OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

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ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Objective: To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice. Methods: Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue. Results: The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05). Conclusion Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Objective To analyze the causes of infection and hemorrhage in patients with malignant obstructive jaundice(MOJ)after ultrasound-guided percutaneous transhepatic biliary drainage(PTBD).Methods A total of 420 patients with MOJ after PTBD in The Third Affiliated Hospital of Naval Medical University from Jun.2023 to Sep.2024 were enrolled,and their condition after PTBD,medical histories,preoperative examinations,and other clinical data were retrospectively analyzed.Univariate and multivariate logistic regression analyses were performed to explore the risk factors for postoperative infection and hemorrhage,and receiver operating characteristic(ROC)curves were plotted.Results Univariate logistic regression analysis showed that ascites,diuretics use,repeated punctures,hepatitis B virus(HBV)DNA and preoperative hemoglobin(Hb)levels,and neutrophil count(NE)were associated with infection after PTBD(all P＜0.05).Multivariate logistic regression analysis showed that ascites,diuretic use,repeated punctures,HBV DNA and preoperative Hb levels,and NE were the independent risk factors for infection after PTBD(all P＜0.05).Six factors including ascites,diuretics use,repeated punctures,HBV DNA and preoperative Hb levels,and NE were used to establish a prediction model.The area under the ROC curve of the model for predicting infection after PTBD was 83.1％(95％confidence interval[CI]75.5％-90.7％,P＜0.001).Univariate logistic regression analysis showed that liver tissue inflammation,ascites,preoperative peritoneal drainage,diuretics use,preoperative Hb and prealbumin(PA)levels were related to bleeding after PTBD(all P＜0.05).Multivariate logistic regression analysis showed that preoperative Hb and PA levels were independent risk factors for bleeding after PTBD.Preoperative Hb and PA levels were included to establish the prediction model.The area under the curve value for predicting bleeding after PTBD was 86.3％(95％CI 80.8％-91.9％,P＜0.001).Conclusion The prediction model for infection and hemorrhage after PTBD can facilitate early preventivon and intervention measures,thereby improving surgical safety.

Acute idiopathic maculopathy(AIM)is an inflammatory lesion of unknown cause that primarily affects the macula. It follows a unique natural course, distinct from other maculopathy, often manifesting as a sudden loss of visual acuity followed by flu-like symptoms that gradually resolve as the disease subsides. A comprehensive understanding of the unique history, multimodal imaging, and a thorough systematic examination are crucial in determining the final diagnosis of AIM. The treatment and prognosis of AIM remain controversial. Meanwhile, it presents similar clinical manifestations and pathological changes to various chorioretinopathy, posing challenges for clinical differentiation. This article provides a review of its pathogenesis, clinical symptoms, multimodal imaging features, diagnosis and differential diagnosis, treatment and prognosis, in order to reduce misdiagnosis and mistreatment while enhancing comprehension of AIM.

Objective To investigate the epidemiological characteristics and changing trend of malignant tumor death in Danjiangkou City, the water source area along the middle route of South-to-North Water Diversion Project. Methods The surveillance data of cancer death cases in Danjiangkou City from 2015 to 2022 were collected, and the mortality rate, gender mortality rate, age-specific mortality rate and the rank of cancer cause of death were calculated. Joinpoint regression model was used to analyze the trend of malignant tumor mortality and standardized mortality. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated to analyze the trend changes. Results From 2015 to 2022, a total of 6 254 deaths from malignant tumors were reported in Danjiangkou City, with a crude mortality rate of 178.57/100 000 and a standardized mortality rate of 152.77/100 000. There were 4 366 male deaths, and the crude mortality and standardized mortality were 244.70/100 000 and 212.87/100 000 , respectively. There were 1 888 female deaths, and the crude mortality rate and the standardized mortality rate were 109.89/100 000 and 92.69/100 000, respectively. The crude death rate of malignant tumors in the whole population in Danjiangkou City showed an increasing trend from 2015 to 2022, and the difference was statistically significant (AAPC=5.18%, t=4.07, P<0.05). The crude mortality rates of malignant tumors in both men and women showed an upward trend, and the differences were statistically significant (AAPC =5.56% and 4.35%, both P<0.05). The standardized mortality rates of malignant tumors in the whole population, women and men remained stable, and the differences were not statistically significant (AAPC=0.68, 1.59 and -0.74, all P>0.05). The trend analysis of age-specific mortality of malignant tumors showed that the age-specific mortality of malignant tumors in the whole population, men and women showed an increasing trend with age, and the differences were statistically significant (AAPC =9.22%, 9.40% and 8.53%, P<0.05). The mortality rate of malignant tumors in 0-, 1-, 10-, 45- and 70- age groups decreased year by year (AAPC =-79.62%, -7.19%, -65.99%, -8.88%, and -5.83%, all P<0.05). The mortality rate in the age group of over 75 years old showed an increasing trend (AAPC =12.24%, P<0.05), and the differences were statistically significant. The top 10 malignant tumor deaths in the whole population were lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal cancer , leukemia , pancreatic cancer , breast cancer , brain malignant tumor and cervical cancer, accounting for 88.49% of all malignant tumor deaths. Mortality rates in lung cancer (AAPC =6.75%), esophageal cancer (AAPC=11.24%), colorectal cancer (AAPC =12.95%), leukemia (AAPC=8.10%), pancreatic cancer (AAPC=15.11%), breast cancer (AAPC=13.11%) and brain malignancies (AAPC=11.16%) showed an increasing trend, and the differences were statistical significant (P<0.05). Conclusion Malignant tumor is the main cause of death in Danjiangkou City. The death rate increases year by year and increases with age. Lung cancer, stomach cancer and liver cancer are the main causes of death. Men and the elderly are high-risk groups of malignant tumors. Early detection and treatment of malignant tumors should be strengthened to reduce the incidence and death.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.