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Liuyi Huang,* Xiaoxia Huang,* Wei Zhou, Yanting Jiang, Haiqing Zhu, Yuehong Lao, Zhenjia Deng, Yuting Tang, Jian Wang, Xi Li Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, Guangxi, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi Li; Jian Wang, Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email cicicats@126.com; wangjian616161@163.comObjective: Idiopathic inflammatory myopathies (IIM) are classified into four subgroups: dermatomyositis (DM), anti-synthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and sporadic inclusion body myositis (sIBM); however, the role of LGALS3BP in IIM remains unclear. Our study aimed to explore the ability of LGALS3BP to discriminate between the IIM subtypes. The correlation between serum LGALS3BP levels, clinical features, and inflammatory markers in patients with IIM was also assessed.Methods: Based on the Gene Expression Omnibus (GEO) database, we used bioinformatics analysis to screen for overlapping extracellular protein-differentially expressed genes between any two groups of DM, ASS, IMNM, and healthy controls (HCs). This study enrolled 84 patients with IIM and 36 HCs, and participant baseline data and laboratory parameters were recorded. Serum LGALS3BP levels were measured using an enzyme-linked immunosorbent assay (ELISA).Results: Through bioinformatics analysis, LGALS3BP was selected as a potential biomarker for the identification of DM, ASS, IMNM, and HC. LGALS3BP expression decreased sequentially in the DM, ASS, IMNM, and HC groups, with significant differences among the two groups. The ELISA results were similar to those of the bioinformatics analysis; however, the difference in serum LGALS3BP expression between DM and ASS was not statistically significant. According to the receiver operating characteristic (ROC) curve analysis, using HC as the control group, the area under the curve (AUC) values of serum LGALS3BP levels for the diagnosis of IIM, DM, and ASS were > 0.8. In addition, patients with elevated serum LGALS3BP levels had a higher prevalence of interstitial lung disease (ILD). Serum LGALS3BP levels correlated with inflammatory markers.Conclusion: LGALS3BP is differentially expressed in DM, ASS, IMNM, and HC and may assist in assessing the severity of IIM-ILD.Keywords: LGALS3BP, idiopathic inflammatory myopathies, dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, interstitial lung disease

Rui Huang,1– 3,* Qingning Huang,1– 3,* Yuhua Lei1– 3 1Cardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bioapplications, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhua Lei, Email yuhualei0319@163.comAbstract: A 60-year-old woman was admitted to the hospital with “repeated loss of consciousness for 20 years.” An electrocardiogram performed revealed sinus rhythm, and echocardiography, head/chest CTs, and a laboratory examination yielded no significant abnormalities. Besides, there were no positive results from the head-up tilt test. The subsequent decrease in heart rate and blood pressure following the ingestion of chili pepper indicated a potential case of vasovagal syncope(VVS) with cardioinhibition. Following cardioneuroablation, there was an observed increase in heart rate compared to pre-procedure levels. Furthermore, no recurrence of similar symptoms was reported during the one-year follow-up period.Keywords: Cardioneuroablation, Vasovagal syncope, chili pepper stimulation, VVS

Lingling Gong,1,2 Tao Jiang,3,4 Ting Xiao,1,2 Bo Feng,1,2 Mouda Wei,5 Chuanzi Liu,3 Weiwei Xiao,1,2 Pin Huang,5 Dan Huang6– 8 1Department of prosthodontics, Changsha Stomatological Hospital, Changsha, Hunan, People’s Republic of China; 2Department of prosthodontics, School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 3The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 4Department of Prosthodontics, Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 5Department of Pediatric Dentistry, Ubcare Dental Clinic Co. Ltd, Changsha, Hunan, People’s Republic of China; 6Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Prosthodontics and Implantology, School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Pin Huang, Department of Pediatric Dentistry, Ubcare Dental Clinic Co. ltd, 768 Xiangzhang Road, Yuhua District, Changsha City, Hunan province, People’s Republic of China, Email huang.pin@outlook.com Dan Huang, Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of China, Email Huangdan@tjh.tjmu.edu.cnIntroduction: Biomineralization has been increasingly adopted for the synthesis of advanced materials with superior properties. Hierarchical architecture growth mimicking biomineralization has been studied using various organic molecules to template inorganic materials with controlled morphology. In our previous study, self-assembled Sr/CS/G(SrCO3-chitosan-gelatin) aggregates were fabricated using electrophoretic deposition (EPD). This study is a further step toward understanding the morphogenesis of Sr/CS/G aggregates and its biomineralization.Methods: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD) were used to investigate the biomimetic morphogenesis of Sr/CS/G composite under various EPD parameters, such as polymer concentration, time, and voltage. The Sr/CS/G aggregates were immersed in H2O, phosphate-buffered saline (PBS), and simulated body fluid (SBF) to study the bioactive apatite formation ability. In addition, biocompatibility of the composites were evaluated by Fluorescence staining, SEM in vitro. The osteogenic ability of the coatings induced by PBS were tested in vivo.Results: The CS/G weight ratio, EPD time, and voltage were found to influence the morphogenesis of Sr/CS/G aggregates. SEM and TEM results showed that the Sr/CS/G aggregates exhibited fractal growth characteristics and morphological self-similarity. XRD results confirmed the formation of SrCO3 crystals within the framework of chitosan and gelatin organic templates. Chitosan played a vital role in branching growth of the crystals, whereas gelatin guided the formation of composite spheres. The microstructural and compositional results reveal that the Sr/CS/G-induced apatite coating yielded a large quantity of apatite. These apatite coatings promote the cytocompatibility and osteogenesis of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. The coatings induced by PBS enhanced proliferation and mineralization in vitro, and enhanced angiogenesis and osteogenesis in vivo.Conclusion: Sr/CS/G composites prepared via EPD are promising organic-inorganic templates for biomineralization. These findings provide important insights into understanding the mineralization process and optimizing the design of advanced biological materials.Keywords: biomineralization, EPD parameter, Sr/CS/G aggregates, morphogenesis, hydroxyapatite

Dongmei Huang,1 Caizhong Zhou,2 Caili Li,3 Huiqiao Huang,4 Xiao Pan,3 Yanfei Pan,3 Qini Pan,3 Lichong Lai3 1Department of Rehabilitation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Internal Medicine, Second People’s Hospital of Teng County, Wuzhou, Guangxi, People’s Republic of China; 3Nursing Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Party Committee Office, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Huiqiao Huang, Email hhq@sr.gxmu.edu.cnObjective: To investigate the current status of elderly health services in medical institutions at all levels within Guangxi Province, China.Methods: Using a purposeful sampling method, a questionnaire survey was conducted from July 24, 2023 to October 24, 2023 on the general situation, human resources, rehabilitation medicine, nursing services, and the development of hospice care at 1305 medical institutions in Guangxi.Results: Among the surveyed 1305 medical institutions in Guangxi, 172 (13.18%) had established departments of geriatrics, while 293 (22.45%) boasted departments of rehabilitation medicine. Furthermore, 909 (69.66%) of these institutions offered annual free physical examination services to individuals aged 65 and above. Notably, a total of 362 medical institutions, encompassing both comprehensive hospitals and grassroots hospitals, were recognized as elderly-friendly institutions, accounting for 31.4% of the surveyed sample.The highest demand for talents in medical institutions at all levels included specialized physicians/general practitioners (74.6%), traditional Chinese medicine practitioners (63.1%), rehabilitation therapists (56.1%), and specialized nurses for the elderly (41.7%). A total of 1038 medical institutions conducted popular science activities on elderly health, accounting for 79.5% of the total, focusing mainly on disease prevention (89.21%), nutritional diets (84.68%), rational medication use (79.77%), physical exercise (68.21%), and mental health (60.79%). Only 88 medical institutions provided hospice care services, accounting for 6.7% of the total.Conclusion: Guangxi medical institutions’ elderly services are inadequate. Geriatrics and rehab departments are scarce, talent is lacking, and hospice care is underdeveloped. As aging accelerates, the country and society must support elderly care. Governments should introduce talent incentives, and medical institutions should enhance services, foster a positive work environment, and advance Guangxi’s elderly health agenda.Keywords: medical institutions, elderly health services, elderly care, hospice care, current status

Jia Zhang,1,* Xi Liu,2,* Jin Huang,3 Songbin Huang,1 Zuolian Zhang4 1Department of Nursing, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China; 2Department of Neurology, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China; 3Department of Cardiovascular Medicine, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China; 4Department of Neurosurgery, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia Zhang, Email 562232317@qq.comObjective: To analyze research trends, frontiers, and hot topics in specialty nurse training over the past 20 years, and provide a reference for researchers to understand the current research landscape in this field.Methods: Studies from the core collection of Web of Science were used. Furthermore, CiteSpace 6.3 R3 was utilized to analyze information on country, institution, authors, keywords and burst words.Results: A total of 296 articles were included in the analysis. The United States had the highest number of articles, and there was limited cooperation between authors and institutions. The research hotspots in this field included “clinical education models for specialist nurses”, “APN role training”, and “interprofessional education”.Conclusion: The future research trend is to explore the effective integration of training models suitable for different regions and cultural backgrounds and cross-professional education models. It is suggested that researchers pay attention to the innovation and development of specialized nursing clinical practice under different cultural backgrounds, and strengthen international exchanges and cooperation.Keywords: specialty nurse, train, bibliometric analysis, CiteSpace, data visualization

Qi Huang,1– 3,* Xu-Yun Huang,1,2,* Yu-Ting Xue,1,2,* Xiao-Hui Wu,1,2,* Yu-Peng Wu,1,2,* Zhi-Bin Ke,1,2 Zhen Kang,1,2 Yi-Cheng Xu,1,2 Dong-Ning Chen,1,2 Yong Wei,1,2 Xue-Yi Xue,1,2 Zhi-Yang Huang,3 Ning Xu1,2,4 1Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 3Department of Urology, Quanzhou First Hospital, Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 4Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xu, Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of China, Tel +86-059187981687, Email drxun@fjmu.edu.cn Zhi-Yang Huang, Department of Urology, Quanzhou First Hospital, Fujian Medical University, No. 250, East Street, Licheng District, Quanzhou, Fujian, 362000, People’s Republic of China, Email hzy8902@126.comIntroduction: This study aims to explore the role of cuproptosis-related genes in ACC, utilizing data from TCGA and GEO repositories, and to develop a predictive model for patient stratification.Methods: A cohort of 123 ACC patients with survival data was analyzed. RNA-seq data of 17 CRGs were examined, and univariate Cox regression identified prognostic CRGs. A cuproptosis-related network was constructed to show interactions between CRGs. Consensus clustering classified ACC into three subtypes, with transcriptional and survival differences assessed by PCA and survival analysis. Gene set variation analysis (GSVA) and ssGSEA evaluated functional and immune infiltration characteristics across subtypes. Differentially expressed genes (DEGs) were identified, and gene clusters were established. A risk score (CRG_score) was generated using LASSO and multivariate Cox regression, validated across datasets. Tumor microenvironment, stem cell index, mutation status, drug sensitivity, and hormone synthesis were examined in relation to the CRG_score. Protein expression of key genes was validated, and functional studies on ASF1B and NDRG4 were performed.Results: Three ACC subtypes were identified with distinct survival outcomes. Subtype B showed the worst prognosis, while subtype C had the best. We identified 214 DEGs linked to cell proliferation and classified patients into three gene clusters, confirming their prognostic value. The CRG_score predicted patient outcomes, with high-risk patients demonstrating worse survival and possible resistance to immunotherapy. Drug sensitivity analysis suggested higher responsiveness to doxorubicin and etoposide in high-risk patients.Conclusion: This study suggests the potential prognostic value of CRGs in ACC. The CRG_score model provides a robust tool for risk stratification, with implications for treatment strategies.Keywords: cuproptosis, overall survival, immune microenvironment, molecular signature

The S100 protein family is a key component of damage-associated molecular patterns(DAMP), which play a vital role in regulating inflammation in the body's innate immune response. S100A8/S100A9 proteins play a wide range of antibacterial and anti-infective functions in many diseases, and promote the occurrence and development of the body's immune and inflammatory responses. In various retinal degenerative diseases, S100A8/S100A9 proteins are significantly upregulated at the transcription and translation stages, promoting the activation of inflammatory factors in ocular tissues, the activation and recruitment of immune cells such as macrophages and neutrophils, and the occurrence and development of ocular inflammation. This review aimsat explaining the biological functions of S100A8/S100A9 proteins and their roles and possible mechanisms in retinal degenerative diseases such as diabetic retinopathy, age-related macular degeneration and ischemic retinopathy.

Abstract We developed an automated high-throughput Smart-seq3 (HT Smart-seq3) workflow that integrates best practices and an optimized protocol to enhance efficiency, scalability, and method reproducibility. This workflow consistently produces high-quality data with high cell capture efficiency and gene detection sensitivity. In a rigorous comparison with the 10X platform using human primary CD4 + T-cells, HT Smart-seq3 demonstrated higher cell capture efficiency, greater gene detection sensitivity, and lower dropout rates. Additionally, when sufficiently scaled, HT Smart-seq3 achieved a comparable resolution of cellular heterogeneity to 10X. Notably, through T-cell receptor (TCR) reconstruction, HT Smart-seq3 identified a greater number of productive alpha and beta chain pairs without the need for additional primer design to amplify full-length V(D)J segments, enabling more comprehensive TCR profiling across a broader range of species. Taken together, HT Smart-seq3 overcomes key technical challenges, offering distinct advantages that position it as a promising solution for the characterization of single-cell transcriptomes and immune repertoires, particularly well-suited for low-input, low-RNA content samples.

Kang-Xin Li,1,* Hui Yuan,1,* Jing Zhang,2,3 Xiao-bin Peng,1 Wei-Fen Zhuang,1 Wen-Tao Huang,1 Hui-Xin Liang,1 Ying Lin,1 Ying-Zhen Huang,1 Shu-Lan Qin1 1Department of Endocrinology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China; 3China Resources Jiangzhong Pharmaceutical Group Co., Ltd., Nanchang, Jiangxi, 330004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Lan Qin, Email qinshulan@smu.edu.cnIntroduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by insulin resistance, hyperglycaemia, and inflammation, with oxidative stress contributing to its progression. Curcumin (CUR), known for its anti-inflammatory, antioxidant, and insulin sensitising effects, has shown potential for the treatment of T2DM but is limited by low solubility and bioavailability. This study investigated long-circulating curcumin-loaded liposomes (CUR-LPs) to improve curcumin stability, solubility, and circulation and assessed their effect on insulin resistance in a murine model of T2DM.Methods: CUR-LPs were prepared using the ethanol injection method and characterized for morphology, particle size, zeta potential, encapsulation efficiency, drug-loading capacity, and in vitro release. Cell viability was tested on murine L929 cells. In a T2DM murine model, after four weeks of CUR-LP treatment, inflammatory markers TNF-α and IL-6 were measured by real-time polymerase chain reaction, and liver tissues were analyzed for glutathione (GSH) and superoxide dismutase (SOD) via colorimetry.Results: CUR-LPs were spherical, with an average diameter of (249 ± 2.3) nm and a zeta potential of (− 33.5 ± 0.8) mV. They exhibited an encapsulation efficiency of (99.2 ± 0.5) %and a drug-loading capacity of (1.63 ± 0.02) %. CUR embedding in liposomes significantly maintained CUR release. In L929 cells, over 80% viability was maintained at 12 uM CUR concentration after 24 h. In HFD/STZ-induced T2DM mice, CUR-LPs improved blood glucose and insulin levels more efficiently than free CUR, and CUR-LPs also reduced hepatic inflammation (TNF-α, IL-6), enhanced hepatic GSH and SOD, and attenuated liver injury.Conclusion: CUR-LPs improved glucose metabolism and insulin resistance in HFD/STZ-induced T2DM mice, which may be associated with a decrease in liver inflammation and oxidative stress.Keyworks: T2DM, curcumin, liposomes, insulin resistance, glucose metabolism, oxidative stress

Abstract Background Empathy is an important factor in the doctor-patient relationship, but mental illness is more difficult to understand than other diseases. Besides traditional skills, virtual reality (VR) has been identified as a promising tool in empathy education. This study aimed to investigate the ability of empathy enhancement, the feasibility of depression education, and the changes in thoughts and attitudes in medical students through a single VR experience. Methods We recruited medical students and randomly assigned them to two groups based on their completed Interpersonal Response Index scores. Two sets of VR systems were provided; the intervention group experienced the daily life of the depressed medical student, while the control group experienced the general medical student scenario. The improvement of empathy was assessed using the Jefferson Scale of Empathy-Health Professional Students (JSE-HPS), and the change of attitude was assessed through the Implicit Association Test. In addition, other questionnaires were used to evaluate the user experience of this VR system, and correlation analysis was conducted to examine the association between the use of VR and changes in the JSE and IAT scores. Results A total of 59 medical students were enrolled in this study. The intervention group showed a significant increase in the perspective-taking (pre: mean 5.817, SD 0.536; post: mean 5.947, SD 0.620; P = .03) and compassionate care (pre: mean 5.546, SD 0.581; post: mean 5.721, SD 0.629; P = .01) domains of the JSE score and a significant decrease in the standing in the patient’s shoes (SP) domain (pre: mean 3.583, SD 1.253; post: mean 2.967, SD 1.252; P = .002). The Pearson correlation analysis found a significant positive correlation between the JSE score with immersion aspect (r = .308, P = .049) and presence aspect (r = .415, P = .01), and we also found a significant negative correlation between the IAT score and presence aspect (r=-.333, P = .04). Conclusions This study is the first randomized case-control study to investigate the effect of two different versions of VR on empathy development toward depression for medical students. Although the single VR experience was unable to induce a great improvement in empathy or attitude, the VR system could help medical students enhance their understanding of depressive disorders. Trial registration This trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (21/03/2024, ACTRN12624000297527). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386683&isReview=true .

Abstract Abnormal apoptosis of ovarian cells caused by oxidative stress is an important cause of premature ovarian failure (POF). Previous studies revealed that proanthocyanidins (PCs) are powerful natural antioxidants that can safely prevent oxidative damage in humans. However, the protective effect and mechanism of PCs on ovarian function during the course of POF remain unknown. In this study, female mice were injected with 3-nitropropionic acid (3-NPA) to establish an ovarian oxidative stress model; at the same time, the mice were treated with PC via gavage. Thereafter, the expression of various apoptosis genes, hormones, and related molecules was assessed. Compared with those in the control group, the ovarian index, follicle count at all levels, expression of MVH, PCNA and BCL2, and estradiol (E2) and progesterone (P) levels were significantly lower in the POF group, but significant recovery was observed in terms of MVH and PCNA expression and E2 and P levels in the POF + PCs group. The apoptosis marker genes BAX and ROS were significantly increased in the POF group but were notably restored in the POF + PCs group. In addition, the expression of Sestrin2, an antiapoptotic protein, was significantly increased in the PCs treatment group, as were the upstream and downstream regulatory factors NRF2 and SOD2, and the indices of the Sestrin2 overexpression group were similar to those of the PCs treatment group. In summary, these findings suggest that PCs have potential as innovative therapeutic agents for preventing and treating POF by activating the protective SESTRIN2-NRF2 pathway against oxidative stress.

Abstract Background Neuroinflammation reportedly plays a critical role in the pathogenesis of sepsis-associated encephalopathy (SAE). We previously reported that circulating plasma extracellular vesicles (EVs) from septic mice are proinflammatory. In the current study, we tested the role of sepsis plasma EVs in neuroinflammation. Methods To track EVs in cells and tissues, HEK293T cell-derived EVs were labeled with the fluorescent dye PKH26. Cecal ligation and puncture (CLP) was conducted to model polymicrobial sepsis in mice. Plasma EVs were isolated by ultracentrifugation and their role in promoting neuronal inflammation was tested following intracerebroventricular (ICV) injection. miRNA inhibitors (anti-miR-146a, -122, -34a, and -145a) were applied to determine the effects of EV cargo miRNAs in the brain. A cytokine array was performed to profile microglia-released protein mediators. TLR7- or MyD88-knockout (KO) mice were utilized to determine the underlying mechanism of EVs-mediated neuroinflammation. Results We observed the uptake of fluorescent PKH26-EVs inside the cell bodies of both microglia and neurons. Sepsis plasma EVs led to a dose-dependent cytokine release in cultured microglia, which was partially attenuated by miRNA inhibitors against the target miRNAs and in TLR7-KO cells. When administered via the ICV, sepsis plasma EVs resulted in a marked increase in the accumulation of innate immune cells, including monocyte and neutrophil and cytokine gene expression, in the brain. Although sepsis plasma EVs had no direct effect on cytokine production or neuronal injury in vitro, the conditioned media (CM) of microglia treated with sepsis plasma EVs induced neuronal cell death as evidenced by increased caspase-3 cleavage and Annexin-V staining. Cytokine arrays and bioinformatics analysis of the microglial CM revealed multiple cytokines/chemokines and other factors functionally linked to leukocyte chemotaxis and migration, TLR signaling, and neuronal death. Moreover, sepsis plasma EV-induced brain inflammation in vivo was significantly dependent on MyD88. Conclusions Circulating plasma EVs in septic mice cause a microglial proinflammatory response in vitro and a brain innate immune response in vivo, some of which are in part mediated by TLR7 in vitro and MyD88 signaling in vivo. These findings highlight the importance of circulating EVs in brain inflammation during sepsis.

In the traditional hybrid cryptosystem, an attacker can generate the previously used session key to decrypt session contents encrypted under the session key due to the leakage of the current private key. To address this issue of leakage of the private key, this paper applies the key encapsulation mechanism and proposes a forward-secure public-key encryption scheme (FS-SM9) based on identity cryptosystem SM9. This paper also proves that the scheme is IND-FS-CPA under the hardness assumption (q, n)-DBDHI in the standard model. In the encryption scheme, the lifetime of the system is divided into multiple periods which are managed by a binary tree, which reduces the overheads of the system to a logarithmic level. The time information is embedded into the ciphertext when encrypting messages. Only the private key of the specific period can decrypt the ciphertext. Each private key is updated via an updating procedure and this updating procedure is unidirectional, during which a new private key is generated while the old one is deleted, so the forward security is preserved. Moreover, as shown by the performance analysis and experimental results, the scheme only introduces negligible overheads in achieving forward security under certain conditions. Therefore, the proposed scheme is practical and can be run on specific resource-constrained devices, providing forward security for these devices.

Vacuum freeze-dried fruit processes consisting of heating and holding are modelled as a mixed batch scheduling with the objective of minimizing the makespan. The jobs differ from each other in job family, size, weight and ready time. The batch processing time is determined by the longest job and the total weight of the jobs in the batch. A mixed-integer linear programming model is developed and tested with small-scale examples. Typical batch scheduling strategies are analysed and a machine-based dynamic programming strategy is proposed. The machine-based dynamic scheduling strategy is applied to design improved genetic and particle swarm optimization algorithms, which demonstrate the effectiveness of this strategy. The worst-case ratio of the algorithms using machine dynamic programming strategy are proved. Numerical experiments show that the heuristic algorithm, genetic algorithm, and particle swarm optimization algorithm based on machine dynamic scheduling strategy outperform related algorithms using greedy and job-based dynamic scheduling strategies.

AIM: To investigate the expression levels and clinical significance of hypoxia-inducible factor-1α(HIF-1α)and interleukin-17(IL-17)in conjunctival epithelial cells and tear fluid of patients with dry eyes.METHODS: Retrospective study. A total of 183 dry eye patients admitted to our hospital from February 2021 to March 2023 were selected, and 181 people who were physically healthy in our hospital during the same period were chosen as the control group. HIF-1α and IL-17 expression levels in conjunctival epithelial cells and tear fluid of the two groups of subjects were tested, and the diagnostic value of HIF-1α and IL-17 in conjunctival epithelial cells and tear fluid of the subjects in testing dry eyes was analyzed through receiver operating characteristics(ROC)curves.RESULTS: Compared with the control group, patients in the dry eye group had elevated levels of HIF-1α and IL-17 expression in conjunctival epithelial cells(all P

AIM: To understand the visual acuity and spectacle usage among primary and secondary school students in Xi'an city, providing scientific evidence for making myopia prevention and control efforts.METHODS:Vision screening and spectacles usage survey was conducted on 38 226 students in 119 primary and secondary schools from 16 counties and districts in Xi'an city, and uncorrected visual acuity, refractive power, glasses wearing rate, full correction rate were statistically analyzed.RESULTS:The myopia rate among primary and secondary school students in Xi'an city is 61.53%, showing an increasing trend as the grade level goes up(χ2trend=5332.203, P

In the dynamic field of the internet in modern life, networks are increasingly vulnerable to a diverse range of cyberattacks. Conventional intrusion detection systems based on machine learning techniques require a large number of samples for training. However, in some scenarios, only a limited number of malicious samples can be collected. To address the issue of insufficient training samples and unbalanced sample classes for intrusion detection system in real network environments, this paper proposes an intrusion detection method named DeepInsight–transfer learning–convolutional neural network (DI–TL–CNN), which is based on DI and TL. First, the DI method is used to convert the intrusion dataset into an image form suitable for CNN model input. The DI method can transform text while maintaining the semantic relationships between data points, thereby providing high-quality images. In this step, we map the 1D feature vector representation of the input data onto the 2D image representation using T-SNE and construct 2D grayscale images. In the second step, we train and optimize the VGG16 model through TL and fine-tuning, enhancing the model’s adaptability and performance. We propose six TL schemes by freezing and fine-tuning the parameters of different modules in the CNN model to enhance intrusion detection performance. In the TL process, the VGG16 model, pretrained on the ImageNet dataset, demonstrates promising results for generic image classification tasks. The bottom layers of CNN models often learn basic feature patterns that are applicable to various tasks, while the features acquired by the top layers of the model are specific to the target domain intrusion dataset. Fine-tuning allows the model to adjust the pretrained architecture’s higher-order features to better match the targeted dataset. During the training process, the bottom layers of the pretrained architecture are frozen, whereas the top layers are unfrozen for fine-tuning. The optimal intrusion detection model is determined through a comparison of the performance of the six TL schemes. Finally, the correctness and effectiveness of the proposed DI–TL–CNN method are validated on a dataset with insufficient training samples, using metrics such as accuracy, precision, recall, and F1-score. In the experiments, compared with existing state-of-the-art models for intrusion detection, the proposed method considerably enhances accuracy in the detection of network traffic data. The experimental results show that the DI–TL–CNN method is suitable for intrusion detection with small samples and unbalanced data, demonstrating the good application prospects of the method in complex networks.

Heart failure patients are prone to depression, and interact with each other, leading to lower quality of life and poor prognosis of patients. As the largest microecosystem in the human body, changes in the composition, structure and function of the gut microbiota are closely related to the physiological and pathological states of the host. Currently, the "gut-heart/brain axis" has been used to explain the link between gut microbiota, cardiovascular diseases, and mood states, which is an important comorbid basis for heart failure and depression. In this paper, we reviewed the mechanisms of gut microbiota, metabolites, and vagus nerve in the development of heart failure and depression, and propose that mediterranean diet, probiotics, and microbiota transplantation have the potential to improve the "microbiota-gut-heart/brain axis", providing a new perspective for the treatment of heart failure patients comorbid with depression.

The anti-Clostridium difficile infection (CDI) drug fidaxomicin is a natural polyketide metabolite mainly produced by Micromonosporaceae, such as Actinoplanes deccanensis, Dactylosporangium aurantiacum, and Micromonospora echinospora. In the present study, we employed a stepwise strategy by combining heterologous expression, chassis construction, promoter engineering, activator and transporters overexpression, and optimization of fermentation media for high-level production of fidaxomicin. The maximum yield of 384 mg/L fidaxomicin was achieved with engineered Streptomyces albus D7-VHb in 5 L-tank bioreactor, and it was approximately 15-fold higher than the native strain Actinoplanes deccanensis YP-1 with higher strain stability and growth rate. This study developed an enhanced chassis strain, and for the first time, achieved the heterologous synthesis of fidaxomicin through a combinatorial metabolic engineering strategy.

Cancer immunotherapy has shown to be a promising method in treating hepatocellular carcinoma (HCC), but suboptimal responses in patients are attributed to cellular and molecular heterogeneity. Iron metabolism-related genes (IRGs) are important in maintaining immune system homeostasis and have the potential to help develop new strategies for HCC treatment. Herein, we constructed and validated the iron-metabolism gene prognostic index (IPX) using univariate Cox proportional hazards regression and LASSO Cox regression analysis, successfully categorizing HCC patients into two groups with distinct survival risks. Then, we performed single-sample gene set enrichment analysis, weighted correlation network analysis, gene ontology enrichment analysis, cellular lineage analysis, and SCENIC analysis to reveal the key determinants underlying the ability of this model based on bulk and single-cell transcriptomic data. We identified several driver transcription factors specifically activated in specific malignant cell sub-populations to contribute to the adverse survival outcomes in the IPX-high subgroup. Within the tumor microenvironment (TME), T cells displayed significant diversity in their cellular characteristics and experienced changes in their developmental paths within distinct clusters identified by IPX. Interestingly, the proportion of Treg cells was increased in the high-risk group compared with the low-risk group. These results suggest that iron-metabolism could be involved in reshaping the TME, thereby disrupting the cell cycle of immune cells. This study utilized IRGs to construct a novel and reliable model, which can be used to assess the prognosis of patients with HCC and further clarify the molecular mechanisms of IRGs in HCC at single-cell resolution.

In this article, we present two new algorithms referred to as the improved modified gradient-based iterative (IMGI) algorithm and its relaxed version (IMRGI) for solving the complex conjugate and transpose (CCT) Sylvester matrix equations, which often arise from control theory, system theory, and so forth. Compared with the gradient-based iterative (GI) (A.-G. Wu, L.-L. Lv, and G.-R. Duan, Iterative algorithms for solving a class of complex conjugate and transpose matrix equations, Appl. Math. Comput. 217 (2011), 8343–8353) and the relaxed GI (RGI) (W.-L. Wang, C.-Q. Song, and S.-P. Ji, Iterative solution to a class of complex matrix equations and its application in time-varying linear system, J. Appl. Math. Comput. 67 (2021), 317–341) algorithms, the proposed ones can make full use of the latest information and need less computations, which leads to higher computational efficiency. With the real representation of a complex matrix as a tool, we establish sufficient and necessary conditions for the convergence of the IMGI and the IMRGI algorithms. Finally, some numerical examples are given to illustrate the effectiveness and advantages of the proposed algorithms.

Abstract The topological attributes of structural covariance networks (SCNs) based on fractal dimension (FD) and changes in brain network connectivity were investigated using graph theory and network-based statistics (NBS) in patients with noise-induced hearing loss (NIHL). High-resolution 3D T1 images of 40 patients with NIHL and 38 healthy controls (HCs) were analyzed. FD-based Pearson correlation coefficients were calculated and converted to Fisher’s Z to construct the SCNs. Topological attributes and network hubs were calculated using the graph theory. Topological measures between groups were compared using nonparametric permutation tests. Abnormal connection networks were identified using NBS analysis. The NIHL group showed a significantly increased normalized clustering coefficient, normalized characteristic path length, and decreased nodal efficiency of the right medial orbitofrontal gyrus. Additionally, the network hubs based on betweenness centrality and degree centrality were both the right transverse temporal gyrus and left parahippocampal gyrus in the NIHL group. The NBS analysis revealed two subnetworks with abnormal connections. The subnetwork with enhanced connections was mainly distributed in the default mode, frontoparietal, dorsal attention, and somatomotor networks, whereas the subnetwork with reduced connections was mainly distributed in the limbic, visual, default mode, and auditory networks. These findings demonstrate the abnormal topological structure of FD-based SCNs in patients with NIHL, which may contribute to understand the complex mechanisms of brain damage at the network level, providing a new theoretical basis for neuropathological mechanisms.

Abstract Background Sarcopenia and knee osteoarthritis (KOA) are two common musculoskeletal disorders, often coexisting in aged population and potentially influencing each other. However, the underlying relationship between two conditions remains unclear and controversial. To fill this knowledge gap, we aimed to investigate the longitudinal association among the older Chinese population. Methods Data were attracted from 2 waves of the China Health and Retirement Longitudinal Study (CHARLS), and 6212 individuals aged ≥ 60 years were included. Sarcopenia status was defined by the Asian Working Group for Sarcopenia 2019 criteria. Multivariate logistic regression and generalized estimation equation models were applied to estimate the impact of sarcopenia on KOA. A prognostic nomogram was developed through train-test cross-validation. Results At baseline in CHARLS 2015, the prevalence of symptomatic KOA was 12.7% (792/6212) in total population, 9% (270/2996) in no-sarcopenia group, 17.5% (286/1638) in possible sarcopenia group, and 15.0% (236/1578) in sarcopenia group. Over a 3-year follow-up, 4980 respondents were included, with incident KOA cases identified as 56 (2.2%), 38 (3.0%), and 43 (3.6%) in no-sarcopenia, possible sarcopenia, and sarcopenia groups, respectively. Sarcopenia was significantly associated with increased new-onset KOA compared to no-sarcopenia peers in the fully adjusted model (OR: 1.91, 95% CI: 1.15–3.18), whereas this association was non-significant for possible sarcopenia. In females, low muscle mass alone significantly increased the incident risk of KOA (OR: 2.58, 95% CI: 1.05–6.49). The final prognostic model and nomogram, including sarcopenia status, age, gender, body mass index, self-reported health status, comorbidities, history of falls and physical activity, had a considerable discrimination (AUC = 0.744, C-index = 0.660). The calibration curve indicated significant agreement between predicted and actual observations. Decision curve analysis revealed net benefits for clinical intervention at a probability threshold of 1–17%. Conclusions Sarcopenia was associated with a higher incident risk of symptomatic KOA, wherein low muscle mass may play an important role. The inferior prognosis of sarcopenia in KOA needs more attention in clinical practice.

Abstract Background Heart failure (HF) is associated with high mortality and rehospitalization rates, highlighting the need for novel therapeutic approaches. Jianxin (JX) granules, a Traditional Chinese Medicine formulation, have been patented for the treatment of HF. However, the specific therapeutic effects and underlying mechanisms of JX granules have not been fully elucidated. This study aimed at investigating the effects and mechanism of JX granules in the treatment of HF based on proteomics and metabolomic profiling. Methods HF model was established in rats by ligation of left coronary artery. The successfully modeled rats were randomly divided into three groups: the model group, the JX granules group, and Sacubitril/Valsartan (S/V) group. Four weeks after treatment, left ventricular (LV) function was evaluated via echocardiography. LV fibrosis and apoptosis were examined through histological analyses, while mitochondrial morphology was assessed using transmission electron microscopy. Quantitative assessment of oxidative stress was also conducted. Proteomics was used to identify the differentially expressed proteins and potential pathways. Metabolomics was utilized to elucidate the variations in metabolism. Then western blotting and in vitro analyses were performed. Results A rat model of HF was established, evidenced by a decrease in left ventricular ejection fraction (LVEF), stroke volume (SV), and left ventricular fractional shortening (LVFS), alongside diminished adenosine triphosphate (ATP) content, elevated oxidative stress, augmented apoptosis, and disrupted pyruvate metabolism. Treatment with JX granules ameliorated these effects, improving systolic function, reducing ventricular chamber size, and increasing LVEF, SV, and LVFS, as assessed by echocardiography. Additionally, JX granules attenuated cardiac fibrosis and improved mitochondrial structure, as evidenced by less vacuolation and clearer mitochondrial cristae, when compared to the model group. The treatment also regulated apoptosis-related protein expression, partially reversing the increase in cleaved Caspase-9, cleaved Caspase-3, and Bax and the suppression of Bcl-2 observed in the heart failure rats. All of these effects were similar to S/V. Proteomic and metabolomic analyses identified key differential genes, such as triosephosphate isomerase 1 (TPI1), lactate dehydrogenase B (LDHB), pyruvate kinase M (PKM), protein kinase B (Akt), Pyruvate Dehydrogenase Beta (PDHB) and lactate dehydrogenase A (LDHA), as well as vital pathways including carbon metabolism, the PI3K-Akt signaling pathway, pyruvate metabolism, and HIF-1α signaling pathway. Moreover, JX granules mitigated oxidative stress, inhibited apoptosis, and activated Akt in H9c2 cells exposed to angiotensin II, which could be reversed by the PI3K inhibitor LY294002. Conclusion JX granules improve HF in parallel to the efficacy of S/V, at least in part, through enhancing pyruvate metabolism, inhibiting oxidative stress and activating PI3K/Akt pathway.

Abstract The proportion of Shanghai residents' non-commuting trips in the total number of urban trips has been increasing year by year. Non-commuting trips, as an important symbol of modernized lifestyles, reflect the use of urban resources by people in production and life, and their dynamic distribution and changes have extremely important guiding roles in the city's fine-tuned management and resource allocation. Taking Shanghai as an example, this paper extracts three types of urban function grids, namely, urban park green space, commercial consumption and public service through the establishment of Shanghai urban grid function identification system based on multi-source data such as Baidu LBS (Location-BasedServices), data, POI (Point of Interest) data, etc. Then 3 types of non-commuting trips, namely, urban park, commercial and public service are further classified and identified, and their characteristics are analyzed. The results show that: ①Urban park travel frequency is low, and the proportion of long-distance trip is high. Zhujiajiao Town, Nanjing East Road Street and Lujiazui Street are three main travel gathering nodes in the city. There is a close relationship between the main urban area and the suburbs and the main urban area is more dependent on the suburbs. ②The travel frequency of commercial is the highest and the average travel distance is the shortest. The trend of trip agglomeration to the main urban area is significant and the trip distribution shows an obvious multi-center trend. ③The travel frequency of public service is high and the average travel distance is short. The trip distribution shows an obvious hierarchical structure, gathering in the main urban area and suburban new towns. ④Songjiang, Jiading and Qingpu in the suburban new towns have stronger attraction. The study suggests that non-commuting trips have an important impact on the urban spatial network structure, which needs to be further analyzed and compared with the spatial network structure formed by commuting trips to find the links and differences, so as to provide research support for the optimization of urban spatial structure.

Yaping Shen,1,2,* Yijiu Wu,3,* Hai Zhuang,4 Zhumei Chen,5 Qiong Zhang,5 Peixin Li,5 Jing Wang,3 Zhi Huang,1 Qingfan Zeng3,5 1Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550002, People’s Republic of China; 2Department of Interventional Radiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 3College of Anesthesiology, Guizhou Medical University, Guiyang, 550002, People’s Republic of China; 4Department of Infectious, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 5Department of Anesthesiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi Huang, Department of interventional radiology, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550002, People’s Republic of China, Email huangzhi@gmc.edu.cn Qingfan Zeng, Department of Anesthesiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China, Email 445483296@qq.comBackground: Isoflurane, as an anesthetic drug, has a neurotoxic effect on the developing brain tissue. Compound 21 (C21) has been reported to be neuroprotective and ameliorate stroke effects. However, the mechanism by which C21 protects against nerve damage remains unclear.Methods: Animal and cellular models of brain injury were constructed using isoflurane (ISO) in neonatal SD rats and primary rat neuronal cells (PRNCs). After treatment with C21, the ultrastructure and morphology of the hippocampus in the model rats were assessed using the transmission electron microscope and H&E staining. Methylation or apoptosis-related genes or proteins were examined using immunohistochemistry, RT-qPCR, and Western blot. The levels of inflammatory factors were monitored using the ELISA kits. m6A modification was analyzed by Dot blot and MeRIP-qPCR. Cell proliferation and apoptosis were also tested using Edu and TUNEL staining.Results: C21 suppresses apoptosis and inflammation and improves hippocampal morphology in ISO-induced neonatal rats. Mechanistically, C21 upregulates m6A modification, PPAR-a, BCL-2, and METTL3 in ISO-induced neonatal rats and ISO-treated PRNCs. C21 promotes cell proliferation, enhances BCL-2 m6A modification, and reduces inflammation by upregulating METTL3 by upregulating METTL3 in ISO-treated PRNCs.Conclusion: These findings suggest that C21 enhances neuronal cell survival and morphology and up-regulates methylation and Bc1-2 levels, potentially offering a therapeutic strategy for neuroprotection in clinical settings, particularly in cases of neurotoxic exposure. The mechanism may be related to the upregulation of METTL3. Keywords: compound 21, isoflurane, METTL3, anesthesia, neuron

Xin Tang,1,2,&ast; Gaoyangzi Huang,1,2,&ast; Qifu Li,1,2 Siwen Zhao,1,2 Ruqin Yang,1,2 Hongyang Wang,1,2 Yuanzheng Deng,1,2 Zili Liu,2 Taipin Guo,1,2 Fanrong Liang3 1Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 3School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taipin Guo, School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Chenggong District, Kunming City, Yunnan Province, People’s Republic of China, Email gtphncs@126.com Fanrong Liang, School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 37 Jinniu District, Chengdu City, Sichuan Province, People’s Republic of China, Email acuresearch@126.comBackground: Appetite plays a crucial role in obesity and weight loss outcomes. while conventional therapies reduce appetite, They often have limitations. Acupoint Catgut Embedding (ACE) is widely used for weight loss, but its impact on subjective appetite, especially across different appetite status, remains underexplored.Objective: To evaluate the differential impact of ACE on the subjective appetite of overweight and obese adults with strong and moderate appetites.Methods: This secondary analysis used data from a multicenter, double-blind, parallel randomized clinical trial of the ACE intervention. A total of 122 overweight and obese patients aged 18– 60 were randomly assigned to the ACE and Non-acupoint Catgut Embedding (NACE) groups, each receiving six sessions over 12 weeks and a 4-week follow-up. Appetite was measured using the Visual Analogue Scale (VAS), and a generalized linear mixed-effects model assessed changes in appetite scores. Bonferroni corrections were applied for multiple comparisons (P < 0.05).Results: Participants with strong appetite in the ACE group showed a significant reduction in appetite VAS score from 7.78 (0.66) at baseline to 5.00 (0.72) at 16 weeks (P < 0.05), compared to a reduction from 7.97 (0.93) to 6.54 (1.17) in the NACE group. The adjusted relative rate ratio between the two groups was 0.411 (95% CI, 0.210 to 0.534; P < 0.05). In participants with moderate appetite, no significant difference was observed between the two groups (P > 0.05). The significant baseline difference in appetite scores between participants with strong and moderate appetite (P < 0.05) became non-significant by week 16 (P > 0.05).Conclusion: This study reveals the stratified effect of ACE on appetite, with greater reduction in those with strong appetite and no significant change in those with moderate appetite. This suggests ACE reduces appetite effectively without excessive suppression, supporting its potential as a sustainable obesity management strategy.Keywords: acupoint catgut embedding, appetite, overweight, obesity, randomized controlled trial

Xiangxiang Peng,1,&ast; Changwei Guo,2,&ast; Jie Yang,2 Shitao Fan,2 Xu Xu,2 Jinfu Ma,2 Zhixi Wang,2 Shihai Yang,2 Wenjie Zi,2 Xianjun Huang,1 Hongjun Wang3 1Department of Neurology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 3Department of Neurology, Chongqing Fengdu People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianjun Huang, Department of Neurology, Yijishan Hospital of Wannan Medical College, No. 92 Zheshan Road, Wuhu, Anhui Province, 241000, People’s Republic of China, Tel +86-553-5739543, Email doctorhuangxj@hotmail.com Hongjun Wang, Department of Neurology, Chongqing Fengdu People’s Hospital, No. 214, West Section of Pingdu Avenue, Sanhe Town, Fengdu County, Chongqing, 408200, People’s Republic of China, Email whj13364012222@163.comPurpose: To investigate the relationship between intravenous tirofiban, the number of retrieval attempts and symptomatic intracranial hemorrhage (sICH) in patients with successful EVT.Patients and Methods: We used the data from the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) Trial. The primary outcome was sICH, which was defined according to the Heidelberg Bleeding Classification. The association between the number of retrieval attempts and the rate of sICH was investigated using multivariable logistic regression.Results: A total of 866 patients were included in our analysis. In overall cohort, tirofiban (OR: 1.853, 95% CI: 1.039– 3.307) and more than 2 passes (3 versus 0– 1: OR: 2.482, 95% CI: 1.124– 5.481; 2 versus 0– 1: OR: 0.813, 95% CI: 0.389– 1.696) were significantly associated with the occurrence of sICH. A significant interaction between the use of tirofiban and the increasing number of attempts was found (p for interaction = 0.02), whereby the presence of sICH was significantly associated with tirofiban (OR: 5.534, 95% CI: 1.586– 19.315) in the subgroup of multiple passes (> 2 passes group), while none was seen in the subgroup of 0– 2 passes. The results of the sensitivity analysis also showed that more than 2 passes (3 versus 1: OR: 2.841, 95% CI: 1.102– 7.323; 2 versus 1: OR: 0.852, 95% CI: 0.346– 2.097) were significantly associated with the occurrence of sICH in the tirofiban group but not in the placebo group.Conclusion: In patients with multiple attempts, intravenous tirofiban may increase the risk of sICH. Further research and individualized risk assessment are necessary to determine the most appropriate strategy of intravenous tirofiban for EVT patients, especially considering details of thrombectomy procedures.Registration: : URL: http:// www.chictr.org.cn; Unique identifier: ChiCTR-INR-17014167.Keywords: tirofiban, hemorrhage, endovascular treatment, stroke

Yanfang Luo,1,&ast; Jianru Hao,2,&ast; Zhenzhen Su,1,&ast; Yujuan Huang,1 Fen Ye,1 Yanhui Qiu,2 Zhimin Liu,2 Yuping Chen,3 Renjuan Sun,1 Yuyu Qiu2 1Department of Neurology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, 214126, People’s Republic of China; 3Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renjuan Sun; Yuyu Qiu, Email 15061885987@163.com; yuyuqiu@jiangnan.edu.cnAim: This study aimed to investigate the prevalence and associated factors of hypokalemia in patients with acute ischemic stroke.Methods: A cohort of 996 patients was assessed using a general data questionnaire, laboratory indicators, the NIH Stroke Scale (NIHSS), the Barthel Index (BI), the Frail scale, Nutritional Risk Screening (NRS-2002), and the Kubota drinking water test.Results: Among the 996 patients, 205 (20.6%) were found to have hypokalemia. Logistic regression analysis identified several independent predictors of hypokalemia: age (OR 1.020, 95% CI 1.001– 1.039, P=0.041), hypertension (OR 2.691, 95% CI 1.190– 6.089, P=0.017), Frail score (OR 1.756, 95% CI 1.034– 2.981, P=0.037), Kubota drinking water test grade 3 (OR 2.124, 95% CI 1.055– 4.276, P=0.035), Kubota drinking water test grade 4 (OR 3.016, 95% CI 1.113– 8.174, P=0.037), NIHSS score (OR 1.135, 95% CI 1.018– 1.264, P=0.022), platelet count (OR 0.997, 95% CI 0.994– 0.999, P=0.021), and urea nitrogen levels (OR 0.833, 95% CI 0.750– 0.926, P=0.001).Conclusion: The prevalence of hypokalemia is high in patients with acute ischemic stroke. Independent risk factors included age, hypertension, frailty, neurological function, swallowing function, platelet count and blood urea level.Keywords: acute ischemic stroke, related factors, neurological function, function of deglutition, frail, laboratory indicators

[Purposes] The development of shale oil and gas often requires a thorough understanding of the internal pore-fracture distribution patterns within shale reservoirs to optimize development strategies and enhance production capacity. In this context, the fractal dimension holds significant importance for reflecting the distribution patterns of pores and fractures within shale formations. [Methods] In this study, a convolutional neural network-based method for predicting the fractal dimension of shale Computed Tomography (CT) images is proposed. An independent convolutional neural network model is constructed, specifically designed for oil shale CT images. CT slices of oil shale samples treated with different temperatures, along with their corresponding fractal dimensions, are employed as the dataset and labels. The constructed convolutional neural network is trained and utilized for prediction to realize, effectively extracting fractal dimensions from shale CT images. [Findings] The trained model is applied to various practical scenarios and compared with the box-counting method. The results demonstrate a high degree of similarity between the predicted fractal dimensions of shale CT images by using the convolutional neural network and those computed through the box-counting method, with a difference of approximately 0.01. Additionally, the convolutional neural network method exhibits robustness against interference while also significantly accelerating the computation process compared with the box-counting method. Therefore, it can be concluded that the proposed method effectively captures the structural characteristics of images, allowing for reliable estimation of image fractal dimensions with notable resilience to noise and artifacts.

Utilizing Ca and TiH2 as the thickening agent and blowing agent， respectively， Al-0.16Sc， Al-0.21Sc， and Al-0.16Sc-0.17Zr cellular foams with porosity of （72±0.5）% were successfully fabricated by the melt-foaming method. The microstructure and compressive strength of the foams with isochronal aging treatment were investigated. The results show that during isochronal aging between 200 ℃ and 600 ℃， Al-0.16Sc and Al-0.21Sc foams achieve their peak yield strengths （about 21.4 MPa and 26.8 MPa， respectively） at 325 ℃ due to the precipitation strengthening of Al3Sc/Al3（Sc1-xTix）. Unlike the Al-Sc foam， the yield strength of the Al-0.16Sc-0.17Zr alloy foam reaches 23.7 MPa at 325 ℃ and 24.7 MPa at 400 ℃， representing an increase of 100.8% and 109% than those of the cast alloy， respectively. Zr addition not only significantly enhances the strength of the Al-Sc foams， but also effectively affects the coarsening of the Al3Sc/Al3（Sc1-xTix） precipitate.

In order to study the effects of lychee wood chips with different toasting degrees used in the aging process on the flavor of lychee brandy, the quality and volatile flavor components of lychee brandy aged with lightly toasted (LT), moderately toasted (MT) or heavily toasted (HT) lychee wood chips were evaluated and analyzed using sensory evaluation, electronic nose and gas chromatography-mass spectrometry. Raw and aged lychee brandy with heavily toasted oak chips were used as controls. The results of electronic nose analysis were in good agreement with those of sensory evaluation, and the brandy aged with heavily roasted lychee wood chip wood had the highest overall sensory score. A total of 44 volatile aroma compounds were identified in the five brandy samples, and the types and contents of volatile components varied greatly among these samples, each with their unique olefinic flavor substances. The major volatile components of aged lychee brandy were alcohols, esters, olefins, along with lesser amounts of aldehydes and ketones, alkanes, and aromatic hydrocarbons. Ethyl decanoate, ethyl acetate, ethyl caprylate, 2-methylbutanol, isoamyl alcohol, isobutanol, alpha stigmasterol and beta stigmasterol together constituted the major flavor profile of the aged lychee brandy. Therefore, aging with a moderate amount of heavily roasted lychee wood chips resulted in better improvement in the quality of lychee brandy compared to heavily toasted oak chips.

In this study, the effects of volatile substances from Trichoderma erinaceum M6-5 on the cell membrane and wall of Alternaria alternata were investigated. To evaluate the antifungal effect, the culture medium inoculated with T. erinaceum and cultured for 5 days was covered with the culture medium containing A. alternata and cultured at 30 ℃ for 3, 5 and 7 days. The mycelia of A. alternata in the treatment and control groups were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and were collected to observe the integrity of the cell membrane by propidiumiodide (PI) staining, and cell membrane-related indexes such as electrical conductivity were measured. The morphological changes of apical growth cells were detected by calcofluor white (CFW) staining, and alkaline phosphatase (AKP) activity and N-acetylglucosamine concentration were determined. The results showed that during the culture period, the volatile substances produced by T. erinaceum had good antifungal effects on A. alternata. SEM and TEM images showed that the mycelia of A. alternata appeared shriveled, swollen and broken partially after the treatment. A greater reduction in cytoplasmic matrix was noted when compared with the control group, which was accompanied by local plasmolysis. For the control group, the mycelium growth was normal, the spore structure was complete, the cross-section structure was clear, the cytoplasm was uniform, and the cell wall and membrane structures were normal. After the treatment, the electrical conductivity, malondialdehyde (MDA) level, protein and nucleic acid leakage significantly increased relative to the control group. PI staining showed that the mycelia of the treated group emitted red fluorescence, indicating that the volatile substances of T. erinaceum damaged the integrity of the cell membrane, thus resulting in the leakage of cellular contents and marked disruption of the normal function of the cell membrane. CFW staining showed no significant differences between the treated and control groups with respect to the fluorescence intensity of mycelia, AKP activity or n-acetylglucosamine concentration indicating that the volatile substances of T. erinaceum did not damage the cell wall of A.alternata, and their major targets were not the cell wall. In conclusion, the antifungal target of volatile substances from T. erinaceum M6-5 is the cell membrane of A. alternata.

Xiaojun Li,1 Donghao Cai,2 Chuangchuang Mei,2 Xinghui Huang3 1Department of Nosocomial Infection, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, People’s Republic of China; 2Department of Laboratory Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, People’s Republic of China; 3Department of Quality Control, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, People’s Republic of ChinaCorrespondence: Xiaojun Li, Department of Nosocomial Infection, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, People’s Republic of China, Email jylixiaojun@sina.comPurpose: To develop and validate a predictive model for the risk of death in patients with Acinetobacter baumannii (A. baumannii) bloodstream infection (BSI) for clinical decision-making and patient management.Methods: In this study, we included demographic and clinical data from 206 patients with Acinetobacter baumannii BSI in China between January 2013 and December 2023. Variables were screened by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, and prognostic models and nomograms were constructed. The models were evaluated using the area under curve (AUC) of Receiver Operating Characteristic (ROC), decision curve analysis (DCA), and standard curves to evaluate the model.Results: Comorbid septic shock, an elevated neutrophil/lymphocyte ratio (NLR), low hemoglobin (HGB) levels, and low platelet counts (PLT) were found to be independent risk factors for death in patients with A. baumannii BSI. With the models constructed from these four variables, the AUCs of the ROC curves of the test and validation cohorts for the prognostic scenarios at 7, 14, and 28 days were not less than 0.850, and the AUCs of the ROC curves of the risk-of-death prediction model were the highest for both groups at 7 days, at 0.907 and 0.886, respectively. The two sets of calibration curves show that the calibration curves oscillate around a 45° diagonal line at 7, 14, and 28 days, and there is a good correlation between the actual risk and the predicted risk, with a high degree of calibration.The clinical decision curve shows that the model has a strong discriminatory ability when the probability is between 10% and 70%.Conclusion: Septic shock status, NLR, HGB and PLT are independent risk factors for 28-day mortality in patients with A. baumannii BSI. These variables are conveniently and readily available, and in patients with A. baumannii BSI these indicators can be closely monitored in clinical practice and timely interventions can be made to improve prognosis.Keywords: Acinetobacter baumannii, bloodstream infection, predictive model, septic shock

Yuqing Song,1,2,&ast; Wenjie Lei,1– 3,&ast; Qianqian Huang,1,2 Jiehan Zhang,1,2 Qiao Zhang,4 Lulu Chen,1,2 Huiqing Li,1,2 Li Liu,5 Tianshu Zeng,1,2 Xiang Hu1,2 1Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, 430022, People’s Republic of China; 3People’s Hospital of Luotian County, Huanggang, 438600, People’s Republic of China; 4Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5The People’s Hospital of Maojian, Shiyan, 442000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianshu Zeng; Xiang Hu, Email tszeng@126.com; huxiang628@126.comBackground: Functional defects caused by mutations in the insulin receptor (INSR) gene often lead to severe hereditary insulin resistance syndromes, including but not limited to type A insulin resistance syndrome.Method and Result: Here, we report a case of a 12-year-old girl with elevated fasting blood glucose detected by opportunistic testing, associated with severe insulin resistance and hyperandrogenemia. She had axillary hair, acne, clitoral hypertrophy, prominent labia minora hypertrophy and thickened voice with BMI 20.57kg/m2, and ultrasound imaging showed that she had multiple follicles in both ovaries. Insulin was initially administered, but the glycemic control was poor. Accordingly, the prescription was later switched to metformin, maintaining euglycemic blood glucose level. The whole exome sequencing from peripheral blood revealed that the patient carries NM_000208.2:c.1225_1227delTTC (p.Phe409del) heterozygous mutation in the INSR gene. She was tentatively diagnosed as type A insulin resistance syndrome based on her clinical features and heterozygous mutation in the INSR gene.Conclusion: Our results demonstrated that type A insulin resistance syndrome in patients presenting with severe insulin resistance and hyperandrogenemia was associated with a heterozygous variant of c.1225_1227delTTC (p.Phe409del), suggesting that exon sequencing would be beneficial to detect the potential mutations in the INSR gene of these patients for precise diagnosis and intervention in clinical practice.Keywords: insulin receptor gene, heterozygous mutation, severe insulin resistance, hyperandrogenemia, type A insulin resistance syndrome, female

Wenchao Huang,1 Hanxiong Liu,1 Yan Luo,1 Shiqiang Xiong,1 Shuwei Suo,1 Zhen Zhang,1 Luxiang Shang,2,3 Huaxin Sun1 1Department of Cardiology, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Jinan, Shandong, 250014, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of ChinaCorrespondence: Huaxin Sun, Department of Cardiology, The Third People’s Hospital of Chengdu, Chengdu Cardiovascular Disease Research Institute, 82 Qinglong St, Chengdu, Sichuan, People’s Republic of China, Email gracekelly1994@163.com Luxiang Shang, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Email shangluxiang@163.comBackground: Serum creatinine and cystatin C levels are influenced by different non-renal factors. The difference between the estimated glomerular filtration rates (eGFRdiff) based on these two markers helps assess cardiovascular risk factors unrelated to kidney function. However, its impact on post-ablation atrial fibrillation (AF) recurrence remains unknown.Methods: From July 2017 to February 2023, we prospectively observed 989 consecutive AF patients who underwent radiofrequency ablation. The association between eGFRdiff and post-ablation AF recurrence was analyzed using Kaplan-Meier methods, adjusted Cox regression analysis, and restricted cubic spline (RCS) analysis.Results: During a median follow-up period of 29 months, 326 cases of AF recurrence were detected. Participants were divided into three groups based on eGFRdiff: high (≥ − 9.22), medium (− 20.98 to − 9.22), and low (≤ − 20.98). Multivariable Cox proportional hazards models revealed that, compared to the medium eGFRdiff group, individuals in the low eGFRdiff group (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.08– 1.94, p < 0.01) and the high eGFRdiff group (HR 1.69, 95% CI 1.27– 2.27, p < 0.01) had a significantly increased risk of AF recurrence. RCS analysis demonstrated a U-shaped association between eGFRdiff and AF recurrence. Stratified analyses confirmed the robustness of the core findings across subgroups, except for females. Notably, the geriatric nutritional risk index and the derived neutrophil-to-lymphocyte ratio partially mediated the association between eGFRdiff and high AF recurrence by 5.7% and 10.7%, respectively.Conclusion: eGFRdiff is related to individual nutritional and inflammatory statuses and can be used to predict the risk of AF recurrence. (Clinical trial registration number: ChiCTR-OIN-17013021).Plain Language Summary: This study investigated the association between eGFRdiff and AF recurrence after ablation. eGFRdiff is calculated from two different markers in the blood (creatinine and cystatin C), which reflect both kidney health and other body conditions like nutrition and inflammation. We followed 989 patients who had AF and underwent ablation from July 2017 to February 2023. We found that eGFRdiff was much higher or lower, the risk of AF recurrence increased, forming a U-shaped curve. This pattern was consistent in most groups of patients, except for women who showed a different trend. Our findings suggest that both nutritional status and inflammation play roles in AF recurrence, but their impacts differ based on eGFRdiff levels. Poor nutrition was more significant at lower eGFRdiff levels, while inflammation was more crucial at higher levels. Interestingly, inflammation seemed to have a stronger impact on women. These insights emphasize the need to monitor and manage patients’ nutritional and inflammatory status to reduce the risk of AF recurrence, especially considering sex-specific factors. Future larger studies are needed to confirm these results and further refine treatment strategies.Keywords: atrial fibrillation, estimated glomerular filtration rate, cystatin C, creatinine, recurrence

Hongli Wang,1,2,* Mingzhu Wang,1,2,* Tengyue Wang,1,2 Xuanlin Li,1,2 Chengping Wen,1,2 Zhexing He,1,2 Lin Huang1,2 1Research Institute of Chinese Medical Clinical Foundation and Immunology, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Huang; Zhexing He, College of Basic Medical Science, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, People’s Republic of China, Email huanglin@zcmu.edu.cn; hzx2015@zcmu.edu.cnBackground: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and bone destruction, leading to severe complications. Previous research has suggested that high humidity conditions may exacerbate RA, however, the underlying mechanisms remain unclear. Furthermore, there is a lack of evidence linking humidity to the worsening of RA symptoms in animal models.Methods: The Collagen-induced arthritis (CIA) mouse model was established using C57BL/6 mice. The arthritis status of the mice was evaluated under two distinct humidity conditions (50% and 80%). The aim of the present study was to investigate the impact of elevated humidity levels on the types of splenic cells present using mass spectrometry flow. Additionally, the study utilized MDSCs, which are significantly upregulated by high humidity, to assess the levels of oxidative stress and conducted mRNA sequencing of sorted MDSCs to investigate their impact on arthritis in CIA mice.Results: Compared to normal humidity, high humidity exacerbated arthritis incidence in mice, resulting in increased arthritis scores, swelling, serum autoantibodies (anti-COII and anti-CCP), and upregulation of pro-inflammatory cytokines. Significant variations were observed in the spleen index under high humidity condition, accompanied by noticeable inflammatory alterations. Moreover, elevated humidity levels induced a substantial modulation in MDSCs population in the spleen of CIA mice, along with alterations in oxidative stress markers such as heightened serum ROS levels, and increased expression of COX, SOD, and Nrf2 mRNA. Following successful sorting of MDSCs, mRNA sequencing revealed a decrease in the expression of Rap1 signaling pathway under high humidity environment, which may contribute to the increase of MDSCs cells and aggravate the progression of RA disease.Conclusion: A comprehensive analysis of the available data reveals a detrimental impact of high humidity on MDSCs numbers within spleen tissue, with potential implications for the development of RA.Keywords: rheumatoid arthritis, high humidity environment, myeloid-derived suppressor cells, Rap1 signaling pathway

Lwin Moe Aung,1 Ting-Yi Renn,1 Jerry Chin-Yi Lin,1,2 Eisner Salamanca,1 Yi-Fan Wu,1,3 Yu-Hwa Pan,1,4,5 Nai-Chia Teng,1,6 Haw-Ming Huang,1 Ying-Sui Sun,7 Wei-Jen Chang1,8 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA; 3Department of Biomedical Engineering, Ming-Chuan University, Taoyuan, Taiwan; 4Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan; 5School of Dentistry, College of Medicine, China Medical University, Taichung, Taiwan; 6Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan; 7School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 8Dental Department, Shuang-Ho Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Wei-Jen Chang; Ying-Sui Sun, Email cweijen1@tmu.edu.tw; yingsuisun@tmu.edu.twPurpose: Nano-engineering techniques have significantly enhanced the various aspects of dentistry, with notable advancements, especially in dental implant surface modification. Dental implants are among the most significant and highly successful developments in contemporary dentistry. The use of nanotechnology for surface modification of zirconia ceramic implant increases interaction with surrounding bone cells, and ultimately leading to increase osseointegration.Materials and Methods: Glow discharge plasma was utilized to graft allylamine and fibronectin nanoproteins onto the surface of zirconia implants. A total of 18 implants were placed in right and left femurs of nine New Zealand rabbits. Implant stability test (IST), 3D bone reconstruction and micro-CT (μCT) analysis, bone-implant contact (BIC) from histomorphometry analysis, and osteogenic gene expression were analyzed after scarification at 4, 8, and 12 weeks.Results: IST results demonstrated a significant secondary stability gain at the end of 12 weeks. The surface-treated group obtained a gradual increase in marginal bone level. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed increased expression of osteogenic genes of alkaline phosphatase (ALP) and transcription factor SP7 (SP7) biomarkers at 4 weeks. Osteoprotegerin (OPG) expression increased at 8 weeks, while runt-related transcription factor 2 (RUNX2), collagen 1A1 (COL1), bone sialoprotein (BSP), and receptor activator of nuclear factor κ B (RANK) exhibited the highest expression at 12 weeks. Importantly, histomorphometric analysis of BIC indicated that new bone formation was significantly higher in the A50F10 group compared to the control group at 12 weeks (P < 0.001).Conclusion: Based on the above findings, we conclude that the nanorough zirconia implant surface grafted with fibronectin nanoproteins prominently stimulated cellular activity and improved osseointegration properties. These results evidence its potential for future applications in dental implant surface modifications. Keywords: nano-roughness, surface modification, glow discharge plasma, zirconia implants, osseointegration, fibronectin

Zixiang Pang,&ast; Yangqin Ou,&ast; Jiawei Liang, Shengbin Huang, Jiayi Chen, Shengsheng Huang, Qian Wei, Yuzhen Liu, Hongyuan Qin, Yuanming Chen Department Orthopedics Ward 3 (Spine and Osteopathy Surgery), Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanming Chen, Department of Spinal Orthopedics, the Second Affiliated Hospital of Guangxi Medical University, No. 166, University East Road, Nanning, Guangxi, People’s Republic of China, Tel +86 13087712603, Email rkyygk@163.comObjective: The objective of this study aimed to investigate the risk factors for poor wound healing (PWH) after posterior lumbar spinal fusion. Currently, there is limited research on the application of machine learning in analyzing PWH after spinal surgery. Thus, our primary aim is to using machine learning identify these risk factors and construct a clinical risk prediction model.Methods: We retrospectively reviewed 2516 patients who underwent posterior lumbar spinal fusion at Guangxi Medical University’s Second Affiliated Hospital between August 2021 and August 2023. The data was divided into test and validation groups in a 7:3 ratio. In the test group, logistic regression analysis, support vector machine (SVM), random forest (RF), decision tree (DT), XGboost, Naïve Bayes (NB), k-Nearest Neighbor (KNN), and Multi-Layer Perceptron (MLP) were used to identify specific variables. The top six models from the eight machine learning models with the highest area under curve (AUC) values were selected and used to construct a dynamic nomograms model. Model performance was evaluated using receiver operating characteristic (ROC) and calibration curves. The model’s internal performance was then verified in the validation group using ROC and calibration curves.Results: Data from 2516 patients were collected, with 411 eligible cases selected. By combining logistic regression analysis with six machine learning algorithms, this study identified six predictors associated with PWH: subcutaneous lumbar spine index(SLSI), albumin, postoperative glucose, cerebrospinal fluid leakage(CSFL), neutrophil (NEU), and C-reactive protein(CRP). These predictors were used to develop a prediction model, visually represented through a nomogram. The AUC value in the test group was 0.981, and the C-index of the model was 0.986 (95% CI 0.966– 0.995), indicating excellent predictive capability. Calibration curve analysis showed good consistency between nomogram-predicted values and actual measurements.Conclusion: SLSI, albumin, postoperative glucose, CSFL, NEU and CRP were identified as significant risk factors for PWH after posterior lumbar spinal fusion. The developed prediction model exhibited excellent predictive accuracy and usefulness.Keywords: poor wound healing, posterior lumbar spinal fusion, machine learning, dynamic prediction model

Jiali Liu,1 Yebao Huang,2 Xiaoshuo Fu,1 Jiali Wei,1 Ping Wei3 1Department of Anorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Anorectal Surgery, Liuzhou People’s Hospital Affiliated of Guangxi Medicine University, Liuzhou, 545000, People’s Republic of China; 3Department of Anorectal Surgery, Lianyungang Hospital of Traditional Chinese Medicine/Affiliated Lianyungang Hospital of Nanjing University of Chinese Medicine, Lianyungang, 222000, People’s Republic of ChinaCorrespondence: Ping Wei, Department of Anorectal Surgery, Lianyungang Hospital of Traditional Chinese Medicine/Affiliated Lianyungang Hospital of Nanjing University of Chinese Medicine, No. 160 Chaoyang Middle Road, Xinpu Area, Lianyungang, Jiangsu, 222000, People’s Republic of China, Email 1996000029@jou.edu.cnObjective: Psychiatric disorders have been associated with Constipation in observational studies, although their causal relationships remain uncertain. We used Mendelian randomization analysis to infer causality between Schizophrenia and Major Depressive Disorder with Constipation.Methods: The exposure of interest was Psychiatric disorders, including Schizophrenia (SCZ) and Major Depressive Disorder (MDD). Summary statistics for psychiatric disorders were recruited from the PGC, SCZ (30,490 cases and 312,009 controls), MDD (170,756 cases and 329,443 controls), whereas Constipation summary genetic data were obtained from a FinnGen involving 17,246 cases and 201,546 controls. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between SCZ and MDD with Constipation.Results: LDSC indicated that Constipation was genetically correlated with Psychiatric disorders (rg range: |0.04– 0.05). The Mendelian randomization analysis indicated that there was significant evidence that genetically determined SCZ (OR = 1.05, 95% CI = 1.02– 1.07, P< 0.01) and MDD (OR = 1.21, 95% CI = 1.10– 1.33, P< 0.01) were statistically significantly causally associated with the risk of Constipation. SCZ effects remained within the range of practical equivalence (ROPE).Conclusion: The Mendelian randomization analysis suggested that SCZ and MDD increase the risk of Constipation. However, the association between SCZ and constipation, predominantly within the ROPE range, suggested only limited clinical implications.Keywords: Mendelian randomization, Schizophrenia, SCZ, major depressive disorder, MDD, constipation

YuanLi Huang,1 JinJie Liu,1,2 ChunLian Lin,1,2 Qing Zhu,1,3 LiGao Wu1,3 1Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Graduate School of Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 3Department of Pathology, School of Basic Medicine, Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: LiGao Wu, Email wlgahbb@126.comBackground: Globally, the disease that has the greatest impact on human health and is the most difficult to overcome is cancer (tumor or malignant tumor is another name for it). Cancers currently known to us can arise from almost any organ or tissue in the human body. Its uncontrolled growth pattern and metastasis characteristics are the fundamental reasons for the high mortality rate of cancer and its current incurability. An increasing number of studies have found that pyroptosis, a mode of programmed cell death, may inhibit tumor growth by changing the tumor immune microenvironment (TIME).Methods: Through a retrospective study, we selected 160 cases of different tumor tissues (including 40 cases each of esophageal cancer, gastric cancer, breast cancer, and cervical cancer), and identified the expression of caspase3/GasderminE in the tumor tissues through immunohistochemical staining and infiltration of tumor-related immune cells. And analyze its relationship with clinical parameters of tumor patients. In addition, we also marked caspase8 and caspase9 among the caspase family members to analyze the main factors upstream of caspase3.Results: The results showed that the expression level of caspase3/GSDME in different tumor tissues was positively correlated with the infiltration degree of tumor-related immune cells (natural killer cells, CD8+T cells, macrophages, etc). In addition, the expression level of caspase3 was positively correlated with caspase8, but not caspase9.Summary: The expression levels of caspase3 and GSDME exhibited significant impacts on the survival prognosis of patients with diverse tumors as well as alterations in the immune microenvironment of tumor tissues, demonstrating statistical significance. After Caspase3/GSDME triggers the pyroptosis pathway, it may change the components of the immune microenvironment of tumor tissue, thereby achieving the effect of inhibiting tumors.Keywords: pyroptosis, caspase3, GSDME, tumor immune microenvironment, cancer

As the capacity of renewable power plants connected to the grid increases year by year， optimizing the control strategies for their converters becomes crucial for enhancing system stability. Currently， the primary control strategies in renewable power plants focus on grid-following （GFL） and grid-forming （GFM） converters. The former tends to exhibit poor stability in weak grids， while the latter may lose stability in strong grids. To address this challenge， the paper first proposes a hybrid synchronous control structure for grid-connected converters that incorporates adaptive coefficients. This structure combines the phase-locked loop （PLL） commonly used by GFL converters with the power-synchronization loop （PSL） utilized by GFM converters， creating a hybrid synchronous control loop through a proportional coefficient. Subsequently， the corresponding small-signal model is developed， and based on the analysis results of small-signal stability， a method for determining adaptive parameter values is introduced. Finally， simulation results validate that the converter-connected system employing adaptive hybrid synchronous control maintains good stability in weak grids with a short-circuit ratio of 1 and in strong grids with a short-circuit ratio of 30. This provides a new control scheme suitable for the stable operation of grid-connected converters in renewable power plants under varying grid conditions.

The VSC-HVDC transmission systems are the typical solution for integrating far offshore wind power. Using diode rectifier units （DRUs） at the rectifier stations can further enhance the system’s economic efficiency and reliability. Therefore， a steady-state power flow calculation method of AC system transmission system for offshore wind power， based on grid-forming （GFM） wind turbines and DRU， is proposed. The topology of the offshore wind power integration system using DRU is described， and the GFM control strategy of the wind turbines， utilizing Q-f（reactive power-frequency） droop control， is introduced. The proposed steady-state power flow calculation method iterates the power flow using the reactive power imbalance in AC bus at the DRU-based converter station and considers the Q-f droop control characteristics of the GFM wind turbines. The steady-state operational characteristics of AC transmission systems for offshore wind power， based on GFM wind turbines and DRU， are analyzed for both the low-frequency and intermediate-frequency AC transmission systems. The effectiveness of the proposed method is validated.

As the rectification-side devices of the offshore wind power transmission systems， the diode uncontrolled rectification units are a technological hotspot in the offshore wind power sector. Multiplex rectifier circuits are usually employed for diode uncontrolled rectification， with a 12-pulse rectifier circuits being the most common. Theoretical analyses of serial and parallel multiplex wiring in the 12-pulse and the 24-pulse rectifier circuits within the multiplex rectifier circuits have been conducted. This entails studying the harmonic characteristics of the alternating current on the AC side and the voltage on the DC side， deriving the calculation methods for the harmonic numbers and the harmonic amplitudes， and determining the total current harmonic distortion rate and the voltage ripple factor. Comparative analyses are made on the characteristics of 12-pulse and 24-pulse rectifier circuits， investigating the feasibility of applying the 24-pulse rectifier circuits in the diode uncontrolled rectification units. Simulations are carried out on the PSCAD/EMTDC platform.

Smart buildings， as prosumers， not only facilitate the local consumption of renewable energy sources （RES） but also coordinate internal flexible loads to reduce electricity consumption costs through peer-to-peer （P2P） electrical energy transactions. Based on this， the paper analyzes wind-photovoltaic （WPV） resources and flexible loads in smart buildings and proposes a P2P optimal scheduling strategy that incorporates joint transactions of electricity and regulation capacity. Initially， flexible load adjustments are used to provide regulation capacity， eliminating the prediction deviations of WPV outputs. Subsequently， the paper introduces a combined transaction mechanism for electricity and regulation capacity， where both electricity and regulation capacity are traded as market commodities in P2P transactions. Finally， case studies are conducted to analyze the proposed method and model. The results demonstrate that the proposed model not only effectively increases the local consumption of WPV but also encourages market participants to actively engage in P2P transactions.

Currently, global uncertainties and instabilities are increasing significantly. Therefore, research on the evolution of urban industrial network resilience is essential for strengthening the ability of urban industries to withstand major events. This study constructs a network of firms using data on corporate headquarters and branches in Dongguan registered between 1979 and 2020. It analyzes the evolution of urban industry network resilience through interruption simulations and complex network invulnerability. The study empirically examines the resilience of Dongguan's industrial network, focusing on single-node resilience, overall network resilience, and regional network resilience. The results indicate the following: (1) In the single-node simulation attack of the Dongguan industrial network, the impact of urban core nodes on network resilience gradually weakens. The differences between urban core nodes and general town nodes continue to diminish, and the network's resistance to single-node disruptions tends to stabilize. (2) Compared to random attacks, deliberate attacks can cause networks to collapse faster. However, as Dongguan's industrial networks evolved toward a multi-center structure, the impact of targeted attacks on network resilience gradually decreased. (3) The resilience of Dongguan's industrial network to Shenzhen is lower than that to Guangzhou. However, the strength of enterprises inside and outside the city tends to balance, and the resilience level of the regional network is gradually stabilizing. (4) Overall, the evolution of industrial network resilience in Dongguan is characterized by a shift from a single-center network with a low level of resilience to a multi-center network with a higher level of resilience. The innovation of this research lies in two key areas: First, it provides valuable contributions to related research on urban network resilience and industrial resilience by introducing the concepts and methods of interruption simulation and complex network invulnerability. Second, by conducting a long-term, continuous analysis of network resilience, this study explores the evolution of network resilience from a dynamic perspective, offering a fresh viewpoint for existing static network resilience studies. Therefore, based on this research, the study suggests that constructing a multi-centric development structure and strengthening coordination among industries at various nodes can effectively improve the resilience level of the industrial network. Meanwhile, it is important to focus on balancing internal and external forces in the development of urban industries to avoid excessive interference from external industries on local urban industries.

Based on the perspective of conflict of interest between low-carbon ecology and economic and social development, this study explores the change mechanism of land use cover change (LUCC) and carbon storage (CS) in the context of “Dual-Carbon” goal and territorial spatial ecological governance, which is of great significance to optimize the construction path of “Dual-Carbon” goal and formulate low-carbon, ecological, high-quality, and sustainable economic and social policies in the urban areas. An integrated framework based on the System Dynamics model, the Patch Generation Land Simulation model, and the Integrated Valuation of Ecosystem Services and Trade-offs model was constructed to dynamically simulate the LUCC demand and CS of Wenzhou under four scenarios in 2035, and to analyze the spatial evolution mechanisms of LUCC and CS. The main results of the study show that in the Natural Development Scenario (NDS) and High-speed Urbanization Scenario (HUS), the expansion mechanism is similar, and the area of woodland decreases greatly, which is mainly caused by the rapid expansion of construction land and cultivated land. Under Low-carbon and High-quality Development Scenario (LHDS) and Ecological Safety Governance Scenario (ESGS), woodland and grassland increased significantly, mainly because low-carbon and ecological governance policies strengthened ecological land protection and limited construction land control. By 2035, the prediction results show that LHDS has the highest CS (2.231 × 105 kt), followed by ESGS (2.226 × 105 kt), NDS (2.191 × 105 kt), and HUS (2.142 × 105 kt). The range of increase and decrease was 0.189, −0.149, −1.676, −3.692%, and only in LHDS, CS increased by 42.05 kt. Therefore, in order to achieve the “Dual-Carbon” goal, Wenzhou needs to prioritize the combination of LHDS and ESGS to formulate relevant policies.