of ILD disease. After data preprocessing, subjects were randomly assigned to the modeling and validation groups in a 7:3 ratio.Univariate analysis comparing baseline characteristics of the two groups of patients. Feature selection was performed using LASSO and SVM-RFE regression algorithms.Screening indicators were analyzed by logistic regression and the results were used to develop a nomograms model for the early diagnosis of RA complicating interstitial lung disease; and the modeling group was evaluated for its performance for internal assessment of the model and internal validation using data from the validation group.Results:A total of 712 subjects participated in the study, of which 498 in the modeling group and 214 in the validation group. Univariate analysis showed that the differences between the two groups were statistically significant ( P<0.05) in 18 characteristic indexes, including male, gender, age, smoking history, drinking history, number of swollen joints, number of painful joints, use of prednisone, WBC, ESR, CRP, IL-2, IL-10, IL-17, TNF-α, INF-γ, AFA family, APF, and serum albumin. The LASSO algorithm identified 13 risk variables for RA-ILD, the SVM-RFE algorithm identified 12 variables for RA-ILD, and the intersecting risk variables were male, age, history of alcohol consumption, number of painful joints, prednisone acetate, IL-2, AFA family, TNF-α, serum albumin, and IL-10. The results of multifactorial logistic regression analysis confirmed that the differences between males [ OR(95% CI)=3.61(2.11, 6.18)], gender, age [ OR(95% CI)=1.05(1.03, 1.08)], number of painful joints [ OR(95% CI)=1.03(1.01, 1.06)], IL-2 [ OR(95% CI)=0.91 (0.84, 0.99)], and TNF-α[ OR (95% CI)=1.06 (1.02, 1.10)] were statistically significant ( P<0.05) and were independently influences on ILD complicated by RA. The modeling and validation groups that were used to construct early diagnostic Nomograms had high calibration curve accuracies, and the model had a high diagnostic power, which was mainly demonstrated by the receiver operating characteristic (ROC) area under the curve (AUC) and decision curve analysis(DCA), the model modeling group had an AUC of 0.76 (95% CI=0.71, 0.81), with net benefit rates of 3%~82% and 93%~99%, whereas the model validation group had an AUC of 0.71 (95% CI=0.64, 0.79), with net benefit rates of 5%~11%, 14%~60% and 85%~89%. Conclusion:Male, gender, age, number of painful joints, IL-2, and TNF-α are independent factors for RA complicated with ILD, and the Nomogram model constructed has good performance in early diagnosis of the disease.

Proteolysis targeting chimera (PROTAC) is a drug discovery strategy using ubiquitin proteasome system (UPS) to degrade the target protein. Unlike traditional small molecule drugs utilizing occupancy-driven pharmacology as the mode of action (MOA) to regulate protein activity, PROTACs function through forming stable target protein-PROTAC-E3 ubiquitin ligase ternary complex and use ubiquitin proteasome system to degrade the target protein. However, only a few E3 ubiquitin ligases have been used in PROTAC drug design now, and the space of target proteins that PROTAC can target needs to be further expanded. On the other hand, the complicated system of ternary crystal structures is difficult to capture and identify, computational simulation provides modeling of PROTAC-mediated ternary complex formation with effective approaches. In view of this, this review describes the recent progress of bioinformatics on expanding the landscape of E3 ubiquitin ligases and target proteins, and summarizes the methods of computation simulation in modeling PROTAC ternary complex. Finally, the trend of development about PROTAC is prospected.

mRNA gene therapy has attracted much attention due to its advantages such as scalability, modification, no need to enter the nucleus and no integration of host genes. In gene therapy, safe and effective delivery of mRNA into cells is critical for the success of gene therapy. In this study, we designed and synthesized an amphiphilic cationic lipopeptide gene vector (dendritic arginine & disulfide bond-containing cationic lipopeptide, RLS) enriched with branched arginine. We achieved a 1.5-fold higher mRNA transfection efficiency in zebrafish compared to the commercial reagent Lipofectamine 2000, and confirmed its good biosafety by in vitro cytotoxicity and in vivo biosafety. First, we characterized the chemical composition of the cationic lipid peptides by nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) and time-of-flight mass spectrometry (MS). The results of particle size and potential tested by dynamic light scattering particle size analysis showed that at a nitrogen/phosphorus (N/P) ratio of 20, the RLS/mRNA composite assemblies formed homogeneous nanoparticles with an average particle size of about 220 nm and a surface ζ potential of about +21 mV. In vitro gene transfection, the transfection experiments demonstrated that RLS exhibited 1.2-fold higher transfection efficiency in human embryonic kidney 293 cells (HEK293) and 3-fold higher transfection efficiency in rat mesenchymal stem cells (MSC) compared to Lipofectamine 2000. In addition, after microinjection of RLS into zebrafish embryos, we evaluated the survival, hatching, and teratogenicity rates, all of which confirmed its favorable in vivo safety profile. Thus, this amphiphilic cationic lipid peptide RLS, enriched with branched arginine, exhibits excellent mRNA delivery properties and safety. These findings highlight its potential as a promising gene therapy tool.