A predictive study of the efficacy of transcutaneous auricular vagus nerve stimulation in the treatment of major depressive disorder: An fMRI-based machine learning analysis.

BACKGROUND: In order to improve taVNS efficacy, the usage of fMRI to explore the predictive neuroimaging markers would be beneficial for screening the appropriate MDD population before treatment. METHODS: A total of 86 MDD patients were recruited in this study, and all subjects were conducted with the clinical scales and resting-state functional magnetic resonance imaging (fMRI) scan before and after 8 weeks' taVNS treatment. A two-stage feature selection strategy combining Machine Learning and Statistical was used to screen out the critical brain functional connections (FC) that were significantly associated with efficacy prediction, then the efficacy prediction model was constructed for taVNS treating MDD. Finally, the model was validated by separated the responding and non-responding patients. RESULTS: This study showed that taVNS produced promising clinical efficacy in the treatment of mild and moderate MDD. Eleven FCs were selected out and were found to be associated with the cortico-striatal-pallidum-thalamic loop, the hippocampus and cerebellum and the HAMD-17 scores. The prediction model was created based on these FCs for the efficacy prediction of taVNS treatment. The R-square of the conducted regression model for predicting HAMD-17 reduction rate is 0.44, and the AUC for classifying the responding and non-responding patients is 0.856. CONCLUSION: The study demonstrates the validity and feasibility of combining neuroimaging and machine learning techniques to predict the efficacy of taVNS on MDD, and provides an effective solution for personalized and precise treatment for MDD.

Prediction of Potential Distribution of Carposina coreana in China under the Current and Future Climate Change.

Carposina coreana is an important pest of Cornus officinalis, distributed in China, Korea, and Japan. In recent years, its damage to C. officinalis has become increasingly serious, causing enormous economic losses in China. This study and prediction of current and future suitable habitats for C. coreana in China can provide an important reference for the monitoring, early warning, prevention, and control of the pest. In this study, the potential distributions of C. coreana in China under current climate and future climate models were predicted using the maximum entropy (MaxEnt) model with ArcGIS software. The distribution point data of C. coreana were screened using the buffer screening method. Nineteen environmental variables were screened using the knife-cut method and variable correlation analysis. The parameters of the MaxEnt model were optimized using the kuenm package in R software. The MaxEnt model, combined with key environmental variables, was used to predict the distribution range of the suitable area for C. coreana under the current (1971-2000) and four future scenarios. The buffer screening method screened data from 41 distribution points that could be used for modeling. The main factors affecting the distribution of C. coreana were precipitation in the driest month (Bio14), precipitation in the warmest quarter (Bio18), precipitation in the coldest quarter (Bio19), the standard deviation of seasonal variation of temperature (Bio4), minimum temperature in the coldest month (Bio6), and average temperature in the coldest quarter (Bio11). The feature class (FC) after the kuenm package optimization was a Q-quadratic T-threshold combination, and the regularization multiplier (RM) was 0.8. The suitable areas for C. coreana under the current climate model were mainly distributed in central China, and the highly suitable areas were distributed in southern Shaanxi, southwestern Henan, and northwestern Hubei. The lowest temperature in the coldest month (Bio6), the average temperature in the coldest quarter (Bio11), and the precipitation in the warmest quarter (Bio18) all had good predictive ability. In future climate scenarios, the boundary of the suitable area for C. coreana in China is expected to shift northward, and thus, most of the future climate scenarios would shift northward.

A modified "outside-in" Broström-Gould procedure yielding favorable outcomes for the management of chronic lateral ankle instability-a retrospective study with mid-term follow-up.

Purpose: There are various surgical interventions available for the management of Chronic lateral ankle instability (CLAI). The Broström-Gould procedure has gained widespread recognition among foot and ankle specialists for its favorable surgical outcomes. However, with advancements in anatomical understanding and medical technology, further enhancements to the effectiveness of the Gould procedure are warranted. This study introduces a all-inside modified "outside-in" Broström -Gould procedure as an alternative approach for addressing lateral ankle instability. Methods: From August 2020 to October 2022, 40 patients with lateral ankle instability who underwent arthroscopic repair of the modified "outside-in" Broström-Gould procedure were retrospectively analyzed. All patients received standard non-surgical treatment before surgery for more than 6 months without symptom relief. Visual Analogue Scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) and Karlsson-Peterson score were used to evaluate the postoperative effect. Results: All patients were followed up for (14.62 ± 2.04) months. One year after operation, all patients could walk normally, ankle instability sensation disappeared, varus stress test and anterior drawer test were negative. The VAS , AOFAS and Karlsson-Peterson scores of all patients were significantly better compared with those before operation, and the difference between before and after operation was statistically significant. Conclusions: The modified "outside-in" Broström-Gould procedure can effectively treat CLAI, which can obtain satisfactory results. The procedure is straightforward, the impact is minimal, and the aesthetics are pleasing.

Effect of cardiac function in patients with gastrointestinal cancer with or without acute kidney injury assessed using a non-invasive impedance cardiography: a case-control study.

OBJECTIVES: This study aimed to analyze the possible causes of changes in cardiac function and investigate the feasibility of clinical assessment of gastrointestinal cancer in patients with or without acute kidney injury (AKI) assessed using a non-invasive impedance cardiography (ICG, Bioz. Cardio Dynamics, USA) to identify independent risk factors. METHODS: Patients admitted to the Fourth Hospital of Hebei Medical University, China, between May 1, 2019, and February 15, 2022, were included in this study. A total of 51 patients with gastrointestinal cancer (31 men and 20 women, mean age 61.1 ± 10.9 years) with or without AKI were evaluated for ICG. A total of 19 patients underwent ultrasound cardiography (UCG) and ICG evaluations. RESULT: There was a significant positive correlation between cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI), and ejection fraction (EF) measured using UCG and ICG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001), CIICG and CIUCG (r = 0.718, P = 0.001), SVICG and SVUCG (r = 0.837, P < 0.001), and LCWIICG and EFUCG (r = 0.540, P = 0.017). Cardiac function parameters measured using ICG were statistically different between patients with gastrointestinal cancer with or without AKI (P ≤ 0.05). Multivariate analysis revealed that AKI independently affects cardiac function in patients with gastrointestinal cancer. CONCLUSIONS: UCG and ICG methods are significantly associated with cardiac function in patients with or without AKI, and patients with gastrointestinal cancer with AKI are worse than those without AKI. AKI is an independent risk factor for cardiac function in patients with gastrointestinal cancer.

Knockdown of long noncoding RNA SAN rejuvenates aged adipose-derived stem cells via miR-143-3p/ADD3 axis.

BACKGROUND: Senescent adipose-derived stem cells (ASCs) exhibit reduced therapeutic efficacy during wound healing. Transcriptional regulation factors including long noncoding RNAs (lncRNAs) reportedly have essential roles in stem cell aging. However, the mechanisms of which lncRNAs influence mesenchymal stem cell aging and how it works need further investigation. METHODS: The expression patterns of lncRNA senescence-associated noncoding RNA (SAN) and miR-143-3p in ASCs obtained from old and young volunteer donors were detected by quantitative polymerase chain reaction. ASCs with overexpression or knockdown of SAN and γ-adducin (ADD3) were constructed by lentiviral transduction. Mimic and inhibitor were used to manipulate the cellular level of miR-143-3p in ASCs. The effects of these RNAs on ASCs proliferation, migration and cellular senescence were examined by EdU, transwell and senescence-activated ß-galactosidase (SA-ß-gal) staining assays. Wound scratch and tube formation assays were conducted to evaluate the capacities of ASCs in promoting fibroblasts migration and endothelial cells angiogenesis. Furthermore, dual-luciferase assays and rescue experiments were performed to identify the RNA interactions. Finally, the therapeutic effects of SAN-depleted aged ASCs were evaluated in a skin injury model. RESULTS: The lncRNA SAN (NONHSAT035482.2) was upregulated in aged ASCs; it controlled cellular senescence in ASCs. lncRNA SAN knockdown in ASCs led to ASC functional enhancement and the inhibition of cellular senescence; it also promoted the effects of conditioned medium (CM) on endothelial cell tube formation and fibroblast migration. Mechanistic analysis showed that SAN serves as a sponge for miR-143-3p, thereby regulating the expression of ADD3. The application of SAN-depleted aged ASCs increased re-epithelialization, collagen deposition, neovascularization and led to accelerated skin wound closure, compared with transplantation of aged ASCs. CONCLUSION: The lncRNA SAN mediates ASC senescence by regulating the miR-143-3p/ADD3 pathway, providing a potential target for rejuvenation of senescent ASCs and enhancement of wound repair.

DFT characterization of a new possible two-dimensional BN allotrope with a biphenylene network structure.

The pioneering work on the newly experimentally synthesized biphenylene network C has triggered a worldwide tide of research on its family material counterparts. In this study, a biphenylene network BN structure was theoretically characterized by density functional theory (DFT) calculations. Initially, the structure's mechanical and thermal stabilities were evaluated. There were no imaginary frequencies in the phonon dispersion curve, indicating that the structure was mechanically stable. Additionally, the energy barrier for forming a biphenylene network BN structure from perfect pristine 2D h-BN is substantially less than that for forming a biphenylene network C from a perfect graphene sheet, as can be explained from the greater structure distortion in the biphenylene network BN with lower bond stress which thus caused lower energy. The electronic band structure and detailed projected density of states analysis indicated that the biphenylene network BN is a semiconductor with the valence band maximum (VBM) and the conduction band minimum (CBM) states from the pz orbitals of N and B atoms with sp2 hybridization. Finally, a bilayer structure was also proposed. Our obtained results provide more insights into two-dimensional biphenylene network BN based structures and those family materials which could be widely used in relevant nanoelectronic devices.

Panax ginseng improves physical recovery and energy utilization on chronic fatigue in rats through the PI3K/AKT/mTOR signalling pathway.

CONTEXT: Panax ginseng C. A. Meyer (Araliaceae) is a tonic herb used in ancient Asia. OBJECTIVE: This study investigated the antifatigue effect of P. ginseng on chronic fatigue rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into control, model and EEP (ethanol extraction of P. ginseng roots) (50, 100 and 200 mg/kg) groups (n = 8). The rats were subcutaneously handled with loaded swimming once daily for 26 days, except for the control group. The animals were intragastrically treated with EEP from the 15th day. On day 30, serum, liver and muscles were collected, and the PI3K/Akt/mTOR signalling pathway was evaluated. RESULTS: The swimming times to exhaust of the rats with EEP were significantly longer than that without it. EEP spared the amount of muscle glycogen, hepatic glycogen and blood sugar under the chronic state. In addition, EEP significantly (p < 0.05) decreased serum triglycerides (1.24 ± 0.17, 1.29 ± 0.04 and 1.20 ± 0.21 vs. 1.58 ± 0.13 mmol/L) and total cholesterol (1.64 ± 0.36, 1.70 ± 0.15 and 1.41 ± 0.19 vs. 2.22 ± 0.19 mmol/L) compared to the model group. Regarding the regulation of energy, EEP had a positive impact on promoting ATPase activities and relative protein expression of the PI3K/Akt/mTOR pathway. CONCLUSIONS: Our results suggested that EEP effectively relieved chronic fatigue, providing evidence that P. ginseng could be a potential dietary supplement to accelerate recovery from fatigue.

The pro-inflammatory factors contribute to the EEG microstate abnormalities in patients with major depressive disorder.

Pro-inflammatory factors may be associated with abnormalities in functional brain networks, which may be a mechanism in the pathogenesis of major depressive disorder (MDD). Electroencephalogram (EEG) microstates reflect the functioning of brain networks. However, the relationship between pro-inflammatory factors and the microstate abnormalities in patients with MDD is poorly understood. 24 MDD patients and 24 age-and sex-matched healthy controls (HC) were recruited. Montgomery-Asberg Depression Rating Scale(MADRS) were assessed. Serum (interleukin- 2(IL- 2), tumor necrosis factor-α (TNF-α) and hs-C-reactive protein (CRP)and EEG data were collected. K-means clustering was performed to characterize different microstates. For each microstate, duration, occurrence and coverage were estimated. Four microstates (e.g. A, B, C, D) were characterized, MDD group showed lower duration, occurrence and coverage of microstate B and microstate D, while higher duration of microstate A and microstate C and levels of IL-2, TNF-α, hs-CRP than HC group. The duration, occurrence and coverage of microstate D were negatively correlated with levels of pro-inflammatory factors (IL-2, TNF- α and hs- CRP) (all P < 0.05). Serum pro-inflammatory induced the abnormalities of microstate D. Together, these findings add to the understanding of the pathophysiology of MDD and point to pro-inflammatory factors contribute to EEG microstate abnormalities in patients with MDD.

Use of a Minimally Invasive Traction Repositor versus Conventional Manual Traction for the Treatment of Tibial Fractures: A Comparative Study from a Tertiary Hospital in China.

Background: Closed reduction and intramedullary nail fixation of tibial fractures may not utilize a fracture table or reduction aids like a femoral distractor, and only manual traction will help aid the reduction process. This study aimed to describe and further investigate the effectiveness of an originally designed minimally invasive traction repositor (MITR) for the treatment of tibial fractures. Methods: From January 2018 to April 2021, a total of 119 eligible patients with tibial shaft fractures were included and retrospectively assigned to two groups according to different reduction methods: MITR group vs conventional manual traction (CMT) group. The baseline characteristics between the two groups were comparable, including age, gender, BMI, residence, smoking history, drinking history, injury mechanism, fracture type, ASA, method of anesthesia, and surgical delay (all P > 0.05). The operation time, fracture reduction duration, intraoperative blood loss, fluoroscopy time, number of intraoperative fluoroscopies, VAS, HSS, fracture healing time, and complications were compared. Results: All patients completed the follow-ups with an average of 18.5 months (range 12-42 months). The operation time, fracture reduction duration, intraoperative blood loss, fluoroscopy time, and number of fluoroscopies were significantly decreased in the MITR group (all P < 0.05). At one month postoperatively, the VAS score was statistically lower in the MITR group (1.8±0.8) than in the CMT group (2.6±1.5). At 6 months postoperatively, the HHS score was statistically higher in the MITR group (90.8±2.3) than in the CMT group (86.4±3.8). We observed no statistical difference in the mean fracture healing time, bone nonunion, implant failure, and infection between the two groups (all P > 0.05). Conclusion: Compared with CMT, MITR facilitates the minimally invasive treatment of tibial fractures and has the advantages of operation time, fracture reduction duration, intraoperative blood loss, fluoroscopy time, number of fluoroscopies, and satisfactory VAS and HSS scores.

Clinical Outcomes of Cannulated Screws versus Ring Pin versus K-Wire with Tension Band Fixation Techniques in the Treatment of Transverse Patellar Fractures: A Case-Control Study with Minimum 2-Year Follow-Up.

Purpose: K-wire with tension band (KTB) technique has long been the primary surgical method for transverse patella fractures; however, it also has shortcomings. This study is aimed at evaluating the three different techniques to see whether the cannulated screw tension band (CSTB) or ring pin tension band (RPTB) techniques could decrease complications and achieve better knee function compared with KTB. Methods: We conducted a retrospective comparison of the KTB, CSTB, and RPTB fixation techniques. We selected and reviewed 90 patients (30 patients in each fixation group) with follow-up at least 2 years. Duration of operation, intraoperative blood loss, mean healing time, visual analog scale score, range of motion, Böstman score, Iowa knee score, modified Lysholm rating scale, and postoperative complications were compared. Multivariate analyses were performed to identify the independent risk factors for fracture healing time, postoperative complications, and knee function recovery. Results: After adjusting for confounding factors, multivariate regression analysis revealed that CSTB was 0.26 times (95% CI: 0.08-0.86, p = 0.027) less likely to prolong fracture healing time, 0.20 times (95% CI: 0.06-0.64, p = 0.007) lesser risk of postoperative complications, and more than four times (95% CI: 1.41-13.56, p = 0.011) as likely to improve the knee function score compared with KTB. Besides, RPTB were also superior to KTB in reducing the incidence of postoperative complications (OR: 0.21, 95% CI: 0.07-0.64, p = 0.006) and improved knee function score (OR: 3.96, 95% CI: 1.30-12.08, p = 0.016); however, the CSTB group being more superior. In addition, AO/OTA C2 fractures (OR, odds ratio: 10.68, 95% CI: 1.30-87.70, p = 0.027) and high-energy fracture (OR: 8.78, 95% CI: 1.57-49.17, p = 0.013) were also associated with prolonged fracture healing time but not with postoperative complications and knee function. No significant differences in related indicators such as gender, age, BMI, AO/OTA classification, fracture side, injury mechanism, duration of operation, and intraoperative blood loss were detected among the three groups. Conclusion: This study demonstrated that the CSTB technique is superior to KTB and RPTB techniques in reducing the incidence of postoperative complications, and it also has advantages in accelerating fracture healing, achieving better VAS, ROM, and functional recovery. Further long-term large-sized prospective randomized trials are needed to evaluate the efficacy of the KTB in treating transverse patellar fractures.

Analysis of the Effect of Posterior Lateral Malleolus Plate Fixation on the Curative Effect and Mechanical Stability of Complex Ankle Fractures.

This paper investigates the effect of lateral and posterior 1/3 tubular plate bone plate fixation on the curative effect, wound healing, and mechanical stability of complex ankle fracture. 80 patients with complex ankle fractures treated in our hospital from January 2018 to July 2020 are selected for the study, and 80 patients are randomly divided into posterior fixation group and lateral fixation group according to the number table method, with 40 patients in each group. Patients in the posterior malleolus fixation group are treated with posterior lateral malleolus plate fixation, and patients in the lateral malleolus fixation group are treated with lateral malleolus plate fixation. The differences in efficacy, mechanical stability, wound healing, visual analog scale (VAS) pain score, and American Association of Foot and Ankle Surgery (AOFAS) ankle function are compared. The subjects are followed up for 6 months until January 2022. In patients with complex ankle fracture, 1/3 tubular plate osteoplate fixation in the posterior lateral malleolus can improve clinical efficacy and mechanical stability, which is helpful to promote incision healing and reduce the risk of complications. The 1/3 tubular plate osteoplate fixation in the posterior lateral malleolus is worthy of clinical promotion and application.

[Application value of D-dimer in preoperative diagnosis of low toxic infectious nonunion].

OBJECTIVE: To evaluate the value of D-dimer and common hematological indexes in the preoperative diagnosis of low toxicity infectious bone nonunion. METHODS: Total of 116 cases of bone nonunion from June 2015 to January 2020 were analyzed retrospectively, including 91 males and 25 females;the age ranged from 18 to 65 years old with an average of(45.3±11.2) years old. According to the diagnostic criteria, 116 cases were divided into low toxicity infectious bone nonunion group(31 cases) and aseptic bone nonunion group(85 cases). D-dimer, total leukocyte count, C-reactive protein and erythrocyte sedimentation rate(ESR) were measured at admission, and the differences between two groups were compared. The diagnostic accuracy, sensitivity and specificity were analyzed through the subject working characteristic curve and the area under the curve. RESULTS: All patients were followed up for 12 to 24 months with an average of (11.5±4.3) months. D-dimer, total leukocyte count, C-reactive protein and ESR in low toxicity infectious bone nonunion group were higher than those in aseptic bone nonunion group(P<0.05);compared with other hematological indexes, the area under the curve of D-dimer was the highest, which is 0.826, and the best cut-off value of D-dimer was 1.57 g/L. The sensitivity and specificity of preoperative diagnosis of low toxicity infectious bone nonunion were 78.3% and 84.2%. CONCLUSION: The preoperative diagnostic value of D-dimer in low toxicity infectious bone nonunion is better than other inflammatory indexes. The combination of D-dimer and other inflammatory indexes is conducive to the early diagnosis of low toxicity infectious bone nonunion and the evaluation of the condition.

Research on thermoeconomic fault diagnosis for marine low speed two stroke diesel engine.

To satisfy the requirements of low fuel consumption, low emission, and high efficiency of the shipping industry, marine diesel engines are developing in the direction of automation and energy-saving, which increases the possibility and complexity of marine diesel engine failures. A one-dimension thermodynamic model for the marine diesel engine is built with AVL Boost software. The model is applied to a low-speed two-stroke 6S50MC diesel engine, and the error between the main performance parameters obtained by simulation and the test bench data is less than 3% under 100% and 75% load. Based on the model, 6 typical single faults and many typical double faults concomitant phenomena of diesel are reproduced. Based on the second law of thermodynamics, the exergy flow among the components and the external environment is analyzed. The thermoeconomic model of a marine diesel engine is established where the "fuel" and "product" of the components are defined according to their function. The fault diagnosis results show that the effects of faults generally propagate through the diesel engine system and affect the behavior of several components, resulting in induced malfunction in normal components. Therefore the malfunction MFi of each component is the superposition of the intrinsic malfunction and the induced malfunction according to the malfunction and dysfunction analysis. The thermoeconomic fault diagnosis method can be used to narrow the search range of abnormal components though it cannot accurately locate the fault.

Study on seafloor hydrothermal systems circulation flow and heat transfer characteristics.

In this work, the numerical simulation study of the hydrothermal flow and heat transfer process in the porous rock under 30 MPa pressure was developed. The flow and heat transfer characteristics of hydrothermal in rocks with different porosities are studied by changing the porosity of the rock. The simulation results show that the average flow velocity decreases and the average temperature increases when the porosity decreases. The velocity field and temperature field are coupled due to the nonlinear thermophysical properties of hydrothermal. The velocity field and temperature field have strongly interacted in the range of 400-450 ℃ and the effect of temperature on velocity is gradually diminishing outside the range. Most of the fluid will be "squeezed" into the crevice and the average velocity is almost three times the no-creviced case when a crevice is present. The existence of the crevice makes the total heat flux decrease from an overall perspective, and the crevice makes a large temperature gradient at the entrance and export of the crevice from a local perspective. These results provide theoretical support for the utilization of submarine hydrothermal fluid shallow circulation heat energy.

Use of Intravenous Paracetamol Preoperatively Favors Lower Risk of Delirium and Functional Recovery in Elderly Patients with Hip Fracture: A Propensity Score-Matched Analysis.

We aimed to investigate whether the use of intravenous paracetamol (IVP) preoperatively in intertrochanteric fracture (IF) patients aged 65 years or over receiving intramedullary fixation had significantly benefits on the pain score at discharge, delirium incidence, length of hospital stay (LOS), functional outcomes, and mortality. A retrospective analysis of all surgically treated patients presenting with IF was conducted at a single Level I trauma center in China between Jan. 2016 and Jan. 2020. The data concerning patients' demographics, injury-related data, surgery-related data, operation-related data, in-hospital data, and postoperative outcomes were extracted. To minimize potential confounding and selection bias, the propensity score matching (PSM) method was performed via the caliper matching method by using a 1 : 1 ratio. After PSM, McNemar's chi-square tests were used to examine the association of using IVP with outcome analyses. The Spearman correlations of IVP using, pain scores, and the factors which may influence them were also computed. After screening 2963 consecutive patients, 2166 were included finally, including 1576 in the non-IVP group and 590 in the IVP group. After PSM, 531 remained in each group. The pain scores at discharge were significantly between the two groups before and after matching (all p < 0.001). The differences of delirium rate and functional outcomes became significant after propensity score-based matching (p=0.001 and 0.033, respectively), although they were not significant before matching. No significant difference was observed in other operation-related data, LOS, and crude mortality rates at 30-day, 90-day, and 12-month before and after PSM. In conclusion, this study highlights the need for preoperative IVP use to optimize pain control, postoperative functional recovery, and minimize pain-related comorbidities such as delirium in elderly patients with hip fracture.

Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis.

The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.

Detection of catecholamine metabolites in urine based on ultra-high-performance liquid chromatography-tandem mass spectrometry.

The excretion of neurotransmitter metabolites in normal individuals is of great significance for health monitoring. A rapid quantitative method was developed with ultra-performance liquid chromatography-tandem mass spectrometry. The method was further applied to determine catecholamine metabolites vanilymandelic acid (VMA), methoxy hydroxyphenyl glycol (MHPG), dihydroxy-phenyl acetic acid (DOPAC), and homovanillic acid (HVA) in the urine. The urine was collected from six healthy volunteers (20-22 years old) for 10 consecutive days. It was precolumn derivatized with dansyl chloride. Subsequently, the sample was analyzed using triple quadrupole mass spectrometry with an electrospray ion in positive and multireaction monitoring modes. The method was sensitive and repeatable with the recoveries 92.7-104.30%, limits of detection (LODs) 0.01-0.05 µg/mL, and coefficients no less than 0.9938. The excretion content of four target compounds in random urine samples was 0.20 ± 0.086 µg/mL (MHPG), 1.27 ± 1.24 µg/mL (VMA), 3.29 ± 1.36 µg/mL (HVA), and 1.13 ± 1.07 µg/mL (DOPAC). In the urine, the content of VMA, the metabolite of norepinephrine and adrenaline, was more than MHPG, and the content of HVA, the metabolite of dopamine, was more than DOPAC. This paper detected the levels of catecholamine metabolites and summarized the characteristics of excretion using random urine samples, which could provide valuable information for clinical practice.

Identification of Immune Infiltration and the Potential Biomarkers in Diabetic Peripheral Neuropathy through Bioinformatics and Machine Learning Methods.

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications in diabetes. Previous studies have shown that chronic neuroinflammation was associated with DPN. However, further research is needed to investigate the exact immune molecular mechanism underlying the pathogenesis of DPN. Expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by R software. After functional enrichment analysis of DEGs, a protein-protein interaction (PPI) network analysis was performed. The CIBERSORT algorithm was used to evaluate the infiltration of immune cells in DPN. Next, the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were applied to identify potential DPN diagnostic markers. Finally, the results were further validated by qRT-PCR. A total of 1308 DEGs were screened in this study. Enrichment analysis identified that DEGs were significantly enriched in immune-related biological functions and pathways. Immune cell infiltration analysis found that M1 and M2 macrophages, monocytes, resting mast cells, resting CD4 memory T cells and follicular helper T cells were involved in the development of DPN. LTBP2 and GPNMB were identified as diagnostic markers of DPN. qRT-PCR results showed that 15 mRNAs, including LTBP2 and GPNMB, were differentially expressed, consistent with the microarray results. In conclusion, LTBP2 and GPNMB can be used as novel candidate molecular diagnostic markers for DPN. Furthermore, the infiltration of immune cells plays an important role in the progression of DPN.

Effect of General vs. Regional Anesthesia on Mortality, Complications, and Prognosis in Older Adults Undergoing Hip Fracture Surgery: A Propensity-Score-Matched Cohort Analysis.

The choice of the type of anesthesia (TOA) used in hip fracture surgery in older adults is still controversial. The main question is not whether regional anesthesia (RA) or general anesthesia (GA) is superior, but in which patients the type of anesthesia may affect the outcome after surgery. In this retrospective analysis of surgically treated intertrochanteric fracture patients, we used propensity score matching (PSM) to investigate whether clinically relevant differences in outcomes were observed in mortality, complications, and functional outcomes between RA and GA. After screening 2934 consecutive patients, 2170 were ultimately included, including 841 in the GA group and 1329 in the RA group. After PSM, 808 remained in each group. Patients receiving GA were more prone to have a shorter duration for their operation and higher total hospital costs than patients with RA (p = 0.034 and 0.004, respectively). We also observed that the GA group has a higher rate of pulmonary complications, while the RA group has a higher rate of cardiac complications (p = 0.017 and 0.011, respectively). No significant difference was observed in mortality, functional outcomes, and other complications (all p > 0.05). The clinical innovation of this study was the potential value of GA for patients with cardiac diseases and of RA for patients with pulmonary diseases.

Preparation, Characterization, and Bioavailability of Host-Guest Inclusion Complex of Ginsenoside Re with Gamma-Cyclodextrin.

This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (ß), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M-1 (α-CD), 612 M-1 (ß-CD), and 14,410 M-1 (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of -4.7 (α-CD), -5.10 (ß-CD), and -6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC0-∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re's inclusion into γ-CD, and explored the inclusion complex's mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.