Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

Objective To establish the fingerprint of Jianggui granules, and evaluate it by chemometrics. Methods The fingerprint of Jianggui granules was established by HPLC. Similarity evaluation system of chromatographic fingerprint of TCM （2012 edition） was used to evaluate the similarity evaluation. Then, the quality of the drug was assessed by cluster analysis （CA）, principal components analysis （PCA） and partial least squares discriminant analysis （PLS-DA）. Results The characteristic fingerprint of Jianggui granules was established and 18 common peaks were verified. Five chromatographic peaks were identified，i.e. Puerarin, glycyrrhizin, cinnamic acid, cinnamaldehyde and ammonium glycyrrhizinate. The similarities of samples were >0.9. Results of CA showed that 14 batches of samples could be classified into two categories：S1 and S4 were grouped into one category；others were grouped into the other category. The results of PCA showed that the cumulative contribution rate of the first two principal components was 96.61%. The results of OPLS-DA showed that the eleven peaks with VIP value >1 were puerarin （peak 8）, glycyrrhizin （peak 14）, cinnamaldehyde （peak 17） and ammonium glycyrrhizinate （peak 18）. Conclusion HPLC fingerprint of Jianggui granules was established. The established method was accurate and reliable，which could be used in quality evaluation of Jianggui granules.

Fused teeth are usually formed by the partial or complete fusion of two normal tooth germs during the development process and belong to dental developmental abnormalities. Fused teeth are relatively rare clinically, and those occurring in the posterior tooth area are even rarer. This article reports a case of fused teeth between the first permanent molar and the second permanent molar in the right mandible. This fused tooth had a complex root canal anatomical structure (seven root canals). The number and location of the root canals were analyzed by cone beam computed tomography, and root canal treatment was successfully completed with the assistance of microscope.
Humans ; Molar/diagnostic imaging* ; Mandible ; Dental Pulp Cavity/abnormalities* ; Cone-Beam Computed Tomography ; Root Canal Therapy/methods* ; Fused Teeth/surgery*

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

Abstract Airborne microorganisms, especially pathogenic microorganisms, are easily transmitted through dust and droplets, leading to various infectious diseases. The study summarizes the status of airborne microbial pollution, potential exposure levels, particle size, and species distribution of microorganisms, discusses the impact of airborne microorganisms on human health, and analyzes specific factors affecting campus air microorganisms from four aspects:climate, anthropogenic factors, time, and space, to provide a scientific basis for formulating effective improvement measures, improving air quality and safeguarding the health of teachers and students.

OBJECTIVE: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People

BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Afatinib/therapeutic use* ; Lung Neoplasms/metabolism* ; Bevacizumab/therapeutic use* ; Bayes Theorem ; Network Meta-Analysis ; Protein Kinase Inhibitors/therapeutic use* ; Pemetrexed/therapeutic use* ; ErbB Receptors/genetics* ; Brain Neoplasms/genetics* ; Mutation/genetics*

Objective:To evaluate deep learning for differentiating invasion depth of colorectal adenomas under image enhanced endoscopy (IEE).Methods:A total of 13 246 IEE images from 3 714 lesions acquired from November 2016 to June 2021 were retrospectively collected in Renmin Hospital of Wuhan University, Shenzhen Hospital of Southern Medical University and the First Hospital of Yichang to construct a deep learning model to differentiate submucosal deep invasion and non-submucosal deep invasion lesions of colorectal adenomas. The performance of the deep learning model was validated in an independent test and an external test. The full test was used to compare the diagnostic performance between 5 endoscopists and the deep learning model. A total of 35 videos were collected from January to June 2021 in Renmin Hospital of Wuhan University to validate the diagnostic performance of the endoscopists with the assistance of deep learning model.Results:The accuracy and Youden index of the deep learning model in image test set were 93.08% (821/882) and 0.86, which were better than those of endoscopists [the highest were 91.72% (809/882) and 0.78]. In video test set, the accuracy and Youden index of the model were 97.14% (34/35) and 0.94. With the assistance of the model, the accuracy of endoscopists was significantly improved [the highest was 97.14% (34/35)].Conclusion:The deep learning model obtained in this study could identify submucosal lesions with deep invasion accurately for colorectal adenomas, and could improve the diagnostic accuracy of endoscopists.