To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

Objectives To develop a multi-stage and multi-epitope vaccine, which consists of epitopes from the early secretory and latency-associated antigens of Mycobacterium tuberculosis (MTB). Methods The B-cell, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes of 12 proteins were predicted using an immunoinformatics. The epitopes with antigenicity, without cytotoxicity and sensitization, were further screened to construct the multi-epitope vaccine. Furthermore, the proposed vaccine underwent physicochemical properties analysis and secondary structure prediction as well as 3D structure modeling, refinement and validation. Then the refined model was docked with TLR4. Finally, an immune simulation of the vaccine was carried out. Results The proposed vaccine, which consists of 12 B-cell, 11 CTL and 12 HTL epitopes, had a flexible and stable globular conformation as well as a thermostable and hydrophilic structure. A stable interaction of the vaccine with TLR4 was confirmed by molecular docking. The efficiency of the candidate vaccine to trigger effective cellular and humoral immune responses was assessed by immune simulation. Conclusion A multi-stage multi-epitope MTB vaccine construction strategy based on immunoinformatics is proposed, which is expected to prevent both active and latent MTB infection.
Mycobacterium tuberculosis/metabolism* ; Molecular Docking Simulation ; Toll-Like Receptor 4 ; Epitopes, T-Lymphocyte/chemistry* ; Epitopes, B-Lymphocyte/chemistry* ; Vaccines, Subunit/chemistry* ; Computational Biology/methods*

Jasminum pentaneurum Hand.-Mazz is widely used in Yao areas,but there are few reports on its composition,pharmacological effects,and quality markers(Q-markers)both domestically and internationally.On the basis of previous research,this article is based on the"Five Principles"of Q-marker research,predicting and analyzing the Q-marker of Jasminum pentaneurum Hand.-Mazz from aspects such as resource distribution,composition,traditional efficacy,plant phylogeny,and component specificity,providing a basis for further in-depth research.

Objective:To study the pathogenic distribution of bronchoalveolar lavage fluid in children with severe pneumonia from Children′s Hospital Affiliated to Soochow University, and to investigate the drug resistance of major pathogenic bacteria.Methods:A total of 177 children with severe pneumonia undergoing fiberoptic bronchoscopy in Children′s Hospital Affiliated to Soochow University from January 2014 to December 2018 were enrolled.Their bronchoalveolar lavage fluid was collected for pathogen identification, pathogen culture and drug sensitivity analysis.The pathogens were detected by direct immunofluorescence quantitative PCR.Results:Of 177 cases enrolled, 100 children had at least one pathogen detected, and the positive rate was 58.13%.Among all the pathogens detected, Mycoplasma pneumonia (MP) had the highest detection rate, which was found in 41 cases.The top three bacteria detected included Streptococcus pneumoniae (9 cases, 10.59%), Staphylococcus aureus (8 cases, 9.41%), and Pseudomonas aeruginosa (6 cases, 7.06%). The top three viruses detected were cytomegalo virus (CMV) (14 cases, 33.33%), human bocavirus (HBoV) (10 cases, 23.81%), and respiratory syncytial virus (RSV) (8 cases, 19.05%). The drug sensitive test indicated that main kinds of Gram-negative bacteria had low resistance to quinolones, aminoglycosides, carbapenems, and enzymatic beta-lactams.Main kinds of Gram-positive bacteria had low resistance to Linezolid and vancomycin.The virus detection rate and MP detection rate in severe pneumonia children under 5 years old were about 30.00% and 20.00%, respectively.The MP detection rate in children above 5 years old exceeded 30.00%.The bacteria detection rates in children under and above 2 years old were over 20.00% and about 15.00%, respectively.Airway abnormalities were common in children with severe pneumonia, mainly including tracheobronchial malacia and stenosis. Conclusions:The most common pathogen of bronchoalveolar lavage fluid in severe pneumonia children under 5 years old in Suzhou is viruses.The bacteria detection rate is high in children under 2 years old.Common Gram-positive bacteria show high susceptibility to vancomycin and Linezolid. Pseudomonas aeruginosa is highly sensitive to quinolones, aminoglycosides, carbapenems, and enzymatic beta-lactams.Importance should be attached to the airway abnormalities in children, especially infants, with severe pneumonia.

Objective:To investigate the relationship between angiopoietin-like protein 4(ANGPTL4) and vascular endothelial growth factor(VEGF) in serum and lower limb arterial lesions in Type 2 diabetes mellitus.Methods:Using the method of retrospective cohort study, 164 inpatients with type 2 diabetes admitted to the Department of Endocrinology, Dahua hospital, Xuhui District, Shanghai from October 2017 to December 2018 were selected as the type 2 diabetes group, and 69 healthy people in the same period were collected as the normal control group.According to the ankle brachial index<0.9, diabetic patients were divided into two groups: the group without lower extremity artery disease and the group with lower extremity artery disease.The levels of ANGPTL4 and VEGF in serum were measured by enzyme-linked immunosorbent assay.Results:(1)Compared with the normal control group: the concentration of ANGPTL4 in serum of lower extremity arterial disease group and no lower extremity arterial disease group((44.78±15.15), (47.46±10.43) μg/L) were lower than that of normal control group((52.87±12.74) μg/L), the difference was statistically significant (all P<0.05). The serum VEGF concentration in lower extremity arterial disease group and no lower extremity arterial disease group((340.98±76.18), (314.83±75.30) ng/L) were higher than that in normal control group((282.58±81.4) ng/L), the difference was statistically significant(all P<0.05). (2)Compared with no lower extremity arterial disease group: the concentration of ANGPTL4 in serum of lower extremity arterial disease group was lower than that of no lower extremity arterial disease group, but the difference was not statistically significant( P>0.05). The serum VEGF concentration in lower extremity arterial disease group was higher than that in no lower extremity arterial disease group, the difference was statistically significant( P<0.05). (3)Correlation analysis: Diabetes mellitus and diabetic course>10 years( OR 4.594, 95% CI2.540-8.311, P<0.001), fasting blood glucose>8 mmol/L( OR 2.353, 95% CI1.023-5.416, P=0.044), glycosylated hemoglobin>8%( OR 6.442, 95% CI 2.874-14.441, P<0.001) and the increase of VEGF( OR 3.745, 95% CI1.566-8.953, P=0.003) are risk factors for lower limb arterial disease in type 2 diabetes, while the increase of ANGPTL( OR 0.154, 95% CI0.064-0.372, P<0.001) can reduce the occurrence of lower limb arterial disease in type 2 diabetes. Conclusion:ANGPTL4 is a protective factor and VEGF is a risk factor of type 2 diabetes mellitus.Both of them influence each other and participate in its occurrence and development.

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Aromatase inhibitors ( AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for ＜60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network ( NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e. g. T3?4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Aromatase inhibitors ( AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for ＜60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network ( NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e. g. T3?4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Objective To explore the effect of prognosis of consolidation radiotherapy for patients after R0 resection of local recurrence after radical mastectomy. Methods Totally 110 breast cancer patients with local recurrence receiving R0 resection were admitted and treated in our hospital from January 1st, 2003 to November 30th, 2015 were retrospectively analyzed. Results The median local progression time of 74 patients receiving consolidation radiotherapy ( 67.3％) was remarkably better than that of those without radiotherapy(36 patients, 32.7％), and the difference was statistically significant (χ2 =8. 526, P<0.05). Meanwhile, there was no statistically significant difference (P>0.05) of distance disease-free survival and overall survival between the radiotherapy group and the non-radiotherapy group. Multifactor analysis indicated that pseudo-adjuvant endocrine therapy (χ2 =7.541,95％CI:27.1％ -80.4％, P <0.05), DDFS(≥2 years vs. <2 years,χ2 =4.068,95％CI:101.4％ -267％,P<0. 05) and pseudo-adjuvant radiotherapy(χ2 =14.126, 95％CI:21.7％ -80.4％, P <0. 05 ) were the independent risk factors affecting the OS of patients with local recurrence after R0 resection. Conclusions For the patients with local recurrence after R0 resection of local recurrence, it is recommended that consolidation radiotherapy should be done and the radiation field should include the same side of the chest wall and clavicle area lymphatic drainage area.

Osteoblastic metastasis of breast cancer is relatively rare, but there are cases of misdiagnosis and mistreatment in clinical treatment. They can only be diagnosed by X ray or CT bone scan and must be identified from bone repair after effective treatment in patients with osteolytic or mixed bone metastases. Bone metastasis is often seen in the disease-free condition of breast cancer, and very few can occur in stage Ⅳ lesions prior to surgery. Based on the analysis of clinical phenomena, we questioned the evaluation criteria of the therapeutic effect on bone metastasis of breast cancer created by the World Health Organization and the MD Anderson Cancer Center and concluded the formation mechanism of bone metastasis. For patients with simple osteoblastic bone metastasis, we broke through the recommendations of the National Comprehensive Cancer Network guideline and advocated the concept of "noninterference" . Patients with positive hormone receptor can be treated with traditional endocrine therapy. Hormone receptor negative and/or human epidermal growth factor receptor 2 positive patients can be observed first, followed by chemotherapy and/or targeted therapy when there is osteolytic bone metastasis or visceral metastasis. Furthermore, bisphosphonates are not required since osteoblastic bone metastasis is generally not associated with the risk of bone related events. The active treatment of primary lesion should be taken into account in stage Ⅳ patient before operation.