Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

Objective To investigate the predictive value of serum circular RNA(circRNA)CDYL and circRNA ACAP2 expression levels for major adverse cardiovascular events(MACE)in pa-tients with acute myocardial infarction(AMI).Methods A total of 98 AMI patients were enrolled into the observation group,and divided into MACE group(n=45)and no-MACE group(n=53)based on whether they experienced MACE.Another 98 healthy individuals who underwent physical ex-amination during the same period were selected as the control group.The expression levels of serum cir-cRNA CDYL and circRNA ACAP2 were compared among groups.Multivariate logistic regression analysis was used to identify factors influencing the occurrence of MACE in AMI patients.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive value of serum circRNA CDYL and circRNA ACAP2 levels for MACE in AMI patients.Results The serum circRNA CDYL level in the observation group was significantly lower than that in the control group,while the circRNA ACAP2 level was significantly higher(P＜0.05).The circRNA CDYL level in the MACE group was significantly lower,and the circRNA ACAP2 level was significantly higher than that in the no-MACE group(P＜0.05).Heart rate and circRNA ACAP2 were identified as independent risk factors for MACE in AMI patients,whereas circRNA CDYL served as independent protective factor(P＜0.05).The area under the ROC curve(AUC)for predicting MACE in AMI patients using se-rum circRNA CDYL,circRNA ACAP2 and their combination were 0.814,0.821 and 0.921,re-spectively.The sensitivity and specificity of combined prediction using serum circRNA CDYL and circRNA ACAP2 were 91.11％and 79.25％,respectively.The combined prediction efficacy of serum circRNA CDYL and circRNA ACAP2 was superior to their individual prediction(Zcombined-circRNA CDYL=1.975,Zcombined-circRNAACAP2=2.064,P=0.048,0.039).Conclusion Serum circRNA CDYL lev-el is down-regulated and circRNA ACAP2 level is up-regulated in AMI patients,and circRNA ACAP2 is an independent risk factor for MACE,while circRNA CDYL is a independent protective factor.The combined value of circRNA CDYL and circRNA ACAP2 in predicting the occurrence of MACE is higher.

Objective To compare the effects of sequential Exoview and Mimics three-dimensional reconstruction with fluorescence method in thoracoscopic pulmonary segmentectomy.Methods The clinical data of 160 patients with lung cancer admitted to our hospital from January 2020 to June 2023 were retrospectively analyzed.Among them,79 patients who underwent thoracoscopic pulmonary segmentectomy with the sequential Exoview three-dimensional reconstruction and fluorescence method before the operation were classified as the Exoview group,and 81 patients who underwent thoracoscopic pulmonary segmentectomy with the sequential Mimics three-dimensional reconstruction and fluorescence method before the operation were classified as the Mimics group.The surgical completion status,the coincidence rate between the number of left and right pulmonary artery branches evaluated before operation and intraoperative findings,reconstruction time,segment display effect,general indicators of operation(operation time,intraoperative blood loss,number of lymph node dissection,thoracic tube placement time,postoperative hospital stay),pulmonary function[forced expiratory volume in one second(FEV1),percentage of forced expiratory volume in one second(FEV1%)]and complications were compared between the two groups.Results All patients in the two groups successfully completed thoracoscopic pulmonary segmentectomy,and indocyanine green was injected once in each group.The operation process was roughly consistent with the preoperative simulation,and no thoracotomy was performed.There was no statistically significant difference in the resection of lung segment between the two groups of patients(P>0.05).The coincidence rate between the number of left and right pulmonary artery branches evaluated before operation and intraoperative findings in the Exoview group was higher than that in the Mimics group(P<0.05).There was no significant difference in the segment display effect between the Exoview group and the Mimics group(P>0.05).The operation time and the reconstruction time in the Exoview group were shorter those that in the Mimics group,and the intraoperative blood loss was less than that in the Mimics group(P<0.05).There was no significant difference in the number of lymph node dissection,the thoracic tube placement time,or the postoperative hospital stay between the two groups(P>0.05).There was no statistically significant difference in FEV1 or FEV1%7 days after surgery compared with those before surgery(P>0.05).The FEV1 and FEV1%of patients in the Mimics group 7 days after surgery were lower than those beforesurgery(P<0.05).There was no statistically significant difference in FEV1 or FEV1%between the Exoview group and the Mimics group before and 7 days after surgery(P>0.05).The total incidence of complications in the Exoview group was 1.27%,compared with 4.94%in the Mimics group,the difference was not statistically significant(P>0.05).Conclusion Both sequential Exoview and Mimics three-dimensional reconstruction with fluorescence method are safe and effective for thoracoscopic pulmonary segmentectomy,while Exoview has more advantages in preoperative assessment of the number of pulmonary artery branches,and it has shorter reconstruction time and operation time,with less impact on lung function.

Objective To compare the effects of sequential Exoview and Mimics three-dimensional reconstruction with fluorescence method in thoracoscopic pulmonary segmentectomy.Methods The clinical data of 160 patients with lung cancer admitted to our hospital from January 2020 to June 2023 were retrospectively analyzed.Among them,79 patients who underwent thoracoscopic pulmonary segmentectomy with the sequential Exoview three-dimensional reconstruction and fluorescence method before the operation were classified as the Exoview group,and 81 patients who underwent thoracoscopic pulmonary segmentectomy with the sequential Mimics three-dimensional reconstruction and fluorescence method before the operation were classified as the Mimics group.The surgical completion status,the coincidence rate between the number of left and right pulmonary artery branches evaluated before operation and intraoperative findings,reconstruction time,segment display effect,general indicators of operation(operation time,intraoperative blood loss,number of lymph node dissection,thoracic tube placement time,postoperative hospital stay),pulmonary function[forced expiratory volume in one second(FEV1),percentage of forced expiratory volume in one second(FEV1%)]and complications were compared between the two groups.Results All patients in the two groups successfully completed thoracoscopic pulmonary segmentectomy,and indocyanine green was injected once in each group.The operation process was roughly consistent with the preoperative simulation,and no thoracotomy was performed.There was no statistically significant difference in the resection of lung segment between the two groups of patients(P>0.05).The coincidence rate between the number of left and right pulmonary artery branches evaluated before operation and intraoperative findings in the Exoview group was higher than that in the Mimics group(P<0.05).There was no significant difference in the segment display effect between the Exoview group and the Mimics group(P>0.05).The operation time and the reconstruction time in the Exoview group were shorter those that in the Mimics group,and the intraoperative blood loss was less than that in the Mimics group(P<0.05).There was no significant difference in the number of lymph node dissection,the thoracic tube placement time,or the postoperative hospital stay between the two groups(P>0.05).There was no statistically significant difference in FEV1 or FEV1%7 days after surgery compared with those before surgery(P>0.05).The FEV1 and FEV1%of patients in the Mimics group 7 days after surgery were lower than those beforesurgery(P<0.05).There was no statistically significant difference in FEV1 or FEV1%between the Exoview group and the Mimics group before and 7 days after surgery(P>0.05).The total incidence of complications in the Exoview group was 1.27%,compared with 4.94%in the Mimics group,the difference was not statistically significant(P>0.05).Conclusion Both sequential Exoview and Mimics three-dimensional reconstruction with fluorescence method are safe and effective for thoracoscopic pulmonary segmentectomy,while Exoview has more advantages in preoperative assessment of the number of pulmonary artery branches,and it has shorter reconstruction time and operation time,with less impact on lung function.

Numerous research conducted in recent years has revealed that gut microbial dysbiosis, such as modifications in composition and activity, might influence lung tissue homeostasis through specific pathways, thereby promoting susceptibility to lung diseases. The development and progression of lung cancer, as well as the effectiveness of immunotherapy are closely associated with gut flora and metabolites, which influence immunological and inflammatory responses. During abnormal proliferation, non-small cell lung cancer cells acquire more substances and energy by altering their own metabolic pathways. Glucose and amino acid metabolism reprogramming provide tumor cells with abundant ATP, carbon, and nitrogen sources, respectively, providing optimal conditions for tumor cell proliferation, invasion, and immune escape. This article reviews the relationship of immune response with gut flora and metabolic reprogramming in non-small cell lung cancer, and discusses the potential mechanisms by which gut flora and metabolic reprogramming affect the occurrence, development, and immunotherapy of non-small cell lung cancer, in order to provide new ideas for precision treatment of lung cancer patients.
Humans ; Gastrointestinal Microbiome/immunology* ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Metabolic Reprogramming