miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Dual-emission red carbon dots for ATP real-time monitoring and quantification to reveal drug and cancer effects on lysosomes.

Monitoring and quantifying ATP levels in vivo is essential to understanding its role as a signaling molecule in tumor progression and therapy. Nevertheless, the real-time monitoring and quantitative assessment of lysosomal ATP remains challenging due to the lack of accurate tools in deep tissues. In this study, based on the crosslinking enhanced emission (CEE) effect, we successfully synthesized red carbon dots (R-CDs) with dual emission properties for efficient quantification of intracellular ATP. The R-CDs emit in the near-infrared range and target lysosomes with rapid detection capabilities, rendering them exceptionally well-suited for directly observing and analyzing the dynamics of lysosomal ATP through live cell imaging techniques. Importantly, R-CDs have proven their efficacy in real-time monitoring of drug stimulus-induced fluctuations in endogenous lysosomal ATP concentration and have also been employed for quantifying and distinguishing lysosomal ATP levels among normal and cancer cell lines. These noteworthy findings emphasize the versatility of the R-CD as a valuable imaging tool for elucidating the functional role of lysosomal ATP in drug screening and cancer diagnostics and hold the promise of becoming a reference tool for deepening our understanding of drug mechanisms of action.

Effect of Group Cognitive Behavioral Therapy on Patients with Early-Onset Schizophrenia.

Objective: To study the clinical effect of group cognitive behavioral therapy to one-on-one treatment on patients with early-onset schizophrenia. Methods: Totally,133 patients with early-onset schizophrenia admitted to the Department of Psychiatry of our hospital from September 2020 to September 2023 were selected and divided into a control group and an observation group according to whether group behavioral cognitive therapy was performed. The general demographic data of the patients were collected, and the propensity score matching method was used to balance the baseline data of the 2 groups. The Positive and negative syndrome scale, Personal and Social Performance Scale, severity of illness (SI), and efficacy index (EI) were compared between the 2 groups after matching. Results: After matching, 72 patients were included in our study. Compared to the control group, observation group PANSS score were decreased including after intervention (P > .05). Both groups showed a decrease between before and after treatments. Positive and Negative Syndrome Scale reduction rate after treatment and total response rate were increased in the observation group (P <.001). Personal and Social Performance Scale of the Clinical Global Impression (CGI) scores were higher than those of the control group. In the CGI scores, there is a significant difference that SI scores were lower in the observation group (P = .002), while EI scores were higher (P <.001). Conclusion: Group cognitive behavioral therapy is beneficial to the improvement of mental symptoms and disease severity, social function, and curative effect, which is advocated and popularized.

Global research status and trends of interactions between Traditional Chinese medicine and pulmonary fibrosis: A new dawn in treatment.

Background: Pulmonary fibrosis (PF) remains a major sequela of COVID-19, yet its pharmacotherapy remains unsatisfactory. Recently, Traditional Chinese medicine (TCM) has garnered increasing recognition among patients and researchers because of its few side effects and efficacy. The objective of this study is to use bibliometric analysis to explore the current research landscape and emerging trajectories of TCM treating PF(TCM/PF) researches, and comprehensively evaluate publications with substantial citations within the domain of TCM/PF. Materials and methods: TCM/PF publications from 1996 to June 15, 2023 were identified by a comprehensive search of the Web of Science Core Collection (WoSCC). The Bibliometrix of Origin, CiteSpace, Gephi, dycharts and VOSviewer were used for bibliometric analysis. Results: A total of 358 papers were included. A rapid increase in the number of papers after 2013 was observed. China had the highest publication output and research contributions in this field. Beijing University of Traditional Chinese Medicine and Nanjing University of Traditional Chinese Medicineare leaders in productive research of this field. Nanjing University of Traditional Chinese Medicine had the highest citations (227). LI JIANSHENG from Henan University of Chinese Medicine was the most prolific author (8), with the highest number of citations (61), and TONG XIAO LIN from China Academy of Chinese Medical Sciences had the highest H-index (30). The leading journal publishing the most research (37) is Frontiers in Pharmacology and the Journal of Ethnopharmacology had the highest total citations (486). Burst analysis of keywords revealed three distinct phases of research. 1996 to 2013 marked the nascent stage of TCM/PF research; from 2014 to 2018, studies gradually focused on the underlying mechanisms governing TCM/PF. The most significant phase occurred from 2019 onward, where TCM/PF exhibited an explosive growth trend. This progression signifies a transition from foundational explorations to a comprehensive understanding of the mechanisms involved, ultimately leading to the current surge in research activities focused on TCM/PF. Notable research teams of this stage, led by LI JIAN SHENG and TONG XIAO LIN, have been at the forefront of advancing TCM/PF research. Their studies on Jinshui Huanxian formula and Qimai Feiluoping decoction have been pivotal in advancing the frontier of research in this domain. Furthermore, the monomeric compounds, including emodin, curcumin, salvianolic acid, baicalin, and oxymatrine, have sustained longstanding prominence. Conclusions: This study gained insight into the research status, focal areas and evolving trends of global TCM/PF research. It also identified the most cited articles in TCM/PF and analyzed their characteristics, which may hold significant relevance for both clinical researchers and practitioners on future directions in this field.

Isoliensinine activated the Nrf2/GPX4 pathway to inhibit glutamate-induced ferroptosis in HT-22 cells.

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate-induced injury model of mouse hippocampal neurons HT-22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate-induced HT-22 cells. The results showed that ISO inhibited glutamate-induced ferroptosis of neuronal cells through nuclear factor E2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT-22 cells with ISO significantly reduced glutamate-induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long-chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT-22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT-22 cells was increased, and the expression of downstream heme oxygenase-1 protein was upregulated. In summary, ISO protects HT-22 cells from glutamate-induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway.

Esketamine vs. placebo combined with erector spinae plane block vs. intercostal nerve block on quality of recovery following thoracoscopic lung resection: A randomized controlled factorial trial.

BACKGROUND: Multimodal analgesic strategy is pivotal for enhanced recovery after surgery. The objective of this trial was to assess the effect of subanesthetic esketamine vs. placebo combined with erector spinae plane block (ESPB) vs. intercostal nerve block (ICNB) on postoperative recovery following thoracoscopic lung resection. MATERIALS AND METHODS: This randomized, controlled, 2×2 factorial trial was conducted at a university hospital in Suzhou, China. One hundred adult patients undergoing thoracoscopic lung surgery were randomized to one of four groups (esketamine-ESPB, esketamine-ICNB, placebo-ESPB, and placebo-ICNB) to receive i.v. esketamine 0.3 mg/kg or normal saline placebo combined with ESPB or ICNB using 0.375% ropivacaine 20 mL. All patients received flurbiprofen axetil and patient-controlled fentanyl. The primary outcome was quality of recovery (QoR) at 24 h postoperatively, assessed using the QoR-15 scale, with a minimal clinically important difference of 6.0. RESULTS: The median age was 57 years and 52% were female. No significant interaction effect was found between esketamine and regional blocks on QoR (P=0.215). The QoR-15 score at 24 h was 111.5±5.8 in the esketamine group vs. 105.4±4.5 in the placebo group (difference=6.1, 95% CI, 4.0-8.1; P<0.001); 109.7±6.2 in the ESPB group vs. 107.2±5.6 in the ICNB group (difference=2.5, 95% CI, 0.2-4.9; P=0.033; not statistically significant after Bonferroni correction). Additionally, esketamine resulted in higher QoR-15 scores at 48 h (difference=4.6) and hospital discharge (difference=1.6), while ESPB led to a higher QoR-15 score at 48 h (difference=3.0). CONCLUSIONS: For patients undergoing thoracoscopic lung resection, subanesthetic esketamine improved QoR after surgery, while ICNB can be used interchangeably with ESPB as a component of multimodal analgesia.

Bioinspired Microgel-Loaded Smart Membrane Filtration with the Thermo- and Ion-Dual Responsive Water Gate for Selective Lead(II) Separation.

Lead (Pb2+) is a ubiquitous pollutant. Membrane filtration represents one of the most common water treatment methods, but nanofiltration and ultrafiltration require high transmembrane pressure, while microfiltration has larger pore sizes than ions, making them unfavorable for direct ion removal at low cost. Selective and direct separation of Pb2+ via membrane filtration at high efficiency without sacrificing the flux of clean water still remains challenging. Herein, inspired by the Pb2+-tolerable oleander that enriches and prevents Pb2+ in roots from permeating the plant body, a smart Pb2+-adsorptive filtration membrane with a temperature- and ion-tunable water gate was prepared by loading dual-responsive poly(N-isopropylacrylamido-co-acrylamido-benzo-18-crown-6) (PNB-5-20) microgels onto a commercial membrane. The PNB-5-20 microgel exhibits pronounced temperature-responsive swelling/deswelling (hydrodynamic diameter, 650-330 nm) with a volume phase transition temperature (VPTT) at ∼33 °C. Moreover, the microgel shows a high Pb2+-adsorption capacity (qmax, 85.4 mg/g) and good selectivity (distribution coefficient Kd ∼ 1000 mL/g) thanks to its complexation with the crown ether, as well as good Pb2+ responsiveness, having the VPTT positively shifted to 40 °C in the presence of Pb2+ with enhanced swelling behaviors. Functionalized with PNB-5-20, the smart membrane integrates Pb2+ detection, adsorption, and tunable water drainage in a single device. The membrane selectively recognizes Pb2+ in the polluted water with the gates in membrane pores switching from "open" to "closed", intercepting and adsorbing Pb2+ with water permeation reduced. Once purified, the gates can be "re-opened" by increasing the temperature. Construction of such an intelligent membrane filtration device with a tunable water gate and excellent Pb2+ recognition and adsorption performance will greatly simplify the remediation of Pb2+-polluted water.

[Causal relationship between relative abundance of gut microbiota and teratozoospermia: A two-sample Mendelian randomization analysis].

OBJECTIVE: To explore the potential causal relationship between gut microbiota and teratozoospermia. METHODS: We searched the database of Genome-Wide Association Study (GWAS) for gut microbiota- and teratozoospermia-related data. We used gut microbiota as an exposure factor, determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance, and derived the outcome variables from the European data on teratozoospermia, with a sample size of 85 716, including 915 cases and 209 006 controls. Using inverse-variance weighting (IVW), MR-Egger regression and the weighted median estimator (WME), we performed two-sample Mendelian randomization (MR) analysis on the retrieved data, and estimated the causal relationship between gut microbiota and teratozoospermia based on the ß value. RESULTS: Two-sample MR analysis indicated that the class Erysipelotrichia, family Erysipelotrichaceae, family Streptococcaceae, genus Coprococcusl, genus Ruminococcaceae UCG009, genus Streptococcus, order Clostridialesm and order Erysipelotrichales were causally related with the increased risk, while the family Porphyromonadaceae with the decreased risk of teratozoospermia. CONCLUSION: The class Erysipelotrichia, family Erysipelotrichaceae, family Streptococcaceae, genus Coprococcusl, genus Ruminococcaceae UCG009, genus Streptococcus, order Clostridialesm and order Erysipelotrichales are one of the causes of teratozoospermia, related to the increased risk of the condition, while the family Porphyromonadaceae has a protective effect on sperm morphology, reducing the risk of teratozoospermia.

Unveiling the multifaceted role of adropin in various diseases (Review).

Adropin is a secreted peptide encoded by the energy homeostasis­associated gene, which also functions as a membrane­bound protein facilitating intercellular communication. This peptide has been detected in various tissues and body fluids, including the brain, liver, kidney, heart, pancreas, small intestine, endothelial cells and colostrum. Notably, the amino acid sequences of adropin are identical in humans, mice and rats. Previous studies have demonstrated that adropin levels fluctuate under different physiological and pathological conditions. Adropin plays a role in regulating carbohydrate metabolism, lipid metabolism and intercellular molecular signaling pathways, implicating its involvement in the progression of numerous diseases, such as acute myocardial infarction, lung injury, non­alcoholic fatty liver disease/non­alcoholic steatohepatitis, kidney disease, polycystic ovary syndrome, obesity, and diabetes, atherosclerosis, systemic sclerosis and cancer. Despite its significance, the precise role and mechanism of this protein remain inadequately understood and studied. To elucidate the function of adropin and its clinical research status, a systematic review of recent studies on adropin across various diseases was conducted. Additionally, several challenges and limitations associated with adropin research in both animal and clinical contexts were identified, aiming to offer valuable insights for future investigation.

Development of a hybrid rhodamine-hydrazine NIR fluorescent probe for sensitive detection and imaging of peroxynitrite in necrotizing enterocolitis model.

This study describes the synthesis and characterization of a novel near-infrared (NIR) fluorescent probe RBNE based on a hybrid rhodamine dye, which shows excellent optical capability for detecting and imaging ONOO- in necrotizing enterocolitis (NEC) mouse model. The probe RBNE undergoes hydrazine redox-process, and subsequently the spirocyclic structure's opening, resulting in a turn-on fluorescence emission with the presence of ONOO-, which exhibits several excellent features, including a significant Stokes shift of 108 nm, near-infrared emission at 668 nm, a lower detection limit of 56 nM, low cytotoxicity, and excellent imaging ability for ONOO- both in vitro and in vivo. The presented study introduces a novel optical tool that has the potential to significantly advance our understanding of peroxynitrite (ONOO-) behaviors in necrotizing enterocolitis (NEC).

Targeted-lung delivery of bardoxolone methyl using PECAM-1 antibody-conjugated nanostructure lipid carriers for the treatment of lung inflammation.

The effective treatment of acute lung injury (ALI) remains a significant challenge. Patients with ALI demonstrate an abundance of proinflammatory mediators in both bronchoalveolar lavage fluid (BALF) and circulating plasma. Bardoxolone methyl (BM) is a semi-synthetic triterpenoid derived from oleanolic acid, a natural product known for its ability to inhibit proinflammatory signaling. GSDMD is a signaling protein involved in pyroptosis, a form of programmed cell death. It has been reported that its upstream proteins play a role in the pathogenesis of ALI. However, there is currently no research examining whether the effect of BM on the occurrence and development of ALI is associated with changes in GSDMD protein. In this study, we prepared nanostructured lipid carriers loaded with BM and conjugated with anti-PECAM-1 antibody (PECAM@BM NLCs). PECAM@BM NLCs were designed to specifically bind to pulmonary vascular endothelial cells that highly express the PECAM-1 receptors. We also aimed to investigate the protective effects of PECAM@BM NLCs on ALI and elucidate the underlying molecular mechanisms. The results demonstrated that PECAM@BM NLCs accumulated in the lung tissues and significantly alleviated the inflammatory injury of ALI. This was evidenced by the changes in the lung wet/dry ratio, the total protein concentration, proinflammatory cytokines in BALF, and the histopathological progress. Additionally, we elucidated that PECAM@BM NLCs had the ability to inhibit the assembly of NLRP3 inflammasome and pro-caspase-1 complex, thereby suppressing the induction of pyroptosis. This mechanism resulted in the inhibition of N-terminal GSDMD expression and effectively prevented the progression of ALI.

Multifunctional bio-nanocomposite films integrated with essential oils@metal-phenolic network nanocapsules for durable fruit preservation.

Food spoilage exacerbates global hunger and poverty, necessitating urgent advancements in food shelf life extension methodologies. However, balancing antibacterial efficacy for food preservation with human and environmental safety remains a significant challenge. Natural essential oils (EOs), known for their potent antibacterial and antioxidant properties, offer eco-friendly alternatives, yet their high volatility and instability limit practical applications. Herein, we conducted the encapsulation of EOs within biocompatible metal phenolic networks (MPNs) to create EOs@MPN nanocapsules. Subsequently, these nanocapsules were integrated into bio-nanocomposite films composed of natural soy protein isolate (SPI) and carboxymethyl cellulose (CMC). The resulting films exhibited robust mechanical properties (Tensile Strength >10 MPa) and significantly enhanced antioxidant activity (7-fold higher than pure films). Importantly, the synergistic combination of EOs and MPNs conferred enhanced antibacterial efficacy. Safety assessments confirmed the bio-nanocomposite films' high biodegradability (> 90 %) and negligible cytotoxicity, ensuring environmental sustainability and human health safety. In practical applications, the bio-nanocomposite films effectively delayed the surface browning of fresh-cut fruits for up to 48 h, demonstrating a pronounced synergistic antioxidative effect against oxidation. Moreover, tomatoes and blueberries packaged with the bio-nanocomposite films still maintained freshness for up to 12 days, offering promising strategies for extending the shelf life of perishable fruits. These findings underscore the potential of EOs@MPN-based bio-nanocomposite films as sustainable solutions for food preservation and highlight their practical viability in mitigating food spoilage and enhancing food security globally.

Characteristics of regional lymph node metastasis in breast cancer and construction of a nomogram model based on ultrasonographic analysis: a retrospective study.

OBJECTIVE: The ultrasonographic characteristics of lymph node metastasis in breast cancer patients were retrospectively analyzed, and a predictive nomogram model was constructed to provide an imaging basis for better clinical evaluation. METHODS: B-mode ultrasound was used to retrospectively analyze the imaging characteristics of regional lymph nodes and tumors. Pathological examination confirmed the presence of lymph node metastasis in breast cancer patients. Univariable and multivariable logistic regression analyses were performed to analyze the risk factors for lymph node metastasis. LASSO regression analysis was performed to screen noninvasive indicators, and a nomogram prediction model was constructed for breast cancer patients with lymph node metastasis. RESULTS: A total of 187 breast cancer patients were enrolled, including 74 patients with lymph node metastasis in the positive group and 113 patients without lymph node metastasis in the negative group. Multivariate analysis revealed that pathological type (OR = 4.58, 95% CI: 1.44-14.6, p = 0.01), tumor diameter (OR = 1.37, 95% CI: 1.07-1.74, p = 0.012), spiculated margins (OR = 7.92, 95% CI: 3.03-20.67, p < 0.001), mixed echo of the breast tumor (OR = 37.09, 95% CI: 3.49-394.1, p = 0.003), and unclear lymphatic hilum structure (OR = 16.07, 95% CI: 2.41-107.02, p = 0.004) were independent risk factors for lymph node metastasis. A nomogram model was constructed for predicting breast cancer with lymph node metastasis, incorporating three significantly correlated indicators identified through LASSO regression analysis, namely, tumor spiculated margins, cortical thickness of lymph nodes, and unclear lymphatic hilum structure. The receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.717 (95% CI, 0.614-0.820) for the training set and 0.817 (95% CI, 0.738-0.890) for the validation set. The Hosmer-Lemeshow test results for the training set and the validation set were p = 0.9148 and p = 0.1648, respectively. The prediction nomogram has good diagnostic performance. CONCLUSIONS: B-mode ultrasound is helpful in the preoperative assessment of breast cancer patients with lymph node metastasis. The predictive nomogram model, which is based on logistic regression and LASSO regression analysis, is clinically safe, reliable, and highly practical.

External validation of a novel nomogram for diagnosis of Protein Energy Wasting in adult hemodialysis patients.

Background: Protein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients. Methods: The novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility. Results: From September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741-0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p > 0.05). Conclusion: Our results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.

Assessment of early factors for identification or prediction severe acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is a rare and serious condition, and severe APIP (SAPIP) can lead to pancreatic necrosis, abscess, multiple organ dysfunction, and other adverse maternal and infant outcomes. Therefore, early identification or prediction of SAPIP is important. AIM: To assess factors for early identification or prediction of SAPIP. METHODS: The clinical data of patients with APIP were retrospectively analyzed. Patients were classified with mild acute pancreatitis or severe acute pancreatitis, and the clinical characteristics and laboratory biochemical indexes were compared between the two groups. Logical regression and receiver operating characteristic curve analyses were performed to assess the efficacy of the factors for identification or prediction of SAPIP. RESULTS: A total of 45 APIP patients were enrolled. Compared with the mild acute pancreatitis group, the severe acute pancreatitis group had significantly increased (P < 0.01) heart rate (HR), hemoglobin, neutrophil ratio (NEUT%), and neutrophil-lymphocyte ratio (NLR), while lymphocytes were significantly decreased (P < 0.01). Logical regression analysis showed that HR, NEUT%, NLR, and lymphocyte count differed significantly (P < 0.01) between the groups. These may be factors for early identification or prediction of SAPIP. The area under the curve of HR, NEUT%, NLR, and lymphocyte count in the receiver operating characteristic curve analysis was 0.748, 0.732, 0.821, and 0.774, respectively. The combined analysis showed that the area under the curve, sensitivity, and specificity were 0.869, 90.5%, and 70.8%, respectively. CONCLUSION: HR, NEUT%, NLR, and lymphocyte count can be used for early identification or prediction of SAPIP, and the combination of the four factors is expected to improve identification or prediction of SAPIP.

The significance of different intervertebral spaces in combined spinal epidural anesthesia in cesarean section.

BACKGROUND: The number of cesarean sections performed is increasing every year, and obstetric anesthesia is of great interest to physicians and research scholars because of its specificity, high risk, and high complication rate. OBJECTIVE: To investigate the effects of combined spinal epidural anesthesia (CSEA) with different intervertebral spaces during cesarean section on anesthesia effect, anesthesia onset time, anesthesia recovery time, maternal adverse reactions, and neonates. METHODS: Ninety-two women who underwent cesarean section in our hospital from September 2022 to February 2023 were selected as the study subjects and randomly divided them into two groups (group A and group B), 46 women in each group. Group A underwent CSEA via an L2-3 gap and group B underwent CSEA via an L3-4 gap puncture. The anesthesia effect, anesthesia onset time, sensory recovery time, adverse effects, and neonatal Apgar score were compared between the two groups. RESULTS: When CSEA was performed from L2-3, the anesthesia efficiency was higher, but the difference was not statistically significant. When anesthesia was performed by puncture from L2-3, the onset of anesthesia and recovery time was shorter, and the incidence of intraoperative maternal nausea and vomiting, hypotension, respiratory depression, and other adverse reactions was low with a statistically significant difference. However, the Apgar scores of the neonates in the two groups have no difference. CONCLUSIONS: When CSEA is induced via L2-3 interspace, anesthesia has a rapid onset of action, shorter recovery time, and few maternal adverse effects, without affecting the final anesthetic outcome.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

Cell membrane patches transfer CAR molecules from a cellular depot to conventional T cells for constructing innovative fused-CAR-T cells without necessitating genetic modification.

Chimeric antigen receptor (CAR) serves as the foundational element of CAR-T cells. Exogenous CAR molecules can exert functional effects on allogeneic T cells, leading to their activation and subsequent functional alterations. Here we show a new method based on this biological principle: the transfer of CAR molecules from exogenous cells to the membrane of receptor T cells. This process facilitates receptor T cell to recognize target antigens and induces their activation. These patches imbued normal T cells with enhanced tumor targeting capabilities and activated their inherent killing functions. This method's efficacy introduces an approach for constructing non-genetically manipulated CAR-T cells and holds potential for application to other immune cells.

Pulsed electromagnetic fields potentiate bone marrow mesenchymal stem cell chondrogenesis by regulating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). PURPOSE: To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. METHODS: BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1ß. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. RESULTS: BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/ß-catenin signaling, regardless of IL-1ß presence or duration of exposure. This inhibition of the Wnt/ß-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. CONCLUSIONS: PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/ß-catenin signaling, irrespective of inflammatory conditions.