Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective To investigate the role of homocysteine(Hcy)in the pathogenesis of irritable bowel syn-drome(IBS)and its effects on intestinal motility,visceral hypersensitivity,and barrier function.Methods Clinical cohorts and animal models were combined for this study.Clinically,fifteen IBS patients meeting Rome Ⅲcriteria and 15 control individuals were enrolled to detect fecal Hcy levels and their correlation with symptoms.As for animal experiments,water avoidance stress(WAS)and 2,4,6-trinitrobenzene sulfonic acid(TNBS)chemical induction were utilized to establish IBS rat and mouse models,combined with a high-methionine diet(HMD)to simulate hyperhomocysteinemia.IBS symptoms were evaluated through fecal water content,carmine red intestinal transit time,and visceral hypersensitivity scores.Immune-fluorescence and Western blot were used to detect intes-tinal epithelial tight junction proteins.Serum and fecal Hcy concentrations were measured to assess Hcy levels.Statistical analyses included t-tests and One-way Anova.Results Fecal Hcy level in IBS patients were signifi-cantly higher than those in the healthy control group which demonstrated a positive correlation with defecation fre-quency(P＜0.01).In animal models,the combination of TNBS administration and a high-methionine diet markedly elevated serum and fecal Hcy levels in mice,while synergistically exacerbated intestinal motility disor-ders and visceral hypersensitivity.In vitro experiments showed that Hcy treatment down-regulates the expression of tight junction proteins in human colon cancer cell line(Caco-2).Conclusions Hcy plays an important role in the pathogenesis of IBS by impairing intestinal barrier function and enhancing visceral hypersensitivity,and it may serve as a potential new target for the treatment of IBS.

Objective:To successfully isolate and identify patient-derived ovarian cancer stem cells(OCSC),and to investigate the expression of monocarboxylate transporter 2(MCT2)in OCSC and its effects on the stem-ness and invasiveness of OCSC.Methods:Primary ovarian cancer cells were obtained,and OCSC models were established through screening and culturing.The screened OCSC were designated as the OCSC group,while the adherent primary cells were employed as control group 1.Two MCT2 inhibition constant Ki-specific inhibitors,namely[α-cyano-4-hydroxycinnamic acid(CHC)and ARC155858],were utilized for intervention,setting up the CHC inhibition group and the ARC155858 inhibition group.The group with only the solvent DMSO added was set respectively as CHC control group 2 and ARC 155858 control group 2.Flow cytometry and qRT-PCR were used for identification of OCSC markers.The expression levels and locations of MCT2 were detected by qRT-PCR and immunofluorescence staining.The effects of MCT2 inhibitors on the stemness and invasiveness of OCSC were verified using sphere formation assays and Matrigel invasion assays.Results:A primary OCSC cell bank consis-ting of 23 clinical models was established.qRT-PCR results showed that the expression level of MCT2 in OCSC group(5.78±3.55 and 122.89±19.90)was significantly higher than that in the control group 1(1.01±0.10 and 1.55±1.45),the difference is statistically significant(P＜0.05).Fluorescent quantitative analysis confirmed that MCT2 expression in OCSC group was higher than that in the control group 1(6.79±0.67 AU vs.2.49±1.78 AU,P=0.030).Treatment with MCT2 inhibitors in OCSC resulted in a significant reduction in sphere formation in the CHC inhibition group(6.00±2.17 spheres/1000 cells)compared to the CHC control group 2(14.62±3.07 spheres/1000 cells),the difference is statistically significant(P＜0.01),and in the ARC155858 inhibition group(11.00±4.42 spheres/1000 cells)compared to the ARC155858 control group 2(23.90±4.72 spheres/1000 cells),the difference is statistically significant(P＜0.01).In Matrigel invasion assays,the invasiveness in the in-hibitor group was significantly lower than in the control group(ARC155858:inhibitor group 10.20±5.98 cells vs.control group 67.20±28.96 cells,P＜0.05).Conclusions:This study observed that MCT2 expression significantly increased in OCSC.Inhibition of MCT2 significantly reduces the stemness and invasiveness of OCSC,providing potential research directions for targeted therapy of ovarian cancer.

Objective:To successfully isolate and identify patient-derived ovarian cancer stem cells(OCSC),and to investigate the expression of monocarboxylate transporter 2(MCT2)in OCSC and its effects on the stem-ness and invasiveness of OCSC.Methods:Primary ovarian cancer cells were obtained,and OCSC models were established through screening and culturing.The screened OCSC were designated as the OCSC group,while the adherent primary cells were employed as control group 1.Two MCT2 inhibition constant Ki-specific inhibitors,namely[α-cyano-4-hydroxycinnamic acid(CHC)and ARC155858],were utilized for intervention,setting up the CHC inhibition group and the ARC155858 inhibition group.The group with only the solvent DMSO added was set respectively as CHC control group 2 and ARC 155858 control group 2.Flow cytometry and qRT-PCR were used for identification of OCSC markers.The expression levels and locations of MCT2 were detected by qRT-PCR and immunofluorescence staining.The effects of MCT2 inhibitors on the stemness and invasiveness of OCSC were verified using sphere formation assays and Matrigel invasion assays.Results:A primary OCSC cell bank consis-ting of 23 clinical models was established.qRT-PCR results showed that the expression level of MCT2 in OCSC group(5.78±3.55 and 122.89±19.90)was significantly higher than that in the control group 1(1.01±0.10 and 1.55±1.45),the difference is statistically significant(P＜0.05).Fluorescent quantitative analysis confirmed that MCT2 expression in OCSC group was higher than that in the control group 1(6.79±0.67 AU vs.2.49±1.78 AU,P=0.030).Treatment with MCT2 inhibitors in OCSC resulted in a significant reduction in sphere formation in the CHC inhibition group(6.00±2.17 spheres/1000 cells)compared to the CHC control group 2(14.62±3.07 spheres/1000 cells),the difference is statistically significant(P＜0.01),and in the ARC155858 inhibition group(11.00±4.42 spheres/1000 cells)compared to the ARC155858 control group 2(23.90±4.72 spheres/1000 cells),the difference is statistically significant(P＜0.01).In Matrigel invasion assays,the invasiveness in the in-hibitor group was significantly lower than in the control group(ARC155858:inhibitor group 10.20±5.98 cells vs.control group 67.20±28.96 cells,P＜0.05).Conclusions:This study observed that MCT2 expression significantly increased in OCSC.Inhibition of MCT2 significantly reduces the stemness and invasiveness of OCSC,providing potential research directions for targeted therapy of ovarian cancer.

BackgroundPatients with depressive disorder commonly experience sleep disturbances. Previous studies have indicated that group exercise therapy is beneficial in alleviating depressive symptom among patients with depressive disorder. However， there is a lack of research on the impact of group exercise therapy on improving sleep quality in patients with depressive disorder. ObjectiveTo explore the impact of group exercise therapy on sleep quality in patients with acute mild-to-moderate depression during the acute phase， so as to provide references for clinically improving the sleep quality of patients with mild to moderate depressive disorder during the acute phase. MethodsFrom December 2018 to July 2021， patients with mild-to-moderate depressive disorder during the acute phase （n=40）， who met the diagnostic criteria for depressive disorder according to International Classification of Diseases， tenth edition （ICD-10） ，were recruited from the outpatient clinic of Beijing Anding Hospital， Capital Medical University. All participants underwent an 8-week moderate-intensity group exercise therapy program comprising three sessions per week， each lasting 60 minutes. Assessments were conducted at baseline and after 2， 4， 6 and 8 weeks of intervention using Visual Analogue Scale （VAS）， Hamilton Depression Scale-17 item （HAMD-17） and Pittsburgh Sleep Quality Index （PSQI）. The reduction scores at each time point relative to baseline treated as the dependent variables， time as the independent variable， baseline scores as covariates， with time as a fixed effect and baseline values as random effects. Data were analyzed using a linear mixed-effects model. ResultsThe PSQI scores of patients at baseline， 2， 4 ， 6 and 8 weeks after the intervention were （10.62±5.12）， （9.07±3.58）， （7.39±3.66）， （6.54±3.84） and （5.50±3.41）， respectively. The results of linear mixed effect model analysis showed that after 2， 4， 6 and 8 weeks of intervention， patients scored lower than baseline， with statistically significant differences observed in all cases （P<0.01）. The HAMD-17 sleep fcctor scores at baseline， 2， 4， 6 and 8 weeks were （2.25±1.56）， （2.06±1.49）， （1.36±1.27）， （1.22±1.46） and （0.97±1.34）， respectively. The results of linear mixed effects model analysis showed that the HAMD-17 sleep factor scores of 4， 6 and 8 weeks of intervention were lower than that of baseline， and the difference was statistically significant （P<0.05 or 0.01）. The VAS scores at baseline， 2， 4， 6 and 8 weeks after the intervention were （3.18±2.17）， （4.74±2.22）， （6.01±2.31）， （6.54±2.16） and （7.90±1.64）， respectively. The results of linear mixed effect model analysis showed that VAS scores of 2， 4， 6 and 8 weeks of intervention were higher than baseline，and the difference was statistically significant （P<0.01）. ConclusionGroup exercise therapy may improve sleep quality and alleviate depressive symptoms in patients with mild-to-moderate depressive disorder during the acute phase. ［Funded by National Key Research and Development Plan Project （number， 2016YFC1307200）； Beijing Municipal Hospital Scientific Research and Cultivation Plan Project （number， PX2024070）］

Objective This clinical study aimed to evaluate the accuracy of a fully digital technique for mea-suring sagittal condylar inclination(SCI),as well as vali-dating whether differences existed between the left and right SCI values of the same participant,to provide a ref-erence for clinical practice.Methods Ten participants with good occlusal relationship and normal temporomandibular joint were recruited.Three methods were used to mea-sure the SCI values of the participants,namely,A(mechanical facebow transferring and mechanical articulator-based measuring method with physical protrusive interocclusal registration),B(face scan-based virtual facebow and virtual ar-ticulator-based measuring method with digital protrusive interocclusal registration),and C(jaw motion tracking system-based measuring method).With the group subjected to methods A and C as the control,the SCI values obtained by the three methods were statistically analyzed.The left and right SCI values of the same participant were also compared.Re-sults The left and right SCI values measured by method A were 41.70°±7.09° and 42.80°±8.62°,those by method B were 35.09°±12.49° and 37.63°±12.10°,and those by method C were 39.43°±8.72° and 38.45°±6.91°.No significant dif-ference existed among the SCI values measured by the three methods(P>0.05).Meanwhile,no statistical difference existed between the SCI values on the left and right sides of the same participant(P>0.05).Conclusion The accuracy of the virtual facebow and digital protrusive occlusal registration based SCI measuring method was the same as that of mechanical facebow based and jaw motion tracking system-based methods.The SCI values on the left and right sides of the same participant were similar.Clinically,an appropriate SCI measurement and setting strategy can be selected based on the actual situations.

Objective This clinical study aimed to as-sess the trueness of three intraoral scanners for the recor-ding of the maximal intercuspal position(MIP)to provide a reference for clinical practice.Methods Ten participants with good occlusal relationship and healthy temporomandibular joint were recruited.For the control group,facebow transferring procedures were performed,and bite registrations at the MIP were used to transfer maxillary and mandibular casts to a mechanical articulator,which were then scanned with a laboratory scanner to obtain digital cast data.For the experimental groups,three intraoral scanners(Trios 3,Carestream 3600,and Aoralscan 3)were used to obtain digital casts of the participants at the MIP following the scanning workflows endorsed by the corresponding manufacturers.Sub-sequently,measurement points were marked on the control group's digital casts at the central incisors,canines,and first molars,and corresponding distances between these points on the maxillary and mandibular casts were measured to calcu-late the sum of measured distances(DA).Distances between measurement points in the incisor(DI),canine(DC),and first molar(DM)regions were also calculated.The control group's maxillary and mandibular digital casts with the added mea-surement points were aligned with the experimental group's casts,and DA,DI,DC,and DM values of the aligned control casts were determined.Statistical analysis was performed on DA,DI,DC,and DM obtained from both the control and ex-perimental groups to evaluate the trueness of the three intraoral scanners for the recording of MIP.Results In the con-trol group,DA,DI,DC,and DM values were(39.58±6.40),(13.64±3.58),(14.91±2.85),and(11.03±1.56)mm.The Trios 3 group had values of(38.99±6.60),(13.42±3.66),(14.55±2.87),and(11.03±1.69)mm.The Carestream 3600 group showed values of(38.57±6.36),(13.56±3.68),(14.45±2.85),and(10.55±1.41)mm,while the Aoralscan 3 group had val-ues of(38.16±5.69),(13.03±3.54),(14.23±2.59),and(10.90±1.54)mm.Analysis of variance revealed no statistically sig-nificant differences between the experimental and control groups for overall deviation DA(P=0.96),as well as local devi-ations DI(P=0.98),DC(P=0.96),and DM(P=0.89).Conclusion With standardized scanning protocols,the three intra-oral scanners demonstrated comparable trueness to traditional methods in recording MIP,fulfilling clinical requirements.

Endometriosis, a heterogeneous, inflammatory, and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus, affects approximately 5-10% of reproductive-age women, causing chronic pelvic pain and reduced fertility. Although the etiology of endometriosis is still elusive, emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris. Peritoneal macrophages and natural killer (NK) cells exhibit deficient cytotoxicity in the endometriotic microenvironment, leading to inefficient eradication of refluxed endometrial fragments. In addition, the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation, which contribute to endometriosis development. Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis, therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression. Here, we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment, focusing on their interactions with microbiota and endocrine and nervous systems, and how these interactions contribute to the etiology and symptomology of endometriosis.
Female ; Humans ; Endometriosis/metabolism* ; Killer Cells, Natural/metabolism* ; T-Lymphocytes/metabolism* ; Estrogens ; Endometrium/metabolism*

Objective:To investigate the expression of PDLIM3 in the ectopic and orthotopic endometrium of endometriosis(EMT)patients,as well as in healthy endometrium,and to explore its relationship with clinical signifi-cance.Methods:Bioinformatics analysis based on the Gene Expression Omnibus(GEO)database was conduc-ted,and a prospective cohort study was undertaken,involving 58 EMT patients treated at West China Second Hospital of Sichuan University and 27 patients with other benign gynecological diseases as the control group from December 2019 to July 2020.Ectopic and orthotopic endometrium samples were obtained from EMT patients,and normal control samples were obtained from patients with other benign gynecological diseases.Real-time quantita-tive polymerase chain reaction(qPCR),western blot,and immunohistochemistry were utilized to investigate PD-LIM3 expression in various tissue samples.Clinical parameters were analyzed to determine the correlation be-tween PDLIM3 and clinical features.Results:Compared to orthotopic endometrial tissues of EMT patients and normal endometrial tissues of control subjects,the mRNA(F =46.05,P<0.05)and protein(F =238.6,P<0.05)expression levels of PDLIM3 in ectopic endometrial lesions were significantly upregulated.The average optical density(AOD)of PDLIM3 protein obtained through immunohistochemical experiments in ectopic endometrial le-sions showed a positive correlation with the degree of dysmenorrhea(r =0.86,P<0.05)and CA 125 level(r = 0.41,P<0.05)in EMT patients.But no obvious correlation was found between the expression level of PDLIM3 and disease stage,menstrual volume,and CA199 level(P>0.05).Conclusions:The expression level of PDLIM3 in endometriosis lesions was significantly upregulated and correlated with the degree of dysmenorrhea and serum CA125 level.These findings suggest that PDLIM3 may play a significant role in the development and progression of endometriosis and could serve as a potential therapeutic target.

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP⁺ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.