[Advances in the study of natural killer (NK) cells' response to Mycobacterium tuberculosis infection].

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB) infection and poses a serious threat to human health. Natural killer (NK) cells, an important component of innate immunity, can differentiate into various subpopulations in response to MTB infection, showing a diversity of receptors and functions. They engage in crosstalk with other immune cells by secreting cytokines, thereby exerting anti-infective actions against MTB infection and enhancing the body's immune response to the infection.

Photocatalytic Formamide Synthesis via Coupling of Electrophilic and Nucleophilic Radicals over Atomically Dispersed Bi Sites.

Formamide (HCONH2) plays a pivotal role in the manufacture of a diverse array of chemicals, fertilizers, and pharmaceuticals. Photocatalysis holds great promise for green fabrication of carbon-nitrogen (C-N) compounds owing to its environmental friendliness and mild redox capability. However, the selective formation of the C-N bond presents a significant challenge in the photocatalytic synthesis of C-N compounds. This work developed a photocatalytic radical coupling method for the formamide synthesis from co-oxidation of ammonia (NH3) and methanol (CH3OH). An exceptional formamide yield rate of 5.47±0.03 mmol ⋅ gcat -1 ⋅ h-1 (911.87±5 mmol ⋅ gBi -1 ⋅ h-1) was achieved over atomically dispersed Bi sites (BiSAs) on TiO2. An accumulation of 45.68 mmol ⋅ gcat -1 (2.0 g ⋅ gcat -1) of formamide was achieved after long-term illumination, representing the highest level of photocatalytic C-N compounds synthesis. The critical C-N coupling for formamide formation originated from the "σ-σ" interaction between electrophilic ⋅CH2OH with nucleophilic ⋅NH2 radical. The BiSAs sites facilitated the electron transfer between reactants and photocatalysts and enhanced the nucleophilic attack of ⋅NH2 radical on the ⋅CH2OH radical, thereby advancing the selective C-N bond formation. This work deepens the understanding of the C-N coupling mechanism and offers an intriguing photocatalytic approach for the efficient and sustainable production of C-N compounds.

THF peroxide as a factor in generating desulphurised products from the solid-phase synthesis of phosphorothioate-modified oligonucleotides.

Antisense oligonucleotides (ASOs) are generally obtained via chemical synthesis on a solid support and phosphorothioate (PS) modification with a phosphate backbone to increase their in vivo stability and activity. However, desulphurised products, in which PS is partially replaced by phosphodiesters, are generally formed during the chemical synthesis of ASO and are difficult to separate from the desired PS-modified ASO by chromatography. Therefore, revealing the unknown factors that cause the formation of desulphurised products and proposing methods to inhibit their formation are highly desirable. In this study, it was found that peroxides in THF, which is used as a solvent for the acetyl capping agent, oxidise phosphite triesters to produce desulphurisation products. The use of THF with antioxidants effectively suppresses the oxidation caused by THF peroxides. Moreover, THF peroxide was found to oxidise phosphoramidites, which are the building blocks of oligonucleotide chemical syntheses, indicating that caution should be taken with the organic solvents used during the synthesis and purification of phosphoramidites.

In situ fabrication of atomically adjacent dual-vacancy sites for nearly 100% selective CH4 production.

The photocatalytic CO2-to-CH4 conversion involves multiple consecutive proton-electron coupling transfer processes. Achieving high CH4 selectivity with satisfactory conversion efficiency remains challenging since the inefficient proton and electron delivery path results in sluggish proton-electron transfer kinetics. Herein, we propose the fabrication of atomically adjacent anion-cation vacancy as paired redox active sites that could maximally promote the proton- and electron-donating efficiency to simultaneously enhance the oxidation and reduction half-reactions, achieving higher photocatalytic CO2 reduction activity and CH4 selectivity. Taking TiO2 as a photocatalyst prototype, the operando electron paramagnetic resonance spectra, quasi in situ X-ray photoelectron spectroscopy measurements, and high-angle annular dark-field-scanning transmission electron microscopy image analysis prove that the VTi on TiO2 as initial sites can induce electron redistribution and facilitate the escape of the adjacent oxygen atom, thereby triggering the dynamic creation of atomically adjacent dual-vacancy sites during photocatalytic reactions. The dual-vacancy sites not only promote the proton- and electron-donating efficiency for CO2 activation and protonation but also modulate the coordination modes of surface-bound intermediate species, thus converting the endoergic protonation step to an exoergic reaction process and steering the CO2 reduction pathway toward CH4 production. As a result, these in situ created dual active sites enable nearly 100% CH4 selectivity and evolution rate of 19.4 µmol g-1 h-1, about 80 times higher than that of pristine TiO2. Thus, these insights into vacancy dynamics and structure-function relationship are valuable to atomic understanding and catalyst design for achieving highly selective catalysis.

Rapid Energy Exchange between In Situ Formed Bromine Vacancies and CO2 Molecules Enhances CO2 Photoreduction.

Photocatalytic reduction of CO2 into fuels provides a prospective tactic for regulating the global carbon balance utilizing renewable solar energy. However, CO2 molecules are difficult to activate and reduce due to the thermodynamic stability and chemical inertness. In this work, we develop a novel strategy to promote the adsorption and activation of CO2 molecules via the rapid energy exchange between the photoinduced Br vacancies and CO2 molecules. Combining in situ continuous wave-electron paramagnetic resonance (cw-EPR) and pulsed EPR technologies, we observe that the spin-spin relaxation time (T2) of BiOBr is decreased by 198 ns during the CO2 photoreduction reaction, which is further confirmed by the broadened EPR linewidth. This result reveals that there is an energy exchange interaction between in situ formed Br vacancies and CO2 molecules, which promotes the formation of high-energy CO2 molecules to facilitate the subsequent reduction reaction. In addition, theoretical calculations indicate that the bended CO2 adsorption configuration on the surface of BiOBr with Br vacancies caused the decrease of the lowest unoccupied molecular orbital of the CO2 molecule, which makes it easier for CO2 molecules to acquire electrons and get activated. In situ diffuse reflectance infrared Fourier transform spectroscopy further shows that the activated CO2 molecules are favorably converted to key intermediates of COOH*, resulting in a CO generation rate of 9.1 µmol g-1 h-1 and a selectivity of 100%. This study elucidates the underlying mechanism of CO2 activation at active sites and deepens the understanding of CO2 photoreduction reaction.

Novel strategy of liver cancer treatment with modified antisense oligonucleotides targeting human vasohibin-2.

Vasohihibin-2 (VASH2) is a homolog of vasohibin-1 (VASH1) and is overexpressed in various cancers. Vasohihibin-2 acts on both cancer cells and cancer microenvironmental cells. Previous analyses have shown that VASH2 promotes cancer progression and abrogation of VASH2 results in significant anticancer effects. We therefore propose VASH2 to be a practical molecular target for cancer treatment. Modifications of antisense oligonucleotide (ASO) such as bridged nucleic acids (BNA)-based modification increases the specificity and stability of ASO, and are now applied to the development of a number of oligonucleotide-based drugs. Here we designed human VASH2-ASOs, selected an optimal one, and developed 2',4'-BNA-based VASH2-ASO. When systemically administered, naked 2',4'-BNA-based VASH2-ASO accumulated in the liver and showed its gene-silencing activity. We then examined the effect of 2',4'-BNA-based VASH2-ASO in liver cancers. Intraperitoneal injection of naked 2',4'-BNA-based VASH2-ASO exerted a potent antitumor effect on orthotopically inoculated human hepatocellular carcinoma cells. The same manipulation also showed potent antitumor activity on the splenic inoculation of human colon cancer cells for liver metastasis. These results provide a novel strategy for the treatment of primary as well as metastatic liver cancers by using modified ASOs targeting VASH2.

Autologous blood transfusion impedes glycolysis in macrophages to inhibit red blood cell injury in type 2 diabetes through PI3K/Akt/PKM2 signaling axis.

AIMS: To explore the effect and mechanism of autologous blood transfusion impeding glycolysis in macrophages and inhibiting red blood cells (RBCs) injury in type 2 diabetes through PI3K/Akt/PKM2 signaling axis. METHODS: Cell transfection were performed and diabetic mice model was constructed. The group were divided into control (NC) and type 2 diabetes model (T2D). T2D model mice were injected with preserved autologous blood, si-PI3K, si-PKM2, si-NC Tran+T2D, (Tran+T2D+si-PI3K, Tran+T2D si-PKM2, Tran+T2D+si-NC) through tail vein. The anti-oxidative effects of transfusion of autologous blood in CD14+ monocytes were detected. The expression of PI3K/Akt/PKM2 protein in CD14+ monocytes were examined by western blot. Effect of autologous blood transfusion ameliorating RBCs injury by regulating PI3K and PKM2 in T2D mice were detected. RESULTS: Effects on oxidative stress in T2D mice were all overturned after autologous blood transfusion in T2D mice. The results manifested that the levels of PI3K, pAkt and PKM2 were downregulated, while the expression of HIF-1α was upregulated in CD14+ monocytes from T2D mice, whereas these influences were all effectively reversed by autologous blood transfusion in T2D mice. The survival rate of RBCs in the serum of T2D mice was declined in the serum of T2D mice, while the effect was reversed by the autologous blood transfusion. CONCLUSION: Autologous blood transfusion can reduce glycolysis in macrophages and inhibit the release of inflammatory factors through the PI3K/PKM2 signal axis, thereby inhibiting red blood cell damage and improving the oxygen-carrying capacity and survival activity of RBCs in diabetic patients.

Development of Phosphoramidite Reagents for the Synthesis of Base-Labile Oligonucleotides Modified with a Linear Aminoalkyl and Amino-PEG Linker at the 3'-End.

Oligonucleotides with an amino linker at the 3'-end are useful for the preparation of conjugated oligonucleotides. However, chemically modified nucleosides, which are unstable under basic conditions, cannot be incorporated into oligonucleotides using the conventional method entailing the preparation of oligonucleotides bearing a 3'-amino linker. Therefore, we designed Fmoc-protected phosphoramidites for the synthesis of base-labile oligonucleotides modified with a 3'-amino linker. The resultant phosphoramidites were then successfully incorporated into oligonucleotides bearing a 3'-amino linker. Various basic solutions were investigated for protecting group removal. All the protecting groups were removed by treating the oligonucleotides with 40% aqueous methylamine at room temperature for 2 h. Thus, the deprotection time and temperature were significantly reduced compared to the conventional conditions (28% NH3 aq., 55 °C, 17 h). In addition, the oligonucleotide protecting groups could be removed using a mild base (e.g., 50 mM potassium carbonate methanol solution). Furthermore, base-labile oligonucleotides bearing an amino linker at the 3'-end were successfully synthesized using the developed phosphoramidite reagents, highlighting the utility of our strategy.

Characterization of relaxin 3 and its receptors in chicken: Evidence for relaxin 3 acting as a novel pituitary hormone.

Mammalian relaxin (RLN) family peptides binding their receptors (RXFPs) play a variety of roles in many physiological processes, such as reproduction, stress, appetite regulation, and energy balance. In birds, although two relaxin family peptides (RLN3 and INSL5) and four receptors (RXFP1, RXFP2, RXFP2-like, and RXFP3) were predicated, their sequence features, signal properties, tissue distribution, and physiological functions remain largely unknown. In this study, using chickens as the experimental model, we cloned the cDNA of the cRLN3 gene and two receptor (cRXFP1 and cRXFP3) genes. Using cell-based luciferase reporter assays, we demonstrate that cRLN3 is able to activate both cRXFP1 and cRXFP3 for downstream signaling. cRXFP1, rather than cRXFP3, is a cognate receptor for cRLN3, which is different from the mammals. Tissue distribution analyses reveal that cRLN3 is highly expressed in the pituitary with lower abundance in the hypothalamus and ovary of female chicken, together with the detection that cRLN3 co-localizes with pituitary hormone genes LHB/FSHB/GRP/CART and its expression is tightly regulated by hypothalamic factors (GnRH and CRH) and sex steroid hormone (E2). The present study supports that cRLN3 may function as a novel pituitary hormone involving female reproduction.

The spatially separated active sites for holes and electrons boost the radicals generation for toluene degradation.

Hydroxyl (⸱OH) and superoxide (⸱O2-) radicals are the main drivers for photocatalysis in toluene degradation, but their generation mechanisms are still ambiguous due to the lack of direct evidence. The spatially separated active sites for holes and electrons can help to clarify the dynamic process of radicals generation. By performing theoretical calculations, it is demonstrated that the spatially separated active sites for holes and electrons on the Bi2O2CO3 surface can be constructed by introducing oxygen vacancies in the [Bi2O2]2+ layer. H2O and O2 molecules can be better adsorbed and activated at hole and electron active sites, separately. Accordingly, the pristine and defective Bi2O2CO3 are prepared. The dynamic behavior of H2O and O2 molecules at the matching active sites is revealed, which indicates the efficient adsorption of reactants and the substantial production of radicals. Significantly, the specificity of the spatially separated holes and electrons active sites for ⸱OH and ⸱O2- radicals generation, respectively, is demonstrated by in situ EPR with the H2O vapor atmosphere. This work provides a design concept for unraveling reaction mechanisms to realize controllable radicals generation.

Effects of a Single Sub-Anesthetic Dose of Ketamine on Postoperative Emotional Responses and Inflammatory Factors in Colorectal Cancer Patients.

Objective: To investigate the effect of a single sub-anesthetic dose of ketamine on postoperative anxiety, depression, and inflammatory factors in patients with colorectal cancer. Methods: A total of 104 patients undergoing selective colorectal surgery in our hospital from Jan 2015 to Oct 2017 were included and randomly assigned (1:1:1:1) into a 0.1 mg kg-1 ketamine group (K1 group), 0.2 mg kg-1 ketamine group (K2 group), 0.3 mg kg-1 ketamine group (K3 group), or control group (C group). Corresponding doses of ketamine were given intravenously in the K groups (K1, K2, and K3 groups) 5 min before operation, and the same amount of normal saline was given in the C group. The intravenous analgesia program was identical in the four groups. The patients' emotional reactions (anxiety and depression) were assessed by the Hospital Anxiety and Depression Scale (HAD), the quality of postoperative recovery was evaluated by the Quality of Recovery-40 (QoR-40) questionnaire, and the levels of IL-6, IL-8, and TNF-α in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA) on the day before operation and within 24, 48, and 72 h post-operation respectively. Pain was estimated by the visual analog scale (VAS), and sedation was assessed with Ramsay score 30 min after extubation. The time points of anesthetic end and extubation were recorded. The complications during anesthesia and recovery such as cough and agitation 30 min after extubation were recorded. Results: The anxiety score (HAD-A) and depression score (HAD-D) of the K3 group were significantly lower than those of the C group post-operation (p < 0.05). The QoR-40 score of the K3 group was significantly higher than that of the C group (p < 0.05). The serum levels of IL-6, IL-8, and TNF-α in the K3 group were significantly lower than those in the C group (p < 0.05 and p < 0.01). There were no significant differences in HAD-A, HAD-D, and QoR-40 scores or serum levels of IL-6, IL-8, and TNF-α between the K1 and K2 groups and the C group. There were no significant differences in VAS pain score or Ramsay sedation score among the four groups 30 min after extubation. There were no significant differences in extubation time, postoperative cough, emergence agitation, or delirium among the four groups. Dizziness, nausea, vomiting, diplopia, or other adverse reactions were not found 30 min after extubation. Conclusion: A single sub-anesthetic dose (0.3 mg kg-1) of ketamine can significantly improve the postoperative anxiety and depression of colorectal cancer patients and reduce the levels of IL-6, IL-8, and TNF-α.

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case-control study.

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case-control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow-up (33% vs 76%, P < .001), decrease in 1-year minor amputation rate (14% vs 3%, P = .007), and decrease in 1-year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.

Promotion mechanism of -OH group intercalation for NOx purification on BiOI photocatalyst.

Bismuth oxyiodide (BiOI) is a traditional layered oxide photocatalyst that performs in a wide visible-light absorption band, owing to its appropriate band structure. Nevertheless, its photocatalytic efficiency is immensely inhibited due to the serious recombination of photogenerated charge carriers. Herein, this great challenge is addressed via a new strategy of intralayer modification by -OH groups in BiOI, which leads to enhancement of the reactants' activation capacity to promote photocatalytic activity and generate more active species. Furthermore, analysis via a combination of experimental and theoretical methods revealed that the -OH group-functionalized samples reduce the energy barriers for conversion of the main intermediate (NO2), which is easily transformed to NO2-, thus accelerating the oxidation of NO to the final product (NO3-). This study gives insight into NO oxidation, improving the photocatalytic efficiency, and mastering the photocatalysis reaction mechanism to curb air pollution.

High-peak-power electro-optically Q-switched laser with a gradient-doped Nd:YAG crystal.

We report on a high-peak-power electro-optically Q-switched laser emitting a near-diffraction-limited beam profile at 1064 nm by using a gradient-doped Nd:YAG crystal. The gradient-doped crystal features a unique combination of a reduced thermal lens effect through effectively spreading the heat load distribution within its volume. Its performance is compared with those of Nd:YAG crystals with uniform volume doping distribution operating in the Q-switched regime with the same laser configuration, demonstrating the higher average and peak power achievable with the gradient-doped crystal. The maximum average output power amounts to 6.9 W at a pulse repetition rate of 2 kHz, which corresponds to a maximum peak power of ∼585kW. Compared to homogeneous dopant crystals, the slope efficiency and average output power increased by 30.8% and 21.1%, respectively.

Clinical evaluation of enhanced recovery after surgery protocol for anterior cervical decompression and fusion (ACDF): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: To improve the efficacy of anterior cervical decompression and fusion (ACDF) and reduce postoperative complications in degenerative cervical myelopathy, our team established a set of perioperative care of enhanced recovery guidelines of ACDF based on the concept of enhanced recovery after surgery. In addition, a prospective, multicentre, randomised clinical trial was designed. METHODS AND ANALYSIS: A total of 260 patients aged 18-65 years will be included. Preoperative MRI and CT will be used to confirm the typical manifestations of cervical spondylosis, such as cervical disc herniation and spinal cord compression. The patient presents with neck and shoulder pain, numbness of upper limbs, weakened grip strength and cotton sense of foot tread. Patients received normal conservative treatment for 3 months with no obvious relief or even aggravation of symptoms. Patients will be assigned to the group in strict accordance with the random allocation table. Patients in groups A and B will receive conventional perioperative care and perioperative care for enhanced recovery, respectively. The main outcome indicators are the Karnofsky Performance Scale score and the Japanese Orthopaedic Association scale. Secondary outcome indicators are pain assessment by Numeric Rating Scale, Neck Disability Index, quality of life index (QL-Index) and postoperative complications. Follow-up will be conducted at 3, 6 and 12 months postoperatively. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China (2020YF034-01). Results of the research will be published in an international peer-reviewed scientific journal and disseminated through presentation at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000040508.

Molecular Cloning and Functional Characterization of Three 5-HT Receptor Genes (HTR1B, HTR1E, and HTR1F) in Chickens.

The serotonin (5-hydroxytryptamine, 5-HT) signaling system is involved in a variety of physiological functions, including the control of cognition, reward, learning, memory, and vasoconstriction in vertebrates. Contrary to the extensive studies in the mammalian system, little is known about the molecular characteristics of the avian serotonin signaling network. In this study, we cloned and characterized the full-length cDNA of three serotonin receptor genes (HTR1B, HTR1E and HTR1F) in chicken pituitaries. Synteny analyses indicated that HTR1B, HTR1E and HTR1F were highly conserved across vertebrates. Cell-based luciferase reporter assays showed that the three chicken HTRs were functional, capable of binding their natural ligands (5-HT) or selective agonists (CP94253, BRL54443, and LY344864) and inhibiting intracellular cAMP production in a dose-dependent manner. Moreover, activation of these receptors could stimulate the MAPK/ERK signaling cascade. Quantitative real-time PCR analyses revealed that HTR1B, HTR1E and HTR1F were primarily expressed in various brain regions and the pituitary. In cultured chicken pituitary cells, we found that LY344864 could significantly inhibit the secretion of PRL stimulated by vasoactive intestinal peptide (VIP) or forskolin, revealing that HTR1F might be involved in the release of prolactin in chicken. Our findings provide insights into the molecular mechanism and facilitate a better understanding of the serotonergic modulation via HTR1B, HTR1E and HTR1F in avian species.

Evaluation of vertical transmission of SARS-CoV-2 in utero: Nine pregnant women and their newborns.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of March 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate. METHODS: In this study, in order to find out whether SARS-CoV-2 can infect fetus through the placental barrier, we performed qualitative detection of virus structural protein (spike protein and nucleoprotein) and targeted receptor protein Angiotensin Converting Enzyme 2 (ACE2), Basigin (CD147) and molecular chaperone GRP78 expression on the placental tissue of seven pregnant women diagnosed with COVID-19 through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room or delivery room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR). RESULTS/DISCUSSION: The result showed that CD147 was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 was expressed on the maternal side, while GRP78 was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. On the basis of these findings, we speculated that it may be due to the placental barrier between mother and baby, for example, villous matrix and interstitial blood vessels have low expression of virus-related receptors (ACE2, CD147, GRP78), the probability of vertical transmission of SARS-CoV-2 through the placenta is low.

Molecular Mechanisms of Chondrocyte Proliferation and Differentiation.

Cartilage is a kind of connective tissue that buffers pressure and is essential to protect joint movement. It is difficult to self-recover once cartilage is damaged due to the lack of blood vessels, lymph, and nerve tissues. Repair of cartilage injury is mainly achieved by stimulating chondrocyte proliferation and extracellular matrix (ECM) synthesis. Cartilage homeostasis involves the regulation of multiple growth factors and the transduction of cellular signals. It is a very complicated process that has not been elucidated in detail. In this review, we summarized a variety of signaling molecules related to chondrocytes function. Especially, we described the correlation between chondrocyte-specific regulatory factors and cell signaling molecules. It has potential significance for guiding the treatment of cartilage injury.

Prognostic role of the recepteur d'origine nantais (RON) expression in primary high-grade osteosarcoma.

BACKGROUND: Osteosarcoma is a common primary malignant bone tumor susceptible to distant metastasis. The clinical outcome for patients remains poor due to the resistance to chemotherapy and lacking effective therapeutic targets. Recepteur d'origine nantais (RON), a transmembrane protein of the c-MET proto-oncogene family, has been reported to contribute to the malignant progression and bone metastasis in several tumors. The present study aimed to explore the prognostic significance of RON in primary high-grade osteosarcoma. METHODS: Immunohistochemistry (IHC) and western blotting (WB) were used to investigate the protein expression of RON in 80 surgically resected specimens (50 high-grade osteosarcoma specimens and 30 non-neoplastic bone tissues) and 6 cell lines. The χ2 test or independent-sample Student's t-test was used to assess the significance of RON difference between osteosarcoma and non-neoplastic bone tissues. The χ2 test and Fisher's exact test were used to analyze the association of RON with the clinicopathological features of osteosarcoma patients. Kaplan-Meier method and Cox proportional hazards model were used to assess the significance of RON for the survival of osteosarcoma patients. RESULTS: The results of IHC and WB observed significant overexpression of RON in osteosarcoma specimens (P < 0.001) and osteosarcoma cell lines. Moreover, immunohistochemical high expression of RON was associated with a poor response to chemotherapy (P = 0.032) as well as worse progression-free (P = 0.003) and overall (P < 0.001) survival of osteosarcoma patients. Multivariate analysis revealed that high expression of RON was independently associated with reduced progression-free (P = 0.027, HR = 2.31) and overall survival (P = 0.004, HR = 5.06) time of osteosarcoma patients. CONCLUSIONS: The present study demonstrated that high expression of RON held independent value for unfavorable survival in primary high-grade osteosarcoma. Its potential role as a therapeutic target for osteosarcoma treatment deserves further research.

Effects of progressive muscle relaxation training on negative emotions and sleep quality in COVID-19 patients: A clinical observational study.

This study investigates the effect of progressive muscle relaxation training on negative mood and sleep quality in Coronavirus Pneumonia (COVID-19) patients.COVID-19 is an emerging infectious disease, and there is still uncertainty about when the outbreak will be contained and the effectiveness of treatments. Considering that this disease is highly contagious, patients need to be treated in isolation. This may lead to psychological symptoms such as anxiety and depression, and even sleep problems.This study is a clinical observation study.Participants included 79 COVID-19 patients admitted to a designated hospital for COVID-19 patients in Wuhan from February to March, 2020. Patients were selected and assigned to the control group and the observation group according to their wishes, with 40 and 39 cases in each group, respectively. The control group received routine treatment and nursing, and the observation group received progressive muscle relaxation training, in addition to the routine treatment and nursing. We compared scores of the Pittsburgh Sleep Quality Index Scale (PSQI), the Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaire (PHQ-9) before and after the intervention.There was no significant difference in PSQI, GAD-7, and PHQ-9 scores between the control group and the observation group before the intervention (P > .05). After the intervention, the difference in scores of PSQI, GAD-7, and PHQ-9 in the 2 groups were statistically significant (P < .05).Progressive muscle relaxation training can significantly reduce anxiety and depression and improve sleep quality in COVID-19 patients during isolation treatment.Progressive muscle relaxation training was shown to improve the treatment effect of patients and is worthy of clinical promotion.