OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

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 analyze the changing trend and characteristics of lymphocyte-platelets ratio (LPR) of early stage in patients with extensive burns, and to explore the prognostic significance of LPR. Methods: A retrospective case series study was conducted. From January 2008 to December 2018, 244 patients with extensive burns were admitted to the First Affiliated Hospital of Naval Medical University, including 181 males and 63 females, aged (44±16) years. The total burned area of patients was 60.0% (42.0%, 85.0%) total body surface area. Platelet and lymphocyte test results of patients were collected on the 1^st, 2^nd and 3^rd day after admission, and LPR of patients was calculated to analyze the changing trend of the three days after admission. Univariate and multivariate logistic regression analysis were conducted to investigate the risk factors or independent risk factors for death of patients, including age, sex, total burn area, area of full-thickness burns and above, inhalation injury, and LPR. According to the 1^st day's LPR after admission of patients, the receiver operating characteristic (ROC) curve predicting death of patients was drawn to find the optimal value of LPR. Patients were divided into high LPR group (n=136) and low LPR group (n=108) based on the optimal value of LPR, and the clinical data of total burn area, area of full-thickness burns and above, inhalation injury, tracheotomy, offline time of patients within 28 days, and mortality in the 2 groups were compared. The surviving curve of patients was drawn by Kaplan-Meier method to predict the difference of the 90-day survival rate between the two groups of patients. Data were statistically analyzed with Student's t test, Mann-Whitney U test, and chi-square test. Results: Within 3 days of admission, the LPR of patients showed a time-dependent upward trend. LPR of patients on the 2^nd and 3^rd day after admission was 8.6 (5.3, 14.4) and 8.6 (4.9, 13.7), respectively, which were significantly higher than the 1^st day's 6.3 (4.2, 9.8), with Z values of -4.25 and -3.43, respectively, P<0.01. Univariate logistic regression analysis showed that age, total burn area, area of full-thickness burns and above, inhalation injury, and LPR were all risk factors for death of patients (with odds ratios of 1.03, 1.73, 1.31, 4.74, and 3.11, respectively, 95% confidence intervals of 1.01-1.06, 1.40-2.13, 1.21-1.42, 1.62-13.86, and 1.41-6.88, respectively, P<0.01). Multivariate logistic regression analysis showed that age, area of full-thickness burns and above, and LPR were independent risk factors for death of patients (with odds ratios of 1.06, 1.36, and 2.85, respectively, 95% confidence intervals of 1.03-1.09, 1.19-1.55, 1.02-7.97, P<0.05 or P<0.01). The area under ROC curve of the 1^st day's LPR, predicting death of patients, was 0.61 (with 95% confidence interval of 0.51-0.71, P<0.05), and the optimal predicted value was 5.8 with corresponding sensitivity of 77% and specificity of 52% respectively. The total burn area, area of full-thickness burns and above, rates of incidence of inhalation injury, tracheotomy, and mortality of patients in high LPR group were significantly higher than those in low LPR group (with Z values of -3.06 and -3.19, χ² values of 5.42, 11.64, and 8.45, respectively, P<0.05 or P<0.01). The offline time of patients within 28 days in high LPR group was significantly shorter than that in low LPR group (Z=-2.98, P<0.01). Kaplan-Meier survival analysis showed that the 90-day survival rate of admission of patients in low LPR group was significantly higher than that of patients in high LPR group (χ²=8.24, P<0.01). Conclusions: The early LPR of patients with extensive burns showed a time-dependent upward trend. The LPR on the first day after admission that is closely correlated with total burn area, area of full-thickness and deeper burns, inhalation injury, tracheotomy, and mortality of patients, is an independent risk factor for the prognosis of patients with extensive burns. The first day's LPR after admission is significantly correlated with the 90-day survival rate of patients, which can be used as an evaluation index for the severity of extensive burns.
Adult ; Blood Platelets ; Burns ; Female ; Humans ; Lymphocytes ; Male ; Middle Aged ; Prognosis ; ROC Curve ; Retrospective Studies

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

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%

Objectives Transmuscular quadratus lumborum block (TQLB) may provide postoperative analgesia in patients undergoing intraperitoneal surgeries. The purpose of this study was to examine the potential efficacy of TQLB among patients undergoing retroperitoneal procedures, such as the laparoscopic partial nephrectomy (LPN). Methods This prospective, randomized, controlled study was conducted from August 2017 to November 2018 at Peking Union Medical College Hospital (Beijing, China). Patients who were scheduled for a LPN, aged 18-70 years old with an ASA physical status score of I - II were randomly assigned to receive either TQLB with 0.6 ml/kg of 0.5% ropivacaine plus general anesthesia (TQLB group) or general anesthesia alone (control group). Patient-controlled intravenous analgesia with morphine was initiated immediately upon surgery completion. The primary outcome was the cumulative consumption of morphine within 8 h after surgery. The secondary outcome included postoperative consumptions of morphine at other time points, pain score at rest and during activity, postoperative nausea and vomitting (PONV), and recovery related parameters. Results Totally 30 patients per group were recruited in the study. The 8 h consumption of morphine was lower in the TQLB group than in the control group (median, 0.023 mg/kg

This paper explored the background, framework and approach, contents and implementation of WHO Rehabilitation in Health System using approaches of ICF and WHO Handbook for Guideline Development. The actions and significances of implementations of seven recommendations and one good practice statements on assistive products had been discussed.