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Background & Objective: To analyze whether there is an association between pre-pregnancy lipid parameters and gestational diabetes mellitus (GDM) in women undergoing assisted reproductive technologies (ART), a group especially at risk for GDM, and if so, which parameter is associated the strongest., Methods: Data was collected at the Reproductive and Genetic Hospital CITIC-Xiangya in Changsha, China from January 2017 to December 2018. The measured lipid parameters include LDL (low-density lipoprotein), HDL (high-density lipoprotein), TC (total cholesterol), and TG (triglycerides)., Results: 119 (15.5%) of the 767 patients developed GDM. On average, women who developed GDM were older, had a higher BMI, LDL, TC, and TG, and lower HDL. After adjusting for confounders, LDL and HDL showed a significant association with GDM (p < 0.05), but TC and TG did not. Binary LDL/HDL and TC/HDL ratios showed the strongest association with GDM incidence (OR 1.957 [95%CI 1.258-3.044] and 1.942 [1.243-3.034] respectively). Subgroup analysis showed that an elevated LDL/HDL ratio also increased GDM risk in subgroups with a typically lower prevalence of GDM, such as young women with a low BMI and low blood pressure. Both lipid ratios (LDL/HDL and TC/HD) show strong interactions with baseline age, fasting plasma glucose, and LH., Conclusions: In this cohort of Chinese women undergoing ART, pre-pregnancy LDL/HDL and TC/HDL were associated with GDM the strongest from the lipid parameters and could be useful to estimate GDM risk even before ART treatments and pregnancy., Clinical Trial Number: NCT03503006 registered on the 21st of March 2018 (on clinicaltrials.gov). https://clinicaltrials.gov/study/NCT03503006?locStr=Changsha,%20Hunan,%20China&country=China&state=Hunan&city=Changsha&cond=ivf&rank=2 ., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the ethical committee of the Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China (approval number: LL-SC-2018-014). All patients gave their informed consent prior to study participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The aim of this study was to introduce and assess the safety and feasibility of single incision laparoscopic totally preperitoneal hernioplasty (SIL-TPP) for bilateral inguinal hernia repair., Method: Forty-two SIL-TPP procedures for bilateral inguinal hernia repair were conducted from June 2018 to July 2022 at the First Affiliated Hospital of Ningbo University using standard laparoscopic instruments and a single-port device. Clinical data such as demographic intraoperative parameters and short-term postoperative outcomes were collected and analysed., Results: SIL-TPP was successful in 42 bilateral inguinal hernia patients, and no conversion occurred. Of these 42 patients, 38 were males and 4 were females. The average age was 57.4 ± 17 years. The participants' mean BMI was 22.67 ± 2.19 kg/m2 (range from 18.65 to 28.71 kg/m2). There were 4 types of bilateral hernias. The percentage of patients who underwent surgery before the SIL-TPP procedure in the same region was 21.43% (9/42). The mean operative time was 114 ± 34.24 min (range, 70-215 min). A total of 11 intraoperative complications occurred in 42 bilateral inguinal hernia patients, including unintentional peritoneum tears and hernia sac tears. No major complications occurred in the study. The postoperative complication rate was 2.38% (1/42). One patient experienced intestinal obstruction after the operation that resolved spontaneously without treatment. The surgical time in the SIL-TPP group decreased gradually as the number of operations increased. Moreover, the operation time trend decreased linearly (P < 0.0001, R²=0.42)., Conclusion: SIL-TPP is a safe and feasible procedure for treating bilateral inguinal hernias. The SIL-TPP procedure requires distinct skills and has specific advantages in treating bilateral hernias. Large-scale randomized controlled studies comparing SIL-TPP with conventional single-port and three-port laparoscopic TEP for bilateral inguinal hernia are needed to confirm these results., Competing Interests: Declarations. Ethics approval and consent to participate: This study is an observational, retrospective research. Patients’ written informed consent was obtained before operation. This study was approved by the Ethics Committee of The First Affiliated Hospital of Ningbo University (2024-123RS). Research involving human data was in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Pancreatic cancer is known for its poor prognosis and resistance to conventional therapies, largely due to the presence of cancer stem cells (CSCs) and aggressive angiogenesis. Effectively targeting these CSCs and associated angiogenic pathways is crucial for effective treatment. This study leverages single-cell multi-omics to explore a novel therapeutic approach involving Chimeric Antigen Receptor (CAR) macrophages engineered to target the c-Met protein on pancreatic CSCs., Methods: We employed single-cell RNA sequencing to analyze pancreatic cancer tissue, identifying c-Met as a key marker of CSCs. CAR macrophages were engineered using a lentiviral system to express a c-Met-specific receptor. The phagocytic efficiency of these CAR macrophages against pancreatic CSCs was assessed in vitro, along with their ability to inhibit angiogenesis. The in vivo efficacy of CAR macrophages was evaluated in a mouse model of pancreatic cancer., Results: CAR macrophages demonstrated high specificity for c-Met + CSCs, significantly enhancing phagocytosis and reducing the secretion of angiogenic factors such as VEGFA, FGF2, and ANGPT. In vivo, these macrophages significantly suppressed tumor growth and angiogenesis, prolonging survival in pancreatic cancer-bearing mice., Conclusion: CAR macrophages targeting c-Met represent a promising therapeutic strategy for pancreatic cancer, offering targeted elimination of CSCs and disruption of tumor angiogenesis. This study highlights the potential of single-cell multi-omics in guiding the development of precision immunotherapies., Competing Interests: Declarations. Ethical statement: All animal experiments reported in this study were approved by the Animal Ethics Committee of Jiaxing University Medical Center (Approval No. JUMC2024-087). Consent for publication: Not Applicable. Consent for publication: The authors declare that this manuscript is original, has not been published before, and is not currently being considered for publication elsewhere. All authors have approved the manuscript and agree with its submission to Molecular Medicine. Competing interests: The authors declare no competing interests. Conflict of interest: The author declares no conflict of interest., (© 2024. The Author(s).)

Background: The underlying pathogenesis of pemphigus vulgaris, an autoimmune skin disorder, remains incompletely understood. An integrative analysis comprising DNA methylation, mRNA expression, and proteomic data in patients with pemphigus vulgaris was conducted to identify potential pathogenic contributors and explore the molecular mechanisms involved in its pathogenesis., Results: The analysis revealed differentially methylated regions (DMRs) in the promoter, exon, intron, and downstream regions in the peripheral blood DNA of patients with pemphigus vulgaris. Associations between methylation levels and both transcriptomic and proteomic profiles revealed that differentially expressed genes between patients with pemphigus vulgaris and healthy controls were primarily linked to biological functions such as platelet activation and coagulation, cellular adhesion, and immunoglobulin binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis highlighted notable pathway abnormalities, including those related to platelet activation, focal adhesions, tight junctions, and infectious inflammatory responses. Notably, genes such as FGA (fibrinogen alpha chain), VWF (von Willebrand factor), and ACTG1 (actin gamma 1) were dysregulated, with a prominent role in platelet activation., Conclusion: The dysregulation of genes such as FGA, VWF, and ACTG1 suggests that alterations in their transcription and expression may contribute to the pathogenesis of pemphigus vulgaris., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted with approval from the Ethics Committee of The Second Affiliated Hospital of Kunming Medical University (No. PJ–2019-76). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: One of the main purposes of clinical treatment for adhesive shoulder capsulitis is pain relief. However, patients often fail to achieve a satisfactory therapeutic response. This study aims to evaluate the impact of a combination therapy involving buprenorphine transdermal patch and celecoxib capsules on improving shoulder pain and function of patients with primary adhesive shoulder capsulitis (ASC)., Methods: This retrospective observational study consecutively enrolled patients with primary ASC from our hospital Outpatient Department between April 2018 and June 2020. The primary outcome was pain evaluated using the visual analog scale (VAS) score. Secondary outcomes included functional improvement evaluated using the Constant-Murley Shoulder (CMS) score, as well as satisfaction and adverse reactions., Results: A total of 198 patients were enrolled and categorized into the celecoxib capsule group (n = 72), buprenorphine transdermal patch group (n = 65), and buprenorphine transdermal patch + celecoxib capsule group (n = 61). Patients treated with buprenorphine transdermal patch + celecoxib capsule have the lowest VAS scores and highest CMS scores at 1, 4, 8 and 12 weeks after treatment (all P < 0.001). Furthermore, there were no significant differences in adverse reactions (P = 0.296) among the three groups. The satisfaction of patient with percutaneous buprenorphine transdermal patch + celecoxib capsule was significantly higher than patients with celecoxib capsules or percutaneous buprenorphine transdermal patch (both P < 0.001)., Conclusion: The combination of buprenorphine transdermal patch with celecoxib capsule may result in good analgesic efficacy and functional improvement in patients with primary ASC., Trial Registration: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: This work has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. This study was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology [2019-(S913)], and the patient ‘s oral informed consent was obtained. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Failure of systemic corticosteroid therapy is common in patients with newly diagnosed acute graft-versus-host disease (aGVHD) above grade II. Mesenchymal stem cells (MSCs) have been used as a tolerable and potentially effective second-line therapy for steroid-refractory aGVHD (SR-aGVHD); however, well-designed, prospective, controlled studies are lacking., Methods: This multicentre, randomized, double-blind, placebo-controlled, exploratory phase 2 study enrolled patients with SR-aGVHD above grade II from 7 centres. Patients were randomized 1:1 to receive umbilical cord-derived MSCs or placebo added to one centre's choice of second-line agents (except for ruxolitinib). The agents were infused twice weekly. Patients with complete response (CR), no response (NR), or progression of disease (PD) at d28 received 8 infusions, and those with partial response (PR) received the above infusions for another 4 weeks. The per-protocol population consisted of patients who received ≥ 8 infusions. The primary endpoint was the overall response rate (ORR, CR + PR) at d28, analyzed in the per-protocol and intention-to-treat populations., Results: Seventy-eight patients (median age 38, range 13-62) were enrolled: 40 in the MSC group and 38 in the control. Patients in the MSC group received a median of 8 doses, with a median response time of 14 days. In intention-to-treat analysis, ORR at d28 was 60% for MSC group and 50% for control group (p = 0.375). The 2-year cumulative incidence of moderate to severe cGVHD was marginally lower in the MSC group than in the control (13.8% vs. 39.8%, p = 0.067). The 2-year failure-free survival was similar between the MSC and control groups (52.5% vs. 44.4%, p = 0.43). In per-protocol analysis (n = 62), ORR at d28 was significantly greater in the MSC group than in the control group (71.9% vs. 46.7%, p = 0.043). Among patients with gut involvement, ORR at d28 was significantly greater in the MSC group than in the control (66.7% vs. 33.3%, p = 0.031). The adverse events incidences were similar between groups., Conclusions: In this exploratory study, there was no superior ORR at d28 demonstrated in the MSC group compared with the control. However, MSCs showed a gradual treatment effect at a median of 2 weeks. Patients who completed 8 infusions may benefit from adding MSCs to one conventional second-line agent, especially those with gut involvement. MSCs was well tolerated in patients with SR-aGVHD., Trial Registration: chictr.org.cn ChiCTR2000035740., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Ethics Committee of the General Hospital of the Chinese People’s Liberation Army (C2020-016–05). Patient’s written consent to participate in this clinical trial was obtained prior to any study-specific procedures. Consent for publication: Not applicable. Competing interests: X.H. is an employee of Platinumlife Biotechnology (Beijing). The other authors have no conflicts of interest to report., (© 2024. The Author(s).)

Flue-curing and redrying are important processing stages before tobacco fermentation, closely linked to microbial actions that influence the fermentation process. It is necessary to investigate the effects of flue-curing and redrying on diversity and succession of tobacco fungal communities. It was shown that a total of 9 phyla, 33 classes, 94 orders, 266 families, 646 genera, and 6,396 amplicon sequence variants (ASVs) were identified in the fungi communities of 36 samples from different processing stages (before flue-curing, after flue-curing, before redrying and after redrying) based on high-throughput sequencing technology. Dominant genera shared by tobacco leaves at different stages were Alternaria and Sampaiozyma. About 80% of fungi in stored tobacco leaves after redrying originated from fresh tobacco leaves before flue-curing, while the rest were primarily enriched in the post-harvest processing environment. After flue-curing, major molds like Aspergillus and Penicillium were notably enriched. The distribution of fungal communities suggested that the flue-curing and redrying had a significant impact on fungal composition. Functional annotation of fungal communities at the guild level exhibited differences during processing stages. Main fungal functional groups were identified. In summary, our study elucidated dynamic changes in the composition of fungal communities and highlighted key stages in mold enrichment during tobacco leaf processing, laying groundwork for mildew prevention and control during tobacco leaf fermentation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. The license (NO. 320000000201803300010) for tobacco production and cigarette sales were obtained. Collection of plant material complied with relevant institutional, national, and international guidelines and legislation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Enterobacter ludwigii has been proven by numerous studies to be an effective plant growth promoter. Enterobacter ludwigii T977 was isolated from leaves of Nicotiana tabacum L. Yunyan 97 which showing high starch degrading ability. The optimal fermentation carbon source of strain T977 was starch, with optimal starch concentration as 2.5 g/L, and the most suitable fermentation nitrogen source for the strain T977 was ammonium acetate, with optimal concentration as 0.25 g/L. The spaying treatment of strain T977 could reduce the starch content of upper leaves from 3.77% to 1.43%, the total sugar and reducing sugar decreased slightly, the starch content of middle leaves decreased from 5.63% to 3.18%, the content of total sugar and reducing sugar increased in middle leaves, and the other chemical components were in the appropriate range. Here, we reported 4.77 MB whole genome of a starch-degrading E. ludwigii T977 that encodes 4501 proteins, 11 α-amylases in GH13 family were identified, and the amylase (GM000159) with signal peptide may play important role in degradation of starch in tobacco leaves. Our study may provide an effective microbiological mean for reducing starch content in tobacco leaves., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Rapid diagnosis of pulmonary tuberculosis (PTB) is urgently needed. We aimed to improve diagnosis rates by combining tuberculosis-interferon (IFN)-γ release assays (TB-IGRA) with metagenomic next-generation sequencing (mNGS) for PTB diagnosis., Methods: A retrospective study of 29 PTB and 32 non-TB patients from our hospital was conducted between October 2022 and June 2023. Samples were processed for TB-IGRA and mNGS tests according to the manufacturer's protocol., Results: The levels of IFN-γ release in PTB patients were significantly higher than those in non-TB patients (604.15 ± 112.18 pg/mL, and 1.04 ± 0.38 pg/mL, respectively; p < 0.0001). Regarding presenting symptoms or signs, cough and thoracalgia were less common in PTB patients than in non-TB patients (p = 0.001 and p = 0.024, respectively). Total protein and albumin levels in the sera of PTB patients were significantly elevated compared to non-TB patients (p = 0.039 and p = 0.004, respectively). The area under the ROC curve (AUC) for TB-IGRA in PTB diagnosis was 0.939. With an optimal IFN-γ cut-off value of 14.3 pg/mL (Youden's index 0.831), sensitivity was 86.2% and specificity was 96.9%. ROC curve analysis for mNGS and TB-IGRA combined with mNGS showed AUCs of 0.879 and 1, respectively. The AUC of TB-IGRA combined with mNGS was higher than that of TB-IGRA and mNGS alone., Conclusions: TB-IGRA combined with mNGS may be an effective method for diagnosing tuberculosis, and can be used in the clinical diagnosis of PTB., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the ethical research committee of the First Affiliated Hospital of Anhui Medical University (Approval No. PJ-2023-13-35) and was conducted in accordance with the Declaration of Helsinki. As the study was based on a retrospective review of anonymous medical records and did not involve patient interaction, informed consents of the patients were waived by the ethical research committee of the First Affiliated Hospital of Anhui Medical University. Consent for publication Not applicable. Clinical trial number Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Patients with migraine often experience not only headache pain but also cognitive dysfunction, particularly in attention, which is frequently overlooked in both diagnosis and treatment. The influence of these attentional deficits on the pain-related clinical characteristics of migraine remains poorly understood, and clarifying this relationship could improve care strategies., Methods: This study included 52 patients with migraine and 34 healthy controls. We employed the Attentional Network Test for Interactions and Vigilance-Executive and Arousal Components paradigm, combined with electroencephalography, to assess attentional deficits in patients with migraine, with an emphasis on phasic alerting, orienting, executive control, executive vigilance, and arousal vigilance. An extreme gradient boosting binary classifier was trained on features showing group differences to distinguish patients with migraine from healthy controls. Moreover, an extreme gradient boosting regression model was developed to predict clinical characteristics of patients with migraine using their attentional deficit features., Results: For general performance, patients with migraine presented a larger inverse efficiency score, a higher prestimulus beta-band power spectral density and a lower gamma-band event-related synchronization at Cz electrode, and stronger high alpha-band activity at the primary visual cortex, compared to healthy controls. Although no behavior differences in three basic attentional networks were found, patients showed magnified N1 amplitude and prolonged latency of P2 for phasic alerting-trials as well as an increased orienting evoked-P1 amplitude. For vigilance function, improvements in the hit rate of executive vigilance-trials were exhibited in controls but not in patients. Besides, patients with migraine exhibited longer reaction time as well as larger variability in arousal vigilance-trials than controls. The binary classifier developed by such attentional deficit features achieved an F1 score of 0.762 and an accuracy of 0.779 in distinguishing patients with migraine from healthy controls. Crucially, the predicted value available from the regression model involving attentional deficit features significantly correlated with the real value for the frequency of headache., Conclusions: Patients with migraine demonstrated significant attentional deficits, which can be used to differentiate migraine patients from healthy populations and to predict clinical characteristics. These findings highlight the need to address cognitive dysfunction, particularly attentional deficits, in the clinical management of migraine., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of the Chinese PLA General Hospital in accordance with the ethical principles of the Declaration of Helsinki (2023 − 460). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Establishing the interaction between aeroallergens and air pollution in children with house dust mite induced allergic rhinitis (HDM-AR) remains challenging, especially in urban areas. The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown measures provided a valuable opportunity., Methods: We analyzed the clinical data of HDM-AR children between March and August in 2018-2020, and classified the children according to the type and the degree of HDM sensitization. The records of patients' hospital visits, allergic rhinitis symptoms assessments, and air pollution measurements in Shanghai were used to assess the differences before (2018-2019) and during the pandemic (2020), as well as during lockdown (March-June) and unlockdown (July-August) period in 2020., Results: The study included 1570 HDM-AR children aged 2 to 8 years old, 815 (51.9%) were monosensitized to HDM (mono-HDM-AR), and 755 (48.1%) were polysensitized to HDM (poly-HDM-AR). There was a significant increase in the rate of clinical visits among children with HDM-AR during the COVID-19 pandemic compared to pre-pandemic (P < 0.001), particularly among older children aged 7-8 years (P = 0.01). During the unlockdown period, there was a notable decrease in clinical visits for children with poly-HDM-AR (P < 0.001). Children with high levels of HDM sensitization exhibited significant symptom improvement in unlockdown period (P < 0.001). Although the air pollutants concentration had improved during the study, there was no effect on the improvement of HDM-AR children as expected., Conclusions: The COVID-19 pandemic and its associated lockdown measures provided a unique context to observe the dynamics of management in children with HDM-AR. The findings underscore the complexity of managing allergic conditions in pediatric populations, highlighting the influence of environmental and lifestyle changes on disease presentation and the need for tailored approaches to treatment during periods of societal disruption., (© 2024. The Author(s).)

Purpose: Maintaining normothermia during the perioperative period is crucial for preventing complications, such as surgical site infections, prolonged hospital stays, and adverse cardiovascular events. This study aimed to elucidate methods of perioperative temperature management by integrating Western and traditional Chinese medicine (TCM) approaches. By combining advanced techniques of Western medicine with holistic and preventative practices of TCM, we aimed to provide a comprehensive strategy for effective perioperative thermal regulation., Methods: And a comprehensive literature review was conducted to analyze the causes of perioperative hypothermia and methods of perioperative temperature management from both Western and traditional Chinese medicine (TCM) perspectives. Special emphasis was placed on evaluating the underlying factors contributing to perioperative hypothermia, as well as the effectiveness, selection criteria, indications, contraindications, adverse reactions, and potential complications associated with various temperature management techniques., Results: Effective prevention and management strategies include preoperative risk assessment, physical warming measures, environmental temperature control, pharmacological interventions, perioperative temperature monitoring, comprehensive warming protocols, and postoperative warming and monitoring. Integrating traditional Chinese medicine provides additional methods to enhance overall effectiveness and patient outcomes. By combining these approaches, healthcare providers can significantly reduce the incidence of inadvertent perioperative hypothermia (IPH) and its associated complications, improving patient safety and recovery., Conclusion: For IPH, a complex and challenging medical condition, both traditional Chinese medicine and Western medicine have established their own theoretical bases and developed corresponding prevention and treatment methods. However, it is important to note that although each of these methods has unique value and potential, they also have specific indications and unavoidable limitations. Therefore, by integrating and combining the complementary strengths and resources of traditional Chinese medicine and Western medicine, we can achieve a more comprehensive and effective prevention of IPH, ultimately improving the health and well-being of those affected., (© 2024. The Author(s).)

Background: Elderly patients often experience severe pain during percutaneous kyphoplasty under local anaesthesia. The aim of this work was to evaluate the effect of lidocaine combined with esketamine on pain improvement in elderly patients receiving local anaesthesia via percutaneous kyphoplasty., Methods: This prospective, randomized comparative trial was conducted on 66 elderly patients, aged 60-80 years, with an American Society of Anaesthesiologists (ASA) grade of I-III, I‒III and a BMI of 18.5-25 kg/m 2 , who underwent single-level lumbar percutaneous kyphoplasty under local anaesthesia. Patients were divided into two equal groups (33 per group). Group LE received 200 mg of 1% lidocaine and 25 mg of esketamine (total volume of 20 ml), and Group L received 200 mg of 1% lidocaine (total volume of 20 ml). Patient characteristics, surgery, VAS scores, MAP, HR, MOAA/S scores, patient satisfaction and related adverse reactions were compared for the groups. The VAS scores during and after surgery were considered the primary outcome., Results: There were statistically significant differences in the VAS score between the two groups at the following time points: channel establishment by the puncture needle, balloon dilation, bone cement injection and postoperative period (P < 0.05). The VAS score decreased in the LE group, but the MAP and HR were more stable, and the difference was statistically significant (P < 0.05). The difference in the MOAA/S score between the two groups was statistically significant (P < 0.05), and the MOAA/S score in the LE group decreased. The patient satisfaction level in the LE group was 100% and 48.48% in the L group (P < 0.05). There were no related complications or adverse reactions in either group., Conclusion: The application of lidocaine combined with esketamine in local episcopal percutaneous vertebral kyphoplasty in elderly patients not only provides an effective analgesic effect but also improves surgical safety and patient comfort, which has important clinical value in promoting the optimization of surgical anaesthesia management in elderly patients., Trial Registration: The study was registered at Chictr.org.cn with the number ChiCTR2400083466 on 06/12/2023., (© 2024. The Author(s).)

Background: Conventional MR acceleration techniques, such as compressed sensing, parallel imaging, and half Fourier often face limitations, including noise amplification, reduced signal-to-noise ratio (SNR) and increased susceptibility to artifacts, which can compromise image quality, especially in high-speed acquisitions. Artificial intelligence (AI)-assisted compressed sensing (ACS) has emerged as a novel approach that combines the conventional techniques with advanced AI algorithms. The objective of this study was to examine the imaging quality of the ACS approach by qualitative and quantitative analysis for brain, spine, kidney, liver, and knee MR imaging, as well as compare the performance of this method with conventional (non-ACS) MR imaging., Methods: This study included 50 subjects. Three radiologists independently assessed the quality of MR images based on artefacts, image sharpness, overall image quality and diagnostic efficacy. SNR, contrast-to-noise ratio (CNR), edge content (EC), enhancement measure (EME), scanning time were used for quantitative evaluation. The Cohen's kappa correlation coefficient (k) was employed to measure radiologists' inter-observer agreement, and the Mann Whitney U-test used for comparison between non-ACS and ACS., Results: The qualitative analysis of three radiologists demonstrated that ACS images showed superior clinical information than non-ACS images with a mean k of ~ 0.70. The images acquired with ACS approach showed statistically higher values (p < 0.05) for SNR, CNR, EC, and EME compared to the non-ACS images. Furthermore, the study's findings indicated that ACS-enabled images reduced scan time by more than 50% while maintaining high imaging quality., Conclusion: Integrating ACS technology into routine clinical settings has the potential to speed up image acquisition, improve image quality, and enhance diagnostic procedures and patient throughput., (© 2024. The Author(s).)

Objective: This study aims to present a case of persistent mycetoma caused by Scedosporium boydii and undertake a systematic literature overview to elucidate the clinical characteristics and antifungal treatment exhibited by such patients., Methods: We report the case of a 24-year-old female who sustained a Scedosporium boydii infection in her right foot over a decade ago following a nail puncture. Concurrently, a comprehensive literature overview was conducted on PubMed, focusing on documented cases of Scedosporium boydii infections with the intent of extracting relevant clinical data., Results: Our analysis revealed that post-transplantation, trauma, near drowning, corticosteroid administration, and prior surgical history were the main risk factors for Scedosporium boydii infection. Prevalent infection sites included skin/bone tissues, the central nervous system, and ocular regions. Among the 49 patients identified, 24 received itraconazole therapy and 25 received voriconazole, with no significant difference in patient outcomes (P = 0.158). Of these, 12 patients experienced treatment failure. Notably, prolonged antifungal treatment duration was identified as a protective factor against mortality in Scedosporium boydii infections [P = 0.022, OR(95%CI): 0.972(0.949-0.996)]. Conversely, a history of post-transplantation emerged as a potential risk factor for mortality[P = 0.046, OR(95%CI): 7.017(1.034-47.636)]., Conclusion: While uncommon, Scedosporium boydii infections carry a significant burden of morbidity and adverse outcomes. Heightened clinical vigilance is warranted in individuals presenting with risk factors for this pathogen. Timely and effective antifungal intervention is crucial, with both voriconazole and itraconazole demonstrating positive treatment outcomes for Scedosporium boydii infection. Therefore, prioritizing these antifungal agents should be considered a key therapeutic strategy in the management of this patient population., (© 2024. The Author(s).)

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin-eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA., (© 2024. The Author(s).)

Alzheimer's disease (AD) has emerged as the most prevalent and complex neurodegenerative disorder among the elderly population. However, the genetic comorbidity etiology for AD remains poorly understood. In this study, we conducted pleiotropic analysis for 41 AD phenotypic comorbidities, identifying ten genetic comorbidities with 16 pleiotropy genes associated with AD. Through biological functional and network analysis, we elucidated the molecular and functional landscape of AD genetic comorbidities. Furthermore, leveraging the pleiotropic genes and reported biomarkers for AD genetic comorbidities, we identified 50 potential biomarkers for AD diagnosis. Our findings deepen the understanding of the occurrence of AD genetic comorbidities and provide new insights for the search for AD diagnostic markers., (© 2024. The Author(s).)

Purpose: Employees within organizations actively pursue and maintain their workplace well-being. Although there are current studies that have examined the linking inclusive leadership to employee workplace well-being, the underlying intrinsic link between the two remains unclear. On the basis of self-determination theory, this research examined the relationship between inclusive leadership, vigor, supervisor developmental feedback, and workplace well-being., Patients and Methods: Data were collected from 61 teams that totaled 342 full-time employees through a 3-stage questionnaire. Multilevel Structural Equation Modeling and Monte Carlo simulations were conducted on data for hypothesis testing., Results: Inclusive leadership positively correlated with employee workplace well-being. Employee vigor mediates the link between inclusive leadership and employee workplace well-being. Supervisor developmental feedback moderated the relationship between inclusive leadership and employee vigor., Conclusions: Inclusive leadership can improve employees' workplace well-being by stimulating their vigor. Therefore, managers need to be able to effectively meet employees' basic needs to stimulate their vigor. Based on meeting employees' basic needs, managers can also provide targeted developmental feedback to meet employees' growth needs, which can more effectively promote employees' vigor and workplace well-being., (© 2024. The Author(s).)

Background: The study aimed to identify the optimal model for predicting rectal cancer liver metastasis (RCLM). This involved constructing various prediction models to aid clinicians in early diagnosis and precise decision-making., Methods: A retrospective analysis was conducted on 193 patients diagnosed with rectal adenocarcinoma were randomly divided into training set (n = 136) and validation set (n = 57) at a ratio of 7:3. The predictive performance of three models was internally validated by 10-fold cross-validation in the training set. Delineation of the tumor region of interest (ROI) was performed, followed by the extraction of radiomics features from the ROI. The least absolute shrinkage and selection operator (LASSO) regression algorithm and multivariate Cox analysis were employed to reduce the dimensionality of radiomics features and identify significant features. Logistic regression was employed to construct three prediction models: clinical, radiomics, and combined models (radiomics + clinical). The predictive performance of each model was assessed and compared., Results: KRAS mutation emerged as an independent predictor of liver metastasis, yielding an odds ratio (OR) of 8.296 (95%CI: 3.471-19.830; p < 0.001). 5 radiomics features will be used to construct radiomics model. The combined model was built by integrating radiomics model with clinical model. In both the training set (AUC:0.842, 95%CI: 0.778-0.907) and the validation set (AUC: 0.805; 95%CI: 0.692-0.918), the AUCs for the combined model surpassed those of the radiomics and clinical models., Conclusions: Our study reveals that KRAS mutation stands as an independent predictor of RCLM. The radiomics features based on MR play a crucial role in the evaluation of RCLM. The combined model exhibits superior performance in the prediction of liver metastasis., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Background: Poly (A) binding protein interacting protein 1 (PAIP1) has been shown to causally contribute to the development and progression of cancer. However, the mechanisms of the PAIP1 regulation in tumor cells remain poorly understood., Results: Here, we used a recently developed UV cross-linking and RNA immunoprecipitation method (iRIP-seq) to map the direct and indirect interaction sites between PAIP1 and RNA on a transcriptome-wide level in HeLa cells. We found that PAIP1 not only binds to 3'UTRs, but also to pre-mRNAs/mRNAs with a strong bias towards the coding region and intron. PAIP1 binding sites are enriched in splicing enhancer consensus GA-rich motifs. RNA-seq analysis revealed that PAIP1 selectively modulates the alternative splicing of genes in some cancer hallmarks including cell migration, the mTOR signaling pathway and the HIF-1 signaling pathway. PAIP1-regulated alternative splicing events were strongly associated with PAIP1 binding, demonstrating that the binding may promote selection of the nearby splice sites. Deletion of a PAIP1 binding site containing seven repeats of GA motif reduced the PAIP1-mediated suppression of the exon 6 inclusion in a VEGFA mRNA isoform. Proteomic analysis of the PAIP1-interacted proteins revealed the enrichment of the spliceosome components and splicing factors., Conclusions: These findings suggest that PAIP1 is both a polyadenylation and alternative splicing regulator, that may play a large role in RNA processing via its role in alternative splicing regulation., (© 2024. The Author(s).)

Aim: To explore, using network pharmacology and RNA-seq technologies, potential active targets and mechanisms underpinning Radix Bupleuri's effectiveness during sepsis treatment., Methods: Following the Sepsis-3.0 criteria, the research cohort, comprising 23 sepsis patients and 10 healthy participants, was obtained from public databases. Peripheral blood samples were collected and subjected to RNA-seq analysis. Active ingredients and potential targets of Radix Bupleuri were identified using the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine 2.0 (BATMAN-TCM 2.0) database and TCMSP database. Subsequently, protein-protein interaction (PPI) network construction, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to explore cross-targets between disease and drugs. Survival analysis of key targets was performed using the GSE65682 dataset, and single-cell RNA-seq was employed for cellular localization analysis of key genes. Finally, molecular docking and Molecular dynamics simulation of the core target was conducted., Results: Differential expression analysis revealed 4253 genes associated with sepsis. Seventy-six active components and 1030 potential targets of Radix Bupleuri were identified. PPI, GO, and pathway enrichment analyses indicated involvement in the regulation of transmembrane transport, monatomic ion transport, and MAPK signaling. Survival curve analysis identified PIK3CD, ARRB2, SUCLG1, and SPI1 as key targets associated with lower mortality in the high expression group, while higher mortality was observed in the high PNP and FURIN expression groups. Single-cell RNA sequencing unveiled the cellular localization of PIK3CD, PNP, SPI1, and FURIN within macrophages, while ARRB2 and SUCLG1 exhibited localization in both macrophages and T-cells. Subsequent molecular docking and Molecular dynamics simulation indicated a potential binding interaction for Carvone-PIK3CD, Encecalin-ARRB2, Lauric Acid-SUCLG1, Pulegone-FURIN, Nootkatone-SPI1, and Saikogenin F-PNP., Conclusion: Radix Bupleuri could modulate immune function by affecting PIK3CD, ARRB2, SUCLG1, FURIN, SPI1, and PNP, thereby potentially improving the prognosis of sepsis., (© 2024. The Author(s).)

Background: The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC., Methods: The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8 + T cell isolation experiment, coculture experiment, enzyme-linked immunosorbent assay (ELISA), and flow cytometric analysis were employed to elucidate the underlying mechanism through which MED1 operates in the progression of OSCC., Results: MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8 + T cells in the tumor microenvironment., Conclusions: Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8 + T cell antitumor immunity, suggesting that MED1 may serve as a novel prognostic marker and therapeutic target in OSCC., (© 2024. The Author(s).)

Background: Abiotrophia (ABI) and Granulicatella (GRA) are rare causative pathogens in infective endocarditis (IE). This study aims to describe the epidemiology, clinical characteristics, and outcome of ABI/GRA-IE. The main features of ABI/GRA-IE were compared with Viridans group streptococci (VGS) IE., Methods: From January 2015 to December 2023, a total of 1531 definite IE in Zhongshan Hospital, Fudan University, Shanghai, China were retrospectively enrolled in this study. Clinical and laboratory data were collected., Results: Forty-five ABI/GRA-IE cases were identified, representing 2.9% of all IE cases in Zhongshan Hospital between 2015 and 2023, compared to 20.1% of VGS-IE. ABI and GRA IE shared similar clinical characteristics. Congenital valvulopathy was reported in 21 (46.7%) ABI/GRA-IE and 85 (28.8%) VGS-IE (P = 0.025). Pulmonary valve was more frequently affected in ABI/GRA-IE (6 [13.3%]) than VGS-IE (7 [2.4%]) (P = 0.002). Congestive heart failure was observed in 30 (66.7%) ABI/GRA-IE and 103 (34.9%) VGS-IE (P < 0.001). Systemic embolization excluding central nervous system (CNS) occurred in 13 (28.9%) ABI/GRA-IE and 39 (13.2%) VGS-IE (P = 0.012). In-hospital mortality was reported as 4.4% in ABI/GRA-IE and 3.7% in VGS-IE (P = 0.854)., Conclusion: GRA/ABI-IE was approximately one-seventh as prevalent as VGS-IE. Congestive heart failure and systemic embolization (excluding CNS) were more frequent in GRA/ABI-IE compared to VGS-IE. Mortality of ABI/GRA-IE in this study was comparable to that of VGS-IE and lower than previously reported results., (© 2024. The Author(s).)

Background: Macrophage pyroptosis is a pivotal inflammatory mechanism in sepsis-induced lung injury, however, the underlying mechanisms remain inadequately elucidated., Methods: Lipopolysaccharides (LPS)/adenosine triphosphate (ATP)-stimulated macrophages and cecal ligation and puncture (CLP)-induced mouse model for sepsis were established. The levels of key molecules were examined by qRT-PCR, Western blotting, immunohistochemistry (IHC) and ELISA assay. The subcellular localization of circMAPK1 was detected by RNA fluorescence in situ hybridization (FISH). Cell viability, LDH release and caspase-1 activity were monitored by CCK-8, LDH assays, and flow cytometry. The bindings between KDM2B/H3K36me2 and WNK1 promoter was detected by chromatin immunoprecipitation (ChIP) assay and luciferase assay, and associations among circMAPK1, UPF1 and KDM2B mRNA were assessed by RNA pull-down or RNA immunoprecipitation (RIP) assays. The pathological injury of lung tissues was evaluated by lung wet/dry weight ratio and hematoxylin and eosin (H&E) staining., Results: CircMAPK1 was elevated in patients with septic lung injury. Knockdown of circMAPK1 protected against LPS/ATP-impaired cell viability and macrophage pyroptosis via WNK1/NLRP3 axis. Mechanistically, loss of circMAPK1 enhanced the association between KDM2B and WNK1 promoter to promote the demethylation of WNK1 and increase its expression. CircMAPK1 facilitated KDM2B mRNA decay by recruiting UPF1. Functional experiments showed that silencing of KDM2B or WNK1 counteracted circMAPK1 knockdown-suppressed macrophage pyroptosis. In addition, silencing of circMAPK1 alleviated CLP-induced lung injury in mice via KDM2B/WNK1/NLRP3 axis., Conclusion: CircMAPK1 exacerbates sepsis-induced lung injury by destabilizing KDM2B mRNA to suppress WNK1 expression, thus facilitating NLRP3-driven macrophage pyroptosis., (© 2024. The Author(s).)

Background: Neurocognitive disorders frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities induced by preoperative cardiac structural changes. We aimed to evaluate subcortical nuclei volume changes and cognition in postoperative tetralogy of Fallot (TOF) children, and analyze their relationship with preoperative cardiac structural changes., Methods: This case-control study involved thirty-six children with repaired TOF and twenty-nine healthy controls (HCs). We utilized three-dimensional (3D) T1-weighted high-resolution structural images alongside the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) to evaluate the cognitive differences between the TOF and HC group., Results: We observed notable differences in subcortical nuclei volume between the TOF and HC group, specifically in the left amygdala nucleus (LAM, TOF: 1292.60 ± 155.57; HC: 1436.27 ± 140.62, p < 0.001), left thalamus proper nucleus (LTHA, TOF: 6771.54 ± 666.03; HC: 7435.36 ± 532.84, p < 0.001), and right thalamus proper nucleus (RTHA, TOF: 6514.61 ± 715.23; HC: 7162.94 ± 554.60, p < 0.001). Furthermore, a diminished integrity of LAM ( β:-19.828, 95% CI: -36.462, -3.193), which showed an inverse relationship with the size of the preoperative ventricular septal defect (VSD), correlated with lower working memory indices in children with TOF., Conclusions: Our findings indicate that subcortical nuclei structural injuries possibly potentially stemming from cardiac anatomical abnormalities, are associated with impaired working memory in preschool-aged children with TOF. The LAM in particular may serve as a potential biomarker for neurocognitive deficits in TOF, offering predictive value for future neurodevelopmental outcomes, and shedding light on the neurophysiological mechanisms of these cognitive impairments., (© 2024. The Author(s).)

Background: Lipid levels have been suggset to be correlated with multiple myeloma (MM) risk, though causality remains unconfirmed. To explore this further, a detailed study combining meta-analysis and Mendelian randomization (MR) was conducted., Methods: Literature searches were performed on PubMed and Embase; summary data for plasma lipid traits were extracted from the IEU and MM data from the FinnGen database. Meta-analysis and MR were utilized to analyze the link of lipids with MM risk, including mediator MR to identify potential mediators. The study was conducted in accordance with PRISMA and STROBE-MR guidelines., Results: Observational studies analyzed through meta-analysis showed that elevated levels of LDL, HDL, total cholesterol (TC), and triglycerides correlate with a lower risk of MM, with HRs of 0.73, 0.59, 0.60, and 0.84, respectively. MR analysis confirmed a potential causal link of triglyceride with a reduced MM risk (OR: 0.67, 95% CI: 0.46-0.98), independent of BMI. Mediation analysis pointed to X-11,423-O-sulfo-L-tyrosine and neuropilin-2 as potential mediators., Conclusions: The findings suggest that higher lipid levels (LDL, HDL, TC, and triglycerides) are linked with a reduced MM risk, and higher triglyceride levels are causally associated with a reduced MM risk. This suggests new avenues for therapeutic interventions targeting MM., (© 2024. The Author(s).)

Objective: To evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI K trans map, and metabolomics., Materials and Methods: 24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI K trans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research., Results: The FF ratio and K trans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P < 0.01). Nine texture feature parameters based on DCE-MRI K trans map were significantly different between the groups at the 16th week (all P < 0.05). Pathway analysis showed that diabetic bone marrow microvascular changes were mainly related to linoleic acid metabolism. Differential metabolites were correlated with the number of adipocytes, FF ratio, and permeability parameters., Conclusion: The integration of metabolomics with texture analysis based on DCE-MRI K trans map may be used to evaluate diabetic bone marrow microvascular changes at an early stage. It remains to be validated in clinical studies whether the integration of metabolomics with texture analysis based on the DCE-MRI K trans map can effectively evaluate diabetic bone marrow., (© 2024. The Author(s).)

Background: The Testis is an important reproductive organ in male mammals and the site for spermatogenesis, androgen synthesis, and secretion. Non-coding RNAs (ncRNAs) play an important regulatory role in various biological processes. However, the regulatory role of ncRNAs in the development of yak testes and spermatogenesis remains largely unclear., Result: In this study, we compared the expression profiles of circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in yak testicular tissue samples collected at 6 months (Y6M), 18 months (Y18M), and 4 years (Y4Y). Using RNA sequencing (RNA-Seq), we observed a significant difference in the expression patterns of ncRNAs in the samples collected at different testicular development stages. Twenty-two differentially expressed (DE) circRNAs, 69 DE miRNAs, and 64 DE mRNAs were detected in Y6M, Y18M, and Y4Y testicular samples, respectively. The results of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the source genes of DE circRNAs, predicted target genes of DE miRNAs, and DE mRNAs were specifically associated with signaling pathways and GO terms that were related to sperm synthesis, sperm vitality, and testicular development, such as cell cycle, Wnt signaling pathway, MAPK signaling pathway, GnRH signaling pathway, and spermatogenesis. The analysis of the circRNA-miRNA-mRNA network revealed that some DE ncRNAs, including miR-574, miR-449a, CDC42, and CYP11A1, among others, may be involved in testicular spermatogenesis. Concurrently, various circRNA-miRNA interaction pairs were observed., Conclusion: Our findings provide a database of circRNAs, miRNAs, and mRNAs expression profiles in testicular tissue of yaks at different developmental stages and a detailed understanding of the regulatory network of ncRNAs in yak testicular development and provide data that can help elucidate the molecular mechanisms underlying yak testicular development., (© 2024. The Author(s).)

The present study utilized network pharmacology to identify therapeutic targets and mechanisms of Rehmannia glutinosa in sepsis treatment. RNA-sequencing was conducted on peripheral blood samples collected from 23 sepsis patients and 10 healthy individuals. Subsequently, the RNA sequence data were analyzed for differential expression. Identification of active components and their putative targets was achieved through the HERB and SwissTarget Prediction databases, respectively. Functional enrichment analysis was performed using GO and KEGG pathways. Additionally, protein-protein interaction networks were constructed and survival analysis of key targets was conducted. Single-cell RNA sequencing provided cellular localization data, while molecular docking explored interactions with central targets. Results indicated significant involvement of identified targets in inflammation and Th17 cell differentiation. Survival analysis linked several targets with mortality rates, while molecular docking highlighted potential interactions between active components and specific targets, such as rehmaionoside a with ADAM17 and rehmapicrogenin with CD81. Molecular dynamics simulations confirmed the stability of these interactions, suggesting Rehmannia glutinosa's role in modulating immune functions in sepsis., (© 2024. The Author(s).)

Background: Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts., Results: In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver., Conclusions: These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases., (© 2024. The Author(s).)

Background: Dermatophagoides farinae proteins (DFPs) are abundantly expressed in D. farinae; however, their functions remain unknown. Our previous transcriptome sequencing analyses revealed that the basal expression of DFP1 and DFP2 in D. farinae was high and, more importantly, upregulated under temperature stress. Therefore, DFPs were speculated to exert a temperature stress response function., Results: Real-time quantitative polymerase chain reaction detection revealed that both DFP1 and DFP2 were significantly upregulated under temperature stress. Particularly, DFP1 was upregulated under cold stress. Electrophoresis of D. farinae total proteins revealed an increased abundance of DFP1 and DFP2 (40-55 kDa bands) under temperature stress, which was corroborated by the mass spectrometry results. After silencing DFP1 and DFP2 further, temperature stress led to decreases in gene expression and survival rates. Moreover, DFP1 was identified as the upstream regulator of DFP2., Conclusion: This study highlights the temperature stress response functions of DFP1 and DFP2 at the mRNA and protein levels. These results provide important insights for applying DFP1 and DFP2 as potential target genes for the molecular prevention and control of D. farinae to prevent allergic diseases. The newly established methods provide methodological guidance for the study of genes with unknown functions in mites., (© 2024. The Author(s).)

Background: Nurses represent China's largest healthcare workforce. Nurse practitioners (NPs) play an essential role in providing cost-effective quality healthcare and bridging the healthcare gaps. However, NPs are relatively new in China, and limited evidence exists on senior nurses' knowledge of and attitudes toward NPs., Aims: This study aimed to describe senior nurses' knowledge, attitudes, and perceived facilitators and barriers of NPs in China using a self-designed, culturally adaptive questionnaire., Methods: A cross-sectional online survey was conducted among 412 senior nurses in Hunan Province from December 2021 to January 2022. The Knowledge and Attitudes towards Nurse Practitioners Questionnaire (KANPQ) was developed based on the Delphi method, which included 30 items under three dimensions: knowledge (22 items), attitude (2 items), and perceived facilitators and barriers (6 items). Multivariate linear regression was conducted to explore factors associated with senior nurses' attitudes toward NPs., Results: The average KANPQ knowledge score was 68.56 ± 22.69, with 55.09%,10.20%, and 34.71% of participants showing good, moderate, and poor levels of knowledge, respectively. The average KANPQ attitude score was 7.79 ± 1.72, with 65.3% thinking NPs were necessary and 69.9% expressing willingness to become NPs. Nurses with higher professional titles and better knowledge of NPs had more positive attitudes toward NPs. The three most frequently mentioned barriers to NP implementation were patient trust, laws, and education., Conclusions: Approximately one-third of senior nurses have poor knowledge and negative attitudes toward NPs, indicating much room for improvement. Strengthening the education and training of NPs, especially among those with lower professional titles and lower knowledge of NPs, may help improve their knowledge and attitudes toward NPs. In addition, continuous political, social, economic, and individual efforts are needed to facilitate the successful development of NPs in China., (© 2024. The Author(s).)

Background: ST-elevation myocardial infarction (STEMI) is a common acute ischemia heart disease that causes serious damage to human health worldwide. Even though morbidity and mortality have significantly decreased by percutaneous coronary intervention (PCI), an additional cardiac protection strategy is still required. Acupuncture therapy has presented a dominant cardiac protection in many studies lately. Thus, we aim to evaluate the effect and safety of acupuncture as an adjunctive therapy in STEMI patients after PCI through a randomized controlled trial., Methods/design: This study describes a protocol of multicenter, double-blinded, parallel-controlled, randomized controlled trial. Ninety-six patients with STEMI aged 18-85 years who undergoing PCI will be recruited from the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, The Affiliated Third Hospital of Chengdu Traditional Chinese Medicine University/Chengdu Pidu District Hospital of Traditional Chinese Medicine, and Zhaotong Municipal Hospital of Traditional Chinese Medicine. Participants will be randomly assigned (1:1 ratio) to the verum acupuncture plus basic therapy (i.e., treatment) group or the sham acupuncture plus basic therapy (i.e., control) group. These participants will be treated for 5 days and then will be followed up for 24 weeks. Any adverse events will be recorded throughout the study to evaluate safety., Discussion: The present study aims to investigate the effect and safety of acupuncture for patients with STEMI after PCI and set up standardized treatment programs for acupuncture of these patients., Trial Registration: This study was registered in the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400081117]), on February 22, 2024., (© 2024. The Author(s).)

Background: Although immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment, only a minority of colorectal cancer (CRC) patients respond to them. Enhancing tumor immunogenicity by increasing major histocompatibility complex I (MHC-I) surface expression is a promising strategy to boost the antitumor efficacy of ICIs., Methods: Dual luciferase reporter assays were performed to find drug candidates that can increase MHC-I expression. The effect of nilotinib on MHC-I expression was verified by dual luciferase reporter assays, qRT-PCR, flow cytometry and western blotting. The biological functions of nilotinib were evaluated through a series of in vitro and in vivo experiments. Using RNA-seq analysis, immunofluorescence assays, western blotting, flow cytometry, rescue experiments and microarray chip assays, the underlying molecular mechanisms were investigated., Results: Nilotinib induces MHC-I expression in CRC cells, enhances CD8 + T-cell cytotoxicity and subsequently enhances the antitumor effects of anti-PDL1 in both microsatellite instability and microsatellite stable models. Mechanistically, nilotinib promotes MHC-I mRNA expression via the cGAS-STING-NF-κB pathway and reduces MHC-I degradation by suppressing PCSK9 expression in CRC cells. PCSK9 may serve as a potential therapeutic target for CRC, with nilotinib potentially targeting PCSK9 to exert anti-CRC effects., Conclusion: This study reveals a previously unknown role of nilotinib in antitumor immunity by inducing MHC-I expression in CRC cells. Our findings suggest that combining nilotinib with anti-PDL1 therapy may be an effective strategy for the treatment of CRC., (© 2024. The Author(s).)

Background: Increased level of stromal tumor-infiltrating lymphocytes (sTILs) are associated with therapeutic outcomes and prognosis in triple-negative breast cancer (TNBC). This study aimed to investigate the associations of clinicopathologic and sonographic features with sTILs level in TNBC., Methods: This study included invasive TNBC patients with postoperative evaluation of sTILs after surgical resection. Tumor shape, margin, orientation, echo pattern, posterior features, calcification, and vascularity were retrospectively evaluated. The patients were categorized into high-sTILs (≥ 20%) and low-sTILs (< 20%) level groups. Chi-square or Fisher's exact tests were used to assess the association of clinicopathologic and sonographic features with sTILs level., Results: The 171 patients (mean ± SD age, 54.7 ± 10.3 years [range, 22‒87 years]) included 58.5% (100/171) with low-sTILs level and 41.5% (71/171) with high-sTILs level. The TNBC tumors with high-sTILs level were more likely to be no special type invasive carcinoma (p = 0.008), higher histologic grade (p = 0.029), higher Ki-67 proliferation rate (all p < 0.05), and lower frequency of associated DCIS component (p = 0.026). In addition, the TNBC tumors with high-sTILs level were more likely to be an oval or round shape (p = 0.001), parallel orientation (p = 0.011), circumscribed or micro-lobulated margins (p < 0.001), complex cystic and solid echo patterns (p = 0.001), posterior enhancement (p = 0.002), and less likely to have a heterogeneous pattern (p = 0.001) and no posterior features (p = 0.002)., Conclusions: This preliminary study showed that preoperative sonographic characteristics could be helpful in distinguishing high-sTILs from low-sTILs in TNBC patients., (© 2024. The Author(s).)

Objective: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults., Methods: A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis., Results: Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho., Conclusion: This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels., (© 2024. The Author(s).)

Objective: Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19., Methods: Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected., Results: Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage., Conclusions: The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage., (© 2024. The Author(s).)

Purpose: This study aims to investigate the association of serum TSH with BMD in Chinese adults with normal thyroid function., Methods: These participants were divided into tertiles based on serum TSH levels. Linear regression model and multinomial logistic regression models were used to analyze the associations of continuous BMD and categorical BMD with serum TSH, respectively., Results: In women younger than 60 years, BMD decreased with the increase of TSH at normal level, while in women older than 60 years, BMD increased with the increase of TSH at normal level; besides, the BMD of women younger than 60 years old was significantly higher than that of women over 60 years old (156.05 ± 39.34 mg/cm 3 vs. 86.95 ± 29.51 mg/cm 3 , P < 0.001). Linear regression results showed negative associations of BMD and normal TSH level in women with age younger than 60 years (β=-4.34, P < 0.001), but this inverse trend was observed in women over 60 years old (β = 2.04, P = 0.041). Both in men younger than 60 years and over 60 years old, BMD decreased with the increase of TSH at normal levels; besides, the BMD of men younger than 60 years was significantly higher than those over 60 years old (143.08 ± 32.76 mg/cm 3 vs. 108.13 ± 31.99 mg/cm 3 , P < 0.001)., Conclusions: The results demonstrated an opposite trend in BMD at normal TSH levels in younger and elder females, that is, in females younger than 60 years, BMD decreased with the increase of TSH, which indicated that TSH might play a different role in younger and elder females. However, this trend was not significant in males., (© 2024. The Author(s).)

Background: Breastfeeding is widely recognized for its potential to reduce childhood obesity. However, research investigating these benefits in children breastfed for a short duration (up to 6 months) remains limited despite this being a common practice globally., Methods: This study focused on a population breastfed for 6 months or less to determine the potential benefits of short-term breastfeeding for preventing childhood obesity. Data were collected from five survey cycles of an US-based population study (the National Health and Nutrition Examination Survey (NHANES)), spanning 2009-2020. A sample of 3,211 children aged 2-6 years was selected, including 1,373 never breastfed and 1,838 ever breastfed. Logistic regression analysis examined the direct association between short-term breastfeeding and childhood obesity. Subsequent subgroup analyses were conducted. Additionally, stratified logistic regression explored the relationship between childhood obesity and the introduction of other early nutrition in both ever-breastfed and never-breastfed children., Results: Overall, breastfeeding for 6 months or less did not directly prevent childhood obesity. However, among participants with older mothers (aged 35 or above), short-term breastfeeding was associated with a lower risk of childhood obesity compared to never being breastfed (OR 0.31, 95% CI: 0.17, 0.59). Similarly, children aged 3-4 years who were breastfed for > 3 ~ 6 months exhibited a lower obesity risk (OR 0.56, 95% CI: 0.35, 0.89). In ever-breastfed children, delayed infant formula introduction was linked to a lower risk of obesity (P-trend < 0.05: introduction at age ≤ 1 vs. >1 ~ 3 vs. >3 months). Conversely, for non-breastfed children, introducing milk (other than breast milk or formula) later (≥ 12 versus < 12 months) and introducing alternatives to whole cow's milk were associated with lower obesity risks (OR 0.54, 95% CI: 0.37, 0.78; OR 0.21, 95% CI: 0.08, 0.60, respectively). Notably, these trends were not observed in ever-breastfed children., Conclusions: Short-term breastfeeding may offer some benefits in preventing childhood obesity for specific populations. Additionally, it could potentially mitigate risks associated with the introduction of formula and cow's milk at inappropriate times., (© 2024. The Author(s).)

Background and Purpose: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC)., Methods: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI., Results: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group., Conclusion: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy., (© 2024. The Author(s).)

Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases' symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential., (© 2024. The Author(s).)

Background: The Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study is a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes (T2D). The study aims to test the efficacy of a personalized behavioral approach for dietary management of moderately controlled T2D, versus a standardized behavioral intervention that uses one-size-fits-all dietary recommendations, versus a usual care control (UCC). The primary outcome will compare the impact of each intervention on the mean amplitude of glycemic excursions (MAGE)., Methods: Eligible participants are between 21 and 80 years of age diagnosed with moderately controlled T2D (HbA1c: 6.0 to 8.0%) and managed on lifestyle alone or lifestyle plus metformin. Participants must be willing and able to attend virtual counseling sessions and log meals into a dietary tracking smartphone application (DayTwo), and wear a continuous glucose monitor (CGM) for up to 12 days. Participants are randomized with equal allocation (n = 255, n = 85 per arm) to one of three arms: (1) Personalized, (2) Standardized, or (3) UCC. Measurements occur at 0 (baseline), 3, and 6 months. All participants receive isocaloric energy and macronutrient targets to meet Mediterranean diet guidelines, in addition to 14 intervention contacts over 6 months (4 weekly then 10 biweekly) to cover diabetes self-management education. The first 4 UCC intervention contacts are delivered via synchronous videoconferences followed by educational video links. Participants in Standardized receive the same educational content as those in the UCC arm, following the same schedule. However, all intervention contacts are conducted via synchronous videoconferences, paired with Social Cognitive Theory (SCT)-based behavioral counseling, plus dietary self-monitoring of planned meals using a mobile app that provides real-time feedback on calories and macronutrients. Participants in the Personalized arm receive all elements of the Standardized intervention, in addition to real-time feedback on predicted post-prandial glycemic response (PPGR) to meals and snacks logged into the mobile app., Discussion: The DiaTeleMed Study aims to address an important gap in the current landscape of precision nutrition by determining the contributions of behavioral counseling and personalized nutrition recommendations on glycemic control in individuals with T2D. The fully remote methodology of the study allows for scalability and innovative delivery of personalized dietary recommendations at a population level., Trial Registration: ClinicalTrials.gov NCT05046886. Registered on September 16, 2021., (© 2024. The Author(s).)

Background: Proteins harboring the SPX domain are crucial for the regulation of phosphate (Pi) homeostasis in plants. This study aimed to identify and analyze the entire SPX gene family within the cucumber genome., Results: The cucumber genome encompassed 16 SPX domain-containing genes, which were distributed across six chromosomes and categorized into four distinct subfamilies: SPX, SPX-MFS, SPX-EXS and SPX-RING, based on their structure characteristics. Additionally, gene duplications and synteny analysis were conducted for CsSPXs, revealing that their promoter regions were enriched with a variety of hormone-responsive, biotic/abiotic stress and typical P1BS-related elements. Tissue expression profiling of CsSPX genes revealed that certain members were specifically expressed in particular organs, suggesting essential roles in cucumber growth and development. Under low Pi stress, CsSPX1 and CsSPX2 exhibited a particularly strong response to Pi starvation. It was observed that the cucumber cultivar Xintaimici displayed greater tolerance to low Pi compared to black-spined cucumber under low Pi stress conditions. Protein interaction networks for the 16 CsSPX proteins were predicted, and yeast two-hybrid assay revealed that CsPHR1 interacted with CsSPX2, CsSPX3, CsSPX4 and CsSPX5, implying their involvement in the Pi signaling pathway in conjunction with CsPHR1., Conclusion: This research lays the foundation for further exploration of the function of the CsSPX genes in response to low Pi stress and for elucidating the underlying mechanism., (© 2024. The Author(s).)

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear., Methods: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients., Results: A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD., Conclusions: These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD., (© 2024. The Author(s).)

The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, through a critical examination of recent clinical trial data. Furthermore, we discuss the challenges posed by resistance mechanisms to these therapies and potential strategies to overcome them. We also explores the synergistic potential of combination therapies, integrating PD1/PD-L1 inhibitors with other immunotherapies, targeted therapies, and conventional modalities such as chemotherapy and radiotherapy. In addition, we examine emerging predictive biomarkers for response to PD1/PD-L1 blockade and biomarkers indicative of resistance, providing a foundation for personalized therapeutic approaches. Finally, we outline future research directions, highlighting the need for novel therapeutic strategies, deeper mechanistic insights, and the development of individualized treatment regimens. Our work summarizes the latest knowledge and progress in this field, aiming to provide a valuable reference for improving clinical efficacy and guiding future research on the application of PD1/PD-L1 inhibitors in ccRCC., (© 2024. The Author(s).)

Background: Self-directed learning ability is crucial for lifelong learning. The inadequate self-directed learning ability of nursing students in China may be due to their deficiency in self-management or learning initiative., Objective: To explore the effect of online learning platform (Tronclass) combined with team-based learning on nursing students' self-directed learning and academic performance., Design: Pretest-posttest design., Participants: From March to July 2023, 69 undergraduate third-year nursing students from a university in Hunan Province were selected through a whole-group sampling method., Methods: This study used Tronclass to carry out team-based learning in the teaching process of pediatric nursing courses. It compared the self-directed learning ability nursing students before and after courses, and juxtaposed their academic performance with those of their counterparts who graduated in previous years., Results: When comparing compare motivation, self-management, teamwork and information literacy, which are four subscale aspects of the self-directed Learning Ability Scale, the post-survey scores for these four dimensions are greater than the pre-survey results. The results of the study showed a statistically significant difference (P < 0.05), in the students who engaged in Tronclass combined with team-based learning. Specifically, these students received higher midterm and final grades than to those who had already graduated and did not participate in these activities. (P < 0.05)., Conclusion: Combining Tronclass with team-based learning enhances nursing students' ability to engage in self-directed learning and improves their performance in midterms and finals, thereby fostering the development of comprehensive competence., (© 2024. The Author(s).)