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AnteayerPLOS ONE Medicine&Health

Comparison efficacy and safety of acupuncture and moxibustion therapies in breast cancer-related lymphedema: A systematic review and network meta-analysis

by Yawen Xu, Jiangxuan Yu, Rui Shen, Xueqi Shan, Wenlu Zhou, Junjie Wang

Objective

Although several acupuncture and moxibustion therapies have been tested in managing breast cancer-related lymphedema (BCRL), there is little consensus regarding the best options for treating this condition. This systematic review and network meta-analysis compared the efficacy of various acupuncture and/or moxibustion therapies for BCRL.

Methods

Seven databases and two clinical registration centers were searched from their inception to December 1st, 2023. The Cochrane Collaboration risk-of-bias assessment tool evaluated the quality of included RCTs. A pairwise meta-analysis was performed in STATA 16.0, while a network meta-analysis was performed in R 4.2.2.

Results

18 studies were included in this analysis. Our results showed that acupuncture and moxibustion methods had great advantages in improving BCRL of patients with breast cancer. In particular, needle-warming moxibustion (NWM) could be the optimal acupuncture and moxibustion method for improving clinical effectiveness and reducing the degree of swelling of affected limbs.

Conclusion

Our findings suggest that NWM has great potential in treating BCRL. It may reduce arm circumference, lower swelling levels, and improve clinical effectiveness. Nevertheless, more multi-center, high-quality, and large sample RCTs will be needed in the future.

Accuracy of artificial intelligence-assisted endoscopy in the diagnosis of gastric intestinal metaplasia: A systematic review and meta-analysis

by Na Li, Jian Yang, Xiaodong Li, Yanting Shi, Kunhong Wang

Background and aims

Gastric intestinal metaplasia is a precancerous disease, and a timely diagnosis is essential to delay or halt cancer progression. Artificial intelligence (AI) has found widespread application in the field of disease diagnosis. This study aimed to conduct a comprehensive evaluation of AI’s diagnostic accuracy in detecting gastric intestinal metaplasia in endoscopy, compare it to endoscopists’ ability, and explore the main factors affecting AI’s performance.

Methods

The study followed the PRISMA-DTA guidelines, and the PubMed, Embase, Web of Science, Cochrane, and IEEE Xplore databases were searched to include relevant studies published by October 2023. We extracted the key features and experimental data of each study and combined the sensitivity and specificity metrics by meta-analysis. We then compared the diagnostic ability of the AI versus the endoscopists using the same test data.

Results

Twelve studies with 11,173 patients were included, demonstrating AI models’ efficacy in diagnosing gastric intestinal metaplasia. The meta-analysis yielded a pooled sensitivity of 94% (95% confidence interval: 0.92–0.96) and specificity of 93% (95% confidence interval: 0.89–0.95). The combined area under the receiver operating characteristics curve was 0.97. The results of meta-regression and subgroup analysis showed that factors such as study design, endoscopy type, number of training images, and algorithm had a significant effect on the diagnostic performance of AI. The AI exhibited a higher diagnostic capacity than endoscopists (sensitivity: 95% vs. 79%).

Conclusions

AI-aided diagnosis of gastric intestinal metaplasia using endoscopy showed high performance and clinical diagnostic value. However, further prospective studies are required to validate these findings.

Xinnaotongluo liquid protects H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3

by Jiankun Cui, Qinwen Wang, Minghao Li

Xinnaotongluo liquid has been used to improve the clinical symptoms of patients with myocardial infarction. However, the molecular mechanism of Xinnaotongluo liquid is not completely understood. H9c2 cells exposed to hypoxia/reoxygenation (H/R) was used to simulate damage to cardiomyocytes in myocardial infarction in vitro. The biological indicators of H9c2 cells were measured by cell counting kit-8, enzyme linked immunoabsorbent assay, and western blot assay. In H/R-induced H9c2 cells, a markedly reduced murine double minute 2 (MDM2) was observed. However, the addition of Xinnaotongluo liquid increased MDM2 expression in H/R-induced H9c2 cells. And MDM2 overexpression strengthened the beneficial effects of Xinnaotongluo liquid on H9c2 cells from the perspective of alleviating oxidative damage, cellular inflammation, apoptosis and ferroptosis of H/R-induced H9c2 cells. Moreover, MDM2 overexpression reduced the protein expression of p53 and Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3). Whereas, STEAP3 overexpression hindered the function of MDM2-overexpression in H/R-induced H9c2 cells. Our results insinuated that Xinnaotongluo liquid could protect H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3, which provide a potential theoretical basis for further explaining the working mechanism of Xinnaotongluo liquid.

Untargeted metabolomics reveals that declined PE and PC in obesity may be associated with prostate hyperplasia

by Guorui Fan, Xiaohai Guan, Bo Guan, Hongfei Zhu, Yongchao Pei, Chonghao Jiang, Yonggui Xiao, Zhiguo Li, Fenghong Cao

Background

Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood.

Methods

A prospective case–control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF).

Results

A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms.

Conclusions

In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults

by Junhao Sun, Siqi Yang, Yue Zhang, Wenzhi Xiang, Xiubo Jiang

As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007–2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P

Characteristics of men who have casual sex with men among Chinese university students: A cross-sectional study

by Weiyong Chen, Qiaoqin Ma, Xiaohong Pan, Lin Chen, Hui Wang, Xin Zhou, Tingting Jiang, Wanjun Chen

Objectives

The characteristics of men who have sex with men (either exclusively or with both men and women; MSM) who engaged in casual sex among Chinese male university students have not been compared with the characteristics of men who have sex with only women (MSW). This information is important for tailoring targeted behavioral interventions to prevent human immunodeficiency virus (HIV)/sexually transmitted infection (STI) transmission in this subgroup of MSM.

Methods

Data were derived from a large cross-sectional electronic questionnaire survey conducted at 13 universities in Zhejiang Province, China, in 2018. Bivariate analyses were used to compare demographic, HIV-related psychosocial, and behavioral characteristics between MSM and MSW students who engaged in casual sex during the previous year. Proportion differences between the two groups and their 95% confidence intervals were analyzed.

Results

Among the 583 sexually active male students who engaged in casual sex during the previous year, 128 and 455 were MSM and MSW, respectively. Compared with MSW students, larger proportions of MSM students reported knowing that male-to-male sexual behavior was the main mode of HIV transmission among Chinese students (62.5% vs. 45.5%), consenting to commercial sex (67.2% vs. 53.4%), wanting to know the HIV serostatus of partners before casual sex (65.8% vs. 51.3%), feeling at risk of HIV infection (40.5% vs. 11.8%), high condom-decision scale scores (55.3% vs. 42.6%), engaging in sex with ≥ 5 casual sex partners (44.6% vs. 25.9%), searching for casual partners online (89.2% vs. 51.3%), consuming alcohol before casual sex (64.8% vs. 45.0%), engaging in sex with regular partners (83.1% vs. 67.0%), engaging in commercial sex (54.2% vs. 26.4%), and visiting a clinic for voluntary counselling and testing (VCT) (16.4% vs. 8.4%). However, compared with MSW students, smaller proportions of MSM students reported knowing that consistent condom use could prevent HIV transmission (80.5% vs. 95.2%) and that VCT should be actively sought after risky sexual behavior (78.9% vs. 93.8%), using condoms sometimes/often (26.4% vs. 44.3%), and consistently using condoms (28.9% vs. 40.1%) while engaging in sex with casual partners.

Conclusions

MSM students who engaged in casual sex were at a greater risk of HIV/STI transmission, compared with MSW students. Comprehensive interventions to address the risks of unprotected male-to-male sex, searching for casual sex partners online, and non-use of HIV testing services are needed to reduce the burden of HIV/STI transmission among this subgroup of MSM.

AE-GPT: Using Large Language Models to extract adverse events from surveillance reports-A use case with influenza vaccine adverse events

by Yiming Li, Jianfu Li, Jianping He, Cui Tao

Though Vaccines are instrumental in global health, mitigating infectious diseases and pandemic outbreaks, they can occasionally lead to adverse events (AEs). Recently, Large Language Models (LLMs) have shown promise in effectively identifying and cataloging AEs within clinical reports. Utilizing data from the Vaccine Adverse Event Reporting System (VAERS) from 1990 to 2016, this study particularly focuses on AEs to evaluate LLMs’ capability for AE extraction. A variety of prevalent LLMs, including GPT-2, GPT-3 variants, GPT-4, and Llama2, were evaluated using Influenza vaccine as a use case. The fine-tuned GPT 3.5 model (AE-GPT) stood out with a 0.704 averaged micro F1 score for strict match and 0.816 for relaxed match. The encouraging performance of the AE-GPT underscores LLMs’ potential in processing medical data, indicating a significant stride towards advanced AE detection, thus presumably generalizable to other AE extraction tasks.

Chinese herbal medicine for post-viral fatigue: A systematic review of randomized controlled trials

by Le-Yan Hu, An-Qi Cai, Bo Li, Zheng Li, Jian-Ping Liu, Hui-Juan Cao

Background

Fatigue is a common symptom after viral infection. Chinese herbal medicine (CHM) is thought to be a potential effective intervention in relieving fatigue.

Purpose

To assess the effectiveness and safety of CHM for the treatment of post-viral fatigue.

Study design

Systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods

The protocol of this systematic review was registered on PROSPERO (CRD42022380356). Trials reported changes of fatigue symptom, which compared CHM to no treatment, placebo or drugs, were included. Six electronic databases and three clinical trial registration platforms were searched from inception to November 2023. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included trials was evaluated using Cochrane risk of bias tool, and the certainty of the evidence was evaluated using GRADE. The meta-analysis was performed using Review Manager 5.4, mean difference (MD) and its 95% confidence interval (CI) was used for estimate effect of continuous data. Heterogeneity among trials was assessed through I2 value.

Results

Overall, nineteen studies with 1921 patients were included. Results of individual trial or meta-analysis showed that CHM was better than no treatment (MD = -0.80 scores, 95%CI -1.43 to -0.17 scores, P = 0.01, 60 participants, 1 trial), placebo (MD = -1.90 scores, 95%CI -2.38 to -1.42 scores, P.00001, 184 participants, 1 trial), placebo on basis of rehabilitation therapy (MD = -14.90 scores, 95%CI -24.53 to -5.27 scores, P = 0.02, 118 participants, 1 trial) or drugs (MD = -0.38 scores, 95%CI -0.48 to -0.27 scores, I2 = 0%, Pto drugs alone also showed better effect of combination therapy (average MD = -0.56 scores). In addition, CHM may improve the percentage of CD4 T lymphocytes and reduce the level of serum IL-6 (MD = -14.64 scores, 95%CI 18.36 to -10.91 scores, I2 = 0%, P Conclusion

Current systematic review found that the participation of CHM can improve the symptoms of post-viral fatigue and some immune indicators. However, the safety of CHM remains unknown and large sample, high quality multicenter RCTs are still needed in the future.

Identification of the single and combined acute toxicity of Cr and Ni with <i>Heterocypris</i> sp. and the quantitative structure-activity relationship (QSAR) model

by Chi Su, Yilong Hua, Yi Liu, Shu Tao, Fei Jia, Wenhui Zhao, Wangyang Lin

Mining wastewater with heavy metals poses a serious threat to the ecological environment. However, the acute single and combined ecological effects of heavy metals, such as chromium (Cr) and nickel (Ni), on freshwater ostracods, and the development of relevant prediction models, remain poorly understood. In this study, Heterocypris sp. was chosen to investigate the single and combined acute toxicity of Cr and Ni. Then, the quantitative structure-activity relationship (QSAR) model was used to predict the combined toxicity of Cr and Ni. The single acute toxicity experiments revealed high toxicity for both Cr and Ni. In addition, Cr exhibited greater toxicity compared to Ni, as evidenced by its lower 96-hour half-lethal concentration (LC50) of 1.07 mg/L compared to 4.7 mg/L for Ni. Furthermore, the combined acute toxicity experiments showed that the toxicity of Cr-Ni was higher than Ni but lower than Cr. Compared with the concentration addition (CA) and independent action (IA) models, the predicted results of the QSAR model were more consistent with the experimental results for the Cr-Ni combined acute toxicity. So, the high accuracy of QSAR model identified its feasibility to predict the toxicity of heavy metal pollutants in mining wastewater.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes

by Luying Jiang, Jingbo Liu, Zhenjia Yang, Jianyu Wang, Wenkai Ke, Kaiyue Zhang, Chunran Zhang, Houjuan Zuo

Background

Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear.

Method and results

In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes.

Conclusion

Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis

by Hong Duo, Mengying Jin, Yanwei Yang, Rewaan Baheti, Yujia Feng, Zirui Fu, Yuyue Jiang, Lanzhuoying Zheng, Jing Wan, Huaqin Pan

Background

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.

Methods

Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.

Results

Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83–1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09–3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83–1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.

Conclusion

According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Causal relationship between diet and knee osteoarthritis: A Mendelian randomization analysis

by Xiaofeng Lv, Fangqi Liang, Shanshan Liu, Xinmin Deng, Rui Lai, Jihang Du, Jian Luo

Background

Knee osteoarthritis (KOA) is a common disabling joint disease that affects millions of people worldwide. Diet may play a role in the etiology and progression of KOA, but evidence for a causal relationship is limited. We aimed to investigate the causal impact of dietary intake on KOA risk using Mendelian randomization (MR).

Methods

We used summary-level data from genome-wide association studies (GWAS) including dietary intake (n = 335, 394–462, 342), and KOA (n = 403, 124). We selected 6–77 genetic variants as instrumental variables for 18 dietary factors, including processed meat, poultry, beef, oily fish, non-oily fish, pork, lamb, frequency of alcohol intake, alcoholic beverages, tea, coffee, dried fruit, cereals, cheese, bread, cooked vegetables, salad/raw vegetables, and fresh fruit. We performed univariate and multivariate MR analyses to estimate the causal effect of each dietary factor on KOA risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis.

Results

We found that higher coffee intake was associated with increased KOA risk, whereas higher intake of dried fruits, grains, cheese, and oily fish was associated with reduced KOA risk. After multivariate adjustment, we found that coffee and oily fish intake may affect KOA through obesity, body mass index (BMI), diabetes, hypertension, and prolonged standing. Sensitivity analyses did not reveal any evidence of pleiotropy.

Conclusions

Our study provides new causal evidence that dietary intake may influence KOA risk. Specifically, we suggest that increased intake of dried fruits, grains, cheese, and oily fish and decreased coffee intake may be beneficial in preventing and mitigating KOA. further studies are needed to elucidate the underlying mechanisms and to confirm our findings in different populations.

DNA barcoding for the identification and authentication of medicinal deer (<i>Cervus</i> sp.) products in China

by Wenlan Li, Qiqi Ren, Jian Feng, Shiou Yih Lee, Yangyang Liu

Deer products from sika deer (Cervus nippon) and red deer (C. elaphus) are considered genuine and used for Traditional Chinese Medicine (TCM) materials in China. Deer has a very high economic and ornamental value, resulting in the formation of a characteristic deer industry in the prescription preparation of traditional Chinese medicine, health food, cosmetics, and other areas of development and utilization. Due to the high demand for deer products, the products are expensive and have limited production, but the legal use of deer is limited to only two species of sika deer and red deer; other wild deer are prohibited from hunting, so there are numerous cases of mixing and adulteration of counterfeit products and so on. There have been many reports that other animal (pig, cow, sheep, etc.) tissues or organs are often used for adulteration and confusion, resulting in poor efficacy of deer traditional medicine and trade fraud in deer products. To authenticate the deer products in a rapid and effective manner, the analysis used 22 deer products (antler, meat, bone, fetus, penis, tail, skin, and wool) that were in the form of blind samples. Total DNA extraction using a modified protocol successfully yielded DNA from the blind samples that was useful for PCR. Three candidate DNA barcoding loci, cox1, Cyt b, and rrn12, were evaluated for their discrimination strength through BLAST and phylogenetic clustering analyses. For the BLAST analysis, the 22 blind samples obtained 100% match identity across the three gene loci tested. It was revealed that 12 blind samples were correctly labeled for their species of origin, while three blind samples that were thought to originate from red deer were identified as C. nippon, and seven blind samples that were thought to originate from sika deer were identified as C. elaphus, Dama dama, and Rangifer tarandus. DNA barcoding analysis showed that all three gene loci were able to distinguish the two Cervus species and to identify the presence of adulterant species. The DNA barcoding technique was able to provide a useful and sensitive approach in identifying the species of origin in deer products.

Aerodynamic noise characteristics of a centrifugal fan in high-altitude environments

Por: Xue Liu · Jian Liu

by Xue Liu, Jian Liu

In high-altitude areas, the air is thin and the atmospheric pressure is low, which can affect the performance of centrifugal fans and aerodynamic noise. In this paper, steady and unsteady simulations of a centrifugal fan flow field are performed at altitudes of 0, 1000, 2000, 3000, 4000, and 5000 m, and the Ffowcs Williams-Hawkings equation is used to predict the aerodynamic noise of the fan. The results indicate that the tonal and broadband noise generated by the fan decrease with increasing altitude, and the A-weighted sound pressure level of each frequency band of the fan decreases when the air volume is held fixed. The maximum sound power level Lwmax, sound pressure pulsation interval, and total noise sound pressure level Lp decrease linearly with increasing altitude. For every 1000 m increase in altitude, Lwmax and Lp decrease by 0.45 dB and 1.05 dB respectively. The fan noise characteristics, performance parameters, and human auditory perception are the main factors that affect the establishment of fan noise standards in high-altitude areas.

Clinical evaluation of a fully electronic microfluidic white blood cell analyzer

by Jianye Sui, Zhongtian Lin, Shahriar Azizpour, Fei Chen, Sunanda Gaur, Kelly Keene, Farzad Soleimani, Tanaya Bhowmick, Zubaid Rafique, Mehdi Javanmard

The White Blood Cell (WBC) count is one of the key parameters signaling the health of the immune system. Abnormal WBC counts often signal a systemic insult to the body such as an underlying infection or an adverse side effect to medication. Typically, the blood collected is sent to a central lab for testing, and results come back within hours, which is often inconvenient and may delay time-sensitive diagnosis or treatment. Here, we present the CytoTracker, a fully electronic, microfluidic based instant WBC analyzer with the potential to be used at point-of-care. The CytoTracker is a lightweight, portable, affordable platform capable of quantifying WBCs within minutes using only 50 μl of blood (approximately one drop of blood). In this study, we clinically evaluated the accuracy and performance of CytoTracker in measuring WBC and granulocyte counts. A total of 210 adult patients were recruited in the study. We validated the CytoTracker against a standard benchtop analyzer (Horiba Point of Care Hematology Analyzer, ABX Micros 60). Linear dynamic ranges of 2.5 k/μl– 35 k/μl and 0.6 k/μl– 26 k/μl were achieved for total WBC count and granulocyte count with correlation coefficients of 0.97 and 0.98. In addition, we verified CytoTracker’s capability of identifying abnormal blood counts with above 90% sensitivity and specificity. The promising results of this clinical validation study demonstrate the potential for the use of the CytoTracker as a reliable and accurate point-of-care WBC analyzer.

Improving structure-based protein-ligand affinity prediction by graph representation learning and ensemble learning

Por: Jia Guo

by Jia Guo

Predicting protein-ligand binding affinity presents a viable solution for accelerating the discovery of new lead compounds. The recent widespread application of machine learning approaches, especially graph neural networks, has brought new advancements in this field. However, some existing structure-based methods treat protein macromolecules and ligand small molecules in the same way and ignore the data heterogeneity, potentially leading to incomplete exploration of the biochemical information of ligands. In this work, we propose LGN, a graph neural network-based fusion model with extra ligand feature extraction to effectively capture local features and global features within the protein-ligand complex, and make use of interaction fingerprints. By combining the ligand-based features and interaction fingerprints, LGN achieves Pearson correlation coefficients of up to 0.842 on the PDBbind 2016 core set, compared to 0.807 when using the features of complex graphs alone. Finally, we verify the rationalization and generalization of our model through comprehensive experiments. We also compare our model with state-of-the-art baseline methods, which validates the superiority of our model. To reduce the impact of data similarity, we increase the robustness of the model by incorporating ensemble learning.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel

by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis

by Song Chen, Qian Zhang, Liyan Sun, Wei Song, Tao Zhang, Weidong Song, Jian Wan

Background

Sepsis, described as an inflammatory reaction to an infection, is a very social health problem with high mortality. This study aims to explore the new mechanism in the progression of sepsis.

Methods

We downloaded the GSE69528 dataset to screen differentially expressed genes (DEGs) for WGCNA, in which the key module was identified and analyzed by DMNC algorithm, expression verification and ROC curve analysis to identify the hub gene. Furthermore, the hub gene was analyzed by immunoassay, and the potential mechanism of hub gene in neutrophils was investigated by in vitro experiments.

Results

The turquoise module was the key module for sepsis in WGCNA on 94 DEGs. The top 20 genes of DMNC network were verified in GSE69528 and GSE9960, and 10 significant genes were obtained for ROC analysis. Based on the ROC curves, HP was considered the hub gene in sepsis, and its expression difference in sepsis and control groups was substantially significant. Further, it was demonstrated the knockdown of HP and PFKFB3 could suppress glycolysis and inflammatory cytokine levels in dHL-60 cell treated with LPS.

Conclusion

In conclusion, HP is identified as a potential diagnostic indicator for sepsis patients, and HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis confirmed by in vitro experiments. These will help us deepen the molecular mechanism of sepsis.

Association between vitamin D and endometriosis among American women: National Health and Nutrition Examination Survey

by Baoli Xie, Ming Liao, Yingqin Huang, Fu Hang, Nana Ma, Qianwen Hu, Jiawei Wang, Yufu Jin, Aiping Qin

Endometriosis is a multifactorial disease associated with inflammation. Vitamin D has anti-inflammatory, antiproliferative, anti-oxidative, and immunomodulatory effects. Whether vitamin D levels are correlated with endometriosis is a subject of ongoing debate. This study aimed to examine the association between endometriosis and serum vitamin D levels. From the National Health and Nutrition Examination Survey, this study examined the cross-sectional data of American women aged 20–54 years from 2001 to 2006. After adjusting for covariates, multivariable logistic regression analysis was used to assess correlations. A total of 3,232 women were included in this study. The multiple linear regression model demonstrated a negative correlation between the serum 25-hydroxyvitamin D3 (cholecalciferol) concentration and the risk of endometriosis after controlling for all confounding variables. The odds ratio was 0.73 with a 95% confidence interval of 0.54–0.97 in the adequate vitamin D level group compared with the insufficient vitamin D level group. Our results showed that endometriosis was inversely correlated with serum 25-hydroxyvitamin D3 levels. Further research is needed to establish a causal relationship and determine the potential benefits of maintaining sufficient vitamin D levels for endometriosis prevention.

Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials

by Qinxi Shu, Chao Kang, Jiaxin Li, Zhenzhu Hou, Minfen Xiong, Xingang Wang, Hongyan Peng

Background

Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels.

Methods

We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement.

Results

A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: −0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: −0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: −0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found.

Conclusions

Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves’ disease.

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