ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objective To investigate the effects of miR-338-3p on interleukin(IL)-13-induced human bronchial epithelial cell line(BEAS-2B)injury and airway inflammation in mice with ovalbumin(OVA)-induced asthma.Methods OVA was used to replicate an asthma model of mice,which were divided into control group,model group,miR-NC agomir and miR-338-3p agomir intervention groups.HE staining microscopy was employed to ob-serve the pathological morphology of lung tissue,while TUNEL staining was used to assess cell apoptosis in lung tis-sue.ELISA was conducted to measure the levels of interleukin-1β(IL-1β)and tumor necrosis factor(TNF)-α in lung tissue.The BEAS-2B cells were subjected to IL-13-induced injury and divided into control group,IL-13 group,IL-13+miR-NC group,and IL-13+miR-338-3p mimic group.Cell viability was assessed with MTT assay.Flow cytometry was employed to evaluate cell apoptosis.The level of IL-1β and TNF-α in cells was measured by ELISA.The targeting relationship between miR-338-3p and Ras homologous(Rho)was investigated using bioinfor-matics analysis,luciferase assay,Western blot,and functional repair assay.Results Compared to the model group,the miR-338-3p agamid intervention group exhibited a significant reduction in inflammatory cell infiltration and airway wall thickening in lung tissue,as well as decreased cell apoptosis and the level of IL-1β and TNF-α in lung tissue(P＜0.05).Compared to the control group,cell viability of BEAS-2B cells in the IL-13+miR-338-3p mimic group exhibited a significant increase(P＜0.05),while apoptosis and level of IL-1β and TNF-α within the cells demonstrated a notable decrease(P＜0.05).Rho was a target gene of miR-338-3p,and over-expression of Rho attenuated the effect of miR-338-3p mimic on IL-13-induced injury and inflammation in BEAS-2B cells.Conclusions Up-regulation of miR-338-3p can inhibit asthma-related airway inflammation and injury of lung epi-thelial cells with a potential mechanism targeting at Rho gene.

Objective To understand the current status of health literacy among caregivers of patients with liver cancer and its influencing factors so as to provide a basis for improving the level of health literacy among caregivers of patients with liver cancer.Methods Using convenience sampling method,the caregivers of the liver cancer patients,who were admitted to the Department of Interventional Radiology of a certain grade ⅢA hospital in Changsha City,Hunan Province of China between April and October of 2022 and who met the inclusion and exclusion criteria,were selected as the research objects.The general information questionnaire,Health Literacy of Caregivers Scale-Cancer(HLCS-C),and Simplified Coping Style Questionnaire(SCSQ)were used to conduct the survey.Multiple linear regression analysis was used to analyze the factors influencing the health literacy among caregivers of patients with liver cancer.Results A total of 204 valid questionnaires were collected.The score of health literacy of caregivers was(123.08±16.66)points.The results of multiple linear regression analysis showed that the residence location,the monthly income per capita of the family,the number of hospitalization times,the length of care,work/study status,and coping style were the main factors influencing the health literacy(P<0.001),which explained 81.9％of the total variance.Conclusion The health literacy among the caregivers of patients with liver cancer is at a moderate level.Clinical medical staff can implement individualized health education by evaluating caregivers with different characteristics,encourage caregivers to seek and grasp disease-related information,and help the caregivers to adopt positive coping styles,so as to improve their health literacy.

BACKGROUND:Vibration environment can cause spinal injury,especially in patients with scoliosis.At present,there is no information about the inherent mode of the whole spine from T1 to the pelvis in scoliosis patients in the free state. OBJECTIVE:To analyze the dynamic characteristics of the whole spine in patients with scoliosis by the finite element method. METHODS:Based on CT scan images,a three-dimensional finite element model of the T1-pelvic total spine of an 11-year-old patient with thoracolumbar biflexion scoliosis was established,and the Cobb angles of thoracolumbar scoliosis were 36° and 24°,respectively.The mode analysis in the free state of the whole spine was carried out by the finite element method. RESULTS AND CONCLUSION:The fifteen-order free modes of the spine were extracted,and the dynamic characteristics of the scolio-curved spine were obtained.The resonance frequency distribution of the spine was concentrated.The thoracic vertebra was the most deformed in the whole spine model,and the amplitude of the thoracic vertebra was larger than that of the lumbar vertebra.Modal analysis was used to analyze the vibration characteristics of scoliosis patients in the vibration environment.It is of great significance to determine the natural frequency,vibration mode,and amplitude of scoliosis patients for analyzing the vibration characteristics of scoliosis.

BACKGROUND:Osteoporosis vertebral compression fracture is a common fracture secondary to osteoporosis,and there is currently a lack of effective predictive indicators and methods for osteoporosis vertebral compression fracture. OBJECTIVE:To investigate the predictive effects of paravertebral muscle degeneration,functional cross-sectional area,and percentage of fat infiltration on osteoporotic vertebral compression fractures. METHODS:The 224 patients with osteoporosis diagnosed from January 2018 to June 2022 were included.They were followed up for more than 2 years.They were divided into fracture group and non-fracture group according to the presence and absence of vertebral fracture.The detailed information of demographics,body mass index,bone mineral density and so on were collected.The functional cross-sectional area and percentage of fat infiltration of bilateral Psoas major muscle and extensor dorsi(Erector spinae muscles muscle and multifidus muscle)at the level of lower endplate of L2 vertebral body were measured and calculated. RESULTS AND CONCLUSION:(1)224 patients were ultimately included,of which 126 had fractures as the fracture group and 98 had no fractures as the non-fracture group.There was no statistically significant difference in age,gender,height,body mass,body mass index,and fracture segment between the two groups(P>0.05).(2)The bone mineral density of the fracture group was significantly lower than that of the non-fracture group(P<0.05).Functional cross-sectional areas of Psoas major muscle and extensor dorsi in the fracture group were significantly lower than those in the non-fracture group(P<0.05).The percentage of fat infiltration of the extensor dorsi in the fracture group was significantly higher than that in the non-fracture group(P<0.05).There was no significant difference in percentage of fat infiltration of Psoas major muscle between the two groups(P>0.05).(3)Receiver operating characteristic analysis showed that the vertebral bone mineral density,percentage of fat infiltration of extensor dorsi,functional cross-sectional area of extensor dorsi and percentage of fat infiltration of Psoas major muscle were 0.903 g/cm2,35.426%,418.875 mm2,and 6.375%,respectively.The areas under curve were 0.634,0.755,0.876,and 0.585,respectively.(4)These findings indicate that paravertebral muscle degeneration is strongly associated with the occurrence of osteoporotic vertebral compression fractures.The functional cross-sectional area of extensor dorsi muscle can effectively predict the occurrence of osteoporotic vertebral compression fractures,which is helpful for early prevention and treatment of osteoporotic vertebral compression fractures.

Objective To explore the gene expression profile in paraspinal muscle degeneration(PMD)and identify key ferroptosis genes.Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes.Through protein-protein interaction(PPI)and gene functional enrichment analysis,the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis.The diagnostic value for PMD disease was analyzed by receiver operating characteristic(ROC)curves.Results A total of 292 differentially expressed genes were identified in PMD.Among them,125 genes were significantly downregulated and 167 genes were significantly upregulated.Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis.Among them,ferroptosis genes MUC1,ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD.Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis,ferroptosis and skeletal muscle tissue development and differentiation.Conclusion Ferroptosis genes MUC1,ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD,providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs.

Objective:To investigate factors influencing the timing of laparoscopic surgery in children with cryptorchidism.Methods:A retrospective analysis was conducted on data from 150 children with cryptorchidism treated at Linyi Central Hospital between January 2020 and June 2023. The children were grouped based on the median age of those who underwent surgery, with 75 children in the low age group and 75 children in the high age group. The timing of operation for included children was analyzed. Univariate and multivariate analyses were performed to assess laparoscopic operation timing in children with cryptorchidism. A predictive model for laparoscopic operation timing was constructed, and its prediction efficiency was analyzed.Results:Univariate analysis revealed significant differences in family income level, medical expense payment method, parents' education level, and residence attributes among children who underwent surgery at different timings ( χ2=12.37, 21.70, 9.28, 9.52, 7.73, all P < 0.05). Multivariate analysis demonstrated that independent risk factors for delayed laparoscopic surgery in children with cryptorchidism included low family income, self-payment of medical expenses, low parents' education level, and rural residence ( OR = 0.31, 0.21, 0.08, 0.05, 0.12, 0.13, 0.14, 0.21, 0.42, all P < 0.05). Based on the results of the multivariate analysis, a nomogram risk model was constructed with a C-index of 0.713. This model utilized independent influencing factors and the prediction probability of the P-value to predict the timing of operation. The Yoden index values were 22.67%, 22.67%, 25.33%, 28.00%, 22.67%, and 60.00%, respectively. Conclusion:Children with cryptorchidism still experience delayed surgery, which is attributed to several factors. The prediction model constructed using these influencing factors demonstrates good prediction efficiency.

Objective:To investigate the risk factors for occurrence of cryptorchidism in children and the timing of surgery.Methods:Ninety-six children with cryptorchidism who received treatment at Linyi Central Hospital between January 2018 and December 2022 (cryptorchidism group) and 60 healthy young children born during the same period (control group) were included in this study. The mothers and fathers of the children were surveyed, and the risk factors for the occurrence of cryptorchidism in children were statistically analyzed. Additionally, the factors that affect the timing of surgery for the children were also evaluated.Results:(1) Children with cryptorchidism typically exhibited poor testicular development and a soft texture. Of the cases studied, 83 (86.4%) had unilateral cryptorchidism, with the left side affected in 21 cases and the right side affected in 62 cases. Additionally, 13 cases (13.6%) exhibited bilateral cryptorchidism. The testicles were located in the inguinal region in 76 cases and in the abdominal cavity in 20 cases. In 79 cases, the cryptorchid was palpable, whereas in 17 cases, it was not. Upon admission, the children's serum luteinizing hormone levels were (1.83 ± 0.25) U/L, follicle-stimulating hormone levels were (1.12 ± 0.13) U/L, and testosterone levels were (0.77 ± 0.09) nmol/L. (2) Multivariate logistic analysis revealed that mother's smoking history, drinking history, occupational exposure to pesticides or diesel/gasoline, use of anti-infective drugs/antipyretic analgesics during early pregnancy, gestational diabetes, father's smoking history, and history of occupational exposure to pesticides were the independent risk factors for the occurrence of cryptorchidism in children (all P < 0.05). (3) Parental education level, family income, and the presence of combined penile malformations emerged as independent risk factors that influence the timing of surgery for cryptorchidism in children (all P < 0.05). Conclusion:The educational level, occupation, and early pregnancy medication history of parents are the primary risk factors influencing the occurrence of cryptorchidism in children. Therefore, it is crucial to enhance health education targeted at low-income and poorly-educated families to prevent surgical delays.