Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

Background Volatile organic compounds (VOCs) in exhaled breath are closely associated with respiratory diseases and are linked to various metabolic reactions in the human body. A quantitative analytical method can provide technical support for studying VOCs related to various diseases. Objective To establish a thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method for the determination of 27 VOCs in exhaled breath. Methods VOCs in exhaled breath were collected using a Bio-VOC sampler and enriched with Tenax TA thermal desorption tubes before TD-GC-MS analysis. Standards were collected using thermal desorption tubes and optimized for thermal desorption conditions as well as chromatographic and mass spectrometric conditions: The separation of the 27 VOCs was achieved by an optimized temperature program, the improvement of sensitivity by optimizing quantitative ions, and the increase of VOCs desorption efficiency by optimizing thermal desorption time and temperature. Limit of detection, limit of quantification, accuracy, precision, and stability of the proposed method were investigated by spiking with a blank gas bag, and exhaled breath samples from 20 healthy individuals were collected for an application study of the proposed method. Results The thermal desorption temperature was 280 ℃, and desorption time was 6 min. A VF-624ms chromatographic column was selected for the separation of target substances. The initial temperature of heating program was 35 ℃, maintained for 1 min, and then increased to 100 ℃ at a heating rate of 3 ℃·min⁻¹ for 1 min, followed by increasing to 210 ℃ at a heating rate of 28 ℃·min⁻¹ for 5 min. A quantitative analysis was conducted with a single ion monitoring (SIM) mode. Under these conditions, the 27 VOCs showed good linear relationships in their respective concentration ranges and the correlation coefficients were higher than 0.9990. The limits of detection of the method were in the range of 0.01-0.13 nmol·mol⁻¹, the limits of quantification were in the range of 0.02-0.44 nmol·mol⁻¹, and the spiked recoveries were in the range of 80.1%-120.5%, with intra-batch and inter-batch precision ≤ 18.8% and 17.9% respectively. All substances can be stored at room temperature (23-28 °C) for 7 d and at 4 °C for 14 d. The proposed method was applied to exhaled breath samples from 20 subjects with detection rates≥ 80% (except for trans-2-pentene and decane) and a concentration range of 0.00-465.50 nmol·mol⁻¹. Conclusion The established TD-GC-MS method for quantification of VOCs in exhaled breath is characterized by high sensitivity and good accuracy, and is suitable for quantitative determination of VOCs in exhaled breath, which can provide technical support for the study of exhaled breath VOCs.

Objective To investigate the application value of multimodal MRI in complex anal fistula.Methods The clinical and MRI data of 50 cases with complex anal fistula confirmed by surgery were collected.All patients were examined with 1.5T MR before surgery,including three major modules of conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Finally,the diagnostic efficacy of different MRI modules in complex anal fistula was evaluated based on the surgical results.Results The surgery detected 73 internal orifices,81 external orifices,58 main fistulas,47 branch fistulas and 37 abscesses.Before the surgery,there were 63 internal orifices(86.3%),75 external orifices(92.6%),53 main fistulas(91.4%),40 branch fistulas(85.1%),and 37 abscesses(100%)correctly diagnosed by conventional MRI.Sixty internal orifices(82.2%),75 external orifices(92.6%),51 main fistulas(87.9%),37 branch fistulas(78.7%),and 37 abscesses(100%)were correctly diagnosed by conventional MRI+DWI,while 68 internal orifices(93.2%),78 external orifices(96.3%),56 main fistulas(96.6%),44 branch fistulas(93.6%),and 37 abscesses(100%)were correctly diagnosed by conventional MRI+DCE-MRI.There were 68 internal orifices(93.2%),78 external orifices(96.3%),56 main fistulas(96.6%),44 branch fistulas(93.6%),and 37 abscesses(100%)correctly diagnosed by conventional MRI+DWI+DCE-MRI.Compared with conventional MRI,conventional MRI+DWI or conventional MRI+ DCE-MRI,conventional MRI+DWI+DCE-MRI could find more internal orifices,main fistulas and branch fistulas,and the difference was statistically significant.The multimodal MRI had the highest consistency with the surgical results(Kappa=0.734,P<0.001).Conclusion MRI can accurately estimate the information of internal orifices,external orifices,main fistula,branch fistula and abscess of cases with complex anal fistula.The diagnostic accuracy of multimodal joint application is superior than that of single-modal and dual-modal application.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Currently， there are many difficulties in formulating recommendations of traditional Chinese medicine （TCM） clinical practice guidelines. This paper analyzed and summarized the unique or prominent difficult issues in the formulation of recommendations faced by TCM guidelines， such as experts' professional background and experience bringing about the preferance from the academic emotion， inconsistency between different academic schools making it difficult to reach consensus， lack of guiding principles of the decision weight of different dimensions for recommendations. Therefore， methodological suggestions have been put forward， including organizing parallel TCM and western medicine consensus group， improving the method of combining TCM and western medicine paradigm， attaching great importance to the evidence-based governance of academic schools， and promoting the research on different dimensions for recommendation formulation， which may provide a methodological reference for the guideline development.

Pancreatic cancer patients often have complaints such as upper abdominal pain and obstructive jaundice when seeking diagnosis and treatment. However, acute pancreatitis as a rare initial clinical manifestation of pancreatic cancer is often overlooked in clinical practice. This oversight often leads to a delayed diagnosis of pancreatic cancer, uncertainty in treatment strategies, and significantly affects patients′ quality of life and prognosis. Therefore, early diagnosis and treatment, and active follow-up are crucial for patients with acute pancreatitis as an initial symptom of pancreatic cancer. Upon admission to such patients, common causes such as gallstones, alcohol abuse, and hyperlipidemia should be initially ruled out. Evaluation with tumor markers, CT and MRI, and endoscopic ultrasound are essential to confirm the diagnosis of pancreatic cancer. For patients with mild pancreatitis, managing peripancreatic inflammation first before radical resection of pancreatic cancer could reduce postoperative complications. Moreover, pancreatitis serves as a high-risk factor for pancreatic cancer, so it is crucial to closely follow up patients with pancreatitis to detect pancreatic cancer early.

AIM:To explore the impact of histidine triad nucleotide-binding protein 2(HINT2)on atheroscle-rosis(AS),and to elucidate its underlying mechanisms.METHODS:Peripheral blood mononuclear cells(PBMCs)were isolated from patients with chest pain and induced to differentiate into macrophages for assessing HINT2 expression.In vitro,RAW264.7 mouse macrophages were cultured to evaluate inflammatory cytokine levels and cell death in superna-tants.An apolipoprotein E gene knockout(apoE-/-)mouse model of AS was developed to analyze plaque formation,lipid metabolism and macrophage foaminess in the aortic root.Pyroptosis-related protein expression in cultured RAW264.7 cells and the aorta of apoE-/-mice was determined by RT-qPCR and Western blot.RESULTS:Significantly reduced HINT2 expression was observed in PBMCs from patients with acute coronary syndrome,which was negatively correlated with pro-inflammatory and positively correlated with anti-inflammatory serum factors,suggesting HINT2's potential role in mitigating AS-related inflammation.In vitro experiments demonstrated that HINT2 overexpression inhibited lipid accumu-lation and foam cell formation in macrophages induced by oxidized low-density lipoprotein(ox-LDL).It also reduced se-cretion of inflammatory cytokines,including interleukin-6(IL-6),IL-1β,IL-18 and tumor necrosis factor-α,and de-creased cell death and pyroptosis-related protein expression.In vivo experiments in apoE-/-mice confirmed that HINT2 overexpression lessened plaque burden in the aortic root,reduced macrophage foaminess,and inhibited the expression of pyroptosis-related proteins such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),IL-1β and IL-18.CONCLUSION:HINT2 potentially inhibits ox-LDL-induced macrophage pyroptosis,attenuates inflammatory responses in AS,and may slow the progression of this disease.

[Objective] To analyze the characteristics of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 allele polymorphisms among cord blood donors in Guangdong population. [Methods] According to HLA high resolution genotyping data of 32 717 samples of cord blood donors from Guangdong Cord Blood Bank from January 2009 to December 2023, the allele frequencies were calculated by direct counting and the haplotype frequencies were calculated by using Arlequin software 3.5.2.2. [Results] A total of 102 HLA-A alleles, 160 HLA-B alleles and 96 HLA-DRB1 alleles were detected in 32 717 samples. Among them, 46 HLA-DPB1 alleles were detected in 5 377 samples, and 66 HLA-C alleles and 35 HLA-DQB1 alleles were detected in 13 310 samples. The most common alleles were HLA-A^*11∶01 (28.96%), HLA-B^*40∶01 (15.23%), HLA-DRB1^*09∶01 (15.72%), HLA-C^*01∶02 (19.40%), HLA-DQB1^*03∶01 (20.85%) and HLA-DPB1^*05∶01 (40.79%). The most common 3 loci haplotype and 6 loci haplotype were HLA-A^*02∶07-B^*46∶01-DRB1^*09∶01 (1.55%), HLA-C^*07∶02-DQB1^*03∶01-DPB1^*05∶01 (1.77%), HLA-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (3.31%) and HLA-A^*02∶07-B^*46∶01-C^*01∶02-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (0.30%). [Conclusion] In this study, the allele and haplotype frequencies of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 were obtained in the cord blood donors in Guangdong, which can provide important reference data for HLA gene related research and the selection of donors for clinical application.

Pancreatic cancer patients often have complaints such as upper abdominal pain and obstructive jaundice when seeking diagnosis and treatment. However, acute pancreatitis as a rare initial clinical manifestation of pancreatic cancer is often overlooked in clinical practice. This oversight often leads to a delayed diagnosis of pancreatic cancer, uncertainty in treatment strategies, and significantly affects patients′ quality of life and prognosis. Therefore, early diagnosis and treatment, and active follow-up are crucial for patients with acute pancreatitis as an initial symptom of pancreatic cancer. Upon admission to such patients, common causes such as gallstones, alcohol abuse, and hyperlipidemia should be initially ruled out. Evaluation with tumor markers, CT and MRI, and endoscopic ultrasound are essential to confirm the diagnosis of pancreatic cancer. For patients with mild pancreatitis, managing peripancreatic inflammation first before radical resection of pancreatic cancer could reduce postoperative complications. Moreover, pancreatitis serves as a high-risk factor for pancreatic cancer, so it is crucial to closely follow up patients with pancreatitis to detect pancreatic cancer early.

The aim of this study was to clarify the genetic diversity and population history of Ixodes persulcatus in some ar-eas of Inner Mongolia in order to provide accurate data for effective vector control programs and reveal the transmission mecha-nism.Samples were collected in 10 areas of Inner Mongolia during the active tick season(April 2021-July 2023)using the flag-dragging and manual sampling methods.The 16S rRNA and COI gene were sequenced to clarify genetic diversity of I.per-sulcatus.The positivity rates for the COI gene and 16S rRNA were 90.00％and 98.33％respectively.Overall,18 and 15 haplotypes were identified for the COI gene and 16S rRNA,respectively,with a total haplotype diversity＞0.762 and total nucleotide diversity＜0.005.The Tajima's values and Fu's Fs were negative for significance.A nucleotide mismatch map was shown as a single peak.The genetic differentiation index FST of the population indicates a small degree of genetic differ-entiation of the population,while analysis of molecular vari-ance indicates that the variation within populations was greater than between populations.Phylogenetic tree and haplotype network plots showed confounding distributions between hap-lotypes.I.persulcatus from the Hinggan League and Hulun-buir regions can adapt to environmental changes and possess abundant genetic diversity.Genetic differentiation is mainly concentrated within the population and no geographical isolation was observed.