Elderly patients with advanced HER2-positive breast cancer with liver metastases benefit from low dose disitamab vedotin (RC48): case series and literature review.

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented. We report on two elderly women with breast cancer who developed recurrent metastatic lesions after breast cancer surgery and were again confirmed HER2-positive by histopathology and immunohistochemistry. They all developed multiple metastases in the liver after second- or third-line anti-HER2 therapy. Subsequent treatment with RC48 produced good responses and tolerable adverse reactions. One patient obtained progression-free survival for more than 7 months. Based on preliminary evidence, this study shows that RC48 in HER2-positive breast cancer with liver metastases can achieve rapid remission, thereby reducing tumor load and improving patients' quality of life. In particular, RC48 has low side effects and can be well tolerated by elderly patients after dose adjustment, providing them with treatment opportunities. It needs to be further discussed in the future research.

Immune dysfunction mediated by the competitive endogenous RNA network in fetal side placental tissue of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder affecting women in their reproductive years. Emerging evidence suggests that the maternal-fetal immune system is crucial for proper pregnancy. However, whether immune function is altered at the end of pregnancy in PCOS women and the underlying molecular mechanisms is currently unexplored. Herein, the basic maternal immune system was investigated (n = 136 in the control group; n = 103 in the PCOS group), and whole-transcriptome sequencing was carried out to quantify the mRNAs, miRNAs, and lncRNAs expression levels in fetal side placental tissue of women with PCOS. GO, KEGG, and GSEA analysis were employed for functional enrichment analysis. The process of identifying hub genes was conducted utilizing the protein-protein interaction network. CIBERSORT and Connectivity Map were deployed to determine immune cell infiltration and predict potential drugs, respectively. A network of mRNA-miRNA-lncRNA was constructed and then validated by qRT-PCR. First, red blood cell count, neutrophil count, lymphocyte count, hypersensitive C-reactive protein, and procalcitonin were significantly elevated, while placental growth factor was hindered in PCOS women. We identified 308 DEmRNAs, 77 DEmiRNAs, and 332 DElncRNAs in PCOS samples. Functional enrichment analysis revealed that there were significant changes observed in terms of the immune system, especially the chemokine pathway. Eight genes, including FOS, JUN, EGR1, CXCL10, CXCR1, CXCR2, CXCL11, and CXCL8, were considered as hub genes. Furthermore, the degree of infiltration of neutrophils was dramatically decreased in PCOS tissues. In total, 57 ceRNA events were finally obtained, and immune-related ceRNA networks were validated. Some potential drug candidates, such as enalapril and RS-100329, could have a function in PCOS therapy. This study represents the inaugural attempt to evaluate the immune system at the end of pregnancy and placental ceRNA networks in PCOS, indicating alterations in the chemokine pathway, which may impact fetal and placental growth, and provides new therapy targets.

Network pharmacology analysis of a patented Chinese herbal medicine for alleviating anxiety disorder in in vitro fertilization-embryo transfer.

Objective: Qu's formula 3 (QUF3) is a patented Chinese herbal medicine used to alleviate anxiety disorders during in vitro fertilization-embryo transfer (IVF-ET). This study aimed to identify the potential active constituents and molecular mechanisms of action of QUF3 in alleviating anxiety disorders during IVF-ET. Methods: The active constituents of QUF3 were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and literatures. Potential targets of anxiety disorder and IVF-ET were identified using GeneCards, Online Mendelian Inheritance in Man, and the UniProt Database. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify the potential mechanisms. Molecular docking and molecular dynamics (MD) simulations were performed to visualize and verify the results. Results: Quercetin, sophoranol, luteolin, kaempferol, and neurotoxin inhibitors were identified as the TOP 5 active constituents of QUF3. Forty common targets were shared among QUF3, anxiety disorders, and IVF-ET. Tumour necrosis factor, interleukin-6, vascular endothelial growth factor A, epidermal growth factor, interleukin-1B, cellular tumour antigen p53, matrix metalloproteinase-9, and oestrogen receptor were identified as the TOP 8 potential targets through PPI analysis. A total of 697 biological processes, 20 cellular components, and 54 molecular functions were identified. Further, 91 KEGG pathways were revealed to be enriched. The TOP 5 active constituents were verified to have good binding activity with the TOP 8 potential targets using molecular docking and MD simulations. Conclusions: The mechanism of QUF3 in alleviating anxiety disorders in patients undergoing IVF-ET may be related to the interleukin-17 and tumour necrosis factor signalling pathways, inhibiting inflammatory responses and antioxidants, which may provide a solid foundation for the clinical application and further study of QUF3.

Polychlorinated biphenyls exposure and type 2 diabetes: Molecular mechanism that causes insulin resistance and islet damage.

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that have been associated with type 2 diabetes (T2DM) in cohort studies. This review aims to comprehensively assess the molecular mechanisms of PCBs-induced T2DM. Recent progress has been made in the research of PCBs in liver tissue, adipose tissue, and other tissues. By influencing the function of nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnancy X receptor (PXR), and peroxisome proliferator activated receptor γ (PPARγ), as well as the inflammatory response, PCBs disrupt the balance of hepatic glucose and lipid metabolism. This is associated with insulin resistance (IR) in the target organ of insulin. Through androgen receptor (AR), estrogen receptor α/ß (ERα/ß), and pancreato-duodenal-homeobox gene-1 (PDX-1), PCBs affect the secretion of insulin and increase blood glucose. Thus, this review is a discussion on the relationship between PCBs exposure and the pathogenesis of T2DM. It is hoped to provide basic concepts for diabetes research and disease treatment.

The effective compounds and mechanisms of Cang-Fu-Dao-Tan Formula in treating polycystic ovary syndrome based on UPLC/Q-TOF-MS/MS, network pharmacology and molecular experiments.

BACKGROUND: Polycystic ovary syndrome (PCOS), as a common endocrine disease in reproductive-age women, which is characterized by both reproductive and metabolic disorders. Cang-Fu-Dao-Tan Formula (CFDTF) is an effective and relatively safe treatment for PCOS. However, the underlying mechanism is poorly understood. PURPOSE: To explore the effective compounds and mechanisms of CFDTF in treating PCOS based on UPLC/Q-TOF-MS/MS, network pharmacology and molecular experiments. METHODS: The UPLC/Q-TOF-MS/MS and TCMSP, SwissTargetPrediction databases were used to identify the active ingredients of CFDTF. Then GeneCards, Disgenet, Drugbank databases were used to obtain the PCOS related targets. Based above, the Drug-component-target (D-C-T) network and protein-protein-interaction (PPI) network were built to analysis the key targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed to find the potential mechanisms. Finally, molecular docking analysis, molecular dynamics (MD) simulations and molecular experiments were used to confirm the interactions among the active compounds, targets and explore the potential mechanisms. RESULTS: A total of 20 compounds were identified by UPLC/Q-TOF-MS/MS, and 136 active compounds by TCMSP from CFDTF. After removing the duplicate results, there were 370 targets related to both CFDTF and PCOS, among which, MAPK3, AKT1, RELA, EGF, TP53 and MYC were proved to have high interactions with the components. The mechanisms of CFDTF against PCOS were related to PI3K-Akt, mTOR, MAPK signaling pathways, and the in vitro experiments proved that the CFDTF positively regulated the cell proliferation and inhibited the apoptosis levels in PCOS cell model. CONCLUSIONS: The combination of UPLC/Q-TOF-MS/MS, systematic network pharmacology and molecular experiments identified that the quercetin, hesperidin, and glycyrrhizin disaccharide are the TOP 3 effective compounds of CFDTF in treating PCOS and the potential mechanisms may involve in regulating proliferation and apoptosis of granulosa cells.

Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases.

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC.

Oral Anlotinib Maintenance Therapy for an Advanced Malignant Peritoneal Mesothelioma Diagnosed by Laparoscopy After Initial Misdiagnosis to Obtain Longer Progression-Free Survival: Case Report and Literature Review.

Malignant peritoneal mesothelioma (MPeM) is a rare and highly invasive malignant tumor with a lack of specificity in clinical manifestations, which can easily lead to misdiagnosis and missed diagnosis. Due to the difficulty of early diagnosis, most patients are already in the advanced stage when diagnosed, and the prognosis is poor. At present, there is no standard treatment strategy, and the existing treatment methods are not effective, the duration of remission is short, which cannot meet the clinical needs. Here we describe a patient with advanced MPeM, initially misdiagnosed as ovarian cancer, who responded to treatment with bevacizumab in combination with albumin-bound paclitaxel and cisplatin. In preparation for cytoreductive surgery (CRS), MPeM was confirmed by laparoscopic peritoneal nodule biopsy combined with histological and immunohistochemical results. Subsequently, due to intolerable neurotoxicity after chemotherapy, she received oral anlotinib therapy on April 25, 2022, and remained stable disease (SD) with the medication, having achieved more than 14 months of progression-free survival (PFS) as of the date of our manuscript submission. The patient's total treatment time was over 19 months. These treatments delayed tumor progression, reduced drug side effects, maintained a good quality of life, and further extended overall survival (OS). Our experience is that on the one hand, it is necessary to increase the clinician's understanding of the disease, and make full use of tissue samples and immunohistochemical staining to reduce the occurrence of misdiagnosis. On the other hand, based on preliminary evidence, we found that oral anlotinib offers a viable maintenance treatment strategy for patients with advanced mesothelioma, which needs to be further explored in future studies.

The value of indocyanine green-FLOW800 in microvasculature for predicting cerebral hyperperfusion syndrome in moyamoya disease patients.

Among the notable complications of direct hemodynamic reconstruction for moyamoya disease (MMD) is cerebral hyperperfusion syndrome (CHS). In this study, we evaluated hemodynamic changes in small regional microvasculature (SRMV) around the anastomosis site by using indocyanine green (ICG)-FLOW800 video angiography and verified that it better predicted the onset of CHS. Intraoperative ICG-FLOW800 analysis was performed on 31 patients (36 cerebral hemispheres) with MMD who underwent superficial temporal artery-middle cerebral artery (MCA) bypass grafting at our institution. The regions of interest were established in the SRMV and thicker MCA around the anastomosis. Calculations were made for half-peak to time (TTP1/2), cerebral blood volume (CBV), and cerebral blood flow (CBF). According to the presence or absence of CHS after surgery, CHS and non-CHS groups of patients were separated. The results showed that ΔCBV and ΔCBF were substantially greater in SRMV than in MCA (p < 0.001). Compared with the non-CHS group, ΔCBF and ΔCBV of SRMV and MCA were considerably greater in the CHS group (p < 0.001). ΔCBF and ΔCBV on the ROC curve for both SRMV and MCA had high sensitivity and specificity (SRMV: ΔCBF, AUC = 0.8586; ΔCBV, AUC = 0.8158. MCA: ΔCBF, AUC = 0.7993; ΔCBV, AUC = 0.8684). ICG-FLOW800 video angiography verified the differential hemodynamic changes in the peri-anastomotic MCA and SRMV before and after bypass surgery in patients with MMD.

Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. Osteopontin (OPN) is thought to be closely related to the occurrence, metastasis and prognosis of many types of tumors. AIM: To investigate the effects of OPN on the proliferation, invasion and migration of GC cells and its possible mechanism. METHODS: The mRNA and protein expression of OPN in the GC cells were analyzed by real-time quantitative-reverse transcription polymerase chain reaction and western blotting, and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC. Next, the effects of OPN knockdown on GC cells migration and invasion were examined. The short hairpin RNA (shRNA) and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer's instructions. Non transfected cells were classified as control in the identical transfecting process. 24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay, and cell invasiveness and migration were detected by Trans well assay. Meanwhile, the expression of protein kinase B (AKT), matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting. RESULTS: The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells. OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation, invasion and migration of SGC-7901 cells. Moreover, in the experiments of investigating the underlying mechanism, results showed that OPN knockdown could down-regulated the expression of MMP-2 and VEGF, it also decreased the phosphorylation of AKT. Meanwhile, the protein expression levels of MMP-2, VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002). CONCLUSION: These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to up-regulate MMP-2 and VEGF expression, which contribute SGC-7901 cells to proliferation, invasion and migration. Thus, our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.

Bu-Shen-Tian-Jing formulas alleviate the mitochondrial damage induced by oxidative stress in ovarian granulosa cells exposed to DEHP through the HDAC3-HSP90AA pathway.

CONTEXT: di-(2-Ethylhexyl) phthalate (DEHP) has potential reproductive toxicity. Bu-Shen-Tian-Jing formulations (BSTJFs) are beneficial for female reproductive capacity. However, BSTJF2 has much lower cytotoxicity than BSTJF1. OBJECTIVE: To investigate the effects of BSTJFs on ovarian granulosa cells exposed to DEHP and determine the potential molecular mechanisms. METHODS AND MATERIALS: Human granulosa-like tumor cell line (KGN) cells were divided into control, DEHP, BSTJF1 and BSTJF2 groups. The DEHP group were given 1 µM DEHP for 24 h. They were then given BSTJF1 at 200 µg/mL or BSTJF2 at 100 µg/mL for 24 h. The control group was treated with the same concentration of DMSO (0.1%). Oxidative stress and mitochondrial function were measured. The mRNA and protein expression levels of HDAC3 and HSP90AA were determined. Integrative network pharmacology analysis of BSTJF2 was also performed. RESULTS: DEHP (1 µM) significantly suppressed the proliferation of KGN cells by 17%, significantly increased ROS levels by 28% and MDA levels by 47%, significantly decreased MMP levels by 22% and mtDNA copy by 30%. DEHP significantly increased protein expression of HDAC3 by 21%and HSP90AA by 64%. All these changes were significantly reversed by BSTJFs. Integrative network pharmacology analysis revealed HSP90AA was a key target (degree = 8). Both RGFP966 and BSTJF2 significantly reversed the increased expression of HDAC3 and HSP90AA, attenuated oxidative stress, and mitochondrial damage which were induced by DEHP. CONCLUSION: BSTJFs might have therapeutic potential on oxidative stress and mitochondrial damage through the HDAC3/HSP90AA pathway which encourages further clinical trials.

Application of WeChat Public Account for Lifestyle Management of Polycystic Ovary Syndrome.

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Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival: A case report.

BACKGROUND: After the failure of second-line standard therapy, effective treatment options for metastatic colorectal cancer are limited, and the duration of remission cannot meet clinical needs. In addition, associated drug toxicity may lead to treatment interruption that may affect patient outcomes. Therefore, more safe, effective and convenient treatments are urgently needed. CASE SUMMARY: Here, we describe a patient with advanced colorectal cancer with multiple metastases in both lungs. Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment, and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression. However, treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea. He received targeted therapy with fruquintinib starting on August 26, 2020 and responded well for 12 mo. After slow progression of the lung metastases, progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy. Overall treatment duration was more than 25.5 mo. The treatments delayed tumor progression, reduced drug side effects, maintained a good quality of life, and further extended overall survival. CONCLUSION: This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.

Contribution of labor related gene subtype classification on heterogeneity of polycystic ovary syndrome.

OBJECTIVE: As one of the most common endocrine disorders in women of reproductive age, polycystic ovary syndrome (PCOS) is highly heterogeneous with varied clinical features and diverse gestational complications among individuals. The patients with PCOS have 2-fold higher risk of preterm labor which is associated with substantial infant morbidity and mortality and great socioeconomic cost. The study was designated to identify molecular subtypes and the related hub genes to facilitate the susceptibility assessment of preterm labor in women with PCOS. METHODS: Four mRNA datasets (GSE84958, GSE5090, GSE43264 and GSE98421) were obtained from Gene Expression Omnibus database. Twenty-eight candidate genes related to preterm labor or labor were yielded from the researches and our unpublished data. Then, we utilized unsupervised clustering to identify molecular subtypes in PCOS based on the expression of above candidate genes. Key modules were generated with weighted gene co-expression network analysis R package, and their hub genes were generated with CytoHubba. The probable biological function and mechanism were explored through Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. In addition, STRING and Cytoscape software were used to identify the protein-protein interaction (PPI) network, and the molecular complex detection (MCODE) was used to identify the hub genes. Then the overlapping hub genes were predicted. RESULTS: Two molecular subtypes were found in women with PCOS based on the expression similarity of preterm labor or labor-related genes, in which two modules were highlighted. The key modules and PPI network have five overlapping five hub genes, two of which, GTF2F2 and MYO6 gene, were further confirmed by the comparison between clustering subgroups according to the expression of hub genes. CONCLUSIONS: Distinct PCOS molecular subtypes were identified with preterm labor or labor-related genes, which might uncover the potential mechanism underlying heterogeneity of clinical pregnancy complications in women with PCOS.

Paeonol ameliorates endometrial hyperplasia in mice via inhibiting PI3K/AKT pathway-related ferroptosis.

BACKGROUND: Paeonol (Pae) is one of the active ingredients from components of Guizhi Fuling Capsule, a traditional Chinese medicine widely used for the treatment of women's diseases, which exhibits various biological and pharmacological activities. PURPOSE: The objective of this study was to investigate the molecular mechanism underlying the role of Pae in protecting against endometrial hyperplasia (EH). METHODS: CCK-8 assay was performed to detect the effect of Pae on cell proliferation. Hematoxylin and eosin (H&E) staining was performed to evaluate uterine tissue structure. A network pharmacology study was performed to search the disease targets. Single-cell transcriptome analysis was performed with uterine tissues from 3 healthy donors and 3 EH patients on 10X Genomics platform. Changes in lipid peroxidation were detected by the MDA reaction. IHC assay, Western blot, immunofluorescence and RT-qPCR were used to study the effects of estradiol and Pae on the expression levels of GPX4, PI3K, AKT, p-PI3K, p-AKT in mice. RESULTS: Pae treatment resulted in a decrease in cell viability of endometrial epithelial cells. Loss of uterus weight and morphology changes were observed in mice. In addition, Fe iron concentration and MDA levels increased, while the expression of GPX4, p-PI3K and p-AKT diminished. CONCLUSIONS: Pae exhibited obvious alleviative activity in estradiol-induced mice via PI3K/AKT signaling pathway-regulated ferroptosis.

Chinese herbal medicine alleviates the pathogenesis of polycystic ovary syndrome by improving oxidative stress and glucose metabolism via mitochondrial Sirtuin 3 signaling.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women, and the curative effects of its current management are not satisfactory. A formula of Chinese herbal medicine (CHM), called Bu-Shen-Tian-Jing Formula (BSTJF), has clinically shown beneficial effects in treating PCOS. PURPOSE: This study aimed to investigate the mechanism underlying BSTJF for treatment of PCOS. METHODS: Whole blood samples were collected from women with PCOS treated and not treated with BSTJF (n = 5 per group). Whole transcriptome sequencing of leukocytes and untargeted metabonomic analysis of the plasma were performed. Three groups of 18 female Sprague-Dawley rats were randomly selected: control, PCOS, and BSTJF. A PCOS rat model was established using testosterone propionate. The estrous cycle; glucose tolerance; ovarian morphology; serum markers of oxidative stress; and expression of Sirtuin 3 (SIRT3), phospho-p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase (PI3K), and phospho-protein kinase B in the ovary were measured. Palmitate was initially applied to KGN cells, followed by freeze-dried BSTJF powder. The glucose uptake, reactive oxygen species (ROS) production, and protein levels of SIRT3, PI3K, and glucose transporter type 4 (GLUT4) were detected in KGN cells. RESULTS: The transcriptomic and metabolomic profiles showed alterations in 572 genes and 73 metabolites in women with PCOS treated with BSTJF. The enriched pathways in women with PCOS treated with BSTJF were mainly involved in inflammation, insulin resistance, glucose and lipid metabolism, and neuro and associated signaling pathways. In PCOS rat models, BSTJF improved the estrous cycle, glucose tolerance, and ovarian morphology; relieved oxidative stress; increased ovarian SIRT3 expression; inhibited p38 MAPK activation; and promoted the activation of PI3K/AKT signaling in the ovary. In the in-vitro study with KGN cells, BSTJF rescued the palmitate-induced impaired glucose uptake and SIRT3 expression, reduced mitochondrial ROS production mediated by SIRT3, and restored the impaired insulin-induced PI3K/AKT signaling pathway. CONCLUSION: BSTJF effectively alleviated the pathogenesis of PCOS by improving oxidative stress and glucose metabolism via mitochondrial SIRT3 and the following insulin signaling pathway. This study innovatively revealed the action mechanism of CHM in treating PCOS.

The Association Between Polycystic Ovary Syndrome and Metabolic Syndrome in Adolescents: a Systematic Review and Meta-analysis.

The association between polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS) is not widely recognized or properly assessed in adolescents. The aim of this study was to conduct a systematic review and meta-analysis to provide reliable results concerning MetS development in adolescents with PCOS. We searched studies published in PubMed, Medline, and Web of Science from January 2010 to December 2020. The quality of studies was assessed by the Newcastle-Ottawa Scale (NOS), and the data analysis was performed with Stata 14.0. Twelve articles were finally included in the systematic review and meta-analysis. The results suggested that adolescents with PCOS have more than three times the odds of having MetS than controls (OR 3.32, 95% CI [2.14, 5.14]). Obese adolescents with PCOS also had a higher risk of MetS than those with obesity but without PCOS (OR 3.97, 95% CI [1.49, 10.53]). Compared to those without PCOS, systolic blood pressure was higher in adolescents with PCOS (weighted mean difference (WMD) 3.85, 95% CI [1.73, 5.97]), while diastolic blood pressure was higher only in girls with PCOS who had a normal weight (WMD 3.52, 95% CI [1.57, 5.48]). The levels of triglycerides were higher in obese adolescents with PCOS than in those with obesity but without PCOS (WMD 27.84, 95% CI [10.16, 45.51]). PCOS could increase the frequency of MetS by influencing blood pressure and lipid metabolism independent of obesity as early as the adolescent period. Thus, clinicians should perform early interventions in adolescents with PCOS and follow up the relevant indicators of MetS to decrease the risk of poor long-term prognosis.

Conjugated/nonconjugated alternating copolymers for enhanced NIR-II fluorescence imaging and NIR-II photothermal-ferrotherapy.

Conjugated polymers hold great promise for NIR-II fluorescence imaging (FI)-guided NIR-II photothermal therapy (PTT) due to the advantages of easy modification of chemical structures and adjustable NIR absorption. However, to make use of these advantages, it is of paramount importance to formulate conjugated polymers with excellent solubility in organic solution, great NIR-II photothermal conversion efficiency, and high NIR-II fluorescence quantum yield. Herein, a new class of conjugated/nonconjugated alternating copolymers (CNACPs) is reported by introducing nonconjugated linkers into a conjugated backbone to modulate the extinction coefficient at 1064 nm and NIR-II fluorescence quantum yield. The NIR-II absorption, NIR-II emission, and NIR-II photothermal properties of the new CNACPs were studied. Interestingly, it is observed that longer nonconjugated linkers in CNACPs result in higher NIR-II fluorescence intensity with sufficient NIR-II absorption and NIR-II photothermal ability. With these newly developed CNACPs (BBT-C6), phototheranostic nanoparticles (BBTD6/Fe@PMA) are prepared through facile nanoprecipitation using PMA-AD-PEG as an iron ion chelator for NIR-II FI-guided NIR-II PTT/ferrotherapy synergistic therapy. In vitro and in vivo, BBTD6/Fe@PMA effectively inhibited 4T1 cells and tumor progression under 1064 nm laser irradiation. Consequently, this work provides new CNACPs by incorporating nonconjugated linkers into a conjugated backbone to design more effective NIR-II fluorescence imaging and NIR-II photothermal therapy agents.

Severe intrahepatic cholestasis of pregnancy due to a Sertoli-Leydig cell tumour in a woman with polycystic ovary syndrome: a case report.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism. CASE PRESENTATION: Here, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli-Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed. CONCLUSION: This unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.

NIR-II Excitation Phototheranostic Platform for Synergistic Photothermal Therapy/Chemotherapy/Chemodynamic Therapy of Breast Cancer Bone Metastases.

To improve bone metastases treatment efficacy, current strategies are focused on the integration of chemotherapy with phototheranostic. However, the success of phototheranostic approaches is hampered by the limited tissue penetration depth of near-infrared-I (NIR-I) light (700-900 nm). In this study, a NIR-II (1000-1700 nm) excitation phototheranostic (BTZ/Fe2+ @BTF/ALD) is presented for NIR-II fluorescence imaging and NIR-II photoacoustic imaging-guided NIR-II photothermal therapy (PTT), chemotherapy, and chemodynamic therapy (CDT) of breast cancer bone metastases. This phototheranostic is developed by integrating a dopamine-modified NIR-II absorbing donor-acceptor-donor small molecule (BBT-FT-DA), the boronate anticancer drug bortezomib (BTZ), and Fe2+ ions, as CDT catalysts, into an amphiphilic PEGylated phospholipid modified with the bone-targeting ligand alendronate. In acidic and hydrogen peroxide (H2 O2 ) over expression tumor microenvironment, the boronate-catechol linkage is cleaved and BTZ and Fe2+ ions are released to initiate the Fenton reaction, that is, chemotherapy and CDT, respectively, are initialized. It is confirmed using the murine 4T1 bone metastasis model that BTZ/Fe2+ @BTF/ALD significantly suppresses the progression of tumor cells in the bone tissue via a synergistic NIR-II PTT/chemotherapy/CDT effect. Overall, this work provides fresh insights to guide the development of NIR-II phototheranostics for breast cancer bone metastases.

The Improvement Effect of D-Chiro-Inositol and Ecklonia cava K. in the Rat Model of Polycystic Ovarian Syndrome.

Introduction: Polycystic Ovarian Syndrome (PCOS) is known to be an endocrine state that is characterized by oligomenorrhea, hyperandrogenism, and highly cystic follicles in the ovaries. The use of food ingredients and traditional medicine in Asian countries is well known, and previous studies have shown that Ecklonia cava K. [Alariaceae] (EC) is able to alleviate PCOS symptoms. D-Chiro-inositol (DCI) administration in pathologies where steroid biosynthesis is a crucial factor, i.e., PCOS, has provided satisfactory results. Methods: Therefore, we studied the synergistic effects of the two previously known active compounds. In rats with letrozole-induced PCOS, we focused on alternative therapies using EC and/or DCI extracts to alleviate ovarian failure. Results: As a nonsteroidal aromatase inhibitor, letrozole inhibits the conversion of testosterone to estrogen and subsequently causes PCOS. We divided 6-week-old female mice into the following six groups and evaluated them: vehicle, PCOS, PCOS + MET (metformin), PCOS + DCI, PCOS + EC, and PCOS + DCI + EC. In our study, PCOS rats treated with EC and DCI had low serum LH and T levels and low serum levels of inflammatory cytokines such as TNFα and IL-6. These treatments also appeared to regulate the production of factors that affect follicle formation and inflammation in the ovaries. Conclusion: We concluded that EC extract and/or DCI administration influenced aromatase production and reduced LH and T stimulation, and cotreatment with EC and DCI consequently restored ovarian dysfunction or anti-inflammatory responses in rats with PCOS-like symptoms.