OBJECTIVES:In this study, we investigated whether neural precursor cell-expressed developmentally down-regulated gene 4-like (NEDD4L) is the E3 enzyme of angiotensin-converting enzyme 2 (ACE2) and whether NEDD4L degrades ACE2 via ubiquitination, leading to the progression of pulmonary arterial hypertension (PAH). METHODS:Bioinformatic analyses were used to explore the E3 ligase that ubiquitinates ACE2. Cultured pulmonary arterial smooth muscle cells (PASMCs) and specimens from patients with PAH were used to investigate the crosstalk between NEDD4L and ACE2 and its ubiquitination in the context of PAH. RESULTS:The inhibition of ubiquitination attenuated hypoxia-induced proliferation of PASMCs. The levels of NEDD4L were increased, and those of ACE2 were decreased in lung tissues from patients with PAH and in PASMCs. NEDD4L, the E3 ligase of ACE2, inhibited the expression of ACE2 in PASMCs, possibly through ubiquitination-mediated degradation. PAH was associated with upregulation of NEDD4L expression and downregulation of ACE2 expression. CONCLUSIONS:NEDD4L, the E3 ubiquitination enzyme of ACE2, promotes the proliferation of PASMCs, ultimately leading to PAH.

Objectives: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in older patients. Chitinase-3-like-1 protein (CHI3L1) is identified as a neuroinflammatory biomarker and impairs cognitive function. This study aimed to evaluate the association between serum levels of CHI3L1 and POCD and explore the levels of interleukin-6 (IL-6), IL-1 ss and Creactive protein (CRP) in the elderly after total hip arthroplasty (THA). Patients and methods: A total of 76 elderly patients undergoing THA were enrolled in the prospective observational study. Serum CHI3L1 levels were measured 1 day before and 1 day after surgery and other perioperative factors were also noted. The correlations between mediators of inflammation in the two groups were compared via Spearman correlation coefficients. The receiver operating characteristic (ROC) curves were implemented to analyze the predictive values of serum CHI3L1 and other inflammatory factors for POCD. And factors associated with POCD were analyzed by univariate and multivariate logistics. Results: POCD was observed in 31.6% of patients 1 week after surgery. Postoperative serum CHI3L1 levels were higher in POCD patients than in non-POCD patients [1348.26 (778.46-1889.77) VS 2322.86(1686.88-2517.35) ng/ml, P < 0.001]. Postoperative serum CHI3L1 level was positively correlated with postoperative IL-6 level (r = 0.284, P = 0.013). Compared with IL-6, IL-1 ss, and CRP, postoperative CHI3L1 level has the highest predictive value for POCD with the area under the curve (AUC) value of 0.779 according to the ROC curve. By the multivariate logistic regression analysis, elevated postoperative serum CHI3L1 level was found to be an independent risk factor for POCD 1 week after surgery (odds ratio = 1.204, 95% confidence interval = 1.087-1.332, P = 0.001). Conclusion: Postoperative elevated serum CHI3L1 level was significantly associated with the incident of POCD, and positively correlated with postoperative IL-6 level in the elderly after THA. This biomarker may have potential utility for further elucidating the etiology of POCD.

Background: Postpartum depression (PPD) is a general depressive episode after childbirth. Studies have shown that unmatched analgesic intention increases the risk of PPD, but the use of labor epidural analgesia (LEA) during childbirth can reduce this risk. We aimed to investigate the association between maternal childbirth intention, LEA, and PPD and risk factors that may be related to PPD. Methods: A total of 590 mothers were included in this prospective cohort study. Demographic, prenatal, intra-partum and postpartum data were recorded. We investigated the association between childbirth intention, LEA and PPD and assessed the interactions between two factors. Logistic regression analysis was used to screen variables that might be associated with the occurrence of PPD. Results: Overall, 130 of 451 women completing the study at 3 months had PPD (28.8 %). We did not find an association between unmatched childbirth intention, use of LEA and PPD (adjustOR = 0.684 CI 0.335-1.396, p = 0.296; adjustOR = 0.892, CI 0.508-1.565, p = 0.690). Chronic pain affecting daily life, prenatal EPDS, SAS, SSRS score, family accompaniment during labor, and 1-day numerical rating scale (NRS) score were significantly associated with PPD (p < 0.05). Limitations: In the 3-month follow-up, we only recorded the EPDS score, not the pain score, and did not evaluate the association between postpartum chronic pain and PPD.Conclusions: The association between maternal childbirth intention, LEA and PPD was not significant. Chronic pain affecting daily life, prenatal EPDS, SAS, SSRS score, family accompaniment during labor, and 1-day NRS score were significantly related to the occurrence of PPD (p < 0.05).

Objective To explore the correlation between peripheral blood monocyte levels and postoperative cognitive dysfunction(POCD)in elderly patients.Methods A total of 96 elderly patients undergoing elective total hip arthroplasty under general anesthesia in the Affiliated Hospital of Xuzhou Medical University from October 2021 to March 2022 were enrolled in the prospective observational stud-y,and the patients were divided into POCD group(26 cases)and Non-POCD group(70 cases)according to the mini-mental state ex-amination(MMSE)score.Peripheral blood monocyte levels and other relevant indicators were recorded.Receiver operating characteristic(ROC)curve were applied to analyze the predictive value of peripheral blood monocyte levels for POCD with total hip arthroplasty in eld-erly patients.Univariate and multivariate Logistic regression analyses were used to evaluate risk factors.Results The optimal cut-off value for preoperative monocyte levels predicting POCD in elderly patients with total hip arthroplasty was 0.55×109/L,and area under the curve value was 0.729.Univariate Logistic regression analysis showed that lower education level,higher American Society of Anesthe-siologists(ASA)grade,and preoperative and postoperative elevated monocyte levels were the risk factors for POCD;multivariate Logistic regression analysis showed that preoperative monocyte levels were independently associated with the occurrence of POCD.Conclusion Preoperative peripheral blood monocyte levels are associated with the occurrence of POCD,and preoperative elevated monocyte level is a risk factor for POCD,helping to predict the potential risk of POCD.

Objective:To explore the effect of labor epidural analgesia (LEA) on the occurrence of postpartum depression (PPD) in women intending to deliver vaginally.Methods:A total of 705 women who intended to deliver vaginally were enrolled. At 2-3 cm cervical dilation, they were allowed to choose whether to accept LEA or not. For those with emergency cesarean section (EmCS) indications during trial delivery, the obstetrician made the decision whether to convert to cesarean section (CS). The parturient women were divided into four groups according to the use of LEA during childbirth and the final delivery method: a vaginal delivery with LEA group (group V/LEA, n=302), a natural vaginal delivery group (group V/NLEA, n=143), a cesarean delivery after failed attempt of trial delivery with LEA group (group T/LEA, n=85), and a cesarean delivery after failed attempt of natural vaginal delivery (group T/NLEA, n=47). Their demographic data, pre-pregnancy history, pregnant conditions, prenatal data (including psychological scales) and maternal spouse data were collected. The highest Numerical Rating Scale (NRS) score during delivery, blood loss volume, accompaniment during childbirth and newborn conditions were recorded. On the first day after delivery, rooming-in for new mother and infant, close contact between mother and infant, 1-day NRS score and nursing satisfaction were recorded. The Edinburgh Postpartum Depression Scale (EPDS) was used to assess the occurrence of PPD at the third month postpartum. To explore the effect of LEA on the occurrence of PPD for the parturient women with successful vaginal delivery and cesarean delivery after failed attempt of trial delivery. The related risk factors of PPD were analyzed by logistic regression. The area under receiver operating characteristic (ROC) curve was used to fit the effects. Results:There were statistical differences in age, the proportion of primiparas, blood loss volume, and the highest NRS score among the four groups ( P<0.05); the labor time and episiotomy rate were statistically different between group V/LEA and group V/NLEA ( P<0.05). There were statistical differences in the degree of cervical dilation before cesarean delivery between group T/LEA and group T/NLEA ( P<0.05), while there were no statistical differences in other indicators ( P>0.05). The three-month follow-up results showed that the total incidence of PPD at the third month postpartum was 28.4%. After secondary analysis and adjusting for confounding factors between groups, no association was found between the use of LEA and PPD [adjusted odds ratio ( OR) 0.774, 95%CI (0.469, 1.276), P=0.315]. Logistic regression analysis showed that the risk factors of PPD in women intending to vaginal delivery included chronic pain during pregnancy, high prenatal EPDS scores, high Zung's Self-Rating Anxiety Scale (SAS) scores, low Social Support Rating Scale (SSRS) scored, no accompaniment during childbirth, and high 1-day NRS score after delivery ( P<0.05). These factors were adopted to fit a logistic regression model and a receiver operating characteristic (ROC) curve was plotted, with the area under curve (AUC) of 0.881, 95%CI (0.851, 0.911). Conclusions:The use of LEA does not reduce the risk of PPD in women intending to deliver vaginally. Chronic pain during pregnancy, high EPDS and SAS scores, low SSRS scores, no accompaniment during childbirth, and high 1-day NRS score are the independent risk factors of PPD.

Objective:To construct a nomogram model to predict the risk of postpartum depression (PPD) after cesarean section.Methods:A total of 341 parturients who underwent cesarean section in the Affiliated Hospital of Xuzhou Medical University from May 2021 to October 2021 were included in this study. If the score of the Edinburgh Postpartum Depression Scale (EPDS) at 3 months postpartum ≥10, the participant was divided into the PPD group ( n=109), otherwise into the non-PPD group ( n=232). Logistic regression was used to screen independent risk factors of PPD. A nomogram model was constructed by integrating these independent risk factors and evaluated by receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA). Finally, the prediction model was then internally verified by Bootstrap. Results:The incidence of PPD was 31.96%. Logistic regression showed that preterm delivery, primiparae, average monthly income of couples <5 000, prenatal depression, prenatal anxiety, low level of social support, and low level of marital satisfaction were independent risk factors for PPD after cesarean section. Odds ratio ( OR) and 95% confidence interval (CI) were 3.514 (1.681, 7.346), 2.105 (1.119, 3.958), 2.145 (1.176, 3.914), 13.491 (5.345, 34.052), 2.841 (1.429, 5.647), 5.231 (1.371, 19.956) and 9.446 (4.208, 21.205), respectively (all P<0.05). The nomogram model was constructed by the above factors. The area under the ROC curve for predicting the risk of PPD was 0.873 (95%CI 0.830-0.915), with the sensitivity and specificity of 80.7% and 82.2%, respectively. The calibration curve was a straight line with a slope of nearly 1, the goodness-of-fit test showed χ2=3.571, P=0.735, the DCA showed a good net gain when the potential risk threshold was 25.1%, and internal validation showed a good consistency of the model. Conclusions:The incidence of PPD in parturients after cesarean section is high and the influencing factors are complicated. The nomogram model constructed in this study can facilitate early screening.

Objective:To determine the median effective dose (ED 50) and 95% effective dose (ED 95) of remimazolam combined with alfentanil for painless gastroscopy. Methods:A total of 60 patients who underwent gastroscopy were enrolled. According to their ages, they were divided into two groups ( n=30): a young group (group Y, 18-44 years old) and a middle-aged group (group M, 45-60 years old). All patients were intravenously infused with 5 μg/kg alfentanil, followed by a bolus injection of remimazolam 30 s later, with an initial dose of 0.1 mg/kg. When the modified Observer's Assessment of Alertness/Sedation Scale (mOAA/S) was less than 3 points, gastroscopy was performed. The current study was carried out using the up and down method, where the dose of remimazolam used by the next patient was determined based on the sedative effect of gastroscopy. If the patient "successfully" sedated, the remimazolam dose used by the next patient decreased by 0.03 mg/kg, otherwise increased by 0.03 mg/kg. The dose of remimazolam, gastroscopy time, recovery time, intraoperative awareness and adverse reactions were recorded. The ED 50 and ED 95 of remimazolam and their 95% confidence interval (CI) were calculated by the probit regression method. Results:The ED 50 of remimazolam was 0.13 (0.11, 0.16) mg/kg and the ED 95 was 0.19 (0.16, 0.33) mg/kg in the group Y. The ED 50 of remimazolam was 0.09 (0.07, 0.12) mg/kg and the ED 95 was 0.18 (0.13, 0.57) mg/kg in the group M. The equivalent ratio of the group M versus the group Y was 0.68 (0.22, 0.98). There were no statistical differences in examination time, recovery time, the incidence of hypotension and respiratory depression between the two groups ( P>0.05), and the dose of remimazolam in group Y was higher than that in group M ( P<0.05). None of the patients had intraoperative awareness Conclusions:When remimazolam is used in combination with 5 μg/kg alfentanil, the ED 50 of remimazolam for painless gastroscopy is 0.13 (0.11, 0.16) mg/kg for young patients and 0.09 (0.07, 0.12) mg/kg for middle-aged patients. The equivalent ratio of the two groups is 0.68 (0.22, 0.98).

Background: Postpartum depression (PPD) is a serious mental health concern affecting approximately 17.22 % of new mothers worldwide. In addition to its obstetric effects, oxytocin (OXT) has also been considered to play a role in PPD. However, most previous studies exploring associations between PPD and OXT levels focus on easier accessible compartments such as blood or saliva. Study aim: To explore the possible association between PPD and OXT levels, and to assess the interaction between peripheral secretion and central release of OXT. Methods: In this study, we prospectively measured OXT concentrations in cerebrospinal fluid (CSF), plasma and saliva of 94 women with elective cesarean section by enzyme-linked immunosorbent assay (ELISA) kits. The participants were divided into the PPD group if the score of Edinburgh Postpartum Depression Scale (EPDS) >= 10 at 3 months postpartum, otherwise into the non-PPD (nPPD) group. Results: The incidence of PPD was 30.85 %. OXT concentrations in CSF (r =-0.518, p < 0.001), plasma (r =-0.240, p = 0.020) and saliva (r =-0.263, p = 0.010) were negatively correlated with EPDS score, and were valuable for the prediction of PPD, with AUC and 95%CI of 0.890 (0.809-0.945), 0.683 (0.579-0.775) and 0.699 (0.596-0.790), respectively. Moreover, OXT concentrations in plasma (r = 0.407, p < 0.001) and saliva (r = 0.624, p < 0.001) were positively correlated with CSF OXT concentrations. Limitations: Only full-term pregnant women undergoing elective cesarean section were included in this study, which may affect study generalizability. Conclusions: The central and peripheral release of OXT is coordinated, and OXT level measured prenatally in CSF, plasma, or saliva is valuable for the prediction of PPD.