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.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

OBJECTIVE: To investigate the effectiveness of Holosight robotic navigation-assisted percutaneous cannulated screw fixation for femoral neck fractures. METHODS: A retrospective analysis was conducted on 65 patients with femoral neck fractures treated with cannulated screw fixation between January 2022 and February 2024. Among them, 31 patients underwent robotic navigation-assisted screw placement (navigation group), while 34 underwent conventional freehand percutaneous screw fixation (freehand group). Baseline characteristics, including age, gender, fracture side, injury mechanism, Garden classification, Pauwels classification, and time from injury to operation, showed no significant differences between the two groups ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy frequency, fracture healing time, and complications were recorded and compared, and hip function was evaluated by Harris score at last follow-up. Postoperative anteroposterior and lateral hip X-ray films were taken to assess screw distribution accuracy, including deviation from the femoral neck axis, inter-screw parallelism, and distance from screws to the femoral neck cortex. RESULTS: No significant difference was observed in operation time between the two groups ( P>0.05). However, the navigation group demonstrated superior outcomes in intraoperative blood loss, fluoroscopy frequency, deviation from the femoral neck axis, inter-screw parallelism, and distance from screws to the femoral neck cortex ( P<0.05). No incision infections or deep vein thrombosis occurred. All patients were followed up 12-18 months (mean, 16 months). In the freehand group, 1 case suffered from cannulated screw dislodgement and nonunion secondary to osteonecrosis of femoral head at 1 year after operation, 1 case suffered from screw penetration secondary to osteonecrosis of femoral head at 5 months after operation; and 1 case suffered from nonunion secondary to osteonecrosis of femoral head at 6 months after operation in the navigation group. All the 3 patients underwent internal fixators removal and total hip arthroplasty. There was no significant difference in the incidence of complications between the two groups ( P>0.05). The fracture healing time and hip Harris score at last follow-up in the navigation group were significantly better than those in the freehand group ( P<0.05). CONCLUSION Compared to freehand percutaneous screw fixation, Holosight robotic navigation-assisted cannulated screw fixation for femoral neck fractures achieves higher precision, reduced intraoperative radiation exposure, smaller incisions, and superior postoperative hip function recovery.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Screws ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Middle Aged ; Aged ; Adult ; Treatment Outcome ; Operative Time ; Fracture Healing ; Surgery, Computer-Assisted/methods* ; Fluoroscopy

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Lirispirolides A-L (1-12), twelve novel sesquiterpene-monoterpene heterodimers featuring distinctive carbon skeletons, were isolated from the branches and leaves of Chinese tulip tree [Liriodendron chinense (L. chinense)], a rare medicinal and ornamental plant endemic to China. The structural elucidation was accomplished through comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray crystallography. These heterodimers exhibit a characteristic 2-oxaspiro[4.5]decan-1-one structural motif, biosynthetically formed through intermolecular [4 + 2]-cycloaddition between a germacrane-type sesquiterpene and an ocimene-type monoterpene. The majority of the isolated compounds demonstrated significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells by reducing the production of pro-inflammatory mediators, specifically tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further investigation revealed that the lirispirolides' inhibition of NO release correlated with decreased messenger ribonucleic acid (mRNA) expression of inducible NO synthase (iNOS).
Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Mice ; Tumor Necrosis Factor-alpha/genetics* ; Nitric Oxide/immunology* ; Microglia/immunology* ; Molecular Structure ; Liriodendron/chemistry* ; Monoterpenes/isolation & purification* ; Plants, Medicinal/chemistry* ; Cell Line ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; China

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective:To determine the content of the released nickel ion through the 7 extraction media to extract the Ni-Ti wires and to plot the curve of the released nickel ion so as to identify a leaching medium that can be substituted for blood for in vitro Ni release evaluation. Methods:The release of Ni through microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) in the goat serum was determined. Because of the high content of Ni release, it could be determined by diluting the extraction medium, and other extraction media could be determined directly. Ni release standard curves were plotted by the release amount and different time point variables. Though the different extraction media Ni release curves confirm the specificity of extraction media instead of blood.Results:By analyzing the Ni release curves of seven leaching media, it was found that none of these seven extraction media was suitable for the evaluation of Ni release in in vitro leaching media. Considering the safety of the leaching medium and the simplicity of preparation, hydrochloric acid solution was chosen as the leaching medium, but the concentration needed to be diluted accordingly. Finally, a hydrochloric acid solution was created as an alternative to blood for the in vitro study of Ni release from Ni-Ti alloy cardiovascular products, with a volume fraction of 0.005%. Conclusions:The in vitro leaching medium that can replace blood was found to be hydrochloric acid for the time being, but its concentration was too high, resulting in too much Ni release as well, which deviated from the actual situation. Therefore, the hydrochloric acid solution was diluted step by step, and the Ni release curve was examined until it was close to the clinical release level, and the actual concentration was determined, thus laying a solid foundation for the subsequent evaluation of the safety and risk.