Systemic lupus erythematosus(SLE)is a heterogeneous autoimmune disease that affects multiple organs.Extracel-lular vesicles(EVs),including exosomes,microparticles and apoptotic bodies,are released by most types of cells and carry nucleic acids,proteins and lipids,which play a crucial role in communication among cells.In SLE,extracellular vesicles can act as autoadju-vants to enhance the formation of immune complexes and maintain inflammatory states.In this review,the biological origin and mes-senger role of EVs in cell communication are reviewed,and the research progress of EVs in immune regulation and pathogenesis in SLE is highlighted.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

OBJECTIVE: To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). METHODS: The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. RESULTS: The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P < 0.05), demonstrating POI-like changes. Compared with the control mice, oocyte-specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL- 2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P < 0.05). CONCLUSION FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/genetics* ; Apoptosis ; Signal Transduction ; Proto-Oncogene Proteins c-bcl-2 ; Granulosa Cells ; Mice, Transgenic ; Mice, Knockout ; TOR Serine-Threonine Kinases

WRKY, a class of conserved transcription factors in plants, plays important roles in plant growth, development and secondary metabolism. In the present study, 65 WRKY members were identified from de novo transcriptome sequencing data of three different tissues (root, stems and leaves) of Baphicacanthus cusia. BcWRKY proteins contained from 221 to 706 amino acids and the isoelectric point is from 4.68 to 9.68. Molecular weights range from 25 711.8 to 75 475 Da. The main secondary structures of BcWRKYs protein are random coil. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Phylogenetic analysis showed that BcWRKYs could be categorized into three groups and five subgroups (Group IIa, Group IIb, Group IIc, Group IId and Group IIe) in Group II. Structural analysis found that all BcWRKY proteins contained a highly conserved motif WRKYGQK. Finally, the transcriptional profiles of ten BcWRKY genes highly expressed in root, stem and leaf tissues under abscisic acid (ABA), methyl jasmonate (MeJA), or salicylic acid (SA) treatment were systematically investigated using qRT-PCR analysis. Results showed that a total of ten BcWRKY genes were differentially expressed in response to ABA, MeJA, and SA treatment. This work would be provided a basis for further elucidating the molecular mechanism of WRKY transcription factors in the biosynthesis of indole alkaloids in B. cusia.

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.
Carcinoma, Squamous Cell/therapy* ; Chemoradiotherapy ; Humans ; Quality of Life ; Retrospective Studies ; Tonsillar Neoplasms/therapy*

OBJECTIVE: Compared with the method of optical microscopy, to evaluate the accuracy of fragmented red cells(FRC) detection by Sysmex XN-3000. METHODS: A total of 111 samples were collected from patients diagnosed as thrombotic thrombocytopenic purpura, autoimmune disease, hematological disease, malignant tumor and health examination in our hospital from June 2019 to February 2021, including 74 cases in the case group and 37 cases in the healthy control group. All samples were detected by optical microscope and Sysmex XN-3000, respectively. ROC was used to evaluate the detection ability of Sysmex XN-3000 for schistocyte. Bland-Altman method was used to evaluate the consistency of the results of the two methods for detection of schistocyte, and Pearson correlation analysis was conducted for the difference of the results. RESULTS: The area under the ROC curve was 0.890(95% CI: 0.828-0.952, P<0.01). Sysmex XN-3000 count did not quantitatively agree with schistocyte counts by microscopy in the case group(mean of difference:-1.53, 95% limits of agreement: -8.78~5.72). There was a weak positive correlation between platelet count and the difference of analyzer and microscopic results (r=0.32,P<0.05). CONCLUSION Sysmex XN-3000 can be used as a reference for qualitative determination of schistocyte. However, the sensitivity of Sysmex XN-3000 should be improved. It is still necessary to combine with manual microscopy. The quantitative results are not reliable now and cannot be used as a reference for monitoring the results of schistocyte in clinical patients after treatment.
Humans ; Neoplasms ; Platelet Count ; Purpura, Thrombotic Thrombocytopenic ; ROC Curve ; Reproducibility of Results

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Pulmonary hypertension ( PH) is occult, with no distinctive clinical manifestations and poor prognosis.Pulmonary vascular remodelling is an important pathological feature in which pulmonary artery smooth muscle cell ( PASMCs) pheno- typic switching plays a crucial role.MicroRNA (miRNA) is a class of evolutionary highly conserved single-stranded small non-coding RNA.Recently, an increasing number of scholars have found that miRNA can play an important role in the occurrence and development of PH by regulating the phenotypic switching of PASMCs, which is expected to be a potential target for the prevention and treatment of PH.It has been found that miR NA such as miR-221 , miR-24, miR-15b, miR-96, miR-23a.miR-9, miR-214, miR-20a can promote the phenotypic switching of PASMCs, while miRNA such as miR-21, miR-132, miR-182, miR-449, miR-206 .miR-124, miR-30c, miR-140.miR-17-92 cluster can inhibit it.This article aims to review the research progress on miRNA that mediates PASMCs phenotypic switching in PH from both growth factor-related miRNA and hy- poxia-related miRNA.

Objective:To explore the feasibility of using pulse oxygen saturation (SpO 2) to evaluate the condition of patients with acute respiratory distress syndrome (ARDS) in the Lijiang region. Methods:Patients with ARDS who visited the department of emergency of People's Hospital of Lijiang from August to December 2020 were selected as study subjects. Patients were divided by severity into mild ARDS group [200 mmHg (1mmHg = 0.133 kPa)≤oxygenation index (PaO 2/FiO 2, P/F)≤300 mmHg] and moderate to severe ARDS group (P/F≤200 mmHg). The general condition, clinical diagnosis, arterial blood gas analysis results of the patients were recorded, and the differences of the above indexes between the two groups of ARDS were compared. Spearman correlation analysis was used to analyze the correlation between SpO 2 and arterial oxygen saturation (SaO 2). SpO 2 was carried into the Ellis equation and the Rice equation to calculate the derived P/F and analyze the correlation between the derived P/F and the P/F measured in arterial blood gas analysis; receiver operator characteristic curve (ROC curves) were plotted, the sensitivity and specificity of SpO 2/fraction of inspiration oxygen (SpO 2/FiO 2, S/F) instead of P/F to assess oxygenation in patients with ARDS was calculated. To evaluate the feasibility of SpO 2 for the condition evaluation of patients with ARDS in the Lijiang region. Results:Compared with the mild ARDS group, the arterial partial pressure of oxygen (PaO 2), SaO 2 and hemoglobin (Hb) were significantly decreased in the moderate to severe ARDS group [PaO 2 (mmHg): 50.5 (39.3, 56.5) vs. 60.0 (55.0, 67.5), SaO 2: 0.86 (0.73, 0.91) vs. 0. 93 (0.90, 0.96), Hb (g/L): 142±27 vs. 156±24, respectively, all P < 0.05]. Correlation analysis revealed a significant positive correlation between SpO 2 and SaO 2 in ARDS patients residing at high altitude ( R = 0.650, P = 0.000). The P/F derived by the Rice formula was significantly and positively correlated with the P/F derived from arterial blood gas analysis ( R = 0.802, P = 0.000). The deduced P/F in mild and moderate to severe ARDS groups were all significantly correlated with the measured P/F ( R values were 0.562, 0.647, both P = 0.000). The P/F derived using the Ellis formula showed a significant positive correlation with the P/F derived from arterial blood gas analysis ( R = 0.822, P = 0.000). The deduced P/F of mild ARDS group and moderate to severe ARDS group were all positively correlated with the measured P/F ( R values were 0.556, 0.589, P values were 0.000, 0.010). There was a significant positive correlation between S/F and P/F in ARDS patients ( R = 0.828, P = 0.000), and the regression equation was S/F = 1.33 P/F+52.41. ROC curve analysis showed that S/F had some predictive value for patients with mild and moderate to severe ARDS, and area under ROC curve (AUC) and 95% confidence interval (95% CI) were 0.903 (0.829-0.977), 0.936 (0.870-1.000), both P = 0.000. When the cut-off value was 452 mmHg, S/F had a sensitivity of 100% and a specificity of 80.9% for predicting mild ARDS. When the cut-off value was 319 mmHg, S/F predicted moderate to severe ARDS with 95.1% sensitivity and 86.2% specificity. Conclusions:At high altitude, SpO 2 and SaO 2 have been correlated in patients with ARDS, and P/F derived using SpO 2 and measured P/F were significantly correlated in patients with ARDS, especially in those with moderate to severe ARDS. SpO 2 may be useful in the assessment of severity of illness in patients with ARDS at high altitude.

A lack of the complete pig proteome has left a gap in our knowledge of the pig genome and has restricted the feasibility of using pigs as a biomedical model.In this study,we developed a tissue-based proteome map using 34 major normal pig tissues.A total of 5841 unknown protein iso-forms were identified and systematically characterized,including 2225 novel protein isoforms,669 protein isoforms from 460 genes symbolized beginning with LOC,and 2947 protein isoforms with-out clear NCBI annotation in the current pig reference genome.These newly identified protein iso-forms were functionally annotated through profiling the pig transcriptome with high-throughput RNA sequencing of the same pig tissues,further improving the genome annotation of the corre-sponding protein-coding genes.Combining the well-annotated genes that have parallel expression pattern and subcellular witness,we predicted the tissue-related subcellular locations and potential functions for these unknown proteins.Finally,we mined 3081 orthologous genes for 52.7％of unknown protein isoforms across multiple species,referring to 68 KEGG pathways as well as 23 disease signaling pathways.These findings provide valuable insights and a rich resource for enhancing studies of pig genomics and biology,as well as biomedical model application to human medicine.