Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations.

Limited knowledge is available on the differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody breadth and T cell differentiation among different COVID-19 sequential vaccination strategies. In this study, we compared the immunogenicity of the third different dose of COVID-19 vaccines, such as mRNA (I-I-M), adenoviral vector (I-I-A), and recombinant protein (I-I-R) vaccines, in terms of the magnitude and breadth of antibody response and differentiation of SARS-CoV-2-specific T and B cells. These studies were performed in the same clinical trial, and the samples were assessed in the same laboratory. IGHV1-69, IGHV3-9, and IGHV4-34 were the dominant B cell receptor (BCR) usages of the I-I-M, I-I-A, and I-I-R groups, respectively; the RBD+ B cell activation capacities were comparable. Additionally, the I-I-R group was characterized by higher numbers of regulatory T cells, circulating T follicular helper cells (cTFH) - cTFH1 (CXRC3+CCR6-), cTFH1-17 (CXRC3+CCR6+), cTFH17 (CXRC3-CCR6+), and cTFH-CM (CD45RA-CCR7+), and lower SMNE+ T cell proliferative capacity than the other two groups, whereas I-I-A showed a higher proportion and number of virus-specific CD4+ T cells than I-I-R, as determined in ex vivo experiments. Our data confirmed different SARS-CoV-2-specific antibody profiles among the three different vaccination strategies and also provided insights regarding BCR usage and T/B cell activation and differentiation, which will guide a better selection of vaccination strategies in the future. IMPORTANCE: Using the same laboratory test to avoid unnecessary interference due to cohort ethnicity, and experimental and statistical errors, we have compared the T/B cell immune response in the same cohort sequential vaccinated by different types of COVID-19 vaccine. We found that different sequential vaccinations can induce different dominant BCR usage with no significant neutralizing titers and RBD+ B-cell phenotype. Recombinant protein vaccine can induce higher numbers of regulatory T cells, circulating TFH (CTFH)1, CTFH17, and CTFH-CM, and lower SMNE+ T-cell proliferative capacity than the other two groups, whereas I-I-A showed higher proportion and number of virus-specific CD4+ T cells than I-I-R. Overall, our study provides a deep insight about the source of differences in immune protection of different types of COVID-19 vaccines, which further improves our understanding of the mechanisms underlying the immune response to SARS-CoV-2.

Effect of fibroblasts small- conductance Ca2+ -activated potassium channel subtype 2 (SK2) on myocardial fibrosis in pressure overload mouse.

Studies have shown that Small conductance Ca2 + -activated K+ (SK) channel are expressed in fibroblasts. We aimed to determine the expression of SK2 channels in cardiac fibroblasts during myocardial hypertrophy and investigate its relationship with fibrotic remodeling. Myocardial hypertrophy and fibrotic remodeling induced by transverse aortic constriction (TAC) were assessed by echocardiography, Masson's trichrome staining and Western blot. Knockdown and overexpression of the SK2 protein were used to assess relationship between SK2 expression in fibroblasts and myocardial fibrosis. There is a positive correlation between myocardial fibrosis and SK2 channel protein expression during the development of myocardial hypertrophy. The differentiation and secretion of fibroblasts in mice with cardiac hypertrophy are enhanced, and the expression of SK2 channel protein is increased. Manipulating SK2 levels in fibroblasts can either promote or inhibit their differentiation and secretory function. Knocking down SK2 reduces the up-regulation of TGF ß1, p-Smad2/3/GAPDH, p-p38/GAPDH, p-ERK1/2/GAPDH, and p-JNK/GAPDH proteins induced by Ang II in cardiac fibroblasts without significantly affecting total protein levels. AAV9-SK2-RNAi injection in mice improves cardiac function. Collectively, our study suggests that the expression of the SK2 channel is significantly increased in fibroblasts of mice with myocardial hypertrophy, potentially impacting myocardial fibrosis remodeling via the TGF-ß signaling pathway.

Case report: is necrotizing fasciitis in a rectal cancer patient after targeted systemic therapy related to the tumor site? - evidence from a hepatocellular carcinoma patient.

Necrotizing fasciitis (NF) is a rare and life-threatening serious infectious disease, characterized by acute onset and rapid progress, leading to extensive necrosis of skin, soft tissue as well as fascia by a variety of aerobic and anaerobic bacteria, localized on external genitalia, scrotum, groin and perianal areas in males. There exist numerous common etiologies for NF, yet NF induced by malignant neoplasms is exceedingly rare. Several studies have reported that NF may be associated with tumor site (rectal/sigmoid colon cancer) and blood supply dysfunction caused by targeted therapy drugs (bevacizumab, aflibercept, ramucirumab). The perforation of colorectal cancer poses a unique risk factor for NF. However, in our two cases, the patient with rectal cancer received CapeOX (oxaliplatin + capecitabine) + bevacizumab + tislelizumab for 3 cycles without perforation but did develop NF. One month after debridement, the patient continued immunotherapy with tislelizumab alone for the fourth cycle and maintained for an additional 3 cycles without any recurrence of NF. Therefore, does the occurrence of NF correlate with the tumor site (rectum) and targeted immunotherapy? Another patient with hepatocellular carcinoma also developed NF after receiving 2 cycles of lenvatinib + sintilimab treatment. The third cycle of sintilimab immunotherapy was administered on the 13th day after operation, which was subsequently maintained for an additional 2 cycles without recurrence of NF. The absence of a direct correlation between hepatocellular carcinoma and rectal tumor location as well as immunotherapy, suggests that NF may be closely linked to targeted therapy.

Case report: A clinical report of photodynamic neoadjuvant combined with fluorescent laparoscopic localization robotic surgery for the treatment of patients with advanced colorectal cancer combined with obstruction.

The incidence of colorectal cancer is relatively high in our country, with the majority of patients being diagnosed at an advanced stage. For individuals with advanced-stage colorectal cancer, conversion or neoadjuvant therapy is frequently necessitated to facilitate surgical intervention and achieve a curative effect. And about 10% to 30% of colon cancer patients are complicated with intestinal obstruction. Surgical intervention remains the primary treatment for managing intestinal obstructions, albeit with a considerable risk of perioperative mortality and an increased likelihood of postoperative complications. PDT, as a neoadjuvant treatment for colon cancer, can shrink the local tumor and relieve obstruction, and is effective in colon cancer combined with obstruction. Robotic surgery has the advantages of high stability and low trauma, and compared with laparoscopic colon cancer surgery, robotic surgery can achieve better results. Fluorescent laparoscopic clarifies the location and size of the tumor lesion, allowing for greater precision when removing colon cancer lesions in robotic surgery. Therefore, in the treatment of colon cancer, PDT can offer an opportunity for surgery after relieving obstruction in patients with obstructive colon cancer. Additionally, when combined with fluorescent laparoscopic robotic colon cancer surgery, it provides a novel treatment approach for patients with obstructive colon cancer. Preoperative photodynamic neoadjuvant therapy combined with robotic colon cancer surgery has not yet been reported. Here, we report a case of colon cancer with obstruction, preoperative TNM stage was T4N1, and the lesion had caused intestinal stenosis. After four sessions of PDT, the patient's intestinal lumen was unobstructed and the lesion had regressed. After evaluation, fluorescent laparoscopic localization and visualization of lymph nodes combined with robotic colon cancer resection were performed. Postoperative pathology showed that the patient's tumor regression grade was grade 1. The patient's tumor was completely resected with good resection effect. No tumor invasion was found on both sides of the resection margin, and the patient did not relapse after surgery.

Research on the impacts of digital economy on carbon emission efficiency at China's City level.

As a new type of economic format, digital economy has three major characteristics: technical, innovative, energy-saving and environmentally friendly. Acting on various sectors of the national economy, it is beneficial for improving carbon emission efficiency and is of great significance for achieving China's two major goals of carbon peak and carbon neutrality. Firstly, theoretical analysis of the impact mechanism of digital economy on carbon emission efficiency, proposing research hypotheses on the direct effect, mediating effect, and spatial effect of digital economy on carbon emission efficiency. Secondly, based on panel data from 279 cities in China from 2011 to 2020, the econometric models are constructed to empirically analyze the direct, mediating, and spatial effects of digital economy on carbon emission efficiency. The results show that: 1) Digital economy can improve carbon emission efficiency; 2) The impact of digital economy on carbon emission efficiency has a "U"-shaped relationship, which is consistent with the "Environmental Kuznets Curve" hypothesis; 3) The impacts of digital economy on carbon emission efficiency exist in urban heterogeneity, specifically manifested as regional heterogeneity and urban scale heterogeneity; 4) Technological innovation is an important mediator for improving carbon emission efficiency in digital economy, and promoting technological innovation in digital economy can improve carbon emission efficiency; 5) Digital economy has spatial effect on carbon emission efficiency, which can improve the carbon emission efficiency of neighboring cities. Finally, based on the above results, suggestions are proposed from three aspects: promoting important industries and key areas for deep cultivation of carbon emission in digital economy, emphasizing regional balance in the development of digital economy, and strengthening regional cooperation in the development of digital economy, in order to continue to play a positive role in improving carbon emission efficiency through digital economy.

Simulated weightlessness procedure, head-down bed rest has reversible effects on the metabolism of rhesus macaque.

It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.

Phase 2 dose-ranging study to evaluate the efficacy and safety of liposomal irinotecan (LY01610) as a second-line treatment for patients with relapsed small cell lung cancer.

Background: This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC). Methods: This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60 mg/m2, 80 mg/m2, and 100 mg/m2. Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Findings: From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval <90 days. In all 66 patients, the ORR was 32% (21/66, 95% confidence interval [CI], 21-44), with a median DoR of 5.2 months (95% CI, 3.0-8.3). Median PFS and OS were 4.0 (95% CI, 2.9-5.5) and 9.7 (95% CI, 7.2-12.3) months, respectively. The ORR of 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose group were 4.2 (95% CI, 2.8-not reached), 6.9 (95% CI, 2.5-9.9), and 4.0 (95% CI, 2.7-6.8) months, respectively. The incidence of ≥ grade 3 treatment-related adverse events (TRAEs) in the 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose group were 33% (2/6), 47% (14/30), and 50% (15/30), respectively. The most common ≥ grade 3 TRAEs of all 66 patients were neutropenia (27%), leukopenia (24%) and anemia (15%). Interpretation: LY01610 exhibited promising clinical efficacy and manageable safety profiles in patients with relapsed SCLC, the 80 mg/m2 dose group had the best benefit-risk ratio. Funding: This study was supported by Luye Pharma Group Ltd.

Orchid2024: A cultivar-level dataset and methodology for fine-grained classification of Chinese Cymbidium Orchids.

BACKGROUND: Chinese Cymbidium orchids, cherished for their deep-rooted cultural significance and significant economic value in China, have spawned a rich tapestry of cultivars. However, these orchid cultivars are facing challenges from insufficient cultivation practices and antiquated techniques, including cultivar misclassification, complex identification, and the proliferation of counterfeit products. Current commercial techniques and academic research primarily emphasize species identification of orchids, rather than delving into that of orchid cultivars within species. RESULTS: To bridge this gap, the authors dedicated over a year to collecting a cultivar image dataset for Chinese Cymbidium orchids named Orchid2024. This dataset contains over 150,000 images spanning 1,275 different categories, involving visits to 20 cities across 12 provincial administrative regions in China to gather pertinent data. Subsequently, we introduced various visual parameter-efficient fine-tuning (PEFT) methods to expedite model development, achieving the highest top-1 accuracy of 86.14% and top-5 accuracy of 95.44%. CONCLUSION: Experimental results demonstrate the complexity of the dataset while highlighting the considerable promise of PEFT methods within flower image classification. We believe that our work not only provides a practical tool for orchid researchers, growers and market participants, but also provides a unique and valuable resource for further exploring fine-grained image classification tasks. The dataset and code are available at https://github.com/pengyingshu/Orchid2024 .

Meldonium, as a potential neuroprotective agent, promotes neuronal survival by protecting mitochondria in cerebral ischemia-reperfusion injury.

BACKGROUND: Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown. METHODS: A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium's neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen-glucose deprivation reperfusion was used to study meldonium's protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker® probes, mitochondrial stress, real-time ATP rate and western blotting. RESULTS: Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia-reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3ß signaling pathway to inhibit mitochondria-dependent neuronal apoptosis. CONCLUSION: Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis.

A Study of the Effects of Moisture on Composite-to-Metal Double-Lap Shear Joints.

This work investigated the effects of moisture absorption treatment on composite-to-metal double-lap shear joints (DLSJs) bonded with epoxy adhesive film through experiments and simulations. The composite-to-metal DLSJ can be divided into five parts (the interface between the composite and adhesive, the interface between the adhesive and metal, the composite adherend, the metal adherend, and the adhesive layer). First, the wet-dependent properties of the adhesive and interfaces were obtained through adhesive tensile tests and GC tests, which showed that the properties of the adhesive and interfaces were significantly affected by the moist environment. Then, tensile tests of the composite-to-metal double-lap shear joints were carried out in dry and wet environments. Finally, based on the experimental investigations, a finite element (FE) model that considered cohesive damage was established for simulating damage evolution and predicting the failure loads and failure modes of the DLSJs. The results of both the experimental and numerical tests show that the DLSJ failure load decreases significantly after immersion in 95 °C water, and the major failure mode transfers from adhesive failure to interface failure. The research results provide a theoretical basis or basic data for the structural design of adhesively bonded composite-to-metal.

Olanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway.

BACKGROUND: Administration of olanzapine (OLA) is closely associated with obesity and glycolipid abnormalities in patients with schizophrenia (SCZ), although the exact molecular mecha- nisms remain elusive. OBJECTIVE: We conducted comprehensive animal and molecular experiments to elucidate the mecha- nisms underlying OLA-induced weight gain. METHODS: We investigated the mechanisms of OLA-induced adipogenesis and lipid storage by em- ploying a real-time ATP production rate assay, glucose uptake test, and reactive oxygen species (ROS) detection in 3T3-L1 cells and AMSCs. Rodent models were treated with OLA using various interven- tion durations, dietary patterns (normal diets/western diets), and drug doses. We assessed body weight, epididymal and liver fat levels, and metabolic markers in both male and female mice. RESULTS: OLA accelerates adipogenesis by directly activating glycolysis and its downstream PI3K sig- naling pathway in differentiated adipocytes. OLA promotes glucose uptake in differentiated 3T3-L1 preadipocytes. In mouse models with normal glycolipid metabolism, OLA administration failed to in- crease food intake and weight gain despite elevated GAPDH expression, a marker related to glycolysis and PI3K-AKT. This supports the notion that glycolysis plays a significant role in OLA-induced met- abolic dysfunction. CONCLUSION: OLA induces glycolysis and activates the downstream PI3K-AKT signaling pathway, thereby promoting adipogenesis.

Bioinspired Total Synthesis of 3-epi-Junipercedrol.

A bioinspired total synthesis of 3-epi-junipercedrol, which contains a strained tricyclo[5.2.2.03,7]undecane allo-cedrane framework and five stereocenters, was accomplished via an effective anionic semipinacol rearrangement of a tricyclic cedrane mesylate. The corresponding cedrane precursor was synthesized efficiently by employing the reductive oxy-Nazarov cyclization and an intramolecular aldol condensation as the key steps. This synthetic approach provided a further evidence for the biogenetic relationship between the typical cedrane and allo-cedrane sesquiterpenoids.

Profile and Determinants for Complications of Imported Malaria in 5 Chinese Provinces From 2014 to 2021: Retrospective Analysis.

Background: In 2021, the World Health Organization officially declared the People's Republic of China as malaria-free. However, despite this milestone achievement, the continued occurrence of severe and fatal cases of imported malaria in China, due to globalization and increased international communication, remains a significant public health concern. Objective: The aim of this study was to elucidate the epidemiological characteristics of imported malaria in 5 Chinese provinces from 2014 to 2021 and to identify the factors that influence complications in imported malaria cases. The findings will provide a basis for enhancing prevention and control measures, thereby consolidating China's achievements in malaria elimination. Methods: A case-based retrospective study was performed, using surveillance data collected from the representative provinces of China from 2014 to 2021. Epidemiological characteristics were analyzed using descriptive statistics. Logistic regression was used to identify the factors influencing the occurrence of complications. Results: A total of 5559 malaria cases were included during the study period. The predominant species was Plasmodium falciparum (3940/5559, 70.9%), followed by Plasmodium ovale (1054/5559, 19%), Plasmodium vivax (407/5559, 7.3%), Plasmodium malariae (157/5559, 2.8%), and 1 case of Plasmodium knowlesi. Most of the cases were male (5343/5559, 96.1%). The complication rates for P falciparum and P ovale were 11.4% and 3.3%, respectively. Multivariate logistic regression analysis of the relevant factors of malaria complications revealed potential protective factors, including a previous infection by Plasmodium (P<.001; odds ratio [OR] 0.512, 95% CI 0.422-0.621), and risk factors, including increased age (P=.004; OR 1.014, 95% CI 1.004-1.024), misdiagnosis at the first clinical visit (P<.001; OR 3.553, 95% CI 2.886-4.375), and the time interval from onset to treatment (P=.001; OR 1.026, 95% CI 1.011-1.042). Subgroup analyses identified risk factors associated with P falciparum, which include advanced age (P=.004; OR 1.015, 95% CI 1.005-1.026), initial misdiagnosis during the first clinical visit (P<.001; OR 3.549, 95% CI 2.827-4.455), the time interval from onset to treatment (P<.001; OR 1.043, 95% CI 1.022-1.063), and a delay of more than 3 days from the first treatment to diagnosis (P<.001; OR 2.403, 95% CI 1.823-3.164). Additionally, the risk factors pertaining to P ovale involve misdiagnosis at the initial clinical visit (P=.01; OR 2.901, 95% CI 1.336-6.298), the time interval from onset to treatment (P=.002; OR 1.095, 95% CI 1.033-1.160), and the duration from the initial treatment to diagnosis (P=.43; OR 1.032, 95% CI 0.953-1.118). Previous infections can prevent the progression of both P falciparum and P ovale. Conclusions: This study showed that the increasing proportion of P ovale in recent years should not be ignored. Furthermore, there is a need to improve diagnostic awareness, enhance the capacity of medical institutions, and provide health education for high-risk groups.

Molecular detection, subtyping of Blastocystis sp. in migratory birds from nature reserves in northeastern China.

Migratory birds play an important role in the cross-regional transmission of zoonotic pathogens. Assessing the presence of zoonotic pathogens carried by migratory birds is critical for disease control. However, information about Blastocystis infection in the migratory birds is very limited. Thus, we conducted this study with the aim to explore the occurrence, prevalence and subtyping of Blastocystis in four breeds of migratory birds in northeastern China. From October 2022 to April 2023, a total of 427 fresh fecal samples were obtained from four breeds of migratory birds in five nature reserves in northeastern China, and screened for Blastocystis by PCR amplification. Twenty-one (4.92 %) of the studied samples were confirmed Blastocystis-positive, and two known zoonotic subtypes ST6 and ST7 were founded, with ST7 being the major subtype. Until now, we firstly reported the infection status and subtyping of Blastocystis in the migratory Greater White-Fronted Goose, White Stork, Oriental White Stork and Bean Goose in China. More importantly, these findings present further data on the genetic diversity and transmission routes of Blastocystis and further arouse public health concerns about this organism.

Diversified Reactivity of Triphenylphosphine: Reinvestigation of the Phosphine-Mediated Reductive Condensation Approach for the Synthesis of Substituted Furans.

A reinvestigation of "Phosphine-Mediated Reductive Condensation of γ-Acyloxy Butynoates: A Diversity Oriented Strategy for the Construction of Substituted Furans" (J. Am. Chem. Soc. 2004, 126, 4118-4119) revealed different chemoselectivity of triphenylphosphine in the reactions with the γ-acyloxy butynoate substrates of varying substitution patterns/electronics. Furthermore, the electronics of the triaryl phosphine reagent could be tuned to trap a putative intermediate such as A, leading to the semihydrogenation of propiolamide substrates.

Preparation and properties of biomimetic bone repair hydrogel with sandwich structure.

One of the critical factors that determines the biological properties of scaffolds is their structure. Due to the mechanical and structural discrepancies between the target bone and implants, the poor internal architecture design and difficulty in degradation of conventional bone implants may cause several adverse outcomes. To date, many scaffolds, such as 3-D printed sandwich structures, have been successfully developed for the repair of bone defects; however, the steps of these methods are complex and costly. Hydrogels have emerged as a unique scaffold material for repairing bone defects because of their good biocompatibility and excellent physicochemical properties. However, studies exploring bioinspired hydrogel scaffolds with hierarchical structures are scarce. More efforts are needed to incorporate bioinspired structures into hydrogel scaffolds to achieve optimal osteogenic properties. In this study, we developed a low-cost and easily available hydrogel matrix that mimicked the natural structure of the bone's porous sandwich to promote new bone growth and tissue integration. A comprehensive evaluation was conducted on the microstructure, swelling rate, and mechanical properties of this hydrogel. Furthermore, a 3D finite element analysis was employed to model the structure-property relationship. The results indicate that the sandwich-structured hydrogel is a promising scaffold material for bone injury repair, exhibiting enhanced compressive stress, elastic modulus, energy storage modulus, and superior force transmission.

Endoscopic minimally invasive treatment of congenital muscular torticollis in children.

BACKGROUND: This study aimed to investigate the clinical efficacy of minimally invasive endoscopic treatment of children with congenital muscular torticollis (CMT). METHODS: In total, 72 children (41 male, 31 female) with CMT who underwent endoscopic surgery at the Department of Orthopedics, Xi'an Children's Hospital, between January 2021 and January 2023 were included. Their mean age was 54 ± 36.1 (range, 12-141) months. Of these, 29 (40.3%) cases involved the left side while 43 (59.7%) involved the right side. Preoperative preparation involved precise body surface markings of the sternocleidomastoid muscle(SCM), clavicle, and important nerve and blood vessels, followed by the establishment of surgical channels through passive separation techniques. An arthroscope and a low-temperature plasma knife were utilized for accurate localization and surgical release of the clavicular and sternal heads of the SCM. The duration of surgery, blood loss, postoperative hospital stay, neck range of motion measurements, and any intraoperative or postoperative complications were analyzed using the rank sum test. Cervical and thoracic braces were applied for three months postoperatively, with follow-up assessments conducted using Cheng's scoring system. RESULTS: All patients successfully underwent endoscopic surgery, without the need for conversion to open surgery. No intra- or postoperative complications were observed. The average surgical duration was 56.4 ± 15.7 min, with minimal intraoperative bleeding (1-5 mL) and no need for blood transfusion. The mean postoperative hospital stay was 2.7 ± 0.8 days. Over a mean follow-up period of 22.2 ± 5.5 (range, 14-32) months, significant improvements were observed in neck rotation (from 20.2° [17.7° to 25°] to only 3.6° [2° to 6.7°]) and lateral flexion (from 19° [17° to 22.6°] to only 3° [2° to 7.8°]) restrictions (p < 0.05). According to Cheng's scoring system, 70 (97.2%) patients achieved excellent or good clinical outcomes, while 2 (2.8%) had average outcomes. The torticollis deformity was corrected during the follow-up period, and all surgical incisions healed without noticeable scarring. CONCLUSION: Endoscopic release is a safe, effective, and minimally invasive treatment option for CMT in children.

Targeting colorectal cancer with Herba Patriniae and Coix seed: Network pharmacology, molecular docking, and in vitro validation.

BACKGROUND: Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated. AIM: To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved. METHODS: Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A "drug-ingredient-target" network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers. RESULTS: Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1, identifying PI3K, AKT, and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro. Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K, p-Akt, and survivin, which likely contributed to CRC apoptosis. CONCLUSION: Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. METHODS: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. RESULTS: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. CONCLUSIONS: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

Research on the characteristics of electro-hydraulic position servo system of RBF neural network under fuzzy rules.

A radial basis function neural network PID controller under fuzzy rules (FUZZY-RBF-PID) was designed for the electro-hydraulic position servo system under the influence of uncertain factors such as load mutation, and load stiffness change. Firstly, the mathematical model of the system is established, and the frequency domain and time domain analysis of the system are carried out. Secondly, based on the analysis results, a radial basis function (RBF) neural network PID controller is designed, and fuzzy rules are innovatively used to adjust the learning rate of PID parameters in the RBF neural network learning algorithm in real time. Thirdly, the simulation results show that under the action of the FUZZY-RBF-PID controller, the unit step response of the system has high steady-state accuracy, fast response speed, and under the condition of large load stiffness, the system can recover to the steady-state value faster after being disturbed. At the same time, when the input signal is the sinusoidal signal of 10 HZ, the system under the action of the FUZZY-RBF-PID controller has no obvious phase lag phenomenon, and the tracking error is minimal. The proposed method can effectively improve the comprehensive performance of the electro-hydraulic position servo system under the influence of uncertain factors.