Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures. Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain. Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001). Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain. Clinical trial registration: ClinicalTrials.gov, identifier NCT04958746.

Value of carotid intima thickness in assessing advanced carotid plaque vulnerability: a study based on carotid artery ultrasonography and carotid plaque histology.

Background: Research has shown that carotid intima-media thickness (CIMT) could help to predict carotid plaque (CP) progression in patients with mild carotid stenosis. However, the debate continues as to the value of carotid intima thickness (CIT) in monitoring the development of CP in patients with severe carotid stenosis. This study sought to evaluate the relationships between CIT and the ultrasonic characteristics of CP and to analyze the value of CIT and the ultrasonic parameters of CP in assessing plaque vulnerability in advanced human carotid atherosclerosis. Methods: A total of 55 individuals who underwent carotid endarterectomy (CEA) were included in the study (mean age: 65±7 years; female: 9.1%). CIMT and CIT were examined at the common carotid artery (CCA). Plaque textural features, such as the gray-scale median (GSM), superb microvascular imaging (SMI) level, and total plaque area (TPA), were also identified. A Spearman correlation coefficient analysis was performed to examine the relationship between CIT and the ultrasonic parameters of CP. The CIT of various plaque types was compared. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic values of the ultrasound characteristics to evaluate CP vulnerability. Results: The mean CIT of all the participants was 0.382±0.095 mm, the mean CIT of the participants with stable plaques was 0.328±0.031 mm, and the mean CIT of participants with vulnerable plaques was 0.424±0.106 mm (P<0.001). CIT was associated with the SMI level (Spearman's correlation coefficient: r=0.392, P=0.005), TPA (Spearman's correlation coefficient: r=0.337, P=0.012). Patients with thicker CIT had larger lipid cores, higher levels of plaque vulnerability, and more intraplaque hemorrhages (IPHs). The areas under the ROCs (AUCs) with 95% confidence interval (CI) for CIMT, CIT, the SMI level, the GSM, the TPA, and the combined model for identifying vulnerable plaques were 0.673 (0.533-0.793), 0.849 (0.727-0.932), 0.771 (0.629-0.879), 0.669 (0.529-0.790), 0.858 (0.738-0.938), and 0.949 (0.854-0.990), respectively. Conclusions: CIT was associated with both the histology and ultrasonic features of CP. CIT may be helpful in the detection of severe CP development.

Impact of maternal neuraxial labor analgesia exposure on offspring's neurodevelopment: A longitudinal prospective cohort study with propensity score matching.

Background: Neuraxial analgesia is widely used to relieve labor pain; its effects on long-term neurodevelopment of offspring remain unclear. This study was designed to investigate the influence of maternal neuraxial labor analgesia on offspring mental development. Methods: This was a predefined secondary analysis of a 2-year prospective longitudinal study. Nulliparous women with single-term cephalic pregnancy preparing for vaginal delivery self-selected neuraxial analgesia or not during labor. Mothers and their offspring were followed up 2 years later. children's mental development was assessed with the bayley scales of infant development. A multivariable logistic model was used to identify factors associated with below-average mental development (Mental Development Index <90). Results: A Total of 508 pairs of mothers and children completed a 2-year follow-up. after propensity score matching, 387 pairs were included in the analysis. In both cohorts, the proportions with below-average mental development were slightly lower in children whose mothers received neuraxial labor analgesia, although not statistically significant [in the full cohort: 9.8 % (36/368) vs. 15.7% (22/140), P = 0.060; In the matched cohort: 8.3% (21/254) vs. 14.3% (19/133), P = 0.065]. A higher 2-year depression score (in the full cohort: Odds Ratio 1.15, 95% CI 1.08-1.22, P < 0.001; In the matched cohort: Odds Ratio 1.09, 95% CI 1.01-1.18, P = 0.037), but not neuraxial analgesia exposure, was associated with an increased risk of below-average mental development. Conclusions: Maternal depression at 2 years was associated with the risk of below-average mental development, whereas maternal exposure to neuraxial labor analgesia was not. Clinical Trial Registration: The study was registered with www.chictr.org.cn (ChiCTR-OCH-14004888) and ClinicalTrials.gov (NCT02823418).

The efficacy and safety of oxycodone in treating the uterine contraction pain after negative pressure aspiration: A randomized, compared, multicenter clinical study.

CONCLUSION: Oxycodone hydrochloride injection could be safely and effectively applied to negative pressure aspiration, and a 0.08 mg/kg dose could significantly reduce postoperative uterine contraction pain of patients with dysmenorrhea.

Difficult Journey to Find the Best Treatment for Homozygous Familial Hypercholesterolemia: Case Report.

Homozygous familial hypercholesterolemia (HoFH) is a rare autosomal recessive genetic disorder. It is difficult to diagnose and treat it at early stage. We present a nine-year-old boy with HoFH from China. At the beginning, he was misdiagnosed as xanthomatosis in the dermatology department of the local hospital, but the disease did not alleviate after three laser ablation operations. Later, blood lipid monitoring, ultrasound of heart and carotid artery were further added in our hospital, and finally the boy was diagnosed with HoFH by genetic testing. A biallelic mutations was observed in the fourth exon of low density lipoprotein receptor (LDLR): c.418G>A (p.E140K). Our patient achieved a relatively satisfactory therapeutic results after a series of lipid-lowering therapies including atorvastatin monotherapy, lipoprotein apheresis and double-filtration plasma pheresis. We found that LDL-C levels obtained 57% reduction from baseline after atorvastatin combined with double-filtration plasma pheresis (DFPP). It was observed that regression of carotid intima-media thickness (cIMT), valve regurgitation and xanthoma occurred after a series of Intensive lipid-lowering therapy.

Neuraxial labor analgesia is associated with a reduced risk of postpartum depression: A multicenter prospective cohort study with propensity score matching.

BACKGROUND: Depression is a common and serious complication in new mothers. We investigated the hypothesis that neuraxial labor analgesia is associated with a decreased risk of postpartum depression. METHODS: In this multicenter prospective cohort study with propensity score matching, 599 nulliparous women with single term cephalic pregnancy who planned vaginal delivery were enrolled and self-selected neuraxial analgesia or not. The primary outcome was 6-week postpartum depression assessed with the Chinese version Edinburgh Postnatal Depression Scale; a score of ≥10 was set as the threshold of postpartum depression. Logistic regression models were established to assess the association between neuraxial labor analgesia and postpartum depression. RESULTS: Of the 577 parturients who completed the study, 417 (72.3%) received neuraxial analgesia and 160 (27.7%) did not. After propensity score matching, 433 parturients were included in the analysis; of whom, 279 (64.4%) received neuraxial analgesia and 154 (35.6%) did not. The incidence of postpartum depression was lower in parturients with neuraxial analgesia than in those without (14.9% [62/417] vs. 23.8% [38/160], P=0.012 before matching; 13.3% [37/279] vs. 23.4% [36/154], P=0.007 after matching). After adjustment for confounding factors, neuraxial analgesia was associated with decreased odds of postpartum depression (odds ratio [OR] 0.50, 95% CI 0.28-0.88, P=0.015 before matching; OR 0.40, 95% CI 0.21-0.77, P=0.006 after matching). LIMITATIONS: As an observational study, unidentified confounders might influence the results. CONCLUSIONS: In nulliparae with single term cephalic pregnancy preparing to give vaginal delivery neuraxial analgesia during labor was associated with a decreased risk of 6-week postpartum depression.

Hemodynamic characteristics in preeclampsia women during cesarean delivery after spinal anesthesia with ropivacaine.

BACKGROUND: Very few studies have been published on the hemodynamic changes associated with spinal anesthesia induced with ropivacaine during cesarean deliveries in preeclamptic women. AIM: To record and analyze hemodynamic data in women with preeclampsia undergoing cesarean delivery after spinal anesthesia induced with ropivacaine. METHODS: Ten eligible women with preeclampsia were enrolled in this prospective observational study. Spinal anesthesia was performed with 2.4 mL of 0.5% ropivacaine. Hemodynamic changes were then analyzed at multiple time points. The hemodynamic responses to vasopressor interventions and uterotonic agents, as well as maternal and neonatal outcomes were also recorded. RESULTS: Stable hemodynamic trends were observed in this study. Cardiac output (CO) and stroke volume increased mildly during surgery. In contrast, mean arterial pressure and systemic vascular resistance showed a moderate decrease from induction until the end of surgery. Central venous pressure dramatically increased after delivery. Oxytocin administration was associated with the most significant hemodynamic fluctuations during surgery, namely, an increase in CO and heart rate. Phenylephrine intervention was only required in three patients, and caused an increase in mean arterial pressure and systemic vascular resistance along with a decrease in heart rate, stroke volume, and CO. No maternal and neonatal complications were observed during this study, except transient episodes of hypotension. CONCLUSION: Spinal anesthesia for caesarian delivery with ropivacaine in women with preeclampsia is linked to modest hemodynamic changes of no clinical significance in this study. Careful cardiovascular monitoring is still recommended, particularly after the delivery of the fetus or the use of oxytocin.

Neuraxial labour analgesia is associated with a reduced risk of maternal depression at 2 years after childbirth: A multicentre, prospective, longitudinal study.

BACKGROUND: Severe labour pain is an important risk factor of postpartum depression, and early depression is associated with an increased risk of long-term depression; whereas the use of epidural analgesia during labour decreases the risk of postpartum depression. OBJECTIVE: To investigate whether neuraxial labour analgesia was associated with a decreased risk of 2-year depression. DESIGN: This was a multicentre, prospective, longitudinal study. SETTING: The study was performed in Peking University First Hospital, Beijing Obstetrics and Gynecology Hospital and Haidian Maternal and Child Health Hospital in Beijing, China, between 1 August 2014 and 25 April 2017. PATIENTS: Five hundred ninety-nine nulliparous women with single-term cephalic pregnancy preparing for vaginal delivery were enrolled. MAIN OUTCOME MEASURE: Depressive symptoms were screened with the Edinburgh Postnatal Depression Scale at delivery-room admission, 6-week postpartum and 2 years after childbirth. A score of 10 or higher was used as the threshold of depression. The primary endpoint was the presence of depression at 2 years after childbirth. The association between the use of neuraxial labour analgesia and the development of 2-year depression was analysed with a multivariable logistic regression model. RESULTS: Five hundred and eight parturients completed 2-year follow-up. Of these, 368 (72.4%) received neuraxial analgesia during labour and 140 (27.6%) did not. The percentage with 2-year depression was lower in those with neuraxial labour analgesia than in those without (7.3 [27/368] vs. 13.6% [19/140]; P = 0.029). After correction for confounding factors, the use of neuraxial analgesia during labour was associated with a significantly decreased risk of 2-year depression (odds ratio 0.455, 95% confidence interval 0.230 to 0.898; P = 0.023). CONCLUSION: For nulliparous women with single-term cephalic pregnancy planning for vaginal delivery, the use of neuraxial analgesia during labour was associated with a reduced risk of maternal depression at 2 years after childbirth. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR-OCH-14004888 and ClinicalTrials.gov: NCT02823418.

Protective effect of dexmedetomidine on kidney injury of parturients with preeclampsia undergoing cesarean section: a randomized controlled study.

The present study aimed to elucidate the effects of dexmedetomidine on kidney injury of parturients with preeclampsia (PE) undergoing cesarean section. Total 134 cesarean delivery women with PE were randomly divided into intervention group (IG) and control group (CG). Both groups underwent combined spinal and epidural anesthesia (CSEA), the IG was treated with 0.4 µg/(kg·min) dexmedetomidine for 10 min before surgery. The CG was treated with equivalent saline. Heart rate (HR), blood pressure, oxygen saturation (SpO2) of the two groups were measured at different time point after administration. Level of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Visual analogue score (VAS), Ramsay sedation score (RSS), and kidney injury related indexes were evaluated at different time points. The plasma-drug concentration of patients was determined by High Performance Liquid Chromatography (HPLC) method. Compared with CG, HR, PE, and diastolic blood pressure (DBP) showed lower level while SpO2 showed higher level in IG. Furthermore, expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-10 in IG was decreased after drug administration, the contents of ß2-MG, KIM-1 and urine protein were also decreased in contrast to the CG (all P<0.05). Besides, VAS score was decreased but Ramsay score was increased in the IG (both P<0.05). The results of HPLC showed that the half life of dexmedetomidine was about 20 min and it is speculated that the drug can be quickly metabolized within 24 h. Dexmedetomidine exerted protective effects on kidney injury of parturients with PE undergoing cesarean section.

Anti-Cancerous Potential of Polyphenol-Loaded Polymeric Nanotherapeutics.

Recent evidence has extensively demonstrated the anticancer potential of nutraceuticals, including plant polyphenols. Polymeric nanocarrier systems have played an important role in improving the physicochemical and pharmacological properties of polyphenols, thus ameliorating their therapeutic effectiveness. This article summarizes the benefits and shortcomings of various polymeric systems developed for the delivery of polyphenols in cancer therapy and reveals some ideas for future work.

Newly discovered COLQ gene mutation and its clinical features in patients with acetyl cholinesterase deficiency.

To investigate the relationship between acetyl cholinesterase associated collagen gene (COLQ) mutation in patients with acetyl cholinesterase deficiency and its clinical characteristics. Serum and red blood cell acetyl cholinesterase from patients with acetyl cholinesterase deficiency (n=6) and normal controls (n=20) were measured by butyryl thiocholine substrate. COLQ gene variations were detected by sequencing. And the cholinesterase (ChE) genotypes were measured by dibucaine inhibition in vitro. The distributions of ChE surrounded the blood vessels and nerve fibers in lung or pancreas tissues were detected by immunohistochemical staining and indirect immunofluorescence. Serum lactic acid, ammonia and other clinical data were analyzed. Serum ChE in patients with acetyl cholinesterase deficiency were only 1/50 to 1/1000 fold of normal controls. Comparing to controls, dibucaine inhibition values of patients were significantly lower, while there were no differences in red blood cells acetyl cholinesterase. Serum lactic acid and ammonia in patients were significantly higher than controls. Inser 1281-1282 GC of COLQ gene was found in 2 patients, while IVS 6 + 21 T > A, IVS 6 + 30 G > T, IVS 6 + 34 T > C and IVS66 + 12 inser T mutations were found in the other 4 patients, respectively. In addition, the patients with COLQ gene mutation were resistant to regular doses of anesthetics. COLQ gene mutation may be an important reason for the lack of serum ChE in patients with acetyl cholinesterase deficiency.

Serum levels of brain-derived neurotrophic factor are associated with depressive symptoms in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to explore potential relationships between serum BDNF levels and depression in systemic lupus erythematosus (SLE) patients. METHODS: We included 208 consecutive SLE patients and 100 age-and sex-matched healthy controls. The presence of depressive symptoms was determined through the Beck Depression Inventory-II (BDI-II) score. RESULTS: The serum BDNF levels were significantly (P<0.0001) higher in SLE patients as compared to normal controls. There was a negative correlation between levels of BDNF and the SLE disease activity index 2000 (SLEDAI-2K) (r=-0.349, P<0.0001). Depression (defined as BDI-II score≥18) was identified in 54 SLE patients (26.0%, 95%CI: 20%-31.9%). The serum BDNF levels were significantly lower in depression patients at the time of admission as compared with patients without depression [27.6(IQR, 23.2-30.4)ng/ml vs. 36.2(IQR, 31.7-42.3)ng/ml; P<0.0001]. Compared with the first quartile of serum BDNF levels, the second quartile OR for depression was 0.72 (95% CI, 0.61-0.80, P=0.033). For the third and fourth quartiles, it was 0.42 (95% CI, 0.33-0.52, P=0.002) and 0.16 (95% CI, 0.09-0.24; P<0.001). CONCLUSION: Serum BDNF levels are decreased in SLE patients with depressive symptoms. In SLE, serum BNDF levels are independently associated with depressive disorders, suggesting the role of neurotrophic factors in depression.

Doppler Echocardiographic Measurements in Normal Chinese Adults (EMINCA): a prospective, nationwide, and multicentre study.

AIMS: Currently, available Doppler echocardiographic reference values are derived mainly from North American and European population studies, which may not applicable to the Chinese population. We aimed to establish normal reference values of Doppler echocardiographic parameters in a nationwide, population-based cohort of healthy Han Chinese adults. METHODS AND RESULTS: A total of 1394 qualified healthy subjects (mean age 47.3 ± 16.0 years, 678 men) were enrolled at 43 collaborating laboratories, 37 transvalvular flow and tissue Doppler parameters were obtained, and the impacts of gender and age on each parameter were analysed. Significant differences were found between men and women in 48.6% (18/37) of the parameters analysed, and among different age groups in 83.8% (31/37) of the parameters in men and in 86.5% (32/37) of the parameters in women. CONCLUSIONS: Normal reference values of Doppler echocardiographic parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Since most of these parameters differed by gender and/or age, reference values specified for gender and age should be recommended in clinical practice.

Echocardiographic measurements in normal chinese adults focusing on cardiac chambers and great arteries: a prospective, nationwide, and multicenter study.

BACKGROUND: Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults. METHODS: A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed. RESULTS: A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women. CONCLUSIONS: Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.

The application of ultrasonic velocity vector imaging technique of carotid plaque in predicting large-artery atherosclerotic stroke.

BACKGROUND: Large-artery atherosclerotic stroke (LAAs) is related to carotid plaque, but the mechanical mechanism is unclear. We aimed to use ultrasonic velocity vector imaging (VVI) technique to study the mechanical difference of carotid plaque in patients with LAAs and controls. METHODS: We enrolled 43 LAAs patients and 38 controls but all showing plaque on carotid ultrasonography. Ultrasonic VVI technique was used to analyze radial systolic and diastolic peak velocity (R-vs, R-vd), radial and circumferential peak strain (R-s, C-s) and radial displacement (R-dis) of carotid plaque. RESULTS: Compared with controls, LAAs patients showed higher pulse pressure (P = .001), pulse pressure index (PPI, P = .006), and greater stress at carotid plaque as manifested by higher absolute value of radial diastolic peak velocity (R-vd, P = .021), radial systolic peak velocity (R-vs, P = .007), radial peak strain (R-s, P = .015), and radial displacement (R-dis, P = .022). PPI was significantly correlated with R-vs (r = -.274, P = .013), R-vd (r = .304, P = .006), and R-dis (r = -.28, P = .011). But there was no correlation between R-s and blood pressure. R-s was screened to be the most predictable parameters for LAAs (odds ratio, 1.118; 95% confidence interval, 1.012∼1.236; P = .029). The area under the curve of R-s was .627. CONCLUSIONS: Radial peak strain (R-s) is a predictable parameter for the occurrence of LAAs. We predict using ultrasonic VVI technique to analyze whether the mechanics of carotid plaque is helpful to screen patients with high risks of LAAs.

Effects of epidural neostigmine and clonidine in labor analgesia: a systematic review and meta-analysis.

AIM: To evaluate the effect and quality of epidural neostigmine and clonidine added to initial spinal analgesia in labor analgesia. METHODS: A systematic search was conducted in the Medline, Embase, Cochrane Library and China National Knowledge Infrastructure electronic databases. Case-control studies reporting epidural administration of neostigmine and clonidine for labor analgesia were retrieved. For continuous variables, mean differences (MD) and 95% confidence intervals (CI) were calculated; for binary classification variables, odds ratio (OR) and risk ratios (RR) with their 95% CI were analyzed. RESULTS: A total of four case-control studies, including 280 parturients, were identified in this meta-analysis. The results showed that epidural clonidine and neostigmine significantly prolonged initial analgesia (MD = 37.79, 95% CI = 9.37-66.21, P = 0.0.009) and reduced hourly local anesthetics and opioid administration (MD = -5.49, 95% CI = -6.78, -4.21, P < 0.0001). There was no significant difference in total duration of labor, mode of delivery (cesarean section rate or instrumental delivery rate) and Apgar scores of the neonates in the two groups. CONCLUSION: Epidural administration of neostigmine and clonidine, following the spinal injection of local anesthetic, has a stronger analgesic effect in managing labor pain and reduces hourly anesthetic consumption. No obvious adverse reactions were found.