Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

Objective:Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment.Methods:Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change.Results:The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend ( t=4.81 ,P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend ( t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions:The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.

Objective:Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment.Methods:Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change.Results:The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend ( t=4.81 ,P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend ( t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions:The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Odontoma is a hamartoma or developmental malformation of dental tissues and often causes delayed or im-pacted permanent teeth.This paper reports a case of surgical removal of an odontoma that is closely attached to the labial bone plait and examines the extraction of accompanying high-impacted maxillary canine beside the nose and maxillary sinus.Digital technology was used in reconstructing a part of a patient's maxilla,odontoma,related teeth,and other adja-cent anatomical structures,accurately determine the lesion boundary,and design an optimal surgical plan.The minimally invasive extraction of lesions and embedded teeth with a double-fenestration technique through the upper and lower paths not only preserved the continuity of the labial alveolar bone plate in the operative area and prevented postoperative bone collapse but also reduced the risk of maxillary sinus mucosal injury and perforation,improved surgical efficiency,and reduced the surgical trauma.These features were in line with the concept of minimally invasive alveolar surgery.

Objective To investigate the expression of IL-18,IL-18BP,and IL-18R in the peripheral blood B lymphocytes and mono-cytes of patients with atopic dermatitis(AD).Methods Peripheral venous blood was collected from 28 patients with AD and 21 healthy controls,and stimulated with Artemisia sieversiana wild allergen extract,house dust mite allergen extract,or Platanus pollen allergen extract.The expression of IL-18+,IL-18BP+,and IL-18R+in B lymphocytes and monocytes was measured using flow cytometry.Results Compared with the healthy control group,the proportions of IL-18+,IL-18BP+,and IL-18R+cells in the B lymphocyte group of patients with AD at rest increased 2.01-,10.35-,and 20.85-fold,respectively.The proportions of IL-18+and IL-18BP+cells in monocytes increased 5.51-and 41.88-fold,respectively,whereas the proportion of IL-18R+cells did not differ significantly between the groups.Conclusion IL-18,IL-18BP,and IL-18R in B lymphocytes and monocytes may play an important role in AD.IL-18,IL-18BP,and IL-18R may be potential targets for the treatment of AD.

Objective To investigate the predictive value of preoperative blood inflammatory markers for the recurrence risk in patients with basal cell carcinoma(BCC).Methods A total of 225 patients with BCC were divided into the high-risk recurrence group(155 cases)and the low-risk recurrence group(70 cases).General information and preoperative hematological indicators were collected in the two groups of patients.The neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),systemic inflammation marker(SIM)and platelet-to-lymphocyte ratio(PLR)were calculated.Receiver operating characteristic(ROC)curves were used to determine the predictive value of hematological markers with statistically significant differences between the two groups for BCC recurrence and to establish optimal cutoff values.Univariate and multivariate Logistic regression analyses were conducted to identify factors influencing BCC recurrence.A multivariate Logistic regression model was established to predict the recurrence risk of BCC.Area under the curve(AUC)and the Hosmer-Lemeshow test were used to evaluate the prediction efficiency and goodness-of-fit of the model.Results ROC analysis identified that optimal cutoff values for LMR and SIM were 5.12 and 0.86,respectively.Univariate Logistic regression analysis showed that LMR,SIM,ulceration at the primary tumor site,UV exposure and tumor maximum diameter were factors influencing BCC recurrence.Multivariate Logistic regression revealed that SIM≥0.86,tumor maximum diameter≥2.0 cm and UV exposure were risk factors for BCC recurrence,while LMR≥5.12 had a protective effect.The Logistic prediction model for BCC recurrence risk was Logit(P)=-1.598-1.517×LMR+1.323×SIM+2.406×UV exposure+3.465×tumor maximum diameter,with good model fit(P=0.725)and an AUC of 0.869(95%CI:0.822-0.917)for predicting BCC recurrence risk.Conclusion Monitoring preoperative LMR and SIM levels can assist in assessing the risk of recurrence in BCC patients and provide important guidance for clinical decision-making.