Optical response of Higgs mode in superconductors at clean limit: formulation through Eilenberger equation and Ginzburg-Landau Lagrangian.

Both macroscopic Ginzburg-Landau Lagrangian and microscopic gauge-invariant kinetic equation suggest a finite Higgs-mode generation in the second-order optical response of superconductors at clean limit, whereas the previous derivations through the path-integral approach and Eilenberger equation within the Matsubara formalism failed to give such generation. The crucial treatment leading to this controversy lies at an artificial scheme that whether the external optical frequency is taken as continuous variable or bosonic Matsubara frequency to handle the gap dynamics within the Matsubara formalism. To resolve this issue, we derive the effective action of the superconducting gap near Tcin the presence of the vector potential through the path-integral approach, to fill the long missing blank of the microscopic derivation of the Ginzburg-Landau Lagrangian in superconductors. It is shown that only by taking optical frequency as continuous variable within the Matsubara formalism, can one achieve the fundamental Ginzburg-Landau Lagrangian, and in particular, the finite Ginzburg-Landau kinetic term leads to a finite Higgs-mode generation at clean limit. To further eliminate the confusion of the Matsubara frequency through a separate framework, we apply the Eilenberger equation within the Keldysh formalism, which is totally irrelevant to the Matsubara space. By calculating the gap dynamics in the second-order response, it is analytically proved that the involved optical frequency is a continuous variable rather than bosonic Matsubara frequency, causing a finite Higgs-mode generation at clean limit. .

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Elevated serum neurofilament light chain levels are associated with hepatic encephalopathy in patients with cirrhosis.

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005-1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130-0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117-0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE.

Autoimmune glial fibrillary acidic protein astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome: A case report and literature review.

RATIONALE: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease of the central nervous system that affects the meninges, brain, spinal cord, and optic nerves. GFAP astrocytopathy can coexist with a variety of antibodies, which is known as overlap syndrome. Anti-NMDAR-positive encephalitis overlap syndrome has been reported; however, encephalitis overlap syndrome with both anti-NMDAR and sulfatide-IgG positivity has not been reported. PATIENT CONCERNS: The patient was a 50-year-old male who was drowsy and had chills and weak limbs for 6 months. His symptoms worsened after admission to our hospital with persistent high fever, dysphoria, gibberish, and disturbance of consciousness. Positive cerebrospinal fluid NMDA, GFAP antibodies, and serum sulfatide antibody IgG were positive. DIAGNOSES: Autoimmune GFAP astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome. INTERVENTIONS: In addition to ventilator support and symptomatic supportive treatment, step-down therapy with methylprednisolone (1000 mg/d, halved every 3 days) and pulse therapy with human immunoglobulin (0.4 g/(kg d) for 5 days) were used. OUTCOMES: After 6 days of treatment, the patient condition did not improve, and the family signed up to give up the treatment and left the hospital. CONCLUSIONS: Patients with autoimmune GFAP astrocytopathy may be positive for anti-NMDAR and sulfatide-IgG, and immunotherapy may be effective in patients with severe conditions. LESSONS: Autoimmune GFAP astrocytopathy with nonspecific symptoms is rarely reported and is easy to be missed and misdiagnosed. GFAP astrocytopathy should be considered in patients with fever, headache, disturbance of consciousness, convulsions, and central infections that do not respond to antibacterial and viral agents. Autoimmune encephalopathy-related antibody testing should be performed as soon as possible, early diagnosis should be confirmed, and immunomodulatory therapy should be administered promptly.

Local adjuncts to minimally invasive endoscopic interventions for benign laryngotracheal stenosis: a meta-analysis.

BACKGROUND: Benign laryngotracheal stenosis is widely managed with minimally invasive endoscopic interventions, such as laser incision or excision scar, and dilation. However, various endoscopic treatments are significantly associated with a high recurrence rate. Local auxiliary measures, including inhalation of steroids, injection of steroids, and local topical application of mitomycin C, have been studied in order to increase the success rate. PURPOSE: To compare the efficacy of endoscopic treatments with and without local adjuncts in patients with benign laryngotracheal stenosis, and analyze their clinical outcomes, recurrence, and complications. METHODS: In the meta-analysis, databases including PubMed, EMBASE, OVID, and Web of Science were searched for papers comparing the outcomes of adjunct therapy with non-adjunct therapy in patients with laryngotracheal stenosis. The duplicate publications, reviews, comments or letters, conference abstracts, and case reports were excluded. The random effect model was used for assessing the pooled risk estimates. RESULTS: Eight studies (1204 cases) referring to two prospective randomized controlled studies, two prospective cohort studies, and four retrospective cohort studies were ultimately included in the meta-analysis. Three delivery modes of adjuncts were identified, including intralesion steroid injection (n = 2), inhaled steroid (n = 2), and topical application of mitomycin C (n = 4). The decreased risk estimates of recurrence rate were detected in patients receiving endoscopic treatments with steroid injection or inhaled steroid, compared with endoscopic interventions alone (P < 0.05). Additionally, patients undergoing adjunct therapies had lower risk estimates of recurrence, compared to those receiving endoscopic procedures alone (P < 0.05), based on the subgroup of prospective cohort studies, subglottis, Mayer-Cotton scale of I-II degree, and stenosis length of < 3 cm. The high heterogeneity of the pooling risk estimates perhaps was due to factors of auxiliary drug, clinical characteristics of patients, and methodology. No discernible difference in the incidence of complication was identified. CONCLUSIONS: Local application of steroids to minimally invasive interventions appear to reduce the recurrence rate of laryngotracheal stenosis. Various adjuncts available, including steroids and mitomycin C, appear to be safe and associated with a low risk estimate of adjuncts-specific complication rate. High quality multi-center randomized controlled studies are needed, with sufficient periods for follow-up and subjective and objective outcome indicators, to properly evaluate the efficacy, safety, and cost-effectiveness of adjuvant drugs.

Temporal Trends of Inflammatory Bowel Diseases in Taiwan from 2016 to 2020: A Population-Based Study.

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

Synthesis of 2-benzyl N-substituted anilines via imine condensation-isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines.

A catalyst- and additive-free synthesis of 2-benzyl N-substituted anilines from (E)-2-arylidene-3-cyclohexenones and primary amines has been reported. The reaction proceeds smoothly through a sequential imine condensation-isoaromatization pathway, affording a series of synthetically useful aniline derivatives in acceptable to high yields. Mild reaction conditions, no requirement of metal catalysts, operational simplicity and the potential for scale-up production are some of the highlighted advantages of this transformation.

Developing an entrustable professional activity for providing health education and consultation in occupational therapy and examining its validity.

BACKGROUND: Entrustable Professional Activities (EPA)-based assessment is easily and intuitively used in evaluating the learning outcomes of competency-based medical education (CBME). This study aimed to develop an EPA for occupational therapy focused on providing health education and consultation (TP-EPA3) and examine its validity. METHODS: Nineteen occupational therapists who had completed online training on the EQual rubric evaluation participated in this study. An expert committee identified six core EPAs for pediatric occupational therapy. TP-EPA3 was developed following the EPA template and refined through consensus meetings. The EQual rubric, a 14-item, five-point criterion-based anchor system, encompassing discrete units of work (DU), entrustable, essential, and important tasks of the profession (EEIT), and curricular role (CR), was used to evaluate the quality of TP-EPA3. Overall scores below 4.07, or scores for DU, EEIT, and CR domains below 4.17. 4.00, and 4.00, respectively, indicate the need for modifications. RESULTS: The TP-EPA3 demonstrated good validity, surpassing the required cut-off score with an average overall EQual score of 4.21 (SD = 0.41). Specific domain scores for DU, EEIT, and CR were 3.90 (SD = 0.69), 4.46 (SD = 0.44), and 4.42 (SD = 0.45), respectively. Subsequent revisions clarified observation contexts, enhancing specificity and focus. Further validation of the revised TP-EPA3 and a thorough examination of its reliability and validity are needed. CONCLUSION: The successful validation of TP-EPA3 suggests its potential as a valid assessment tool in occupational therapy education, offering a structured approach for developing competency in providing health education and consultation. This process model for EPA development and validation can guide occupational therapists in creating tailored EPAs for diverse specialties and settings.

An SNP Marker Predicts Colorectal Cancer Outcomes with 5-Fluorouracil-Based Adjuvant Chemotherapy Post-Resection.

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.

Role of Phenylethanolamine-N-methyltransferase on Nicotine-Induced Vasodilation in Rat Cerebral Arteries.

OBJECTIVE: The sympathetic-parasympathetic (or axo-axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on ß2-adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak ß2-adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine-N-methyltransferase (PNMT) and then acts on the ß2-adrenoceptors to induce neurogenic vasodilation. METHODS: Blood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats. RESULTS: Nicotine-induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and Nω-nitro-l-arginine. Nicotine- and exogenous NE-induced vasorelaxation was partially inhibited by LY-78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY-78335; it then induced the release of nitric oxide (NO). Epinephrine-induced vasorelaxation was not affected by LY-78335. However, these vasorelaxations were completely inhibited by atenolol (a ß1-adrenoceptor antagonist) combined with ICI-118,551 (a ß2-adrenoceptor antagonist). CONCLUSIONS: These results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo-axonal interaction mechanism in regulating brainstem vascular tone.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Utilizing deep learning for automated detection of oral lesions: A multicenter study.

OBJECTIVES: We aim to develop a YOLOX-based convolutional neural network model for the precise detection of multiple oral lesions, including OLP, OLK, and OSCC, in patient photos. MATERIALS AND METHODS: We collected 1419 photos for model development and evaluation, conducting both a comparative analysis to gauge the model's capabilities and a multicenter evaluation to assess its diagnostic aid, where 24 participants from 14 centers across the nation were invited. We further integrated this model into a mobile application for rapid and accurate diagnostics. RESULTS: In the comparative analysis, our model overperformed the senior group (comprising three most experienced experts with more than 10 years of experience) in macro-average recall (85 % vs 77.5 %), precision (87.02 % vs 80.29 %), and specificity (95 % vs 92.5 %). In the multicenter model-assisted diagnosis evaluation, the dental, general, and community hospital groups showed significant improvement when aided by the model, reaching a level comparable to the senior group, with all macro-average metrics closely aligning or even surpassing with those of the latter (recall of 78.67 %, 74.72 %, 83.54 % vs 77.5 %, precision of 80.56 %, 76.42 %, 85.15 % vs 80.29 %, specificity of 92.89 %, 91.57 %, 94.51 % vs 92.5 %). CONCLUSION: Our model exhibited a high proficiency in detection of oral lesions, surpassing the performance of highly experienced specialists. The model can also help specialists and general dentists from dental and community hospitals in diagnosing oral lesions, reaching the level of highly experienced specialists. Moreover, our model's integration into a mobile application facilitated swift and precise diagnostic procedures.

Computed tomography three-dimensional reconstruction in the diagnosis of bleeding small intestinal polyps: A case report.

BACKGROUND: Computed tomography (CT) small bowel three-dimensional (3D) reconstruction is a powerful tool for the diagnosis of small bowel disease and can clearly show the intestinal lumen and wall as well as the outside structure of the wall. The horizontal axis position can show the best adjacent intestinal tube and the lesion between the intestinal tubes, while the coronal position can show the overall view of the small bowel. The ileal end of the localization of the display of excellent, and easy to quantitative measurement of the affected intestinal segments, the sagittal position for the rectum and the pre-sacral lesions show the best, for the discovery of fistulae is also helpful. Sagittal view can show rectal and presacral lesions and is useful for fistula detection. It is suitable for the assessment of inflammatory bowel disease, such as assessment of disease severity and diagnosis and differential diagnosis of the small bowel and mesenteric space-occupying lesions as well as the judgment of small bowel obstruction points. CASE SUMMARY: Bleeding caused by small intestinal polyps is often difficult to diagnose in clinical practice. This study reports a 29-year-old male patient who was admitted to the hospital with black stool and abdominal pain for 3 months. Using the combination of CT-3D reconstruction and capsule endoscopy, the condition was diagnosed correctly, and the polyps were removed using single-balloon enteroscopy-endoscopic retrograde cholangiopancreatography without postoperative complications. CONCLUSION: The role of CT-3D in gastrointestinal diseases was confirmed. CT-3D can assist in the diagnosis and treatment of gastrointestinal diseases in combination with capsule endoscopy and small intestinal microscopy.

A deep learning-powered diagnostic model for acute pancreatitis.

BACKGROUND: Acute pancreatitis is one of the most common diseases requiring emergency surgery. Rapid and accurate recognition of acute pancreatitis can help improve clinical outcomes. This study aimed to develop a deep learning-powered diagnostic model for acute pancreatitis. MATERIALS AND METHODS: In this investigation, we enrolled a cohort of 190 patients with acute pancreatitis who were admitted to Sichuan Provincial People's Hospital between January 2020 and December 2021. Abdominal computed tomography (CT) scans were obtained from both patients with acute pancreatitis and healthy individuals. Our model was constructed using two modules: (1) the acute pancreatitis classifier module; (2) the pancreatitis lesion segmentation module. Each model's performance was assessed based on precision, recall rate, F1-score, Area Under the Curve (AUC), loss rate, frequency-weighted accuracy (fwavacc), and Mean Intersection over Union (MIOU). RESULTS: Upon admission, significant variations were observed between patients with mild and severe acute pancreatitis in inflammatory indexes, liver, and kidney function indicators, as well as coagulation parameters. The acute pancreatitis classifier module exhibited commendable diagnostic efficacy, showing an impressive AUC of 0.993 (95%CI: 0.978-0.999) in the test set (comprising healthy examination patients vs. those with acute pancreatitis, P < 0.001) and an AUC of 0.850 (95%CI: 0.790-0.898) in the external validation set (healthy examination patients vs. patients with acute pancreatitis, P < 0.001). Furthermore, the acute pancreatitis lesion segmentation module demonstrated exceptional performance in the validation set. For pancreas segmentation, peripancreatic inflammatory exudation, peripancreatic effusion, and peripancreatic abscess necrosis, the MIOU values were 86.02 (84.52, 87.20), 61.81 (56.25, 64.83), 57.73 (49.90, 68.23), and 66.36 (55.08, 72.12), respectively. These findings underscore the robustness and reliability of the developed models in accurately characterizing and assessing acute pancreatitis. CONCLUSION: The diagnostic model for acute pancreatitis, driven by deep learning, exhibits excellent efficacy in accurately evaluating the severity of the condition. TRIAL REGISTRATION: This is a retrospective study.

Formulation and Characterization of Triamcinolone Acetonide Acetate-Loaded Microspheres Prepared by a Static Mixing Technique.

PURPOSE: Reproducibility and scale-up production of microspheres through spray drying present significant challenges. In this study, biodegradable microspheres of Triamcinolone Acetonide Acetate (TAA) were prepared using a novel static mixing method by employing poly( lactic-co-glycolic acid) (PLGA) as the sustained-release carrier. METHODS: TAA-loaded microspheres (TAA-MSs) were prepared using a static mixing technique. The PLGA concentration, polyvinyl alcohol concentration (PVA), phase ratio of oil/water, and phase ratio of water/solidification were optimized in terms of the particle size, drug loading (DL), and encapsulation efficiency (EE) of TAA-MSs. The morphology of TAA-MSs was examined using Scanning Electron Microscopy (SEM), while the physicochemical properties were evaluated through X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of TAA-MSs was compared to that of the pure drug (TAA) using a water-bath vibration method in the medium of pH 7.4 at 37°C. RESULTS: The formulation composition and preparation condition for the preparation of TAA-MSs were optimized as follows: the PLGA concentration was 1%, the phase ratio of oil(dichloromethane) /water (PVA solution) was 1:3, the phase ratio of water (PVA solution)/solidification was 1:2. The optimized TAA-MSs displayed spherical particles with a size range of 30-70 µm, and DL and EE values of 27.09% and 98.67%, respectively. Moreover, the drug-loaded microspheres exhibited a significant, sustained release, with 20% of the drug released over a period of 28 days. The XRD result indicated that the crystalline form of TAA in microspheres had been partly converted into the amorphous form. DSC and FT-IR results revealed that some interactions between TAA and PLGA occurred, indicating that the drug was effectively encapsulated into PLGA microspheres. CONCLUSION: TAA-loaded PLGA microspheres have been successfully prepared via the static mixing technique with enhanced EE and sustained-release manner.

Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing.

BACKGROUND: Bone grafting is the standard treatment for critical bone defects, but autologous grafts have limitations like donor site morbidity and limited availability, while commercial artificial grafts may have poor integration with surrounding bone tissue, leading to delayed healing. Magnesium deficiency negatively impacts angiogenesis and bone repair. Therefore, incorporating magnesium into a synthetic biomaterial could provide an excellent bone substitute. This study aims to evaluate the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM), which could serve as an excellent bone substitute by incorporating magnesium. METHODS: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. RESULTS: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 minutes and a compressive strength of 4.39±0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. CONCLUSION: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

[Spatial distribution patterns and intraspecific and interspecific spatial associations of Quercus myrsinifolia population in Shennongjia, China]. / ç¥žå†œæž¶å°å¶é’å†ˆç§ç¾¤çš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† ç§é—´ç©ºé—´å ³è”.

Quercus myrsinifolia is one of the dominant species in the evergreen broad-leaf forest on the southern slope of Shennongjia. The study of spatial distribution pattern and spatial correlation of Q. myrsinifolia population will help to understand population development and potential ecological processes, as well as the structure and biodiversity maintenance mechanism of evergreen broad-leaf forests at the northern edge of the subtropics. Based on forest dynamic monitoring data from one 1 hm2 permanent plot on the southern slope of Shennongjia, we employed pair correlation functions g(r) and marked correlation functions to analyze the diameter structure of the Q. myrsinifolia population, spatial distribution patterns at different diameter classes, and intraspecific and interspecific spatial associations. The results showed that diameter structure of Q. myrsinifolia population exhibited an inverted 'J'-shaped distribution, suggesting a healthy regeneration status and belonging to a growing population type. The spatial distribution showed a decreasing trend in aggregation with increasing diameter. Positive correlations among individuals strengthened with closer diameter classes, while weakening with larger diameter differences. Interspecific spatial associations showed an increasing correlation of Q. myrsinifolia with understory dominant species with increasing spatial scales, but no correlation was observed with canopy-dominant species. Our results suggested that the spatial pattern of Q. myrsinifolia populations on the southern slope of Shennongjia was mainly influenced by habitat filtering, seed dispersal limitation, and intraspecific and interspecific competition. Furthermore, the adaptive strategies of Q. myrsinifolia varied when they coexisted with different species.

Assessing the association between a sedentary lifestyle and prevalence of primary osteoporosis: a community-based cross-sectional study among Chinese population.

OBJECTIVES: To reveal the association between a sedentary lifestyle and the prevalence of primary osteoporosis (POP). DESIGN: A community-based cross-sectional study was conducted. SETTING: This study was conducted in communities in Hefei city, Anhui province, China. PARTICIPANTS: A total of 1346 residents aged 40 and above underwent POP screening via calcaneus ultrasound bone mineral density (BMD) testing and completed a questionnaire survey. OUTCOME MEASURES: The average daily sitting time was included in the study variable and used to assess sedentary behaviour. The 15 control variables included general information, dietary information and life behaviour information. Logistic regression was used to analyse the association between the POP prevalence and study or control variables in different models. RESULTS: 1346 participants were finally included in the study. According to the 15 control variables, the crude model and 4 models were established. The analysis revealed that the average daily sitting time showed a significant correlation with the prevalence of POP in the crude model (OR=2.02, 95% CI=1.74 to 2.36, p<0.001), Model 1 (OR=2.65, 95% CI=2.21 to 3.17, p<0.001), Model 2 (OR=2.63, 95% CI=2.19 to 3.15, p<0.001), Model 3 (OR=2.62, 95% CI=2.18 to 3.15, p<0.001) and Model 4 (OR=2.58, 95% CI=2.14 to 3.11, p<0.001). Besides, gender, age and body mass index showed a significant correlation with the POP prevalence in all models. CONCLUSIONS: This study suggests a potential association between a sedentary lifestyle and the prevalence of POP within the Chinese population. Modifying sedentary behaviours could contribute to a reduction in POP risk. However, longitudinal cohort studies are necessary to confirm this hypothesis in the future.

Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

Crafting Docetaxel-Loaded Albumin Nanoparticles Through a Novel Thermal-Driven Self-Assembly/Microfluidic Combination Technology: Formulation, Process Optimization, Stability, and Bioavailability.

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.