ObjectiveBased on 16S rDNA technology and molecular biology methods， the molecular mechanism of Shenling Baizhusan in the treatment of diarrhea-predominant irritable bowel syndrome （IBS-D） was investigated. MethodsThe 42 SD rats with SPF were randomly divided into no control group， SLBZS-H， medium （SLBZS-M）， low （SLBZS-L） dose group， positive control group and model group， with 7 rats in each group. The rat model of IBS-D was prepared by ice-cold senna （0.45 g∙mL^-1） gavage （10 mL∙kg^-1） combined with restraint stress for 14 consecutive days. After successful modeling， the corresponding drugs were given to each group with a gavage volume of 10 mL∙kg^-1： The positive group was administered with 2.36 ， 1.18， 0.59 g∙mL^-1 of Shenling Baizhusan in the Positive group and the Model group with the same volume of normal saline for 14 d. The general condition of the rats： Weight， feces， mental state and death were observed and recorded. The body weight， abdominal wall retraction reflex score （AWR） and loose stool rate of rats in each group were measured before （the first day）， after the model （day 14） and after treatment （day 28）. Hematoxylin-eosin staining was used to observe the morphological characteristics of colon tissues of experimental animals. Enzyme-linked immunosorbent assay was used to quantitatively analyze the concentration of inflammatory mediators in the peripheral blood of experimental animals. Western blotting was used to detect the expression levels of key proteins of Toll-like receptor 4 （TLR4）， Toll-like receptor 2 （TLR2）， myeloid differentiation factor 88 （MyD88） and nuclear factor-κB （NF-κB） signaling pathway in rat colon tissue. 16S rDNA technology was used to detect the structural changes of intestinal microbiota in rats. ResultsCompared with Control， the colon of the Model group showed partial mucosal epithelial shedding and inflammatory cell infiltration. The contents of TNF-α， IL-1β， IL-6 and 5-HT in serum increased （P<0.05）， the protein expressions of TLR2， TLR4， MyD88 and NF-κB in colon tissue increased （P<0.05）， the diversity indices of Richness， Chao1， abundance-based coverage estimator（ACE） and Shannon decreased （P<0.05）， and the phylum Firmicutes， Actinobacteria， The relative richness of Bacteroides-H， Lactobacillus and Ligilactobacillus decreased （P<0.05）， while the relative richness of Bacteroidetes， Proteobacteria and Prevotella increased （P<0.05）. Compared with the model group， the colonic structure and organization of the SLBZS-H group， SLBZS-M group， SLBZS-L group and Positive group were clearer， and only a small number of inflammatory cells were present in some areas， and the serum contents of TNF-α， IL-1β， IL-6 and 5-HT were decreased （P<0.05）， TLR2， TLR4， The protein expressions of MyD88 and NF-κB decreased （P<0.05）， and compared with the model group， the diversity indices of Richness， Chao1， ACE and Shannon in the SLBZS-H， SLBZS-M and SLBZS-L groups increased （P<0.05）， and the richness of Firmicutes and Actinobacteria increased （P<0.05）. The richness of Proteobacteria and Prevotella decreased （P<0.05）， and the abundance of Prevotella decreased （P<0.05）， Bacteroides-H， Muribaculum， Lactobacillus and salivarius in the Positive group salivarius （P<0.05）. ConclusionShenling Baizhusan can effectively treat IBS-D， and its molecular mechanism may be to play a therapeutic role by improving intestinal flora and inhibiting the TLRS/MyD88/NF-κB signaling pathway to reduce inflammatory response.

Objective To investigate the role of long non-coding RNA-small nucleolar RNA host gene 3(lncRNA-Snhg3)and its regulatory mechanism in the hepatic glucose metabolism of mice.Methods Adenovirus Snhg3 was over-expressed by the tail vein injection in db/db mice,and then glucose tolerance and pyruvate tolerance were meas-ured.The mRNA expression of mouse liver gluconeogenesis-related genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pc)and stress-inducing protein 2(Sestrin2,Sesn2,a gene adjacent to Snhg3)were de-tected by RT-qPCR.The dual luciferase reporter assay was used to detect the effect of Snhg3 on the Sesn2 promoter activity in 293T cells.Results Snhg3 over-expression improved glucose tolerance and pyruvate tolerance in db/db mice.Snhg3 over-expression inhibited the mRNA of gluconeogenesis genes of Pepck(P＜0.05)and G6pc(P＜0.05),while promoted the mRNA of Sesn2(P＜0.01).Meanwhile,Snhg3 over-expression promoted Sesn2 promoter activity in 293T cells(P＜0.05).Conclusions Snhg3 improves glucose metabolism in mice by promoting Sestrin2 expression.

ObjectiveTo study the traditional Chinese medicine （TCM） syndromes of children with alopecia areata， and provide evidence for TCM differentiation and treatment in clinic. MethodsA retrospective analysis was conducted on the clinical data of 800 children with alopecia areata admitted to the Hair Medicine Center of the China-Japan Friendship Hospital from January 1， 2012 to December 31， 2021. The clinical data of the children were collected using a four-examination information questionnaire， including clinical characteristics （age of consultation， age of onset， course of disease， family history， severity grading）， alopecia areata-related factors （triggers）， and four-examination information （including sleep， diet， emotions， bladder and bowel function， etc.）. Descriptive frequency analyses， rank sum tests， factor analyses and cluster analyses were performed， and the distribution of the major TCM syndromes was summarised with the clinical data. ResultsThere were 800 children with alopecia areata， including 449 males and 351 females； 8 cases （1.00%） were in infancy， 36 cases （4.50%） were in early childhood， 180 cases （22.50%） were in preschool， 380 cases （47.50%） were in school age， and 196 cases （24.50%） were in puberty at the time of consultation； the average age of consultation was 8.31±3.86 years， the average age of onset of disease was 5.40±3.82 years， and the average duration of disease was 2.94±2.77 years； 527 children （65.87%） with severe alopecia areata； 85 children （13.56%） had a family history of alopecia areata； 772 children （96.50%） had unknown triggers for their first alopecia areata， and 28 children （3.50%） reported the presence of obvious triggers， including fright （9 cases）， high fever （5 cases）， allergic reactions （4 cases）， micronutrient （zinc， iron， etc.） deficiencies （4 cases）， inappropriate diet （2 cases）， environmental factors （1 case， new house renovation）， atopic dermatitis （1 case）， atopic asthma （1 case）， and pneumonia （1 case）. A total of 40 four-examination information items were collected， among which the frequency of kicking quilts was the highest with 380 cases （47.50%）， followed by picky eating （369 cases， 46.13%）， sleeplessness （334 cases， 41.75%）， irritability （334 cases， 41.75%）， partiality towards certain foods （306 cases， 38.25%）， impulsiveness （297 cases， 37.13%）， dry stools （233 cases， 29.13%）， yellow urine （215 cases， 26.88%）， nail biting （213 cases， 26.63%）， bad breath （211 cases， 26.38%）. According to factor analysis and cluster analysis， five types of TCM syndromes were obtained， in order as qi and blood deficiency syndrome （110 cases， 13.75%）， spleen deficiency syndrome （114 cases， 14.25%）， kidney essence deficiency syndrome （140 cases， 17.50%）， dietary stagnation syndrome （150 cases， 18.75%）， and liver depression and spleen deficiency syndrome （286 cases， 35.75%）. Patients in each age group and SALT grading are mainly liver depression and spleen deficiency syndrome. ConclusionThe TCM symptoms of children with alopecia areata are mainly based on qi and blood deficiency syndrome， spleen deficiency syndrome， kidney essence deficiency syndrome， dietary stagnation syndrome， and liver depression and spleen deficiency syndrome， of which liver depression and spleen deficiency syndrome is the most common type at different ages and stages of the disease.

Objective To generate and identify the Itgbl1(integrin beta-like)promoter-driven Cre knock-in mouse line.Methods Itgbll-Cre knock-in mice were generated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing.The Itgbl1-Cre mice were crossed with the Cre reporter ROSALSL-tdTomato)mice to detect the expression profile of Cre activity.The tdTomato expression pattern across tissues and cell-specific markers were used to identify the cell types of Itgbl1-expressing cells and their progeny.Results and Conclusion tdTomato was specifically expressed in mucous acinar cells of the sublingual gland,pancreatic islet cells,and gastric endocrine cells.In addition,tdTomato expression was also found in some of the neurons of the retina and brain,as well as in a few cells in the serosal layer of the intestine,articular cartilage,periosteum,and bone marrow.The first Itgbl1-Cre recombinase transgenic mouse line was established,which can specifically label the mucous acinar cells of the sublingual gland.

Objective:To investigate the optimal delay time in the quantitative assessment of myocardial fibrosis based on dual-energy CT extracellular volume fraction (DECT-ECV), using MRI as a reference.Methods:Thirty patients with confirmed or suspected of cardiomyopathy were prospectively enrolled in this study. All the patients underwent both cardiac DECT and MRI examination within one week. According to the imaging features of late gadolinium enhancement (LGE) on MRI, myocardial segments were classified into 3 types: ischemic LGE segments, non-ischemic LGE segments and negative LGE segments. According to the DECT delay time, the whole and segmental myocardium were divided into 3 groups: delay of 3 min (Group A), delay of 5 min (Group B) and delay of 7 min (Group C). Correlation and agreement between CT-ECV and MRI-ECV were performed on a basis of overall myocardium and segmental myocardium. Pearson or Spearman test was used for correlation analysis and Bland-Altman test was used for consistency analysis.Results:Thirty patients with 480 segments were finally included in our study. In the analysis based on overall myocardium, MRI-ECV was 33.12%±4.29%, and CT-ECV were 35.81%±4.48%, 36.02%±4.56%, and 36.58%±4.69% in Group A, B, and C, respectively. The agreement between DECT-ECV and MRI-ECV results was good, with the correlation coefficients of 0.878 (group A), 0.955 (Group B) and 0.947 (Group C) (all P<0.001). In the analysis based on segmental myocardium, as for the ischemic LGE myocardial segments, MRI-ECV was 34.60%(31.70%,39.40%), and CT-ECV were 37.50 (34.20, 41.90), 38.20%(36.20%, 40.60%)and 39.40%(35.50%,42.40%)in Group A, B, and C, respectively. The agreement between DECT-ECV and MRI-ECV results was good, with the correlation coefficients of 0.559, 0.695 and 0.682 (all P<0.001) for groups A, B and C, and as for non-ischemic LGE myocardial segments, MRI-ECV was 35.10% (32.68%, 38.70%), and CT-ECV were 38.15% (35.13%, 41.75%), 39.25% (35.78%, 42.20%) and 39.60% (35.88%,42.90%) in Group A, B, and C. The correlation coefficients of CMR-ECV and DECT-ECV of groups A, B and C were 0.531, 0.772 and 0.744 (all P<0.001), showing good agreement; as for negative LGE myocardial segments, MRI-ECV and CT-ECV of Group A, Group B, Group C were 28.50%(27.00%, 30.10%), 31.10%(28.70%, 34.60%), 31.30%(28.40%, 33.80%), 31.30%(29.20%, 34.80%). The correlation coefficients between MRI-ECV and DECT-ECV of group A, B and C were 0.273, 0.508 and 0.425 (all P<0.001), which also showed good agreement. Conclusions:DECT-ECV can be used for quantitative evaluation of myocardial histological features. DECT-ECV with a 5 min and 7 min delay shows good correlation and agreement with MRI-ECV. In order to make this technology more well-known and improve its application capability, our recommendation for clinical practice is a 5 min delay after contrast administration in clinical practice.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

Objective:To analyze the changes in electrical impedance tomography (EIT) during the extubation phase in critically ill patients undergoing invasive mechanical ventilation (MV),and evaluate the value of EIT and EAdi in predicting extubation failure in critically ill patients.Methods:The clinical data of patients undergoing invasive mechanical ventilation and SBT in the emergency intensive care unit (EICU) of the First Affiliated Hospital of Anhui Medical University from January 2022 to June 2024 were prospectively collected. The values of EIT were monitored and recorded at pressure support ventilation, 2 hours after extubation and 6 hours after extubation. According to whether the patient was re-intubated within 48 hours after extubation,patients were divided into successful extubation group and extubation failure group. The values of EIT were compared at the same time point between the two groups, and the correlation analysis of the values of EIT was carried out. The ROC curve was used to analyze the predictive ability of EIT at pressure support ventilation, 2 hours after extubation and 6 hours after extubation after SBT passage for extubation failure.Results:A total of 110 patients were included in the study, of which 52 patients failed to extubation. Patients in the failed extubation group had a smaller available ventilation area (SAV) before and after extubation compared to those in the successful extubation group, and had a higher Global Inhomogeneity Index (GI) ( P<0.001). The regional ventilation delay and the the center of ventilation were not different between groups. Conclusions:The values of EIT are valid predictors of extubation failure in critically ill patients and are suitable for clinical application.

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To investigate the clinical efficacy of elderly patients with diffuse large B-cell lymphoma (DLBCL) and the influencing factors of prognosis.Methods:The clinical data of 76 elderly (≥60 years old) patients with DLBCL admitted to Huadong Hospital Affiliated to Fudan University between January 2015 and December 2019 were retrospectively analyzed. The R-CHOP regimen was the preferred treatment for 54 patients, while the remaining patients received R-miniCHOP, CHOP or other regimens or supportive treatments due to age, physical condition, economic factors, etc., which were not included in the efficacy analysis. Kaplan-Meier method was used to analyze the survival status of patients. Multivariate Cox proportional risk model was used to analyze the prognostic factors.Results:Among the 54 patients who preferred R-CHOP regimen for treatment, 26 cases (48.1%) achieved complete remission and 14 cases (25.9%) achieved partial remission, and the total effective rate was 74.1% (40/54); Among them, the total effective rate of 37 cases aged 60-69 years was 70.3% (26/37), and the total effective rate of 17 cases aged 70-79 years was 82.4% (14/17); there was no statistically significant difference in the total effective rate between the two groups ( χ2 = 3.01, P = 0.390). All 76 patients were followed up for 1-60 months. As of the last follow-up, 49 patients (64.5%) died, with the median overall survival (OS) time of 16 months and 5-year OS rate of 35.5%. Kaplan-Meier method showed that age ≥ 70 years old at initial diagnosis, Eastern Cooperative Oncology Group (ECOG) score ≥ 2 points, presence of B symptoms, international prognosis index (IPI) score >3 points, elevated lactate dehydrogenase, immunohistochemistry positive for bcl-2, and non-germinal center type were associated with poor OS (all P < 0.05). Multivariate Cox analysis showed that age ≥ 70 years old at initial diagnosis, presence of B symptoms, positive expression of bcl-2, non-germinal center type were independent risk factors for OS (all P < 0.05). Conclusions:Elderly DLBCL patients have poor survival. Old age at initial diagnosis, B symptoms, bcl-2 positive, and non-germinal center type are independent risk factors of prognosis.