Quinic acid regulated TMA/TMAO-related lipid metabolism and vascular endothelial function through gut microbiota to inhibit atherosclerotic.

BACKGROUND: Quinic acid (QA) and its derivatives have good lipid-lowering and hepatoprotective functions, but their role in atherosclerosis remains unknown. This study attempted to investigate the mechanism of QA on atherogenesis in Apoe-/- mice induced by HFD. METHODS: HE staining and oil red O staining were used to observe the pathology. The PCSK9, Mac-3 and SM22a expressions were detected by IHC. Cholesterol, HMGB1, TIMP-1 and CXCL13 levels were measured by biochemical and ELISA. Lipid metabolism and the HMGB1-SREBP2-SR-BI pathway were detected by PCR and WB. 16 S and metabolomics were used to detect gut microbiota and serum metabolites. RESULTS: QA or low-frequency ABX inhibited weight gain and aortic tissue atherogenesis in HFD-induced Apoe-/- mice. QA inhibited the increase of cholesterol, TMA, TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe-/- mice induced by HFD. Meanwhile, QA or low-frequency ABX treatment inhibited the expression of CAV-1, ABCA1, Mac-3 and SM22α, and promoted the expression of SREBP-1 and LXR in the vascular tissues of HFD-induced Apoe-/- mice. QA reduced Streptococcus_danieliae abundance, and promoted Lactobacillus_intestinalis and Ileibacterium_valens abundance in HFD-induced Apoe-/- mice. QA altered serum galactose metabolism, promoted SREBP-2 and LDLR, inhibited IDOL, FMO3 and PCSK9 expression in liver of HFD-induced Apoe-/- mice. The combined treatment of QA and low-frequency ABX regulated microbe-related Glycoursodeoxycholic acid and GLYCOCHENODEOXYCHOLATE metabolism in HFD-induced Apoe-/- mice. QA inhibited TMAO or LDL-induced HCAECs damage and HMGB1/SREBP2 axis dysfunction, which was reversed by HMGB1 overexpression. CONCLUSIONS: QA regulated the gut-liver lipid metabolism and chronic vascular inflammation of TMA/TMAO through gut microbiota to inhibit the atherogenesis in Apoe-/- mice, and the mechanism may be related to the HMGB1/SREBP2 pathway.

Role of the gut microbiota in the pathogenesis of endometriosis: a review.

Endometriosis is classically defined as a chronic inflammatory heterogeneous disorder occurring in any part of the body, characterized by estrogen-driven periodic bleeding, proliferation, and fibrosis of ectopic endometrial glands and stroma outside the uterus. Endometriosis can take overwhelmingly serious damage to the structure and function of multi-organ, even impair whole-body systems, resulting in severe dysmenorrhea, chronic pelvic pain, infertility, fatigue and depression in 5-10% women of reproductive age. Precisely because of a huge deficiency of cognition about underlying etiology and complex pathogenesis of the debilitating disease, early diagnosis and treatment modalities with relatively minor side effects become bottlenecks in endometriosis. Thus, endometriosis warrants deeper exploration and expanded investigation in pathogenesis. The gut microbiota plays a significant role in chronic diseases in humans by acting as an important participant and regulator in the metabolism and immunity of the body. Increasingly, studies have shown that the gut microbiota is closely related to inflammation, estrogen metabolism, and immunity resulting in the development and progression of endometriosis. In this review, we discuss the diverse mechanisms of endometriosis closely related to the gut microbiota in order to provide new approaches for deeper exploration and expanded investigation for endometriosis on prevention, early diagnosis and treatment.

Prevalence of pediatric lower urinary tract symptoms in a national claims database of privately insured patients, 2003-2014.

BACKGROUND: We conducted this study to estimate the prevalence of pediatric lower urinary tract symptoms (pLUTS) in a US privately insured pediatric population who are 6-20 years old by age, sex, race/ethnicity from 2003-2014. This has not been previously described in the literature. METHODS: We retrospectively reviewed Optum's de-identified Clinformatics® Data Mart Database between 2003-2014. A pLUTS patient was defined by the presence of ≥ 1 pLUTS-related ICD-9 diagnosis code between the age of 6-20 years. Neurogenic bladder, renal transplant and structural urologic disease diagnoses were excluded. Prevalence by year was calculated as a proportion of pLUTS patients among the total population at risk. Variables reviewed included age, sex, race, geographic region, household factors and clinical comorbidities including attention-deficit/hyperactivity disorder (ADHD), constipation, and sleep apnea. Point of service (POS) was calculated as a proportion of pLUTS-related claims associated with a POS compared to the total claims at all POS in the time period. RESULTS: We identified 282,427 unique patients with ≥ 1 claim for pLUTS between the ages of 6-20 years from 2003 to 2014. Average prevalence during this period was 0.92%, increasing from 0.63% in 2003 to 1.13% in 2014. The median age group of patients was 6-10 years. More patients were female (59.80%), white (65.97%), between 6 and 10 years old (52.18%) and resided in the Southern US (44.97%). Within a single household, 81.71% reported ≤ 2 children, and 65.53% reported ≥ 3 adults. 16.88% had a diagnosis of ADHD, 19.49% had a diagnosis of constipation and 3.04% had a diagnosis of sleep apnea. 75% of pLUTS-related claims were recorded in an outpatient setting. CONCLUSIONS: Families consistently seek medical care in the outpatient setting for pLUTS. The demographic and clinical characteristics of our cohort reflect prior literature. Future studies can help define temporal relationships between household factors and onset of disease as well as characterize pLUTS-related healthcare resource utilization. Additional work is required in publicly insured populations.

The Association Between Insomnia, Insomnia Medications, and Erectile Dysfunction.

BACKGROUND: Sleep quality and duration have been investigated for their association with health. Insomnia affects up to one-third of adults and may impact male erectile function. In addition, medical treatments for insomnia (many of which are sedatives) may also affect erectile quality. OBJECTIVE: To investigate the association of erectile dysfunction (ED) in patients diagnosed with and treated for insomnia. DESIGN, SETTING, AND PARTICIPANTS: We utilized the IBM MarketScan (2007-2016) Commercial and Medicare Supplemental Databases (v 2.0). Age- and enrollment-matched controls were selected among patients without insomnia diagnosis or treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard models were used to estimate the risk of incident ED (ie, diagnosis alone, or diagnosis and treatment with phosphodiesterase-5 inhibitors [PDE5i], intracavernous injection (ICI)/urethral suppositories, and penile prosthesis) after the diagnosis or treatment of insomnia while adjusting for relevant comorbidities. RESULTS AND LIMITATIONS: In total, 539 109 men with an insomnia diagnosis were identified. Of these men, 356 575 were also medically treated for insomnia. The mean (±standard deviation) follow-up times for patients diagnosed with insomnia and those diagnosed with and treated for insomnia were 2.8 ± 1.6 and 3.1 ± 1.8 yr, respectively. Men with insomnia were more commonly smokers and had a higher number of office visits and comorbidities than controls (p < 0.001). On an adjusted analysis, both untreated and treated insomnia were associated with increased risks of ED diagnosis (hazard ratio or HR [95% confidence interval {CI}]: 1.58 [1.54-1.62] and 1.66 [1.64-1.69], respectively; p < 0.001). Similarly, men with treated insomnia had a higher risk of having ED treated with PDE5i (HR [95% CI]: 1.52 [1.49-1.55]; p < 0.001) and ICI (HR [95% CI]: 1.32 [1.14-1.54]; p < 0.001) when compared with controls. A limitation of this study was that a lack of granularity regarding patient clinical characteristics (eg, severity of disease, laboratory data, etc.) is inherent to insurance claims data. In addition, the follow-up was limited and may affect associations at longer time points. CONCLUSIONS: In the current report, a consistent association between insomnia and ED diagnosis was identified. Men diagnosed with insomnia only were found to have a higher risk of developing ED. Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED. Given the prevalence of insomnia, future studies are warranted to delineate the association of insomnia and its treatment with erectile function. PATIENT SUMMARY: Insomnia affects up to one-third of adults and impact male erectile function. Men only diagnosed with insomnia were found to have a higher risk of developing erectile dysfunction (ED). Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED.

Design and synthesis of oridonin derivatives as cytotoxic agents.

Oridonin is one of the ent-kaurane diterpenes that have been studied extensively for various bioactivities. In an effort to expand natural scaffold-based library as anticancer agents, we have designed and synthesised a number of novel oridonin derivatives and evaluated their bioactivities on a panel of human cancer cell lines (HCT116, A375, MCF-7, HepG2, and A549). Compound 4b bearing a 4-fluorophenyl moiety was found to be the most active compound with an IC50 value of 0.3 µM against MCF-7 cells, which was 7.4-fold more active than oridonin. This study could provide some insightful information for further synthesis of oridonin derivatives as anticancer agents.

Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events.

BACKGROUND: Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). AIM: We investigated the risk for SRD, RVO, and ION in patients using PDE5is. METHODS: We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments. OUTCOMES: HRs for SRD, RVO, and ION. RESULTS: In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO. CLINICAL IMPLICATIONS: We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION). STRENGTHS AND LIMITATIONS: Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding. CONCLUSIONS: Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.

Prevalence of pediatric lower urinary tract symptoms in a US population seeking medical care, 2003- 2014.

Background: We conducted this study to estimate the prevalence of pediatric lower urinary tract symptoms (pLUTS) in a US privately-insured pediatric population who are 18 years of age or older by age, sex, race/ethnicity from 2003-2014. This has not been previously described in the literature. Methods: We retrospectively reviewed Optum's de-identifed Clinformatics® Data Mart Database database between 2003-2014. A pLUTS patient was defined by the presence of ≥ 1 pLUTS-related ICD-9 diagnosis code between the age of 6-20 years. Neurogenic bladder, renal transplant and structural urologic disease diagnoses were excluded. Prevalence by year was calculated as a proportion of pLUTS patients among the total population at risk. Variables reviewed included age, sex, race, geographic region, household factors and clinical comorbidities including attention-deficit/hyperactivity disorder (ADHD), constipation, and sleep apnea. Point of service (POS) was calculated as a proportion of pLUTS-related claims associated with a POS compared to the total claims at all POS in the time period. Results: We identified 282,427 unique patients with ≥ 1 claim for pLUTS between the ages of 6-20 years from 2003-2014. Average prevalence during this period was 0.92%, increasing from 0.63% in 2003 to 1.13% in 2014. Mean age was 12.15 years. More patients were female (59.80%), white (65.97%), between 6-10 years old (52.18%) and resided in the Southern US (44.97%). Within a single household, 81.71% reported ≤ 2 children, and 65.53% reported ≥ 3 adults. 16.88% had a diagnosis of ADHD, 19.49% had a diagnosis of constipation and 3.04% had a diagnosis of sleep apnea. 75% of pLUTS-related claims were recorded in an outpatient setting. Conclusions: Families consistently seek medical care in the outpatient setting for pLUTS. The demographic and clinical characteristics of our cohort reflect prior literature. Future studies can help define temporal relationships between household factors and onset of disease as well as characterize pLUTS-related healthcare resource utilization. Additional work is required in publicly-insured populations.

A Fully Implantable and Programmable Epidural Spinal Cord Stimulation System for Rats with Spinal Cord Injury.

Epidural spinal cord stimulation (ESCS) is a potential treatment for the recovery of the motor function in spinal cord injury (SCI) patients. Since the mechanism of ESCS remains unclear, it is necessary to study the neurophysiological principles in animal experiments and standardize the clinical treatment. In this paper, an ESCS system is proposed for animal experimental study. The proposed system provides a fully implantable and programmable stimulating system for complete SCI rat model, along with a wireless charging power solution. The system is composed of an implantable pulse generator (IPG), a stimulating electrode, an external charging module and an Android application (APP) via a smartphone. The IPG has an area of 25×25 mm2 and can output 8 channels of stimulating currents. Stimulating parameters, including amplitude, frequency, pulse width and sequence, can be programmed through the APP. The IPG was encapsulated with a zirconia ceramic shell and two-month implantable experiments were carried out in 5 rats with SCI. The main focus of the animal experiment was to show that the ESCS system could work stably in SCI rats. The IPG implanted in vivo can be charged through the external charging module in vitro without anesthetizing the rats. The stimulating electrode was implanted according to the distribution of ESCS motor function regions of rats and fixed on the vertebrae. The lower limb muscles of SCI rats can be activated effectively. The two-month SCI rats needed greater stimulating current intensity than the one-month SCI rats The results indicated that the stimulating system provides an effective and simplified tool for studying the ESCS application in motor function recovery for untethered animals.

Association of preoperative monocyte/lymphocyte ratio with postoperative oxygenation impairment in patients with acute aortic syndrome.

BACKGROUND: Postoperative oxygenation impairment represents a common complication in patients with the acute aortic syndrome (AAS). The study aimed to explore the relationship between inflammatory indicators and AAS patients with oxygenation impairment after operation. METHODS: In this study, 330 AAS patients who underwent surgery were enrolled and divided into 2 groups based on postoperative oxygenation impairment (non-oxygenation impairment group and oxygenation impairment group). Regression analysis was performed to assess the relationship between inflammatory indicators and postoperative oxygenation impairment. A smooth curve and interaction analysis were further conducted. Stratified analysis was used according to preoperative monocyte/lymphocyte ratio (MLR) (Tertiles). RESULTS: Multivariate analysis showed that preoperative MLR was independently related to oxygenation impairment after surgery in AAS patients (OR, 95% CI, P: 2.77, 1.10-7.00, 0.031). The smooth curve indicated the risk of postoperative oxygenation impairment was higher with the elevated preoperative MLR. Interaction analysis revealed that patients with AAS with high preoperative MLR who had coronary artery disease (CAD) had a higher risk of oxygenation impairment after operation. Moreover, stratified analysis was performed according to baseline MLR (Tertiles), and a higher baseline MLR level in AAS patients was correlated with a lower arterial oxygen tension (PaO2) / inspiratory oxygen fraction (FiO2) ratio perioperatively. CONCLUSIONS: In AAS patients, preoperative MLR level was independently related to postoperative oxygenation impairment.

Congenital male genital malformations and paternal health: An analysis of the US claims data.

OBJECTIVE: To investigate the potential association between paternal health and male genital malformations in the offspring. MATERIALS AND METHODS: We analyzed data from 2007 to 2016 derived from the IBM MarketScan Research database, which reports on reimbursed private healthcare claims in the United States. The association between paternal comorbidities (defined as individual and combined measures) and genital malformations in male offspring was analyzed. RESULTS: Of 376,362 male births, 22% of fathers had at least one component of metabolic syndrome (≥1) prior to conception. Totals of 2880 cases of cryptorchidism (0.77%) and 2651 cases of hypospadias (0.70%) were identified at birth. While 0.76% of sons born to fathers with no metabolic syndrome components were diagnosed with cryptorchidism, 0.82% of sons with fathers with multiple metabolic syndrome components had cryptorchidism. Similarly, 0.69% versus 0.88% of sons had hypospadias when fathers had 0 or 2+ components of metabolic syndrome. After adjusting for maternal and paternal factors, the odds of a son being diagnosed with hypospadias increased with two or more paternal metabolic syndrome components (Odds ratio [95% confidence interval]: 1.27 [1.10-1.47]). Specific components of paternal metabolic syndrome were not generally more associated with a son's genital malformations. When we performed a subgroup analysis where genital malformations were defined based on surgical correction, the association with hypospadias persisted. CONCLUSIONS: Fathers with multiple components of metabolic syndrome in the preconception period were observed to be at increased risk for having sons born with hypospadias. The results support the association between a man's andrological and overall health.

The association of preconception paternal metabolic syndrome on early childhood emergency department visits and hospitalizations.

BACKGROUND: Increasing preconception paternal comorbidity has been associated with adverse pregnancy outcomes. However, whether the father's health impacts the child after birth is uncertain. OBJECTIVES: In the present study, we examined the association of preconception paternal metabolic syndrome status with childhood emergency department visits and hospitalizations. MATERIALS AND METHODS: This is a longitudinal cohort study of children (295,355 boys and 278,735 girls) born to linked pairs of fathers and mothers in the United States between 2009 and 2016 within the IBM MarketScan Research database. Associations between paternal and maternal metabolic syndrome component diagnoses and subsequent hospitalizations and emergency department visits for offspring within the first 2 years of life were determined. RESULTS: Note that, 35.5% (203,617/574,090) of children had at least one emergency room visit and 6.1% (35,141/574,090) of children had an inpatient admission. After adjustment, the odds of inpatient admission and emergency department visits increased in a dose-dependent fashion among fathers with higher comorbidities. Similar trends were seen for emergency department visit utilization. DISCUSSION AND CONCLUSION: Increasing paternal preconception comorbidity is associated with a higher risk that a child requires the emergency department and inpatient care in the first years of life. An opportunity exists to engage men in preconception counseling to optimize their and their offspring's health.

Preconception paternal comorbidities and offspring birth defects: Analysis of a large national data set.

BACKGROUND: Despite the fact that the father contributes half the genome to a child, associations between paternal factors and birth defects are poorly understood. OBJECTIVES: To investigate the association between preconception paternal health and birth defects in the offspring. MATERIALS AND METHODS: We conducted analysis of a national cohort study utilizing the IBM Marketscan Research Database, which includes data on reimbursed private healthcare claims in the United States from 2007 to 2016. The potential association between paternal comorbidities, as measured by the components of metabolic syndrome (MetS), and any birth defect in the offspring was analyzed. RESULTS: Of the 712,774 live births identified, 21.2% of children were born to fathers with at least one component of the metabolic syndrome (MetS ≥1) prior to conception. Compared to infants born to fathers with no components of the metabolic syndrome, a modestly higher percentage of infants with cardiac birth defects were born to fathers with more components of MetS (MetS = 1, OR [95% CI]: 1.07 [1.01-1.13]; MetS ≥2, 1.17 [1.08-1.26], in comparison to MetS = 0) after adjusting for maternal and paternal factors. Similarly, a higher percentage of infants with respiratory defects were born to fathers with two or more components of metabolic syndrome (MetS ≥2, OR [95% CI]: 1.45 [1.22-1.71]). DISCUSSION AND CONCLUSION: In this private insurance claims-based study, we found that fathers with metabolic syndrome-related diseases before conception were at increased risk for having a child affected by birth defects, especially cardiac and respiratory defects, and this association was not influenced by paternal age or assessed maternal factors.

The association between body mass index and risk of preoperative oxygenation impairment in patients with the acute aortic syndrome.

Objective: The study aimed to determine the relationship between body mass index (BMI) and the risk of acute aortic syndrome (AAS) with preoperative oxygenation impairment. Methods: A meta-analysis of published observational studies involving BMI and AAS with preoperative oxygenation impairment was conducted. A total of 230 patients with AAS were enrolled for retrospective analysis. All patients were divided into 2 groups (Non-oxygenation impairment group and Oxygenation impairment group). Logistic regression analysis was performed to assess the relation between BMI and the risk of preoperative oxygenation impairment after the onset of AAS. Dose-response relationship curve and subgroup analysis were conducted to test the reliability of BMI as an independent factor of it. Results: For the meta-analysis, the quantitative synthesis indicated that excessive BMI increased the risk of preoperative oxygenation impairment (OR: 1.30, 95% CI: 1.05-1.60, P heterogeneity = 0.001). For the retrospective analysis, a significant association was observed after adjusting for a series of variables. BMI was significantly related to preoperative oxygenation impairment after the onset of AAS (OR: 1.34, 95% CI: 1.15-1.56, p <0.001), and compared with normal weight group (18.5 kg/m2 ≤ BMI < 23.0 kg/m2), the individuals with excessive BMI were at higher risk of preoperative oxygenation impairment for the obese group (BMI ≥ 25 kg/m2) (OR: 17.32, 95% CI: 4.03-74.48, p <0.001). A J-shape curve in dose-response relationship analysis further confirmed their positive correlation. Subgroup analysis showed that diastolic blood pressure (DBP) ≥ 90mmHg carried an excess risk of preoperative oxygenation impairment in obese patients. Conclusion: Excessive BMI was an independent risk factor for AAS with preoperative oxygenation impairment.

Bioactive isopimarane and 3,4-seco isopimarane diterpenoids from Isodon amethystoides.

Isodon amethystoides (Lamiaceae) is a popular plant in folk medicine in the southern provinces of China. Our phytochemical investigation of the twigs and leaves of this plant led to the discovery of five new diterpenoids with isopimarane and 3,4-seco isopimarane scaffolds [isoamethinols A-E (1-5)], along with the known compound 3,4-seco isopimara-4(18),7,15-triene-3-oic acid methylester (6). The chemical structures of these compounds, including the absolute configurations of the new diterpenoids, were determined by comprehensive spectroscopic analyses and single crystal X-ray diffraction measurements. These compounds were evaluated for their biological activities against a panel of human cancer cell lines, gram-positive bacterial strains and HIV. Notably, the 3,4-seco-isopimarane isoamethinol D (4) showed toxicity to the cervical Hela cancer (Hela) cells with an IC50 value of 27.21 µM and the lung (A549) cancer cells with an IC50 value of 21.47 µM. Compound 4 also exhibited mild antimicrobial activity against the oral bacterial strain Streptococcus mutans. These findings suggested that the diterpenoids with a 3,4-seco-isopimarane diterpenoids isolated from I. amethystoides could provide a novel structure scaffold for the discovery of anticancer and antimicrobial compounds.

Impact of body mass index on postoperative oxygenation impairment in patients with acute aortic syndrome.

Objective: Oxygenation impairment is a common complication of acute aortic syndrome (AAS) patients after surgical repair. The aim of this study is to identify the relationship between body mass index (BMI) and the risk of postoperative oxygenation impairment in AAS patients. Methods: A total of 227 consecutive patients who were diagnosed as AAS and underwent surgical repair were recruited. They were divided into two groups based on the postoperative oxygenation impairment (non-oxygenation impairment group and oxygenation impairment group). Logistic regression was conducted to evaluate the association between BMI and the risk of oxygenation impairment after surgery. Dose-response curve and subgroup analysis were used to test the reliability of the results of regression analysis. A meta-analysis was then performed to further confirm these results using Pubmed, Embase, and Web of Science databases. Results: For the retrospective study, a significant association was observed after adjusting for a series of variables. BMI was significantly correlated with postoperative oxygenation impairment in patients with AAS (OR, 95% CI, P: 1.27, 1.17-1.46, 0.001). Compared with the normal weight group (18.5 kg/m2 ≤ BMI <23.0 kg/m2), patients with excessive BMI were at a higher risk of oxygenation impairment for the overweight group (23.0 kg/m2 ≤ BMI <25 kg/m2) and obesity group (BMI ≥25 kg/m2) (OR, 95% CI, P: 4.96, 1.62-15.15, 0.005; 9.51, 3.06-29.57, <0.001). The dose-response curve showed that the risk of oxygenation impairment after surgery increased with the increased BMI. Besides, subgroup analysis showed that AAS patients who have an excess weight with a TNF-α ≥ 8.1 pg/ml carried an excess risk of postoperative oxygenation impairment. For the meta-analysis, the pooled result also indicated that AAS patients with high BMI had a significantly increased risk of oxygenation impairment after surgery (OR, 95% CI, P: 1.40, 1.18-1.66, 0.001). Conclusion: Excessive BMI was an independent risk factor for AAS with postoperative oxygenation impairment.

Differential expression profile of plasma exosomal microRNAs in acute type A aortic dissection with acute lung injury.

MicroRNAs (miRNAs) packaged into exosomes mediate cell communication and contribute to the pathogenesis of acute type A aortic dissection (ATAAD) with acute lung injury (ALI). The expression profile of plasma exosomal miRNAs in ATAAD patients with ALI hasn't been identified. We performed a miRNA-sequencing to analyze the differentially expressed miRNAs (DE-miRNAs) of circulating exosomes in ATAAD patients with ALI compared to patients without ALI, founding 283 specific miRNAs in two groups. We respectively selected the top 10 downregulated and upregulated DE-miRNAs for further studies. The predicted transcription factors (TFs) of these DE-miRNAs were SMAD2, SRSF1, USF1, etc. The Gene Ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) analysis predicted their target genes mainly involved acute inflammatory response, cell junction, cytoskeleton, NF-κB signaling pathway, etc. Construction and analysis of the PPI network revealed that RHOA and INSR were considered hub genes with the highest connectivity degrees. Moreover, we confirmed two exosomal miRNAs (hsa-miR-485-5p and hsa-miR-206) by real-time quantitative polymerase chain reaction (RT-qPCR) in a validation cohort. Our study identified a plasma exosomal miRNAs signature related to ATAAD with ALI. Certain DE-miRNAs may contribute to the progression of this disease, which help us better understand the pathogenesis of ATAAD with ALI.

Platelet-to-Lymphocyte Ratio and CA125 Level as a Combined Biomarker for Diagnosing Endometriosis and Predicting Pelvic Adhesion Severity.

Adhesion is a significant biological characteristic of endometriosis, and accurate evaluation of the pelvic adhesion is necessary for surgical treatment. Serum CA125 is yet the most common used biomarker in the diagnosis and follow-up of patients with endometriosis despite of its high false-positive rate and low specificity. Herein, we aimed to examine the diagnostic value of the combination of the platelet-to-lymphocyte ratio (PLR) and CA125 for patients with different stages of endometriosis and their correlations with pelvic adhesion. We retrospectively analyzed the clinical data and blood count parameters of patients with both endometriosis and other benign ovarian tumors. The mean level of CA125, the PLR and the combined marker (the CA125 level multiplied by the PLR) in the EMs group were significantly higher than those in the Cyst group (P < 0.05). ROC curve analysis was used to compare the diagnostic values of serum PLR, CA125, and the combined marker in ovarian endometriosis. The cut-off value of the PLR was 176.835, with 28.3% sensitivity and 96.9% specificity. The cut-off value of CA125 was 31.67 U/mL, with 84.1% sensitivity and 87.4% specificity. The cut-off value of the combined marker was 3894.97, with 83.4% sensitivity and 95.8% specificity. It was found that the severity of adhesion in endometriosis was positively correlated with the PLR (r = 0.286, P < 0.01), CA125 (r = 0.276, P < 0.01), and combined marker (r = 0.369, P < 0.01). The combined marker showed the highest AUC value (0.751, 95% CI: 0.666-0.837), with a sensitivity of 56.0% and a specificity of 89.6%, and the cut-off value was 9056.94. Besides, the levels of CA125, PLR, and their combination were significantly elevated in patients with endometriosis. The combined marker was not only positively correlated with pelvic adhesion but also showed a greater diagnostic value and specificity than CA125 alone. These findings indicate that the combined marker may be a potential inflammatory biomarker playing an important role in the diagnosis and assessment of adhesion in endometriosis.

Postoperative complications and pelvic organ prolapse recurrence following combined pelvic organ prolapse and rectal prolapse surgery compared with pelvic organ prolapse only surgery.

BACKGROUND: There is a growing interest in combined pelvic organ prolapse and rectal prolapse surgery for concomitant pelvic floor prolapse despite a paucity of data regarding complications and clinical outcomes of combined repair. OBJECTIVE: The primary objective of this study was to compare the <30-day postoperative complication rate in women undergoing combined POP + RP surgery with that of women undergoing pelvic organ prolapse-only surgery. The secondary objectives were to describe the <30-day postoperative complications, compare the pelvic organ prolapse recurrence between the 2 groups, and determine the preoperative predictors of <30-day postoperative complications and predictors of pelvic organ prolapse recurrence. STUDY DESIGN: This was a multicenter, retrospective cohort study at 5 academic hospitals. Patients undergoing combined pelvic organ prolapse and rectal prolapse surgery were matched by age, pelvic organ prolapse stage by leading compartment, and pelvic organ prolapse procedure compared with those undergoing pelvic organ prolapse-only surgery from March 2003 to March 2020. The primary outcome measure was <30-day complications separated into Clavien-Dindo classes. The secondary outcome measures were (1) subsequent pelvic organ prolapse surgeries and (2) pelvic organ prolapse recurrence, defined as patients who complained of vaginal bulge symptoms postoperatively. RESULTS: Overall, 204 women underwent combined surgery for pelvic organ prolapse and rectal prolapse, and 204 women underwent surgery for pelvic organ prolapse only. The average age (59.3±1.0 vs 59.0±1.0) and mean parity (2.3±1.5 vs 2.6±1.8) were similar in each group. Of note, 109 (26.7%) patients had at least one <30-day postoperative complication. The proportion of patients who had a complication in the combined surgery group and pelvic organ prolapse-only surgery group was similar (27.5% vs 26.0%; P=.82). The Clavien-Dindo scores were similar between the groups (grade I, 10.3% vs 9.3%; grade II, 11.8% vs 12.3%; grade III, 3.9% vs 4.4%; grade IV, 1.0% vs 0%; grade V, 0.5% vs 0%). Patients undergoing combined surgery were less likely to develop postoperative urinary tract infections and urinary retention but were more likely to be treated for wound infections and pelvic abscesses than patients undergoing pelvic organ prolapse-only surgery. After adjusting for combined surgery vs pelvic organ prolapse-only surgery and parity, patients who had anti-incontinence procedures (adjusted odds ratio, 1.85; 95% confidence interval, 1.16-2.94; P=.02) and perineorrhaphies (adjusted odds ratio, 1.68; 95% confidence interval, 1.05-2.70; P=.02) were more likely to have <30-day postoperative complications. Of note, 12 patients in the combined surgery group and 15 patients in the pelvic organ prolapse-only surgery group had subsequent pelvic organ prolapse repairs (5.9% vs 7.4%; P=.26). In the combined surgery group, 10 patients (4.9%) underwent 1 repair, and 2 patients (1.0%) underwent 2 repairs. All patients who had recurrent pelvic organ prolapse surgery in the pelvic organ prolapse-only surgery group had 1 subsequent pelvic organ prolapse repair. Of note, 21 patients in the combined surgery group and 28 patients in the pelvic organ prolapse-only surgery group reported recurrent pelvic organ prolapse (10.3% vs 13.7%; P=.26). On multivariable analysis adjusted for number of previous pelvic organ prolapse repairs, combined surgery vs pelvic organ prolapse-only surgery, and perineorrhaphy at the time of surgery, patients were more likely to have a subsequent pelvic organ prolapse surgery if they had had ≥2 previous pelvic organ prolapse repairs (adjusted odds ratio, 6.06; 95% confidence interval, 2.10-17.5; P=.01). The average follow-up times were 307.2±31.5 days for the combined surgery cohort and 487.7±49.9 days for the pelvic organ prolapse-only surgery cohort. Survival curves indicated that the median time to recurrence was not statistically significant (log-rank, P=.265) between the combined surgery group (4.2±0.4 years) and the pelvic organ prolapse-only surgery group (5.6±0.4 years). CONCLUSION: In this retrospective cohort study, patients undergoing combined pelvic organ prolapse and rectal prolapse surgery had a similar risk of <30-day postoperative complications compared with patients undergoing pelvic organ prolapse-only surgery. Furthermore, patients who underwent combined surgery had a similar risk of recurrent pelvic organ prolapse and subsequent pelvic organ prolapse surgery compared with patients who underwent pelvic organ prolapse-only surgery.

Association Between Endometriosis and Prognosis of Ovarian Cancer: An Updated Meta-Analysis.

Objective: Increased risk of ovarian cancer (OC) among endometriosis patients has been proposed. However, the association between endometriosis and prognosis of OC remains controversial. This study evaluated whether endometriosis had influence on the survival outcomes of OC through a meta-analysis. Methods: Relevant studies were retrieved from PubMed, Embase, and Web of Science databases and were evaluated using the Newcastle-Ottawa Quality Assessment Scale. Effect size was presented as hazard ratio (HR) and 95% confidence interval (CI). Heterogeneity test evaluation was performed using Cochran's Q test and I2 statistics. Publication bias was determined using Egger's test. Statistical analysis was performed using Stata 12.0 software. Results: Twenty-one studies involving 38641 patients were included. For the total OC, there were significant differences in overall survival (OS) [HR (95% CI)=0.67 (0.55, 0.80), P<0.001] and progression-free survival (PFS) [HR (95% CI)=0.58 (0.42, 0.81), P=0.001] between endometriosis-associated ovarian cancer (EAOC) and non-EAOC patients in the random-effects models (P<0.05). For ovarian clear cell cancer, there were significant differences in terms of OS [HR (95% CI)=0.63 (0.48, 0.83), P=0.001] and PFS [HR (95% CI)=0.67 (0.52, 0.87), P=0.002] between EAOC and non-EAOC patients in the fixed-effects models (P>0.05). Subgroup analysis suggested no significant differences between EAOC and non-EAOC in OS and PFS in the univariate analysis per subgroup, and PFS in the American subgroup (P>0.05). Conclusion: EAOC patients tended to have better OS and PFS than non-EAOC patients. Conducting higher quality prospective cohort studies with large sample sizes is recommended to confirm the authenticity of the current study's results. Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0109/.

Delayed Ejaculation After Lumbar Spine Surgery: A Claims Database Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine. METHODS: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE. RESULTS: We identified 117 918 men who underwent 162 646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE. CONCLUSIONS: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.