Associations of Diabetes and Prediabetes With Mortality and Life Expectancy in China: A National Study.

OBJECTIVE: To investigate the excess mortality and life-years lost associated with diabetes and prediabetes in China. RESEARCH DESIGN AND METHODS: This national cohort study enrolled 135,405 participants aged 18 years or older from the general population in China. Cox proportional hazards regression models were used to estimate adjusted mortality rate ratio (RR). The life table method was used to estimate life expectancy. RESULTS: Among the 135,405 participants, 10.5% had diabetes and 36.2% had prediabetes in 2013. During a median follow-up of 6 years, 5517 deaths were recorded, including 1428 and 2300 deaths among people with diabetes and prediabetes, respectively. Diabetes and prediabetes were significantly associated with increased risk of all-cause (diabetes: RR, 1.61 [95% CI 1.49, 1.73]; prediabetes: RR, 1.08 [95% CI 1.01, 1.15]), and cardiovascular disease (diabetes: RR, 1.59 [95% CI 1.41, 1.78]; prediabetes: RR, 1.10 [95% CI 1.00, 1.21]) mortality. Additionally, diabetes was significantly associated with increased risks of death resulting from cancer, respiratory disease, liver disease, and diabetic ketoacidosis or coma. Compared with participants with normoglycemia, life expectancy of those with diabetes and prediabetes was shorter, on average, by 4.2 and 0.7 years at age 40 years, respectively. The magnitude of the associations of diabetes and prediabetes with all-cause and cardiovascular disease mortality varied by age and residence. CONCLUSIONS: In this national study, diabetes and prediabetes were significantly associated with reduced life expectancy and increased all-cause and cause-specific mortality risks. The disparities in excess mortality associated with diabetes and prediabetes between different ages and residences have implications for diabetes and prediabetes prevention and treatment programs.

Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy.

Background: Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway. Methods: In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 µM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers. Results: DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells. Conclusions: This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.

Isoimperatorin Inhibits Angiogenesis by Suppressing VEGFR2 Signaling Pathway.

PURPOSE: Angiogenesis involves in many pathological processes, including tumor metastasis, diabetic retinopathy, and rheumatoid arthritis. Therefore, identifying therapeutic drugs that target angiogenesis may be a promising strategy for disease treatment. Isoimperatorin is a furanocoumarin with anti-inflammatory and anti-microbial effects. However, the impacts of isoimperatorin on angiogenesis and its underlying mechanisms remain unclear. This study aimed to verify its effects on vascular endothelial growth factor (VEGF)-induced endothelial angiogenesis. METHODS: We employed various assays including 5-ethynyl-2'-deoxyuridine incorporation assay, transwell migration assay, wound healing assay, tube formation assay, and Western blot to evaluate the effects of isoimperatorin on angiogenesis in vitro. Additionally, we utilized Western blot and immunofluorescence analysis to examine the activation of vascular endothelial growth factor receptor (VEGFR) 2 and its downstream signaling pathways following isoimperatorin treatment. To further validate the anti-angiogenic effects of isoimperatorin in vivo, we conducted a matrigel plug assay and established an orthotopic tumor model. RESULTS: We demonstrated that pretreatment with isoimperatorin inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation. Isoimperatorin also suppressed angiogenesis in vivo in a matrigel plug assay and in an orthotopic tumor model. Our results revealed that isoimperatorin exhibited anti-angiogenic effects via inhibiting VEGFR2 and its downstream signaling pathways activation. CONCLUSIONS: Our study showed that isoimperatorin suppressed angiogenesis by targeting the VEGFR2 signaling pathway and could be a potential therapeutic agent for targeting angiogenesis.

CeRNA Network Reveals the Circular RNA Characterization in Goat Ear Fibroblasts Reprogramming into Mammary Epithelial Cells.

Circular RNAs (circRNAs) are a type of non-coding RNA that play a crucial role in the development and lactation of mammary glands in mammals. A total of 107 differentially expressed circRNAs (DE circRNAs) were found, of which 52 were up-regulated and 55 were down-regulated. We also found that DE circRNA host genes were mainly involved in GO terms related to the development process of mammary epithelial cells and KEGG pathways were mostly related to mammary epithelial cells, lactation, and gland development. Protein network analysis found that DE circRNAs can competitively bind to miRNAs as key circRNAs by constructing a circRNA-miRNA-mRNA network. CircRNAs competitively bind to miRNAs (miR-10b-3p, miR-671-5p, chi-miR-200c, chi-miR-378-3p, and chi-miR-30e-5p) involved in goat mammary gland development, mammary epithelial cells, and lactation, affecting the expression of core genes (CDH2, MAPK1, ITGB1, CAMSAP2, and MAPKAPK5). Here, we generated CiMECs and systematically explored the differences in the transcription profile for the first time using whole-transcriptome sequencing. We also analyzed the interaction among mRNA, miRNA, and cirRNA and predicted that circRNA plays an important role in the maintenance of mammary epithelial cells.

A deletion variant Arg616 of androgen receptor in a Chinese family with complete androgen insensitivity syndrome.

Background: Complete androgen insensitivity syndrome (CAIS, OMIM; 300068) is a disorder of sex development with X-linked recessive inheritance. Cases of CAIS usually present as female phenotype, with primary amenorrhea and/or inguinal hernia. Family aggregation is a rare scenario. Methods: This study is a retrospective analysis of CAIS cases in a three-generation pedigree. The patients' genomes were determined by sequencing the androgen receptor (AR) gene. The clinical data of the patients, including manifestations, hormone levels, and AR variants, were analyzed. Results: Sixteen people in this family were involved. A deletion variant (c.1847_1849del; p. Arg616del) was identified in exon 3 of AR, which encodes the DNA binding domain. Until now, four patients and four carriers have been identified in three generations of this family. All the patients live as female, and one has developed gonadal malignancy. Conclusion: The present study identified a deletion variant in three generations of a family with CAIS, including four carriers and four patients. This study verified the genetic pattern and the corresponding clinical characteristics of CAIS. Furthermore, a case with gonadal malignancy was discovered. The information on diagnosis and treatment in this pedigree is useful for prenatal diagnosis and genetic counseling of similar families.

RNF207 exacerbates pathological cardiac hypertrophy via post-translational modification of TAB1.

AIMS: The heart undergoes pathological remodelling, featured by the hypertrophic growth of cardiomyocytes and increased cardiac fibrosis, under biomechanical stress such as haemodynamic overload. Ring Finger Protein 207 (RNF207) is an E3 ubiquitin ligase that is predominantly expressed in the heart, but its function remains elusive. In this study, we aimed to explore the role of RNF207 in the development of pathological cardiac hypertrophy and dysfunction. METHODS AND RESULTS: Transverse aortic constriction (TAC) surgery was performed on mice to induce cardiac hypertrophy. Cardiac function and remodelling were evaluated by echocardiography, histological assessment, and molecular analyses. Our data indicated that RNF207 overexpression (OE) exacerbated cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, TAC-induced cardiac remodelling was profoundly blunted in RNF207 knockdown (KD) hearts. In line with the in vivo findings, RNF207 OE augmented, whereas RNF207 KD alleviated, phenylephrine-induced cardiomyocyte hypertrophy in vitro. Mechanistically, we demonstrated that RNF207 elicited detrimental effects by promoting K63-linked ubiquitination of TAK1-binding protein 1 (TAB1), which triggered the autophosphorylation of transforming growth factor-ß activated kinase 1 (TAK1) and the activation of downstream p38 and c-Jun N-terminal kinase (JNK)1/2 signalling pathways. In the TAB1-KD cardiomyocytes, RNF207-OE-induced cell hypertrophy was significantly attenuated, indicating that RNF207-induced hypertrophy is, at least in part, TAB1-dependent. CONCLUSIONS: This study demonstrates that RNF207 exacerbates pressure overload-induced cardiac hypertrophy and dysfunction via post-translational modification of TAB1.

Effect of tea polyphenols supplement on growth performance, antioxidation, and gut microbiota in squabs.

Early life nutritional supplementation can significantly improve pigeon health. Both the nutritional crops of parental pigeons and the intestinal development of squabs play key roles in the growth rate of squabs. Tea polyphenols (TPs), as natural plant extracts, exhibit potential biological activities. However, the impact of TPs on the intestinal function of squabs is not known. This study evaluated the effects of TPs on growth performance, immunity, antioxidation, and intestinal function in squabs. A total of 432 young pigeons (1 day old) were divided into four groups: a control group (fed a basic diet) and three treatment groups (low, medium, and high dose groups; 100, 200, and 400 mg/kg TPs, respectively). On the 28th day, samples of serum, mucosal tissue, and digests from the ileum of squabs were collected for analysis. The results revealed that TP supplementation significantly reduced the feed-to-meat ratio and improved the feed utilization rate and serum biochemical indices in squabs. Additionally, it enhanced the intestinal barrier function of birds by promoting intestinal development and integrity of tight junctions and regulating digestive enzyme activities and intestinal flora. Mechanistically, TPs activated the Nrf2-ARE signaling pathway, which may be associated with improved antioxidant and immune responses, correlating with an increased abundance of Candida arthritis and Corynebacterium in the ileum.

Identification of diagnostic genes for both Alzheimer's disease and Metabolic syndrome by the machine learning algorithm.

Background: Alzheimer's disease is the most common neurodegenerative disease worldwide. Metabolic syndrome is the most common metabolic and endocrine disease in the elderly. Some studies have suggested a possible association between MetS and AD, but few studied genes that have a co-diagnostic role in both diseases. Methods: The microarray data of AD (GSE63060 and GSE63061 were merged after the batch effect was removed) and MetS (GSE98895) in the GEO database were downloaded. The WGCNA was used to identify the co-expression modules related to AD and MetS. RF and LASSO were used to identify the candidate genes. Machine learning XGBoost improves the diagnostic effect of hub gene in AD and MetS. The CIBERSORT algorithm was performed to assess immune cell infiltration MetS and AD samples and to investigate the relationship between biomarkers and infiltrating immune cells. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD and normal individuals were visualized with the Seurat standard flow dimension reduction clustering the metabolic pathway activity changes each cell with ssGSEA. Results: The brown module was identified as the significant module with AD and MetS. GO analysis of shared genes showed that intracellular transport and establishment of localization in cell and organelle organization were enriched in the pathophysiology of AD and MetS. By using RF and Lasso learning methods, we finally obtained eight diagnostic genes, namely ARHGAP4, SNRPG, UQCRB, PSMA3, DPM1, MED6, RPL36AL and RPS27A. Their AUC were all greater than 0.7. Higher immune cell infiltrations expressions were found in the two diseases and were positively linked to the characteristic genes. The scRNA-seq datasets finally obtained seven cell clusters. Seven major cell types including CD8 T cell, monocytes, T cells, NK cell, B cells, dendritic cells and macrophages were clustered according to immune cell markers. The ssGSEA revealed that immune-related gene (SNRPG) was significantly regulated in the glycolysis-metabolic pathway. Conclusion: We identified genes with common diagnostic effects on both MetS and AD, and found genes involved in multiple metabolic pathways associated with various immune cells.

Therapeutic potential of NR4A1 in cancer: Focus on metabolism.

Metabolic reprogramming is a vital hallmark of cancer, and it provides the necessary energy and biological materials to support the continuous proliferation and survival of tumor cells. NR4A1 is belonging to nuclear subfamily 4 (NR4A) receptors. NR4A1 plays diverse roles in many tumors, including melanoma, colorectal cancer, breast cancer, and hepatocellular cancer, to regulate cell growth, apoptosis, metastasis. Recent reports shown that NR4A1 exhibits unique metabolic regulating effects in cancers. This receptor was first found to mediate glycolysis via key enzymes glucose transporters (GLUTs), hexokinase 2 (HK2), fructose phosphate kinase (PFK), and pyruvate kinase (PK). Then its functions extended to fatty acid synthesis by modulating CD36, fatty acid-binding proteins (FABPs), sterol regulatory element-binding protein 1 (SREBP1), glutamine by Myc, mammalian target of rapamycin (mTOR), and hypoxia-inducible factors alpha (HIF-1α), respectively. In addition, NR4A1 is involving in amino acid metabolism and tumor immunity by metabolic processes. More and more NR4A1 ligands are found to participate in tumor metabolic reprogramming, suggesting that regulating NR4A1 by novel ligands is a promising approach to alter metabolism signaling pathways in cancer therapy. Basic on this, this review highlighted the diverse metabolic roles of NR4A1 in cancers, which provides vital references for the clinical application.

Effect and Role of miR-196b in Ectopic Pregnancy.

Ectopic pregnancy (EP) is associated with significant morbidity and mortality, but the molecular mechanism of this condition is still unclear. miR-196b, a hot research direction for the past few years, participates in the occurrence of various diseases but whether it plays a regulatory role in EP is still unclear. This research was set to investigate the expression and potential value of miR-196b in EP. qRT-PCR was utilized to determine the relative expression of miR-196b in peripheral blood of EP patients and to observe the expression changes of miR-196b before and after treatment. Correlation analysis of miR-196b with HCG and progesterone was performed. Logistic regression analysis was applied to independent risk factors affecting EP patients. TargetScan was utilized to predict the downstream target genes of miR-196b, and GO and KEGG analysis was carried out using the R language pack. qRT-PCR showed that miR-196b expression in peripheral blood of EP patients was lower than that of normal people. miR-196b expression in patients after treatment was notably higher than that before treatment. In addition, correlation analysis showed that miR-196b was positively correlated with the expression of HCG, progesterone, and estradiol. Risk factor analysis revealed that abortion history, pelvic inflammatory disease history, lower abdominal surgery history, and miR-196b were independent risk factors for EP, and the AUC of the combined ROC curve was 0.899. GO function enrichment and KEGG signal pathway enrichment found 10 potential functions and 2 potential signal pathways of miR-196b. miR-196b is expressed in EP patients, is differentially expressed according to the change in EP condition, and is expected to become a promising index for clinical diagnosis of EP.

Simplified stroke imaging selection modality for endovascular thrombectomy in the extended time window: systematic review and meta-analysis.

BACKGROUND: The impact of imaging selection modality on clinical outcomes of endovascular thrombectomy (EVT) in the 6-24-hour time window remains undetermined. We compared the clinical outcomes of a simplified stroke imaging selection modality using non-contrast computed tomography (NCCT)±CT angiography (CTA) with using advanced CT perfusion (CTP). METHODS: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched from inception to 1 May 2022 to compare NCCT±CTA and CTP for patient selection for EVT in late-presenting stroke with large vessel occlusions (LVO). The primary outcome was the proportion of patients achieving functional independence (modified Rankin Scale score 0-2) within 180 days. The secondary outcomes included mortality within 90 days, successful recanalization, and any intracranial hemorrhage. RESULTS: A total of 3419 patients in six articles were included in this meta-analysis. There was no significant difference between NCCT±CTA (no-CTP) and CTP in functional independence either in overall or subgroup analysis. However, the mortality in the no-CTP group was higher than in the CTP group. Furthermore, within the DAWN/DEFUSE 3-like subgroup, there were no significant differences in mortality, successful recanalization, and any intracranial hemorrhage between the two groups. CONCLUSION: There was no significant difference between the simplified NCCT±CTA modality and the advanced CTP modality. The use of NCCT±CTA may represent a reasonable option for selecting patients for EVT in the extended time window, especially in the absence of CTP and acute phase MRI capabilities.

Clinical characteristics and molecular etiology of partial 17α-hydroxylase deficiency diagnosed in 46,XX patients.

Introduction: Complete 17α-hydroxylase deficiency (17OHD) is relatively common, with typical juvenile female genitalia, severe hypertension, hypokalemia, and the absence of sexual development, but partial (or non-classical) 17OHD (p17OHD) is extremely rare. The p17OHD patients can present with a broad spectrum of symptoms in 46,XX karyotype including various degree of spontaneous breast development after puberty, recurrent ovarian cysts, oligomenorrhea and infertility depending on specific gene mutations and other influencing factors. Methods: This paper is a retrospective analysis of p17OHD cases from 1997 to 2021 in a Chinese tertiary hospital. Eight patients were recruited from unrelated families according to clinical data. Genotypes of patients were determined by sequencing the CYP17A1 genes. Clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments. Results: All seven post-pubertal patients had abnormal menses. All patients had enlarged multilocular ovaries, and six (6/8) had a history of ovarian cystectomy prior to a definite diagnosis of p17OHD. All eight patients' sex hormone levels were in accord to hypogonadism with mildly elevated follicle-stimulating hormone levels, and oral contraceptives effectively suppressed the ovarian cysts. Of the four patients who underwent plasma renin activity tests, all showed results below the reference range. Fourteen alleles with a CYP17A1 mutation were found. Exon 6 was the most frequent mutation site (5/14), and four out of these five mutations were c.985_987delTACinsAA, being the most common one. In Case 2, c.1220dupA was a newly reported mutation of CYP17A1. Conclusions: 46,XX p17OHD patients were born with highly fragile ovarian reserve due to diverse mutations of CYP17A1. However, their multi-ovarian cysts can be managed conservatively for fertility preservation. This study focuses on p17OHD in 46,XX by locating the complex genetic causes in novel mutations, summarizing the puzzling spectrum of clinical manifestations, and illustrating the significance of fertility preservation in these scarce cases.

Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation.

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3-30 µmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation.

Endostar, an Antiangiogenesis Inhibitor, Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer.

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

The Role of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Predicting Treatment Response for Cervical Cancer Treated with Concurrent Chemoradiotherapy.

PURPOSE: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting early treatment response. MATERIALS AND METHODS: Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) were enrolled. Pelvic DCE-MRI scans were performed before RT (pre-RT), in the middle of RT (mid-RT), and at the end of RT (post-RT), separately. Parameters (ie, Ktrans, Kep, and Ve) were measured. Pre-, mid-, and post-RT Ktrans were denoted as Ktrans-preTx, Ktrans-midTx, and Ktrans-postTx, respectively. And the same denoting rule also went for Kep and Ve. Difference for the same parameter such as Ktrans measured between two consecutive time points was calculated as second Ktrans value minus first Ktrans value. The differences in Ktrans between pre-RT and post-RT, between pre-RT and mid-RT, and between mid-RT and post-RT were denoted as ΔKtrans-post-preTx, ΔKtrans-mid-preTx, and ΔKtrans-post-midTx, respectively, and the same denoting rule was also applied to Kep and Ve. RESULTS: A total of 57 patients were enrolled. After the treatment, 31 patients had complete response (CR group). The remaining 26 patients had partial response (NCR group). Significant differences were found in Ktrans-postTx, Kep-postTx, Ve-midTx, ΔKtrans-post-preTx, ΔKtrans-post-midTx, ΔKep-post-preTx, ΔKep-mid-preTx and ΔKep-post-midTx between the two groups. Receiver operating characteristic (ROC) analysis for their performances in predicting treatment response showed an area under curve (AUC) of 0.656-0.849, sensitivity of 61.3-93.5%, specificity of 46.1-73.1%, and maximal Youden Index of 36.5-66.6. Among those parameters, Kep-postTx was the best, and its AUC, sensitivity, specificity, maximal Youden Index, and cutoff value were 0.849, 87.1%, 73.1%, 60.2, and 0.341, respectively. These combined parameters showed an AUC of 0.952, with sensitivity of 87.1%, specificity of 96.1%, and maximal Youden Index of 83.2. CONCLUSION: DCE-MRI parameters can predict early treatment outcome. Among those parameters, Kep-postTx is the best predictor. The combination of multi-parameters can increase the predictive potency.

Effects of Dexmedetomidine as an Analgesic Adjuvant for Surgery of Femur Fracture: A Systematic Review and Meta-Analysis.

Patients who undergo surgery of femur fracture suffer the excruciating pain. Dexmedetomidine (DEX) is a unique α2-adrenergic receptor agonist with sedative and analgesic properties, whose efficacy and safety are still unclear for surgery of femur fracture. Randomized controlled trials comparing the effects of addition of DEX to general or local anesthesia in surgery of femur fracture were searched from MEDLINE, EMBASE, and the Cochrane Library database. Patients who received DEX infusion had a significant longer time to rescue analgesia compared with those without DEX coadministration. DEX treatment seemed to reduce the visual analog score; however, the significance did not reach any statistical difference. DEX as an analgesic adjuvant did not reduce the onset of sensory block time, shorten the time to achieve maximum sensory block level, and provide a longer duration of sensory block. The difference in mean sedation scores between 2 groups was not statistically significant. As for adverse effects, DEX therapy significantly increased the rate of hypotension. In conclusion, dexmedetomidine as a local anesthetic adjuvant in femur fracture surgery had a longer duration of rescue analgesia. However, the incidence of hypotension was markedly increased in these patients. It was worth noting that the evidence was of low to moderate quality.

Association of a unicornuate uterus with adverse obstetric outcomes: A retrospective cohort study.

OBJECTIVE: To estimate the association of unicornuate uterus (UU) with adverse obstetric outcomes. METHODS: Using data from 26 737 singleton childbirths from a tertiary hospital from 1999 to 2019, we identified 44 births from women with a UU. A total of 367 births from women with a normal uterus were randomly selected as controls. The outcome measures were preterm birth (PTB), breech presentation, and cesarean delivery. The subdivisions of PTB and indications for cesarean delivery were described. RESULTS: The presence of UU was associated with an increased risk of PTB (adjusted risk ratio [aRR], 2.3; 95% confidence interval [CI], 1.1-4.9), breech presentation (aRR, 6.2; 95% CI, 2.9-13.2), and cesarean delivery (aRR, 2.1; 95% CI, 1.8-2.7). For women with a UU, most PTBs (7/9) were moderate to late PTBs, and approximately half of the PTBs (4/9) were iatrogenic due to preeclampsia (PE). Breech presentation, PE, and prior surgery for rudimentary horn resection were UU-related indications for cesarean delivery. CONCLUSIONS: Women with a UU have a higher risk of PTB, breech presentation, and cesarean delivery. Understanding of the subdivisions of PTBs and indications for cesarean delivery might help clinicians when counseling women with pregnancy complicated by a UU.

Clinical characteristics and management of Turner patients with a small supernumerary marker chromosome.

OBJECTIVE: To summarize the clinical characteristics of Turner syndrome (TS) with a small supernumerary marker chromosome (sSMC) and discuss the clinical significance and management of TS patients with sSMC. METHODS: A retrospective analysis was conducted on the clinical data of 244 patients with disorders of sexual development admitted to Peking Union Medical College Hospital from February 1984 to July 2020. RESULTS: Among the 244 patients with a disorder of sexual development, 69 cases of TS were identified in which 13 patients had sSMC. Their ages ranged from 3 to 28 years old with an average of 14.31 ± 6.40 years. All 13 sSMC-positive patients had typical clinical manifestations of TS except ambiguous genitalia in four cases. SRY gene testing was performed in 11sSMC-positive patients and 10 patients were positive for SRY and one was negative. Among the 10 SRY-positive patients, two cases had hirsutism and clitoral enlargement and two cases had clitoral enlargement only. Nine sSMC and SRY-positive patients underwent gonadectomy and one had left gonadal gonadoblastoma with seminoma in situ and right gonadal seminoma in situ. CONCLUSIONS: Although the sSMC positive detection rate in DSD patients is uncommon (5.33% in our sample), the positive SRY detection rate in sSMC-positive TS patients was extremely high in our TS patients. And TS patients with sSMC and SRY positive had a significantly increased risk of gonadal germ cell tumors. Routine SRY screening should be performed in TS patients with sSMC, and a gonadectomy should be performed in TS patients with sSMC and SRY positive to prevent the occurrence of tumors.

Clinical characteristics and survival outcomes of malignant struma ovarii confined to the ovary.

BACKGROUND: Malignant struma ovarii (MSO) is a unique type of ovarian malignancy that data on the survival outcome is limited and management strategy remains controversial due to its extreme rarity. METHODS: To investigate the clinical characteristics and treatment options in patients with MSO confined to the ovary, while also evaluating the recurrent-free survival (RFS) and overall survival (OS) rate in this population, a retrospective study was conducted. One hundred twenty-five cases of MSO confined to the ovary were enrolled and their clinical characteristics, treatment strategies, and results of follow-up were analyzed. OS and RFS were assessed by Kaplan-Meier analyses and Cox regression models. RESULTS: The most common pathological subtype in this cohort was papillary carcinoma (44.8%). Other reported subtypes, in order of prevalence, were follicular variant of papillary carcinoma, follicular carcinoma, and mixed follicular-papillary carcinoma. Surgical treatment options varied in this cohort that 8.0% of the patients received ovarian cystectomy, 33.6% underwent unilateral salpingo-oophorectomy (USO), 5.6% received bilateral salpingo-oophorectomy (BSO), 21.6% received total abdominal hysterectomy with BSO (TAH/BSO), and 17.6% were treated with debulking surgery; 20.0% of them received radioiodine therapy (RAI). Twenty-seven patients experienced recurrence with a median RFS of 14.0 years (95% confidence interval [CI], 9.5-18.5). The 5-year and 10-year recurrent rate were 27.1, 35.2%, respectively. Eight patients died during follow-up, with five attributed to MSO; the 5-year, 10-year, and 20-year OS rate was 95.3, 88.7 and 88.7%, respectively. However, the univariate and multivariate Cox regression showed no potential risk factor for RFS and OS. CONCLUSION: Patients with MSO confined to the ovary had an excellent survival outcome, despite varied treatment strategies, and the recurrent rate was relatively high. We recommend USO as the preferred surgical option in this population since more aggressive surgery does not improve outcomes and the benefits of RAI are uncertain.