Objective By organizing and implementing a laboratory proficiency validation plan for air change rate testing, this study aims to explore proficiency testing approaches in laboratory animal facilities, assess the current status of relevant laboratories regarding standard application and test capabilities, standardize air change rate testing methods, and ensure the accuracy and reliability of test results. Methods From September to November 2023, the National Institutes for Food and Drug Control (NIFDC) organized a laboratory proficiency validation plan for air change rate testing in laboratory animal facilities (Plan Number: NIFDC-PT-417). The proficiency testing was conducted on-site and consisted of two parts: a written test and practical operation. The written test was open-book. True/false questions focused on participants' understanding of specific clauses in relevant standards, while application-based questions assessed their ability to handle data processing in simulated testing scenarios. The practical operation was conducted according to the relevant criteria of the China National Accreditation Service for Conformity Assessment (CNAS). Two laboratory animal rooms were prepared as proficiency testing samples using a sample splitting approach. These rooms underwent uniformity and stability testing according to CNAS requirements and were approved. Participating laboratories were required to conduct three tests on each of the two laboratory animal rooms, complete the testing and calculation of air change rate within the specified timeframe, and submit their test result reports and original records. Results A total of 27 laboratories registered and participated in the proficiency testing. All participating laboratories submitted their results within the designated timeframe, and the outcomes of all tested laboratories were rated as satisfactory. Conclusion This proficiency validation program objectively and scientifically evaluates the air change rate testing capabilities of selected domestic laboratories, effectively promoting the overall improvement of testing capabilities in the industry. It provides technical support for regulatory authorities to standardize testing institutions and offers reliable references for the purchase of testing services. Through this activity, it was identified that some laboratories need to further enhance their calibration of instruments and the utilization of calibration results. Future efforts should focus on refining related standards to improve the accuracy and reliability of testing.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.

The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.

The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

OBJECTIVE: To investigate the predictive value of early lactate/albumin ratio (LAR) combined with quick sequential organ failure assessment (qSOFA) for the 28-day prognosis of patients with sepsis caused by emergency community-acquired pneumonia (CAP). METHODS: The clinical data of patients with sepsis caused by CAP admitted to the department of emergency of Beijing Haidian Hospital from June 2021 to August 2022 were retrospectively analyzed, including gender, age, comorbidities, lactic acid (Lac), serum albumin (Alb), LAR, procalcitonin (PCT) within 1 hour, and 28-day prognosis. Patients were divided into two groups based on 28-day prognosis, and risk factors affecting patients' prognosis were analyzed using univariate and multivariate Cox regression methods. Patients were divided into two groups according to the best cut-off value of LAR, and Kaplan-Meier survival curves were used to analyze the 28-day cumulative survival of patients in each group. Time-dependent receiver operator characteristic curve (ROC curve) were plotted to analyze the predictive value of sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), and qSOFA+LAR score on the prognosis of patients with sepsis caused by CAP at 28 days. The area under the curve (AUC) was calculated and compared. RESULTS: A total of 116 patients with sepsis caused by CAP were included, of whom 80 survived at 28 days and 36 died, 28-day mortality of 31.0%. There were no statistically significant differences in age, gender, comorbidities, pH, platelet count, and fibrinogen between the survival and death groups, and there were significantly differences in blood urea nitrogen (BUN), white blood cell count (WBC), hemoglobin, Lac, Alb, PCT, D-dimer, LAR, as well as qSOFA score, SOFA score, and APACHE II score. Univariate Cox regression analyses showed that BUN, WBC, pH, Lac, Alb, PCT, LAR, qSOFA score, SOFA score, and APACHE II score were associated with mortality outcome. Multifactorial Cox regression analysis of the above variables showed that BUN, WBC, PCT, and APACHE II score were independent risk factors for 28-day death in the emergency department in patients with sepsis caused by CAP [hazard ratio (HR) were 1.081, 0.892, 1.034, and 1.135, respectively, all P < 0.05]. The best cut-off value of early LAR for predicting the 28-day prognosis of sepsis patients was 0.088, the Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of sepsis patients in the LAR ≤ 0.088 group was significantly higher than that in the LAR > 0.088 group [82.9% (63/76) vs. 42.5% (17/40), Log-Rank test: χ² = 22.51, P < 0.001]. The qSOFA+LAR score was calculated based on the LAR cut-off value and qSOFA score, and ROC curve analysis showed that the AUCs of SOFA score, APACHE II score, and qSOFA+LAR score for predicting 28-day death of patients with sepsis caued by CAP were 0.741, 0.774, and 0.709, respectively, with the AUC of qSOFA+LAR score slightly lower than those of SOFA score and APACHE II score, but there were no significantly differences. When the best cut-off value of qSOFA+LAR score was 1, the sensitivity was 63.9% and the specificity was 80.0%. CONCLUSION The qSOFA+LAR score has predictive value for the 28-day prognosis of patients with sepsis caused by CAP in the emergency department, its predictive value is comparable to the SOFA score and the APACHE II score, and it is more convenient for early use in the emergency department.
Emergency Service, Hospital/statistics & numerical data* ; Sepsis/etiology* ; Prognosis ; Community-Acquired Pneumonia/mortality* ; Organ Dysfunction Scores ; Predictive Value of Tests ; Lactic Acid/blood* ; Serum Albumin, Human/analysis* ; Biomarkers/blood* ; Retrospective Studies ; Hospital Mortality ; Kaplan-Meier Estimate ; APACHE ; Procalcitonin/blood* ; ROC Curve ; Area Under Curve ; Humans

Objective:To explore the causal relationship between gut microbiota and lung function (FEV1/FVC) using two-sample Mendelian randomization method; To explore its application in the TCM field.Methods:This was a Mendelian randomization study. The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function (FEV1/FVC) published by IEU OpenGWAS in the public database were used, and instrumental variables were extracted according to prespecified thresholds. The inverse variance weighted method (IVW) was mainly used for analysis. The results were evaluated according to the effect indicator β value and 95% CI. When the IVW method was statistically significant, further sensitivity analysis was performed. Leave-one-out test, heterogeneity test, horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results. Results:A total of 10 causal relationships between gut microbiota and lung function (FEV1/FVC) were determined using the IVW method: family. BacteroidalesS24.7group ( β=-0.029, P=0.015), family. ClostridialesvadinBB60group ( β=-0.028, P=0.040), family. Streptococcaceae ( β=-0.056, P=0.042), genus. LachnospiraceaeFCS020group ( β=0.025, P=0.029), genus. Lactococcus ( β=-0.024, P=0.038), genus. Peptococcus ( β=0.025, P=0.049), genus. RuminococcaceaeUCG011 ( β=-0.030, P=0.038), genus. Ruminococcus2 ( β=0.028, P=0.033), genus. Terrisporobacter ( β=-0.030, P=0.018), phylum. Cyanobacteria ( β=0.027, P=0.039). Leave-one-out analysis showed that the results were stable, and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed. Conclusion:The gut microbiota may play a role in the changes of lung function, which to a certain extent confirms the TCM theory of "exterior-interior relationship between the lung and large intestine", and can provide certain reference for the research direction of TCM.

Objective·To explore the correlation between serum small ubiquitin-like modifier 1(SUMO1)levels and hypertriglyceridemia in patients with type 2 diabetes mellitus(T2DM).Methods·A total of 239 newly diagnosed T2DM patients were recruited from the endocrinology clinic of Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,between September 2020 and March 2021.Among them,92 patients had hypertriglyceridemia,and 147 patients did not.Basic information and laboratory parameters were collected.The differences in serum SUMO1 levels between the two groups were analyzed.Factors influencing hypertriglyceridemia in patients with T2DM were analyzed,and the impact of serum SUMO1 levels on the risk of hypertriglyceridemia in T2DM patients was investigated.Results·Patients with T2DM and hypertriglyceridemia had significantly higher serum SUMO1 levels compared to those without hypertriglyceridemia(1 114.99 pg/mL vs 902.43 pg/mL,P＜0.001).Binary Logistic regression analysis suggested that serum SUMO1 levels(OR=1.527,95%CI 1.200?1.943),glycated hemoglobin(OR=1.202,95%CI 1.038 ? 1.391),and blood uric acid(OR=1.006,95%CI 1.003 ? 1.010)were independent risk factors for hypertriglyceridemia in patients with T2DM.After adjusting for various confounding factors and stratifying serum SUMO1 levels into quartiles,the risk of hypertriglyceridemia in T2DM patients with the highest quartile(Q4)of serum SUMO1 levels was 2.707 times higher compared to those in the lowest quartile(Q1)(95%CI 1.231?5.951).Multiple linear stepwise regression analysis revealed that female gender,waist-to-hip ratio,triglycerides and serum creatinine were independent risk factors for elevated serum SUMO1 levels.Conclusion·Serum SUMO1 level in patients with T2DM complicated with HTG is significantly higher than that in patients without HTG,and the serum SUMO1 level is an independent risk factor for T2DM complicated with HTG.