[This corrects the article DOI: 10.1016/j.apsb.2021.07.024.].

Objective:To investigate effects of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSCs-Exo)on bisphenol AF(BPAF)-induced oxidative damage and inflammatory factor release from endometrial stromal cells(hESCs).Methods:hESCs were divided into Control group,BPAF group(25 μmol/L BPAF treatment),BPAF+Exo group(25 μmol/L BPAF+hUCMSCs-Exo treatment),BPAF+Exo+LY group(25 μmol/L BPAF+hUCMSCs-Exo+10 μmol/L LY294002 treatment).Cell prolifera-tion was detected by MTT assay;apoptosis,intracellular ROS level,and mitochondrial membrane potential level were detected by flow cytometry;protein expressions of Bcl-2,Bax,Cleaved-caspase-3 and PI3K/AKT signaling pathway were detected by Western blot;mRNA expressions of inflammatory factors TNF-α,IL-6 and IL-1β were detected by RT-qPCR.Results:Compared with Control group,hESCs survival rate was gradually decreased(P<0.01),apoptosis rate was gradually increased with the increased concentration of BPAF(≥25 μmol/L).Compared with Control group,BPAF group showed increased ROS level,decreased mitochondrial membrane potential level,increased Bax and Cleaved-caspase-3 protein expressions,and decreased Bcl-2,p-PI3K and p-AKT protein expressions.Compared with BPAF group,cell survival rate of BPAF+Exo group was increased(P<0.01),ROS level decreased,mitochondrial membrane potential level increased,expressions of Bax and Cleaved-caspase-3 proteins decreased,and expressions of Bcl-2,p-PI3K and p-AKT increased.Compared with BPAF+Exo group,expressions of Bax and Cleaved-caspase-3 protein in cells of BPAF+Exo+LY group were increased,while expressions of Bcl-2,p-PI3K and p-AKT protein were decreased.Expressions of inflammatory factors TNF-α,IL-6 and IL-1β mRNA were significantly up-regulated in BPAF group compared with Control group(P<0.01),and expressions of inflammatory factors mRNA were significantly down-regulated in BPAF+Exo group compared with BPAF group(P<0.05).Conclu-sion:BPAF(≥25 μmol/L)inhibits proliferation of hESCs and promoted apoptosis.hUCMSCs-Exo inhibits BPAF-induced oxidative dam-age and inflammatory factors expressions in hESCs through PI3K/AKT signaling pathway.

Objective:To investigate effects of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSCs-Exo)on bisphenol AF(BPAF)-induced oxidative damage and inflammatory factor release from endometrial stromal cells(hESCs).Methods:hESCs were divided into Control group,BPAF group(25 μmol/L BPAF treatment),BPAF+Exo group(25 μmol/L BPAF+hUCMSCs-Exo treatment),BPAF+Exo+LY group(25 μmol/L BPAF+hUCMSCs-Exo+10 μmol/L LY294002 treatment).Cell prolifera-tion was detected by MTT assay;apoptosis,intracellular ROS level,and mitochondrial membrane potential level were detected by flow cytometry;protein expressions of Bcl-2,Bax,Cleaved-caspase-3 and PI3K/AKT signaling pathway were detected by Western blot;mRNA expressions of inflammatory factors TNF-α,IL-6 and IL-1β were detected by RT-qPCR.Results:Compared with Control group,hESCs survival rate was gradually decreased(P<0.01),apoptosis rate was gradually increased with the increased concentration of BPAF(≥25 μmol/L).Compared with Control group,BPAF group showed increased ROS level,decreased mitochondrial membrane potential level,increased Bax and Cleaved-caspase-3 protein expressions,and decreased Bcl-2,p-PI3K and p-AKT protein expressions.Compared with BPAF group,cell survival rate of BPAF+Exo group was increased(P<0.01),ROS level decreased,mitochondrial membrane potential level increased,expressions of Bax and Cleaved-caspase-3 proteins decreased,and expressions of Bcl-2,p-PI3K and p-AKT increased.Compared with BPAF+Exo group,expressions of Bax and Cleaved-caspase-3 protein in cells of BPAF+Exo+LY group were increased,while expressions of Bcl-2,p-PI3K and p-AKT protein were decreased.Expressions of inflammatory factors TNF-α,IL-6 and IL-1β mRNA were significantly up-regulated in BPAF group compared with Control group(P<0.01),and expressions of inflammatory factors mRNA were significantly down-regulated in BPAF+Exo group compared with BPAF group(P<0.05).Conclu-sion:BPAF(≥25 μmol/L)inhibits proliferation of hESCs and promoted apoptosis.hUCMSCs-Exo inhibits BPAF-induced oxidative dam-age and inflammatory factors expressions in hESCs through PI3K/AKT signaling pathway.

Objective To explore the construction idea and application method of knowledge base and knowledge mining system for the prevention and treatment of diseases in traditional Chinese medicine.Methods Guided by the theory of traditional Chinese medicine(TCM),firstly,the knowledge system of TCM Prevention and treatment was sorted out,and the structure and relationship of TCM Prevention and treatment knowledge base were designed according to the classification method of TCM Prevention and treatment;Secondly,according to the needs of pre treatment research,the ancient and modern literature data sources and knowledge collection methods of TCM pre treatment database are proposed;Then,under the framework of the pre treatment classification system,the core knowledge is studied in the aspects of professional annotation,relationship extraction,knowledge audit,and a variety of data mining algorithms are introduced to analyze and mine the knowledge;Finally,the massive data obtained are combined with big data analysis and computer machine learning to realize intelligent information collection,disease analysis and diagnosis and treatment suggestions.Results Under the guidance of traditional Chinese medicine theory,the knowledge base of traditional Chinese medicine for prevention and treatment of diseases can digitize,digitize and intellectualize the basic knowledge and clinical knowledge of traditional Chinese medicine for prevention and treatment of diseases,and can objectively mine and analyze the data,providing a basis for the service and sharing of knowledge of traditional Chinese medicine for prevention and treatment of diseases.Conclusion The knowledge base of TCM Prevention and treatment is an important way for the digital storage of TCM Prevention and treatment knowledge,and provides literature knowledge support and objective evidence of data mining for TCM Prevention and treatment research.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the relationship between serum soluble CD155 (sCD155), soluble CD163 (sCD163) and chemotherapy efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).Methods:A total of 126 patients with DLBCL admitted to Handan Central Hospital from May 2018 to May 2020 (DLBCL group) and 126 healthy subjects (control group) were prospectively selected to compare serum sCD155 and sCD163 levels. According to the chemotherapy effect of DLBCL patients, they were divided into effective group and ineffective group, and the serum sCD155 and sCD163 levels were compared before and after treatment. The effective rate of chemotherapy in patients with different serum sCD155 and sCD163 levels was compared. Kaplan-Meier method was used to analyze the relationship between serum sCD155 and sCD163 levels and 3-year overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Cox proportional risk regression model was used to analyze the prognostic factors of DLBCL patients.Results:The serum levels of sCD155 and sCD163 in DLBCL group were higher than those in control group before treatment (all P<0.05). The effective rate of chemotherapy in 126 DLBCL patients in this group was 69.8%(88/126). Compared with the effective group, the serum levels of sCD155 and sCD163 were higher in the ineffective group before and after treatment (all P<0.05). Compared with before treatment, serum sCD155 and sCD163 levels in the effective group were decreased after treatment (all P<0.05). The effective rate of DLBCL patients in sCD155 and sCD163 high level groups was lower than that in sCD155 and sCD163 low level groups (all P<0.05). Kaplan-Meier analysis showed that the 3-year OS and PFS of DLBCL patients in the low level group of sCD155 and sCD163 were higher than those in the high level group (all P<0.05). The high level of sCD155 and sCD163 were independent risk factors for 3-year PFS and OS in DLBCL patients (all P<0.05). Conclusions:Abnormal levels of serum sCD155 and sCD163 in DLBCL patients may reduce the efficacy of chemotherapy and lead to poor prognosis.

BACKGROUND: The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. METHODS: Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. RESULTS: In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. CONCLUSIONS Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.
Humans ; Arthritis, Psoriatic/drug therapy* ; East Asian People ; Enthesopathy/complications* ; Registries ; Severity of Illness Index ; Spondylarthritis/epidemiology*

Objective:To understand the molecular transmission characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome(AIDS) patients in the mountainous area of southwest Zhejiang Province(Lishui city).Methods:A total of 147 blood samples were collected from newly-diagnosed HIV-1 infected who received no antiviral therapy, and pol gene was amplified, followed by sequencing. MEGA6.0 software was used to construct phylogenetic tree and determine gene subtypes. HIVDB online was used to analyze drug resistance mutation, then the pairwise genetic distance(GD) was calculated and the opitimal threshold of GD was selected, finally the molecular transmission network was constructed by Cytoscape3.7.0 software. Chi-square or Fisher′s exact probability method was used for statistical analysis. Results:A total of 134 sequences were obtained successfully, and nine subtypes were detected. The dominant subtypes were CRF08_BC (34.33%, 46/134), CRF01_AE (29.85%, 40/134) and CRF07_BC (23.88%, 32/134). It also found that age, registered residence, education level and transmission route had significant differences in distribution of subtypes ( P<0.05). Nineteen drug resistance individuals were found, and the total drug resistance rate was 14.18% (19/134). The HIV-1 molecular transmission network was plotted based on 1.2% GD threshold. A total of 15 transmission clusters (cluster size ranging from 2 to 29) were found. The network access rate was 49.25% (66/134), mainly including male (75.76%, 50/66), heterosexual (81.82%, 54/66) and patientsrinfected with CRF08_ BC (50.00%, 33/66). A transmission cluster including two cases of female sex workers and seven cases of drug resistance was identified, in which the average age of the patients was 57.21 years old and the average degree value was 22.7, and the cases were mainly infected through heterosexual contact (96.55%, 28/29). The highest homology of the sequences in the cluster was in Yunnan. Conclusions:The HIV-1 subtypes were diverse in the mountainous area of southwest Zhejiang Province(Lishui city). Drug resistant transmission had reached a moderate epidemic level. There were molecular transmission clusters with the aggregation characteristics of elderly clients in specific regions. It was urgent to formulate and implement precise intervention strategies to curb the spread of HIV.

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.

As a digestive organ, the liver has the functions of metabolism, synthesis, and detoxification. It is also an immune organ and plays an important role in maintaining anti-infection, autoimmune stability, and anti-tumor. In particular, the liver has unique immunological advantages. Its immune cells can maintain the liver's immune homeostasis and participate in immunoregulation. A variety of immunotherapy is used in clinical trials for the treatment of difficult and critical liver diseases. This review mainly summarizes the recent clinical trials of immunotherapy in chronic hepatitis B, cirrhosis, hepatocellular carcinoma, and autoimmune liver disease.