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.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective To investigate the expression of trophoblast cell-surface antigen 2(TROP2)in salivary ade-noid cystic carcinoma(SACC)in order to analyze its relationship with TROP2 expression and clinicopathological features,as well as to clarify the correlation between TROP2 expression and the prognosis of patients with SACC.Methods With approval from the ethics committee,the expression of TROP2 in 85 SACC and paracancer tissue sam-ples was detected by using the immunohistochemical method,and the relationship between TROP2 expression and clini-copathological characteristics was analyzed.The Kaplan-Meier method was used to analyze the relationship between TROP2 protein expression and 5-year disease-free survival(DFS)in 40 patients with SACC.Furthermore,the logistic re-gression model was used to analyze the prognostic factors of patients with SACC.Results The low or no expression rate of TROP2 in SACC tissues was significantly higher than that in paracancer tissues(P＜0.001).Low or no expres-sion of TROP2 was significantly positively correlated with tumor growth and clinical staging in patients with SACC(P＜0.05).Kaplan-Meier survival analysis showed that the DFS of patients with SACC with low or no expression of TROP2 protein was significantly lower than those of patients with high expression of TROP2 protein(P＜0.05),and the progno-sis was poor.The logistic regression model showed that low or no expression of TROP2 protein(OR=5.37;95%CI:1.03-28.08;P=0.046)and Ⅲ-Ⅳ clinical staging(OR=6.89;95%CI:1.37～34.77;P=0.019)were risk factors affect-ing the prognosis of patients with SACC.Conclusion Low or no expression of TROP2 protein in SACC tissues leads to poor prognosis of patients and is positively correlated with tumor growth and clinical staging.In addition,low or no ex-pression of TROP2 can be used as an independent prognostic risk factor for poor prognosis in patients with SACC,and TROP2 is a marker of poor prognosis in patients with SACC.

Objective:To compare the effectiveness of the Moses holmium laser and the traditional holmium laser in the treatment of kidney stones using flexible ureteroscopy.Methods:The data of 425 patients with kidney stones treated with flexible ureteroscopic holmium laser lithotripsy at Hebei University Affiliated Hospital from January 2017 to January 2023 were retrospectively analysed. Among them, 136 cases were treated with traditional holmium laser (traditional group), and 289 cases were treated with Moses holmium laser (Moses group). To minimize selection bias due to non-random allocation, 1∶1 propensity score matching (PSM) was employed, ensuring comparability between the two groups in baseline characteristics (age, gender) and stone characteristics (stone location, number, diameter, CT value, and stone composition). The differences in operation time, laser action time, stone clearance rate (SFR), postoperative complications and secondary treatment rate were compared between the two groups after matching. The risk factors affecting SFR were analyzed by multivariate logistic regression. The efficacy of Moses group and traditional group in treating kidney stones with diameter ≥20 mm was also compared.Results:After PSM, 108 patients were selected from each group for data analysis. Traditional group and Moses group demonstrated good consistency in baseline characteristics, including age [57.0(49.0, 65.0) years old vs. 58.5(51.8, 66.0) years old], male gender [58.3% (63/108) vs. 60.2% (65/108)], stone location(upper calyx / mid calyx / lower calyx / pelvis: 33/35/38/42 cases vs. 35/33/40/42 cases), multiple stones [33.3% (36/108) vs. 35.2% (38/108)], diameter [14.0(11.0, 16.0)mm vs. 14.0(12.0, 17.0)mm], CT value [1 115.5(993.2, 1 228.2) HU vs. 1 114.5(1 000.2, 1 216.5) HU], and the presence of calcium stones [83.3% (90/108) vs. 79.6% (86/108)], and all showing absolute standardized mean difference(ASMD) <0.1. The Moses group had shorter operation time [48.5(36.0, 56.0)min vs. 60.0(48.8, 68.0)min, P<0.01], higher post-operative stone-free rate (SFR) [88.9%(96/108) vs. 67.6(73/108), P<0.01], and lower rate of secondary surgery [1.8%(2/108) vs. 9.3%(10/108), P=0.04], indicating advantages in surgical efficiency and post-operative outcomes. Multivariable logistic regression analysis revealed that using Moses holmium laser ( OR=0.029, P<0.01), stone diameter ( OR=1.492, P<0.01), stone CT value ( OR=1.007, P<0.01), presence of calcium stones ( OR=1.551, P<0.01), holmium laser application time ( OR=0.863, P<0.01), preoperative placement of a double-J stent ( OR=0.193, P<0.01), and preoperative moderate to severe hydronephrosis ( OR=1.651, P<0.01) were significant factors affecting SFR. In treating stones with a diameter of 20-30 mm, the surgery time of Moses group was shorter than that of traditional group [50.5(43.8, 58.3)min vs. 72.0(68.0, 78.0)min, P<0.05], and the laser application time of Moses group was also shorter [29.5(22.8, 36.0)min vs. 36.0(32.0, 41.0)min, P<0.05]. The post-operative SFR of Moses group was higher than that of traditional group [65.6%(42/64) vs. 35.3%(6/17), P<0.05], and the rate of secondary surgery was lower[7.8%(5/64) vs. 29.4(5/17), P<0.05]. Conclusions:Flexible ureteroscopy combined with Moses holmium laser lithotripsy demonstrated significant advantages over traditional holmium laser in enhancing stone clearance rate, reducing operation time, and lowering the need for secondary surgeries in the treatment of kidney stones. Flexible ureteroscopy combined with Moses holmium laser lithotripsy also proves its efficacy and clinical value in managing complex kidney stone cases.

AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.

OBJECTIVE: To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients. METHODS: A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis. RESULTS: A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05). CONCLUSIONS The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.
Humans ; Organ Dysfunction Scores ; Retrospective Studies ; C-Reactive Protein ; ROC Curve ; Sepsis/metabolism* ; Prognosis ; Anticoagulants ; Antithrombin III ; Intensive Care Units

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Objective:To investigate the clinical effects of tibial transverse bone transport assisted by nose ring drainage (NRD) in the treatment of foot and ankle chronic osteomyelitis.Methods:A retrospective study was conducted to analyze the data of 32 patients with foot and ankle chronic osteomyelitis who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from March 2013 to February 2022. The patients were assigned into a study group and a control group. In the control group, there were 12 males and 3 females, aged (39.5±8.8) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 2 cases, at the midfoot in 4 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 5 cases of type Ⅰ and 10 cases of type Ⅱ. The control group was treated with Ilizarov transverse tibial bone transport in combination with thorough debridement and anti-infection therapy. In the study group, there were 12 males and 5 females, aged (42.3±13.4) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 3 cases, at the midfoot in 5 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 7 cases of type Ⅰ and 10 cases of type Ⅱ. The study group was treated with NRD drainage in addition to the procedures in the control group. The curative effects were evaluated by comparing the cure, recurrence, amputation (toe amputation), antibiotic use time, wound healing time, relevant inflammatory indicators [WBC, neutrophil percentage (NEU), erythrocyte sedimentation rate (ESR), procalcitonin, interleukin-6 (IL-6), C-reactive protein (CRP)], and postoperative functional recovery between the 2 groups.Results:The 2 groups were comparable because there was no statistically significant difference in the general data between them ( P>0.05). The follow-up period was (36.0±9.8) months. There was no significant difference between the 2 groups in the cure or amputation (toe amputation) ( P>0.05), but the recurrence rate in the study group was significantly lower than that in the control group ( P<0.05). The antibiotic use time [(20.7±3.6) d] and wound healing time [(88.3±17.1) d] in the study group were significantly shorter than those [(37.9±6.5) d and (102.2±22.6) d] in the control group ( P<0.05). The ESR, IL-6 and CRP at 1 week after operation in the study group were significantly lower than those in the control group ( P<0.05), but there was no significant difference between the 2 groups in the WBC, NEU or PCT at 1 week after operation ( P>0.05). There was no significant difference either in the inflammatory indicators between the 2 groups at 1 month after operation ( P>0.05). In all patients, the inflammatory indicators like WBC, NEU, ESR, PCT, IL-6 and CRP at 1 week and 1 month after operation were significantly better than those before operation, and the Maryland foot functional score at 12 months after operation was significantly higher than the preoperative one ( P<0.05). There was no significant difference between the 2 groups in the Maryland foot functional score at 12 months after operation ( P>0.05). Conclusion:In the treatment of foot and ankle chronic osteomyelitis, compared with the Ilizarov transverse tibial bone transport, our tibial transverse bone transport assisted by NRD can achieve satisfactory therapeutic effects, shorten antibiotic use time and treatment cycle, and reduce recurrence rate.

Botulinum toxin is a potent protein toxin produced by Clostridium botulinum. It acts directly on the brain nerve nucleus and peripheral neuromuscular junction, blocking the release of acetylcholine and thereby affecting nerve impulse transmission, ultimately leading to muscle paralysis. Mild cases may present with ocular muscle involvement, whereas severe cases may involve dysphagia, general paralysis, respiratory depression, and even death. This article reports on a patient who experienced severe poisoning symptoms after using type A botulinum toxin obtained through informal channels. The patient was treated with antitoxin on the 13th day after symptoms onset and achieved a significant improvement in their condition.