Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.

ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

Objective: To explore the effects of intergenerational parent-child separation on internalizing and externalizing behavioral problems among rural preschoolers aged 3-6 years, so as to provide empirical evidence for formulating targeted intervention strategies and blocking the intergenerational transmission of parent-child separation. Methods: From March to June, 2024, ten kindergartens were selected from rural areas of Nanling County, Wuhu City, Anhui Province, and 2 279 preschool children aged 3- 6 years, along with their fathers, mothers and primary caregivers, were recruited for survey by cluster convenient sampling method. Children s fathers and mothers reported their own childhood parent-child separation information separately. Information on the children s history of psychological and behavioral problems was reported by the primary caregivers. Information of internalizing and externalizing behavioral problems in preschool children was reported with Strengths and Difficulties Questionnaire (SDQ).The Chi square test was used to compare the differences in the detection rates of psychological and behavioral problems among children with different intergenerational continuity of parent-child separation. Binary Logistic regression model was applied to analyze the association between intergenerational continuity of parent-child separation and internalizing and externalizing behavioral problems in preschool children. Results: The detection rate of internalizing behavioral problems was 27.5% and externalizing behavioral problems was 19.1% among rural preschool children. There were significant differences in internalization behavior, externalization behavior, hyperactivity impulse and peer communication problems among preschool children in different types of parent-child separation groups( χ 2=14.29, 8.80, 17.26, 13.84, all P <0.05). Binary Logistic regression analysis showed that after adjusting for covariates such as children s gender, birth weight, and delivery mode, compared with children without separation, intergenerational continuity of parent-child separation group( OR =1.95), only child separation( OR =1.74) were associated with significant higher risk of conduct problems(both P ＜0.05). Parent-child separation intergenerational continuation groups( OR =1.68), only child separation( OR = 1.47) were associated with significant higher risk of peer problems(both P ＜0.05). Both types of parent-child separation experiences significantly increased the risk of children s prosocial behavior problems，among them, the intergenerational continuation group was 1.99 times that of the control group ( OR =1.99), and the childhood only separation group was 2.09 times that of the control group ( OR =2.09)(both P ＜0.05). Compared with children whose parents and children had no experience of parent-child separation, children in the intergenerational continuation group of parent-child separation had increased risks of both internalizing and externalizing behavior problems ( OR =1.53, 1.65, both P <0.05). Conclusion All types of parent-child separation are associated with internalizing and externalizing behavioral problems among rural children aged 3 to 6 years.

The early angiopathy of systemic sclerosis (SSc) is a key hub connecting inflammation and fibrosis. The animal models that simulate the pathological characteristics of SSc are of great significance to study the etiology, pathogenesis and treatment of SSc with vascular involvement. This review of the characteristics of different animal models of SSc with vascular involvement provides a reference for relevant researchers to select appropriate models in the process of exploring the pathogenesis of SSc with vascular involvement.

Ulcerative colitis （UC） is a chronic， non-specific intestinal inflammatory disease. Its pathogenesis is complex， involving interactions among genetic， immune， and environmental factors， and remains incompletely elucidated. Mitochondrial damage can trigger the abnormal release of mitochondrial damage-associated molecular patterns （mtDAMPs）， activating inflammatory pathways and thereby exacerbating the inflammatory response in UC. Mitophagy， a core mitochondrial quality control mechanism， can clear damaged mitochondria and effectively reduce the abnormal release of mtDAMPs and the accumulation of harmful substances， thereby mitigating inflammatory damage resulting from mitochondrial dysfunction. Mitophagy plays a crucial role in maintaining the integrity of the intestinal epithelial barrier function and in the prevention and intervention of UC. Notably， the function of the spleen governing transportation and transformation in traditional Chinese medicine shares similarities with the role of mitochondria in energy transformation and substance metabolism. Furthermore， the pathological state of the spleen failing in transportation and transformation may be related to mitochondrial dysfunction， while the pathogenic characteristics of "endogenous turbid pathogen" align with the inflammatory cascade responses triggered by abnormal release of mtDAMPs. Based on this theoretical correlation， this paper aims to explore the correlation between the traditional Chinese medicine theory of "spleen dysfunction in essence distribution leading to endogenous turbid pathogens" and mitophagy. Using the correlation as an entry point， the potential role of mitophagy in the pathogenesis of UC was elucidated. Additionally， by considering the epidemiological characteristics of UC in the Southwest region of China， a new thinking for the treatment of UC from the perspective of turbid pathogens was proposed based on the "fortifying the spleen and resolving turbidity" method to provide theoretical support and research enlightenment for further exploring the prevention and treatment of UC with traditional Chinese medicine.

Objective:To explore the diagnostic value of the macrophage activation syndrome/systemic juvenile idiopathic arthritis（MS）score in macrophage activation syndrome（MAS）associated with systemic juvenile idiopathic arthritis（sJIA），and to provide a reference for clinical work.Methods:This study was a retrospective case-control analysis，conducted on the patients initially diagnosed as sJIA-associated with MAS and admitted into the Department of Rheumatology and Immunology of Children's Hospital Affiliated to Xi 'an Jiaotong University from July 1st，2016 to June 30th，2023. All of the patients met the diagnostic criteria for patients with MAS associated with sJIA according to the 2016 European Alliance of Associations for Rheumatology（EULAR）/American College of Rheumatology（ACR）/Pediatric Rheumatology International Trials Organization（PRINTO）standards. The basic information at baseline，clinical manifestations，and auxiliary examination results were collected. The MS score was applied to re-evaluate the children diagnosed as sJIA-associated with MAS. When the MS score ≥-2.1，the possibility of sJIA with MAS was high. Thirty cases of sJIA without MAS were randomly selected as the control group.Results:There were 28 cases in the MAS group，including 13 males（46.43%）and 15 females（53.57%），with an average age of（7.51±4.01）years. Compared with the control group，the MAS group were significantly more likely to have high fever（ χ2=8.539， P=0.003），hepatomegaly（ χ2=11.621， P<0.001），splenomegaly（ χ2=11.710， P<0.001）and neurological involvement（ χ2=27.619， P<0.001），with the differences being statistically significant. Meanwhile，there were statistically significant differences between the two groups in terms of white blood cell count（ Z=-4.001， P<0.001），neutrophil count（ Z=-3.659， P<0.001），platelet count（ Z=-4.687， P<0.001），albumin level（ Z=-4.018， P<0.001），alanine aminotransferase（ Z=-3.846， P<0.001），aspartate aminotransferase（ Z=-5.932， P<0.001），lactate dehydrogenase（ Z=-6.150， P<0.001），triglycerides（ Z=-5.874， P<0.001），fibrinogen（ Z=-5.808， P<0.001），ferritin（ Z=-5.280， P<0.001），erythrocyte sedimentation rate（ Z=-3.971， P<0.001），ferritin/erythrocyte sedimentation rate（ Z=-5.433， P<0.001），reduction of two-line cells in blood（ χ2=11.408， P<0.001）and the presence of hemophagocytosis in bone marrow smears（ χ2=28.260， P<0.001）. Moreover，there was a statistically significant difference in MS scores between the two groups（ Z=-6.148， P<0.001），with higher MS scores in the MAS group. Nevertheless，this study showed the median MS scores of both groups ≥-2.1. Conclusion:The MS score was significant to a certain degree as reference for the diagnosis of MAS，and this study showed that the MS score in the MAS group was significantly higher than the control group. However，the median MS scores in both groups were no less than -2.1. This might be related to the influence of factors during the assessment，which made it necessary to optimize the cutoff values of the MS score. Therefore，prospective studies should be carried out on the role of MS score in early identification of MAS.

Objective To investigate the effect and mechanism of circular RNA nuclear receptor interacting protein 1(circNRIP1)expression on exhaustion of CD8+T cells in cervical cancer cells.Methods Real-time quantitative PCR was used to detect the expression of circNRIP1 in cervical epithelial cells HCerEpic and cer-vical cancer cells C-33A,Hela,SiHa,and CS121.C-33A cells were divided into Vector group,circNRIP1 group,and circNRIP1+miR-138-5p group,while CS121 cells were divided into sh-NC group,sh-circNRIP1 group,and sh-circNRIP1+miR-138-5p inhibitor.Human peripheral blood CD8+T cells were extracted,and C-33A cells in Vector group and circNRIP1 group were co-incubated with CD8+T cells for 24 hours(CD8+T/Vector group and CD8+T/Vector group).CS121 cells in sh-NC group and sh-circNRIP1 group were co-incu-bated with CD8+T cells for 24 hours(CD8+T/sh NC group and CD8+T/sh-circNRIP1 group).Cytotoxicity experiments were conducted to detect the killing ability of CD8+T cells,ELISA was used to detect the levels of interleukin(IL)-2,interferon(IFN)-γ,and tumor necrosis factor(TNF)-α in the cell supernatant.Flow cy-tometry was used to detect the expression of programmed death receptor-1(PD-1),T cell Immunoglobulin domain and Mucin domain protein-3(TIM3),and lymphocyte activation gene 3(LAG3)in CD8+T cells.Dual luciferase reporter gene experiments were conducted to verify the targeting relationship between circNRIP1 and miR-138-5p,as well as the targeting relationship between miR-138-5p and PD-L1.Results The expres-sions of circNRIP1 in C-33A,Hela,SiHa,and CS121 cells were significantly higher than those in HCerEpic(P＜0.05).The killing ability of CD8+T cells against C-33A cells in the circNRIP1 group was lower than their killing ability against Vector group cells.The levels of IL-2,IFN-γ,and TNF-α secreted by CD8+T cells in the CD8+T/circNRIP1 group were significantly lower than those in the CD8+T/Vector group(P＜0.05),and the levels of PD-1,LAG-3,and TIM-3 expressed by CD8+T cells in the CD8+T/circNRIP1 group were al-so significantly higher than those in the CD8+T/Vector group(P＜0.05).The killing ability of CD8+T cells against sh-circNRIP1 group CS121 cells was higher than their killing ability against sh-NC group cells(P＜0.05).The levels of IL-2,IFN-γ,and TNF-α secreted by CD8+T cells in the CD8+T/sh-circNRIP1 group were significantly higher than those in the CD8+T/sh-NC group(P＜0.05).The PD-1,LAG-3,and TIM-3 levels of CD8+T cells in the CD8+T/sh-circNRIP1 group were also significantly lower than those in the CD8+T/sh-NC group(P＜0.05).The results of the dual-luciferase reporter gene experiment showed that miR-138-5p was the target gene of circNRIP1,and PD-L1 was the target gene of miR-138-5p.Conclusion circNRIP1 can in-duce the exhaustion of CD8+T cells by upregulating the expression of PD-L1.