Objective:To detect the expression levels of long non-coding RNAs(lncRNA)in elderly patients with pulmonary tuberculosis(PTB)and those with non-tuberculous lung diseases(non-TB), and to assess the performance of these lncRNA in the differential diagnosis of PTB.Methods:A total of 300 elderly patients with suspected PTB were recruited from Beijing Chest Hospital between January 2024 and September 2024, and were further divided into the PTB group and the non-TB lung disease group based on the results of mycobacterium tuberculosis(MTB)pathogenicity testing.Peripheral blood mononuclear cells were isolated using a lymphocyte separation solution, and RNA was extracted using the TRIzol method.Nine lncRNAs, previously identified as differentially expressed in PTB through our group's microarray analysis, were selected and detected by real-time fluorescence quantitative polymerase chain reaction to evaluate the expression levels of these lncRNAs between the PTB and non-TB lung disease groups.The overall patients were randomly divided into training and validation sets in a 7∶3 ratio.Lasso regression was employed to select the characteristic variables, and a random forest algorithm was then used to construct the lncRNA diagnostic portfolio.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic performance of individual lncRNAs and the combined panel in differentiating elderly patients with PTB from those with other non-TB lung diseases.Results:A total of 201 cases were included, with 105 confirmed elderly patients diagnosed with PTB(52.2%)and 96 elderly patients suffering from non-TB lung disease(47.8%).Compared to the elderly patients with non-TB lung disease, the expression levels of ENST00000417346.1, ENST00000620744.1, lncRNA PWP1, ENST00000583184.1, lncRNA ABHD17B, ENST00000607464.1, ENST00000516057.1, and NR_003000 were significantly downregulated in the PTB patients, whereas the expression level of lncRNA BCL2L10 was significantly upregulated in the PTB patients.ROC analysis revealed that the area under the curve(AUC)for each lncRNA ranged from 0.659 to 0.848.The diagnostic panel, which included NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1 as determined by Lasso analysis, exhibited AUC values of 0.917 and 0.906 in the training and validation sets, respectively.The performance of this panel was superior to that of each individual lncRNA.Conclusions:The random forest model, which incorporates NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1, demonstrates potential in differentiating between PTB and non-TB lung diseases.

Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Objective:To detect the expression levels of long non-coding RNAs(lncRNA)in elderly patients with pulmonary tuberculosis(PTB)and those with non-tuberculous lung diseases(non-TB), and to assess the performance of these lncRNA in the differential diagnosis of PTB.Methods:A total of 300 elderly patients with suspected PTB were recruited from Beijing Chest Hospital between January 2024 and September 2024, and were further divided into the PTB group and the non-TB lung disease group based on the results of mycobacterium tuberculosis(MTB)pathogenicity testing.Peripheral blood mononuclear cells were isolated using a lymphocyte separation solution, and RNA was extracted using the TRIzol method.Nine lncRNAs, previously identified as differentially expressed in PTB through our group's microarray analysis, were selected and detected by real-time fluorescence quantitative polymerase chain reaction to evaluate the expression levels of these lncRNAs between the PTB and non-TB lung disease groups.The overall patients were randomly divided into training and validation sets in a 7∶3 ratio.Lasso regression was employed to select the characteristic variables, and a random forest algorithm was then used to construct the lncRNA diagnostic portfolio.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic performance of individual lncRNAs and the combined panel in differentiating elderly patients with PTB from those with other non-TB lung diseases.Results:A total of 201 cases were included, with 105 confirmed elderly patients diagnosed with PTB(52.2%)and 96 elderly patients suffering from non-TB lung disease(47.8%).Compared to the elderly patients with non-TB lung disease, the expression levels of ENST00000417346.1, ENST00000620744.1, lncRNA PWP1, ENST00000583184.1, lncRNA ABHD17B, ENST00000607464.1, ENST00000516057.1, and NR_003000 were significantly downregulated in the PTB patients, whereas the expression level of lncRNA BCL2L10 was significantly upregulated in the PTB patients.ROC analysis revealed that the area under the curve(AUC)for each lncRNA ranged from 0.659 to 0.848.The diagnostic panel, which included NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1 as determined by Lasso analysis, exhibited AUC values of 0.917 and 0.906 in the training and validation sets, respectively.The performance of this panel was superior to that of each individual lncRNA.Conclusions:The random forest model, which incorporates NR_003000, ENST00000607464.1, ENST00000583184.1, and ENST00000620744.1, demonstrates potential in differentiating between PTB and non-TB lung diseases.

To implement the strategy of healthy China and promote the construction of "new medicine science", it is urgent to focus on new needs and challenges to advance the reform of medical education curricula in China. Using literature research methods, we summarize the process of modern medical education curriculum reforms in the United States, and discuss the main features of the third-round reforms—introducing the concept of value-based medicine, offering health systems science courses, and promoting the curriculum system reform from the perspectives of learning time, curriculum integration, and learning methods. Based on these features, we put forward the enlightenment for the reform of medical education curricula in China.

Background::Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods::Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. Results::The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.Conclusion::The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

In order to provide scientific basis for health education and patient timely seeking behavior, this article summarizes the definition, the status quo and influencing factors of delayed on health seeking behavior of patients with obstructive sleep apnea hypopnea syndrome. Influencing factors mainly include clinical character, individual and environment.

Objective:To explore the expression of peptidyl prolyl cis-trans isomerase (Pin1) activity in peripheral blood of patients with rheumatoid arthritis (RA) and the value and correlation of T helper cell 17/regulatory cells (Th17/Treg) cells, and to analyze the effect and influence of all-transretinoic acid (ATRA) on it.Methods:① Comparing the difference of Pin1 expression and absolute counts of Th17 and Treg between RA patients before and after treatment and healthy control group, Kruskal-Wallis rank sum test was used for analysis. ② To analyze the correlation between the expression of Pin1 and its general data, activity indicators [such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score 28 joints (DAS28) scores], Th17, Treg and some cytokines in RA patients, and to use Pearson and Spearman correlation tests. ③ To analyze the difference of Pin1 expression and Th17/Treg in peripheral blood of RA patients treated with low-dose all-trans retinoic acid (10 mg twice a week) and traditional immunosuppressants such as hydroxychloroquine for 3 months respectively. Mann-Whitney U test was used for comparison between the two groups, and the difference was statistically significant with ( P<0.05). Results:① The activity of Pin1 in peripheral blood of the newly treated group of RA was [13.62(9.16, 19.42)] higher than that of the healthy control group [8.97(7.62, 11.45)]( Z=42.82 , P<0.05), and Th17 was [18.28(12.76, 24.08)] higher than that of the healthy control group [6.04(4.96, 4.96)]( Z=48.83 , P<0.05). Treg [11.06(5.31, 21.87). It was lower than that of healthy control group [40.41(24.33, 48.52)]( Z=42.21 , P<0.05). ② the activity of Pin1 in peripheral blood of RA patients was positively correlated with CRP, the number of involved joints, DAS28 score, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) ( r=0.396, P<0.05; r=0.683, P<0.05; r=0.466, P<0.05; r=0.315, P<0.05; r=0.416, P<0.05). ③ Compared with the newly treated RA group, the activity of Pin1 [6.94(5.96, 8.77), Z=42.82 , P<0.05] and Th17 7.38 decreased [7.38(3.85, 11.21), Z=48.83 , P<0.05], while Treg [40.41 (17.77, 33.47)] increased ( Z=42.21 , P<0.05). ④ Compared with the traditional medicine group, Treg [28.9(21.73, 37.36)] was higher in the retinoic acid group, and the difference was statistically significant ( Z=-2.683 , P<0.05). The activity of Pin1 was [6.23(5.58, 8.75)], but there was no statistical significance ( Z=-1.622 , P=0.104). Conclusion:Pin1 in peripheral blood of RA patients is over-expressed. Th17 is increased and Treg is decreased. ATRA combined with other traditional drugs can reduce Pin1 activity, promote Treg growth and improve disease activity of RApatients to a certain extent.