Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Efficacy and safety of tranexamic acid in the treatment of gastric cancer complicated with upper gastrointestinal bleeding.

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) in preventing upper gastrointestinal (GI) bleeding in patients with gastric cancer. METHODS: The clinical data of patients with gastric cancer complicated with acute non-operative GI bleeding treated in the Fourth Hospital of Hebei Medical University from 2020 to 2022 were collected and retrospectively analyzed. The survival status of the patients was followed up by telephone. The dataset of 168 patients was divided into a control group (n=85) and a TXA group (n=83), at a 1:1 ratio. The patients in the control group were treated with esomeprazole, and the patients in the TXA group received additional TXA. The hemostatic effect, rebleeding rate, and mortality of patients were compared between the two groups. The Cox proportional hazard model was used to evaluate the overall survival of patients as well as the related risk factors. RESULTS: The success rate of hemostasis and the normal blood coagulation rate in the TXA group were significantly higher than those in the control group (P=0.003 and P=0.016). The secondary bleeding rate, thrombus formation rate and digestive tract perforation rate in the TXA group were significantly lower than those in the control group (P=0.002, P=0.003 and P=0.035). The improvement of all indicators in the TXA group was better than that in the control group (all P<0.05). For patients with gastric cancer complicated with acute GI bleeding treated with TXA, the Cox proportional hazard model identified III~IV stage, time of TXA treatment, surgical treatment after hemorrhage, and an increase of D-dimer as independent risk factors for upper GI bleeding (all P<0.05). CONCLUSION: TXA can be an effective treatment for patients with gastric cancer complicated by GI bleeding.

Causes and impact of delays during the COVID-19 pandemic on head and neck cancer diagnosis.

BACKGROUND: The causes for delays during the COVID19 pandemic and their impact on head and neck cancer (HNC) diagnosis and staging are not well described. METHODS: Two cohorts were defined a priori for review and analysis-a Pre-Pandemic cohort (June 1 to December 31, 2019) and a Pandemic cohort (June 1 to December 31, 2020). Delays were categorized as COVID-19 related or not, and as clinician, patient, or policy related. RESULTS: A total of 638 HNC patients were identified including 327 in the Pre-Pandemic Cohort and 311 in the Pandemic Cohort. Patients in the Pandemic cohort had more N2-N3 category (41% vs. 33%, p = 0.03), T3-T4 category (63% vs. 50%, p = 0.002), and stage III-IV (71% vs. 58%, p < 0.001) disease. Several intervals in the diagnosis to treatment pathway were significantly longer in the pandemic cohort as compared to the Pre-Pandemic cohort. Among the pandemic cohort, 146 (47%) experienced a delay, with 112 related to the COVID-19 pandemic; 80 (71%) were clinician related, 15 (13%) were patient related, and 17 (15%) were policy related. CONCLUSIONS: Patients in the Pandemic cohort had higher stage disease at diagnosis and longer intervals along the diagnostic pathway, with COVID-19 related clinician factors being the most common cause of delay.

AURKA knockdown inhibits esophageal squamous cell carcinoma progression through ferroptosis.

Aurora kinase A, as a pro-carcinogenic in gastric cancer and glioma kinase, is enhanced in several human tumors. However, it's regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Thus, this study aimed to investigate the expression status, functional roles, and molecular mechanisms of AURKA in ESCC development. AURKA expression was analyzed by the screening of the GEO database and detected using an immunohistochemical method. The biological function of AURKA on ESCC was evaluated in vitro and in vivo. Western blot assay, malondialdehyde (MDA), iron, and glutathione (GSH) kits were utilized to assess changes in ferroptosis. Database analysis results showed that AURKA was a differential gene in ESCC and was highly expressed in human ESCC tissues. Functionally, AURKA knockdown decreased ESCC cell proliferation, invasion, and metastasis both in vitro and in vivo. Moreover, when AURKA was knockdown, cells were more correctly blocked in the G2/M phase, and the ferroptosis-related MDA and Fe increased, whereas the GSH reduced. Consistently, Glutathione peroxidase 4 (GPX4) and solute carrier family 7a member 11 (SLC7A11) expression were downregulated by AURKA knockdown. However, ferroptosis inhibitor partially restore ESCC cell proliferation, invasion, and metastasis caused by AURKA knockdown. AURKA knockdown enhances ferroptosis and acts against cancer progression in ESCC. AURKA acts as a tumor-promoting gene and may serve as potential target for ESCC treatment.

Preoperative localization for pulmonary nodules: a meta-analysis of coil and liquid materials.

PURPOSE: This study was designed to conduct pooled comparisons of the relative clinical efficacy and safety of computed tomography (CT)-guided localization for pulmonary nodules (PNs) using either coil- or liquid material-based approaches. MATERIAL AND METHODS: Relevant articles published as of July 2023 were identified in the Web of Science, PubMed, and Wanfang databases, and pooled analyses of relevant endpoints were then conducted. RESULTS: Six articles that enrolled 287 patients (341 PNs) and 247 patients (301 PNs) that had respectively undergone CT-guided localization procedures using coil- and liquid material-based approaches prior to video-assisted thoracic surgery (VATS) were included in this meta-analysis. The liquid material group exhibited a significantly higher pooled successful localization rate as compared to the coil group (p = 0.01), together with significantly lower pooled total complication rates (p = 0.0008) and pneumothorax rates (p = 0.01). Both groups exhibited similar rates of pulmonary hemorrhage (p = 0.44) and successful wedge resection (p = 0.26). Liquid-based localization was also associated with significant reductions in pooled localization and VATS procedure durations (p = 0.004 and 0.007). CONCLUSIONS: These data are consistent with CT-guided localization procedures performed using liquid materials being safer and more efficacious than coil-based localization in patients with PNs prior to VATS resection.

Decision Regret Following the Choice of Surgery or Active Surveillance for Small, Low-Risk Papillary Thyroid Cancer: A Prospective Cohort Study.

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3-18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery.

SC912 inhibits AR-V7 activity in castration-resistant prostate cancer by targeting the androgen receptor N-terminal domain.

Androgen deprivation therapies (ADT) are the mainstay treatments for castration-resistant prostate cancer (CRPC). ADT suppresses the androgen receptor (AR) signaling by blocking androgen biosynthesis or inhibiting AR with antiandrogens that target AR's ligand-binding domain (LBD). However, the ADT's effect is short-lived, as the AR signaling inevitably arises again, which is frequently coupled with AR-V7 overexpression. AR-V7 is a truncated form of AR that lacks the LBD, thus being constitutively active in the absence of androgens and irresponsive to AR-LBD-targeting inhibitors. Though compelling evidence has tied AR-V7 to drug resistance in CRPC, pharmacological inhibition of AR-V7 is still an unmet need. Here, we discovered a small molecule, SC912, which binds to full-length AR as well as AR-V7 through AR N-terminal domain (AR-NTD). This pan-AR targeting relies on the amino acids 507-531 in the AR-NTD. SC912 also disrupted AR-V7 transcriptional activity, impaired AR-V7 nuclear localization and DNA binding. In the AR-V7 positive CRPC cells, SC912 suppressed proliferation, induced cell-cycle arrest, and apoptosis. In the AR-V7 expressing CRPC xenografts, SC912 attenuated tumor growth and antagonized intratumoral AR signaling. Together, these results suggested the therapeutic potential of SC912 for CRPC.

Preparation and Evaluation of Folate Modified PEG-PLLA Nanoparticles Loaded with Lycorine for Glioma Treatment.

Lycorine is a kind of natural active ingredient with a strong antitumor effect. In this study, folate ligand-conjugated polyethylene glycol-block-poly(l-lactide) (PEG-PLLA) nanoparticles (FA-PEG-PLLA NPs) were designed to deliver lycorine to enhance its anti-glioma activity. The successful preparation of the FA-PEG-PLLA polymer was confirmed by 1H-NMR, FT-IR, XRD, TGA, and DSC. The optimal formulation for LYC@FA-PEG-PLLA NPs was determined by response surface analysis as follows: sodium dodecyl sulfate (SDS) of 1%, carrier material of 0.03 g, organic phase volume of 3 mL, and ultrasonic power of 20%. The LYC@FA-PEG-PLLA NPs exhibited an encapsulation efficiency of 83.58% and a particle size of 49.71 nm, demonstrating good stability. Hemolysis experiments, MTT assays, and cell scratch assays revealed excellent biocompatibility of FA-PEG-PLLA and superior anti-glioma activity of LYC@FA-PEG-PLLA NPs compared to the raw drug. Additionally, cell apoptosis assays, ROS experiments, and western blot analysis demonstrated that LYC@FA-PEG-PLLA NPs contributed to cell apoptosis by inducing ROS generation and increasing the expression of NF-κB inhibitory protein IκBα. These results suggested that LYC@FA-PEG-PLLA NPs hold promise for glioma treatment.

Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report.

BACKGROUND: Pulmonary tuberculosis (PTB) is prevalent in immunocompromised populations, including patients with hematologic malignancies, human immunodeficiency virus infections, and chronic diseases. Effective treatment for acute promyelocytic leukemia (APL) combined with PTB is lacking. These patients show an extremely poor prognosis. Therefore, studies should establish efficient treatment options to improve patient survival and prognosis. CASE SUMMARY: A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital. Peripheral blood smear revealed 54% blasts. Following bone marrow examinations, variant APL with TNRC18-RARA fusion gene was diagnosed. Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions, partial atelectasis in the lower lobes of both lungs, and the bronchoalveolar lavage fluid gene X-Pert test was positive, indicative of PTB. Carrimycin, ethambutol (EMB), and isoniazid (INH) were administered since he could not receive chemotherapy as the WBC count decreased continuously. After one week of treatment with carrimycin, the patient recovered from fever and received chemotherapy. Chemotherapy was very effective and his white blood cells counts got back to normal. After being given five months with rifampin, EMB and INH and chemotherapy, the patient showed complete remission from pneumonia and APL. CONCLUSION: We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Deep learning radiomics model based on PET/CT predicts PD-L1 expression in non-small cell lung cancer.

Purpose: Programmed cell death protein-1 ligand (PD-L1) is an important prognostic predictor for immunotherapy of non-small cell lung cancer (NSCLC). This study aimed to develop a non-invasive deep learning and radiomics model based on positron emission tomography and computed tomography (PET/CT) to predict PD-L1 expression in NSCLC. Methods: A total of 136 patients with NSCLC between January 2021 and September 2022 were enrolled in this study. The patients were randomly divided into the training dataset and the validation dataset in a ratio of 7:3. Radiomics feature and deep learning feature were extracted from their PET/CT images. The Mann-whitney U-test, Least Absolute Shrinkage and Selection Operator algorithm and Spearman correlation analysis were used to select the top significant features. Then we developed a radiomics model, a deep learning model, and a fusion model based on the selected features. The performance of three models were compared by the area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Results: Of the patients, 42 patients were PD-L1 negative and 94 patients were PD-L1 positive. A total of 2446 radiomics features and 4096 deep learning features were extracted per patient. In the training dataset, the fusion model achieved a highest AUC (0.954, 95% confident internal [CI]: 0.890-0.986) compared with the radiomics model (0.829, 95%CI: 0.738-0.898) and the deep learning model (0.935, 95%CI: 0.865-0.975). In the validation dataset, the AUC of the fusion model (0.910, 95% CI: 0.779-0.977) was also higher than that of the radiomics model (0.785, 95% CI: 0.628-0.897) and the deep learning model (0.867, 95% CI: 0.724-0.952). Conclusion: The PET/CT-based deep learning radiomics model can predict the PD-L1 expression accurately in NSCLC patients, and provides a non-invasive tool for clinicians to select positive PD-L1 patients.

The PPO family in Nicotiana tabacum is an important regulator to participate in pollination.

Polyphenol oxidases (PPOs) are type-3 copper enzymes and are involved in many biological processes. However, the potential functions of PPOs in pollination are not fully understood. In this work, we have screened 13 PPO members in Nicotiana. tabacum (named NtPPO1-13, NtPPOs) to explore their characteristics and functions in pollination. The results show that NtPPOs are closely related to PPOs in Solanaceae and share conserved domains except NtPPO4. Generally, NtPPOs are diversely expressed in different tissues and are distributed in pistil and male gametes. Specifically, NtPPO9 and NtPPO10 are highly expressed in the pistil and mature anther. In addition, the expression levels and enzyme activities of NtPPOs are increased after N. tabacum self-pollination. Knockdown of NtPPOs would affect pollen growth after pollination, and the purines and flavonoid compounds are accumulated in self-pollinated pistil. Altogether, our findings demonstrate that NtPPOs potentially play a role in the pollen tube growth after pollination through purines and flavonoid compounds, and will provide new insights into the role of PPOs in plant reproduction.

Diagnostic value of combined FVC%/DLCO% and echocardiography in connective tissue disorder­associated pulmonary hypertension.

The main objective of the present study was to investigate whether forced vital capacity (FVC)%/diffusing capacity of the lungs for carbon monoxide (DLCO)% can be used to predict the presence of pulmonary hypertension (PH) in connective tissue disorders (CTDs). For this purpose, a total of 53 individuals who were diagnosed with CTDs and had undergone right heart catheterization between July, 2019 and July, 2022 were included in the present study. Based on the mean pulmonary artery pressure (mPAP) measured during right heart catheterization, the participants were divided into the PH and non-PH groups. The differences in demographic characteristics, including sex, age, body mass index, smoking index, FVC%/DLCO% and pulmonary artery systolic pressure (PASP) were determined by echocardiography; moreover, the 6-min walk distance, plasma brain natriuretic peptide (BNP) levels, white blood cell count, red blood cell distribution width, erythrocyte sedimentation rate and C-reactive protein levels were compared between the two groups to identify independent predictors of PH. The independent predictors were subsequently evaluated for their correlation with mPAP to assess their predictive value for PH. FVC%/DLCO%, echocardiographic PASP, and plasma BNP levels were identified as independent predictors of PH. FVC%/DLCO% and echocardiographic PASP exhibited a significant correlation with mPAP, while the correlation between plasma BNP and mPAP levels was not statistically significant. The area under the curve (AUC) value for FVC%/DLCO% alone in predicting PH was 0.791, with an optimal diagnostic threshold of 1.35, a sensitivity of 0.794 and a specificity of 0.789. The AUC for echocardiographic PASP alone in predicting PH was 0.783, with an optimal diagnostic threshold of 39.5 mmHg, a sensitivity of 0.794 and a specificity of 0.684. When combined, the AUC of the two factors in predicting PH was 0.872, with a sensitivity of 0.941 and a specificity of 0.684. Collectively, the data of the present study indicate that FVC%/DLCO% may be used as a predictive factor for CTD-PH, and its combined application with echocardiographic PASP measurement may provide additional evidence for the clinical diagnosis of CTD-PH.

Molecular mechanism of lycorine in the treatment of glioblastoma based on network pharmacology and molecular docking.

Lycorine is a naturally active alkaloid that has been shown to have inhibitory effects on a variety of cancers. However, the underlying mechanism of lycorine in the treatment of glioblastoma (GBM) is unclear. In this study, we investigated the mechanism of lycorine in the treatment of GBM based on network pharmacology and molecular docking. Lycorine-related targets overlapped with GBM-related targets to obtain intersections that represent potential anti-GBM targets for lycorine. The protein-protein interaction (PPI) network was constructed using the STRING online database and analyzed by Cytoscape software, and 10 key target genes (AKT1, SRC, HSP90AA1, HRAS, MMP9, BCL2L1, IGF1, MAPK14, STAT1, and KDR) were obtained, which played an important role in the therapeutic effect of lycorine on GBM. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that lycorine acts on GBM by multiple pathways, including inducing apoptosis and reactive oxygen species production. The molecular docking results showed that lycorine had strong binding efficiency with the 10 key genes. In addition, we found that the use of lycorine-induced apoptosis in U-87 MG glioblastoma cells. Here, the mechanism of action of lycorine against GBM was elucidated and verified by experiments, which provided evidence support for its clinical application.

CDC-NET: a cell detection and confirmation network of bone marrow aspirate images for the aided diagnosis of AML.

Standardized morphological evaluation in pathology is usually qualitative. Classifying and qualitatively analyzing the nucleated cells in the bone marrow aspirate images based on morphology is crucial for the diagnosis of acute myoid leukemia (AML), acute lymphoblastic leukemia (ALL), and Myelodysplastic syndrome (MDS), etc. However, it is time-consuming and difficult to accurately identify nucleated cells and calculate the percentage of the cells because of the complexity of bone marrow aspirate images. This paper proposed a deep learning analysis model of bone marrow aspirate images, termed Cell Detection and Confirmation Network (CDC-NET), for the aided diagnosis of AML by improving the accuracy of cell detection and recognition. Specifically, we take the nucleated cells in the bone marrow aspirate images as the detection objects to establish the model. Since some cells from different categories have similar morphology, classification error is inevitable. We design a confirmation network in which multiple trained classifiers work as pathologists to confirm the cell category by a voting method. To demonstrate the effectiveness of the proposed approach, experiments on clinical microscopic datasets are conducted. The Recall and Precision of CDC-NET are 78.54% and 91.74% respectively, and the missed rate of our method is lower than those of the other popular methods. The experimental results demonstrated that the proposed model has the potential for the pathological analysis of aspirate smears and the aided diagnosis of AML.

Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

BACKGROUND: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). METHODS: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Bailing capsule on polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated. METHODS: Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein-protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR. RESULTS: The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug-disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways. DISCUSSION: This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.