Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Purpose To evaluate the classification criteria of triple negative breast cancer(TNBC)based on histomorphol-ogy and immunohistochemistry(IHC),and to provide theoreti-cal basis for the classification and treatment of TNBCs.Methods TNBC subtyping was performed according to the histomorphologi-cal characteristics and the expression of immune markers AR,CD8 and FOXC1,and the clinicopathological features and prog-nostic differences were compared.Results Among 93 cases of TNBC,there were 23 cases(24.7％)of luminal androgen re-ceptor subtypes,24 cases(25.8％)of immunomodulatory type,39 cases(42.0％)of basal immunosuppressive type,and 7 ca-ses(7.5％)of mesenchymal type.There were significant differ-ences in the clinicopathological features of subtypes,including pT stage(P=0.030),histological grade(P＜0.001),intersti-tial lymphocyte infiltration pattern(P＜0.001),expression of PD-L1(P＜0.001),and HER2-low(P=0.024).There was no significant difference in disease-free survival among the sub-types(P＞0.05).Univariate survival analysis showed there was significant difference in disease-free survival among the subtypes at pT1 stage(P=0.011),and other clinicopathological features were not independent prognostic factors.Conclusion The clini-copathological characteristics of TNBC subtypes are different,which are expected to be an alternative choice for complex gene expression profile analysis and to provide theoretical basis for subtypic therapy and targeted therapy.

Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women.Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development.Stress leads to dysfunctions of cells,molecules and neural circuits,thus promoting depression.Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients.

Objective:To explore the airway pathogen characteristics and examine the correlation between donor-derived pathogens and post-transplant outcomes in patients after lung transplantation (LT).Methods:Between January 1, 2015 and December 31, 2019, retrospective review was conducted for clinical and microbiological data of 88 LT recipients.Airway pathogen percentage of different microorganisms and evolution of drug-resistance were examined.Drug-resistant pathogen positive group (n=71) and negative group (n=17) were assigned according to whether or not drug-resistant pathogens were detected.Survival analysis was conducted by Log-rank with 3-year follow-ups.Between April 11, 2020 and September 5, 2020, prospective study was conducted in 14LT recipients.The potential pathogenic bacteria from donor lungs were detected by metagenomic next generation sequencing and the impact of those bacteria was examined on 1-year post-transplantation outcome in 2020.Microbial diversity and richness were shown with Shannon index.The outcome variables included heart rate, neutrophil count, lymphocyte count, immunoglobulin level and pulmonary spirometry.ANOVA and Pearson's correlation analysis were performed for elucidating the relationship between airway microbiota and post-LT outcomes.Results:From 2015 to 2019, 88 recipients were recruited and 992 strains of airway pathogens were isolated, including bacteria 796 strains and fungi 196 strains.Gram-negative bacteria (704 strains) accounted for 88.4% of all bacteria.The detection rates of Gram-positive bacteria, Klebsiella pneumonia (Kp), Acinetobacter baumannii (Ab), Stenotrophomonas maltophilia and Candida increased in 2019 than that in 2015 (8.2% vs. 5.3%, 13.6% vs. 13.2%, 33.2% vs. 17.5%, 6.5% vs. 5.3%, 26.6% vs. 20.2%). Drug resistance rate of Kp to imipenem was 68.18% in 2019 and drug resistance rate of Ab to imipenem 98.44%.The 3-year survival rate was 46.3% and 35.3% in drug-resistance positive and negative groups and the difference was insignificant ( P=0.410). Fourteen recipients were enrolled in 2020.Potential pathogenic bacteria could be detected in all donor samples.Five recipients carried the same bacteria and two died during 1-year follow-up.Nine recipients did not carry the donor-derived pathogens and two died during 1-year follow-up.The diversity of donor/recipient-derived airway microbiota (Shannon index) showed no correlation with the outcomes of 1-year follow-up by Pearson's correlation test. Conclusions:Gram-negative bacteria predominated in airway pathogens of recipients post-LT.The drug resistance rate to imipenem remained high.The donor/recipient-derived pathogen isolates showed no correlation with immediate outcomes post-LT.

ObjectiveTo determine the situation and challenges of innovation platforms in China， and to explore the construction strategy of Shanghai Nutrition Innovation Platform， which is suitable for Shanghai and may achieve the research and transformation of nutrition innovation and population health， so as to coordinate， unite and gather the superior resources of all parties and promote nutrition innovation. MethodsConstruction scheme and operational mechanism of Shanghai Nutrition Innovation Platform were explored by literature review， expert consultation and questionnaire. ResultsThere were various forms of innovation platforms in China. However， challenges were identified， such as decentralizing force， resource rearrangement and insufficient sharing effect. Shanghai Nutrition Innovation Platform adopted a modular organizational structure， which was divided into central group， node group， and subject group. Shanghai Center for Disease Control and Prevention， as the central organization， is responsible for the platform operation management. The expert database as an academic committee selected key organizations from nutrition-related universities， research institutes， academic associations， centers for disease control and prevention， hospitals and the industry. Based on the opening of its own innovation resources， the platform made effective use of external innovation resources and formed a closely integrated nutrition innovation network of multiple disciplines. ConclusionThis study promotes the construction of innovation platform model of cooperation， co-construction and resource sharing， and provides reference for the construction of innovation platform in China.

Background::Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods::The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results::A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P= 0.011) and N3b status (OR= 1.752, P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1-2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16-29: 8.6% vs. 10.4%, ELN30-44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1-2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16-29: 8.6% vs. 7.9%, ELN30-44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1-2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16-29: 3.6 vs. 4.6, ELN30-44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN. Conclusions::DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.

Background and Objectives: Mesenchymal stem cells (MSCs) have the multipotent capacity to differentiate into multiple tissue lineages as well as to self-renew, which is the main origin of adipocytes. IL6/IL6R pathway exerts a significant role in tissue regeneration and cell differentiation. Whereas, the underlying mechanism between IL6/IL6R pathway and MSCs adipogenesis differentiation remains elusive. Methods: MSCs from healthy donors were cultured in adipogenesis differentiation medium for 0∼14 days, during which their adipogenesis differentiation degree was evaluated by Oil Red O staining. The expression of IL6R was detected in MSCs during adipogenesis differentiation. Knockdown and overexpression of IL6R were respectively performed using siRNA and lentivirus to investigate its effect on MSCs adipogenesis differentiation. The adipogenesis marker genes expression and MAPK pathway activation were detected by Western blotting. The role of P38 pathway in the adipogenesis differentiation of MSCs was determined using the specific inhibitor SB203580. Results: The expression of IL6 and IL6R increased during adipogenesis differentiation in MSCs, which were positively correlated with Oil Red O quantification result. Knockdown and overexpression experiments demonstrated a positive correlation between the expressions of IL6R and MSCs adipogenesis differentiation, accompanied by same trend of P38 phosphorylation. Besides, the specific P38 inhibitor SB203580 markedly inhibited the adipogenesis differentiation potential of MSCs. Conclusions This study reveals IL6R facilitates the adiogenesis differentiation of MSCs via activating P38 pathway.

Objective: To study the efficacy and safety of Cefpodoxime proxetil granules in the treatment of acute bronchitis in children. Methods: One hundred and sixty children of the First People′s Hospital of Nanning from June to December 2018 with acute bronchitis were randomly divided into cefpodoxime group and cefaclor group, with 80 cases in each group.All patients received routine treatment.On this basis, 80 patients in the cefpodoxime group received oral Cefpodoxime proxetil granules 5 mg/kg (not more than 100 mg/time), twice a day; 80 patients in the cefaclor group received oral Cefaclor.The granules were 10 mg/kg (not more than 250 mg/time), 3 times a day, and the course of treatment was 5 days.The clinical efficacy and adverse reactions were observed. Results: The cure rate and effective rate of Cefpodoxime group were 91.3% (73/80 cases) and 95.0% (76/80 cases), respectively, while the cure rate and effective rate of Cefaclor group were 66.3%(53/80 cases) and 81.3%(65/80 cases), respectively, and the differences between the 2 groups were statistically significant (χ²=14.94, 7.23, all P<0.05). Sixty-three strains of pathogenic bacteria and 66 strains of pathogenic bacteria were obtained in Cefpodoxine group and Cefaclor group, respectively, and the detection rates of bacteria in the 2 groups were 78.75% and 82.50%, respectively.There was no significant diffe-rence in the number of bacterial strains and strains detected in each group (χ²=0.36, P>0.05), but the total bacterial clearance rate in Cefpodoxine group was 88.9%(56/63 cases) while the bacterial Clearance rate in Cefaclor group was 74.2%(49/66 cases), and the difference between the 2 groups was statistically significant (χ²=4.57, P<0.05). In particular, the bacterial clearance rate in Cefpodoxine group to Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae were significantly higher than those in Cefaclor group, while the bacterial Clearance rate of Proteus and Escherichia coli were lower than those in Cefaclor group.The incidence of adverse reactions in Cefpodoxine group and Cefaclor group were 5.0% and 3.8%, respectively, with no significant difference (P>0.05). Conclusions The clinical effect of Cefpodoxime pro-xetil granules in treating children with acute bronchitis is more significant than that of Cefaclor.It has high safety and no serious side effect.

Objective To explore whether tumor necrosis factor receptor-associated protein 1 (TRAP1)gene copy number variation was associated with susceptibility and clinical characteristics of systemic lupus erythematosus (SLE).Methods The study enrolled 304 SLE patients and 391 healthy controls.They were used to investigate the association between TRAP1 gene copy number variation and SLE susceptibility.Then,304 SLE patients were divided into copy number=2 group and copy number＞2 group to study the association between TRAP1 gene copy number variation and disease activity or clinical characteristics of SLE.AccuCopyTM Kit was used to detect the TRAP1 gene copy number.Data analyses were performed by SPSS 10.01 software.The suitable method was selected among t test,rank sum test and x2 test for analysis based on the data type and distribution,univariate and multivariate logistic regression analysis were performed to investigate the associ-ation between TRAP1 gene copy number variation and susceptibility and clinical characteristics of SLE.Results The copy number variation of TRAP1 gene showed an association with the susceptibility to SLE crude OR=5.257,95％CI (1.108,24.937),P=0.037;the adjusted OR=5.578,95％CI (1.172,26.556),P=0.031].There was no association between TRAP1 gene copy number variation and SLE disease activity index (SLEDAI) score (Z=-0.117,P=0.907).The copy number variation of TRAP1 gene had a marginal association with skin lesions in SLE [OR=0.130,95％CI (0.016,1.069),P=0.058],but it disappeared after adjusting for potential confounders [OR=0.288,95％CI (0.029,2.831),P=0.286,PBH=0.808].There was no correlation between TRAP1 gene copy number variation and arthritis,alopecia,oral ulcers,fever,hematologic disorder,lupus nephritis as well as photosensitivity in SLE [x2=0.751,OR=1.234,95％CI (0.767,1.988),P=0.386].No multiplicative interaction was found between TRAP1 gene copy number variation and age or body mass index (BMI) [age:x2=0.751,OR=1.234,95％CI (0.767,1.988),P=0.386;BMI:x2=0.282,OR=1.172,95％CI(0.652,2.109),P=0.596].Conclusions The copy number variation of TRAP1 gene may be associated with susceptibility to SLE.Increased TRAP1 gene copy number may be a risk factor for SLE.

Objective To investigate the characteristics and feasibility of genipin-crosslinked amniotic membrane(AM) as bio-scaffold.Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from fresh umbilical cord and cultured by adherent method.The expressions of PE-CD34,PE-CD45,PE-CD90,FITC-105 and FITC-Oct-4,the markers of hUCMSCs,were detected by flow cytometry.Alizarin red and oil red O staining were performed to identify the cells after adipogenesis and osteogenesis induction on the third-generation cells.Human AMs were treated at 37 ℃ and 45 ℃ by 0.5％ and 1％ genipin solution for 24,36 and 48 hours respectively,and the mechanical properties of AM in each group were measured and compared.The hUCMSCs were divided into only hUCMSCs culture group,fresh AM group,crosslinked AM group,gelatin group and crosslinked AM+gelatin group,and the cells were cultured in the corresponding medium.The content of hydroxyproline among the groups was detected with hydroxyproline kit,and proliferation of the cells (absorbance) was assayed by MTT method to evaluate the biological compatibility of crosslinked AM.Results The maximum tensile displacement of the crosslinked-AM by 0.5％ and 1％ genipin was (8.31±0.43)mm and (4.49±0.37)mm respectively,and those after crosslinked with 0.5％ genipin under the 37 ℃ and 45 ℃ for 24 hours was (9.89±1.09)mm and (5.39±0.59)mm,respectively,showing a significant difference between them (t =6.389,P＜0.05).The maximum tensile displacement of the crosslinked-AM was gradually decreased as the lapse of crosslinking time,and an insignificant difference was found among 24,36 and 48 hours after 0.5％ genipin treatment under the 37 ℃ (P＞0.05).The loading force of the crosslinked-AM was significantly higher in the 1％ genipin treated group than that in the 0.5％ genipin treated group (P＜0.05),and the loading force of the AM was significantly increased in 45 ℃,0.5％ genipin,24 hours crosslinked group compared with the 37 ℃,0.5％ genipin,24 hours crosslinked group (t =5.528,P＜0.05).The content of hydroxyproline in the AM was (1.28±0.36),(2.03 ±0.49) and (2.11 ±0.10) mg/g in the 1％ genipin crosslinked AM group,0.5％ genipin crosslinked AM group and fresh AM group,respectively,and the content of hydroxyproline in the AM in the 1％ genipin group was significantly lower than that in the 0.5％ genipin group in the fresh AM group (both at P＜0.05).The proliferative values of the hUCMSCs were significantly lower in the only hUCMSCs culture group,fresh AM group and gelatin group were significantly reduced in comparison with the crosslinked AM group and crosslinked AM+gelatin group (all at P＜0.05).There was no significant difference in the proliferative values of the hUCMSCs between crosslinked AM group and crosslinked AM+gelatin group (P＞0.05).Conclusions Different crosslinked temprature,crosslinking period and concentration of genipin impact the mechanical properties of AM.Crosslinked AM with genipin is feasible as a carrier scaffold of artificial cornea because of less tissue toxicity and better plasticity.