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Abstract Background Neurological complications are a significant concern of Coronavirus Disease 2019 (COVID-19). However, the pathogenic mechanism of neurological symptoms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is poorly understood. Methods We used Drosophila as a model to systematically analyze SARS-CoV-2 genes encoding structural and accessory proteins and identified the membrane protein (M) that disrupted mitochondrial functions in vivo. The M protein was stereotaxically injected to further assess its effects in the brains of wild-type (WT) and 5 × FAD mice. Omics technologies, including RNA sequencing and interactome analysis, were performed to explore the mechanisms of the effects of M protein both in vitro and in vivo. Results Systematic analysis of SARS-CoV-2 structural and accessory proteins in Drosophila identified that the M protein induces mitochondrial fragmentation and dysfunction, leading to reduced ATP production, ROS overproduction, and eventually cell death in the indirect flight muscles. In WT mice, M caused hippocampal atrophy, neural apoptosis, glial activation, and mitochondrial damage. These changes were further aggravated in 5 × FAD mice. M was localized to the Golgi apparatus and genetically interacted with four wheel drive (FWD, a Drosophila homolog of mammalian PI4KIIIβ) to regulate Golgi functions in flies. Fwd RNAi, but not PI4KIIIα RNAi, reversed the M-induced Golgi abnormality, mitochondrial fragmentation, and ATP reduction. Inhibition of PI4KIIIβ activity suppressed the M-induced neuronal cell death. Therefore, M induced mitochondrial fragmentation and apoptosis likely through disruption of Golgi-derived PI(4)P-containing vesicles. Conclusions M disturbs the distribution and function of Golgi, leading to mitochondrial abnormality and eventually neurodegeneration via a PI4KIIIβ-mediated mechanism. This study reveals a potential mechanism for COVID-19 neurological symptoms and opens a new avenue for development of therapeutic strategies targeting SARS-CoV-2 M or mitochondria.

Abstract Objective A ureteric stone is a type of urinary tract stone that is found within the ureter. While most cases can be managed with conservative treatment or minimally invasive surgery, these methods often cause significant pain for the patient. Interestingly, a new type of ureteroscope has shown considerable promise in treating patients with ureteric stones, and this study aims to explore its clinical application. Methods A total of 120 patients with ureteric stones were recruited from our hospitals between January 1, 2023, and December 31, 2023. These patients were randomly assigned to either the control group, which received the traditional straight ureteroscope, or the experimental group, which was treated with the new type of ureteroscope. Both groups provided general data and blood samples for further analysis. A logistic regression analysis was conducted to examine the factors influencing infection following surgery in patients with ureteric stones, including preoperative CRP greater than 8 mg/L, postoperative CRP greater than 8 mg/L, preoperative white blood cell count (> 109/L), postoperative white blood cell count (> 109/L), preoperative urinalysis count greater than 28 (/ul), postoperative urinalysis count greater than 28 (/ul), and urine routine leukocyte count. Results The findings indicated no significant differences between the observation group and the control group regarding preoperative demographic, participants general data (P > 0.05). Postoperative CRP > 8 mg/L, white blood cell count > 10 × 109/L, urinalysis count > 28/µL, and urine leukocyte count significantly decreased in the experimental group compared to the control group (P 8 mg/L (OR = 7.03), white blood cell count > 109/L (OR = 3.86), urinalysis count > 28/µL (OR = 2.83), and urine leukocyte count (OR = 1.004) were predictive factors for ureteric stones. Preoperative values showed no significant difference (P > 0.05). Conclusions The binary logistic regression analysis identified Postoperative CRP > 8 mg/L, white blood cell count > 10 × 109/L, urinalysis count > 28/µL, and urine leukocyte count as significant predictors of postoperative infections. Our research findings indicate that the new ureteroscope has significant advantages over traditional ureteroscopes in terms of ease of entry into the ureteral lumen, stone fragmentation angle during surgery, surgical field of view, surgical operability, and reducing the risk of postoperative potential infections. These characteristics demonstrate that the new ureteroscope has significant potential in clinical applications, warranting further promotion and use.

Na Li,1,2 Junli Zhang,3 Fei Yu,1,2 Fanghang Ye,1,2 Wanying Tan,4 Liyuan Hao,1,2 Shenghao Li,1,2 Jiali Deng,1,2 Xiaoyu Hu2 1Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, People’s Republic of China; 4Center for Infectious Diseases, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiaoyu Hu, Email TCMxiaoyuhu@aliyun.comAbstract: In recent years, the incidence of fungal infections has been rising annually, especially among immunocompromised populations, posing a significant challenge to public health. Although antifungal medications provide some relief, the escalating problem of resistance sharply curtails their effectiveness, presenting an urgent clinical dilemma that demands immediate attention. Research has shown that fungal resistance is closely related to quorum sensing (QS), and QS inhibitors (QSIs) are considered an effective solution to this issue. Garlic, as a natural QSI, has demonstrated significant effects in inhibiting fungal growth, preventing biofilm formation, enhancing immunity, and combating resistance. This study explores the potential of garlic in mitigating fungal drug resistance and identifies its key role in inhibiting the QS mechanism, these findings offer a new perspective for the treatment of fungal infections, especially in addressing the increasingly severe problem of resistance. However, the clinical application of garlic still faces several challenges, such as ensuring the standardization of active ingredient extraction, as well as issues of safety and stability. Future research should focus on the QS mechanism and promote interdisciplinary collaboration to develop more natural, effective, and safe QSI drugs like garlic, while actively conducting clinical trials to validate their efficacy and safety. Additionally, incorporating advanced technologies such as nanotechnology to enhance drug stability and targeting, provide a more comprehensive strategy for the treatment of fungal infections. Overall, Our study provides scientific evidence supporting the potential of garlic as a novel antifungal treatment and lays the groundwork for the development of future natural QSIs for therapeutic use. It offers new insights, particularly for the treatment of immunocompromised populations and drug-resistant fungal strains. Keywords: fungal infection, drug resistance, garlic, quorum sensing, quorum sensing inhibitors

Jing Zhu,1 Yiming Huang,1,2 Chao Ye,3 Xiaoxia Deng,1,2 Yuxuan Zou,1,2 En Yuan,2 Qi Chen2 1Research Center for Chinese Medicine Resources and Ethnic Minority Medicine, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China; 2School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China; 3The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of ChinaCorrespondence: Jing Zhu, Research Center for Chinese Medicine Resources and Ethnic Minority Medicine, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China, Tel +86-13755654318, Email 277836041@qq.comObjective: The main objective of this study was to elucidate the effector material basis of Cimicifugae Rhizoma (CR) for the treatment of acute pneumonia (AP) and to explore the potential mechanisms underlying the anti-AP effects of these active components in a lipopolysaccharide (LPS)-induced inflammation model of lung epithelial cells.Methods: Chemical components were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-TOF-MS), and a CR component library was subsequently established based on a combination of databases and available literature. Bioinformatics techniques were used to construct “component-target” and “protein-protein interaction (PPI)” networks, and the potential active components and core targets screened according to degree value, followed by molecular docking and in vitro experiments for verification. Inflammation was induced in normal human lung epithelial cells using lipopolysaccharide (LPS) to mimic the occurrence of AP.Results: In total, 122 CR components were identified. The therapeutic effects of potential active components against AP were associated with 147 targets involving 165 signaling pathways. Molecular docking experiments revealed the strong affinity of N-cis- feruloyltyramine, ferulic acid, cimifugin, and isoferulic acid for core AP-associated targets. In vitro cellular experiments showed that the above compounds and CR alcoholic extracts inhibited the expression of inflammatory factors in the following order: isoferulic acid > cimifugin > CR alcoholic extract > N-cis-feruloyltyramine > ferulic acid.Conclusion: N-cis- feruloyltyramine, ferulic acid, cimifugin, and isoferulic acid were the effector components of CR with activity against AP. These compounds potentially co-regulate the IL-6/JAK/STAT3 and TLR4/IL-1β-IRAK pathways through the inhibition of cytokines such as IL-6, TNF-α, and IL-1β, and downregulation of P-STAT3, TLR4, PIK3CA, and NF-κB involved in TLR4/IL-1β-IRAK/NF-κB and PI3K-Akt signaling pathways to exert therapeutic effects on AP.Keywords: acute pneumonia, molecule docking, lung epithelial cells, LPS, signaling pathway

Jiang Wang,1,2,&ast; Aizhang Zhu,1,2,&ast; Jie Chen,3,&ast; Rui Zeng,4,&ast; Siyi Wang,1,2 Lihuan Chen,5 Ying Chen,1,2 Qianqian Min,1,2 Wei Li,4,6 Dongmei Ye,4 Ruohan Wu,1,2 Fayi Xie,4 Tenghui Fan,4 Ke Zhu,4 Wan Zhu,4 Hongmei Hu,1 Conghua Wang,3 Xiaoming Zhang3 1School of Basic Medicine, Jinggangshan University, Ji’an, Jiangxi, People’s Republic of China; 2Online Collaborative Research Center for Evidence-Based Medicine Ministry of Education, Jinggangshan University Branch, Ji’an, Jiangxi, People’s Republic of China; 3Department of Emergency, The People’s Hospital of Baoan Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 4School of Clinical Medicine, Jinggangshan University, Ji’an, Jiangxi, People’s Republic of China; 5School of Chinese Medicine, Jinggangshan University, Ji’an, Jiangxi, People’s Republic of China; 6Clinical Medical Research Center, Affiliated Hospital of Jinggangshan University, Jiangxi Province Key Laboratory of Organ Development and Epigenetics, Clinical College of Jinggangshan University, Ji’an, Jiangxi, 343009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongmei Hu; Xiaoming Zhang, Email huhongmei1218@126.com; zhangmuxi0310@163.comBackground: The interplay between cognitive frailty and depression remains inadequately understood, with a paucity of evidence from prospective cohort studies. Our study aims to elucidate the relationship between cognitive frailty and the risk of incident depression.Methods: Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011, 2013, and 2015, subjects were classified according to cognitive frailty criteria established by an international consensus panel. Multiple logistic regression models were employed to examine the cross-sectional and longitudinal associations between frailty, cognitive impairment, cognitive frailty, and depression. Subgroup analyses and interaction tests were conducted to identify potential effect modifiers.Results: In 2011, the study encompassed 4514 participants, with 2330 individuals followed up through 2015. Cross-sectional analyses revealed that participants classified in frailty, cognitive impairment, and cognitive frailty exhibited multivariable-adjusted odds ratios (ORs) for depression of 1.87 (95% CI 1.60– 2.18; P < 0.001), 1.97 (95% CI 1.58– 2.47; P < 0.001), and 3.38 (95% CI 2.66– 4.29; P < 0.001), respectively, compared to no diseased group. Longitudinal analyses from 2011 to 2015 indicated that participants in frailty, cognitive impairment, and cognitive frailty had multivariable-adjusted ORs of 1.28 (95% CI 1.05– 1.58; P = 0.0165), 1.39 (95% CI 1.01– 1.91; P = 0.0411), and 1.57 (95% CI 1.05– 2.35; P = 0.0273), respectively, for new-onset depression relative to no diseased group.Limitations: The definition of depression relied solely on self-reported data.Conclusion: In the middle-aged and elderly Chinese population, patients with cognitive frailty have a higher risk of depression than those with only frailty and cognitive impairment. This may suggest that health care providers should pay more attention to the mental health of those patients with cognitive frailty.Keywords: cognitive frailty, cognitive impairment, physical frailty, depression, CHARLS

In the cascaded H-bridge inverter (CHBI) with supercapacitor and dc-dc stage, inherent second-order harmonic power flows through each submodule (SM), causing fluctuations in both the dc-link voltage and the dc-dc current. There exist limitations in handling these fluctuations at variable output frequencies when employing proportional-integral (PI) control to the dc-dc stage. This paper aims to coordinately control these second-order harmonic voltage and current fluctuations in the CHBI. The presented method configures a specific second-order harmonic voltage reference, equipped with a maximum voltage fluctuation constraint and a suitable phase, for the dc-dc stage. A PI-resonant controller is used to track the configured reference. This allows for regulating the second-order harmonic fluctuation in the average dc-link voltage among the SMs within a certain value. Importantly, the second-order harmonic fluctuation in the dc-dc current can also be reduced. Simulation and experimental results demonstrate the effectiveness of the presented method.

Abstract We study thermal leptogenesis in realistic supersymmetric flipped SU(5) × U(1) unification. As up-type quarks and neutrinos are arranged in the same multiplets, they exhibit strong correlations, and it is commonly believed that the masses of right-handed (RH) neutrinos are too hierarchical to fit the low-energy neutrino data. This pattern generally predicts a lightest RH neutrino too light to yield successful leptogenesis, with any lepton-antilepton asymmetry generated from heavier neutrinos being washed out unless special flavour structures are assumed. We propose a different scenario in which the lightest two RH neutrinos N 1 and N 2 have nearby masses of order 109 GeV, with thermal leptogenesis arising non-resonantly from both N 1 and N 2. We show that this pattern is consistent with all data on fermion masses and mixing and predicts the lightest physical left-handed neutrino mass to be smaller than about 10−7 eV. The Dirac phase, which does not take the maximal CP-violating value, plays an important role in leptogenesis.

Abstract Objective High triglyceride (TG) levels are important risk factors for cardiovascular disease (CVD). Some recent studies have shown that snoring is also closely related to elevated TG levels. The specific pathogenesis of elevated TG levels in snoring patients is still unclear. Therefore, we performed this meta-analysis to evaluate the relationship between snoring and elevated TG levels. Materials and methods A systematic search was conducted in four online electronic databases as of Jul 1, 2024. The standardized mean difference (SMD) and corresponding 95% confidence interval (CI) for TG levels in each study were pooled. Moreover, we performed subgroup analysis according to snoring status and body mass index (BMI). All the data were pooled and analysed with Review Manager 5.3. Results The meta-analysis included five studies with 39,102 participants. Our results revealed that snoring was associated with elevated TG levels, with a pooled SMD of 0.23 (95% CI 0.14 to0.32; P

Abstract Penetrating orocutaneous or oropharyngeal fistulas (POFs), severe complications following unsuccessful oral or oropharyngeal reconstruction, remain complex clinical challenges due to lack of supportive tissue, contamination with saliva and chewed food, and dynamic oral environment. Here, we present a Janus hydrogel adhesive (JHA) with asymmetric functions on opposite sides fabricated via a facile surface enzyme-initiated polymerization (SEIP) approach, which self-entraps surface water and blood within an in-situ formed hydrogel layer (RL) to effectively bridge biological tissues with a supporting hydrogel (SL), achieving superior wet-adhesion and seamless wound plugging. The tough SL hydrogel interlocked with RL dissipates energy to withstand external mechanical stimuli from continuous oral motions like chewing and swallowing, thus reducing stress-induced damage. In male New Zealand rabbit POF models, the JHA demonstrates strong adhesion and fluid-tight sealing, and maintained firm sealing for over 3 days without any decreased signs under a normal diet. After 12 days, both extraoral cutaneous and mucosal wounds achieved complete closure, with mechanical strengths comparable to normal tissues. Similar therapeutic efficacy was also confirmed in male beagle dog POF models. Thus, the proposed JHA hydrogel shows great potential for deep wound sealing and providing mechanical support to assist healing in penetrating fistulas and other injuries.

Abstract Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to streamline the identification of individuals at elevated risk for postoperative AAEs, and therapeutic targets to optimize the efficacy of TEVAR for patients with AD. Here, we perform proteomic and single-cell transcriptomic analyses of peripheral blood and aortic lesions, respectively, from patients with AD and healthy subjects. The integrated multi-omics profiling identifies that highly phenotype-associated macrophages orchestrate neutrophil extracellular traps (NETs) through CXCL3/CXCR2 axis, thereby promoting the development of AD. Increased NETs formation is a defining feature of systemic immunity and aortic microenvironment of AD. Inhibiting NETs formation through the blockade of citrullinated histone H3 or CXCL3/CXCR2 axis ameliorates the progression and rupture of aortic dissection in male mice. The plasma level of citrullinated histone H3 predicts AAEs following endovascular therapy, facilitating the risk stratification and prognostic evaluation for patients with AD.

Abstract Background The interplay between gut microbiota and immune responses is crucial in ulcerative colitis (UC). Though Akkermansia muciniphila (Akk) shows therapeutic potential, the mechanisms remain unclear. This study sought to investigate differences in therapeutic efficacy among different forms or strains of Akk and elucidate the underlying mechanisms. Results Employing a dextran sulfate sodium (DSS)-induced colitis mouse model, we assessed Akk’s impact on colitis using cellular cytokine analysis, immune phenotyping, proteomics, and biochemical methods. Our results suggest that treatment with live Akk effectively reduced colitis in the DSS-induced model, whereas heat-inactivated Akk did not yield the same results. Notably, Akk exhibited protective properties by promoting the secretion of IL-22 by Group 3 innate lymphoid cells (ILC3s), as evidenced by the absence of protection in IL-22 knockout mice. Additionally, Akk augmented the population of CD103+CD11b− dendritic cells (DCs) and enhanced their retinoic acid (RA) synthesis through the modulation of RALDH2, a crucial enzyme in RA metabolism. The depletion of RALDH2 in DCs diminished Akk’s protective properties and impaired IL-22-mediated mucosal healing. Mechanistically, Akk activated RA production in DCs by enhancing the JAK2-STAT3 signaling pathway. Additionally, various strains of Akk may exhibit differing abilities to alleviate colitis, with the novel strain Am06 derived from breast milk showing consistent efficacy similar to the reference strain. Conclusions In summary, our findings indicate that certain strains of Akk may mitigate colitis through the promotion of RA synthesis and IL-22 secretion, underscoring the potential efficacy of Akk as a therapeutic intervention for the management of UC. Video Abstract

Abstract Objective This study aimed to analyse the correlation between the expression of cell proliferation-associated antigen (Ki-67), cell cycle protein-dependent kinase 4 (CDK4), epidermal growth factor receptor (EGFR), tumour-infiltrating lymphocytes (TILs) and circulating tumour DNA (ctDNA) with the outcome and prognosis of patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT). Methods We retrospectively analysed the clinicopathological data of 231 patients with BC who underwent preoperative NACT at XX Hospital between 1 January 2018 and 31 December 2021. Logistic regression models were used to analyse factors influencing NACT efficacy. The Cox risk regression model was used to analyse prognostic factors. The TILs were assessed on pre-treatment biopsies, and ctDNA levels were monitored during NACT. Propensity score matching and subgroup analyses were performed. Results After 4–6 cycles of chemotherapy, the response rate was 77.92% (180/231), with 58.87% (136/231) achieving pathological complete response (pCR). Multifactorial analysis showed that tumour, node and metastasis (TNM) stage II, EGFR positivity, low Ki-67 expression, CDK4 negativity, non-triple-negative subtypes and effective NACT results were associated with higher pCR rates. Higher TIL levels correlated with increased pCR rates (72.4% for high TILs vs 39.1% for low TILs, p

Institutions of higher education undertake a significant number of animal experiment projects with diverse types. To standardize animal experiments and ensure animal welfare, ethical review has become a core task for the Institutional Animal Care and Use Committee (IACUC) in these higher education institutions. A key issue worth exploring is how to improve the efficiency of animal ethical reviews while maintaining systematic quality of supervision. Based on the current status of ethical reviews at the Laboratory Animal Center of Huazhong University of Science and Technology, this paper designs and implements a full-process ethical review software system. This system seeks to offer solutions for the ethical review and supervision of animal welfare in institutions of higher education through information technology. The system employs a full-process supervision philosophy of "pre-approval, in-process supervision, post-review," focusing on strengthening the review and approval of animal research protocols, as well as post-approval monitoring. At the pre-approval stage, the system optimizes the process for designated members involved in the project review, ensuring that all projects comply with ethical standards and legal regulations. At the in-process stage, veterinary verification and consultation are carried out by executive veterinarians, using a method of "offline inspections and online records" for supervision. At the post-review stage, researchers are required to provide retrospective data to evaluate the experimental process. Additionally, this paper provides an in-depth exploration of the software, detailing its functional and non-functional requirements, as well as its security considerations. It also delves into the comprehensive software architecture, process design, and operational details. Furthermore, it illustrates the system's operational efficacy and impact since its launch. This paper discusses the software's applicability and practicality, analyzing existing limitations and challenges, such as the difficulty of balancing experiment urgency with the stringent nature of review processes, and the traceability blind spots in post-approval supervision. Future research will continue to enhance the accuracy and strength of animal welfare ethical reviews and supervision through new technologies and methods.

Lei Zhang,1 Chuanfa Fang,1 Weiquan Zhu,1 Wu Zhong,1 Rongqiang Ye2 1Department of Gastrointestinal Hernia, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaCorrespondence: Rongqiang Ye, Department of Hepatobiliary and Pancreatic Surgery, Ganzhou People’s Hospital, No. 16 Meiguan Avenue, Zhanggong District, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-07975889858, Email yerongqiang394@163.comBackground: The diversity of available chemotherapeutic modalities for colorectal cancer (CRC) entails the implementation of personalized therapeutic regimens to optimize patient outcomes. Currently, the clinical use of biological markers for treatment selection is inadequate to achieve individualization. Circulatory RNAs (circRNAs), which function as plasma biomarkers, play a critical role in regulating biological processes in different types of cancer.Methods: The samples (serum) were obtained from 80 CRC patients and 80 healthy individuals (controls) to assess the level of hsa_circ_0023919 via qRT-PCR analysis.Results: In findings, hsa_circ_0023919 has a positive association with the disease stage and is greatly elevated in chemoresistant CRC patients. In addition, the area under the curve for hsa_circ_0023919 was modest, and an increase in hsa_circ_0023919 expressions was linked with a decreased overall survival (OS) and progression-free survival (PFS). Serum hsa_circ_0023919 levels serve as a diagnostic indicator for chemoresistance in CRC.Conclusion: The findings suggested that hsa_circ_0023919 contributes to promoting chemoresistance in CRC patients. Consequently, it can be considered a potent therapeutic target for CRC treatment.Keywords: hsa_circ_0023919, biomarker, chemoresistance, CRC

Aim of the work: to assess the results of a complex use of cycle- and power-ergometry in determining the aerobic and anaerobic-aerobic performance in young athletes for the selection of criteria in predicting athletes’ sports abilities and performance results at competitions in certain sports. Materials and methods. Young athletes aged 15–16 (n = 636) took part in the study in which they represented two groups of athletes according to a training process direction: group A (n = 260) – speed-power sports (boxing, freestyle wrestling); group B (n = 376) – endurance sports (athletics, skiing, cycling, swimming). According to the results of their performance at competitions, all athletes were additionally divided into two groups: 1) a group of people who won prize places at competitions in their chosen sports – winners, 2) a group of their peers who unsuccessfully performed at competitions – outsiders. Physical working capacity was determined using two methods: cycle ergometric test PWC170 and power-ergometric test PWC170. Submaximal ergometric test PWC170 (Physical Working Capacity, PWC) is a method based on the determination of physical working capacity (load capacity) upon reaching a heart rate of 170 beats·min-1. Results. The fact of possible prediction of sports results at competitions of adolescents in sports chosen by them, depending on the nature of changes in indicators of aerobic and anaerobic-aerobic performance PWC170, was established. Examples of the performance of young athletes at competitions are given. Statistically significant differences were found in the indicators of aerobic (cycle-ergometry) and anaerobic-aerobic performance (power-ergometry) of athletes-winners and outsiders. Conclusions. A complex use of cycle- and power-ergometry allows to determine the level of contribution of each type of energy potential separately – aerobic (aerobic performance PWC170) and anaerobic-aerobic (anaerobic-aerobic performance PWC170) to the general physical working capacity (PWC). In our opinion, the level of aerobic and anaerobic-aerobic performance PWC170 (according to PWC index proposed by us) may be one of the criteria in predicting athletes’ sports abilities and performance results at competitions in certain sports.

The current work deals with the precipitation behaviors and mechanical properties of the high zinc content of the Mg-Zn-Cu system alloys using gravity casting. Differential scanning calorimetry (DSC) was conducted to describe the solidification process and precipitation behaviors. Thermodynamic calculations were carried out to determine the precipitation conditions using the Thermo-calc software. The microstructures were characterized by an optical microscope (OM), scanning electron microscope (SEM), electron probe micro analysis (EPMA), transmission electron microscopy (TEM), and confocal laser scanning microscope (CLSM). Tensile tests and micro-hardness tests were applied to investigate the mechanical properties. The results substantiated that the MgZnCu phase precipitates in Cu-containing alloys and that the precipitate content, as well as the precipitate temperature, increased with the Cu content from 0 to 3 wt.% according to the thermodynamic calculations and the DSC results. The measured micro-hardness of the alloy was 53.2, 57.9, 55.8, and 52.5 VHN, respectively. The ultimate tensile strength (UTS), yield strength (YS), and elongation (EL) revealed a λ-like trend of the alloys, and Mg-7Zn-1Cu alloy exhibits the optimum tensile properties with the UTS of 258.9 MPa, YS of 126.2 MPa, and the EL of 14.2%.

【Objective】Silicon photonic chips can achieve low-loss coupling with optical fibers through the on-chip silicon-based edge couplers (here in after referred to as edge couplers) integrated on the chips. In the packaging process of commercial silicon photonic chips, the demand for large-scale alignment of optical fibers and silicon photonic chips has raised higher requirements for the alignment efficiency of optical fibers and edge couplers. The research purpose of this paper is to optimize the alignment process between optical fibers and edge couplers based on the Fabry-Perot (FP) cavity formed between the optical fiber facet and the edge coupler facet. After measuring the distance between the optical fiber and the edge coupler in the axial direction of the fiber (represented as the x- axis in this article), high-precision alignment of the optical fiber and the edge coupler can be achieved by a single adjustment of the fiber position in this direction.【Methods】This paper studied the FP cavity structure formed between the optical fiber facet and the edge coupler facet. It also established the physical model between the reflection / transmission spectrum of the FP cavity and the distance between the facets. The optical fiber alignment platform is constructed to experimentally measure the distance between the facets through the FP cavity. Based on the distance measurement results, a single position adjustment of the optical fiber is realized along the axial direction of the optical fiber to achieve the alignment with the edge coupler.【Results】The deviation between the FP cavity length obtained in the experiment and the FP cavity length simulated by the ideal FP cavity model is less than 1 μm. The measured displacement of the optical fiber is within the error range (± 1 μm) of the actual displacement. After adjusting the position of the optical fiber based on the distance measurement results, the optical coupling loss is 3.52 dB between the optical fiber and the edge coupler at the output port, and the error with the reference value (3.30 dB) is only 0.22 dB.【Conclusion】The work verifies the feasibility of achieving efficient alignment between optical fibers and edge couplers based on FP cavity. Through the FP cavity, the measurement accuracy of the distance between the optical fiber and the edge coupler is at the sub-micrometer level and the measurement accuracy of the optical fiber displacement is also at the sub-micrometer level. The experiments demonstrate that the high-precision alignment between the optical fiber and the edge coupler could be realized with only a single adjustment of fiber position according the measurement results obtained by the FP cavity.

Acute mastitis is one of the common diseases of postpartum lactating women, also known as lactational mastitis, which can occur during breastfeeding, especially in the postpartum 3–4 weeks. Acute mastitis can lead to the cessation of breastfeeding. Improving breastfeeding behavior and extending breastfeeding duration have become a global strategy to promote maternal and child health. Manual lactation traditional Chinese medicine technology is one of the important measures to improve the rate of breastfeeding, which can solve the problems of breast swelling, pain, and reduction of milk production. This article introduces the definition, indications, standard operating procedures, precautions, and treatment of adverse events of manual lactation in traditional Chinese medicine technology, so as to provide more comprehensive guidance for clinical workers to carry out manual lactation operations.

The diagnosis of cancer is typically based on histopathological sections or biopsies on glass slides. Artificial intelligence (AI) approaches have greatly enhanced our ability to extract quantitative information from digital histopathology images as a rapid growth in oncology data. Gynecological cancers are major diseases affecting women's health worldwide. They are characterized by high mortality and poor prognosis, underscoring the critical importance of early detection, treatment, and identification of prognostic factors. This review highlights the various clinical applications of AI in gynecological cancers using digitized histopathology slides. Particularly, deep learning models have shown promise in accurately diagnosing, classifying histopathological subtypes, and predicting treatment response and prognosis. Furthermore, the integration with transcriptomics, proteomics, and other multi-omics techniques can provide valuable insights into the molecular features of diseases. Despite the considerable potential of AI, substantial challenges remain. Further improvements in data acquisition and model optimization are required, and the exploration of broader clinical applications, such as the biomarker discovery, need to be explored.

The article emphasizes the need to take into account the long-term negative consequences of unacceptably large water capacity of the Ukrainian economy with the construction of a large number of reservoirs and ponds, which caused the support of river flow and regional disruption of the equilibrium interaction of surface and underground flow. The consequence of this was the regional intensification of land flooding and overwetting, especially within the boundaries of industrial and urban agglomerations, mining areas, zones of reservoirs influence, irrigation arrays. Moreover, it is the flooding and overwetting of soils that become the trigger for the activation of dangerous changes in engineering and geological conditions, primarily destructive landslides, karst, drawdown and subsidence. Therefore, when developing measures to protect critical infrastructure objects, as well as plans and projects for their post-war restoration, it is necessary to take into account the engineering and geological threats of technogenic intensification of the destructive impact of dangerous exogenous geological processes. First of all, it is necessary to take into account: flooding and overwetting of soils, karst, landslides, subsidence. Since the stability of the main structures directly depends on ensuring the stability of subsoil, which “holds” the foundations of structures. The results of the GIS analysis of main engineering and geological threats are given. It is shown that areas of high threat level are primarily concentrated in the partially occupied southern and eastern regions of Ukraine covered by active hostilities. This circumstance needs to be reflected in the post-war critical infrastructure objects recovery programs and the allocation of special funding for in-depth engineering and geological research.

Hui Ye,1,2,&ast; Wei Li,1– 3,&ast; Yichuan Gan,1,2 Enyi Zhu,1,2 Hongkai Zheng,1,2 Quan Luo,1,2 Sanquan Zhang,1,2 Xibao Zhang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of China; 3Department of Dermatology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sanquan Zhang; Xibao Zhang, Guangzhou Dermatology Hospital, Guangzhou, People’s Republic of China, Email zhangsq2000@sohu.com; gzpfbfzs@163.comAbstract: Psoriasis is a chronic autoimmune skin disorder characterized by high morbidity and a tendency for recurrence. Although biologic therapy for lesion clearance can achieve PASI 90/100, refractory sites remain challenging to completely clear, particularly on the lower legs and elbows. To explore the efficacy of novel treatments for these resistant sites, we present a clinical observation on the safety and effectiveness of fractional carbon dioxide (CO2) laser therapy combined with secukinumab for four patients with moderate-to-severe plaque psoriasis. After receiving at least 3 months of maintenance treatment with secukinumab 300 mg, these patients received fractional CO2 laser therapy aimed at refractory sites on the lower legs. Treatments were administered every four weeks for a maximum course of 16 weeks. All four patients demonstrated improvement in the treatment of psoriasis lesions at refractory sites following the combined treatment approach. However, the degree of improvement differed among individuals. Leg Psoriasis Area and Severity Index (Leg-PASI) scores were reduced by 50% to 88%, while leg Physician’s Global Assessment (PGA) scores showed a reduction of 50% to 75%. And no adverse effects were observed.Keywords: fractional carbon dioxide laser, refractory sites, psoriasis, secukinumab, lower legs

Liubing Li,1,&ast; Dubo Chen,1,&ast; Pingjuan Liu,1,&ast; Luqi Dai,2 Zhaoxia Tang,3 Siting Yi,1 Mengmin Ye1 1Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengmin Ye; Siting Yi, Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China, Email yemm7@mail.sysu.edu.cn; yist@mail.sysu.edu.cnBackground: Bloodstream infections (BSIs) caused by Acinetobacter baumannii (AB), especially carbapenem-resistant Acinetobacter baumannii (CRAB), can lead to a high patient mortality rate.Methods: This study aimed to analyze the clinical data and prognosis of 191 patients with AB-BSI hospitalized in Southern China from January 2017 to December 2023.Results: CRAB was diagnosed in 128 (67.0%) of the 191 patients with AB-BSI. Endotracheal intubation (OR = 23.957, 95% CI: 5.123– 112.022, P < 0.001), carbapenem treatment (OR = 6.422, 95% CI: 1.554– 26.542, P = 0.010) and ≥ 2 antimicrobial drugs therapy (OR = 6.131, 95% CI: 1.763– 21.324, P = 0.004) prior to the onset of BSI were independent risk factors for the development of CRAB-BSI, as revealed by the binary logistic regression analysis. The overall mortality rate of patients with AB-BSI was 27.7%, while that of patients with CRAB was significantly higher than that of patients with carbapenem-sensitive Acinetobacter baumannii (CSAB) (39.1% vs 4.8%, P < 0.001). Multivariate Cox regression analysis revealed septic shock (HR = 3.664, 95% CI: 1.537– 8.736, P = 0.003) as an independent risk factor for mortality in CRAB-BSI patients. Kaplan–Meier survival analysis showed a significantly lower 28-day survival rate for CRAB-BSI patients who developed septic shock compared to those who did not (58.4% vs 87.1%, P = 0.001).Conclusion: Clinicians should closely monitor patients at high risk for CRAB-BSI, focusing on invasive procedure management and antimicrobial stewardship. Timely supportive care is crucial for CRAB-BSI patients at risk of septic shock to improve survival outcomes.Keywords: risk factors, bloodstream infections, carbapenem-resistant Acinetobacter baumannii

Hao-Yue Sun,1 Le-Can Wu,1 Meng-Jie Xu,2 En-Dian Zheng,1 Ying-Cong Yu,1 Yi Ye1 1Department of Gastroenterology, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Department of Laboratory Medicine, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Yi Ye; Ying-Cong Yu, Department of Gastroenterology, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, No. 299, Guan Road, Ouhai District, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13695853687; +86 13868322200, Email yeyiywst_yy@126.com; yuyingcong001@126.comObjective: This study aims to investigate the alterations in serum bile acid profiles among individuals with fatty liver (including non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) and evaluate their clinical significance when combined with liver enzyme levels.Methods: A cohort of 110 individuals with fatty liver (including non-alcoholic fatty liver 58 individuals and alcoholic fatty liver 52 individuals) was selected from the Department of Gastroenterology at Wenzhou People’s Hospital between January 2021 and December 2022, while a control group of 66 healthy individuals was recruited from the hospital’s health examination center during the same period. Clinical data and blood samples were collected from all participants. Serum bile acid profiles were quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Statistical analysis was conducted in conjunction with liver enzyme indicators.Results: In the NAFL group, GCA, TCA, and TCDCA levels were significantly elevated compared to the control group, with GCA (AUC 0.754, sensitivity 0.707, specificity 0.712), TCA (AUC 0.770, sensitivity 0.724, specificity 0.712), and TCDCA (AUC 0.782, sensitivity 0.810, specificity 0.652) showing strong diagnostic value. In the AFL group, TCDCA, TCA, GCA, TUDCA, and GUDCA were significantly elevated, with AUC values ranging from 0.848 to 0.912. Among these, TUDCA had the highest sensitivity (0.885) and specificity (0.773) for AFL diagnosis. TUDCA (sensitivity 0.615, specificity 0.897) was the key bile acid distinguishing AFL from NAFL, with an optimal cut-off of 36.33 nmol/L. These bile acids show significant diagnostic potential for differentiating NAFL and AFL.Conclusion: The bile acid profiles in both NAFL and AFL patients show changes, which hold potential clinical significance and may serve as serum biomarkers to differentiate NAFL from AFL.Keywords: bile acid profile, diagnosis, non-alcoholic fatty liver, alcoholic fatty liver

Jiyuan Zhang,1,&ast; Peixian Xu,1,&ast; Yingying Huang,1,&ast; Juan Li,1 Chaoping Ma,1 Guoxiang Liu,1 Jiawei Ye,1 Yiran Guo,1 Zhihui Feng,1 Bojie Jiang,1 Shuming Pan,1,2 Chengjin Gao1 1The Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Putuo District Hospital, Shanghai, 200062, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao; Shuming Pan, Email gaochengjin@xinhuamed.com.cn; panshuming1103@163.comBackground: The correlation between RAR is linked to negative outcomes in sepsis, but it remains uncertain if RAR is connected to prognosis in patients with sepsis-related NTIS. So we investigated it in this study.Methods: Patients with sepsis-associated NTIS admitted to Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, between March 2013 and April 2017 were included in the study. Participants were divided into two groups according to the optimal threshold value for RAR determined by the receiver operating characteristic curve. Cox proportional hazards regression and graphed with Kaplan–Meier curves examined the relationship between RAR and survival in patients with sepsis-associated NTIS. To account for potential confounding variables, a propensity score matching method was conducted to verify the relationship. Subgroup analysis was performed for different sex, age, comorbidities, infection location and other scores.Results: A total of 328 patients with sepsis-related NTIS were analyzed in our study. The univariate and multivariate regression analysis indicated that RAR was a significant risk factor for 30-day mortality (HR 1.039(1.012, 1.067), p = 0.004). However, subgroup analysis suggested that RAR may not be an independent risk factor for 30-day mortality in sepsis patients with NTIS combined with tumor or urogenital infection. ROC analysis demonstrated that RAR had a high discriminatory ability for predicting 30-day mortality (AUC 0.751, p < 0.001). Kaplan-Meier curve analysis indicated increased 30-day mortality in the higher RAR group. Following PSM, 108 pairs of patients with matched scores were created. The multivariate regression model demonstrated that RAR was an independent factor associated with 30-day mortality risk (HR 1.049 (1.015, 1.085), p = 0.005). ROC analysis revealed that RAR was a strong discriminator for the 30d-mortality (AUC: 0.695, 95% CI: (0.598– 0.792)).Conclusion: A strong correlation was found between RAR and unfavorable clinical results in sepsis-related NTIS, where a greater RAR was linked to increased 30-day and in-hospital death rates.Keywords: sepsis, red blood cell distribution width, albumin, nonthyroidal illness syndrome, prognosis

Qiuping Ye, Yang Hu, Qijing Xing, Yun Wu, Ye Zhang Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Ye Zhang, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, People’s Republic of China, Tel +86-551-63869485, Email zhangye_hassan@sina.comPurpose: The routine perioperative use of opioids has recently been questioned due to opioid-related side effects, which can be potentially harmful in geriatric patients. This study aimed to evaluate the effects of opioid-free anesthesia in geriatric patients undergoing hip surgery.Patients and Methods: A total of 121 patients, aged 60 years or older, undergoing elective hip surgery were randomized to receive either opioid-free anesthesia with dexmedetomidine and esketamine (OFA group) or balanced anesthesia with opioids (CON group). All patients received a preoperative fascia iliaca block and postoperative patient-controlled analgesia using tramadol. The primary outcome was the incidence of a composite of anesthetic-related complications (nausea and vomiting, hypoxemia, ileus, urinary retention and delirium) within 48 hours postoperatively. The hemodynamics, postoperative pain and quality of life were also assessed.Results: The incidence of composite adverse events was significantly reduced in the OFA group compared with the CON group (35.0% vs 62.3%, estimated difference: 27.3%, 95% confidence interval: 10.2%– 44.4%, P = 0.003). Notably, patients in the OFA group experienced less postoperative nausea and vomiting (P = 0.040), and hypoxemia (P = 0.025) compared with those in the CON group. However, the incidences of postoperative ileus, urinary retention and delirium were comparable between the two groups. Also, patients in the OFA group had less pain in motion at 24 h postoperatively, as well as less risks of intraoperative hypotension and bradycardia (P < 0.05). No significant differences in the postoperative quality of life were observed between the two groups.Conclusion: Opioid-free anesthesia with dexmedetomidine and esketamine reduced postoperative anesthetic-related complications and provided improved hemodynamic stability in geriatric patients undergoing hip surgery.Keywords: nonopioid, dexmedetomidine, esketamine, geriatric, hip injuries

Liang-Ling Cheng,1,&ast; Feng Ye,1,&ast; Tian Xu,2 Hong-Jian Li,3 Wei-Min Li,4 Xiao-Fang Fan4 1Wuxi school of medicine, Jiangnan University, Wuxi, People’s Republic of China; 2School of Environmental Engineering, Wuxi University, Wuxi, People’s Republic of China; 3Department of Ultrasound, Huai’an Cancer Hospital, Huai’an, People’s Republic of China; 4Department of Ultrasound, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Fang Fan; Wei-Min Li, Department of Ultrasound, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214000, People’s Republic of China, Tel +86-13861843829 ; +86-13912362309, Email fanxiaolll@126.com; 1005342597@qq.comPurpose: To construct a nomogram prediction model on minimal breast cancer (≦ 10 mm) based on clinical and ultrasound parameters.Methods: Clinical and ultrasound data of 433 patients with minimal breast lesions was conducted in this retrospective study. Patients were randomly divided into a training set and a validation set with a ratio of 7:3. Independent risk factors for minimal breast cancer were selected by the least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis to construct a nomogram prediction model. The calibration curve, the clinical decision curve analysis (DCA) and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic efficacy of the model.Results: Age, margin, shape, and breast density were independent risk factors for malignant minimal breast lesions (P < 0.05). The AUC of the training set and validation set of the nomogram prediction model were 0.875, the sensitivity were 75.0% and 88.9%, the specificity were 83.8% and 77.7%, respectively. The mean absolute error (MAE) of the training set and validation set of the calibration curve were 0.01 and 0.024, respectively.Conclusion: The nomogram prediction model has good discrimination, calibration and clinical practical value in the training set and validation set. The minimal breast cancer prediction model based on clinical and ultrasonic features possesses high clinical value, facilitating the early diagnosis of minimal breast cancer.Keywords: predictive model, nomogram, minimal breast cancer, ultrasonography

Bei Ye,1 Jiying Xiao,2 Caiyun Zhang3 1Department of Pediatrics, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Pediatric Intensive Care Unit, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Caiyun Zhang, Department of Pediatric Intensive Care Unit, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, People’s Republic of China, Email zcyzwj@163.comObjective: To investigate the predictive value of T-lymphocyte activation-related cytokines in non-responsive Kawasaki disease.Methods: Eighty-two children with Kawasaki disease, hospitalized from June 2022 to December 2023, were divided into two groups based on treatment response: the sensitive Kawasaki disease group (n=71) and the non-responsive Kawasaki disease group (n=11). Serum levels of T-lymph activation-related cytokines, including interleukin-2, 6, 7, 12, 15, 17, and tumor necrosis factor alpha, were measured before and after IVIG treatment in both groups. The differences in cytokine levels between the two groups were compared pre- and post-treatment. The ability of these cytokines to discriminate non-responsive Kawasaki disease was evaluated using ROC curves to determine the cut-off value.Results: Before initial treatment, IL-2, IL-6, IL-7, IL-12, IL-15, IL-17, and tumor necrosis factor-α values were significantly higher in the non-responsive Kawasaki disease group compared to the sensitive Kawasaki disease group. Comparisons before and after initial treatment showed significant decreases in IL-6 and 17 in the sensitive Kawasaki disease group and significant decreases in IL-6 and 7 in the non-responsive Kawasaki disease group. IL-6 and 17 significantly increased in the sensitive group compared to the non-responsive group after initial treatment. The ROC curves indicated that IL-6 predicted the area under the curve (AUC) for non-responsive Kawasaki disease to be 0.859 before treatment and 0.920 after treatment. Similarly, IL-17 had AUC values of 0.699 before treatment and 0.884 after treatment.Conclusion: Reassessing IL-6 and IL-17 following the initial treatment for Kawasaki disease may improve early warning signals for unresponsive Kawasaki disease.Keywords: Kawasaki disease, unresponsive Kawasaki disease, cytokines, T-lymphocyte activation, immunoglobulin

Jialin Gu,1,&ast; Hongqun Zhang,2,&ast; Kang Qian,1 Xunwen Ye,3 Guolin Wu1 1Department of TCM, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Hunan Engineering Research Center of TCM Real-World Clinical Practice, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, Hunan, 418000, People’s Republic of China; 3Department of Oncology, Ningbo Municipal Hospital of Traditional Chinese Medicine, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, Zhejiang, 315500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guolin Wu, Department of TCM, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China, Email wuguolin28@163.comObjective: Obesity has become a significant public health concern, strongly linked to various diseases, particularly gynecologic and breast cancers. This bibliometric review aims to analyze global research trends on overweight women, particularly those with gynecologic and breast cancers, to identify research hotspots, key contributors, and emerging areas of study.Methods: A comprehensive bibliometric analysis was conducted using the Web of Science Core Collection (WoSCC) database, covering the period from January 2013 to September 2024. Articles were screened and analyzed using tools such as VOSviewer and Biblioshiny platform, with metrics including publication volume, citation analysis, and co-authorship networks. Key areas of focus were global research trends, leading countries, institutions, authors, journals, and keyword analysis.Results: A total of 1452 publications were analyzed. Research activity on the association between obesity and gynecologic/breast cancer has steadily increased, with the United States leading in publications and citations, followed by China and Italy. Core journals included Breast Cancer Research and Treatment and Gynecologic Oncology. Key research areas identified through keyword analysis include the relationship between body mass index (BMI) and cancer risk, survival rates in cancer patients, physical activity, and the role of adipose tissue inflammation in tumor progression. Emerging topics include extracellular vesicles and cancer-associated fibroblasts.Conclusion: Global research on the relationship between obesity and female-specific cancers has shown significant growth. The findings highlight BMI, survival, and physical activity as central themes. Future research should explore the molecular mechanisms linking obesity to cancer and evaluate weight loss interventions for cancer prevention and treatment.Keywords: obesity, gynecologic cancer, breast cancer, bibliometrics, women health

Jiazhen Chen,1,2,&ast; Duanni Xu,1,2,&ast; Zezhi He,1,2 Shaoyin Ma,1,2 Jiahui Liu,1,2 Xiangnong Dai,1,2 Yuwu Luo,1,2 Xingdong Ye1,2 1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095 People’s Republic of China; 2Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingdong Ye; Yuwu Luo, Department of Dermatology, Guangzhou Dermatology Hospital, 56 Hengfu Road, Yuexiu District, Guangzhou, Guangdong, 510095, People’s Republic of China, Tel +86 020 83591975, Email yxingdong@qq.com; 1263009@qq.comBackground: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing the immune system’s ability to target cancer cells. However, ICIs can lead to immune-related adverse events (irAEs), including dermatologic manifestations such as bullous pemphigoid (BP).Objective: To evaluate the efficacy and safety of omalizumab and other biologics in the treatment of ICI-induced refractory bullous pemphigoid and to derive a strategy for selecting biologic treatments for this condition.Methods: A 48-year-old female with pulmonary squamous cell carcinoma developed erythema and blisters following tislelizumab treatment. Despite initial steroid therapy (1.8 mg/kg/day), new blisters formed. Laboratory tests revealed elevated BP180/230 levels, confirming BP diagnosis. Treatments with intravenous corticosteroids, cyclosporine, and dapsone were ineffective. Omalizumab 300 mg every four weeks was initiated based on elevated serum IgE levels. The patient’s response was monitored over four weeks. A comprehensive literature review was conducted, including 4 relevant articles.Results: Omalizumab treatment resulted in the cessation of blister formation and significant symptom alleviation within one week. The overall treatment duration was four weeks, with stable improvement observed. Follow-up for 4 months with no recurrence.Conclusion: This case illustrates the challenges of managing ICI-induced BP and highlights omalizumab as a potentially effective treatment option. The study proposes a personalized therapeutic strategy for refractory ICI-induced BP, emphasizing the selection of biologic agents based on specific immune profiles, including serum markers like IgE, eosinophils, and cytokine levels.Keywords: immune checkpoint inhibitors, bullous pemphigoid, omalizumab, adverse events, case report

Ziyao Zheng,1 Liyuan Ke,1 Shumin Ye,1 Peiying Shi,2 Hong Yao1,3 1Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Traditional Chinese Medicine Resource and Bee Products, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 3Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, 350122, People’s Republic of ChinaCorrespondence: Peiying Shi; Hong Yao, Email peiyshi@126.com; yauhung@126.com, hongyao@mail.fjmu.edu.cnAbstract: Cryptotanshinone (CTS) is an important active ingredient of Salvia miltiorrhiza Bge. In recent years, its remarkable pharmacological effects have triggered extensive and in-depth studies. The aim of this study is to retrieve the latest research progress on CTS and provide prospects for future research. The selection of literature for inclusion, data extraction and methodological quality assessment were discussed. Studies included (1) physicochemical and ADME/Tox properties, (2) pharmacological effects and mechanism, (3) conclusion and bioinformatics analysis. A total of 915 titles and abstracts were screened, resulting in 184 papers used in this review; CTS has shown therapeutic effects on a variety of diseases by modulating multiple molecular pathways. For example, CTS primarily targets NF-κB pathway and MAPK pathway to have a therapeutic role in cardiovascular diseases; in cancer, CTS shows superior efficacy through the PI3K/Akt/mTOR pathway and the JAK/STAT pathway; CTS act on the Nrf2/HO-1 pathway to combat neurological diseases. In addition, key targets of CTS were predicted by bioinformatics analysis, referring to disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis, with R Studio; AKT1, MAPK1, STAT3, P53 and EGFR are predicted to be the key targets of CTS against diseases. The key proteins were then docked by Autodock software to preliminarily assess their binding activities. This review provided new insights into research of CTS and its potential applications in the future, and especially the targets and directly binding modes for CTS are waiting to be investigated. Keywords: cryptotanshinone, pharmacological effects, molecular mechanism, bioinformatics analysis

Abstract The number of quantitative systems pharmacology (QSP) submissions to the U.S. Food and Drug Administration has continued to increase over the past decade. This report summarizes the landscape of QSP submissions as of December 2023. QSP was used to inform drug development across various therapeutic areas and throughout the drug development process of small molecular drugs and biologics and has facilitated dose finding, dose ranging, and dose optimization studies. Though the majority of QSP submissions (>66%) focused on drug effectiveness, QSP was also utilized to simulate drug safety including liver toxicity, risk of cytokine release syndrome (CRS), bone density, and others. This report also includes individual contexts of use from a handful of new drug applications (NDAs) and biologics license applications where QSP modeling was used to demonstrate the utility of QSP modeling in regulatory drug development. According to the models submitted in QSP submissions, an anonymous case was utilized to illustrate how QSP informed development of a bispecific monoclonal antibody with respect to CRS risk. QSP submissions for informing pediatric drug development were summarized along with highlights of a case in inborn errors of metabolism. Furthermore, simulations of response variability with QSP were described. In summary, QSP continues to play a role in informing drug development.

Xingchi Hu,1,2 Hongwei Wang,1,2 Haitao Sun,3 Jingxin Zhang,3 ZhenXiong Ye,4 Zhenhua Huang3 1Department of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, Jiangsu, 224000, People’s Republic of China; 2Department of General Surgery, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, 224000, People’s Republic of China; 3Department of General Surgery, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China; 4Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Xingchi Hu, Department of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, Jiangsu, 224000, People’s Republic of China, Email xingchihu@163.com Zhenhua Huang Department of General Surgery, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China, Email zhenhuahuangzj@163.comBackground: Transient receptor potential canonical 6 (TRPC6), a key member of the TRPC family, is involved in diverse physiological and pathological processes. Although previous studies have implicated TRPC6 in the progression of stomach adenocarcinoma (STAD), its precise functions and mechanisms remain unclear. Understanding TRPC6’s role in STAD may provide insights into its prognostic and therapeutic potential.Methods: Using transcriptional and clinical data from The Cancer Genome Atlas (TCGA) database, we assessed the expression and prognostic value of TRPC6 in STAD through Kaplan-Meier survival curve analysis and correlation studies. Immune-related parameters, including immune cell infiltration and immune checkpoint gene expression, were also evaluated. Additionally, drug response analyses explored TRPC6’s association with therapeutic agents. In vitro experiments were conducted to investigate TRPC6’s role in STAD cell proliferation, migration, and invasion, focusing on its regulation of the PI3K-Akt signaling pathway.Results: TRPC6 was significantly overexpressed in STAD tissues compared to normal tissues, with high TRPC6 expression associated with poor overall survival. TRPC6 expression correlated strongly with immune cell infiltration, immune checkpoint genes, and sensitivity to therapies such as Lapatinib, anti-CTLA4, and anti-PD1 treatments. Functional assays confirmed that TRPC6 promotes STAD cell proliferation, migration, and invasion by activating the PI3K-Akt signaling pathway.Conclusion: This study highlights the prognostic significance of TRPC6 in STAD and its potential as a therapeutic target. TRPC6’s involvement in immune regulation and cancer cell progression underscores its dual role in STAD pathogenesis and treatment, offering new avenues for targeted therapy development.Keywords: TRPC6, stomach adenocarcinoma, immunotherapy, biomarkers

［Objective］To determine the optimal metrics indicators for measuring parking lot congestion and road congestion levels, it is essential to study their impact on the modal share of urban rail transit. ［Method］Eight potential metrics indicators for measuring parking lot congestion are proposed, considering factors such as the number of parking lots, the number of parking spaces, the walking influence range of urban rail transit stations, and travel distance reductions. Additionally, two possible metrics for road congestion are introduced, taking into account road section length and congestion level. Using the inter district transportation data in Kinki metropolitan region of Japan, covering passenger flow, road traffic and parking lots, an empirical analysis is conducted to evaluate the influence of each metric indicator on the variation in urban rail transit modal share. Correlation analysis is then used to determine the optimal metrics. ［Result & Conclusion］Increasing the destination parking lot and road congestion levels leads to a higher all-day urban rail transit modal share between traffic zones. When the O (origin) traffic zone is located in urban or suburban areas, the optimal metric for destination parking lot congestion is advisable to adopt the proportion of highly saturated parking spaces within a traffic zone, adjusted according to distance. When the O-zone is in the central district, the optimal metric indicator for congestion in destination parking lots should adopt the proportion of highly saturated parking lots within the traffic zone, adjusted according to distance reductions. The best metric indicator for road congestion should adopt the total length of congested roads between traffic zones weighted by congestion levels.

Abstract Objective To assess seizure outcomes, prognostic factors, and developmental changes in children undergoing total posterior quadrant disconnection (PQD) for drug‐resistant epilepsy (DRE). Methods We conducted a retrospective analysis of the clinical data of children with DRE who underwent total PQD surgery. The study focused on Engel's classification for seizure outcomes, exploring correlation of preoperative data and surgical effectiveness, and predictors of seizure prognosis. It involved a comparative analysis of developmental levels pre‐ and 3 months postoperatively using Griffiths Mental Development Scales‐China (GMDS‐C), and the correlation between clinical characteristics and GMDS‐C results. Results Out of 61 pediatric patients, 70.5% showed no seizure recurrence postoperatively. In the univariate analysis, interictal electroencephalogram (EEG), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG‐PET), and acute postoperative seizure (APOS) were significantly related to surgical prognosis. In multivariate analysis, interictal EEG and APOS were identified as predictors of seizure prognosis. Survival analysis indicated significant associations between MRI, interictal EEG, FDG‐PET, APOS and postoperative seizure occurrence. Preoperative GMDS‐C levels were significantly correlated with epilepsy duration, seizure frequency, interictal EEG, and FDG‐PET. GMDS‐C scores improved postoperatively, while developmental quotients remained stable. Significance For patients with structural abnormalities in the entire posterior quadrant, thorough preoperative assessment and timely total PQD surgery can effectively control seizures without causing neurological development deterioration. APOS and interictal EEG abnormalities beyond the posterior quadrant are predictors for seizure prognosis but should not be deemed contraindications for surgery. Plain Language Summary Due to lack of analysis on pediatric total PQD cases, 61 pediatric patients who underwent total PQD surgery were retrospectively enrolled. Seizure and development results were collected and analyzed as dependent variables. The study found that 70.5% of patients were seizure‐free and showed development improvement, with no deaths or severe complications reported. Prognosis predictors included APOS and interictal EEG abnormalities beyond the posterior quadrant.

ABSTRACT Background Cancer cachexia can impact prognosis, cause resistance to anticancer treatments and affect the tolerability of treatments. This study aims to identify hepatocellular carcinoma (HCC) with cachexia by characterizing longitudinal body composition (BC) trajectories. Methods This longitudinal, multicentre cohort study included unresectable HCC patients treated with first‐line programmed death‐(ligand)1 inhibitors plus anti‐vascular endothelial growth factor antibody/tyrosine kinase inhibitors between 01/2018–12/2022. BC measurements including skeletal muscle mass (SMM) and total adipose tissue area (TATA) were evaluated by computed tomography at the third lumbar vertebra at baseline and follow‐up imaging. Unsupervised latent class growth mixed models were applied to distinguish potential longitudinal SMM and TATA trajectories for identifying cachexia. The primary study endpoint was overall survival (OS), with secondary endpoints including progression‐free survival (PFS), objective response rate (ORR) and safety. Multiple Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) for survival. Results A total of 411 patients with 2138 time‐point measurements were included. The median age was 56 years, and 50 (12.2%) patients were female. Two distinct trajectories were identified for SMM and TATA: sharp‐falling and stable. SMM sharply declined in 58 patients (14.1%) and TATA in 71 of 406 patients (17.5%) with significant worse OS (for SMM, 17.0 vs. 24.9 months; p

Rongzong Ye,1,&ast; Yating Wei,1,&ast; Jingwen Li,2,&ast; Meili Xu,1 Haiyang Xie,2 Jiahao Huang,3 Liehua Deng,3 Chaoqian Li1 1Department of Emergency Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liehua Deng, Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, 57 People’s Ave South, Zhanjiang, Guangdong, 524000, People’s Republic of China, Email glinson@126.com Chaoqian Li, Department of Emergency Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lichaoqiangood@163.comPurpose: The pathogenesis of sepsis-induced organ dysfunction remains elusive, and the mortality remains alarmingly high. We sought to investigate the profile of extracellular vesicles (EVs)-mediated communication between plasma and polymorphonuclear neutrophils (PMNs) in sepsis, and to elucidate whether miRNAs and PMN-related membrane proteins from plasma-derived EVs (plasma-EVs) are associated with sepsis-induced organ dysfunction and prognosis.Methods: PMN-derived EVs (PMN-EVs) were isolated from the blood samples of healthy controls (N=3) and patients with septic shock (N=3) after ICU admission. We performed miRNA sequencing of the isolated EVs, followed by bioinformatic analysis. A miRNA model for comparing PMN-EVs and plasma-EVs was successfully established in the training cohort. Furthermore, miRNAs and PMN-related membrane proteins from the plasma-EV model were confirmed in the validation cohort. A logistic regression model, receiver operating characteristic (ROC) curves, and Kaplan-Meier analyses were performed to evaluate the efficiency of diagnostic and/or prognostic performance. Further, in vivo and in vitro experiments were conducted to explore the involvement of plasma-EVs in PMNs autophagy.Results: Fifty-five miRNAs from PMN-EVs differed significantly between the healthy controls and patients with septic shock. Furthermore, the plasma-EV model (six miRNAs and eight PMN-related membrane proteins) was confirmed in the validation cohort, demonstrating that miR-34a-5p, miR-503-5p, miR-4772-3p, ITGAM, MPO, and MMP9 serve as sepsis biomarkers for distinguishing lung, liver, and kidney dysfunction. Kaplan–Meier survival analysis showed that miR-34a-5p, miR-4772-3p, ITGAM, and MMP9 were potential prognostic predictors. Finally, we found that plasma-EVs from sepsis patients exert an inhibitory effect on PMNs autophagy, which can be reversed by EV inhibitors such as GW4869 and enoxaparin.Conclusion: These findings suggest that miRNAs and PMN-related membrane proteins from plasma-EVs could be valuable diagnostic tools for identifying sepsis-induced organ dysfunction and predicting prognosis, enabling proactive management of sepsis by physicians and improving the prognosis of sepsis patients.Keywords: extracellular vesicles, MicroRNAs, membrane proteins, sepsis-induced organ dysfunction, neutrophils, autophagy

Hui Ye,1,2,&ast; Weifeng Chen,1,2,&ast; Wenyan Liu,1,2 Junhui Zhu,1,2 Jingyao Liang,1,2 Xibao Zhang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyao Liang; Xibao Zhang, Guangzhou Dermatology Hospital, No. 56 hengfu Road, Guangzhou, 510095, People’s Republic of China, Email ljy20221228@163.com; gzpfbfzs@163.comAbstract: Darier’s disease (DD) is a rare chronic keratinizing skin disease characterized by dyskeratosis of epidermal cells. We report a case of DD with a medical history spanning over 20 years and recurring symptoms. Pathologically confirmed DD was treated with a combination of abrocitinib and acitretin, resulting in rapid symptom resolution within 2 weeks. No recurrence was noted in an 11-week follow-up. The mechanism may involve acitretin’s inhibition of proliferation and anti-inflammation, while abrocitinib acts on IL-6 implicated in DD pathogenesis, exerting an immunomodulatory and anti-inflammatory effect, leading to rapid symptom relief. The combination of abrocitinib and acitretin is an effective therapy for DD, offering a promising new option for refractory patients.Keywords: keratosis follicularis, Darier’s disease, abrocitinib, acitretin

Xinyi Ye,1– 4,&ast; Pengfeng Xu,1– 4,&ast; Jianping Jiao,1– 4 Haoyang Zhao,1– 4 Kangyu Jin,1– 5 Shiyi Zhang,1– 4 Fen Pan,1– 4 Jingkai Chen,1– 4 Hao Jiang,1– 4 Jianbo Hu,1– 4 Manli Huang1– 4 1Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Zhejiang Key Laboratory of Precision psychiatry, Hangzhou, 310003, People’s Republic of China; 3Brain Research Institute of Zhejiang University, Hangzhou, 31003, People’s Republic of China; 4Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, 310003, People’s Republic of China; 5Institute of Translational Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Manli Huang, Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China, Email huangmanli@zju.edu.cnObjective: To assess the efficacy and safety of Vortioxetine and Escitalopram in improving cognition in patients with major depressive disorder (MDD).Methods: At baseline, 131 MDD patients and 70 healthy controls completed the Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), Snaith-Hamilton Pleasure Scale (SHAPS) and MATRICS Consensus Cognitive Battery (MCCB). Patients with MDD were randomly divided into Vortioxetine (n = 62) and Escitalopram (n = 69) groups with an 8-week follow-up research. ANOVA for repeated measurement was utilized to compare the efficacy of Vortioxetine and Escitalopram.Results: The total scores of HAMD-17, HAMA and SHAPS scales had statistical difference between MDD cases and healthy controls (P < 0.001) at baseline. After 8 weeks of treatment, the scale scores of the HAMD-17, HAMA and SHAPS had lowered in both groups, with no statistical difference between two groups (P > 0.05). At baseline, MDD patients had defects in Speed of Processing, Attention Vigilance, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition, compared with healthy controls. After 8 weeks of treatment with Vortioxetine or Escitalopram, the patients had improved in the aspects of cognitive functions above except Social Cognition. Numerical improvements of MCCB scale were found in the two groups, P > 0.05. Most adverse events were mild or moderate, with nausea being the most common adverse event.Conclusion: Both Vortioxetine and Escitalopram can improve the mental status and cognitive functions in MDD patients, with mild or moderate adverse events.Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900024858.Keywords: vortioxetine, escitalopram, major depressive disorder, randomized controlled trial, efficacy

The Tropical Cyclone (TC) Rainfall Climatology and Persistence Model (R-CLIPER) is a statistical parametric model for TC precipitation based on observations of North Atlantic TCs or global TCs. It boasts simple inputs and quick calculations, enabling climate-scale TC precipitation simulations, thus providing technical support for TC precipitation forecasting and risk assessments. This study focuses on TCs in the Western North Pacific region and performs localization of the R-CLIPER model. Firstly, based on precipitation data from Tropical Rainfall Measuring Mission (TRMM) satellite and Fengyun satellite (FY2C/2E) precipitation data, the radial average profiles of precipitation from TCs of 6 different intensity levels (i.e., super typhoon, strong typhoon, typhoon, severe tropical storm, tropical storm, tropical depression) are extracted. Secondly, combined with the R-CLIPER model framework, a globally optimal parameterization fitting method for TC precipitation profiles is developed. Two models are constructed, including the R-CLIPER for the Western North Pacific Ocean based on TRMM data/FY data, namely TRMM-R-CLIPER-WNP (Model 1) and FY-R-CLIPER-WNP (Model 2). Finally, based on the 62 tropical cyclones in the Northwest Pacific from 2012 to 2013 and the 26 cyclones that affected Zhejiang from 2009 to 2021 the models are evaluated in terms of fitting error and precipitation falling area. The results are as follows. (1) The TC rainfall profiles derived from TRMM data are relatively sharp near the maximum rainfall, while those from FY2C/2E satellite data are smoother and more detailed due to its higher spatial resolution. (2) The RMSE of TRMM parameterized profiles is 0.28 mm·h-1, and that of FY2C/2E profiles is 0.51 mm·h-1. (3) Based on the ground-based station data evaluation, when the rainfall threshold is less than 3 mm·h-1, the ETS score of Model 1 is better than that of Model 2. But when the threshold is greater than 3 mm·h-1, Model 2 is better. Both models perform better when the TC is centered over the sea than over land, indicating higher accuracy of TC central rainfall intensity prediction over the ocean than over land. In conclusion, using the parameterized fitting method, the accuracy of the R-CLIPER model in simulating TC precipitation in the Northwest Pacific region can be improved by 5.5%. Additionally, it was revealed that the error in TC precipitation simulations is influenced by factors such as model data sources, model framework, and parameterization schemes.

In order to explore the changes of antioxidant performance of Lactiplantibacillus plantarum IMAIJIBP3 strain under 6.5% NaCl stress, antioxidant apparent indexes and transcriptomics of IMAUJBP3 strain were investigated. The results showed that the scavenging rates of DPPH radical and hydroxyl radical of bacterial suspension, fermentation supernatant and intracellular extract of IMAUJBP3 treated by NaCl were higher than those of the control group. However, in terms of superoxide anion clearance, the scavenging rate of bacterial suspension and fermentation supernatant treated with NaCl was higher than that of the control group, while the superoxide anion scavenging ability of intracellular extracts was significantly (P

Objective: We investigated the relation between man papillomavirus (HPV) integration status and the immediate risk of cervical intraepithelial neoplasia (CIN), as well as the triage strategy based on HPV integration test. Methods: 4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective, population-based, clinical observational study to evaluate the triage performance of HPV integration. Cervical exfoliated cells were collected for HPV testing and cytologic test. If high-risk HPV was positive, HPV integration test was performed at baseline, 2-year and 5-year follow-up. Results: At baseline, HPV integration was positively correlated with the severity of cervical pathology, ranging from 5.0% (15/301) in normal diagnosis, 6.9% (4/58) in CIN1, 31.0% (9/29) in CIN2, 70% (14/20) in CIN3, and 100% (2/2) in cervical cancer (P < 0.001). Compared with cytology, HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+, higher specificity (92.8% [90.2%–95.4%] vs. 75.5% [71.2%–79.8%], P < 0.001) and higher positive predictive value (36.4% [22.1%–50.6%] vs. 15.2% [8.5%–21.8%], P < 0.001). HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy (10.7% [44/410] vs. 27.3% [112/410], P < 0.001). The HPV integration-negative group exhibited the lowest immediate risk for CIN3+ (1.6%) and accounted for the largest proportion of the total population (89.3%), when compared with the normal cytology group (risk, 1.7%; proportion, 72.7%). Conclusion: As a key molecular basis for the development of cervical cancer, HPV integration might be a promising triage strategy for HPV-positive patients.

Abstract Arcopilus aureus is a plant-beneficial fungal species showing remarkable biocontrol capabilities. We investigated the antifungal activity of A. aureus YZXR strain and found that it strongly suppressed Polygonatum odoratum leaf spot disease caused by Fusarium fujikuroi. However, the antifungal substances and antifungal mechanisms remain unknown. To identify the antifungal substances, we extracted the fermentation liquid with ethyl acetate and found that the antifungal activity was mainly in the organic phase. Using column chromatography, semi-preparative HPLC, and GC–MS assays, we analyzed the compounds in the ethyl acetate phase and identified phenylethyl alcohol and 3,5-dihydroxytoluene as two compounds showing antifungal activity. The phenylethyl alcohol completely inhibited the growth of F. fujikuroi at a concentration of 0.25% (v/v), whereas the inhibition rate of 10.00 mg/mL 3,5-dihydroxytoluene on fungal growth was 80.60%. The fermentation broth of strain YZXR efficiently inhibited mycelial growth and conidiation of F. fujikuroi. Thus, this study uncovered the antifungal metabolites of A. aureus and the potential of A. aureus as a biological fungicide for managing P. odoratum leaf spot disease, providing a foundation for further research on its biocontrol mechanisms and field applications.

Abstract The hydrological cycle in South America during austral summer, including extreme precipitation and floods, is significantly influenced by northerly low-level jets (LLJs) along the eastern Andes. These synoptic weather events have been associated with three different types of LLJs (Central, Northern, and Andes) and are sensitive to remote large-scale forcings. This study investigates how tropical forcings related to El Niño/Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) regulate the duration and frequency of each LLJ type and their impacts on extreme precipitation. Our analysis reveals that ENSO and PDO are important in driving the variability of LLJs over the past 65 years. Specifically, the Central LLJ type is more prevalent during El Niño and Warm/Neutral PDO phases, leading to heightened extreme precipitation in southern South America. Conversely, La Niña years during Cold PDO phases tend to favor the Northern and Andes LLJs, which are associated with increased precipitation extremes in the western Amazon and southeastern South America. Central and Andes LLJs tend to persist longer during these favored conditions, causing more pronounced precipitation events in the areas under their influence. This study enhances our understanding of the influence of large-scale atmospheric forcings on the regional precipitation dynamics in South America.

Abstract Atopic dermatitis (AD) is an immune-related skin disease with a genetic background. Numerous loci have been identified associated with AD to better comprehend its complicated genetic mechanisms by genome‑wide association studies (GWASs). However, current studies reveal the underlying mechanisms of these loci in the pathogenesis of AD inadequately. Therefore, we integrated the GWAS statistics of AD with plasma proteins to explore candidate proteins correlated with the pathogenesis of AD based on protein-centered omics studies. Herein, we adopted the updated AD GWAS statistics (N = 864,982) and the dataset of plasma protein quantitative trait loci (pQTLs), comprising 1,348 proteins from individuals of European descent. We first conducted the AD-related proteome-wide association studies (PWASs) (N = 7,213) by integrating pQTLs with the AD GWAS statistics and identified twenty-six significant plasma proteins by PWAS (FDR

Abstract Rationale and Objectives The management of complex renal cysts is guided by the Bosniak classification system, which may be inadequate for risk stratification of patients to determine the appropriate intervention. Radiomics models based on CT imaging may provide additional useful information. Materials and Methods A total of 322 patients with Bosniak II-IV cysts were included in the study from January 2010 to December 2019. Contrast-enhanced CT scans were performed on all patients. ITK-snap was used for segmentation, and the PyRadiomics 3.0.1 package was used for feature extraction. The radiomics features were screened via the least absolute shrinkage and selection operator (LASSO) regression method. After feature selection, a logistic regression (LR) model, support vector machine (SVM) model and random forest (RF) model were constructed. Results In the present study, 217 benign renal cysts (67.4%) and 105 cystic renal cell carcinomas (32.6%) were identified. According to the Bosniak classification, the sample included 179 (55.6%) Bosniak II cysts, 38 (11.8%) Bosniak IIF cysts, 44 (13.7%) Bosniak III cysts and 61 (18.9%) Bosniak IV cysts. A total of 1334 radiomics features were extracted from both unenhanced and cortical CT scans. After LASSO regression, all the models (LR, SVM and RF) showed satisfactory discrimination and reliability in both unenhanced and cortical CT scans (AUC > 0.950). In the Bosniak IIF-III subgroup analysis, the diagnostic accuracy of the LR model was very low for both the unenhanced and cortical scans. In contrast, the SVM model and RF model showed excellent and stable performance in classifying Bosniak IIF-III cysts. The AUCs of the models were all > 0.85, with a maximum of 0.941. The sensitivity, specificity, accuracy, and AUC of the RF model were 0.889, 0.913, 0.902, and 0.941, respectively. Conclusion Our data indicate that radiomics models can effectively distinguish between cystic renal cell carcinoma (cRCC) and complex renal cysts (Bosniak II-IV). Radiomics models may still have high diagnostic accuracy even for Bosniak IIF-III cysts that are clinically difficult to distinguish. However, external validation of these findings is still needed.

Abstract Background The prognostic value of Albumin and D-dimer has been established for multiple tumor types, indicating their potential for predicting tumor development. Nevertheless, the predictive capability of the DDI-to-albumin ratio (DAR) in locally advanced rectal cancer (LARC) remains uncertain. Purpose The objective of this study was to investigate the prognostic significance of the DAR in LARC. Methods A total of 513 patients who underwent neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) between March 2013 to October 2019 were included in this study. Patients were divided into high-level DAR (> 0.016) or low-level DAR (≤ 0.016) groups based on ROC curve analysis optimum cut-off value. The prognostic value of the DAR in LARC was analyzed. Results The study enrolled 513 patients. Patients were stratified into high-level DAR (> 0.016) and low-level DAR (≤ 0.016) cohorts according to the optimal cut-off value determined by ROC curve analysis. The 5-year overall survival (OS) rates for patients in the low DAR group (≤ 0.016) and the high DAR group (> 0.016) were 89.4% and 80.9%, respectively (p = 0.013). The 5-year disease-free survival (DFS) rates were 85.7% and 77.4% (p = 0.027). Multivariate analyses demonstrated that DAR were independent prognostic factors for OS (p = 0.02) and DFS (0.025). Predictive nomograms that included the DAR score group (C-index: OS-0.743, DFS-0.705) were superior to those without DAR scores (C-index: OS-0.721, DFS-0.697). Conclusion The DAR demonstrates high usability and prognostic value in predicting OS and DFS outcomes among patients diagnosed with LARC who undergo nCRT.

Abstract Iron-based nanozymes, recognized for their biocompatibility and peroxidase-like activities, hold promise as catalysts in tumor therapy. However, their concurrent catalase-like activity undermines therapeutic efficacy by converting hydrogen peroxide in tumor tissues into oxygen, thus diminishing hydroxyl radical production. Addressing this challenge, this study introduces the hemin–cysteine–Fe (HCFe) nanozyme, which exhibits exclusive peroxidase-like activity. Constructed through a supramolecular assembly approach involving Fmoc-l-cysteine, heme, and Fe²⁺ coordination, HCFe distinctly incorporates heme and [Fe–S] within its active center. Sulfur coordination to the central Fe atom of Hemin is crucial in modulating the catalytic preference of the HCFe nanozyme towards peroxidase-like activity. This unique mechanism distinguishes HCFe from other bifunctional iron-based nanozymes, enhancing its catalytic selectivity even beyond that of natural peroxidases. This selective activity allows HCFe to significantly elevate ROS production and exert cytotoxic effects, especially against cisplatin-resistant esophageal squamous cell carcinoma (ESCC) cells and their xenografts in female mice when combined with cisplatin. These findings underscore HCFe’s potential as a crucial component in multimodal cancer therapy, notably in augmenting chemotherapy efficacy.

Abstract Subduction initiation remains elusive because no present example exists. Ophiolites formed over nascent subduction zones in the past provide the key to constraining the processes of subduction initiation. Here we document three Cambrian ophiolites with supra-subduction zone affinity, which likely reflect the inception of a plate-boundary scale subduction zone within the Paleo-Asian Ocean. Our findings, together with a compilation of Cambrian ophiolites in the Central Asian Orogenic Belt, indicate diachronous subduction initiation(s) along a > 6000 kilometer zone within the Paleo-Asian Ocean between 536 and 528 million years ago. The subduction initiation of the Paleo-Asian Ocean coincides with the closure of the Mirovoi Ocean following the collision of a series of microcontinents with the Siberian craton, likely representing a typical record of collision-induced subduction jump. Our observations and numerical modeling provide a new scenario that subduction initiations would locate at oceanic weak zones rather than passive margins of accreted microcontinents during collision-induced subduction process.

Xinqia Huang,1,&ast; Ziquan Zhao,1,&ast; Weiqiang Zhan,1 Mingzhu Deng,1 Xuyang Wu,1 Zhoutao Chen,1 Jiahao Xie,2 Wei Ye,3 Mingyan Zhao,1,4 Jiaqi Chu3,4 1Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 3Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 4Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiaqi Chu; Mingyan Zhao, Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Avenue South Road, Zhanjiang, Guangdong, 524001, People’s Republic of China, Email chujiaqi@gdmu.edu.cn; mingyan.zhao@gdmu.edu.cnPurpose: To investigate the osteogenic potential of human embryonic stem cell-derived exosomes (hESC-Exos) and their effects on the differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs).Methods: hESC-Exos were isolated and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. hUCMSCs were cultured with hESC-Exos to assess osteogenic differentiation through alizarin red staining, quantitative PCR (qPCR), and Western blotting. miRNA profiling of hESC-Exos was performed using miRNA microarray analysis. In vivo bone regeneration was evaluated using an ovariectomized rat model with bone defects treated with exosome-loaded scaffolds.Results: hESC-Exos significantly promoted the osteogenic differentiation of hUCMSCs, as evidenced by increased alizarin red staining and the upregulation of osteogenesis-related genes and proteins (ALP, RUNX2, OCN). miRNA analysis revealed that miR-21-5p is a key regulator that targets YAP1 and activates the Wnt/β-catenin signaling pathway. In vivo, hESC-Exos enhanced bone repair in ovariectomized rats, as demonstrated by increased bone mineral density and improved bone microarchitecture compared to those in controls.Conclusion: hESC-Exos exhibit significant osteogenic potential by promoting the differentiation of hUCMSCs and enhancing bone regeneration in vivo. This study revealed that the miR-21-5p-YAP1/β-catenin axis is a critical pathway, suggesting that the use of hESC-Exos is a promising therapeutic strategy for bone regeneration and repair. Keywords: human embryonic stem cells, exosomes, osteogenic differentiation, bone regeneration, miR-21-5p, YAP1