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OBJECTIVE@#To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism.@*METHODS@#Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis.@*RESULTS@#DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01).@*CONCLUSIONS@#DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Subject(s)
Mice , Male , Animals , Proto-Oncogene Proteins c-akt/metabolism , Lipopolysaccharides , Phosphatidylinositol 3-Kinases/metabolism , Interleukin-1beta/metabolism , Vascular Endothelial Growth Factor A/metabolism , Tumor Necrosis Factor-alpha/metabolism , Claudin-5/metabolism , Acute Lung Injury/chemically induced , Lung/pathology , Interleukin-6/metabolism , Drugs, Chinese Herbal摘要
Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.
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Objective:To analyze the positive detection rate, main genotypes of β-thalassemia in western region of Guangxi Zhuang Autonomous Region (referred to as Guangxi).Methods:Retrospective analysis of 26 189 individuals who underwent gene testing for thalassemia at the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2013 to December 2019. Using the crossing breakpoint PCR (Gap-PCR) and reverse dot blot (RDB) techniques to detect Chinese common type of 7 kinds of α-thalassemia and 17 kinds of β-thalassemia genotypes, high-throughput sequencing(Sanger) was performed for suspected rare β-thalassemia. Gap-PCR was used for suspected deletion β-thalassemia types.Results:β-thalassemia was diagnosed in 4 495 (17.16%) of 26 189 samples. A total of 6 177 alleles of 20 types of β-thalassemia were detected, mainly CD17 (2 712 cases, 43.90%) and CD41-42 (2 240 cases, 36.26%), including 7 rare alleles: Gγ +( Aγδβ) 0, SEA-HPFH, Hb New York, Hb G-Taipei, Hb Hezhou, Hb G-Coushatta and IVS-Ⅱ-81. There were 3 903 case (86.83%) heterozygous, 273 case (6.07%) double heterozygous, and 319 case (7.10%) homozygous among 4 495 β-thalassaemia subjects. A total of 48 genotypes were detected. The two most common genotypes were CD17/β N (1 890 cases, 42.05%) and CD41-42/β N (1 212 cases, 26.96%), accounted for 69.01% (3 102/4 495). Seven rare genotypes were detected: Gγ +( Aγδβ) 0/β N in 3 cases, Hb New York/β N in 3 cases, Hb G-Taipei/β N in 2 cases, SEA-HPFH/β N, Hb Hezhou/β N, Hb G-Coushatta/β N and IVS-Ⅱ-81/β N in 1 case each. A total of 1 041 cases (3.97%, 1 041/26 189) of 116 types of αβ-thalassemia were detected, mainly -- SEA/αα composite CD17/β N (144 cases, 13.83%), followed by -α 3.7/αα composite CD17/β N (112 cases, 10.76%). Conclusions:Western region of Guangxi is a high prevalence area of β-thalassemia, CD17/β N and CD41-42/β N are the main genotypes. The variation spectrum of β-thalassemia is complex and diverse, with rich genotype.
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Objective To investigate the clinical value of serum soluble Axl receptor tyrosine ki-nase(sAxlTK)in evaluating short-term prognosis in patients with acute decompensated heart failure(ADHF).Methods A total of 238 elderly ADHF patients admitted to Bozhou People's Hospital from January 1,2018 to October 1,2021 were recruited and divided into poor prognosis group(45 patients)and good prognosis group(193 patients)according to the occurrence of com-plex events within 90 d of follow-up.Based on the optimal cut-off value of serum sAxlTK level,they were also assigned into high level group(80 cases)and low level group(158 cases).Serum levels of sAxlTK,troponin Ⅰ(cTnⅠ)and N-terminal B-type natriuretic peptide precursor(NT-proBNP)were detected.Results Serum sAxlTK level was significantly higher in the poor prognosis group than the good prognosis group[43.89(33.95,51.44)μg/L vs 23.89(18.73,33.92)μg/L,P＜0.01].Multivariate logistic regression analysis showed that serum cTnⅠ and sAxlTK levels were independent risk factors for short-term poor prognosis in ADHF patients(OR=1.922,95％CI:1.035-3.568,P=0.039;OR=1.021,95％CI:1.008-1.034,P=0.001).ROC curve analysis indicated that the AUC value of combined serum sAxlTK,cTnⅠ and NT-proBNP levels to predict short-term poor prognosis was 0.836(95％CI:0.778-0.895).The incidence of complex events within 90 d was significantly higher in the high level group than the low level group(45.0％vs 5.7％,P＜0.05).Kaplan-Meier curve analysis revealed that the cumulative inci-dence of complex events was also higher in the high level group than the low level group(X2=66.991,Plog rank＜0.01).The high level group had significantly lower overall survival rate and worse survival prognosis than the low level group(X2=16.899,Plog rank＜0.01).Conclusion High serum sAxlTK level in elderly ADHF patients at admission is associated with a higher risk of 90-day short-term poor prognosis.Serum sAxlTK has the potential to become a useful tool for early prediction of short-term poor prognosis,and its combination with cTnⅠ and NT-proBNP can fur-ther improve the accuracy of prognosis prediction.
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Liver macrophages are important immune cells in the liver， and they express proinflammatory factors and anti-inflammatory factors through polarization into M1 type and M2 type， respectively， thereby playing a role in regulating inflammatory damage response. The malignant transformation of hepatic progenitor cells is the core mechanism of the malignant progression of hepatic precancerous lesions， and its key factor is the continuous stimulation of inflammatory microenvironment， which is closely associated with M1/M2 macrophage polarization. This review mainly focuses on the association between macrophage polarization， chronic inflammation， and malignant transformation of hepatic progenitor cells， so as to provide a theoretical basis for the prevention and treatment of hepatic precancerous lesions.
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Objective @#To investigate the effects of immunoglobulin gene superfamily 10 (IGSF10) on prolifera- tion，migration and invasion of lung adenocarcinoma cells．@*Methods @#ioinformatics was applied to study the ex- pression levels of IGSF10 in tumor tissues and normal tissues． Western blot and quantitative real-time PCR ( qPCR) were used to detect the expression level of IGSF10 in lung adenocarcinoma cell lines and normal lung epi- thelial cells．Knockdown of IGSF10，the effect of knockdown of IGSF10 on proliferation，migration and invasion of lung adenocarcinoma A549 cells was examined using cell counting kit-8 ( CCK-8) ，Transwell migration and inva- sion assay，scratch assay and plate cloning assay．The effects of knockdown of IGSF10 on the expression of invasion and migration-related genes in A549 cells were examined by Western blot and qPCR assays. @*Results @#IGSF10 ex- pression in lung adenocarcinoma tissues was lower than that in normal tissues (P ＜0. 05) ．IGSF10 expression in lung adenocarcinoma cell lines was lower than that in lung epithelial cells (P＜0. 05) ．Knockdown of IGSF10 pro- moted the ability of lung adenocarcinoma A549 cells to proliferate ，proliferation ，migration and invasion ( P < 0. 05) ．Knockdown of IGSF10 promoted the expression of regulatory epithelial-mesenchymal transition marker Neu- ral-cadherin (N-cadherin) and key transcription factors Snail family transcriptional repressor 1 (Snail) and Snail family transcriptional repressor 2 (Slug) (P＜0. 05) and inhibited the expression of Epithelial-cadherin (E-cad- herin) (P＜0. 05) ．@*Conclusion @# Knockdown of IGSF10 may promote proliferation，migration and invasion of lung adenocarcinoma cells through activation of Snail，Slug / E-cadherin signaling axis，and this result may provide a po- tential new target for clinical diagnosis and treatment of lung adenocarcinoma.
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Objective:To investigate the current situation of sitting time and health literacy among high school students in China,in order to provide a basis for improving their physical and mental health levels.Methods:A stratified random cluster sampling method was used to investigate the length of sitting time and health literacy of first and second grade high school students from 31 provinces,cities,and au-tonomous regions in China(data did not include that of Hong Kong and Macao Special Administrative Re-gion,and Taiwan Province of China).The Kruskal-Wallis H method,independent sample Mann-Whit-ney U test,and regression model were used to analyze the influencing factors of sitting time and total health literacy score.Results:(1)The total score of health literacy was statistically significant(P＜0.01)in different regions,urban and rural distribution,annual family income,parents'educational background,age,and gender.(2)The length of sitting was statistically significant(P＜0.01)among multiple groups in different regions,family annual income,parental education,and gender.However,there was no statistically significant difference between groups of different ages and urban-rural distribution(P＞0.05).(3)The analysis of multiple linear regression model showed that the total score of health literacy was positively correlated with the family's annual income and the mother's education,and nega-tively correlated with the father's education and the length of sitting.Standardized regression coefficientβcomparison:Father's education(-0.32)＞family annual income(0.15)＞mother's education(0.09)＞average daily sitting time(-0.02),with father's education having the greatest impact,fol-lowed by family annual income.The length of sitting was positively related to the family's annual income and the mother's educational background,and negatively related to the total score of health literacy.Standardized regression coefficientβ comparison:Annual family income(0.14)＞education background of mother(0.13)＞total score of health literacy(-0.02),with the impact of annual family income the largest,followed by education background of mother.Conclusion:China's first and second grade high school students generally spend a long time sitting every day,and the level of health literacy is generally low.The level of health literacy and sitting time are negatively correlated with each other,and are most in-fluenced by the educational background of high school students'parents and their family economic levels.
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Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.
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Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
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Background@#Data on the efficacy and incidence of adverse effects associated with dexmedetomidine (DEX) as a local anesthetic adjuvant for patient-controlled epidural analgesia (PCEA) are inconclusive. This meta-analysis assessed the efficacy and risks of DEX for PCEA using opioids as a reference. @*Methods@#Two researchers independently searched PubMed, Embase, Cochrane Library, and China Biology Medicine for randomized controlled trials comparing DEX and opioids as local anesthetic adjuvants in PCEA. @*Results@#In total, 636 patients from seven studies were included in this meta-analysis. Postoperative patients who received DEX had lower visual analog scale (VAS) scores than those who received opioids at 4–8 h (mean difference [MD]: 0.61, 95% CI [0.45, 0.76], P < 0.001, I2 = 0%), 12 h (MD: 0.85, 95% CI [0.61, 1.09], P < 0.001, I2 = 0%), 24 h (MD: 0.59, 95% CI [0.06, 1.12], P = 0.030, I2 = 82%), and 48 h (MD: 0.54, 95% CI [0.05, 1.02], P = 0.030, I2 = 91%). Additionally, patients who received DEX had a lower incidence of itching (odds ratio [OR]: 2.86, 95% CI [1.18, 6.95], P = 0.020, I2 = 0%) and nausea and vomiting (OR: 6.83, 95% CI [3.63, 12.84], P < 0.001, I2 = 24%). In labor analgesia, no significant differences in neonatal (pH and PaO2 of cord blood, fetal heart rate) or maternal outcomes (duration of labor stage, mode of delivery) were found between the DEX and opioid groups. @*Conclusions@#Compared with opioids, using DEX as a local anesthetic adjuvant in PCEA improved postoperative analgesia and reduced the incidence of itching and nausea and vomiting without increasing the incidence of adverse events.
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Objective To construct a canine model of vocal cord scar by low-termperature plasma ablation and screen the target genes closely related to the formation of vocal cord scar.Methods Four Chinese rural canines were treated with plasma ablation under the support of laryngoscope and endoscope,and the left vocal cords were injured to the muscle layer.The contralateral sides were left untreated.The gross morphology of vocal cord was observed before operation,immediately after operation,3 weeks after operation and 12 weeks after operation.The pathologi-cal structure of vocal cords was observed by HE stainning,and the ultrastructure of vocal cords was observed by transmission electron microscopy.In addition,high-throughput sequencing was used to analyze the differences in gene expression between the bilateral vocal cords,and the target genes with significantly different expression were screened out.Results In general morphology,the normal vocal cords were banded and well closed.At 3 weeks af-ter operation,the vocal cords were congested and swollen,with uneven edges and red granulation tissues were seen.At 12 weeks after operation,the vocal cord wound was localized contracture and depression,and scar was formed.HE staining showed obvious thickening of the squamous epithelium of the scarred vocal cords,thickening and disor-dered arrangement of the fiber layer,local clumping or bundle aggregation,and scattered fiber bundles were also seen in the muscle layer.Transmission electron microscopy showed interstitial thickening,uneven density,cell swelling,unclear intercellular boundary,proliferation of nuclei and mitochondria,and cells in an active state.High-throughput sequencing analysis revealed that many gene families were involved in the process of vocal cord scar re-pair,including IL family,CCL and CXCL family,MMPs family and its inhibitor TIMPs family,Wnt family,HSP family,MAPK family and TGF-β family.Conclusion We successfully constructed the canine model of vocal cord scar by low-temperature plasma ablation and screened out the target genes closely related to the formation of vocal cord scar by high-throughput sequencing,which provides certain reference value for exploring the mechanism of vo-cal cord scar.
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Objective To investigate the effect of ERK inhibitor PD98059 on the proliferation and differentia-tion of rat otocyst osteoblasts.Methods SD neonatal rat osteoblasts were extracted by two-step digestion with 0.25％pancreatin and type Ⅰ collagenase,and co-cultured with ERK inhibitor PD98059 at concentrations of 0 μmol/L,10 μmol/L,25 μmol/L and 50 μmol/L,respectively.Then,the osteoblasts proliferation of the four groups were assessed by EDU method for 4 consecutive days.The proliferation trend of each group was compared and analyzed.Osteoblasts were differentiated by β-sodium glycerophosphate,L-vitamin C and dexamethasone at concentrations of 10 mmol/L,50 ug/ml and 10-7 mol/L.After 24 h,the mRNA expression levels of osteogenic fac-tors which include Ocn,Bsp,Runx2,Bmp2,OPG and RANKL in each group were detected by RT-qPCR,and the differences of the results were analyzed.Results All the concentrations of ERK inhibitor PD98059 could inhibit the proliferation of osteoblasts in SD neonatal rat,and the inhibitory effect of PD98059 at concentrations of 10 μmol/L was significantly greater than that of the other three groups(P＜0.05).In addition,all the concentrations of PD98059 could inhibit the expressions of Ocn,Bsp,Runx2,Bmp2 and OPG mRNA.The mRNA expressions of Ocn,Bsp,Runx2 and Bmp2 in 10 μmol/L PD98059 group were significantly lower than those in 0 μmol/L,25μmol/L and 50 μmol/L PD98059 groups(P＜0.05).The mRNA expressions of OPG in 10 and 25 μmol/L PD98059 groups were significantly lower than those in 0 and 50 μmol/L PD98059 groups(P＜0.05),and there was no significant difference between the first two groups(P＞0.05).The CT value of RANKL mRNA was not detec-ted in all groups.Conclusion ERK pathway inhibitor PD98059 can both inhibit the proliferation and differentiation of osteoblasts in rat otocyst.Therefore,we speculate that ERK1/2-MAPK pathway may mediate the formation of tympanosclerosis by affecting the proliferation and differentiation of rat otocyst osteoblasts.
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BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.
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AIM: To systematically evaluate the efficacy of intense pulsed light(IPL)combined with meibomian gland expression(MGX)in the treatment of meibomian gland dysfunction(MGD)-related dry eye disease(DED).METHODS: Chinese and English databases such as Chinese national knowledge infrastructure(CNKI), Wanfang, VIP, CBM, ClinicalTrials, PubMed, Embase and Web of Science were searched, and clinical randomized controlled trials(RCTs)using IPL combined with MGX in the experimental group and MGX alone in the control group from January 2017 to September 2022 were included. Six outcome indicators including clinical efficacy, ocular surface disease index(OSDI)score, break-up time(BUT), corneal fluorescein staining(CFS)score, tear meniscus height(TMH)and meibomian gland yielding secretion score(MGYSS)were Meta analyzed by Review Manager 5.3 and Stata 14 software.RESULTS: A total of 15 RCTs were included, with 1 345 patients with MGD-related dry eye. Meta-analysis results showed that the treatment of MGD-related dry eye in the experimental group improved better clinical efficacy(OR=4.95, 95%CI: 2.76～8.90, Z=5.35, P&#x003C;0.00001), BUT(SMD=1.26, 95%CI: 0.84～1.69, Z=5.78, P&#x003C;0.00001), TMH(SMD=0.37, 95%CI: 0.15～0.59, Z=3.33, P=0.0009), and reduced OSDI scores(SMD=-0.86, 95%CI: -1.44～-0.27, Z=2.85, P=0.004)as well as MGYSS(SMD=-2.43, 95%CI: -4.31～-0.54, Z=2.52, P=0.01)than the control group. However, there was no statistically significant difference in CFS scores(SMD=-0.19, 95%CI: -0.46～0.07, Z=1.43, P=0.15).CONCLUSION: IPL combined with MGX in the treatment of MGD related dry eye can increase the overall effective rate and improve the symptoms and signs of patients with MGD related dry eye better than MGX alone.
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The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
Subject(s)
Humans , Mice , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Acrylamides/pharmacology , ErbB Receptors/metabolism , Cell Line, Tumor , CD47 Antigen/therapeutic use摘要
@#Abstract： Objective To analyze the value and influencing factors of cross-primer isothermal amplification technology(CPA) in clinical screening and diagnosis of tuberculosis (TB). Methods We collected 543 inpatients in the Second Affiliated Hospital of Hainan Medical College from January 1, 2018 to December 31, 2021, including 179 patients with tuberculosis, 187 patients with pneumonia and 177 patients with other diseases. The patients' sputum, alveolar lavage fluid, pleural effusion and midstream urine were detected by CPA, smear microscopy, culture method and gene detection. The value of CPA detection in the diagnosis of tuberculosis and its influencing factors were evaluated. Statistical analysis was performed using SPSS 26.0. Results The total positive rate of CPA was 14.4% (78/543), and the positive rate of sputum samples accounted for 29.1% (39/134). Among the 78 cases of CPA positive patients, the tuberculosis group accounted for 69.2% (54/78), followed by pneumonia group 21.8% (17/78), and other diseases group accounted for 9.0% (7/78). Taking CPA test as the reference method, the "sensitivity" of smear microscopy was lower than that of genetic testing and culture, while the "specificity" was higher than that of culture and gene testing, and the "missed diagnosis rate" of smear microscopy was higher than that of genetic testing and culture. CPA test positive was related to gender, ESR and pneumonia. There is a good agreement between CPA test and culture method and gene test (Kappa>0.9), and a moderate agreement between CPA test and smear microscopy (Kappa=0.616). Conclusions Sputum specimen is the best choice for CPA detection, while the value of pleural effusion detection is relatively limited. Sputum, alveolar lavage fluid and midcourse urine can be used as clinical specimens for screening and diagnosis of "tuberculosis group and other disease group", while sputum can be used for screening and diagnosis of "tuberculosis group and pneumonia group". Gender, ESR and pneumonia are the influencing factors of CPA positive patients. Therefore, CPA testing is worthy of clinical promotion, but more clinical research data are needed.
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@#Abstract: Objective To explore the regional, age and annual characteristics of distribution and variation trend of children and adolescents with poor vision in Hainan Province, and to provide a theoretical basis for the formulation of targeted and effective prevention and treatment strategies. Methods The eyesight monitoring data of 5 657 231 children and adolescents aged 6 to 19 from 17 cities and counties in Hainan Province from 2013 to 2020 were analyzed. Using the "Standard Logarithmic Vision Chart" (GB11533-2011) that complies with national standards for testing. Results The rate of poor vision among children and adolescents in Hainan Province increased significantly from 2013 to 2020, and the difference between the years was statistically significant (P<0.001). The total poor vision rate in the left eye increased 10.09% (32.79% to 42.88%), and that of severe poor vision rate increased 6.68%, while that of the right eye increased 9.80% (33.11% to 42.91%) and 6.49%. The poor vision rate was significantly higher in females than in males of same year (P<0.001), but the increase pattern was the same. In 2020, there were significant differences between the same age groups in different cities and counties and between different age groups in the same city and county (P<0.001), and they all tended to increase with age. The result of analyzing the distribution characteristics of the total poor vision rate of different age groups children in the eastern (Qionghai), southern (Sanya), western (Changjiang), northern (Haikou) and central (Dingan) cities showed that the regional rate difference was small at 6-7 years old, and then increased with the increase of age. The poor vision rate of Haikou City ranked the first in all age groups, and reached the highest at 17 years old, with 76.32% and 80.89% of total poor vision rate of left and right eyes respectively. Sanya City ranked second, Qionghai ranked third. The poor vision rate of Changjiang County was lower and the growth rate was slower according to age. Conclusions From 2013 to 2020, the total and severe poor vision rates in left and right eyes of children aged 6-19 in Hainan Province increased year by year, with the ascension range of female higher than that of male, and right eye higher than that of left eye. In the same year, the poor vision rate increase rapidly with age. It is recommended to further strengthen the daily intervention and management of key populations and special age groups to reduce the rate of low vision in children and adolescents.
摘要
This paper aims to investigate the intervention effect of Qufeng Gutong Cataplasm(QFGT) on myofascial pain syndrome(MPS) in rats and to preliminarily explain its mechanism from the perspective of improving muscle inflammation and pain. Male SD rats were divided into 6 groups, namely normal group, model group, positive control drug(Huoxue Zhitong Ointment, HXZT) group, and low, medium, and high-dose QFGT groups(75, 150, and 300 mg·d~(-1)). The rat model of MPS was established by striking combined with centrifugation for 8 weeks, during which QFGT and HXZT were used for corresponding intervention. Standard VonFrey fiber was used to evaluate the mechanical pain threshold, and acetone was used to detect the cold pain threshold. The electrophysiological activity of muscle at trigger point was detected, and the electromuscular analysis of trigger point was performed. CatWalk gait analyzer was used to detect pain-induced gait adaptation changes. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in muscle and skin tissues at the trigger point of rats. Immunohistochemistry was used to detect the expression of capsaicin receptor transient receptor potential vanilloid 1(TRPV1) in muscle tissues and interleukin(IL)-33 in skin tissues at the trigger point. The protein expression levels of TRPV1, protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), IL-1β, and tumor necrosis factor-α(TNF-α) in muscle tissues at the trigger point were detected by Western blot. The results showed that as compared with the model group, the mechanical pain threshold and cold pain threshold of rats in other groups were increased after treatment with QFGT. The spontaneous electromyography(EMG) activity was observed in the model group, but QFGT alleviated the EMG activity in a dose-dependent manner. Gait analysis showed that standing duration, average intensity, swing speed, maximum contact point, maximum contact area, paw print length, paw print width, and paw print area were significantly improved in all QFGT groups. Pathological results showed that the disorder of muscle arrangement at the trigger point was decreased, muscle fiber adhesion and atrophy were reduced, and inflammatory cell infiltration was alleviated after treatment with QFGT. In addition, QFGT and HXZT both inhibited the protein expression of TRPV1, PI3K, Akt, p-Akt, IL-1β, and TNF-α in the muscle tissues of rats with MPS. However, there was no significant difference in the pathological structure and expression of IL-33 in the treated skin as compared with the normal group. The related results have proved that QFGT can inhibit the release of inflammatory factors by inhibiting the TRPV1/PI3K/Akt signaling pathway in the muscle trigger point of rats with MPS and finally attenuate the atrophy and adhesion of local muscles and inflammatory infiltration, thereby relieving the muscle pain of rats with MPS, and local administration has no skin irritation.
Subject(s)
Rats , Male , Animals , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha , Phosphatidylinositol 3-Kinases , Myofascial Pain Syndromes/drug therapy , Pain摘要
How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Neoplasm, Residual/pathology , Biomarkers, Tumor/genetics , Computational Biology摘要
Objective: To understand the status of autism spectrum disorder (ASD) cohort studies and explore the feasibility of constructing ASD disease-specific cohorts based on real-world data (RWD). Methods: ASD cohort studies published by December 2022 were collected by literature retrieval from major Chinese and English databases. And the characteristics of the cohort were summarized. Results: A total of 1 702 ASD cohort studies were included, and only 60 (3.53%) were from China. A total of 163 ASD-related cohorts were screened, of which 55.83% were birth cohorts, 28.22% were ASD-specific cohorts, and 4.91% were ASD high-risk cohorts. Most cohorts used RWD such as hospital registries or conducted community-based field surveys to obtain participant information and identified patients with ASD by scales or clinical diagnoses. The contents of the studies included ASD incidence and prognostic risk factors, ASD comorbidity patterns and the impact of ASD on self-health and their offspring's health. Conclusions: ASD cohort studies in developed countries have been in the advanced stage, while the Chinese studies are still in their infancy. RWD provides the data basis for ASD-specific cohort construction and offers new opportunities for research, but work such as case validation is still needed to ensure the scientific nature of cohort construction.