血管生成素样蛋白4和Ⅱ型肺泡细胞表面抗原-6与急性呼吸窘迫综合征严重程度的关系及对预后的评估效能研究

摘要 目的：分析血管生成素样蛋白4(ANGPTL4)和Ⅱ型肺泡细胞表面抗原-6(KL-6)与急性呼吸窘迫综合征严重程度的关系及对预后的评估效能。方法：选择我院自2020年1月至2022年12月收治的120例急性呼吸窘迫综合征患者作为研究对象（观察组）,根据氧合指数（PaO₂/FiO₂）分为轻度组、中度组和重度组;另选120例非急性呼吸窘迫综合征患者作为对照组。检测所有患者血清ANGPTL4和KL-6的表达水平,分析血清ANGPTL4和KL-6与APACHE Ⅱ评分、PaO₂/FiO₂的关系,使用受试者工作特征曲线（ROC）下面积（AUC）评价血清ANGPTL4联合KL-6对急性呼吸窘迫综合征预后的评估效能。结果：对比对照组,观察组血清ANGPTL4、KL-6的表达水平均明显升高（P＜0.05）;血清ANGPTL4、KL-6的表达水平在轻度组、中度组和重度组中差异有统计学意义,且急性呼吸窘迫综合征越严重,升高越明显（P＜0.05）;经Pearson相关性分析,急性呼吸窘迫综合征患者血清ANGPTL4、KL-6的表达水平与PaO₂/FiO₂呈负相关,与APACHE Ⅱ评分呈正相关（P＜0.05）;经ROC曲线分析,血清ANGPTL4联合KL-6预测急性呼吸窘迫综合征患者入院28d内死亡的敏感度为90.14%、特异度为65.74%,AUC为0.900。结论：血清ANGPTL4、KL-6表达水平升高与急性呼吸窘迫综合征严重程度增大密切相关,两者联合在患者预后评估中具有一定价值,可作为判断病情及预后的辅助指标。     

罗格列酮结合二甲双胍对多囊卵巢综合征患者胰岛素抵抗指数的影响及临床疗效

目的:探讨罗格列酮与二甲双胍联合给药对多囊卵巢综合征(PCOS)患者胰岛素抵抗指数(HOMA-IR)的变化影响与临床效果的评价。方法:回顾性选取我院收治的PCOS患者127例列为研究样本,按照用药方案差异分为两组,对照组62例采用二甲双胍进行治疗;研究组65例采用罗格列酮联合二甲双胍治疗。观察并比较两组患者治疗前后HOMA-IR、血清性激素水平、排卵率及副反应发生情况。结果:治疗后,研究组HOMA-IR低于对照组,排卵率高于对照组(P0.05);研究组患者血清E2及T水平低于对照组,而FSH及SHBG水平高于对照组(P0.05);两组患者副反应发生率比较,差异无统计学意义(P0.05)。结论:罗格列酮辅助二甲双胍治疗PCOS可显著改善患者HOMA-IR,对性激素平衡有良好作用,副作用较小。     

Elevated ovarian expression and serum concentration of α inhibin in the luteal phase during follicular development in the squirrel monkey (Saimiri boliviensis) compared to the human

The goal of the present investigation was to determine in the squirrel monkey the source and pattern of inhibin, a hormone known to effect reproductive steroid levels via pituitary and ovarian mechanisms. Since this seasonally polyestrous species is known to have elevated serum levels of reproductive steroids compared to other primates, the levels of ovarian alpha subunit mRNA expression and serum total alpha inhibin, estradiol, progesterone, and luteinizing hormone were measured and compared to human levels. Expression of the alpha subunit was robust in monkey luteal tissue compared to expression in human luteal tissue. Squirrel monkey serum inhibin peaked 4 days after the luteinizing hormone surge and correlated with progesterone changes. These luteal serum levels of inhibin were greater than 12 times higher than the human levels yet bio‐LH activities were less than in the human during the luteal phase. Inhibin concentrations during the non‐breeding season were generally half the levels measured in the breeding season and undetectable in ovariectomized animals. However, exogenous FSH stimulation induced a marked rise in inhibin, which correlated with an estradiol rise. In conclusion, abundant alpha inhibin subunit expression in the luteal ovary of the squirrel monkey and loss of serum delectability in ovariectomized animals indicates that the principle source of inhibin in the squirrel monkey is the ovary. Elevated serum inhibin levels during the luteal phase concurrent with ovulatory‐size follicular development is unique among species studied thus far. Possible simultaneous inhibin production from both follicular and luteal tissue may be responsible for the exceptionally high inhibin levels. Am. J. Primatol. 47:165–179, 1999. © 1999 Wiley‐Liss, Inc.     

Secretory phospholipase A2 in SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C)

Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.     

Telmisartan ameliorates cardiac fibrosis and diastolic function in cardiorenal heart failure with preserved ejection fraction

Chronic kidney disease (CKD) is a major contributor to the development of heart failure with preserved ejection fraction (HFpEF), whereas the underlying mechanism of cardiorenal HFpEF is still elusive. The aim of this study was to investigate the role of cardiac fibrosis in a rat model of cardiorenal HFpEF and explore whether treatment with Telmisartan, an inhibitor of renin-angiotensin-aldosterone system (RAAS), can ameliorate cardiac fibrosis and preserve diastolic function in cardiorenal HFpEF. Male rats were subjected to 5/6 subtotal nephrectomy (SNX) or sham operation (Sham), and rats were allowed four weeks to recover and form a stable condition of CKD. Telmisartan or vehicle was then administered p.o. (8 mg/kg/d) for 12 weeks. Blood pressure, brain natriuretic peptide (BNP), echocardiography, and cardiac magnetic resonance imaging were acquired to evaluate cardiac structural and functional alterations. Histopathological staining, real-time polymerase chain reaction (PCR) and western blot were performed to evaluate cardiac remodeling. SNX rats showed an HFpEF phenotype with increased BNP, decreased early to late diastolic transmitral flow velocity (E/A) ratio, increased left ventricular (LV) hypertrophy and preserved ejection fraction (EF). Pathology revealed increased cardiac fibrosis in cardiorenal HFpEF rats compared with the Sham group, while chronic treatment with Telmisartan significantly decreased cardiac fibrosis, accompanied by reduced markers of fibrosis (collagen I and collagen III) and profibrotic cytokines (α-smooth muscle actin, transforming growth factor-β1, and connective tissue growth factor). In addition, myocardial inflammation was decreased after Telmisartan treatment, which was in a linear correlation with cardiac fibrosis. Telmisartan also reversed LV hypertrophy and E/A ratio, indicating that Telmisartan can improve LV remodeling and diastolic function in cardiorenal HFpEF. In conclusion, cardiac fibrosis is central to the pathology of cardiorenal HFpEF, and RAAS modulation with Telmisartan is capable of alleviating cardiac fibrosis and preserving diastolic dysfunction in this rat model.     

Long-term data on basic reproductive parameters and evaluation of endocrine,morphological, and behavioral measures for monitoring reproductive status in a group of semifree-ranging Tonkean macaques (Macaca tonkeana)

Cycle and gestation lengths, menstruation patterns, female genital swelling characteristics, and male-female consortship durations are reported in a semifree-ranging group of Tonkean macaques (Macaca tonkeana) studied over a 12 year period. In addition, profiles of urinary estrone conjugates (E1C) and immunoreactive pregnanediol glucuronide (PdG) throughout four complete menstrual cycles in two females and three full-term pregnancies are presented. Based on intermenstrual intervals, a mean cycle length of 37–41 days (n = 55 cycles in 10 females) was found. Gestation length averaged 173 days (n = 27 pregnancies in eight females). Measurement of PdG immunoreactivity in urine revealed a cyclic pattern with a 5–15-fold increase between follicular and luteal phase concentrations, suggesting that PdG is a reliable indicator of ovarian cyclicity and luteal function. In contrast to PdG, E1C excretion showed no clear pattern throughout the cycle; however, highest values of E1C were usually found shortly before the onset of the luteal phase PdG rise at the presumed time of ovulation. Levels of both hormones were elevated during the first half of gestation and showed a marked increase throughout the second half, with maximum E1C concentrations being up to 100-fold higher than nonpregnant levels. Consortships by the male and occurrence of female genital swelling were long lasting (on average 5–10 days and 13 days, respectively) and were restricted to the follicular phase of the cycle. The day of maximal swelling and day of detumescence as well as the end of male consortship were closely associated with the periovulatory period. Swellings and consortships were longer following lactational ammenorhea than for subsequent cycles. The evolutionary significance of the cyclical changes undergone by females upon their relations with males is discussed. © 1996 Wiley-Liss, Inc.     

The effects of infant births on the sociosexual behavior and hormonal patterns of a cooperatively breeding primate (Cebuella pygmaea)

This study examined changes in the behavioral and hormonal patterns of cooperatively breeding pairs in a primate species with the passing of time and with specific reproductive events. We (1) compared patterns of sexual, agonistic, and affiliative behavior of newly paired pygmy marmosets with the same behavioral patterns immediately after the birth of their first set of infants; (2) determined if postpartum behavioral differences existed between pairs whose infants lived and those whose infants died; and (3) examined whether behavioral patterns changed over the course of ovarian cycles in parous pygmy marmosets as had been documented in nulliparous pairs. The behavior of pairs was recorded during daily half-hour focal samples for 60 days after pairing, and 30 or 60 days after the birth of infants for pairs whose litters died or lived, respectively. Daily urine samples from females during the study were analyzed for luteinizing hormone and pregnanediol glucuronide concentrations to determine dates of ovulation. The results indicated that males consistently altered their sexual behavior and olfactory monitoring of mates during periovulatory periods in the females' cycles both postpairing and postpartum, while similar rates of social and sexual behavior were maintained between the conditions. Sexual behavior occurred throughout the females' ovarian cycles. Peaks in sexual behavior during the periovulatory period in nulliparous pairs disappeared after the birth of infants. Pairs whose infants died showed higher rates of sexual behavior than pairs with surviving infants. Social and sexual behavior may function to maintain the relationship both during and outside of ovulation, especially with the loss of infants. © 1996 Wiley-Liss, Inc.     

Information content of sexual swellings and fecal steroids in sooty mangabeys (Cercocebus torquatus atys)

The accuracy and precision of sexual swellings and fecal steroids as measures of ovarian function and the periovulatory period were compared in 4 sexually mature, individually housed, sooty mangabey females. Fecal samples were collected daily over a 10-week period during the normal breeding season. Serum was collected 3×/week, daily during peak swelling, and sex skin was rated 5×/week on a 0–5 relative scale. Both fecal estradiol (fE₂) and progesterone (fP₄) were significantly correlated with serum values in composite E₂-aligned profiles and within the cycles of individual females with average correlations of r_s = 0.6. Follicular phase means for fE₂ and luteal phase means for fP₄ were significantly correlated with the serum means across cycles, suggesting that fecal concentrations could be used to accurately evaluate cycle phases within and across females. In contrast, the timing of peak swelling relative to the periovulatory period varied considerably across the cycles of individual females. Although maximum tumescence appears to bracket the periovulatory period, individual differences in the duration of peak swelling and the timing of its onset and end tend to obscure the exact time of ovulation in relation to maximal tumescence. These data illustrate the utility of fecal steroid analysis as a tool for further evaluation of the signal value of sexual skin and its role in mating interactions. © 1996 Wiley-Liss, Inc.     

Seasonal pattern in bipolar disorders and cardio-vascular risk factors: A study from the FACE-BD cohort

Seasonal pattern (SP) and metabolic syndrome (MetS) are major contributors to poor outcome in bipolar disorders (BD). Patients with seasonal bipolar depression present increased appetite, carbohydrate cravings, weight gain, and hypersomnia, which can increase the development of MetS. MetS also appears to be associated with seasonal mood changes in the general population. This study examines whether a SP in BD is associated with an increased risk of MetS and its sub-components. One thousand four hundred and seventy-one outpatients with BD were systematically enrolled from 2009 to 2016. Inclusion required a disease duration of at least 5 years, with 486 (33%) patients with SP (SP+) and 985 (67%) without (SP–) according to the DSM IV-TR criteria. When using continuous measures of metabolic components, SP+ patients, as compared to SP–, suffered from higher levels for systolic blood pressure (p = 0.01), low-density lipoprotein cholesterol (p = 0.009), fasting glucose (p = 0.007), triglycerides levels (p = 0.03), a larger abdominal circumference (p = 0.02), and a higher body mass index (p = 0.07). In the covariance analysis, adjusted for gender, age, and bipolar subtype, as well as the number of depressive and hypomanic episode, SP+ patients had a significantly higher level of fasting glucose and higher systolic blood pressure. The frequency of MetS did not differ between groups (21.2% in SP– versus 23.9% in SP+). When using categorical definitions for abnormal metabolic components (International Diabetes Federation criteria), there were no differences between groups, except that SP+ patients were more overweight/obese as compared to SP– patients (55.03% versus 46.7%, respectively; p = 0.002) and tended to have more frequently high fasting glucose (18.2% versus 14.3%, respectively; p = 0.07). MetS was frequent in patients with BD, however not associated with SP. Patients with SP appeared more vulnerable to overweight/obesity and presented with higher levels of MetS subcomponents although these parameters were mainly in the normal range. All patients with BD should benefit from early screening and targeted management of cardio-vascular risk factors.