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Abstract Objective Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS. Methods A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike’s information criterion (AIC) and integrated discrimination improvement (IDI). Results Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes. Conclusions Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction.

The increasing incidence of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Tm), known for causing invasive enteric infections, presents a significant public health challenge. Given the diminishing efficacy of existing antibiotics, it is imperative to explore novel alternatives for the treatment of MDR S. Tm infections. Here, we identified esculetin (EST), a natural coumarin abundant in dietary foods and herbs, as a compound exhibiting broad-spectrum antibacterial properties against a range of MDR bacteria. Our findings demonstrate that EST effectively inhibited the proliferation and expansion of MDR S. Tm in both in vitro experiments and animal models. Specifically, EST significantly downregulated the type 3 secretion system-1 (T3SS-1) virulence expression of MDR S. Tm, thereby preventing its invasion into intestinal epithelial cells. In S. Tm-infected mice, we observed cecal injury characterized by the upregulation of inflammatory cytokines, a reduction in goblet cell numbers, a decreased expression of tight junction proteins, and microbial dysbiosis. Conversely, EST treatment ameliorated these pathological changes induced by S. Tm infection and reduced oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, thereby improving intestinal barrier function. These results suggest that dietary coumarins or a targeted plant-based diet may offer a promising strategy to counteract MDR bacteria-induced enteric diseases.

In this study, a magnetic deep eutectic solvent coupled with dispersive liquid–liquid microextraction using high-performance liquid chromatography (MDES-DLLME-HPLC) was developed to detect strobilurin fungicides. The green hydrophobic MDES synthesized by methyltrioctylammonium chloride, ferric chloride, and heptanoic acid was used as an extraction solvent, which was dispersed by vortex and separated by an external magnetic field. The use of toxic solvents was avoided, and the separation time was reduced. The best experimental results were obtained through single factor and response surface optimization. The method had a good linear relationship with R2 > 0.996. The limit of detection (LOD) ranged from 0.001 to 0.002 mg L−1. The extraction recoveries were 81.9–108.9%. The proposed method was rapid and green, and it has been successfully applied to detection of strobilurin fungicides in water, juice, and vinegar.

Diabetes has become one of the seven major diseases affecting human death, so early prediction of the disease to prevent it is critical. Several existing works of literature, however, make predictions about diabetes with few considerations of missing and imbalanced data proper. To overcome these problems, in this paper, we propose an efficient Probabilistic Ensemble classification algorithm for Diabetes handling class Imbalance Missing values (PE_DIM) which can effectively handle the issue of missing imbalances and improve classification accuracy. First, a novel method based on Local Median-based Gaussian Naive Bayes (LMeGNB) is proposed to compensate for the missing values, combined with the K-means SMOTE method to adjust the positive and negative samples of diabetes to obtain the normalized balanced data. Then, a probability-based multi-stage ensemble is devoted to building ensemble models on the different types of machine learning algorithms. When extreme gradient boosting, random forests, and weighted $k$ nearest neighbors are integrated, the highest classification accuracy of 94.53% is obtained on Pima Indian diabetes dataset. Finally, to evaluate the PE_DIM model, the experiment equally considered two diabetes datasets, RSMH and Tabriz, to demonstrate the generality of the method in diabetes prediction. Additionally, in terms of area under the receiver operating characteristic curve metric uses several statistical tests to measure the performance of different classification methods. The ultimate results demonstrate that the average rank of this method is ranked first after 5-fold cross-validation, which is significantly different from the basic classifiers. Promisingly, the proposed method effectively solves the lack of diabetes imbalance and plays a significant role in intelligent medical treatment to improve diabetes research.

Aiming at the puncture and drainage of clinical intracranial hematoma, we proposed an adaptive bifurcation algorithm based on the hematoma point cloud and optimized the design of the drainage tube. Firstly, based on the CT data of intracranial hematoma patients, a three-dimensional hematoma model was established, the point cloud on the surface of the hematoma was extracted and simplified, and the location of the main drainage tube was located by using the long-axis extraction algorithm. Secondly, the Eight Diagrams algorithm was used to identify the internal point cloud of hematoma, and the positions of multiple absorption points were determined by the K-means clustering algorithm. The locations of the bifurcation points of the main drainage tubes were calculated by the numerical method, and the telescopic lengths and directions of multiple subdrainage tubes were obtained. Finally, connect the main tube and the subtube, design an adaptive bifurcation drainage tube model, and apply it to intracranial hematoma puncture and drainage surgery. The algorithm can accurately determine the puncture point, puncture path, number, and location of subdrainage tubes according to the geometric characteristics of hematoma, achieve a uniform and accurate dose adjustment and drainage of intracranial hematoma, and accelerate the dissolution and drainage speed. The application of an adaptive bifurcation drainage tube can significantly reduce the risk of intracerebral hemorrhage, intracranial infection, and other complications, which has certain guiding significance and application value in clinical practice.

Objective: To evaluate the effectiveness and safety of fire needling for herpes zoster from randomized clinical trials (RCTs). Methods: We searched Cochrane Central Register of Controlled Trials, Pubmed, Sino-Med, CNKI, VIP, WanFang databases, and conference proceedings to November, 2017. RCTs were eligible if they tested fire needling for treating herpes zoster more than 3 times. Two authors screened all references, assessed the risk of bias, extracted data, independently, and analyzed data using Trial Sequential Analysis (TSA). Treatment effects were presented as risk ratio (RR) for binary data and standardized mean difference (SMD) for continuous data with 95% confidence interval (CI). Results: We included 27 RCTs with a total of 1933 participants. Only one RCT had low risk of bias, and the others were of high or moderate risk of bias. For total effectiveness rate (proportion of total number of people who were cured or significant symptom improved), there was no significant difference between Western medicine (acyclovir, valacyclovir, adenosine cobalamin) and fire needling (risk ratio 1.05,95% CI 0.98 to 1.12; n = 5). For pain relief (VAS scale): fire needling used alone showed lower scores than Western medicine (SMD -1.37, 95% CI -1.77 to −0.97; n = 2) or external medicine (diclofenac) (SMD-2.23, 95% CI -2.81 to −1.64; n = 1). Combination of fire needling and Western medicine was better than Western medicine alone in relieving pain (VAS scale) (SMD-2.19, 95% CI -3.40 to −0.97, I2 = 94%; n = 4). Patients receiving fire needling had lower incidence of neuralgia than those receiving Western medicine (3.3% vs 26.7%, RR 0.09, 95% CI 0.01 to 0.82; n = 1) at follow up for 30 days. No serious adverse events such as infection were reported. Conclusion: Fire needling appears to offer relief for alleviating pain in herpes zoster. As the sample size of included trials was small and the quality of studies was generally low, rigorous clinical trials with robust reporting and appropriate outcome measures are still needed. Keywords: Fire needling, Acupuncture, Herpes zoster, Postherpetic neuralgia, Trial sequential analysis

The pulsed electric field (PEF) technology has been widely applied to inactivate pathogenic bacteria in food products. Though irreversible pore formation and membrane disruption is considered to be the main contributing factor to PEF’s sterilizing effects, the exact molecular mechanisms remain poorly understood. In this study, by using mass spectrometry (MS)-based label-free quantitative proteomic analysis, we compared the protein profiles of PEF-treated and untreated Escherichia coli. We identified a total of 175 differentially expressed proteins, including 52 candidates that were only detected in at least two of the three samples in one experiment group but not in the other group. Functional analysis revealed that the differential proteins were primarily involved in the regulation of cell membrane composition and integrity, stress response, as well as various metabolic processes. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was conducted on the genes of selected differential proteins at varying PEF intensities, which were known to result in different cell killing levels. The qRT-PCR data confirmed that the proteomic results could be reliably used for further data interpretation, and that the changes in the expression levels of the differential candidates were, to a large extent, caused directly by the PEF treatment. The findings of the current study offered valuable insight into PEF-induced cell inactivation.

To comprehensively evaluate the effects of drying methods on the nutritional quality and antioxidant activity of Jiangyong fragrant ginger, seven different drying methods including natural drying (ND), hot air drying (HAD), infrared drying (ID), microwave drying (MD), vacuum drying (VD), hot air-microwave combined drying (HAMCD), infrared-hot air combined drying (IHACD) were used to dry Jiangyong fragrant ginger. Thirteen indexes such as total phenols, total flavonoids, gingerols, curcumin, vitamin C, starch, cellulose, free amino acids, soluble protein, soluble sugar, DPPH free radical scavenging rate, hydroxyl radical scavenging rate and total reducing capacity of the dried samples were determined, and the core indexes were screened by principal component analysis. The comprehensive evaluation model of the quality of dried ginger was constructed for comprehensive scoring. The results showed that MD had the shortest drying time and the highest drying efficiency; The determination of quality indicators found that the total phenol content of ID was the highest; The total flavonoid content of ND was the highest; The gingerol, curcumin content and vitamin C content of MD were the highest; The starch content of HAD was the highest; The soluble sugar content of HAMCD was the highest; The soluble protein and free amino acid content of IHACD was the highest; The highest cellulose content and the best antioxidant activity were VD. Through principal component analysis, 13 quality indicators were summarized into four principal component factors, with contribution rates of 34.942%, 26.725%, 17.602%, and 12.016%, respectively, and the cumulative contribution rate was 91.285%. The quality evaluation model of Jiangyong fragrant ginger was established through principal component analysis, it was concluded that VD had the highest comprehensive score. The research results can provide a reference for the deep processing of Jiangyong fragrant ginger and the development of high-value products.

Abstract Background There are some changes in the new 9th edition Tumor-Node-Metastases (TNM) staging system for lung cancer, including subdividing M1c into M1c1 and M1c2 stage. The aim of this study was to assess the prognostic performance of the updated classification system and try to provide some real-world application data among advanced lung adenocarcinoma patients with bone metastases. Methods Advanced lung adenocarcinoma patients in M1c stage with bone metastases who receiving first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and T790M-guided osimertinib as the second-line therapy were retrospectively screened from December 2016 to December 2021. A total of 126 patients were enrolled in this study. 62 patients and 64 patients were subdivided into M1c1 and M1c2 groups according to the 9th edition of TNM staging system.The first-line real-world progression-free survival (1LrwPFS), the second-line real-world progression-free survival (2LrwPFS), post-progression survival (PPS) and real-world overall survival (rwOS) were analyzed. Results The overall median rwOS was 40.1 months (95% CI 35.996–44.204). 1LrwPFS was 13.9 months (95% CI 12.653–15.147) and 2LrwPFS was 14.5 months (95% CI 11.665–17.335) for all patients.Patients in M1c2 stage was inferior to M1c1 stage patients in rwOS (35.2 months vs. 42.9 months, HR = 0.512, P = 0.005). 2LrwPFS was moderately correlated with rwOS (r = 0.621, R2 = 0.568, P = 0.000). Multivariate analysis showed performance status (PS) score ≥ 2 and TP53 alteration positive were independent prognostic factors of worse rwOS. Conclusions More refined stratification of M1c according to the 9th edition of TNM staging system is conducive to the judgment of prognosis and the implementation of precision medicine for patients.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion exchangers. This study unveils the structural insights into human AE3, including the cryo-electron microscopy structures for AE3 transmembrane domains (TMD) and a chimera combining AE3 N-terminal domain (NTD) with AE2 TMD (hAE3NTD2TMD). Our analyzes reveal a substrate binding site, an NTD-TMD interlock mechanism, and a preference for an outward-facing conformation. Unlike AE2, which has more robust acid-loading capabilities, AE3’s structure, including a less stable inward-facing conformation due to missing key NTD-TMD interactions, contributes to its moderated pH-modulating activity and increased sensitivity to the inhibitor DIDS. These structural differences underline AE3’s distinct functional roles in specific tissues and underscore the complex interplay between structural dynamics and functional specificity within the anion exchanger family, enhancing our understanding of the physiological and pathological roles of the anion exchanger family.

BackgroundTelehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. ObjectiveThe primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician’s perspective. MethodsA telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform’s registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. ResultsOver a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. ConclusionsThis study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.