Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Metabolic dysfunction-associated fatty liver disease （MAFLD） has the core pathological feature of liver lipid accumulation， which is closely associated with the factors such as lipid metabolism disorders， insulin resistance， and inflammation， and abnormal lipid accumulation can exacerbate these factors and further intensify lipid accumulation， thereby forming a vicious circle. Huanglian Wendan decoction has shown unique advantages in alleviating lipid accumulation associated with MAFLD， but its mechanism of action is relatively complex. With reference to the latest literature evidence， this article systematically summarizes the mechanism of action of Huanglian Wendan decoction in improving lipid accumulation by regulating lipid metabolism， ameliorating insulin resistance， and exerting an anti-inflammatory effect， as well as the pharmacological actions of related active components， in order to provide a theoretical basis for the clinical application of Huanglian Wendan decoction in the management of MAFLD.

Background and purpose:Salivary duct carcinoma(SDC)is a group of rare and highly heterogeneous diseases.It predominantly arises in the parotid glands of middle-aged and elderly males,with high rates of recurrence and metastasis,as well as a poor prognosis.Currently,there is a lack of clinical data on SDC.This study aimed to evaluate the clinical characteristics of SDC patients and explore high-risk factors affecting prognosis,so as to provide clinical references for physicians.Methods:Clinical data of patients with primary SDC who were admitted to Tianjin Medical University Cancer Institute and Hospital and Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine from 2012 to 2024,were collected retrospectively.Inclusion criteria:① patients diagnosed with primary SDC;② availability of American Joint Committee on Cancer(AJCC)staging data.Exclusion criteria:① concurrent other malignant tumors;② incomplete or missing medical records;③ death due to non-SDC causes;④ duplicate cases from the two participating hospitals.Data retrieved encompassed epidemiological information(gender,age)and clinical details(time of diagnosis,tumor characteristics,treatment regimen,recurrence and metastasis status,and pathological data).Survival analysis was performed using the Kaplan-Meier method,and factors related to prognosis were explored through univariate COX proportional hazards regression model analysis.This study was approved by the Ethics Committee of Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine(ethics number:PH2023-B-016),and patient informed consent was waived.Results:A total of 87 patients with primary SDC were included in this study,among whom 77%were male,69%had primary lesions in the parotid gland,29.9%in the submandibular gland,and one patient had a primary lesion in the minor salivary gland of the nasal cavity.49.3%of the patients had concurrent cervical lymph node metastasis.The median overall survival(OS)of the entire group was 31.2 months,the median progression-free survival(PFS)was 20.3 months,and the 5-year OS rate was 52.6%.The 5-year OS rate for tumors originating from the parotid gland was 60%,which was better than the 32.9%for those originating from the submandibular gland.Among the 85 patients who received surgical treatment,65.9%underwent both resection of the primary tumor and neck dissection.Postoperative radiotherapy was administered to 49 patients.During the follow-up period,46%of the patients developed recurrence or metastasis,with lung and bone metastases being the most common.The median OS and local progression-free time in the postoperative radiotherapy group were significantly longer compared with those in the group without radiotherapy,however,the difference was not statistically significant.Conclusion:SDC is a malignant and aggressive disease that predominantly occurs in the parotid glands of middle-aged and elderly males,with a high rate of lymph node metastasis and poor prognosis.Clinically,it is recommended that patients with SDC undergo radical resection of the primary lesion and cervical lymph node dissection,combined with postoperative adjuvant radiotherapy.Targeted therapy and immunotherapy are worthy of further exploration.

Background and purpose:Salivary duct carcinoma(SDC)is a group of rare and highly heterogeneous diseases.It predominantly arises in the parotid glands of middle-aged and elderly males,with high rates of recurrence and metastasis,as well as a poor prognosis.Currently,there is a lack of clinical data on SDC.This study aimed to evaluate the clinical characteristics of SDC patients and explore high-risk factors affecting prognosis,so as to provide clinical references for physicians.Methods:Clinical data of patients with primary SDC who were admitted to Tianjin Medical University Cancer Institute and Hospital and Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine from 2012 to 2024,were collected retrospectively.Inclusion criteria:① patients diagnosed with primary SDC;② availability of American Joint Committee on Cancer(AJCC)staging data.Exclusion criteria:① concurrent other malignant tumors;② incomplete or missing medical records;③ death due to non-SDC causes;④ duplicate cases from the two participating hospitals.Data retrieved encompassed epidemiological information(gender,age)and clinical details(time of diagnosis,tumor characteristics,treatment regimen,recurrence and metastasis status,and pathological data).Survival analysis was performed using the Kaplan-Meier method,and factors related to prognosis were explored through univariate COX proportional hazards regression model analysis.This study was approved by the Ethics Committee of Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine(ethics number:PH2023-B-016),and patient informed consent was waived.Results:A total of 87 patients with primary SDC were included in this study,among whom 77%were male,69%had primary lesions in the parotid gland,29.9%in the submandibular gland,and one patient had a primary lesion in the minor salivary gland of the nasal cavity.49.3%of the patients had concurrent cervical lymph node metastasis.The median overall survival(OS)of the entire group was 31.2 months,the median progression-free survival(PFS)was 20.3 months,and the 5-year OS rate was 52.6%.The 5-year OS rate for tumors originating from the parotid gland was 60%,which was better than the 32.9%for those originating from the submandibular gland.Among the 85 patients who received surgical treatment,65.9%underwent both resection of the primary tumor and neck dissection.Postoperative radiotherapy was administered to 49 patients.During the follow-up period,46%of the patients developed recurrence or metastasis,with lung and bone metastases being the most common.The median OS and local progression-free time in the postoperative radiotherapy group were significantly longer compared with those in the group without radiotherapy,however,the difference was not statistically significant.Conclusion:SDC is a malignant and aggressive disease that predominantly occurs in the parotid glands of middle-aged and elderly males,with a high rate of lymph node metastasis and poor prognosis.Clinically,it is recommended that patients with SDC undergo radical resection of the primary lesion and cervical lymph node dissection,combined with postoperative adjuvant radiotherapy.Targeted therapy and immunotherapy are worthy of further exploration.

Objective:To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of N-desalkylquetiapine, hydroxybupropion, N-desmethyl clozapine, N-desmethyl clomipramine, O-desmethyvenlafaxine and dehydro aripiprazole in human plasma.Methods:In June 2023, plasma samples were treated with methanol-acetonitrile (volume ratio of 1∶1) for protein precipitation and then detected by LC-MS/MS. It was separated by C18 column and eluted with 5 mmol/L ammonium acetate water and 5 mmol/L ammonium acetate methanol solution as mobile phase gradient. The metabolites of six psychotropic drugs were qualitatively and quantitatively by using electrospray positive ion multi-reactive ion monitoring scanning mode (MRM) .Results:The linear relationships of six psychotropic drug metabolites were good in the concentration range of 2-100 μg/L. The linear correlation coefficients were 0.9971-0.9999, the limits of quantification of the method were 0.10-6.00 μg/L, and the inter-and intra-day precision were 4.6%-9.8% and 1.5%-8.6%, with the recoveries of the spiked standards ranged from 90.0% to 106.1%.Conclusion:The LC-MS/MS method for the determination of metabolites of six psychotropic drugs in human plasma is simple, rapid and sensitive, and can be used for the qualitative and quantitative determination of metabolites in plasma samples of patients suspected of psychotropic drug poisoning.

Objective To investigate the effects of Fuzheng Touxie Prescription on pulmonary injury of Pseudomonas aeruginosa pneumonia(PAP)in rats;To discuss its possible mechanism.Methods A total of 36 SD rats were divided into blank group,model group,piperacillin group and Fuzheng Touxie Prescription low-,medium-and high-dosage groups according to random number table method,with 6 rats in each group.Except for the blank group,0.1 mL of Pseudomonas aeruginosa suspension with a concentration of 3×109 CFU/mL was injected through oral catheterization.In the blank group,0.1 mL sterile saline was injected by oral catheterization.Fuzheng Touxie Prescription low-,medium-and high-dosage groups were gavaged 1.6 mL of Fuzheng Touxie Prescription solution with the concentration of 0.43,0.86 and 1.73 g/mL respectively,the blank group and model group were gavaged equal volume of distilled water,piperacillin group was intraperitoneal injected 0.53 mL piperacillin tazobactam sodium solution with a concentration of 0.11 g/mL,once a day,for consecutive 3 days.HE staining was used to observe the pathological changes of lung tissue,lung injury score was performed and bronchial wall thickness was measured,flow cytometry was used to detect Th17/Treg ratio in peripheral blood,the serum contents of RORγt,FoxP3,TGF-β and inflammatory factors TNF-α,IL-6 and IL-10 were detected by ELISA,the mRNA expression of RORγt,FoxP3 and inflammatory factors in lung tissue were detected by RT-qPCR,the protein expressions of RORγt,FoxP3 and inflammatory factors in lung tissue were detected by Western blot.Results Compared with the blank group,a large amount of inflammatory cell infiltration was observed in lung tissue of the model group rats,accompanied by bronchial wall hyperplasia,alveolar dilation,interstitial edema,and a significant increase in lung injury score and bronchial wall thickness(P<0.01),the proportion of Th17 in peripheral blood increased(P<0.01),the proportion of Treg decreased(P<0.01),and the Th17/Treg ratio increased(P<0.05),the contents of serum RORγt,TNF-α,TGF-β and IL-6 significantly increased(P<0.01),the contents of FoxP3 and IL-10 significantly decreased(P<0.01),the mRNA and protein expressions of RORγt,TNF-α,TGF-β and IL-6 in lung tissue significantly increased(P<0.01),while the mRNA and protein expressions of FoxP3 and IL-10 significantly decreased(P<0.01).Compared with the model group,the alveoli of rats in each treatment group were relatively intact and the structure was clearer,inflammatory cell infiltration,pulmonary interstitial edema and congestion were reduced,and lung injury scores and bronchial wall thickness were reduced(P<0.05,P<0.01),the proportion of Th17 in peripheral blood decreased(P<0.05),the proportion of Treg increased(P<0.05),and the Th17/Treg ratio decreased(P<0.05)in Fuzheng Touxie Prescription high-dosage group and piperacillin group,the contents of serum RORγt,TNF-α,TGF-β and IL-6 significantly decreased in Fuzheng Touxie Prescription medium-and high-dosage groups and piperacillin group(P<0.05,P<0.01),the contents of FoxP3 and IL-10 significantly increased(P<0.05,P<0.01),the mRNA and protein expressions of RORγt,TNF-α,TGF-β and IL-6 in lung tissue significantly decreased(P<0.05,P<0.01),the mRNA and protein expressions of FoxP3 and IL-10 significantly increased(P<0.05,P<0.01).Conclusion Fuzheng Touxie Prescription can improve pulmonary inflammatory symptoms,reduce the level of inflammatory factors and increase the level of anti-inflammatory factors in PAP rats.The mechanism may be through the TGF-β/RORγt/FoxP3 pathway to regulate immune balance.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

Objective : To investigate the effectiveness of an extraoral guide plate system targeting the superior and inferior heads of the lateral pterygoid muscle in improving the accuracy of injection therapy for anterior disc displacement (ADD) of the temporomandibular joint (TMJ) with lateral pterygoid myalgia, and to provide a reference for precise clinical treatment. Methods: With approval from the institutional medical ethics committee and informed consent from patients, spiral CT scans were performed on seven patients with ADD accompanied or not accompanied by lateral pterygoid myalgia to acquire craniofacial data. Mimics 21.0 software was used to reconstruct three-dimensional craniofacial structures, identify attachment points of the superior and inferior heads of the lateral pterygoid muscle, and design dual injection paths along with a retention system. Personalized templates were fabricated using digital light procession-based 3D printing. Under the guide plate, a single targeted injection of 20 U of botulinum toxin type A (BTX-A) was administered into both the superior and/or inferior heads of the lateral pterygoid muscle. Immediate postoperative CT scans were conducted to compare actual needle placement with preoperative plans. Pain was assessed using the visual analogue scale (VAS) at 3 days and 1, 2, and 4 weeks postoperatively. Joint clicking was recorded at 2 and 4 weeks, and complications were monitored throughout the duration of the study. Results : A total of 15 sites in 7 patients were injected into the upper / lower head of the lateral pterygoid muscle under the guidance of the guide plate. Under the guide plate, all of the injections achieved an angular deviation within 2.5° (superior head: 2.49° ± 0.17°, inferior head: 2.31° ± 0.16°) and a needle tip positional deviation within 2 mm [superior head: (1.96 ± 0.25) mm, inferior head: (1.65 ± 0.21) mm]. The significant pain improvement rate (defined as ≥3-point reduction in VAS score) increased from 60% (9/15) at day 3 to 85% (13/15) at 2 weeks post-operation, stabilizing at 86.7% (13/15) at 4 weeks post-operation. Joint clicking improvement rates reached 72% (11/15) at 2 weeks post-operation and 75% (11/15) at 4 weeks post-operation. Regarding safety, only one case of injection site swelling and one case of transient paresthesia were observed; both resolved spontaneously within a short period of time. No neurovascular injury events occurred. Conclusion CT-guided guide plate achieves precise targeting design to minimize injection errors in the lateral pterygoid muscle. This technology is effective and safe, and it can provide an anatomically specific and operationally versatile targeted therapy for temporomandibular disorders.

BACKGROUND: The objective of this study was to investigate the potential link between myopia in adolescents and exposure to per- and polyfluoroalkyl substances (PFASs). METHODS: This investigation included 1971 subjects with accessible PFAS level data, myopia status, and associated variables from four cycles of the National Health and Nutritional Examination Survey (NHANES). The investigation focused on specific PFAS compounds found in the serum, including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), chosen for their frequent detection. Owing to the skewed nature of the PFAS level data, the PFAS levels were log-transformed (Ln-PFAS) prior to analysis. Logistic regression, restricted cubic spline modeling, subgroup analysis, and sensitivity analysis were used to examine the associations between exposure to PFASs and the onset of myopia. RESULTS: PFOA levels were significantly associated with myopia risk (OR: 1.33; 95% CI: 1.05-1.69; P = 0.019). More specifically, with respect to the first quartile, the second quartile (OR_Q2: 1.69; 95% CI: 1.16-2.46; P = 0.007), third quartile (OR_Q3: 1.45; 95% CI: 1.03-2.03; P = 0.035), and highest quartile (OR_Q4: 1.58; 95% CI: 1.12-2.21; P = 0.010) of participants presented with increased myopia risk. Mediation analysis revealed that PFOA and myopia risk were partially mediated by serum albumin (ALB), with a mediation percentage of 22.48% (P = 0.008). A nonlinear inverted U-shaped relationship was identified between the level of PFOA and myopia risk (P for nonlinearity = 0.005). CONCLUSION Our findings suggest a potential link between exposure to PFOA and the likelihood of myopia development in young individuals and a mediating effect of serum ALB on this relationship. Notably, PFOA was identified as a key PFAS significantly contributing to the observed link between PFAS exposure and myopia risk. The potential threat of PFOA to myopia should be examined further.
Humans ; Fluorocarbons/adverse effects* ; Myopia/blood* ; Adolescent ; Male ; Female ; Prevalence ; Environmental Exposure/adverse effects* ; Nutrition Surveys ; Environmental Pollutants/adverse effects* ; United States/epidemiology* ; Alkanesulfonic Acids/blood* ; Caprylates/blood* ; Serum Albumin/metabolism* ; Child ; Sulfonic Acids