A novel image deep learning-based sub-centimeter pulmonary nodule management algorithm to expedite resection of the malignant and avoid over-diagnosis of the benign.

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.

The oral microbiome in autoimmune diseases: friend or foe?

The human body is colonized by abundant and diverse microorganisms, collectively known as the microbiome. The oral cavity has more than 700 species of bacteria and consists of unique microbiome niches on mucosal surfaces, on tooth hard tissue, and in saliva. The homeostatic balance between the oral microbiota and the immune system plays an indispensable role in maintaining the well-being and health status of the human host. Growing evidence has demonstrated that oral microbiota dysbiosis is actively involved in regulating the initiation and progression of an array of autoimmune diseases.Oral microbiota dysbiosis is driven by multiple factors, such as host genetic factors, dietary habits, stress, smoking, administration of antibiotics, tissue injury and infection. The dysregulation in the oral microbiome plays a crucial role in triggering and promoting autoimmune diseases via several mechanisms, including microbial translocation, molecular mimicry, autoantigen overproduction, and amplification of autoimmune responses by cytokines. Good oral hygiene behaviors, low carbohydrate diets, healthy lifestyles, usage of prebiotics, probiotics or synbiotics, oral microbiota transplantation and nanomedicine-based therapeutics are promising avenues for maintaining a balanced oral microbiome and treating oral microbiota-mediated autoimmune diseases. Thus, a comprehensive understanding of the relationship between oral microbiota dysbiosis and autoimmune diseases is critical for providing novel insights into the development of oral microbiota-based therapeutic approaches for combating these refractory diseases.

Baseline serum tumor markers predict the survival of patients with advanced non-small cell lung cancer receiving first-line immunotherapy: a multicenter retrospective study.

BACKGROUND: This study aimed to investigate the association between baseline serum tumor markers (STMs) (carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], cytokeratin-19 fragment [CYFRA21-1], carbohydrate antigen 19-9 [CA19-9], and carbohydrate antigen 125 [CA125]) and the efficacy of first-line immunotherapy in patients with advanced non-small cell lung cancer. METHODS: This multicenter retrospective study evaluated patients who received first-line immunotherapy between July 2017 and July 2022. The endpoints were progression-free survival (PFS) and overall survival (OS), as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. We divided the patients into three groups based on STM levels: Group A ≥ threefold upper limit of normal, threefold upper limit of normal > Group B > upper limit of normal, and Group C ≤ upper limit of normal. RESULTS: In total, 716 patients were included in this study. In Cox proportional hazards analyses, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung adenocarcinoma (LUAD). Except for CA19-9 level, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung squamous carcinoma (LUSC). Except for CEA and CA19-9 levels, the levels in Group A were independently associated with inferior PFS and OS in patients with LUAD and LUSC. CONCLUSIONS: Serum CEA, NSE, CYFRA21-1, and CA125 levels can predict PFS and OS in patients with LUAD and LUSC, and serum CA19-9 levels can predict PFS and OS in patients with LUAD. The higher the serum NSE, CYFRA21-1, and CA125 levels, the worse the PFS and OS in patients with LUAD and LUSC. In addition, the higher the serum CA19-9 level, the worse the OS in patients with LUAD.

Analysis of epidemiological trends of and associated factors for tooth loss among 35- to 44-year-old adults in Guangdong, Southern China, 1995-2015: a population-based cross-sectional survey.

BACKGROUND: Tooth loss is a known marker of oral and systemic health, but large-scale population-based and cross-sectional multi-year comparative studies on tooth loss have yet to be much studied in China. This study explores the changing trends in tooth loss status and the associated factors influencing the prevalence of tooth loss over the past two decades in Guangdong, Southern China. METHODS: Data from three cross-sectional, representative oral epidemiological surveys in Guangdong Province were analyzed, including 400 in 1995, 720 in 2005, and 288 in 2015, for a total of 1408 participants. Sample selection is based on the National Census of China published by the National Bureau of Statistics. In this study, each year, the number of missing teeth (MT) and the prevalence of tooth loss (MT > 0) were calculated. Basic demographic information, socioeconomic status, caries and periodontal status, personal lifestyle factors, and dental health care behaviors were analyzed by multivariate logistic regression to estimate their associations with tooth loss. Statistical significance was evaluated with 2-sided tests with a significance level of P < 0.05. RESULTS: This study found that the mean number of missing teeth and the prevalence of tooth loss among adults aged 35-44 years in Guangdong Province did not change significantly in the first decade (1995-2005) but decreased significantly in the second decade (2005-2015) (0.94 and 40.8% in 1995, 0.99 and 42.9% in 2005, and 0.63 and 33.3% in 2015, respectively). The mean number of MT by tooth position was highest for the first and second molars, and both were larger in the mandible than in the maxilla. In 1995, populations with low educational attainment and the presence of caries or periodontal pocket (periodontal probing depth ≥ 4 mm) were associated with a higher chance of MT > 0. In 2005, those with low educational attainment, the presence of caries, and 40-44 years old were associated with a higher chance of MT > 0. Moreover, in 2015, females, rural residents, and those with caries or periodontal pocket were associated with a higher chance of MT > 0. CONCLUSIONS: Although tooth retention has improved recently (2005-2015) and the preventive effect of education level on tooth loss has increased over time, efforts to prevent tooth loss in adults need to be strengthened. Particular attention should be given to preventive interventions for women, rural residents, and those suffering from caries or periodontal pocket.

Oral health-related quality of life in patients with osteoarthritis of the temporomandibular joint-Results of a systematic review.

OBJECTIVES: The aim of this systematic review was to assess the oral health-related quality of life (OHRQoL) of patients with osteoarthritis (OA) of the temporomandibular joint (TMJ). METHODS: This systematic literature search applied the search terms "oral health-related quality of life AND osteoarthritis of jaw OR arthritis of temporomandibular joint AND oral health-related quality of life" in PubMed, Medline, Web of Science and Scopus. Eligibility criteria were publication until 31 August 2021, examination of children or adults with OA of TMJ, reporting of any OHRQoL measurement and a full text in English language. Two different, independent and experienced reviewers performed this systematic literature search. The analysis of respective data was qualitative. For quality appraisal, the available checklist from the Agency for Healthcare Research and Quality (AHRQ) was applied. RESULTS: Out of 102 findings, eight studies were included in qualitative analysis. Seven clinical investigations were performed in adults aged between 34 and 43 years. The other included study was performed on children. The quality of two studies was moderate, and six studies were evaluated as of high quality. Most studies applied the 14-item short form of the oral health impact profile (OHIP 14) for assessment of OHRQoL. OHIP 14 ranged between 9.24 and 38.86 points in means of sum score. Comparison with healthy individuals revealed worse OHRQoL of OA patients in two studies. Associations between OHRQoL with either oral health, general quality of life or disease-related parameters were rarely reported and heterogeneous. Five of the included studies reported subscales of OHIP 14, showing an impairment in all subscales. CONCLUSIONS: There are hints that patients with OA of the TMJ show a reduced OHRQoL. More studies are needed, especially regarding oral health, disease-related parameters and pain intensity and its potential influence on OHRQoL.

Greater inequalities in dental caries treatment than in caries experience: a concentration index decomposition approach.

BACKGROUND: The aim of the current study was to (a) measure the socioeconomic inequalities in oral health and examine whether the inequalities are greater in disease experience or in its treatment and to (b) decompose the factors that influence oral health inequalities among the adults of Guangdong Province. METHODS: A cross-sectional study was conducted among 35- to 44-year-old and 65- to 74-year-old adults in Guangdong Province. All participants underwent oral health examinations and answered questionnaires about their oral health. We measured the concentration indices of the DMFT and its separate components, namely, decayed teeth (DT), missing teeth (MT), and filled teeth (FT), to explore the inequalities in oral health status; then, we analysed its decomposition to interpret the factors that influence the inequalities. RESULTS: The results showed that significant inequality was concentrated on FT (CI = 0.24, 95% CI = 0.14/0.33, SE = 0.05). The concentration indices for the DMFT (CI = 0.02, 95% CI = 0.02/0.06, SE = 0.02) and MT (CI = 0.02, 95% CI 0.03/0.08, SE = 0.03) were small and close to zero, while the concentration for DT (CI = - 0.04, 95% CI = - 0.01/0.02, SE = 0.03) was not statistically significant. The results from the decomposition analysis suggested that a substantial proportion of the inequality was explained by household income, high education level, regular oral examination and type of insurance (5.1%, 12.4%, 43.2%, - 39.6% (Urban Employee Basic Medical Insurance System) and 34.5% (New-Type Rural Medical Collaboration System), respectively). CONCLUSIONS: The results indicated greater inequalities in dental caries than in caries experience. Among the included factors, household income, high education level, and regular oral health examinations had the greatest impact on the inequalities in the number of FT. In addition, the current medical insurance systems, including the Urban Employee Basic Medical Insurance System, Urban Resident Basic Medical Insurance System, and the New-Type Rural Medical Collaboration System, have not been effectively used in oral treatment. Policy-making and the implementation of interventions for tackling socioeconomic oral health inequalities should focus on reducing the burden of treatment and providing greater access to dental care for low-income groups. Welfare policies are skewed towards rural areas and low-income people.

Epidemiology and associated factors of gingivitis in adolescents in Guangdong Province, Southern China: a cross-sectional study.

BACKGROUND: Gingivitis is the most prevalent form of periodontal disease in children and adolescents, being strongly associated to some socioeconomic factors and oral health behaviours. This study aimed to assess the prevalence of gingivitis and its association with socio-demographic factors and oral health-related behaviours in children aged 12-15 years in Guangdong, Southern China. METHODS: A total of 7680 children were sampled using an equal-sized, stratified, multistage, random sampling method and clinically examined between December 2015 and April 2016. A questionnaire on socio-demographic factors and oral health-related behaviours related to gingivitis was completed by each of the selected children. Gingival bleeding was recorded using the Community Periodontal Index probe, and children with a gingival bleeding positive score ≥ 10% were defined as having gingivitis. A multivariate logistic regression analysis was performed to assess the association between socio-demographic factors and gingivitis. All statistical tests were performed at a two-sided significance level of 0.05. RESULTS: The weighted prevalence of gingivitis among 12-15-year-old children was 29.6%, with 22.6% having localised gingivitis and 7.0% having generalised gingivitis. Age differences were observed in the prevalence of gingivitis, whereas urban-rural differences were not. According to the multivariate logistic regression analysis results, factors such as increasing age, being the only child, lack of regular annual dental check-up, and heavy dental calculus were significantly associated with higher prevalence of gingivitis. In addition, the association of gingivitis with these factors was inconsistent among the urban and rural areas. CONCLUSIONS: Dental calculus and oral health behaviour were found to be important factors for maintaining the gingival health of children aged 12-15 years in Guangdong. Maintaining gingival health in children requires promoting positive oral health behaviours and regular dental prophylaxis.

The status and associated factors of early childhood caries among 3- to 5-year-old children in Guangdong, Southern China: a provincial cross-sectional survey.

BACKGROUND: Dental caries of deciduous teeth (Early Childhood Caries, ECC) has become a crucial oral health problem over the decades in China. The aim of this study was to examine the prevalence and severity of ECC among preschool children from Guangdong Province, Southern China. In addition, to assess the association of ECC with reported oral health-related behaviors. METHODS: A cross-sectional survey of 2592 participants was carried out in Guangdong Province by means of an equal-sized, stratified, multistage random sampling method during December 2015 and April 2016. The participants were divided into three groups according to their ages (3-, 4-, and 5-year-olds). Half of the participants were derived from urban areas, while the other from rural areas. According to the standard for clinical dentition examination of the WHO 2013 criteria, the presence of ECC was determined by the dmft (decayed-missing-filled tooth) index using a CPI (Community Periodontal Index) probe. A questionnaire about caries-related factors was completed by each of the participants' parents or grandparents through a face-to-face and one-on-one interview. Then, t-test, Chi2 tests, One-Way ANOVA served for statistical analysis, and logistic regression analysis as well as covariance analysis were executed to identify potential associated factors for ECC. RESULTS: The prevalence (% dmft > 0) of ECC was 68.3 (95% CI: 66.5-70.1), the mean dmft was 4.36 (95% CI: 4.17-4.55), and the filled rate was 1.2%. In multivariable modeling, associated factors for both prevalence and mean dmft were older age, rural areas, consumption of sweets before sleep, dental visit history, low household income, and low parental education level. Initiating toothbrushing after 3 years of age and being exclusively/ predominantly breastfed indicated only the prevalence; being female and frequently consuming sweetened milk/powdered milk indicated only the mean dmft. CONCLUSIONS: Preschool children in Guangdong Province, especially children from rural areas, experienced a significant amount of ECC. Associated factors for ECC included demographics, oral health measures, dietary factors, and socioeconomic factors. More attention should be given to prevention of ECC from early life. The construction of social support for oral health should be strengthened. Oral health education and promotion, especially of rural areas, should be intensified to reduce the inequality between urban and rural areas.

MicroRNA-145 performs as a tumor suppressor in human esophageal squamous cell carcinoma by targeting phospholipase C epsilon 1.

Esophageal squamous cell carcinoma (ESCC) is the leading pathologic type in China. miR-145 has been reported to be downregulated in multiple tumors. This study was aimed to investigate the role of miR-145 in ESCC. miR-145 expression was investigated in 65 ESCC samples as well as four ESCC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Targetscan 6.2 website (http://www.targetscan.org/) was used to predict the targets of miR-145. Expression of phospholipase C epsilon 1 (PLCE1) messenger RNA and protein was detected by qRT-PCR or Western blot. MTT and wound healing assay were conducted to explore the effects of miR-145 on the proliferation and migration of ESCC cell lines, respectively. miR-145 was significantly decreased in ESCC tissues. An inverse correlation between miR-145 and invasion depth and TNM stage were observed. PLCE1 was a direct target of miR-145, and the expression of PLCE1 was inversely correlated with miR-145 expression in ESCC tissues. In addition, overexpression of miR-145 suppressed cell proliferation and migration in ESCC cells. The enforced expression of PLCE1 partially reversed the suppressive effect of miR-145. These results prove that miR-145 may perform as a tumor suppressor in ESCC by targeting PLCE1.

Toward an Expert Level of Lung Cancer Detection and Classification Using a Deep Convolutional Neural Network.

BACKGROUND: Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical fields, we attempt to integrate a well-trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images. MATERIALS AND METHODS: Open-source data sets and multicenter data sets have been used in this study. A three-dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results. RESULTS: The sensitivity and specificity of this well-trained model were found to be 84.4% (95% confidence interval [CI], 80.5%-88.3%) and 83.0% (95% CI, 79.5%-86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10-30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three-dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment. CONCLUSION: Under the companion diagnostics, the three-dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices. IMPLICATIONS FOR PRACTICE: The three-dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice.

A survey on the prevalence and risk indicators of erosive tooth wear among adolescents in Guangzhou, South China.

BACKGROUND: Erosive tooth wear (ETW) has become a crucial oral health problem over the decades in China. OBJECTIVES: To explore the prevalence and risk indicators of ETW among adolescents in Guangzhou, south China. METHODS: A cross-sectional survey of 720 participants was conducted in Guangzhou, using an equal-sized, stratified, multistage random sampling approach. The participants were from two different age groups (12- and 15-year-olds), 360 per group. The ratio of males to females was 1:1 in each group. ETW was recorded utilising the basic erosive wear examination (BEWE) index as the dependent variable. Independent variables included age, gender, region, socioeconomic status, dietary factors, oral health measures and others. RESULTS: The prevalence rates (weighted) of ETW and dentin exposure (DE) were 56.1% and 26.2% among adolescents in Guangzhou, with mean teeth (weighted) of 1.8 ± 2.5 and 0.6 ± 1.5, respectively. No matter the prevalence or the mean teeth, the 15-year-olds were higher than the 12-year-olds; the mean teeth of ETW of males was higher than that of females; the mean teeth of ETW and DE of the adolescents of low socioeconomic status were higher than those of high socioeconomic status. Medium to high risk levels were found for 10.1%. In the multiple regression model, age, gender and taking acidic foods/drinks before sleep were associated with ETW. CONCLUSIONS: Moderate ETW in the permanent dentition was common among adolescents in Guangzhou. However, the teeth involved were low. Dietary factors and demographics were the main risk indicators.

The anticaries effects of pit and fissure sealant in the first permanent molars of school-age children from Guangzhou: a population-based cohort study.

BACKGROUND: Analyses of the effects of pit and fissure sealant have been based on small samples and lack large-scale field evaluation data in China. The aim of this study was to understand the effect of pit and fissure sealant in preventing caries in the first permanent molars (FPMs) of children in Guangzhou. METHODS: We conducted a population-based cohort study using the database of the pit and fissure sealant program of Guangzhou. The carious status and sealant retention of the FPMs were assessed in 4,822 school children who received pit and fissure sealant 3 years prior to the study. The control group included 4,396 children who had indications for receiving pit and fissure sealant but were not treated and were matched according to sex, age and school. RESULTS: In the sealant group, the rate of sealant retention in the FPMs was 72.2%. Children in the sealant group had a 37% decreased risk of dental caries compared with the control group (adjusted HR = 0.63 [95% confidence interval (CI), 0.57-0.69], P < 0.001). Compared to no sealant use, the use of pit and fissure sealants reduced the risk of developing dental caries by 44% after 3 years in the FPMs of children from rural areas, reflecting a greater reduction than that among urban children (35%) during the same period (urban: adjusted hazard ratio (HR) = 0.65 [95% CI, 0.58-0.72]; rural: adjusted HR = 0.56 [95% CI, 0.45-0.70], P < 0.001). The mean number of decayed, missing, or filled permanent teeth (DMFT) in the control group was higher than that in the sealant group, and the difference was statistically significant regardless of sex. CONCLUSIONS: Pit and fissure sealant has a significant preventive effect against dental caries in the FPMs, especially for children in rural areas; thus, this sealant represents an effective technique for preventing and controlling dental caries.

Esophageal cancer-derived microvesicles induce regulatory B cells.

The role of B cells in the generation of cancer-immune tolerance is unclear. This study aims to investigate the role of cancer-derived microvesicles (Mvcs) in the generation of transforming growth factor (TGF)-ß(+) B cells. In this study, esophageal cancer (Eca) cells were isolated from surgically removed cancer tissue. Mvcs were purified from the culture supernatant and characterized by Western blotting. The immune suppression assay was carried out with a cell culture model and flow cytometry. The results showed that Eca-derived Mvcs were LAMP1 positive and carried MMP9. Exposure to the Mvcs induces naive B cells to differentiate into TGF-ß-producing regulatory B cells; the latter show immune suppressor functions on CD8(+) T-cell proliferation. In conclusion, Eca-derived Mvc can induce TGF-ß(+) B cells; the latter suppress CD8(+) T-cell activities. The MMP9-laden Mvcs may be a new therapeutic target in the treatment of Eca.

Comparison of anomalous systemic artery to left lower lobe and pulmonary sequestration in left lower lobe by computed tomography.

BACKGROUND: Differentiation of anomalous systemic artery to the left lower lobe (ASALLL) from pulmonary sequestration (PS) is essential, as ASALLL can be corrected by anastomosis, embolization, or ligation of the anomalous artery. PURPOSE: To compare computed tomography (CT) findings of ASALLL and PS in the left lower lobe (LLL). MATERIALS AND METHODS: This study included 16 patients with ASALLL and 25 patients with PS in LLL confirmed by operative and pathologic findings. RESULTS: Cough and sputum were more common in PS (84% and 60%, respectively) than in ASALLL (25% and 12.5%, respectively) (P < 0.05). Hemoptysis was more common in ASALLL (100%) than in PS (24%) (P < 0.05). The frequency of ground glass opacity (GGO), normal bronchial distribution, dilated left inferior pulmonary veins, and absence of the interlobar artery distal to the origin of the superior segmental artery in LLL differed significantly between ASALLL and PS. Mass was less common in ASALLL (0%) than in PS (88%) (P < 0.01). The mean diameter of the anomalous artery (11.88 ± 1.13 mm) in ASALLL was significantly larger than that (5.96 ± 0.98 mm) in PS (P < 0.01). The presence of anomalous artery arising from thoracic aorta was not different between ASALLL (100%) and PS (72%). CONCLUSION: Radiographic indications of ASALLL differ from those of PS in the LLL. Indications that may suggest ASALLL include an enlarged anomalous systemic artery arising from the thoracic aorta, dilated left inferior pulmonary veins, absence of the interlobar artery distal to the origin of the superior segmental artery, normal bronchial distribution, and GGO in the LLL.

PLCE1 suppresses p53 expression in esophageal cancer cells.

The apoptotic mechanism dysfunction plays a critical role in cancer cell growth and escaping from cancer therapies; the underlying mechanisms are to be further elucidated. This study aims to investigate the role of phospholipase C epsilon 1 (PLCE1) in modulating the apoptosis mechanism in esophageal cancer (Eca) cells. The results showed that Eca cell lines, OE33 and CP-C cells expressed high levels of PLCE1. Knockdown of PLCE1 markedly increased 9.26 folds of the expression of p53 and 13.8 folds of the frequency of apoptotic CP-C cells via modulating the p53 promoter methylation.

Airway epithelial cell-derived insulin-like growth factor-1 triggers skewed CD8(+) T cell polarization.

Skewed CD8(+) T cell responses are important in airway inflammation. This study investigates the role of the airway epithelial cell-derived insulin-like growth factor 1 (IGF1) in contributing to CD8(+) T cell polarization. Expression of IGF1 in the airway epithelial cell line, RPMI2650 cells, was assessed by quantitative real time RT-PCR and Western blotting. The role of IGF1 in regulating CD8(+) T cell activation was observed by coculture of mite allergen-primed RPMI2650 cells and naïve CD8(+) T cells. CD8(+) T cell polarization was assessed by the carboxyfluorescein succinimidyl ester-dilution assay and the determination of cytotoxic cytokine levels in the culture medium. Exposure to mite allergen, Der p1, increased the expression of IGF1 by RPMI2650 cells. The epithelial cell-derived IGF1 prevented the activation-induced cell death by inducing the p53 gene hypermethylation. Mite allergen-primed RPMI2650 cells induced an antigen-specific CD8(+) T cell polarization. We conclude that mite allergens induce airway epithelial cell line, RPMI2650 cells, to produce IGF1; the latter contributes to antigen-specific CD8(+) T cell polarization.

Effect of lowering or restricting sympathectomy levels on compensatory sweating.

OBJECTIVE: There is controversy on whether lowering or restricting the level of sympathectomy can reduce compensatory sweating (CS). This study compared the results from sympathectomies performed to treat severe palmar hyperhidrosis using two distinct levels of T2-4 and T3-4. METHODS: One hundred and sixteen patients with primary palmar hyperhidrosis were randomly allocated to undergo either T2-4 sympathectomy treatment (T2-4 group) or T3-4 sympathectomy treatment (T3-4 group). Follow-up data were collected using a telephone questionnaire to assess efficacy, side effects, overall satisfaction, and factors affecting CS and the degree of satisfaction. RESULTS: There were no significant differences with respect to either CS or severe CS between the two treatment groups at 1, 6, or 12 months of follow-up. The total scores of the quality-of-life questionnaires after surgery were remarkably decreased compared with those before surgery in the two groups. However, no significant differences in quality-of-life scores were found between the two groups before surgery, or at 1, 6, or 12 months of follow-up. Age was predictive of severe CS at 6 months of follow-up (P = 0.045). Severe CS was inversely associated with patient satisfaction at 1, 6, and 12 months of follow-up. INTERPRETATION: The issue of whether lowering or restricting the level of sympathectomy reduces CS is controversial and needs more supportive evidence. Age may be a predictive factor for severe CS at 6 and 12 months of follow-up. Severe CS is the only known factor that affects patient satisfaction, and family history may also be associated with patient satisfaction.

Dynamics of interstitial calcium in rat myocardial ischemia reperfusion injury in vivo.

Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury (IR). However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium dynamics in rat myocardial IR model in vivo. A microdialysis system was involved, and the time delay of the system and recovery time was introduced and tested with a fluids switching method. Twelve SD rats were divided into IR or control group. Myocardial IR was induced by ligating (20 min) then releasing (60 min) the suture underlying left anterior descending branch. Mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area for occlusion. Dialysate samples were collected every 10 min. Dialysate calcium concentration was detected with an atomic absorption spectrophotometer. Recovery time for the microdialysis system was 20 min, and recovery rate was 16%. Dialysate calcium concentration showed no changes during ischemia, descended immediately after reperfusion, reached the lowest level (67% of baseline value) 20 min after reperfusion, then escalated slowly. Recovery time was an important parameter for mycrodialysis technique, and it should not be neglected and needed to be tested. Our data suggest that interstitial calcium concentration in rats with myocardial IR in vivo kept steady in ischemia, descended rapidly at the initial reperfusion, then rebounded slowly. In conclusion, we introduced the concept of recovery time for microdialysis and provided a simple testing method.

Controllable Adaptive Molybdate-Oligosaccharide Nanoparticles Regulate M2 Macrophage Mitochondrial Function and Promote Angiogenesis via PI3K/HIF-1α/VEGF Pathway to Accelerate Diabetic Wound Healing.

The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders and vascular injury are the primary causes of death in such patients. Herein, a sprayable, controllable adaptive, pH-responsive nanosystem of molybdate and oligosaccharide (CMO) is specially developed as an immunomodulatory and angiogenesis-promotion material for diabetic wound healing. CMO exhibited pH-responsive release of Mo2+ and oligosaccharide (COS), specifically in response to the alkalescent environment observed in diabetic wounds. CMO provide an anti-inflammatory environment by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, CMO with a certain concentration reduce reactive oxygen species (ROS) and tumor necrosis factor α (TNF-α) expression, and upregulated mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and interleukin 10 (IL-10) expression in macrophages. Moreover, CMO facilitate angiogenesis via upregulating the PI3K/HIF-1α/VEGF pathway-a critical process for the formation of new blood vessels that supply nutrients and oxygen to the healing tissue. Remarkably, CMO promote cell viability and migration of endothelial cells, and enhance the expression of angiogenic genes. In vitro and in vivo studies suggest this simple but powerful nanosystem targeting mitochondrial function has the potential to become an effective treatment for diabetic wound healing.

The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.