Objective: To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice. Methods: Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue. Results: The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05). Conclusion Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.

Lung cancer is the cancer with the highest incidence and mortality rate worldwide. In addition to the diversified treatment and prolonged lifespan in view of the development of medical technology, the side effect of medicine should not be ignored. Drug-induced interstitial lung disease (DI-ILD) is also commonly encountered during this process, and ILD triggered by the treatment of lung cancer characterized by the inflammation and scarring of lung tissue after the antitumor treatment in lung cancer leads to a poor prognosis and high mortality. The diagnosis and treatment of ILD caused by anti-lung cancer agents remains challenging in clinical settings and requires joint efforts from multidisciplinary team (MDT). This review systematically updates the epidemiology, molecular pathogenesis, genomics/genetics study, diagnosis and treatment of ILD related to anti-lung cancer agents. By the integration of the latest evidences, the paper offers clinical work references for early diagnosis of ILD related to anti-lung cancer agents to enhance the survival and quality of life of the lung cancer patients.
.
Humans ; Lung Diseases, Interstitial/therapy* ; Lung Neoplasms/drug therapy* ; Antineoplastic Agents/therapeutic use*

Environmental factors play a pivotal role in the pathogenesis and progression of lung cancer, with epigenetic regulation, particularly DNA methylation, serving as a central molecular mechanism. This review systematically elaborated on the mechanisms by which environmental exposures dynamically regulate lung cancer development through influencing DNA methylation and summarized recent advances in the clinical translation of related epigenetic biomarkers for early diagnosis and targeted therapy. Relevant studies published between December 2018 and March 2025 were retrieved from Chinese and English databases, and 64 articles were included in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Environmental exposures can specifically induce abnormal methylation of tumor suppressor genes such as the aryl hydrocarbon receptor repressor (AHRR) and Ras‑associated domain family 1 isoform A (RASSF1A), thereby promoting genomic instability and activation of oncogenes. In terms of clinical translation, methylation detection of genes including short stature homeobox 2 (SHOX2) and RASSF1A in plasma has demonstrated favorable diagnostic performance, with a sensitivity of 87.0% (95%CI: 80.2%, 91.5%) and a specificity of 98.0% (95%CI: 94.9%, 99.4%), indicating its applicability for early screening of lung cancer. However, although current DNA methyltransferase (DNMT) inhibitors can achieve epigenetic reprogramming, their applications still face challenges related to insufficient selectivity among different tumor subtypes. Given that environmental factors drive lung carcinogenesis via epigenetic mechanisms, there is an urgent need to establish a three‑tier prevention and control framework encompassing “environmental monitoring – methylation biomarker screening – targeted intervention.” Future efforts should focus on deepening integrated multi‑omics analyses, developing subtype‑selective DNMT inhibitors, and optimizing multimodal detection strategies for methylation biomarkers to advance precision prevention and treatment of lung cancer.

ObjectiveTo explore the role and molecular mechanism of Weifuchun （WFC） in inhibiting inflammation and alleviating gastric precancerous lesions （GPL）. MethodHuman gastric mucosal epithelial cells （GES-1） were stimulated with N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPL （MC cells）， with Caspase-3 inhibition by Z-DEVD-FMK. MC cells were divided into control （20% blank serum）， WFC （15% and 20% WFC-containing serum）， and caspase-3 inhibitor groups. The cell counting kit-8 （CCK-8） was used to examine the viability of GES-1 cells or MC cells. The Transwell assay and 5-acetylidene-2′-deoxyuridine （EdU） staining were employed to examine cell invasion and proliferation， respectively. Flow cytometry was employed to determine the level of reactive oxygen species. Real-time PCR was conducted to determine the mRNA levels of interleukin （IL）-1， IL-6， and tumor necrosis factor （TNF）-α. Gene Expression Omnibus （GEO） was used to analyze the role of pyroptosis in gastric cancer progression. Western blotting was employed to determine the protein levels of nuclear factor-κB （NF-κB） p65， gasdermin E （GSDME）， and Caspase-3. Immunofluorescence staining was employed to detect the NF-κB p65 protein level and nuclear translocation. Hematoxylin-eosin staining was carried out to observe the pathological changes in the gastric mucosa before and after WFC treatment in the patients. ResultCompared with the control group， MC cells presented enhanced proliferation and invasion energy （P<0.01）. Compared with the blank serum group， WFC-containing serum inhibited the proliferation and invasion of MC cells （P<0.01）， down-regulated the mRNA levels of IL-1， IL-6， and TNF-α， and lowered the level of reactive oxygen species （P<0.05， P<0.01）. The transcriptome data at different stages of gastric cancer showed that pyroptosis was involved in gastric cancer progression， and the GSDME level was significantly higher in GPL patients than in the normal group. Compared with the blank serum， WFC-containing serum lowered the level of NF-κB and inhibited the nuclear translocation of NF-κB （P<0.05）， and it inhibited pyroptosis by suppressing the cleavage of Caspase-3 on GSDME （P<0.05， P<0.01）. The analysis of patient specimens further demonstrated that WFC treatment down-regulated the NF-κB level and GSDME cleavage （P<0.01）， inhibited pyroptosis， and alleviated gastric mucosal inflammation and intestinal epithelial metaplasia. ConclusionPyroptosis is involved in the progression of gastric cancer， and WFC inhibits pyroptosis via the NF-κB/GSDME pathway， thereby alleviating gastric mucosal inflammation in GPL.

ObjectiveTo explore the mechanism of Buzhong Yiqitang on pyroptosis in autoimmune thyroiditis （AIT） mice based on the NOD-like receptor hot protein domain related protein 3 （NLRP3）/cysteinyl aspartate specific proteinase-1（Caspase-1）/Gasdermin D （GSDMD） pathway. MethodSixty NOD.H-2^h4 mice were divided into normal group， model group， low， medium， and high dose groups （4.10， 8.19， 16.38 g·kg^-1）of Buzhong Yiqitang， and selenium yeast tablet group （0.26 mg·kg^-1）， with 10 mice in each group. Except for the normal group， all other groups were given 0.05% NaI by gavage for eight weeks to establish a model and then received the drug treatment for eight weeks. The serum levels of thyroid peroxidase antibody （TPO-Ab） and thyroglobulin antibody （TgAb） were detected using enzyme-linked immunosorbent assay （ELISA） method. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in mouse thyroid tissue. The immunohistochemical method was used to detect the protein expression of NLRP3， Caspase-1， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18. Western blot was used to detect the levels of pyroptosis-related proteins in thyroid tissue. ResultCompared with the normal group， the serum levels of TPO-Ab and TgAb in the model group were significantly increased （P<0.01）. Thyroid follicles either increased in a cubic shape or were damaged and atrophied， with a large number of lymphocytes infiltrating around the follicles. Compared with the model group， the levels of TPO-Ab and TgAb in other groups were significantly reduced （P<0.01）， and the morphology and structure of follicles were improved. The degree of lymphocyte infiltration was reduced. Among them， the medium dose group of Buzhong Yiqitang had the most significant reduction and improvement effect. Compared with the normal group， the positive products and mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18 proteins in the thyroid tissue of the model group significantly increased （P<0.01）， and the protein expression levels of NLRP3， cleaved Caspase-1， IL-1β， IL-18， and GSDMD-N were significantly increased （P<0.05， P<0.01）. Compared with the model group， the positive products and mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18 proteins in other groups were significantly reduced （P<0.05， P<0.01）， with the most significant reduction effect in the medium dose group of Buzhong Yiqitang. The protein expression levels of NLRP3， cleaved Caspase-1， IL-1β， IL-18， and GSDMD-N were significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can improve AIT， and its mechanism may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit pyroptosis.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective To investigate the effect of visual soft lens assisted nasotracheal intubation in the treatment of dental caries in children under general anesthesia.Methods Eighty children aged 3-5 years undergoing dental caries treatment under general anesthesia in Stomatological Hospital Affiliated to Nanchang University from April 2020 to April 2023 were selected.According to the random number table method,they were divided into visual laryngoscope group and visual soft lens group,with 40 cases in each group.Children in visual laryngoscope group were used visual laryngoscope endotracheal intubation,children in visual soft lens group were used visual soft lens endotracheal intubation.The incidence of intubation complications such as cuff rupture,oral soft tissue injury and hoarseness were compared between two groups.The glottis exposure time,endotracheal intubation,endotracheal intubation success rate for the first time,heart rate(HR)and mean arterial pressure(MAP)were measured 30min before induction,immediately after induction,immediately after tracheal intubation and 3min after tracheal intubation.Results HR,MAP,tracheal intubation time,the incidence of cuff rupture and oral soft tissue injury immediately after tracheal intubation in visual soft lens group were lower than those in visual laryngoscope group(P＜0.05).Conclusion The use of visual soft lens for nasotracheal intubation in children with dental caries under general anesthesia has stable hemodynamics,short intubation time,and low incidence of intubation complications,which can be effectively applied in clinical practice.

Objective:To investigate the influencing factors of falls in patients with chemotherapy-induced peripheral neuropathy for gynecological cancer, and establish a Nomogram model based on independent influencing factors.Methods:A total of 216 patients with peripheral neuropathy who received chemotherapy for gynecological cancer in The First Affiliated Hospital of Army Military Medical University of the People′s Liberation Army from February 2021 to April 2023 were retrospectively selected, and were divided into the modeling set and the validation set according to the ratio of 7∶3 using random number table method. According to the occurrence of falls in the modeling set, the patients were divided into the fall group and the non-fall group. Independent influencing factors were obtained through univariate analysis and multivariate Logistic regression analysis, and a prediction model was constructed based on the regression analysis. A Nomogram map was drawn using R language software. Receiver operating characteristic curve (ROC) and calibration curve were used to test the prediction efficiency, and the predictive benefits were evaluated by clinical decision curve.Results:Among the 216 patients, 151 were included in the modeling set and 65 in the validation set. Among the patients in the modeling set, 53 cases were in the fall group, aged (62.89 ± 8.58) years old, and 98 cases were in the non-fall group, aged (59.48 ± 8.12) years old. Chemotherapy cycle, Neuropathy Impairment Score-Lower Limbs, Barthel index, Home Falls and Accidents Screening Tool, regular exercise habits, diabetes and depression were all independent influencing factors for falls in patients with chemotherapy-induced peripheral neuropathy of gynecologic cancer ( OR values were 0.312-3.727, all P<0.05). The area under the curve (AUC) of the established Nomogram model was 0.873, with good discriminating ability. The mean absolute error (MAE) of calibration curve was 0.048, which fitted the ideal curve, indicating that the model has good calibration performance. The AUC of the validation set was 0.873 and the MAE of calibration curve was 0.073, indicating that the model has good external prediction efficiency. Conclusions:This Nomogram model can predict falls in patients with chemotherapy-induced peripheral neuropathy of gynecological cancer and provide evidence for clinical prevention of falls.