Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

Objective: To examine the effect of intracellular vesicles (IVs) and extracellular vesicles (EVs) that originated from periodontal ligament stem cells (PDLSCs) on the osteogenic differentiation of PDLSCs within a lipopolysaccharide (LPS)-simulated inflammatory microenvironment, and to provide new insights for the application of IVs in the repair and regeneration of periodontal tissue in periodontitis. Methods: Ethical approval was obtained from the institution. Human-origin PDLSCs were extracted, and the IVs and EVs from PDLSCs at the 3rd-6th passages were gathered and identified using transmission electron microscopy, nano flow cytometry (Nano FCM) analysis, and Western Blot. The 3rd-6th generations of PDLSCs were categorized into the following groups: Control group, LPS group, LPS + 100 μg/mL EVs group (LPS+EVs group), and LPS + 100 μg/mL IVs group (LPS+IVs group). The effects of the IVs and EVs on the anti-inflammatory and osteogenic differentiation of PDLSCs in an inflammatory microenvironment were assessed by using a Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot, alkaline phosphatase (ALP) staining, and alizarin red staining (ARS). Results: Under transmission electron microscopy, the IVs and EVs derived from PDLSCs displayed a double-layer membrane structure. NanoFCM analysis revealed that the average diameters of the IVs and EVs were 79.6 nm and 82.1 nm, respectively. Western Blot analysis indicated that the surface proteins CD9, CD63, and CD81 of the IVs and EVs were positively expressed, while calnexin was negatively expressed, indicating that IVs and EVs were successfully obtained. Compared with the Control group, the proliferation of PDLSCs in the LPS group was reduced, while the levels of inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the cell supernatant were increased, the mRNA expressions of osteogenic differentiation-related genes, including osteoblast-related genes runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN) of PDLSCs were reduced, the protein expressions of RUNX2 and osteopontin (OPN) were also decreased (P<0.05); compared with the LPS group, the proliferation of PDLSCs in the LPS+EVs group and LPS+IVs group were significantly increased, while the levels of IL-6, TNF-α were significantly reduced, and the mRNA expressions of RUNX2, ALP, OCN were significantly increased, the protein expressions of RUNX2 and OPN were also significantly increased (P<0.05). Further, in the inflammatory microenvironment, Compared with EVs, IVs more significantly promote the proliferation of PDLSCs, inhibit TNF-α expression, enhance the expression of RUNX2 mRNA, upregulate the expression of RUNX2 and OPN proteins, increase ALP activity, and promote the formation of mineralized nodules (P<0.05). Conclusion IVs and EVs derived from PDLSCs can boost the proliferation of PDLSCs in an inflammatory microenvironment, inhibit the expression of inflammatory factors, and advance the osteogenic differentiation of PDLSCs. The anti-inflammatory and osteogenic effects of IVs are superior to those of EVs.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely used in various products, leading to population exposure and long-term accumulation. At present, there is a lack of research on the relationships between pre-pregnancy PFAS and menstrual characteristics among women undergoing assisted reproductive technology (ART) in China. Objective To explore the relationships between pre-pregnancy PFAS exposure among women undergoing ART and menstrual characteristics prior to assisted reproductive treatment. Methods This study employed a cross-sectional research design, recruiting women undergoing ART treatment at the Reproductive Clinic of the International Peace Maternity & Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, from 2017 to 2020 as study participants. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to detect 42 types of PFAS in pre-pregnancy serum samples. Questionnaires were administered to collect information on demographic characteristics, lifestyle habits, and menstrual characteristics (average menstrual cycle length, average menstrual period length, menstrual irregularities, and menstrual bleeding volume) of women undergoing ART. Multiple linear regression, binary logistic regression, and multinomial logistic regression analyses were performed to investigate the relationships between individual PFAS exposure before pregnancy and menstrual characteristics among ART women. Additionally, weighted quantile sum (WQS) model was applied to analyze the association between PFAS mixtures and menstrual characteristics. Results In the pre-pregnancy serum samples of the study population, 15 PFAS were detected in more than 60% of the samples, including perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), perfluoro-2-propoxypropanoic acid (HFPO-DA), perfluoro-2-methoxyacetic acid (PFMOAA), and perfluoro-(3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA). Among them, PFOA had the highest median concentration of 9.160 ng·mL⁻¹. The single PFAS exposure analysis revealed a positive correlation between PFAS and irregular menstrual cycles. Specifically, for every natural-log unit (e) increase in PFOA, PFBS, or PFHxS level, the incidence of irregular menstrual cycles increased by 57%, 42%, or 39%, respectively. Most PFAS were positively correlated with the average number of menstrual cycle days, such as PFHpA (b=1.08, 95%CI: 0.11, 2.05), PFOA (b=1.69, 95%CI: 0.39, 3.00), PFBS (b=1.23, 95%CI: 0.25, 2.22), PFHxS (b=1.47, 95%CI: 0.61, 2.32), PFHpS (b=1.48, 95%CI: 0.35, 2.61), and 6:2 Cl-PFESA (b=0.90, 95%CI: 0.08, 1.72). Furthermore, levels of PFHpA (OR=1.39, 95%CI: 1.06, 1.82), PFOA (OR=1.58, 95%CI: 1.09, 2.30), PFBS (OR=1.37, 95%CI: 1.04, 1.80), PFHxS (OR=1.34, 95%CI: 1.05, 1.71), PFHpS (OR=1.53, 95%CI: 1.10, 2.14), and 6:2 Cl-PFESA (OR=1.34, 95%CI: 1.06, 1.70) were positively correlated with low menstrual blood volume, while PFOA (OR=0.40, 95%CI: 0.23, 0.71), PFHpS (OR=0.45, 95%CI: 0.29, 0.71), and HFPO-DA (OR=0.68, 95%CI: 0.48, 0.97) were negatively correlated with high menstrual blood volume. The mixed exposure model showed that PFAS mixtures were positively correlated with the average number of menstrual cycle days (b=1.60, 95%CI: 0.49, 2.71), irregular menstrual cycles (OR=1.77, 95%CI: 1.19, 2.63), and low menstrual blood volume (OR=1.59, 95%CI: 1.08, 2.35), but negatively correlated with high menstrual blood volume (OR=0.40, 95%CI: 0.22, 0.73). Conclusion Women undergoing ART in Shanghai are widely exposed to PFAS prior to conception. Exposure to PFAS before pregnancy may be related to menstrual characteristics among women seeking ART before undergoing fertility treatments, but additional data from larger populations are required to validate the findings of this study.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.