Machine Learning-Driven discovery of immunogenic cell Death-Related biomarkers and molecular classification for diabetic ulcers.

In this study, we redefine the diagnostic landscape of diabetic ulcers (DUs), a major diabetes complication. Our research uncovers new biomarkers linked to immunogenic cell death (ICD) in DUs by utilizing RNA-sequencing data of Gene Expression Omnibus (GEO) analysis combined with a comprehensive database interrogation. Employing a random forest algorithm, we have developed a diagnostic model that demonstrates improved accuracy in distinguishing DUs from normal tissue, with satisfactory results from ROC analysis. Beyond mere diagnosis, our model categorizes DUs into novel molecular classifications, which may enhance our comprehension of their underlying pathophysiology. This study bridges the gap between molecular insights and clinical practice. It sets the stage for transformative strategies in DUs management, marking a significant step forward in personalized medicine for diabetic patients.

Chemically induced degradation of PRC2 complex by EZH2-Targeted PROTACs via a Ubiquitin-Proteasome pathway.

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that plays an important role in cancer cells biology. However, present EZH2 inhibitors in clinic have not achieved satisfactory efficacy. Herein, a number of EZH2-targeted PROTAC compounds were designed and synthesized by selecting different linkers, using Tazemetostat as the protein of interest (POI) portion of PROTAC molecules, hoping to improve the defects of existing EZH2 inhibitors effectively. Among all the target compounds, ZJ-20 showed the best performance with an IC50 value of 5.0 nM against MINO cells, good pharmacokinetics parameters and a limited acceptable oral bioavailability. Significantly, ZJ-20 could achieve degradation of the entire PRC2 complex by targeting EZH2, which can serve as a lead compound for further study.

Mirids secrete a TOPLESS targeting protein to enhance JA-mediated defense and gossypol accumulation for antagonizing cotton bollworms on cotton plants.

Most coexisting insect species exhibit stunted growth compared to the single species on plants. This phenomenon reflects an interspecific antagonism that draws extensive attention while the underlying mechanisms remain largely unknown. Mirids (Apolygus lucorum) and cotton bollworms (Helicoverpa armigera) are two common pests in cotton fields. We identified a secretory protein, ASP1, from the oral secretion of mirids, which was found in the nucleus of mirid-infested cotton leaves. ASP1 specifically targets the transcriptional corepressor TOPLESS (TPL) and inhibits NINJA-mediated recruitment of TPL, thereby promoting plant defense response and gossypol accumulation in cotton glands. ASP1-enhanced defense inhibits the growth of cotton bollworms on cotton plants, while having little impact on mirids. The mesophyll-feeding characteristic allows mirids to avoid most cotton glands, thereby invalidating cotton defense. Our investigation reveals the molecular mechanism by which mirids employ cotton defense to selectively inhibit the feeding of cotton bollworms.

New ideas for the development of acupuncture and moxibustion under the background of medicine-engineering translation. / 医工转化背景下针灸发展新思路.

With the increasing value of translational medicine and medical engineering in the medical field, the collaborative innovation of acupuncture and engineering has become a trend. The mode and concept of the discipline of medicine-engineering junction can promote the development of translational research with acupuncture characteristics, including the rule of syndrome evolution, the application of meridians and acupoints, the exploration of treatment methods, the research of effect mechanism and the innovation of diagnosis and treatment. This paper put forward the future underlying research ideas, the existing questions and challenges for medicine-engineering junction, so as to provide the evidences for the clinical promotion of "combination of medicine and engineering" in the application of modern acupuncture and moxibustion.

LH promotes the proliferation of porcine primordial germ cell-like cells (pPGCLCs) by regulating the ceRNA network related to the TGF-ß signaling pathway.

Primordial germ cells (PGCs), as the precursors of gametes found in early embryos, provide a new direction for solving the problem of reproductive disorders. In vitro, conversion of adult stem cells (ASCs) into primordial germ cell-like cells (PGCLCs) is feasible. The means of increasing PGCLCs number in vitro has been a focus of recent stem cell research. In this study, we found that luteinizing hormone (LH) could promote porcine PGCLCs (pPGCLCs) proliferation. To investigate the proliferation regulatory network, whole transcriptome sequencing technology was employed. Results showed that the TGF-ß signaling pathway played a key role. In addition, we found that TGFßR1 and SMAD4, TGF-ß signaling pathway-related genes, were significantly upregulated after LH treatment. Subsequently, we predicted their target microRNAs (miRNAs) and long non-coding RNAs (lncRNAs): ssc-miR-128, ssc-miR-146b, ssc-miR-361-3p, MSTRG.11473, MSTRG.11475, MSTRG.11553, and MSTRG.11554, and constructed the competitive endogenous RNAs (ceRNA) network. Finally, to further verify the ceRNA network, the miRNA-inhibitors were transfected into cells. RT-qPCR results indicated a significant increase in the expression of MSTRG.11473, MSTRG.11475, MSTRG.11553, MSTRG.11554, TGFßR1, and SMAD4 compared to the negative control (NC) group. In conclusion, these results highlight that LH could regulate the pPGCLCs proliferation by modulating the expression of TGF-ß signaling pathway-related ncRNAs.

Effects of different traditional Chinese exercise for knee osteoarthritis patients: A network meta-analysis of randomized controlled trials.

BACKGROUND: The most popular traditional Chinese exercise (TCE) techniques include Tai Chi, Yijinjing, Baduanjin, Wuqinxi, and Qigong. Exercise is advised as a primary treatment for knee osteoarthritis (KOA) according to clinical standards. According to several studies, TCE may be an effective way to help people with KOA manage their pain, stiffness, and physical function. Which TCE therapy is the most effective and whose particular usefulness is still debatable. The network meta-analysis (NMA) method is used in this study to evaluate and compare the effects of various TCE therapies on KOA patients. METHODS: We will search PubMed, Embase, Scopus, Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Wanfang, the Chinese Scientific Journal Database (VIP), and the China Biology Medical Literature Database (CBM) for randomized controlled trials reporting TCE therapy for KOA patients published before October 25, 2023. The Stata 16.0 program will compare the effectiveness of various TCE therapies on KOA patients using conventional pairwise and NMA. RESULTS: The final 29 studies included 15 articles on Tai Chi, 7 articles on Baduanjin, 4 articles on Wuqinxi, and 3 articles on Yijinjing. Tai Chi was first for the effect sizes of VAS scores, WOMAC pain scores, and WOMAC available scores, while Baduanjin was ranked top for WOMAC stiffness scores. Research should continue to be conducted on the effect of Qigong on KOA intervention. CONCLUSIONS: This NMA will help determine the best TCE treatment for KOA and offer evidence-based bias for clinical decision-making.

An alternative method to the Takagi-Taupin equations for studying dark-field X-ray microscopy of deformed crystals.

This study introduces an alternative method to the Takagi-Taupin equations for investigating the dark-field X-ray microscopy (DFXM) of deformed crystals. In scenarios where dynamical diffraction cannot be disregarded, it is essential to assess the potential inaccuracies of data interpretation based on the kinematic diffraction theory. Unlike the Takagi-Taupin equations, this new method utilizes an exact dispersion relation, and a previously developed finite difference scheme with minor modifications is used for the numerical implementation. The numerical implementation has been validated by calculating the diffraction of a diamond crystal with three components, wherein dynamical diffraction is applicable to the first component and kinematic diffraction pertains to the remaining two. The numerical convergence is tested using diffraction intensities. In addition, the DFXM image of a diamond crystal containing a stacking fault is calculated using the new method and compared with the experimental result. The new method is also applied to calculate the DFXM image of a twisted diamond crystal, which clearly shows a result different from those obtained using the Takagi-Taupin equations.

Mechanisms of action and applications of Polygonatum sibiricum polysaccharide at the intestinal mucosa barrier: a review.

As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer's disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings.

Development and validation of a nomogram for individualizing fall risk in patients with hematologic malignancies.

Inpatient falls are common adverse events especially for patients with hematologic malignancies. A fall-risk prediction model for patients with hematologic malignancies are still needed. Here we conducted a multicenter study that prospectively included 516 hospitalized patients with hematologic malignancies, and developed a nomogram for fall risk prediction. Patients were divided into the modeling group (n = 389) and the validation group (n = 127). A questionnaire containing sociodemographic factors, general health factors, disease-related factors, medication factors, and physical activity factors was administered to all patients. Logistic regression analysis revealed that peripheral neuropathy, pain intensity, Morse fall scale score, chemotherapy courses, and myelosuppression days were risk factors for falls in patients with hematologic malignancies. The nomogram model had a sensitivity of 0.790 and specificity of 0.800. The calibration curves demonstrated acceptable agreement between the predicted and observed outcomes. Therefore, the nomogram model has promising accuracy in predicting fall risk in patients with hematologic malignancies.

Efficacy and safety of a Chinese medicine formula Diankuang Mengxing Decoction combined with antipsychotics in the treatment of schizophrenia: A meta-analysis of randomized controlled trials.

BACKGROUND: In patients with schizophrenia, Diankuang Mengxing Decoction with antipsychotics is one of the treatments for it. However, little information is available regarding the difference between the therapeutic effect of Diankuang Mengxing Decoction with antipsychotics and other treatments. Systematic evaluation is conducted to assess the efficacy and safety of Diankuang Mengxing Decoction and other antipsychotics, which are used to treat schizophrenia. METHODS: We performed a systematic review (PROSPERO ID: CRD42023414603). This entailed a computerized search of several research databases from their respective dates of establishment until April 11, 2023, which collected clinical randomized controlled trials of Diankuang Mengxing Decoction combined with antipsychotics. The databases that contributed to this study were PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. Each publication was screened according to defined inclusion and exclusion criteria, and appropriate literature was extracted and evaluated for quality, for which meta-analysis was performed using RevMan 5.4. RESULTS: A literature review of 456 publications resulted in the inclusion of 18 randomized controlled trials with data collected from a total of 1636 patients. Meta-analytical results showed combination with risperidone, olanzapine, chlorpromazine, clozapine, ziprasidone, or aripiprazole increased the overall effectiveness of Diankuang Mengxing Decoction when treating schizophrenia (P < . 00001), among whom olanzapine demonstrated the greatest enhancement (Z = 3.65, odds ratio = 4.26, 95% CI: 1.96-9.28, P = .0003). The 4-week/30-day treatment (P = .0003) and a dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were more effective. Also, there were widespread reductions to the Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, general psychopathology scores (P < .05 for all), as well as the incidence of adverse effects (Z = 2.79, odds ratio = 0.34, 95% CI: 0.16-0.73, P = .005) in patients with schizophrenia. CONCLUSION: The combination of Diankuang Mengxing Decoction with different antipsychotics can improve the overall prognosis of patients with schizophrenia; Diankuang Mengxing Decoction combined olanzapine, a dosage of 400 mL/d and a duration of 4 weeks/30 days being the best in this regard, by alleviating the symptoms and diminishing the disorder's adverse effects. To build on this work, more large-sample, multi-center, and high-quality clinical studies in the future would help to further validate our findings.

Acupuncture Modulation of Chronic Neuropathic Pain and Its Association With Brain Functional Properties.

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.

A radiomics nomogram based on multiparametric MRI for diagnosing focal cortical dysplasia and initially identifying laterality.

BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.

Hyperglycemia induced cathepsin L maturation linked to diabetic comorbidities and COVID-19 mortality.

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

People with diabetes are at greater risk of developing severe COVID-19 and dying from the illness, which is caused by a virus known as SARS-CoV-2. The high blood sugar levels associated with diabetes appear to be a contributing factor to this heightened risk. However, diabetes is a complex condition encompassing a range of metabolic disorders, and it is therefore likely that other factors may contribute. Previous research identified a link between an enzyme called cathepsin L and more severe COVID-19 in people with diabetes. Elevated cathepsin L levels are known to contribute to diabetes complications, such as kidney damage and vision loss. It has also been shown that cathepsin L helps SARS-CoV-2 to enter and infect cells. This raised the question of whether elevated cathepsin L is responsible for the increased COVID-19 vulnerability in patients with diabetes. To investigate, He, Zhao et al. monitored disease severity and cathepsin L levels in patients with COVID-19. This confirmed that people with diabetes had more severe COVID-19 and that higher levels of cathepsin L are linked to more severe disease. Analysis also revealed that cathepsin L activity increases as blood glucose levels increase. In laboratory experiments, cells exposed to glucose or fluid from the blood of people with diabetes were more easily infected with SARS-CoV-2, with cells genetically modified to lack cathepsin L being more resistant to infection. Further experiments revealed this was due to glucose promoting maturation and migration of cathepsin L in the cells. The findings of He, Zhao et al. help to explain why people with diabetes are more likely to develop severe or fatal COVID-19. Therefore, controlling blood glucose levels in people with diabetes may help to prevent or reduce the severity of the disease. Additionally, therapies targeting cathepsin L could also potentially help to treat COVID-19, especially in patients with diabetes, although more research is needed to develop and test these treatments.

The efficacy of acupuncture for trigeminal neuralgia: an overview of systematic reviews.

Background: Many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy of acupuncture treatment for primary trigeminal neuralgia (PTN), but the quality of evidence is unknown and therefore needs to be evaluated comprehensively. Methods: Eight electronic databases were searched from their inception until January 5, 2024. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the assessment of multiple systematic reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: We identified 13 SRs/MAs met inclusion criteria. According to the results of the AMSTAR-2, six were rated as critically low quality and seven as low quality. According to ROBIS assessment, 8 SRs/MAs were classified as low risk, and 5 SRs/MAs were found to be high risk. The PRISMA report still has some reporting deficiencies in aspects such as protocol and registration, search strategy, risk of bias, additional analyzes and funding. According to the GRADE system, no high-quality evidence was found, 1 was of moderate quality, 4 were of low quality, and 8 were of critical low quality. Conclusion: Based on the evidence collected, acupuncture shows promise as a treatment for PTN patients. However, it is important to note that the included SRs/MAs generally have low methodological quality and evidence quality. Therefore, caution must be exercised when interpreting this conclusion. To enhance future research in this area, it is recommended to adequately report methodological details and adhere to guidelines for conducting SRs/MAs.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024499280.

Identification of Escherichia coli strains using MALDI-TOF MS combined with long short-term memory neural networks.

The current study aims to develop a new technique for the precise identification of Escherichia coli strains, utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with a long short-term memory (LSTM) neural network. A total of 48 Escherichia coli strains were isolated and cultured on tryptic soy agar medium for 24 hours for the generation of MALDI-TOF MS spectra. Eight hundred MALDI-TOF MS spectra were obtained per strain, resulting in a database of 38,400 spectra. Fifty percent of the data was utilized for LSTM neural network training, with fine-tuned parameters for strain-level identification. The other half served as the test set to assess model performance. Traditional PCA dimension reduction of MALDI-TOF MS spectra indicated 47 out of 48 strains to be unclassifiable. In contrast, the LSTM neural network demonstrated remarkable efficacy. After 20 training epochs, the model achieved a loss value of 0.0524, an accuracy of 0.999, a precision of 0.985, and a recall of 0.982. When tested on the unseen data, the model attained an overall accuracy of 92.24%. The integration of MALDI-TOF MS and LSTM neural network markedly enhances the identification of Escherichia coli strains. This innovative approach offers an effective and accurate tool for MALDI-TOF MS-based strain-level identification, thus expanding the analytical capabilities of microbial diagnostics.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Phylogenetic and Comparative Genomics Study of Papilionidae Based on Mitochondrial Genomes.

Most species of Papilionidae are large and beautiful ornamental butterflies. They are recognized as model organisms in ecology, evolutionary biology, genetics, and conservation biology but present numerous unresolved phylogenetic problems. Complete mitochondrial genomes (mitogenomes) have been widely used in phylogenetic studies of butterflies, but mitogenome knowledge within the family Papilionidae is limited, and its phylogeny is far from resolved. In this study, we first report the mitogenome of Byasa confusa from the subfamily Papilioninae of Papilionidae. The mitogenome of B. confusa is 15,135 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an AT-rich control region (CR), closely mirroring the genomic structure observed in related butterfly species. Comparative analysis of 77 Papilionidae mitogenomes shows gene composition and order to be identical to that of an ancestral insect, and the AT bias, Ka/Ks, and relative synonymous codon usage (RSCU) are all consistent with that of other reported butterfly mitogenomes. We conducted phylogenetic analyses using maximum-likelihood (ML) and Bayesian-inference (BI) methods, with 77 Papilionidae species as ingroups and two species of Nymphalidae and Lycaenidae as outgroups. The phylogenetic analysis indicated that B. confusa were clustered within Byasa. The phylogenetic trees show the monophyly of the subfamily Papilioninae and the tribes Leptocircini, Papilionini, and Troidini. The data supported the following relationships in tribe level on Papilioninae: (((Troidini + Papilionini) + Teinopalpini) + Leptocircini). The divergence time analysis suggests that Papilionidae originated in the late Creataceous. Overall, utilizing the largest number of Papilionidae mitogenomes sequenced to date, with the current first exploration in a phylogenetic analysis on Papilionidae (including four subfamilies), this study comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny, providing information for further studies on the mitogenome, phylogeny, evolution, and taxonomic revision of the Papilionidae family.

[Coronary heart disease: innovative understanding from traditional Chinese medicine and treatment by classic formulas].

Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.

[Value of single-phase gonadotropin-releasing hormone stimulation test in diagnosis of central precocious puberty in girls with different levels of body mass index]. / 单时相GnRHæ¿€å‘è¯•éªŒå¯¹ä¸åŒä½“é‡æŒ‡æ•°å¥³ç«¥ä¸­æž¢æ€§æ€§æ—©ç†Ÿè¯Šæ–­ä»·å€¼çš„ç ”ç©¶.

OBJECTIVES: To investigate the value of single-phase gonadotropin releasing hormone (GnRH) stimulation test in the diagnosis of central precocious puberty (CPP) in girls with different levels of body mass index (BMI). METHODS: A retrospective analysis was performed for the data of 760 girls with breast development before 7.5 years of age who attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2023. According to the results of GnRH stimulation test and clinical manifestations, they were divided into a CPP group (297 girls) and a non-CPP group (463 girls). According to the values of BMI, the girls were divided into a normal weight group (540 girls), an overweight group (116 girls), and an obese group (104 girls). The receiver operating characteristic (ROC) curve was used to investigate the value of single-phase GnRH stimulation test in the diagnosis of CPP in girls with different levels of BMI. RESULTS: Luteinizing hormone (LH)/follicle-stimulating hormone at 30 minutes after GnRH stimulation had an area under the curve (AUC) of 0.985 in the diagnosis of CPP, which was higher than the AUC at 0, 60, and 90 minutes (P<0.05). LH at 30 minutes had a similar diagnostic value to LH at 60 minutes (P>0.05). LH at 30 minutes was negatively correlated with BMI and BMI-Z value (P<0.05).The AUC for diagnosing CPP in normal weight, overweight, and obese girls at 30 minutes LH was 0.952, 0.965, and 0.954, respectively (P<0.05). CONCLUSIONS: The 30-minute GnRH stimulation test has a good value in the diagnosis of CPP in girls with different levels of BMI and is expected to replace the traditional GnRH stimulation test, but the influence of BMI on LH level should be taken seriously.

Identification of Angiogenesis-Related Genes and Molecular Subtypes for Psoriasis Based on Random Forest Algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithms. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis (PCA). A diagnostic model was developed using random forest algorithm (ntree=400) and validated by ROC curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by qRT-PCR. We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P<0.0001) and interleukins pathway (R=0.79, P<0.0001). Furtherer, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.