Improving predictions: Enhancing in-hospital mortality forecast for ICU patients with sepsis-induced coagulopathy using a stacking ensemble model.

The incidence of sepsis-induced coagulopathy (SIC) is high, leading to increased mortality rates and prolonged hospitalization and intensive care unit (ICU) stays. Early identification of SIC patients at risk of in-hospital mortality can improve patient prognosis. The objective of this study is to develop and validate machine learning (ML) models to dynamically predict in-hospital mortality risk in SIC patients. A ML model is established based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to predict in-hospital mortality in SIC patients. Utilizing univariate feature selection for feature screening. The optimal model was determined by calculating the area under the curve (AUC) with a 95% confidence interval (CI). The optimal model was interpreted using Shapley Additive Explanation (SHAP) values. Among the 3112 SIC patients included in MIMIC-IV, a total of 757 (25%) patients experienced mortality during their ICU stay. Univariate feature selection helps us to pick out the 20 most critical variables from the original feature. Among the 10 developed machine learning models, the stacking ensemble model exhibited the highest AUC (0.795, 95% CI: 0.763-0.827). Anion gap and age emerged as the most significant features for predicting the mortality risk in SIC. In this study, an ML model was constructed that exhibited excellent performance in predicting in-hospital mortality risk in SIC patients. Specifically, the stacking ensemble model demonstrated superior predictive ability.

Enhancing predictions with a stacking ensemble model for ICU mortality risk in patients with sepsis-associated encephalopathy.

OBJECTIVE: We identified predictive factors and developed a novel machine learning (ML) model for predicting mortality risk in patients with sepsis-associated encephalopathy (SAE). METHODS: In this retrospective cohort study, data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database were used for model development and external validation. The primary outcome was the in-hospital mortality rate among patients with SAE; the observed in-hospital mortality rate was 14.74% (MIMIC IV: 1112, eICU: 594). Using the least absolute shrinkage and selection operator (LASSO), we built nine ML models and a stacking ensemble model and determined the optimal model based on the area under the receiver operating characteristic curve (AUC). We used the Shapley additive explanations (SHAP) algorithm to determine the optimal model. RESULTS: The study included 9943 patients. LASSO identified 15 variables. The stacking ensemble model achieved the highest AUC on the test set (0.807) and 0.671 on external validation. SHAP analysis highlighted Glasgow Coma Scale (GCS) and age as key variables. The model (https://sic1.shinyapps.io/SSAAEE/) can predict in-hospital mortality risk for patients with SAE. CONCLUSIONS: We developed a stacked ensemble model with enhanced generalization capabilities using novel data to predict mortality risk in patients with SAE.

Zishen Qingre Lishi Huayu recipe promotes proliferation and inhibits apoptosis of GCs of PCOS via KLF4-C/EBPß pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zishen Qingre Lishi Huayu recipe (ZQLHR) is a herbal recipe created on the basis on the theory of traditional Chinese medicine and clinical practice, and is mainly used in the treatment of polycystic ovary syndrome (PCOS). However, the underlying mechanism for this fact has not been clearly elucidated. AIM OF THE STUDY: To verify whether ZQLHR regulates granulosa cells (GCs) proliferation and apoptosis through the Krüppel-like factor 4 (KLF4) - CCATT enhancer-binding proteinß (C/EBPß) pathway, and to provide in vitro molecular mechanism supporting for the effects of ZQLHR to enhance follicular development and treat patients with PCOS. MATERIALS AND METHODS: Based on previous experiments, we performed the following experiments. Firstly, we treated KGN cells (a steroidogenic human granulosa-like tumor cell line) for 48 h using different concentrations of ZQLHR in order to observe apoptosis in each group. Secondly, the mRNA and protein expression levels of KLF4 and C/EBPß in KGN cells after administrated with ZQLHR were examined by quantitative real-time PCR(q-PCR) and Western blot assay. Thirdly, after knocking down KLF4 and C/EBPß using siRNAs, the relationship between KLF4 and C/EBPß in KGN cells was detected. Further, cell counting kit-8 assay, colony formation assay and flow cytometry were used to verify whether ZQLHR promotes proliferation and facilitates apoptosis in KGN cells through the KLF4-C/EBPß pathway. Finally, q-PCR and Western blot were used to test whether ZQLHR mediated proliferation and apoptosis-related factors such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (BAX), proliferating cell nuclear antigen (PCNA) and cleaved caspase-3 to affect the proliferation and apoptosis of KGN cells through the KLF4-C/EBPß pathway. CONCLUSIONS: ZQLHR, containing 0.2% by volume, administered to KGN cells resulted in the lowest rate of apoptosis. The expression levels of KLF4 and C/EBPß were increased in KGN cells following ZQLHR treatment. Additionally, ZQLHR promoted proliferation and inhibited apoptosis of KGN cells by modulating proliferation and apoptosis-related factors via the KLF4-C/EBPß pathway. Furthermore, we confirmed that KLF4 and C/EBPß regulate each other in KGN cells. These findings indicate that ZQLHR enhances the proliferation of GCs and suppresses their apoptosis, which constitutes a therapeutic mechanism for treating patients with PCOS.

Effects of Acupuncture Combined with Moxibustion on Reproductive and Metabolic Outcomes in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Objectives: In this systematic review, the effects of acupuncture combined with moxibustion on reproductive and metabolic outcomes in patients with polycystic ovary syndrome (PCOS) were evaluated. Methods: Randomized controlled trials (RCTs) assessing acupuncture combined with moxibustion + basic treatment (experimental group) versus basic treatment alone (control group) for treating PCOS were identified from English and Chinese databases up to November 3, 2021. Outcomes related to pregnancy, ovulation, miscarriage, sex hormones, and metabolic disorders were of interest. In the meta-analysis, risk ratios (RRs) and mean differences (MDs) and their 95% confidence intervals (CIs) were used as effect measures. Results: Twenty-five RCTs (n = 1991) were included. The pooled results showed that the experimental group had significant increases in the pregnancy rate (RR 1.81, 95% CI 1.58 to 2.08) and ovulation rate (RR 1.31, 95% CI 1.22 to 1.40) and decreases in the miscarriage rate (RR 0.45, 95% CI 0.28 to 0.73), and ovarian volume (MD -0.75 cm3, 95% CI -1.30 to -0.20). In the experimental group, improvements in the luteinizing hormone (LH) level, the LH-to-follicle-stimulating hormone (FSH) ratio, total testosterone level, fasting insulin level, and body mass index, but not in FSH, oestradiol, or dehydroepiandrosterone sulfate levels, were significantly greater. All reported adverse events were mild. Based on the limitations of risk of bias, inconsistency, imprecision, and/or publication bias, the level of evidence was judged to be moderate for the pregnancy rate, ovulation rate, miscarriage rate, LH level, and LH/FSH ratio and very low for the other outcomes. Conclusion: Among patients with PCOS, using acupuncture combined with moxibustion as a complementary therapy to basic treatments can improve pregnancy, ovulation, and miscarriage rates, the levels some sex hormones, and metabolic indicators, with good safety. Additionally, this combination therapy may have no effect on the FSH, oestradiol, or dehydroepiandrosterone sulfate level.

Effect assessment of laparoscopy in combination with traditional Chinese medicine decoction in the treatment of endometriosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Endometriosis (EMs) affects about 10% of women of childbearing age. It is defined as functional endometrial tissue appearing in other parts of the uterine cavity, manifested by varying degrees of pelvic pain and pelvic mass, etc. Therefore, to improve the therapeutic effect of endometriosis, we must constantly explore new ways to treat the disease. The purpose of this study is to evaluate the effectiveness and safety of the combined use of laparoscopy and traditional Chinese medicine in the treatment of patients with EMs. METHODS: A systematic literature search will be conducted at China National Knowledge Infrastructure, WanFang databases, VIP, SinoMed, PubMed, Embase, Web of Science, and the Cochrane library. The search period limit is from the time the date of database establishment to June 21, 2021. To ensure the comprehensiveness of the search, relevant references and conference literature are also included. The risk of bias in the final included studies will be evaluated based on the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The RevMan software will be employed to perform data synthesis and statistical analysis. RESULTS: The effectiveness and safety of laparoscopic surgery combined with traditional Chinese medicine decoction in the treatment of patients with EMs will be systematically evaluated. CONCLUSION: The results of this study will provide strong evidence for judging whether laparoscopy combined with traditional Chinese medicine decoction is an effective strategy for the treatment of patients with EMs.

Effects of aromatherapy on sleep disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: The progress of modern society and changes in lifestyle have not only increased the proportion of sub-healthy people, but also caused many people to suffer from sleep disorders and mental anxiety. Long-term lack of high-quality sleep will not only cause psychological problems such as anxiety and fatigue, but also cause physical abnormalities, such as abnormal hormone secretion, weakened immunity, neuroendocrine disorders, and high blood pressure. Therefore, the purpose of this study is to systematically evaluate the effectiveness of aromatherapy in improving sleep quality in people with sleep disorders. METHODS: Computer search CNKI, SinoMed, Wanfang, PubMed, Web of science, and EMbase collect randomized controlled trials on aromatherapy to improve sleep quality of people with sleep disorders. The search time limit is to build the database until April 5, 2021. RevMan5.3 software is used for meta-analysis. RESULTS: This systematic review will provide an assessment of the current state of sleep disorders, aiming to assess the efficacy of aromatherapy for patients with sleep disorders. CONCLUSION: This systematic review will provide a credible evidence-based for the clinical treatment of sleep disorders with aromatherapy.

Kuntai capsules improve glucolipid metabolism in patients with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: The aim of this study was to observe the effect and safety of Heyan Kuntai Capsule (HYKT) on glucose and lipid metabolism in patients with polycystic ovary syndrome (PCOS). METHODS: Hundred patients with PCOS were randomly divided into HYKT group (n = 50) and placebo groups (n = 50) in which the individuals were treated with HYKT and its placebo continuously for 6 months. Meanwhile, all participants received health education (such as exercise and diet). The primary outcomes were serum sex hormone levels, a series of blood lipid, fasting and postprandial 2 hours blood glucose. Body mass index (BMI), waist-hip ratio (WHR), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and insulin-sensitive index (ISI) were also observed. In addition, adverse events were recorded to evaluate the drug safety. RESULTS: After treatment, the BMI and WHR of all the patients were decreased. The fasting and postprandial 2 hours blood glucose levels were significantly declined when treated with HYKT, which were not observed in the placebo group. Similarly, serum sex hormones including luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and testosterone were lowered after treated with HYKT instead of the placebo. Besides, blood lipids outcomes such as total cholesterol, triglyceride, and low-density lipoprotein cholesterol, as well as insulin and HOMA-IR were decreased with significance in HYKT group when compared with those in the placebo group, whereas high-density lipoprotein cholesterol and ISI increased obviously. CONCLUSION: HYKT showed the effect on ameliorating the glucose and lipid metabolism disorder and improving insulin resistance and increase insulin sensitivity of PCOS patients, which is similar to insulin sensitizing agent.

Association between the effect of controlled fluid resuscitation on massive hemorrhage and expression of human neutrophil lipocalin.

The present study was designed to investigate the association between the effect of controlled fluid resuscitation on massive hemorrhage and expression of human neutrophil lipocalin (HNL). A total of 112 patients confirmed with traumatic hemorrhage were enrolled as study subjects and were randomly divided into the control group (n=56) and observation group (n=56). The control group was treated with rapid fluid resuscitation, and the observation group was treated with controlled fluid resuscitation. The success rate of resuscitation, incidence rate of complications, and HNL levels were compared both before and after resuscitation at multiple time intervals. The success rate of resuscitation showed a significant improvement while the incidence rate of complications were decreased. The HNL levels in both groups revealed increase after resuscitation at 3-10 h, thereby, they showed decline following peak point. However, the peak reduction in the observation group appeared earlier, while the HNL levels at 24 and 72 h were significantly lower than those in the control group. The study concluded that the effect of controlled fluid resuscitation on massive hemorrhage was superior to that of rapid fluid resuscitation. Moreover, controlled fluid resuscitation was also able to decrease the level of HNL as well as inflammatory response.

Efficacy of acupuncture on pelvic pain in patients with endometriosis: study protocol for a randomized, single-blind, multi-center, placebo-controlled trial.

BACKGROUND: Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture. METHODS/DESIGN: This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment. DISCUSSION: The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03125304 . Registered on 30 April 2017.

Ping-Chong-Jiang-Ni Formula Induces Apoptosis and Inhibits Proliferation of Human Ectopic Endometrial Stromal Cells in Endometriosis via the Activation of JNK Signaling Pathway.

Endometriosis is a common gynecological condition in childbearing age women and its therapy in modern medicine achieves usually temporary cure. Ping-Chong-Jiang-Ni formula (PCJNF), a Chinese herbal medicine (CHM), was shown to be clinically effective on endometriosis. Meanwhile, c-Jun N-terminal kinase (JNK) signaling pathway was involved in the therapeutic process of CHM on endometriosis. Here, we explored the effect of PCJNF on the ectopic endometrial stromal cells (EESCs) from endometriosis and test whether JNK signaling was involved. After being treated with PCJNF-containing serum obtained from Sprague Dawley rat, cell proliferation, migration, invasion, and apoptosis were evaluated in EESCs, and the total and phosphorylated JNK, ERK, and p38 proteins were detected. Our results showed that PCJNF could suppress cell proliferation, migration, and invasion and induce apoptosis in EESCs. The suppressed proliferation and increased apoptosis were dependent on JNK activation. Additionally, PCJNF caused cell cycle arrest at G2/M phase and this effect was mediated by JNK signaling, while the decreased cell migration and invasion treated by PCJNF were independent of JNK signaling. In summary, our results provided the first evidence that PCJNF could suppress cell proliferation, migration, and invasion, while increasing apoptosis in EESCs, and the suppressed proliferation and enhanced apoptosis were mediated by JNK signaling.