Objective Through integrative bioinformatics analysis of multi-source transcriptomic data, potential biomarkers to asthma epithelial cells were identified. The expression of these candidate target was subsequently validated in lung tissues and epithelial cells from asthma models. Methods The gene expression profile data of epithelial cells from three asthma patient cohorts and corresponding healthy controls were integrated from the Gene Expression Omnibus (GEO) database. Differential expression analysis and gene co-expression network analysis were performed to identify key genes and biological pathways associated with asthma. The key genes were validated in lung tissues and epithelial cells in asthma animal models. Results Differential gene expression analysis revealed 1121 upregulated and 1484 downregulated genes in epithelial cells from asthma patients compared with healthy controls. The biological pathway enrichment analysis revealed that the upregulated genes were mainly involved in glycosylation processes, whereas the downregulated genes were mainly associated with immune cell differentiation process. The gene co-expression network analysis revealed that module 9, enriched in glycosylation-related pathways, was significantly positively correlated with asthma, whereas module 17, associated with insulin and other signaling pathways, showed a significant negative correlation with asthma. We identified the genes of polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), pyrroline-5-carboxylate reductase 1 (PYCR1), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key genes within module 9, all of which were significantly upregulated in asthma. Finally, we validated that the expression levels of GALNT5, PYCR1, and CEACAM5 were significantly upregulated in epithelial cells from asthmatic lung tissue. Additionally, using a rat asthma model, we further confirmed that the protein levels of these three genes were significantly upregulated in lung tissues of the model group. Conclusion Through data integration and experimental validation, this study identified key genes and biological pathways closely associated with asthma pathogenesis. These findings provide a novel theoretical basis and potential targets for the diagnosis and treatment of asthma.
Asthma/metabolism* ; Humans ; Epithelial Cells/metabolism* ; Animals ; Biomarkers/metabolism* ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Rats ; Computational Biology

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P＜0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P＜0.05 or P＜0.01),significantly lower spontaneous alternation percentage in Y-maze test(P＜0.05),and significantly elevated hippocampal Aβ1-42 level(P＜0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P＜0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P＜0.05),significantly higher spontaneous alternation percentage in Y-maze test(P＜0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P＜0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P＞0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P＞0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.

Objective:To compare the distribution differences of serum protein electrophoresis (SPE) among different gender and age individuals, and to explore the clinical application of SPE screening monoclonal gammopathy.Methods:A retrospective analysis was conducted based on the SPE results obtained from 533 989 cases enrolled from January 2018 to December 2019 at Zhongshan Hospital Affiliated to Fudan University. Among these patients, 435 479 inpatients were from departments of hematology, nephrology, spinal surgery, endocrinology, and rheumatology and immunology; and 98 510 were apparently healthy individuals. The distributions of albumin, α1 globulin, α2 globulin, β1 globulin, β2 globulin and γ globulin in different gender and age groups (≤20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, ≥91 years old) were compared. A total of 10 014 cases were selected by immunofixation electrophoresis (IFE). The positive detection rates of different SPE bands and IFE bands were analyzed. The sensitivity and specificity of SPE methods were determined according to IFE results as the gold standard.Results:No significant difference was examined in the proportion of SPE bands between different genders ( P>0.05). There were statistically significant differences in the proportion of albumin bands between apparently healthy individuals and hospitalized patients at different ages (apparently healthy individuals: F=5.12, P<0.05, inpatients: F=4.18, P<0.05), and all of them decreased with the increase of age. The proportion of γ globulin bands increased with age (apparently healthy individuals: F=1.34, P<0.05; inpatients: F=1.24, P<0.05). The sensitivity of SPE was 69% (2 098/3 051), and the specificity was 97% (6 721/6 963). Compared with IFE method, the positive detection rate of monoclonal gammopathy was significantly different (χ2=5 049.94, P<0.05). The positive rate of monoclonal gammopathy in γ globulin region (21.11%, 2 114/10 014) was higher than that in β globulin region (3.28%, 328/10 014) (χ2=90.74, P<0.05) and β-γ globulin region (1.63%, 163/10 014) (χ2=44.34, P<0.05). IgG and IgM bands are common in γ globulin region. Among them, IgG-κ type accounted for 94.1% (995/1 058), IgG-λ type accounted for 94.8% (690/728), IgM-κ type accounted for 89.2% (222/249), IgM-λ accounted for 83.8% (62/74). IgA bands are common in β region, of which IgA-κ accounted for 49.8% (103/207) and IgA-λ accounted for 51.6% (149/289). The positive rate of monoclonal gammopathy of IgG-κ type was the highest (10.57%, 1 058/10 014), and the positive rate of monoclonal gammopathy of IgM-λ type was the lowest (0.74%, 74/10 014). Conclusions:With increasing age, the proportion of albumin band in SPE decreased and the proportion of γ globulin band increased. IgG and IgM type monoclonal gammopathy is mostly found in the gamma region, with a higher detection rate in IgG type. IgA type monoclonal gammopathy is mostly found in the β region, with a lower detection rate.

BACKGROUND:Dexmedetomidine has the effect of anti-ischemia-reperfusion injury,but the comprehensive and systematic review of its signaling pathway is less. OBJECTIVE:To focus on the review of dexmedetomidine's signaling pathway in the mechanisms of antioxidant stress,inhibition of inflammation,anti-apoptosis,autophagy,and so on. METHODS:The relevant articles on PubMed,CNKI,WanFang,and VIP databases were searched by computer with the key words"ischemia-reperfusion inquiry;dexmedetomidine;signal path;oxidative stress;inflammation;apoptosis"in Chinese and English.After excluding repetitive research and some basic articles with low correlation,57 articles were finally included for review. RESULTS AND CONCLUSION:(1)Dexmedetomidine plays an important role in organ protection through many mechanisms,such as anti-oxidative stress injury,anti-inflammation,anti-apoptosis and autophagy.This involves many pathways,including Nrf2 and its downstream protein antioxidant stress pathway,Toll-like receptor 4 family and nuclear factor-κB-related anti-inflammatory pathway,JAK2/STAT3-related anti-inflammatory pathway,and cholinergic anti-inflammatory pathway,and the cholinergic pathway is the upstream mechanism of many nuclear factor-κB signaling pathways.(2)PI3K/Akt pathway plays different roles according to its activated downstream signals,inhibiting the activation of NLRP3 inflammatory body,activating signal molecules endothelial nitric oxide synthase,mammalian target of rapamycin,and hypoxia-inducible factor 1α to play an anti-inflammatory role,and activate Bad or Bax residues to play an anti-apoptotic role,and PI3K/Akt activates glycogen synthetase kinase-3β.It can also play an anti-inflammatory and anti-apoptotic role.(3)Dexmedetomidine activates SIRT3 to mediate anti-apoptosis and inhibit endoplasmic reticulum stress to produce anti-apoptosis.(4)The detailed review of the anti-ischemia-reperfusion injury signaling pathway of dexmedetomidine can provide a basis for future mechanism research and diagnosis and treatment decisions.

ObjectiveTo investigate the levels of serum antibodies against novel coronavirus （SARS-CoV-2） in healthcare workers after one month of natural infection， to explore the influencing factors and their correlations with the levels of antibodies， and to provide reference for strengthening the protection of healthcare workers and preventive intervention in Pudong New Area in Shanghai. MethodsVenous blood samples were collected from 1 102 medical staff in Pudong hospitals one month after infection. The serum levels of new coronavirus specific antibodies IgM， IgG and neutralizing antibodies were detected by chemiluminescent immunoassay. The information of gender， age， position， infection severity， vaccination， basic diseases and use of immunosuppressants were obtained by questionnaire to explore the influencing factors and their correlation with the antibody level. ResultsOne month after natural infection， 99.00% （1 091/1 102） of the subjects were found to be positive for IgG antibody against the new coronavirus， 17.79% （196/1 102） of the subjects were IgM antibody positive， and 99.00% （1 091/1 102） of the samples were positive for the neutralizing antibody. The level of antibody might be influenced by the severity of infection， the time of the last dose of vaccination， and the long-term use of immunosuppressants. The more severe the disease， the stronger the neutralizing antibody response. The antibody level in the people who received the final dose of vaccine within 6 months was higher than that of the people who received the vaccine 6 months ago， and the difference was statistically significant. The antibody levels were low in the subjects who received long-term immunosuppressants. ConclusionThe specific IgM， IgG and neutralizing antibody were found， one month after infection， in the medical workers in Pudong New Area， Shanghai， and the antibody titers were high， which had a good protective effect. The antibody level of the people who were vaccinated within 6 months was higher， it is recommended that people who receive the last vacination more than 6 months should be re-vaccinated with the booster vaccine， to improve the autoimmunity against the novel coronavirus.

Objective To investigate independent risk factors for unintended initial dissection of the posterior plane(UIDPP)during small incision lenticule extraction(SMILE)by surgeons with different qualifications.Methods A total of 1 600 patients(3 003 eyes)who underwent SMILE performed by three surgeons with different qualifications from April to September 2021 were selected as the research subjects,including 911 males and 689 females,with an average age of(21.82±3.55)years.The incidence of UIDPP in patients was recorded,along with a comprehensive summary of the age,gender,eyes,surgeons,surgical proficiency,subjective refraction,central corneal thickness,lenticule thickness,side cut angle,and peripheral lenticule thickness of the patients.Independent risk factors of UIDPP were analyzed using the binary logistic regression.Test level:α=0.05.Results In this study,the incidence of UIDPP was 6.56％(197/3 003),and the lenticule was successfully removed in all eyes.Multivariate logistic regression analysis demonstrated that surgeon(P=0.035),surgical proficiency(P=0.026),eyes(P=0.007),lenticule thickness(P＜0.001),and peripheral lenticule thick-ness(P＜0.001)were independent risk factors associated with the UIDPP during SMILE surgery.No significant differences were observed in other parameters(all P＞0.05).Conclusion Surgeons,surgical proficiency,eyes,lenticule thick-ness,and peripheral lenticule thickness are independent risk factors of UIDPP.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Objective:To retrospectively compare the clinical effects of the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the European Kidney Function Consortium (EKFC) equation based on creatinine to estimate glomerular filtration rate (eGFRcr) in a Chinese population.Methods:Patients and healthy individuals who visited the Zhongshan Hospital, Fudan University, between January 1, 2023, and December 31, 2023, were enrolled. The exclusion criteria were age<18 years, amputees, pregnant women, patients with muscle-related diseases, and patients who had undergone ultrafiltration or dialysis. The final study population included 660 078 individuals with a median age of 58 years (44, 68), 56.51% (372 987/660 078) of them were men. eGFRcr was calculated using the 2021 CKD-EPI, EKFC equations and initial 2009 CKD-EPI equation. Results were compared by differences (P 10), charges in population distribution and impact on staging of chronic kidney disease (CKD) by gender, age and creatinine results. Results:Compared with the results of 2009 and 2021 CKD-EPI eGFRcr, the P 10was 99.99% ( R 2=0.997). When applying the 2021 CKD-EPI eGFRcr equation, there was a slight overestimation of 3.77 (2.92, 4.47) ml/(min×1.73 m 2). 86.42% (570 455/660 078)participants had higher eGFRcr owing to the utilization of the 2021 CKD-EPI equation, which did not cause CKD stage change. A total of 12.35% (81 514/660 078) of subjects had different CKD stage with the higher 2021 CKD-EPI eGFRcr. 1.23% (8 109/660 078) had lower eGFRcr but no change in the CKD stage with the 2021 equation. Compared to the 2009 CKD-EPI eGFRcr results, the EKFC eGFRcr demonstrates P 10 values of 89.79%, with a correlation coefficient of R 2=0.976. The overall eGFRcr values using the EKFC equation were decreased by 4.63(-2.22, -7.04) ml/(min×1.73 m 2). There were 75.14% (495 992/660 078) individuals whose eGFRcr results were lower in EKFC equation, which did not cause CKD stage change. There were 15.63% (103 161/660 078) leading to a different CKD stage. Additionally, 8.80% (58 077/660 078) individuals with a higer eGFRcr result did not change CKD stage, while 0.43% (2 848/660 078) experienced a change in CKD staging due to the overestimation. Conclusions:Compared with the 2009 CKD-EPI eGFRcr results, the 2021 CKD-EPI eGFRcr results were slightly higher and had good consistency in different genders and ages. However, the EKFC eGFRcr was generally lower than 2009 CKD-EPI eGFRcr, showing poor consistency. The differences between eGFR equations should be considered when judging the CKD stage of patients.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.