[Research and development strategy of new traditional Chinese medicine drugs for syndromes based on human use experience].

Chinese drug registration laws and regulations have always reserved a place for the new traditional Chinese medicine(TCM) drugs for syndromes, but so far no such new drugs have been approved for registration. This paper expounded on the relevant policies, regulations, and technologies of new TCM drugs for syndromes in China and pointed out that the application of the animal model of TCM syndromes to carry out pharmacodynamics research and clinical efficacy evaluation criteria of TCM syndromes were the main technical difficulties in the research and development of new TCM drugs for syndromes. Not all syndromes are suitable for developing new drugs, and the indications for new TCM drugs should be constant syndromes. Among the three research and development models of simple syndrome, syndrome-unified disease, and combined disease and syndrome, the research and development model of combined disease and syndrome is recommended. Clinical positioning is the key to new TCM drugs for syndromes. It is encouraged to conduct high-quality human use experience studies to determine the clinical positioning of new TCM drugs for syndromes, as well as the target population, dose, course of treatment, and initial therapeutic and safety, and apply for exemption from non-clinical effectiveness studies. Clinical trials of new TCM drugs for syndromes should take the target symptoms or signs as the main efficacy index and the efficacy of TCM syndromes as the secondary efficacy index. Clinical research program design should implement the "patient-centered" concept and introduce clinical outcome evaluation indicators. In the clinical safety evaluation, special conditions such as characteristic syndromes and changes should be considered. With the construction of the human use experience technology system and the promotion of the TCM registration and evaluation evidence system featuring the "combination of TCM theory, human use experience, and clinical trials", it is believed that many high-quality new TCM drugs for syndromes will be developed in the future.

Clinical characteristics and removal approaches of tracheal and bronchial foreign bodies in elders.

The symptoms of tracheobronchial foreign body in the elderly are not typical, so they are often missed or misdiagnosed. This study aims to depict the clinical characteristics of tracheobronchial foreign body inhalation in the elderly. We retrospectively analysed the clinical data of elder patients (age ≥ 65 years) diagnosed with tracheal and bronchial foreign bodies. The data included age, sex, clinical symptoms, type and location of foreign bodies, prehospital duration, Chest CT, bronchoscopic findings, and frequencies and tools for removing these elderly patients' tracheal and bronchial foreign bodies. All patients were followed up for a half year. Fifty-nine cases were included, of which only 32.2% had a definite aspiration history. Disease duration > 30 days accounted for 27.1% of the patients. 27.1% of the patients had a history of stroke, and 23.8% had Alzheimer's Disease. Regarding clinical symptoms, patients mainly experience cough and expectoration. The most common CT findings were abnormal density shadow (37.3%) and pulmonary infiltration (22.0%). Under bronchoscopy, purulent secretions were observed in 52.5% of patients, and granulation tissue hyperplasia was observed in 45.8%. Food (55.9%) was the most common foreign object, including seafood shells (5.1%), bones (20.3%), dentures (18.6%), and tablets (20.3%). The success rate of foreign body removal under a bronchoscope was 96.7%, 28.8% of the foreign bodies were on the left and 69.5% on the right. 5.1% of the elderly patients required rigid bronchoscopy, and 6.8% required two bronchoscopies. In elderly cohorts, tracheal foreign bodies are obscured by nonspecific clinical presentations and a paucity of aspiration history, challenging timely diagnosis. Predominantly constituted by food particles, with a notable predilection for the left bronchial tree, these cases demand skilled bronchoscopic management, occasionally requiring sophisticated approaches for successful extraction.

Gearbox fault diagnosis method based on lightweight channel attention mechanism and transfer learning.

In practical engineering, the working conditions of gearbox are complex and variable. In varying working conditions, the performance of intelligent fault diagnosis model is degraded because of limited valid samples and large data distribution differences of gearbox signals. Based on these issues, this research proposes a gearbox fault diagnosis method integrated with lightweight channel attention mechanism, and further realizes the cross-component transfer learning. First, time-frequency distribution of original signals is obtained by wavelet transform. It could intuitively reflect local characteristics of signals. Secondly, based on a local cross-channel interaction strategy, a lightweight efficient channel attention mechanism (LECA) is designed. The kernel size of 1D convolution is affected by channel number and coefficients. Multi-scale feature input is used to retain more detailed features of different dimensions. A lightweight convolutional neural network is constructed. Finally, a transfer learning method is applied to freeze lower structures of the network and fine-tune higher structures of the model using small samples. Through experimental verification, the proposed model could effectively utilize samples. The application of transfer learning could realize accurate and fast fault classification of small samples, and achieve good gearbox fault diagnosis effect under varying working conditions and cross-component conditions.

The influence of H2O or/and O2 introduction during the low-temperature gas-phase sulfation of organic COS + CS2 on the conversion and deposition of sulfur-containing species in the sulfated CeO2-OS catalyst for NH3-SCR.

Herein, the typical components of blast furnace gas, including H2O and O2, were introduced to improve the NH3-SCR activity of the sulfated CeO2-OS catalyst during the gas-phase sulfation of organic COS + CS2 at 50 °C. The characterization results demonstrate that the introduction of O2 or H2O during gas-phase sulfation enhances the conversion of organic COS + CS2 on a cubic fluorite CeO2 surface and reduces the formation of sulfur and sulfates in the catalyst, but decreases the BET surface area and pore volume of the sulfated CeO2-OS catalyst. However, the introduction of O2 or H2O during the gas-phase sulfation increases the molar ratios of Ce3+/(Ce3+ + Ce4+) and Oß/(Oα + Oß + Oγ) on the sulfated CeO2-OS catalyst surface, thus promoting the formation of surface oxygen vacancies and chemisorbed oxygen, and these properties of the catalyst are further enhanced by the co-existence of O2 and H2O. Furthermore, the reduction of sulfates formed under the action of O2 or H2O decreases the weak acid sites of the sulfated CeO2-OS catalyst, but the few and highly dispersive sulfates present stronger reducibility, and the proportion of medium-strong acid sites of the catalyst increases. These factors help to improve the NH3-SCR activity of the sulfated CeO2-OS catalyst. Thus, there exists a synergistic effect of H2O and O2 introduction during gas-phase sulfation on the physical-chemical properties and catalytic performance of the sulfated CeO2-OS catalyst by organic COS + CS2 at 50 °C.

Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice.

We investigated the effect of eldecalcitol on disuse muscle atrophy. C57BL/6J male mice aged 6 weeks were randomly assigned to control, tail suspension (TS), and TS-eldecalcitol-treated groups and were injected intraperitoneally twice a week with either vehicle (control and TS) or eldecalcitol at 3.5 or 5 ng for 3 weeks. Grip strength and muscle weights of the gastrocnemius (GAS), tibialis anterior (TA), and soleus (SOL) were determined. Oxidative stress was evaluated by malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase. Bone microarchitecture was analyzed using microcomputed tomography. The effect of eldecalcitol on C2C12 myoblasts was analyzed by measuring myofibrillar protein MHC and the atrophy markers Atrogin-1 and MuRF-1 using immunofluorescence. The influence of eldecalcitol on NF-κB signaling pathway and vitamin D receptor (VDR) was assessed through immunofluorescence, (co)-immunoprecipitation, and VDR knockdown studies. Eldecalcitol increased grip strength (P < 0.01) and restored muscle loss in GAS, TA, and SOL (P < 0.05 to P < 0.001) induced by TS. An improvement was noted in bone mineral density and bone architecture in the eldecalcitol group. The impaired oxidative defense system was restored by eldecalcitol (P < 0.05 to P < 0.01 vs. TS). Eldecalcitol (10 nM) significantly inhibited the expression of MuRF-1 (P < 0.001) and Atrogin-1 (P < 0.01), increased the diameter of myotubes (P < 0.05), inhibited the expression of P65 and P52 components of NF-κB and P65 nuclear location, thereby inhibiting NF-κB signaling. Eldecalcitol promoted VDR binding to P65 and P52. VDR signaling is required for eldecalcitol-mediated anti-atrophy effects. In conclusion, eldecalcitol exerted its beneficial effects on disuse-induced muscle atrophy via NF-κB inhibition.

[Quality requirements of human use experience research on traditional Chinese medicine].

The human use experience of traditional Chinese medicine(TCM) is of great significance for the development of new traditional Chinese medicine. In 2023, the National Medical Products Administration(NMPA) issued the Special Regulations on Registration Management of Traditional Chinese Medicine, which explicitly encouraged the conduct of high-quality human use experience research on TCM clinical practice to obtain sufficient evidence for registration support. It also required that human use experience research should comply with relevant requirements and undergo registration verification. The quality of human use experience research on TCM directly determines the reliability of the evidence. This article discussed the quality requirements for human use experience research on TCM from the perspectives of basic requirements, organizational management, key pharmaceutical information, scientific research, risk management, ethical compliance, and study implementation and proposed differential treatment in quality requirements and registration verification focus based on different research purposes, stages, and types of studies. While ensuring the authenticity of data, retrospective studies should pay particular attention to the integrity of the data, and prospective studies should focus on the normativity of the data, which may affect the research conclusions. Human use experience research, as part of drug registration materials, falls within the scope of relevant regulatory oversight. Researchers should have a strong awareness of regulations to avoid serious quality issues. The standardized conduct of human use experience research on TCM requires joint efforts from regulatory authorities, applicants, research institutions, and researchers to establish a research quality management system based on the clinical characteristics of TCM.

[Construction of clinical efficacy evaluation system based on optimal clinical experience].

Evidence-based medicine plays an important role in promoting the scientific nature of clinical decision-making. Howe-ver, there is a problem where evidence derived from clinical research may not necessarily be applicable to individual patients. Evidence-based medicine has been introduced into the field of traditional Chinese medicine(TCM) for over 20 years, and although certain achievements have been made, the overall level of clinical research evidence based on the principles of evidence-based medicine in TCM is not high. The acceptance of TCM diagnosis and treatment guidelines developed based on evidence-based medicine methods is generally low. As revealed by the analysis of the problems in the application of evidence-based medicine in the field of TCM, it is found that there is a structural contradiction between clinical randomized controlled trial(RCT) of TCM and the characteristics of TCM clinical practice. They cannot comprehensively, objectively, and truthfully reflect the clinical efficacy and safety of TCM. Conducting clinical RCTs of TCM in pursuit of "evidence" actually means giving up the advantages of TCM in clinical treatment based on syndrome differentiation, prescription changes along with syndromes, and treatment in accordance with three categories of disease cause, which leads to sacrificing some clinical effectiveness of TCM. Based on the concept of evidence-based medicine, this article proposed the construction of "clinical syndrome-based medicine" based on the optimal clinical experience, which was suitable for the characteristics of TCM clinical practice. The key to clinical syndrome-based medicine is the optimal clinical experience, and the core elements of the optimal clinical experience are regularity and reproducibility. Real-world research methods are recommended as a reference for obtaining the optimal clinical experience. Clinical syndrome-based medicine, combining the characteristics of TCM clinical practice and incorporating the concept of evidence-based medicine, is the product of integrating TCM into evidence-based medicine. It is dedicated to improving the clinical efficacy of TCM along with evidence-based medicine.

SERPINE1 and SERPINB7 as potential biomarkers for intravenous vitamin C treatment in non-small-cell lung cancer.

High dose intravenous vitamin C (IVC) has been proposed as a pro-oxidant anticancer agent. However, there is a lack of biomarkers that are specific for this treatment. Here, we explored profiles of gene expression responding to IVC treatment in non-small cell lung cancer (NSCLC) cells as an effort for potential biomarker discovery. Genome-wide RNA-seq was performed in human NSCLC cell lines treated with pharmacological concentrations of vitamin C(VitC) for differential expression of genes. The identified genes were analyzed for correlations with patient prognosis using data from the Kaplan-Meier Plotter and the Human Protein Atlas databases. Further, tumor samples from a retrospective study of 153 NSCLC patients were analyzed with immunohistochemistry for expression of targeted genes, and patient prognosis was correlated to these genes. Two genes, namely SERPINE1 and SERPINB7 were found to be downregulated in NSCLC cells following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that these 2 genes presented an unfavorable prognostic prediction of overall survival (OS) in NSCLC patients receiving standard of care. However, high expression level of these 2 genes were associated with prolonged OS in NSCLC patients receiving IVC in addition to standard of care. These data revealed that SERPINE1 and SERPINB7 have the potential to serve as predictive factors indicating favorable responses to IVC treatment in patients with NSCLC. Further validations are warranted.

Optimization of Gearbox Fault Detection Method Based on Deep Residual Neural Network Algorithm.

Because of its long running time, complex working environment, and for other reasons, a gear is prone to failure, and early failure is difficult to detect by direct observation; therefore, fault diagnosis of gears is very necessary. Neural network algorithms have been widely used to realize gear fault diagnosis, but the structure of the neural network model is complicated, the training time is long and the model is not easy to converge. To solve the above problems and combine the advantages of the ResNeXt50 model in the extraction of image features, this paper proposes a gearbox fault detection method that integrates the convolutional block attention module (CBAM). Firstly, the CBAM is embedded in the ResNeXt50 network to enhance the extraction of image channels and spatial features. Secondly, the different time-frequency analysis method was compared and analyzed, and the method with the better effect was selected to convert the one-dimensional vibration signal in the open data set of the gearbox into a two-dimensional image, eliminating the influence of the redundant background noise, and took it as the input of the model for training. Finally, the accuracy and the average training time of the model were obtained by entering the test set into the model, and the results were compared with four other classical convolutional neural network models. The results show that the proposed method performs well both in fault identification accuracy and average training time under two working conditions, and it also provides some references for existing gear failure diagnosis research.

PIK3R6 Promotes Angiogenesis in Hepatocellular carcinoma by Activating STAT3 Signaling Pathway.

Objective: Abundant angiogenesis in hepatocellular carcinoma (HCC) is critical in its malignant course; however, its mechanism is incompletely understood. Meanwhile, the corresponding roles of PIK3R6 molecules in HCC have not been investigated. This study aims to explore the intrinsic mechanism of PIK3R6 and provide theoretical reference for the treatment of hepatocellular carcinoma. Methods: Differential expressions of PIK in ovarian cancer and normal ones were detected by Western blotting and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Analyze the relationship between the expression of PIK3R6 and patient prognosis through the TCGA database. Subsequently constructed corresponding stable cell lines, combined with transcriptome sequencing and several cell biology experiments, we explored the inner mechanism and clinical significance of PIK3R6. Results: By analyzing multiple cohorts, we found that high PIK3R6 expression in tumor tissues negatively correlates with patient prognosis. PIK3R6 could increase angiogenesis in HCC by boosting the activity of the STAT3 signalling pathway to hasten the malignant progression of the disease, according to corresponding cellular and molecular experimental studies. Then again, immunohistochemistry on a series of tissue chips confirmed the important clinical significance of PIK3R6-STAT3 regulatory axis. Couclusions: This study initially addressed the clinical significance of PIK3R6 and revealed its mechanism for promoting angiogenesis in hepatocellular carcinoma, providing a reliable working foundation for future in-depth research and clinical translation.

High-Flow Nasal Oxygen versus Noninvasive Ventilation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients: A Meta-Analysis of Randomized Controlled Trials.

Background: High-flow nasal cannula (HFNC) can be used in stable chronic obstructive pulmonary disease (COPD) patients, but the effect of HFNC on clinical outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is still uncertain. Methods: We searched electronic literature databases for randomized controlled trials (RCTs) comparing HFNC with noninvasive ventilation (NIV) in hypercapnic patients with AECOPD. The primary endpoint of this meta-analysis was PaCO2, PaO2, and SpO2. The secondary outcomes were the respiratory rate, mortality, complications, and intubation rate. Results: We included 7 RCTs with a total of 481 patients. There were no significant differences on measures of PaCO2 (MD = -0.42, 95%CI -3.60 to 2.75, Z = 0.26, and P = 0.79), PaO2 (MD = -1.36, 95%CI -4.69 to 1.97, Z = 0.80, and P = 0.42), and SpO2 (MD = -0.78, 95%CI -1.67 to 0.11, Z = 1.72, P = 0.08) between the HFNC group and the NIV group. There was no significant difference in measures of the mortality and intubation rate between the HFNC group (OR = 0.72, 95%CI 0.30 to 1.69, Z = 0.76, and P = 0.44) and the NIV group (OR = 2.38, 95%CI 0.49 to 11.50, Z = 1.08, and P = 0.28), respectively. But the respiratory rate in the HFNC group was lower than that in the NIV group (MD = -1.13, 95%CI -2.13 to -0.14, Z = 2.23, and P = 0.03), and fewer complications were found in the HFNC group (OR = 0.26, 95%CI 0.14 to 0.47, Z = 4.46, and P < 0.00001). Conclusion: NIV was noninferior to HFNC in decreasing PaCO2 and increasing PaO2 and SpO2. Similarly, the mortality and intubation rate was similar among the two groups. The respiratory rate and complications were inferior in the AECOPD group treated with HFNC.

Comparison of vasoactive-inotropic score, vasoactive-ventilation-renal score, and modified vasoactive-ventilation-renal score for predicting the poor prognosis after coronary artery bypass grafting.

BACKGROUND: Exploring reliable prediction scoring systems is valuable for the poor prognosis of patients after coronary artery bypass grafting (CABG). Herein, we explored and compared the predictive performance of vasoactive-inotropic score (VIS), vasoactive-ventilation-renal (VVR) score, and modified VVR (M-VVR) score in the poor prognosis of patients undergoing CABG. METHODS: A retrospective cohort study was performed in Affiliated Hospital of Jining Medical University, and data of 537 patients were collected from January 2019 to May 2021. The independent variables were VIS, VVR, and M-VVR. Study endpoint of interest was the poor prognosis. Association between VIS, VVR, M-VVR and poor prognosis was assessed using logistic regression analysis, and odds ratios (OR) and 95% confidence intervals (CIs) were reported. The performance of VIS, VVR, and M-VVR to predict the poor prognosis was assessed by calculating the area under the curve (AUC), and differences of the AUC of the three scoring systems were compared using DeLong test. RESULTS: After adjusting gender, BMI, hypertension, diabetes, surgery methods, and left ventricular ejection fraction (LVEF), VIS (OR: 1.09, 95%CI: 1.05-1.13) and M-VVR (OR: 1.09, 95%CI: 1.06-1.12) were associated with the increased odds of poor prognosis. The AUC of M-VVR, VVR, and VIS was 0.720 (95%CI: 0.668-0.771), 0.621 (95%CI: 0.566-0.677), and 0.685 (95%CI: 0.631-0.739), respectively. DeLong test displayed that the performance of M-VVR was better than VVR (P = 0.004) and VIS (P = 0.003). CONCLUSIONS: Our study found the good prediction performance of M-VVR for the poor prognosis of patients undergoing CABG, indicating that M-VVR may be a useful prediction index in the clinic.

Novel nano spinel-type high-entropy oxide (HEO) catalyst for hydrogen production using ethanol steam reforming.

Catalyst sintering caused by high temperature operating conditions during ethanol steam reforming (ESR) is a common issue for traditional catalysts with low Tammann temperature metals. In recent years, high entropy oxides have been popular in thermal catalysis due to their special thermodynamics and kinetics characteristics, which is expected to be a suitable approach for enhancing catalyst stability. This paper first reports the application of HEO in ESR and the characterization. The results exhibited a nano structure (CoCrFeNiAl)3O4 HEO with a spinel-phase and was successfully synthesized by a polyol hydrothermal precipitation-calcination method. An abundance of oxygen vacancies were formed, and were further enriched in a hydrogen atmosphere as the M-O bond opened. Interestingly, its self-reorganization featured the rendered the metals spilling out of the HEO bulk phase as active species for hydrogen production during ESR, whereas the isolated metal cation randomly dissolved into the parent metal oxide cell again after the reaction instead of agglomerating over the catalyst surface. This gave the (CoCrFeNiAl)3O4 a large number of dispersed active sites, as well as a high thermal stability. In addition, 81% of the hydrogen yield as well as 85% of H2 selectivity were achieved at 600 °C. This research might offer possibilities for the development of thermal catalytic hydrogen production under high temperature conditions such as steam reforming.

[Technical points of human use experience of ethnic medicine].

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.

BJTJ-1837, a novel FXI activation-blocking antibody.

Background: Factor (F)XI contributes to thrombosis development while it plays a limited role in normal hemostasis. FXI targeting has the potential for preventing and treating thrombosis with little bleeding risk. Objectives: The aim of this study was to develop novel antibody therapeutics against FXI for the treatment of thrombosis-related diseases. Methods: Mouse hybridoma technology was applied to screen for anti-FXI antibodies. Surface plasma resonance, enzyme inhibition, activated partial thromboplastin time, and prothrombin time assays were conducted to characterize the binding affinity and activity of antibodies. A cynomolgus monkey arterial venous shunt model was applied to validate the antithrombotic activities. Results: A humanized antibody, BJTJ-1837, reported here bound to the protease domain of FXI and activated FXI with high affinity. BJTJ-1837 fully inhibited the activation of FXI by activated FXII and thrombin. BJTJ-1837 also demonstrated strong anticoagulant activity in human and cynomolgus monkey plasma as measured by activated partial thromboplastin time. Moreover, BJTJ-1837 showed favorable antithrombotic activity with a dose-dependent protection in an arterial venous shunt thrombosis model in cynomolgus monkeys without the bleeding adverse effect. Furthermore, BJTJ-1837 displayed favorable pharmacokinetic and pharmacodynamic properties and good developability. Conclusion: As a potential antithrombotic therapeutic agent with a safe profile, BJTJ-1837 is a very promising FXI activation-blocking antibody candidate.

RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression.

Increased angiogenesis in the liver plays a critical role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying increased angiogenesis in HCC is not well understood. Current study was designed to identify the potential angiogenic effect of RNA-binding motif 4 (RBM4)through a small-scale overexpression screening, followed by comparison of the expression level of RBM4 in cancer and adjacent tissues in multiple malignancies to explore the relationship between RBM4 and CD31 protein expression level and related clinical indicators, and understand the role of RBM4 in the hepatocellular carcinoma. To understand the specific mechanism of RBM4 in detail, transcriptome sequencing, mass spectrometry and multiple molecular cytological studies were performed. These cellular level results were verified by experiments in animal models of nude mice. The increased expression of RBM4 in cancer tissues, suggested its use as a prognostic biomarker. The RBM4 expression was found to be strongly correlated with tumor microvessel density. Mechanistically, RBM4 mediated its effects via interaction with HNRNP-M through the latter's WDR15 domain, which then stabilized RelA/p65 mRNA. Consequently, RBM4 induced the activation of the NF-kB signaling pathway, upregulating the expression of proangiogenic factor VEGF-A. The results confirmed the mechanism by which RBM4 promotes angiogenesis in hepatocellular carcinoma suggesting RBM4 as a crucial promoter of angiogenesis in HCC, helping understand regulation of NF-kB signaling in HCC.

[Advances in the study of vasoactive-inotropic score in critically ill patients].

The degree of hemodynamic support by vasoactive drugs in critically ill patients is often considered one of the markers of disease severity. The sequential organ failure assessment (SOFA), European system for cardiac operative risk evaluation II (EuroScore II), and other scores only roughly quantify the drug support of cardiovascular system. When patients need large doses of vasoactive drugs, the mortality increases accordingly. The vasoactive-inotropic score (VIS) objectively quantifies the degree of cardiovascular support using a simple formula that standardizes the dose of different agents, and it is recommended as a simple, effective, and accurate prognostic indicator. In recent years, there are more and more clinical applications and related studies at home and abroad. This paper reviews the application and progress of VIS score in critically ill patients, providing help for doctors to judge the condition and prognosis of patients and guiding the decision-making of diagnosis and treatment.

Association between Serum Oxytocin, Bone Mineral Density and Body Composition in Chinese Adult Females.

Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.

Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice.

Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.

Review on LSPR assisted photocatalysis: effects of physical fields and opportunities in multifield decoupling.

Since nano scale local surface plasmon resonance (LSPR) can broaden the visible absorption region, enhance the local electromagnetic field and produce a thermal effect simultaneously, the appropriate utilization of the LSPR effect is a noteworthy research direction towards visible light driven photocatalysts with high efficiency and low cost. In this study, the influence mechanism of the optical, electric, magnetic, and thermal physical fields on the photocatalytic efficiency of the LSPR system is for the first time reviewed, based on which the research bottlenecks of this method including the accurate predesign and regulation of the photocatalyst, the interpretation of electron movement and energy transfer mechanism, are specifically analyzed. Due to the micro-nano localization of LSPR, auxiliary methods are needed to reflect the micro electromagnetic and temperature field distribution which are otherwise formidable to measure experimentally. Alternatively, numerical methods with decoupling calculations of nano-scale physical fields are necessary to develop. Therefore, the development potential of different numerical simulation methods including mainstream FDTD, FEM and DDA is subsequently expounded, providing opportunities in resolving the bottleneck issues associated with photocatalysis. It is worth mentioning that although many important advances have been achieved in the preparation and application of LSPR assisted photocatalysts, the convincing function mechanism of LSPR is still lacking due to its multifield synergistic enhancement effect.