Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

As a common medical condition， vertigo can be induced by multiple diseases in the modern medical system. Its incidence rate shows an upward trend with the increase in age. According to the theory of mutual interference between clear Qi and turbid Qi in Huangdi's Internal Classic （Huang Di Nei Jing）， this paper systematically analyzes the pathogenesis of vertigo and explores the mechanism and clinical application value of Xiao Chaihutang in the treatment of vertigo. It is believed that the mutual inference between clear Qi and turbid Qi leads to the failure of clear Yang to ascend， resulting in the lack of nourishment for the brain and the inability of turbid Yin to descend， which disturbs the clear orifices， thus causing vertigo. The core pathogenesis lies in the dysfunction of Qi movement， the disorder of body fluid distribution， and the imbalance between Yin and Yang. The compatibility of Xiao Chaihutang takes into account the methods of pungent medicinal materials opening and bitter medicinal materials descending， tonifying deficiency and purging excess， and regulating Qi movement. This prescription can regulate the pathological state of the mutual interference between clear Qi and turbid Qi from three aspects： regulating Qi movement throughout the body， harmonizing the distribution of body fluids， and coordinating Yin and Yang as well as the interior and exterior， thus preventing and treating vertigo. Modern research findings show that Xiao Chaihutang can improve hemodynamics to promote cerebral blood circulation and has anti-inflammation， immunomodulatory， and anti-tumor functions， which correspond to the therapeutic effects of Xiao Chaihutang under the theory of mutual interference between clear Qi and turbid Qi. The decoction exerts therapeutic effects on vertigo caused by hypertension， stroke， otitis media， Meniere’s disease， and brain tumor as well as benign paroxysmal positional vertigo. Further exploration of the theoretical connotation of mutual inference between clear Qi and turbid Qi and analysis of the pathogenesis of vertigo and the therapeutic effect of Xiao Chaihutang can better interpret the internal correlations among the three， thus providing new ideas for the syndrome differentiation and treatment of vertigo.

Objective The objective of this study was to analyze the longitudinal trend of multidimensional treatment quality of breast cancer based on the latent growth mixture model(LGMM),identify potential change patterns and influencing factors,and pro-vide scientific basis for improving treatment quality and patient prognosis.Methods The quality monitoring data of breast cancer from four consecutive years were obtained in the National"Quality Monitoring System for Specific(single)Disease";Based on the item response theory(IRT),the treatment quality of breast cancer in the three dimensions of preoperative examination,treatment,and out-come was calculated;LGMM was constructed to analyze the independent and joint change trend of breast cancer treatment quality in all dimensions,and the optimal model was determined based on practical significance and statistical indicators.Results In the inde-pendent trend analysis,2 potential categories were identified for preoperative examination,treatment,and outcome dimensions.Among them,9%showed a rapid upward trend in the preoperative examination dimension,and 91%showed a relatively stable trend;The sta-ble growth accounted for 23%and slow decline accounted for 77%in the treatment dimension;13%of the outcome dimensions showed an upward trend,while 87%showed a downward trend.In the joint trend analysis of changes,2 potential categories were identified:the first category accounted for about 8%,and the preoperative examination dimension of this category had a good treatment quality,with mean intercepts and slopes of 3.326 and 3.367,respectively.The treatment quality in the treatment and outcome dimensions had steadily improved;The second category accounted for about 92%,and the treatment quality in this dimension was relatively good.Its mean intercept and slope were 0.548 and 0.018,respectively.There is still room for improvement in the treatment quality of the pre-operative examination and outcome dimensions;BMI and M stage in patient characteristics are important influencing factors on the trend of combined changes in treatment quality.Conclusion The treatment quality of breast cancer during this study period has im-proved to varying degrees in all dimensions of preoperative examination,treatment and outcome;In the joint trend analysis of the three dimensions,the improvement of treatment quality in the preoperative examination dimension can provide feasible references for subse-quent treatment and achieve the goal of reducing complications.

Objective Based on polynomial logistic regression model,this study aimed to analyze the optimal length of hospi-tal stay for patients with non-small cell lung cancer(NSCLC)at different stages to achieve the best treatment quality,providing refer-ence for improving treatment quality and formulating relevant policies.Methods The data of NSCLC cases were collected and 16 di-agnosis and treatment process indicators were selected.Patients were stratified according to the stage of lung cancer.A polynomial lo-gistic regression model was constructed,including patient characteristics to analyze the impact of first hospitalization days on the quali-ty of comprehensive treatment.Results A total of 10,053 patients with NSCLC were collected in this study,with a median compre-hensive treatment quality score of 0.60.According to the staging of lung cancer,patients were divided into the early stage group(stageⅠ-Ⅱ),locally advanced stage group(stage Ⅲ),and advanced stage group(stage Ⅳ).The first hospitalization days and treatment quality of each subgroup showed a non-linear relationship.The polynomial model results showed that after adjusting the characteristics of patients,the length of hospitalization day and the quadratic term of hospital stay had a statistically significant impact on treatment quality in each subgroup:early patients had a first hospital stay of 18 days,and locally advanced and advanced patients had a first hos-pital stay of 22 days,with the highest probability of achieving high treatment quality.Conclusion Patients in different stages have va-rying degrees of illness and treatment plans,resulting in different first hospitalization days corresponding to the highest probability of obtaining high-quality treatment.Hospitals can improve the treatment quality and medical efficiency by implementing standardized di-agnosis and treatment guidelines,strengthening the management of the diagnosis and treatment process,and reasonably controlling the first hospitalization time of patients in different stages.

Objective The aim of this study was to use the fast causal inference(FCI)algorithm to construct a causal graph model,analyze the direct and indirect factors that affect the quality of treatment for non-small cell lung cancer(NSCLC),and provide a basis for improving the quality of patient treatment.Methods Case information of NSCLC patients from 10 tertiary hospitals was collected;the influencing factors were determined as the research variable,and the incidence of adverse events was the evaluation indi-cator of patient treatment quality,i.e.the outcome variable;the FCI algorithm to mine case data were used to construct a causal dia-gram model of research variables and outcomes,and analyze causal relationships between research variables and outcome variables,as well as between different research variables.Results A total of 2,846 patients with an average age of 56.00±7.70 years were includ-ed in this study,and the incidence of adverse events was 9.63%.The causal diagram model consisted 24 nodes and 71 edges,inclu-ding 54 directed edges and 7 bidirectional edges.The direct factors affecting the occurrence of adverse events included hospital type,histological grade,lymph node dissection,and length of hospitalization;indirect factors included occupation,medical insurance type,current medical history,pathological stage,comprehensive treatment,surgical nature,and type of lung resection;The analysis of the in-teraction between factors showed that the current medical history,histological classification,comprehensive treatment,surgical nature,and type of lung resection determined whether the patient received lymph node dissection;The nature of surgery,method of lung resec-tion,and comprehensive treatment affected the length of hospitalization;Medical history affected the histological classification of lung cancer;The type of occupation and medical insurance affected the type of hospital where patients sought medical treatment.Conclusion In the analysis of factors affecting the quality of NSCLC treatment,the causal diagram model can obtain direct and indi-rect factors that affect the occurrence of adverse events,identify target variables that can be intervened,and provide a basis for impro-ving the quality of NSCLC treatment;Hospitals can reduce the incidence of adverse events by increasing the acceptance rate of lymph node dissection and comprehensive treatment.

Objective The aim of this study was to estimate the causal effects of non-small cell lung cancer(NSCLC)treat-ment process on in-hospital mortality based on the double robust estimation(DR)method,and provide a reference basis for reducing in-hospital mortality of NSCLC.Methods According to the quality evaluation system of NSCLC treatment,the utilization rate of treatment process indicators was calculated,and patients were divided into the high-quality or low-quality groups based on the aver-age score of treatment process quality.In-hospital mortality was used as the outcome indicator,Kaplan-Meier method and Cox regres-sion adjusted for propensity score inverse probability of treatment weighting(IPTW)correction were used to analyze the impact of treat-ment process quality on in-hospital mortality in NSCLC.DR was combined to estimate the causal effects of the treatment process on in-hospital mortality.Results The median utilization rate of treatment process indicators was 66.88%,and the mean and standard de-viation of patients′ treatment process quality scores were 0.270±0.124,including 0.358±0.069 in the high-quality group,and 0.158±0.081 in the low-quality group.After the IPTW weighting,the standardized mean difference(SMD)of patients′baseline characteris-tics decreased;The difference in survival curves between the two groups of patients before and after ITPW was statistically significant(P<0.05),and the prognosis of patients in the high-quality group was better than that of patients in the low-quality group(pre-IPTW:HR=0.367,95%CI:0.275-0.491;post-IPTW:HR=0.228,95%CI:0.167-0.312).Compared with the low-quality group,the average causal effect of treatment process on in-hospital mortality was-0.026 in the high-quality group.Conclusion DR can compensate for the shortcomings of logistic or IPTW,avoid the risk of model error,and obtain for the causal effect of treatment process on in-hospital mortality.In medical practice,the utilization rate of treatment process indicators should be increased to improve patient prognosis;The study of causal effects suggests that besides the treatment process,other factors that affect in-hospital mortality cannot be ignored.

Objective To investigate the optimal blood concentration range of tacrolimus(TAC)for the treatment of nephrotic syndrome(NS)in children.Methods Children with NS admitted to the Department of Nephrology and Immunology of Hebei Children's Hospital from January 2021 to December 2023 were retrospectively selected as study subjects.They were divided into the effective group and the ineffective group according to whether the treatment was effective or not,and the TAC threshold for effective treatment was determined by using the receiver operator characteristic(ROC)curve.The children with NS were divided into a low concentration group(＜3 ng/mL),a medium concentration group(3-5 ng/mL)and a target concentration group(5-10 ng/mL)according to the TAC concentration,and the relationships between the TAC concentration and the clinical efficacy and adverse reactions was analyzed.Results A total of 160 children were enrolled in the study.The numbers of complete remission(CR),partial remission(PR),and null remission(NR)cases of NS children were 91,37,and 32,respectively,and the treatment was effective in 128 cases(80％).The ROC curve analysis results showed that the area under the ROC curve(95％CI),sensitivity,specificity,and threshold of the mean trough concentration of TAC for predicting the efficacy of the treatment were 0.779(0.704,0.853),62.5％,84.45％,and 3.33 ng/mL,respectively.In terms of clinical efficacy,CR and PR were lower and NR was higher in the low concentration group compared with the target concentration group(P＜0.05);whereas,CR was lower and PR was higher in the medium concentration group(P＜0.05),and the difference in NR was not statistically significant(P＞0.05).In terms of different hormone-responsive phenotypes of NS,the CR of the low concentration group was lower(P＜0.05),while there was no significant difference in CR and PR between the medium concentration group and the target concentration group(P＞0.05).As for the different pathological types of NS,CR was lower in the low concentration group when compared with the target concentration group or medium concentration group(P＜0.05);while the differences in CR and PR between the medium concentration group and the target concentration group were not statistically significant(P＞0.05).Regarding adverse reactions,the incidence of limb tremor and abnormal blood glucose was significantly higher in the target concentration group than in the other two groups(P＜0.05).In addition,the differences in serious infections and hypertension among the three groups were not statistically significant(P＞0.05).Conclusion When TAC is used to treat NS in children,the recommended TAC concentration range is 3-5 ng/mL.

Objective: To explore the association of the interaction between vitamin D deficiency and dyslipidemia with the comorbidity risk of overweight and obesity in children and adolescents, so as to provide the theoretical basis for prevention and control of overweight and obesity in children and adolescents. Methods: The data for the study was obtained from the population aged 6-17 in Hebei Province during the 2022-2023 monitoring of nutrition and health status of Chinese residents. A stratified cluster random sampling method was used to conduct questionnaire surveys, physical measurements, and laboratory tests on 2 118 children and adolescents. Logistic regression was used to analyze the association of vitamin D deficiency and dyslipidemia with overweight and obesity, and multiplication and addition models were used to analyze the interaction of vitamin D deficiency and dyslipidemia with overweight and obesit. Results: The prevalence of vitamin D deficiency in the surveyed children and adolescents was 67.80%, the incidence of dyslipidemia was 24.46%, and the prevalence of overweight and obesity was 41.97%. After adjusting for confounding factors, the results of multivariate Logistic regression analysis showed that there was no multiplicative interaction of vitamin D deficiency and dyslipidemia with overweight and obesit ( OR=0.90, 95%CI=0.57-1.43, P >0.05). However, the risk of overweight and obesity among children and adolescents with vitamin D deficiency and dyslipidemia was 3.99 times higher than that of those with sufficient vitamin D and normal blood lipids ( OR=3.99, 95%CI=2.93-5.45, P <0.01). There was a positive additive interaction between vitamin D deficiency and dyslipidemia, with relative excess risk of interaction, attributable proportion of interaction and synergy index of 14.40, 81.50% and 7.35, respectively. Conclusions For children and adolescents, there is a synergistic effect between vitamin D deficiency and dyslipidemia, and the coexistence of both increases the risk of overweight and obesity. Comprehensive prevention and control measures should be taken to timely supplement vitamin D and maintain normal blood lipid levels, to reduce the occurrence of overweight and obesity in children and adolescents.

Objective:To explore the mechanism of Yupingfeng Powder on patients with chronic obstructive pulmonary disease (COPD) through UHPLC-QE-MS combined with network pharmacology and molecular docking technology.Methods:UHPLC-QE-MS technology was used to detect the chemical composition of Yupingfeng Powder, and its targets were obtained using ChEMB and TCMIO databases; COPD treatment targets were obtained from TTD, GeneCards, SymMap, and DisGeNET databases, and the intersection of the two was taken. GO enrichment analysis and KEGG pathway analysis were performed on intersection targets. Top 20 metabolites with the most matching targets were selected, their corresponding targets with the top 20 KEGG pathway targets were merged, and potential targets for the treatment of COPD with Yupingfeng Powder were obtained. A target protein-target protein interaction network (PPI) was constructed, key targets of Yupingfeng Powder for the treatment of COPD were screened, and molecular docking was used for validation.Results:Under positive and negative ion modes, a total of 73 active components were identified in Yupingfeng Powder. The top three ranked in terms of degree were genistein, apigenin, and kaempferol. 449 targets of 73 active components and 3 455 disease targets were obtained from the database. The intersection of the two was obtained, resulting in 294 common targets. A total of 69 pathways were identified through KEGG pathway analysis, involved in the pathogenesis of cancer, non-small cell lung cancer signaling pathway, VEGF signaling pathway, T cell receptor (TCR) signaling pathway, arachidonic acid metabolism, Toll like receptor signaling pathway, etc. GO enrichment analysis obtained 2 647 biological processes, 126 cellular components, and 289 molecular functions, involving reactions to nutritional levels, extracellular stimuli, oxidative stress, etc. The top 20 KEGG pathways and the top 20 metabolites with the most matching targets correspond to a total of 281 targets. The key targets were TP53, STAT3, c-Jun, AKT1, and ESR1. The molecular docking results showed that genistein, apigenin, and kaempferol bound well with core targets TP53, STAT3, and c-Jun.Conclusion:Yupingfeng Powder may affect the levels of inflammation, immune regulation, and oxidative stress in COPD through multiple components, targets, and pathways, thereby affecting the progression of COPD.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.