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.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: To observe the efficacy and safety of 21-day venetoclax (VEN) plus azacitidine (AZA) (21-day VA) in newly diagnosed unfit acute myeloid leukemia (AML) patients in the real-world. METHODS: The clinical data of patients with unfit-AML who received 21-day VA regimen from December 2020 to July 2024 in our center and completed at least 1 cycle of therapeutic effect assessment was retrospectively collected to analyze the safety, efficacy and its influencing factors. RESULTS: A total of 59 patients were enrolled in our study, with a median age of 67(48-87) years old. After 1 cycle of therapy, the composite complete remission (cCR) rate was 74.5%, 54.2% of cases were negative for minimal residual disease (MRD). Among them, the MRD negative rate of patients with NPM1 mutation was significantly higher than that of patients without NPM1 mutation ( P =0.032). The median follow-up of patients was 19(2-38) months, the best cCR and MRD negative rates were 78% and 64.4%, respectively, the median overall survival (OS) time was 12 months, and the median progression free survival (PFS) time was 5 months. Multivariate Cox regression analysis showed less than 4 cycles of VA chemotherapy were independent risk factor for PFS and OS ( P < 0.05). After achieving remission, anemia and thrombocytopenia improved with the increase of the number of chemotherapy cycle. CONCLUSION In real-world, 21-day VA regimen still shows significant efficacy in the treatment of newly diagnosed unfit-AML, without adversely affecting remission rate and MRD negative rate of the first cycle.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Middle Aged ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Azacitidine/therapeutic use* ; Aged, 80 and over ; Male ; Female ; Retrospective Studies ; Nucleophosmin ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Remission Induction ; Mutation ; Treatment Outcome

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Objective:To discuss the improved methods for the isolation and culture of primary chondrocytes from the neonatal rats,and to establish an efficient and economical in vitro chondrocyte culture system.Methods:The primary chondrocytes were isolated from the joints of neonatal rats and divided into overnight digestion(OD)group and rapid digestion(RD)group for separation.The chondrocytes in OD group were digested overnight by type Ⅱ collagenase,while the chondrocytes in RD group were separated by the combination of pre-digestion with physical and chemical digestion methods.The chondrocytes were cultured in modified media containing 0％(blank group 1),1％,2％,4％,and 10％fetal bovine serum(FBS),0(blank group 2),0.1,0.2,0.4,0.8,1.0,and 2.0 g·L-1 vitamin C(VC),and 0(blank group 3),0.5,1.0,2.0,4.0,8.0,10.0 μg·L-1 poly(lactic-co-glycolic acid)(PLGA)nanoparticles.The media containing different concentrations of FBS,VC,and PLGA were mixed with Dulbecco's modified Eagle's medium/nutrient mixture F-12(DMEM/F12),and were divided into related groups based on the concentrations of ingredients.Cell counter was used to count the chondrocytes in various groups and the survival rates and diameters of the chondrocytes in various groups were detected;Toluidine blue staining was used to detect the morphology of the chondrocytes in various groups;CCK-8 method was used to detect the proliferative activities of the chondrocytes in various groups;cell adhesion assay was used to detect the adhesion rates of the chondrocytes in various groups;Hoechst/propidium iodide(PI)staining was used to detect the apoptosis of the chondrocytes in various groups;MTT assay was used to detect the proliferation activities of the chondrocytes in various groups after treated with modified media.The cells were divided into DMEM/F12+10％FBS group,DMEM/F12+1％FBS group,and DMEM/F12+1％FBS+0.4 g·L-1 VC+1 μg·L-1 PLGA group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of sex-determining region Y-box 9(SOX9),collagen type Ⅱ alpha 1 chain(Col2A1),collagen type X alpha 1 chain(Col10A1),and matrix metallopeptidase 13(MMP13)mRNAs in the chondrocytes in various groups after treated with modified media;immunofluorescence staining was used to detect the expressions of type Ⅱ collagen(COL Ⅱ)and SOX9 in the chondrocytes in various groups after treated with modified media.Results:The survival rate of primary chondrocytes in OD group was lower than that in RD group,and the average cell diameter was larger than that in RD group.The primary chondrocytes in OD group were larger and spindle-shaped,and most cells exhibited pseudopodia;in RD group,the primary chondrocytes were smaller,mostly rhomboid in shape,with only a portion of the cells showing pseudopodia.The Toluidine blue staining results showed significant coloration in both groups,but the digestion time of the chondrocytes in RD group was shorter,and compared with OD group,the actual culture time of the chondrocytes was reduced by 9-13 h,and more immature morphology of the primary chondrocytes were observed.The proliferation activity of the primary chondrocytes in OD group was slow at 24 h of culture but increased at 48 h of culture,and the proliferation activity of the primary chondrocytes was significantly higher at 48 h of culture compared with 12 h of culture(P＜0.01).Compared with 12 h of culture,the proliferation rates of the primary chondrocytes in RD group were increased at 24 and 48 h of culture(P＜0.01).At 24 and 48 h of culture,compared with OD group,the proliferation rates of the primary chondrocytes in RD group were increased(P＜0.05).The number of apoptotic chondrocytes in RD group was lower than that in OD group,and no necrotic chondrocytes were observed in either group.The proliferation activities of chondrocytes of the rats were increased with the rising of FBS concentration in the culture medium.Compared with blank group 1,the proliferation activities of chondrocytes of the rats after treated with culture mediums containing 1％,2％,4％,and 10％FBS were significantly increased(P＜0.05).Compared with blank group 2,the proliferative activities of chondrocytes of the rats after treated with culture mediums containing 0.2-1.0 g·L-1 VC were significantly increased(P＜0.05),and the highest proliferation activity was found when the concentration of VC was 0.4 g·L-1(P＜0.01).Compared with blank group 3,the proliferation activities of chondrocytes of the rats after treated with culture mediums containing 1-4 μg·L-1 PLGA were significantly increased(P＜0.05),and the highest proliferation activity was found after treated with culture medium containing 1 μg·L-1 PLGA(P＜0.05).Compared with DMEM/F12+10％FBS group,the expression levels of SOX9 mRNA and Col2A1 mRNA in the chondrocytes in DMEM/F12+1％FBS group were significantly increased(P＜0.05 or P＜0.01).Compared with DMEM/F12+10％FBS group,the expression levels of SOX9 mRNA and Col2A1 mRNA in the chondrocytes in DMEM/F12+1％FBS+0.4 g·L-1 VC+1 μg·L-1 PLGA group were significantly increased(P＜0.01).The immunofluorescence staining results showed that the green fluorescence signal of COL Ⅱ and the red fluorescence signal of SOX9 were observed in some chondrocytes in DMEM/F12+10％FBS group under fluorescence microscope,and the fluorescence intensity was weak.In DMEM/F12+1％FBS group,most chondrocytes exhibited COL Ⅱ green fluorescence signal and SOX9 red fluorescence signal,and the fluorescence intensity was significantly stronger than that in DMEM/F12+10％FBS group.In DMEM/F12+1％FBS+0.4 g·L-1 VC+1 μg·L-1 PLGA group,the COLⅡ green fluorescence signal and SOX9 red fluorescence signal were found in all the chondrocytes,and the fluorescence intensity was significantly higher than those in DMEM/F12+10％FBS and DMEM/F12+1％FBS groups.The expression levels of COLⅡ and SOX9 proteins in the chondrocytes in DMEM/F12+1％FBS group were significantly higher than those in DMEM/F12+10％FBS group,and the expression levels of COL Ⅱ and SOX9 proteins in the chondrocytes in DMEM/F12+1％FBS+0.4 g·L-1 VC+1 μg·L-1 PLGA group were significantly higher than those in DMEM/F12+10％FBS group.Conclusion:The improved methods for the isolation and culture of primary chondrocytes of the rats can overcome the shortcomings of traditional methods,shorten the isolation time of primary chondrocytes,and improve the quality of in vitro culture of primary chondrocytes.

Objective To study the distribution of intestinal flora in osteoporosis patients with spleen deficiency syndrome.Methods According to the diagnostic criteria of osteoporosis of the World Health Organization(WHO)and the syndrome differentiation criteria of spleen deficiency syndrome in traditional Chinese medicine(TCM),26 healthy attenders with normal bone mass while without spleen deficiency were selected from the population visited Shunde Hospital of Guangzhou University of Chinese Medicine from January 2022 to September 2023 as the normal bone mass group,23 patients with bone mass reduction and spleen deficiency syndrome served as decreased bone mass with spleen deficiency group(shorten as DBM-SD group),and 69 patients with osteoporosis and spleen deficiency syndrome diagnosis were osteoporosis with spleen deficiency group(shorten as OS-SD group).A total of 118 attenders were enrolled in the analysis.The gender,age,body height,body weight,and body mass index(BMI)of the subjects were collected.The bone mineral density(BMD)and serum levels of calcium and alkaline phosphatase(ALP)of the subjects were measured.Stools were collected for the detection of the sequence of the 16SrRNA V3-V4 region,and the sequencing results were given species annotation,and then the correlation of community difference between groups and BMD with the intestinal flora was explored.Results(1)There were significant differences in the relative abundance of intestinal flora between the normal bone mass group and the OS-SD group:differences were shown in Firmicutes(t=2.490,P=0.016),Verrucomicrobia(t=2.180,P=0.003)and Fusobacteria(t=2.270,P=0.026),in Acidobacteria(t=3.003,P=0.003),Lactobacillus(t=3.150,P=0.002)and Bifidobacterium(t=7.248,P=0.001),and in Fecalibacterium(t=2.810,P=0.006)and Rothia(t=2.810,P=0.006).(2)There were significant differences in the relative abundance of intestinal flora between the normal bone mass group and the DBM-SD group:differences were shown in Lactobacillus(t=3.841,P=0.001)and Bifidobacterium(t=2.712,P=0.01),and in Faecalibacterium(t=2.466,P=0.017).(3)There were significant differences in the relative abundance of intestinal flora between the OS-SD group and DBM-SD group:differences were shown in Firmicutes(t=2.321,P=0.025),Bacteroidetes(t=0.393,P=0.020)and Verrucomicrobia(t=3.109,P=0.031).(4)The results of logistic regression analysis showed that in the OS-SD group,lumbar BMD was negatively correlated with Lactobacillus(R=0.355,P=0.003)and Bifidobacterium(R=0.366,P=0.002),positively correlated with Bacteroides(R=0.245,P=0.042),and was negatively correlated Rothia(R=0.330,P=0.006).Conclusion Some bacteria in the intestinal flora are related to the BMD of osteoporosis patients with spleen deficiency syndrome,and significant difference exists in the distribution of intestinal flora between the normal bone mass group and the OS-SD group.The results will provide a theoretical basis for the prevention and treatment of osteoporosis patients with spleen deficiency syndrome from the perspective of the changes of intestinal flora.

Objective Objective To investigate the clinical characteristics of a hereditary protein S deficiency family with acute cerebral infarction and to analyze the mutational characteristics of the PROS1 gene.Methods Clinical data of the proband and their immediate family members were collected,blood samples were obtained,protein S activity levels were analyzed,and PROS1 genes were sequenced.Results The family consisted of three generations and eight direct relatives.Among them,three individuals were diagnosed with hereditary protein S deficiency.The proband and his brother suffered from acute cerebral infarction,while the other family members had not yet experienced thrombotic events.The protein S activity levels of the proband,his brother and their mother were 16.8%,38.0%and 31.8%,respectively,while the father's levels were normal.Gene test found that the proband,his brother and their mother possessed a heterozygous variant c.1323G>A in exon 11 in PROS1,while his father exhibited the wild-type.Conclusions The study reports the identification of a familial protein S deficiency,which is attributed to a novel synonymous mutation(c.1323G>A)in the PROS1 gene.This genetic alteration may lead to ischemic stroke in youth.