Objective To investigate the expression of Midkine(MDK)in cholangiocarcinoma(CCA)and its value in predicting the prognosis of CCA,as well as the potential mechanism of the effect of MDK on the progression of CCA.Methods The data of CCA samples were obtained from TCGA database to analyze the difference in the expression of MDK between cancer tissue and paracancerous tissue and its association with clinical features,and the data collected from GEO database and 11 CCA patients who underwent surgical resection in The Fifth Medical Center of Chinese PLA General Hospital from June 2018 to September 2021 were used for validation.STRING and Cytoscape were used to construct a protein-protein interaction network,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to investigate the biological functions and tumor-related pathways involving MDK-related genes.In addition,TIMER and TISIDB databases were used to analyze the correlation between MDK expression and immune cell infiltration in CCA tissue.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the Fisher's exact test was used for comparison of categorical data between two groups.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used for comparison between groups.The Spearman correlation analysis was used to investigate the correlation between two variables.Results The expression level of MDK in cancer tissue and paracancerous tissue of CCA patients was compared based on TCGA database,and the results of the non-paired and paired analyses showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in paracancerous tissue(P<0.001).Transcriptome sequencing was performed for the tumor tissue and its corresponding paracancerous tissue from 11 CCA patients,and the results showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in corresponding paracancerous tissue(P<0.01).High expression of MDK was associated with lymph node metastasis(P=0.045)and vascular invasion(P=0.044).Survival analysis showed that compared with the CCA patients with low MDK expression,the CCA patients with high MDK expression had significantly shorter overall survival time(χ2=5.30,P=0.028)and disease-specific survival time(χ2=6.25,P=0.019).The GO and KEGG enrichment analyses showed that the 30 MDK-related genes were closely associated with ubiquitin-mediated proteolysis and affected the prognosis of CCA patients.The TIMER analysis showed that the expression level of MDK was positively correlated with the infiltration of B cells(r=0.356,P=0.035 6)and dendritic cells(r=0.409,P=0.014 7)in tumor microenvironment of CCA;the TISIDB analysis showed that the expression level of MDK was positively correlated with CXCL16(r=0.465,P=0.004 67)and was negatively correlated with CXCL12(r=-0.389,P=0.019 7)and CXCR5(r=-0.393,P=0.018 5),and it was also negatively correlated with the immune checkpoint regulators VTCN1(r=-0.393,P=0.018 3),LTA(r=-0.380,P=0.022 7),and PVR(r=-0.350,P=0.037 3).Conclusion High expression of MDK is associated with poor prognosis in CCA patients,and MDK has the potential of being used as a molecular marker for predicting the prognosis of CCA.MDK may promote the development and progression of CCA by regulating ubiquitin-mediated proteolysis and the infiltration of B cells and dendritic cells.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To establish a multi-factor prediction model for vascular aging based on psychological behavior and physical exercise using nomogram and structural equation method.Methods:A total of 701 inpatients or physical examination patients who underwent carotid ultrasound examination in the Affiliated Hospital of Qingdao University from October 2021 to March 2023 were selected by cross-sectional method. The subjects were randomly divided into training queue( n=492) and verification queue( n=209) according to the ratio of 7∶3.The psychological and behavioral factors, lifestyle, demography and accompanying diseases data were collected. Multi-factor binary Logistic regression method in SPSS 25.0 software was used to screen independent influencing factors of vascular aging, R 4.2.2 software was used to build a nomogram prediction model of vascular aging, and the ROC curve, calibration chart and decision curve analysis were used to evaluate the nomogram, and AMOS software was used to build a structural equation model of vascular aging. Results:Multivariate Logistic regression analysis showed that type A behavior( B=1.757, OR(95% CI)=5.790(2.750-12.210), P<0.001), physical exercise( B=-3.019, OR(95% CI)=0.050(0.020-0.100), P<0.001), high-fat diet( B=0.679, OR(95% CI)=1.970(1.350-2.880), P<0.001), sleep quality( B=-1.451, OR(95% CI)=0.230(0.120-0.460), P<0.001), tea drinking habits( B=-2.349, OR(95% CI)=0.100(0.050-0.200), P<0.001), age( B=0.061, OR(95% CI)=1.060(1.020-1.110), P=0.005), sex( B=-1.263, OR(95% CI)=0.280(0.140-0.570), P<0.001), hyperlipidemia( B=0.679, OR(95% CI)=1.970(1.350-2.880), P<0.001) and diabetes( B=0.838, OR(95% CI)=2.310(1.140-4.700), P=0.021)were independent influencing factors of vascular aging. The nomogram model showed that type A behavior, physical exercise, high-fat diet, sleep quality, tea drinking habits, age, sex, hyperlipidemia and diabetes were independent influencing factors of vascular aging.Advanced age, type A behavior, hyperlipidemia, diabetes and the score of high-fat diet were risk factors for vascular aging, while better sleep quality, tea drinking habit and the score of physical exercise were protective factors for vascular aging.Men were more prone to vascular aging than women. Structural equation model showed that type A behavior had the strongest direct positive effect on vascular aging (the effect coefficient=0.197, P<0.01), and physical exercise had the strongest direct negative effect on vascular aging (the effect coefficient=-0.452, P<0.01), which could indirectly affect vascular aging through various factors. Conclusions:The nomogram model shows the independent influencing factors of vascular aging and has certain predictive value.Structural equation model shows that many factors such as psychological behavior and lifestyle can directly or indirectly affect the occurrence of vascular aging, among which type A behavior and physical exercise have more extensive effects.

Objective:To evaluate the safety and efficacy of endoscopic resection in the treatment of patients with primary non-ampullary duodenal early cancer.Methods:A total of 20 cases with primary non-ampullary duodenal early cancer receiving endoscopic resection were collected from Jan 2015 to Dec 2019 at the Department of Endoscopy, the First Affiliated Hospital of Shandong First Medical University.Results:The size of lesions ranged from 0.3-2.5 cm (0.9±0.5)cm.The size of removed membrane samples ranged from 1.5-3.5 cm (2.5±0.7)cm. The edges were all negatiue pathologically. Duodenal perforation occurred in 2 cases, and all were successfully clipped by endoscopy. The follow-up time was from 4-42 months (20.4±11.4)m and no recurrence was found.Conclusion:Endoscopic resection is a safe and effective method for primary non-ampullary duodenal early cancer.

Objective:To evaluate the clinical efficacy and safety of SpyGlass-guided laser lithotripsy for large common bile duct (CBD) stones with diameter>2 cm.Methods:From August 2015 to August 2018, a total of 157 patients with large CBD stones at the First Affiliated Hospital of Shandong First Medical University who met the inclusion criteria were randomly divided into SpyGlass group ( n=78, underwent SpyGlass-guided laser lithotripsy) and laparoscopic common bile duct exploration (LCBDE) group ( n=79, underwent LCBDE) by using random numbers. Non-inferiority test was used for rates of one-time stone removal and total stone removal, and the non-inferiority margin was set to 10%. The transform rate, incidence of short-term complications, hospital stay, and quality of life (assessed by the gastrointestinal quality of life index) were compared between the two groups. Results:The total success rates of stone clearance were 92.3% (72/78) and 96.2% (76/79) in the SpyGlass group and LCBDE group, respectively ( P=0.023), with valid non-inferiority hypothesis. The one-time stone removal rates were 83.3% (65/78) and 96.2% (76/79), respectively ( P=0.124), with invalid non-inferiority hypothesis. There were no significant differences in the incidence of transform [7.7% (6/78) VS 3.8% (3/79), P=0.294] or short-term complications [5.1% (4/78) VS 10.1% (8/79), P=0.246] between the two groups. Compared with the LCBDE group, the SpyGlass group had a shorter hospital stay (5.65±0.94 d VS 8.84±1.54 d, P=0.001) and higher scores of gastrointestinal quality of life index (1 month after operation: 99.85±4.36 VS 91.51±5.47, P=0.001; 3 months after operation: 131.24±3.32 VS 112.32±7.77, P=0.001). Conclusion:For large CBD stones, the efficacy of SpyGlass-guided laser lithotripsy is not inferior to LCBDE, and it is less invasive. In the future, SpyGlass-guided laser lithotripsy could be an important option for the treatment of large CBD stones.

OBJECTIVE: To develop a self deep breathing training device which can improve lung function compliance and blood oxygen saturation. METHODS: The device consists of four parts:flow tube, measuring cylinder, mobile phone holder and meridian guidance audio-visual synthesis training software. The flow tube measures the flow rate of inhaled gas, the metering cylinder measures the total amount of inhaled gas, and the mobile phone rack is equipped with a mobile phone storing the meridian guidance audio-visual synthesis training software. RESULTS: The device is reasonable in structure and flexible in operation, which can meet the requirements of self deep inspiration training under the guidance of training module. CONCLUSIONS Deep inspiration training under the guidance of guidance training module can form "deep and slow" abdominal breathing, and then improve lung function.
Cell Phone ; Lung ; Meridians ; Software

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*

A variety of cytokines work synergistically to participate in wound healing. Although there are many studies on cytokines, the current clinical use of cytokines to treat wounds has not achieved the desired effect. The sequential administration of cytokines or the study of its drug delivery system may be its strategy to promote chronic wound healing. This article reviews the research progress of major growth factors, chemokines and inflammatory factors in wound repair in recent years.

To investigate Streptococcus suis ( S.suis) isolated from patients in Shandong province using genomic epidemiology and pathogenologic analysis. To provide the foundation to establish reasonable and accurate prevention and control measures of human S. suis infection. Molecular typing, whole genome phylogenetic tree, virulence gene typing, antibiotic resistance profile and mobile genetic elements carrying antibiotic resistance genes of isolated S. suis strains were investigated. The pathogenicity of isolated strains was also evaluated by comparing their capacity to induce pro-inflammatory cytokine production in vitro. S. suis infections in Shandong province were predominantly due to serotype 2 and sequence type 1 strains. The major symptoms were meningitis. The studied strains could be divided into five lineages. All strains belong to highly pathogenic type in Shandong province,Strains from lineage 2 possessed higher capacity to stimulate pro-inflammatory cytokine production than other strains did, even though other strains belong to highly pathogenic strains. In addition, multiple antibiotic resistance genes and corresponding mobile genetic elements werewidespread in S. suis strains from Shandong province, except strains from lineage 3. High diversities in genome, evolutionary path and pathogenicity of S. suis strains from Shandong province were revealed. It was necessary to surveillant the S. suis strain in genomic level.

To investigate Streptococcus suis ( S.suis) isolated from patients in Shandong province using genomic epidemiology and pathogenologic analysis. To provide the foundation to establish reasonable and accurate prevention and control measures of human S. suis infection. Molecular typing, whole genome phylogenetic tree, virulence gene typing, antibiotic resistance profile and mobile genetic elements carrying antibiotic resistance genes of isolated S. suis strains were investigated. The pathogenicity of isolated strains was also evaluated by comparing their capacity to induce pro-inflammatory cytokine production in vitro. S. suis infections in Shandong province were predominantly due to serotype 2 and sequence type 1 strains. The major symptoms were meningitis. The studied strains could be divided into five lineages. All strains belong to highly pathogenic type in Shandong province,Strains from lineage 2 possessed higher capacity to stimulate pro-inflammatory cytokine production than other strains did, even though other strains belong to highly pathogenic strains. In addition, multiple antibiotic resistance genes and corresponding mobile genetic elements werewidespread in S. suis strains from Shandong province, except strains from lineage 3. High diversities in genome, evolutionary path and pathogenicity of S. suis strains from Shandong province were revealed. It was necessary to surveillant the S. suis strain in genomic level.