Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Objective To investigate the protective effect of folic acid against cholestatic liver injury in mice induced by bis(2-ethylhexyl)phthalate(DEHP)exposure and its mechanism.Methods ICR mice were randomly divided into control group,high-dose folic acid(H-FA)group,DEHP group,DEHP+low-dose folic acid(DEHP+L-FA)group,and DEHP+high-dose folic acid(DEHP+H-FA)group,with 6 mice in each group.The mice in the H-FA group,the DEHP+L-FA group,and the DEHP+H-FA group were given folic acid by gavage at the corresponding dose,and those in the control group and the DEHP group were given an equal volume of PBS solution by gavage.After 2 hours,the mice in the DEHP group,the DEHP+L-FA group,and the DEHP+H-FA group were given corn oil containing 200 mg/kg DEHP,and those in the control group and the H-FA group were given an equal volume of pure corn oil,by gavage for 4 weeks.Body weight and food intake were recorded every day,and blood and liver tissue samples were collected.A biochemical analyzer was used to measure the serum levels of total bile acid(TBA)and alkaline phosphatase(ALP);HE staining was used to observe the histopathological changes of liver tissue;kits were used to measure the content of malondialdehyde(MDA)and superoxide dismutase(SOD)in the liver;LC-MS/MS was used to measure serum bile acid profiles;Western blot was used to measure the expression levels of proteins associated with hepatic bile acid metabolism.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the control group,the daily food intake of the mice in the DEHP group decreased significantly,and the body weight decreased significantly from day 10(P＜0.05),and compared with the DEHP group,the DEHP+L-FA group and the DEHP+H-FA group had basically unchanged body weight and daily food intake(P＞0.05).Compared with the control group,the DEHP group had significant increases in liver weight index and the serum levels of TBA and ALP(all P＜0.05),with enlarged portal area,bile duct deformity and hyperplasia,and a small amount of inflammatory cell infiltration in liver tissue;compared with the DEHP group,the DEHP+L-FA group and the DEHP+H-FA group had a significant reduction in liver weight index(P＜0.01),and the DEHP+H-FA group had significant reductions in the serum levels of TBA and ALP(P＜0.05),with a significant improvement in liver histomorphology and structure after folic acid intervention.Compared with the control group,the DEHP group had a significant reduction in the content of SOD(P＜0.05)and a significant increase in the content of MDA in the liver(P＜0.01),and compared with the DEHP group,the DEHP+H-FA group had significant reductions in the content of MDA and SOD(P＜0.05).Compared with the control group,the DEHP group had significant increases in the serum levels of α-muricholic acid(α-MCA),β-muricholic acid(β-MCA),deoxycholic acid(DCA),lithocholic acid(LCA),taurocholic acid(TCA),taurodeoxycholic acid(TDCA),tauroursodeoxycholic acid(TUDCA),tauro-β-muricholic acid(T-β-MCA),tauro-α-muricholic acid(T-α-MCA),taurohyodeoxycholic acid(THDCA),and taurolithocholic acid(TLCA)(P＜0.05)and a significant reduction in ursodeoxycholic acid(UDCA)(P＜0.05);compared with the DEHP group,the DEHP+H-FA group had significant reductions in the serum levels of DCA,LCA,TCA,TDCA,TUDCA,T-β-MCA,T-α-MCA,THDCA,and TLCA(P＜0.05).Compared with the control group,the DEHP group had significant increases in the protein expression levels of FXR and CYP3A11 in the liver(P＜0.01)and significant reductions in the protein expression levels of CYP7A1 and MRP2(P＜0.01);compared with the DEHP group,the DEHP+L-FA group and the DEHP+H-FA group had significant reductions in the protein expression levels of FXR and CYP3A11 in the liver(P＜0.05)and a significant increase in the protein expression level of MRP2(P＜0.05),and the DEHP+H-FA group had a significant increase in the protein expression level of CYP7A1(P＜0.05).Conclusion Folic acid has a protective effect against cholestatic liver injury in mice induced by DEHP exposure,possibly by regulating bile acid synthesis,catabolism,and transport and maintaining bile acid homeostasis.

Objective Although goal-directed fluid therapy (GDFT) has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator. Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications. We conducted mediation analysis using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates. Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI: 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.
Humans ; Blood Pressure ; Goals ; Postoperative Complications/epidemiology* ; Hemodynamics ; Fluid Therapy/methods*

Objective To develop a risk prediction model combining pre/intraoperative risk factors and intraoperative vital signs for postoperative healthcare-associated infection(HAI)based on deep learning. Methods We carried out a retrospective study based on two randomized controlled trials(NCT02715076,ChiCTR-IPR-17011099).The patients who underwent elective radical resection of advanced digestive system tumor were included in this study.The primary outcome was HAI within 30 days after surgery.Logistic regression analysis and long short-term memory(LSTM)model based on iteratively occluding sections of the input were used for feature selection.The risk prediction model for postoperative HAI was developed based on deep learning,combining the selected pre/intraoperative risk factors and intraoperative vital signs,and was evaluated by comparison with other models.Finally,we adopted the simulated annealing algorithm to simulatively adjust the vital signs during surgery,trying to explore the adjustment system that can reduce the risk of HAI. Results A total of 839 patients were included in this study,of which 112(13.3%)developed HAI within 30 days after surgery.The selected pre/intraoperative risk factors included neoadjuvant chemotherapy,parenteral nutrition,esophagectomy,gastrectomy,colorectal resection,pancreatoduodenectomy,hepatic resection,intraoperative blood loss>500 ml,and anesthesia time>4 h.The intraoperative vital signs significantly associated with HAI were in an order of heart rate>core body temperature>systolic blood pressure>diastolic blood pressure.Compared with multivariable Logistic regression model,random forest model,and LSTM model including vital signs only,this deep learning-based prediction model performed best(ACC=0.733,F1=0.237,AUC=0.728).The simulation via simulated annealing algorithm reduced the incidence of postoperative HAI.Moreover,the incidence decreased most in the case of reducing the initial annealing temperature and choosing the last 20% of surgery procedure. Conclusions This study developed a risk prediction model for postoperative HAI based on deep learning,which combined pre/intraoperative risk factors and intraoperative basic vital signs.Using simulated annealing algorithm to adjust intraoperative vital signs could reduce the incidence of postoperative HAI to some extent.
Cross Infection ; Deep Learning ; Delivery of Health Care ; Humans ; Postoperative Period ; Retrospective Studies

Objective To reveal the incidence,mortality,and risk factors of bleeding-related perioperative cardiac arrest(POCA). Methods We carried out a single-center retrospective case-control study which enrolled all the POCA cases reported from January 2010 to September 2020 in the patient safety incident reporting system of Peking Union Medical College Hospital.For the screening of risk factors,the patients were respectively assigned into the POCA group and the control group at a ratio of 1∶3 according to the same sex,age,American Society of Anesthesiologists(ASA)physical status,and type of surgery in the same month.Potential risk factors for POCA were first selected by univariate analysis.The significant risk factors were then checked based on the clinical experience and further included in the multivariate Logistic regression model. Results Totally 16 bleeding-related POCA cases were collected from the patient safety incident reporting system among the study period,with an overall incidence of 0.36/10 000.The blood loss volume of POCA group and control group was(7 037.50±5 477.70)ml and(375.63±675.14)ml,respectively(P<0.001),and 14(87.5%)patients suffering from bleeding-related POCA died within three days after anesthesia.According to the univariate analysis,patients' body mass index[(21.79±3.57)kg/m² vs.(24.26±3.91)kg/m²,P=0.043],hemoglobin level[(113.44±31.08)g/L vs.(131.75±19.70)g/L,P=0.039],and alanine aminotransferase level[(17.31±7.73)U/L vs.(26.91±24.73)U/L,P=0.022]were significantly lower in the POCA group than in the control group.Further Logistic regression analysis showed that smaller body mass index and lower preoperative hemoglobin level were independently associated with the occurrence of bleeding-related POCA. Conclusions Bleeding-related POCA rarely occurred but had high mortality.Adequate precautions should be taken for the patients who are to receive surgeries with high risk of intraoperative massive bleeding.Elevating preoperative hemoglobin level might decrease the incidence of bleeding-related POCA.
Case-Control Studies ; Heart Arrest/etiology* ; Hemoglobins ; Humans ; Retrospective Studies ; Risk Factors

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.
Anesthetics, Local/therapeutic use* ; Double-Blind Method ; Hepatectomy/adverse effects* ; Humans ; Morphine/therapeutic use* ; Pain Measurement ; Pain, Postoperative/etiology* ; Ultrasonography, Interventional

Objective Airway-related patient safety incident (PSI) has always been the top concern of anesthesiologists because this type of incidents could severely threaten patient safety if not treated immediately and properly. This study intends to reveal the composition, prognosis, and to identify risk factors for airway related incidents reported by anesthesiologists. Methods All airway related PSIs reported by anesthesiologists in a Chinese academic hospital between September 2009 and May 2022 were collected from the PSI reporting system. Patients with airway incidents reported were matched 1:1 with controls based on sex and type of surgery. Univariable and multivariable analysis were performed to find risk factors associated with airway incident occurrence, and to evaluate influence of airway PSIs on patient prognosis. Results Among 1,038 PSIs voluntarily reported by anesthesiologists during the study period, 281 cases (27.1%) were airway-related incidents, with an overall reporting incidence of 4.74 per 10,000 among 592,884 anesthesia care episodes. Only ASA physical status was found to be significant independent predictor of these airway PSIs (P = 0.020). Patients with airway PSIs reported had longer extubation time (0.72 ± 1.56 d vs. 0.16 ± 0.77 d, 95%CI: 0.29 to 0.82, P < 0.001), longer ICU length of stay (LOS) (1.63 ± 5.71 d vs. 0.19 ± 0.84 d, 95%CI: 0.57 to 2.32, P= 0.001), longer post operative LOS (10.56 ± 13.09 d vs. 7.59 ± 10.76 d, 95%CI: 0.41 to 5.53, P = 0.023), and longer total in-hospital LOS (14.99 ± 15.18 d vs. 11.62 ± 11.88 d, 95%CI: 0.46 to 6.27,P = 0.024). Conclusions This single-center retrospective case-control study describes the composition of airway-related PSIs reported by anesthesiologists within thirteen years. Airway incidents might influence patient prognosis by elongating extubation time and LOS. Airway PSI data were worth analyzing to improve patient safety.
Humans ; Patient Safety ; Retrospective Studies ; Case-Control Studies ; Anesthesia/adverse effects* ; Risk Factors

Objective To investigate the risk factors for patients using intraoperative vasopressor infusions during carotid body tumor(CBT)excision.Patients' mean arterial pressure(MAP)and heart rate(HR)fluctuations as well as their requirements for vasoactive agents during surgery were assessed. Methods The patients receiving CBT excision in Peking Union Medical College Hospital from May 1,2013 to July 31,2017 were included for a retrospective cohort study.The potential factors of intraoperative requirement for vasopressor infusions were investigated using univariate analysis and Logistic multivariate analysis.Furthermore,the relationships of Shamblin types of CBT with intraoperative MAP/HR fluctuations and requirements for vasoactive agents were analyzed. Results A total of 108 patients with 116 CBTs were included.Univariate analysis revealed that maximum tumor diameter >4 cm,intraoperative internal carotid artery injury,internal carotid artery reconstruction,malignant pathology,advanced Shamblin types(type Ⅱ and Ⅲ),estimated blood loss ≥400 ml,and operation duration >4 hours were associated with intraoperative requirements for vasopressor infusions.Logistic analysis showed that Shamblin type Ⅲ(OR=2.286,95% CI=1.324-14.926,P=0.016)and operation duration >4 hours(OR=3.874,95% CI=1.020-14.623,P=0.046)were risk factors for intraoperative requirements for vasopressor infusions during CBT surgery.In addition,Shamblin type Ⅲ was associated with intraoperative abnormal HR elevation and requirements for vasopressors.Conclusions Shamblin type Ⅲ and operation duration>4 hours are risk factors for intraoperative requirements of patients for using vasopressor infusions during CBT surgery.Shamblin type Ⅲ is associated with intraoperative abnormal HR elevation and requirements for vasopressors.
Carotid Body Tumor ; Humans ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Vascular Surgical Procedures

Objective Burnout is a triad of emotional exhaustion, depersonalization, and reduced personal accomplishment resulting from job stress. Although with distinct regional and cultural characteristics, burnout among anesthesiologists in the Tibet has not been described. This study aimed to explore the prevalence of burnout among anesthesiologists in Tibet and its associated factors. Methods A cross-sectional survey was conducted in Tibet, China, with an anonymous questionnaire. Social-demographic characteristics, work status, three dimensions of burnout assessed by the Maslach Burnout Inventory-Human Service Survey were collected and analyzed. Results A total of 133 individuals from 17 hospitals completed the survey from March to June 2018. The prevalence of moderate- to high-level of emotional exhaustion, depersonalization, and burnout in personal accomplishment was 65.4% (95%

BACKGROUND: Whether regional anesthesia may help to prevent disease recurrence in cancer patients is still controversial. The stage of cancer at the time of diagnosis is a key factor that defines prognosis and is one of the most important sources of heterogeneity for the treatment effect. We sought to update existing systematic reviews and clarify the effect of regional anesthesia on cancer recurrence in late-stage cancer patients. METHODS: Medline, Embase, and Cochrane Library were searched from inception to September 2020 to identify randomized controlled trials (RCTs) and cohort studies that assessed the effect of regional anesthesia on cancer recurrence and overall survival (OS) compared with general anesthesia. Late-stage cancer patients were primarily assessed according to the American Joint Committee on Cancer Cancer Staging Manual (eighth edition), and the combined hazard ratio (HR) from random-effects models was used to evaluate the effect of regional anesthesia. RESULTS: A total of three RCTs and 34 cohort studies (including 64,691 patients) were identified through the literature search for inclusion in the analysis. The risk of bias was low in the RCTs and was moderate in the observational studies. The pooled HR for recurrence-free survival (RFS) or OS did not favor regional anesthesia when data from RCTs in patients with late-stage cancer were combined (RFS, HR = 1.12, 95% confidence interval [CI]: 0.58-2.18, P = 0.729, I2 = 76%; OS, HR = 0.86, 95% CI: 0.63-1.18, P = 0.345, I2 = 48%). Findings from observational studies showed that regional anesthesia may help to prevent disease recurrence (HR = 0.87, 95% CI: 0.78-0.96, P = 0.008, I2 = 71%) and improve OS (HR = 0.88, 95% CI: 0.79-0.98, P = 0.022, I2 = 79%). CONCLUSIONS RCTs reveal that OS and RFS were similar between regional and general anesthesia in late-stage cancers. The selection of anesthetic methods should still be based on clinical evaluation, and changes to current practice need more support from large, well-powered, and well-designed studies.
Anesthesia, Conduction ; Humans ; Neoplasms ; Recurrence