Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3ß-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3ß-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

Glycyrrhizic acid inhibits DNA damage repair and enhances cisplatin-induced apoptosis of melanoma cells.

This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 µm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.

A Systematic Review and Meta-Analysis Comparing the Effectiveness of Transversus Abdominis Plane Block and Caudal Block for Relief of Postoperative Pain in Children Who Underwent Lower Abdominal Surgeries.

Background and Objectives: Postoperative pain after lower abdominal surgery is typically severe. Traditionally, in pediatric anesthesia, a caudal block (CB) has been used for pain management in these cases. Nowadays, a transversus abdominis plane block (TAPB) seems to be an effective alternative. However, which technique for perioperative analgesia is better and more effective remains unclear in children who undergo abdominal surgeries. The aim of this study was to compare the efficacy and safety of a TAPB and CB for pain management in children after abdominal surgery by conducting a meta-analysis of published papers in this area. Methods: We conducted a thorough search of PubMed, EMBASE, the Cochrane Library, and the Web of Science for randomized controlled trials (RCTs) that compared a TAPB and CB for pain management in children who had abdominal surgery. Two researchers screened and assessed all the information with RevMan5.3 used for this meta-analysis. Pain scores, the total dose of rescue analgesic given, the mean duration of analgesia, the intraoperative and postoperative hemodynamic conditions 24 h after surgery, and adverse events were compared. Results: 15 RCTs that involved a total of 970 pediatric patients were included in this study. The results of this meta-analysis showed that there were no significant differences between the 2 groups in terms of postoperative pain scores at 1 h (SMD = 0.35; 95% CI = -0.54 to 1.24; p = 0.44, I2 = 94%), 6 h (SMD = -0.10; 95% CI = -0.44 to -0.23; p = 0.55, I2 = 69%), 12 h (SMD = -0.02; 95% CI = -0.45 to -0.40; p = 0.93, I2 = 80%), and 24 h (SMD = -0.66; 95% CI = -1.57 to -0.25; p = 0.15, I2 = 94%); additional analgesic requirement (OR 0.25; 95% CI 0.09 to 0.63; p = 0.004, I2 = 72%); total dose of rescue analgesic given in 24 h (SMD = -0.37; 95% CI = -1.33 to -0.58; p = 0.44; I2 = 97%); mean duration of analgesia (SMD = 1.29; 95% CI = 0.01 to 2.57; p = 0.05, I2 = 98%); parents' satisfaction (SMD = 0.44; 95% CI = -0.12 to 1.0; p = 0.12; I2 = 80%); and intraoperative and postoperative hemodynamic conditions 24 h after the surgery and adverse events (SMD = 0.78; 95% CI = 0.22 to 2.82; p = 0.70; I2 = 62%). Compared to a CB, a TAPB resulted in a small but significant reduction in additional analgesic requirement after surgery (OR 0.25; 95% CI 0.09 to 0.63; p = 0.004). Conclusions: TAPBs and CBs result in similar efficient early analgesia and safety profiles in children undergoing abdominal surgeries. Moreover, no disparities were observed for adverse effects between TAPBs and CBs.

Polymorphism in genes encoding two fatty acid binding proteins increases risk of ischemic stroke in a Chinese Han population.

Background: Dyslipidemia is an independent predictor of ischemic stroke (IS). Genetic variations in lipid-metabolism related genes may increase the risk of IS. Fatty acid-binding protein 1 (FABP1) and fatty acid-binding protein 2 (FABP2) are lipid chaperones responsible for lipid transport and metabolism. The present study aimed to determine the association between FABP1 or FABP2 and ischemic stroke. Methods: A total of 251 participants were recruited composed of 138 patients with ischemic stroke and 113 healthy subjects. DNA was extracted from peripheral blood samples. The rs2241883 polymorphism in FABP1 and rs1799883 polymorphism in FABP2 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between two SNPs and environmental factors. Results: The GA genotype of FABP2 rs1799883 increased susceptibility to ischemic stroke under overdominant inheritance model (p = 0.042). After adjusting for the risk factors of IS, it was associated with a significantly higher risk of IS in the codominant inheritance model (adjust OR = 3.431, 95%CI = 1.060-11.103, p = 0.04). The interactions of FABP1 rs2241883 and FABP2 rs1799883 were not associated with IS risk (p = 0.172). Moreover, interaction analysis of two genes (rs1799883 and rs2241883) and two environmental factors (smoking and alcohol consumption) was associated with an increased risk of IS (p = 0.011). Conclusion: The GA genotype of FABP2 rs1799883, interactions between rs1799883, rs2241883 and smoking and alcohol consumption were associated with IS risk in Chinese Han populations.

Association of estimated glomerular filtration rate and all-cause mortality in acute pancreatitis: a retrospective analysis.

BACKGROUND: Our primary objective was to explore the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in acute pancreatitis (AP) admission to intensive care units. METHODS: This study is a retrospective cohort analysis based on the Medical Information Mart for Intensive Care III database. The eGFR was calculated based on Chronic Kidney Disease Epidemiology Collaboration equation. Cox models with restricted cubic spline functions were used to evaluated the association of eGFR with all-cause mortality. RESULTS: The mean eGFR was 65.93 ± 38.56 ml/min/1.73 m2 in 493 eligible patients. 28-day mortality was 11.97% (59/ 493), which decreased by 15% with every 10 ml/min/1.73 m2 increase in eGFR. The adjusted hazard ratio (95% confidence interval) was 0.85 (0.76-0.96). A non-linear association was proved between eGFR and all-cause mortality. When eGFR < 57 ml/min/1.73 m2, there was a negative correlation between eGFR and 28-day mortality, hazard ratio (95% CI) was 0.97 (0.95, 0.99). The eGFR was also negatively correlated with in-hospital and in-ICU mortality. Subgroup analysis confirmed that the association between eGFR and 28-day mortality in different characteristics was stable. CONCLUSIONS: The eGFR was negatively correlated with all-cause mortality in AP when eGFR is less than the threshold inflection point.

Intraoperative hypothermia in the neonate population: risk factors, outcomes, and typical patterns.

The risk factors, outcomes, and typical patterns of intraoperative hypothermia were studied in neonates to better guide the application of insulation measures in the operating room. This retrospective study enrolled 401 neonates undergoing surgery under general anaesthesia with tracheal intubation, including abdominal surgery, thoracic surgery, brain surgery, and others. The study collected basic characteristics, such as age, sex, weight, birth weight, gestational week, primary diagnosis and American Society of Anaesthesiologists (ASA) grade. Perioperative data included preoperative body temperature, length of hospital stay, length of intensive care unit (ICU) stay, intubation time, postoperative bleeding, postoperative pneumonia, postoperative death, and total cost of hospitalization. Intraoperative data included surgical procedures, anaesthesia duration, operation duration, blood transfusion, fluid or albumin infusion, and application of vasoactive drugs. The incidence of intraoperative hypothermia (< 36 °C) was 81.05%. Compared to normothermic patients, gestational week (OR 0.717; 95% CI 0.577-0.890; P = 0.003), preoperative temperature (OR 0.228; 95% CI 0.091-0.571; P = 0.002), duration of anaesthesia (OR 1.052; 95% CI 1.027-1.077; P < 0.001), and type of surgery (OR 2.725; 95% CI 1.292-5.747; P = 0.008) were associated with the risk of intraoperative hypothermia. Patients with hypothermia had longer length of ICU stay (P = 0.001), longer length of hospital stay (P < 0.001), and higher hospital costs (P < 0.001). But there were no association between clinical outcomes and intraoperative hypothermia in the multivariable regression adjusted analysis. The lowest point of intraoperative body temperature was approximately 1 h 30 min. Then, the body temperature of patients successively entered a short plateau phase and a period of slow ascent. The greatest decrease in body temperatures occurred in preterm babies and neonates with preoperative hypothermia. The lowest core temperatures that occurred in neonates with preoperative hypothermia was lower than 35 °C. This study shows that there is a high incidence of intraoperative hypothermia in the neonate population. The intraoperative body temperature of neonates dropped to the lowest point in 1-1.5 h. The greatest decrease in core temperatures occurred in preterm babies and neonates with lower preoperative temperature.

Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice.

BACKGROUND: Fibroblast growth factor 21 (FGF21), primarily secreted by the pancreas, liver, and adipose tissues, plays a pivotal role in regulating glucose and lipid metabolism. Acute pancreatitis (AP) is a common inflammatory disease with specific clinical manifestations. Many patients with diabetes present with concurrent inflammatory symptoms. Diabetes exacerbates intestinal permeability and intestinal inflammation, thus leading to the progression to AP. Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice. AIM: To investigate the potential protective role of FGF21 against AP in diabetic mice. METHODS: In the present study, a mouse model of AP was established in diabetic (db)/db diabetic mice through ceruletide injections. Thereafter, the protective effects of recombinant FGF21 protein against AP were evaluated, with an emphasis on examining serum amylase (AMS) levels and pancreatic and intestinal inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-), and intestinal IL-1ß]. Additionally, the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP. An antibiotic (Abx) cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformatics software package, was used to predict different pathways between the groups and to explore the potential mechanisms by which the gut microbiota influenced the protective effect of FGF21. RESULTS: The results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01) and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ± 0.051, P < 0.01), and IL-1ß (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notable signs of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation in the small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantly altered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment with an Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ± 0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21 group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinal tissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P < 0.001). These findings underscored the superior protective effects of the combination therapy involving an Abx cocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota composition across different groups was further characterized, and a differential expression analysis of gene functions was undertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confer therapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathway of n-acetylceramide degradation in the gut microbiota. CONCLUSION: This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing blood glucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effects of FGF21 are augmented when combined with the Abx cocktail.

Protective Effects of Lactobacillus reuteri on Intestinal Barrier Function in a Mouse Model of Neonatal Necrotizing Enterocolitis.

OBJECTIVE: The intestinal mucosal and immune barriers play considerable roles in the pathogenesis of necrotizing enterocolitis (NEC). The present research was designed to assess the protective effects of Lactobacillus reuteri (LR) DSM 17938 (LR 17938) on the intestinal barriers and its beneficial effects on inflammation in a neonatal mouse model of NEC. STUDY DESIGN: Overall, 7-day-old 75 C57BL/6 neonatal mice were separated into three groups (n = 25) as follows: (1) control, (2) NEC, and (3) NEC + LR17938 (LR group). NEC mice were administered a hypertonic feeding formula and subjected to asphyxia and hypothermia. Hematoxylin and eosin (HE) staining and pathological scores were used to assess the pathological changes in the intestine. Oxidative stress was evaluated based on the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels were detected to assess inflammation. Gut permeability levels, bacterial translocation, and the levels of secretory idioglobulin A (sIgA), ß-defensin, and tight junction (TJ) proteins were detected to evaluate gut mucosal and immune barrier function, and gut microbial diversity was detected to assess the composition of the gut flora. RESULTS: LR 17938 administration decreased the NEC-induced increase in intestinal scores, mortality rate, gut damage, the MDA level, and TNF-α and IL-1ß expressions. Besides, LR 17938 improved the survival rate of NEC mice. Moreover, LR 17938 administration improved gut permeability levels, SOD activity and the bacterial translocation, ameliorated the expression of TJ proteins, and improved the gut microbiota compared with those of NEC mice. CONCLUSION: LR 17938 reduced intestinal inflammation and played a protective role in a neonatal animal model of NEC, possibly by regulating oxidative stress and exerting a protective effect on the gut mucosal and immune barriers. KEY POINTS: · Our research indicated a protective effect of LR 17938 on gut barrier function in NEC mice.. · LR 17938may affect the diversity of gut flora, which are known to target beneficial bacteria.. · LR 17938 protected gut barrier function in the NEC pups by improving gut permeability..

Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4.

Calreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulatory effects as well as immunoregulation effects on immune cells. Here, we constructed stable B16 melanoma cell lines expressing recombinant CRT/39-272 on the membrane (B16-tmCRT/39-272) to investigate the roles of cell surface CRT on tumor progression. We found that B16-tmCRT/39-272 cells subcutaneously inoculated into C57BL/6 mice exhibited stronger tumorigenicity than the B16-EGFP control cells. The tumor associated macrophages infiltrated in tumors were mainly M2 phenotype. Regulatory T cells (Tregs) were also expanded more in bearing mice. Consistent with the in vivo results, B16-tmCRT/39-272 promoted macrophage polarization toward F4/80+CD206+ M2 macrophages and promoted transforming growth factor beta (TGF-ß) secretion in vitro, which could promote naïve CD4+ T cell differentiation into Tregs. These results imply that the tmCRT/39-272 could accelerate tumor development by enhancing M2 macrophage polarization to induce TGF-ß secretion, and then promoted Treg differentiation in the tumor microenvironment. Our data may provide useful clues for better understanding of the potentiating roles of CRT in tumorigenesis.

Atmospheric diffuse transmittance of the linear polarization component of water-leaving radiation.

The polarization characteristics of water-leaving radiation contain rich information on oceanic constituents. Determining the atmospheric diffuse transmittance is crucial for extracting the polarization information of water-leaving radiation from the radiation acquired by polarimetry satellites at the top of the atmosphere. However, there is still a lack of understanding of the atmospheric diffuse transmittance of the linear polarization component of water-leaving radiation. Here, we first evaluated the difference between the atmospheric diffuse transmittance of the linear polarization component (TQ, TU) and the intensity component (TI) of the water-leaving radiation based on the Ocean Successive Orders with Atmosphere Advanced radiative transfer model. As a consequence, there were apparent differences between TQ, TU and TI. In the case of a large solar zenith angle and a large viewing zenith angle, the difference between TQ, TU and TI will exceed 1. Meanwhile, compared with TI, the oceanic constituents had a prominent interference with TQ and TU, and the sediment concentration had little interference with TQ and TU in low- and medium-turbidity water with respect to the aerosol model, optical thickness, observation geometry, and phytoplankton. Moreover, TQ and TU lookup tables were generated for medium- and low-turbidity water, which laid the foundation for extracting the water-leaving radiation polarization information from the satellite observation polarization signal.

A retrospective study on the relationship between fibrosis­4 index and all­cause mortality in patients with acute myocardial infarction.

The fibrosis-4 (FIB-4) index is a non-invasive score used to determine liver fibrosis. The present study aimed to assess the predictive ability of FIB-4 for all-cause mortality in patients with acute myocardial infarction (AMI). It retrospectively analyzed a total of 797 patients who were diagnosed with AMI. The patients were equally divided into three tertiles based on the values of the FIB-4 index scores: Group A (FIB-4 index <3.19; n=265), group B (3.19 ≤FIB-4 <8.14; n=267) and group C (FIB-4 index ≥8.14 group; n=265). Kaplan-Meier curves were used to analyze the incidence of all-cause mortality among the three groups. Multivariate Cox regression analysis was used to assess the association of risk of all-cause mortality in the patients. The Kaplan-Meier curves showed that the incidence of all-cause mortality was statistically significantly higher in group C than in groups A and B (P<0.001). After adjusting for confounding factors, multivariate Cox analysis demonstrated the risk of all-cause mortality in group C was significantly higher than in group A (hazard ratio: 2.898, 95% confidence interval: 1.069-7.857, P=0.037). In receiver-operating characteristics (ROC) analysis, an FIB-4 index of 6.647 and a Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score of 26.75 had sensitivities of 67.3 and 55.8% and specificities of 63 and 71.9%, respectively. Comparing the area under the ROC curve revealed no statistical differences between the FIB-4 index and SYNTAX score (0.654 vs. 0.661; P=0.864). Higher FIB-4 index were associated with increased risks of all-cause mortality among AMI patients. The FIB-4 index, a noninvasive and convenient tool, plays a potential role in the prognosis of AMI.

Calreticulin as an Adjuvant In Vivo to Promote Dendritic Cell Maturation and Enhance Antigen-Specific T Lymphocyte Responses against Melanoma.

An endoplasmic reticulum resident protein, calreticulin (CRT), participates in many cellular processes. CRT is a tumor-associated antigen with an important role in antitumor immunity. Previously, we reported that the recombinant CRT fragment 39-272 (CRT/39-272) exhibited superior immunobiological activity, activating macrophages to release cytokines and promoting dendritic cell (DC) maturation. However, the effect of CRT/39-272 in vivo, especially its adjuvant effect on in vivo antitumor immune responses, was not fully investigated. In this study, we constructed a fusion protein linking CRT/39-272 to an ovalbumin (OVA) peptide (residues 182-297, OVAp) and used the fusion protein (OVAp-CRT) to examine the adjuvant effect of CRT. We investigated whether CRT/39-272 could induce bone marrow-derived DC maturation and strongly promote the proliferation of OVA-specific T cells in vitro. Compared with OVAp, OVAp-CRT induced stronger antigen-specific T lymphocyte responses, including antigen-specific T cell proliferation, interferon-γ secretion, and cytotoxic T lymphocyte responses. OVAp-CRT-immunized mice generated significantly increased OVAp-specific antibody and CD4+/CD8+ memory T cells, which mediated long-term protective effects. OVAp-CRT upregulated CD40, CD80, and CD86 expressions in splenic conventional DCs. Furthermore, OVAp-CRT protected immunized mice against OVA-expressing B16 melanoma cells in vivo. Moreover, mice that were adoptively transferred with OVAp-CRT-pulsed DCs showed inhibited tumor growth and prolonged mouse survival. Our results demonstrate that CRT/39-272 can be used as a potential new adjuvant for tumor vaccines, and this finding may be useful in tumor vaccine development.

Effects of Breast-Conserving Surgery Combined with Immediate Autologous Fat Grafting on Oncologic Safety, Satisfaction and Psychology in Patients with Breast Cancer: A Retrospective Cohort Study.

Purpose: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients. Patients and Methods: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients. Results: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P>0.05). The average follow-up time of the two groups was 40.58±2.630 and 40.28±2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P>0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85±4.833 vs 51.93±5.045, P<0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P>0.05). Conclusion: BCS combined with immediate AFG can significantly improve patients' satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.

Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow-derived mesenchymal stem cells via the PKA-AMPK-SIRT1 axis.

Osteoporosis is a bone disease characterized by reduced bone density, thin cortical bone and large gaps in the bone's honeycomb structure, which increases the risk of bone fragility. Uncarboxylated osteocalcin (unOC), a vitamin K-dependent bone protein, is known to regulate carbohydrate and energy metabolism. A previous study demonstrated that unOC promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into osteoblasts, but inhibits their differentiation into adipocytes. However, the underlying mechanism remains unknown. The present study showed that unOC regulated the differentiation potential of BMSCs via protein kinase A (PKA)/AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling. SIRT1, a member of the sirtuin family with deacetylation functions, was upregulated by unOC in BMSCs. Transfection analyses with SIRT1 small interfering RNA indicated that the unOC-induced differentiation shift in BMSCs required SIRT1. Examination of SIRT1 downstream targets revealed that unOC regulated the acetylation levels of runt-related transcription factor (RUNX) 2 and peroxisome proliferator-activated receptor γ (PPARγ). Therefore, unOC inhibited adipogenic differentiation by PPARγ acetylation and promoted osteogenic differentiation by RUNX2 deacetylation. Moreover, phosphorylated PKA and AMPK protein levels increased after unOC treatment, which led to the upregulation of SIRT1. Western blot analysis with PKA and AMPK inhibitors indicated that the PKA-AMPK signaling pathway functioned upstream of SIRT1 and positively regulated SIRT1 expression. These findings led us to propose a model in which unOC regulated BMSC osteogenic differentiation through the PKA-AMPK-SIRT1 axis, giving evidence towards the therapeutic potential of unOC in osteoporosis treatment.

Thoracoscopic radical resection in the treatment of NSCLC patients (stage IIIA) after neoadjuvant chemotherapy.

PURPOSE: We aimed to investigate the efficacy and safety of thoracoscopic radical resection of lung cancer in the treatment of patients with stage IIIA non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy. METHODS: A total of 132 NSCLC patients (stage IIIA) were collected. Among them, 66 received preoperative neoadjuvant chemotherapy and thoracoscopic radical resection of lung cancer (NACT group), and 66 underwent thoracoscopic radical resection of lung cancer directly (control group). Next, the downstaging of the tumor was analyzed after neoadjuvant chemotherapy, and the R0 resection rate, surgical conditions, postoperative complications, and changes in the levels of serum tumor markers were compared between the two groups of patients. RESULTS: The response rate of neoadjuvant chemotherapy was 51.5% (34/66), and the overall downstaging rate was 53.0% (35/66) after neoadjuvant chemotherapy, with 34 cases of T downstaging and 35 cases of N downstaging. The operative time was clearly shorter in the NACT group than that in control group. The R0 resection rate in the NACT group was prominently higher than that in the the control group. The follow-up results uncovered that the 3-year overall survival (OS) and 3-year progression-free survival (PFS) rates were 50.0% and 21.2％ in the NACT group, and 36.4% and 6.1% in the control group, respectively. Based on the results of log-rank test, the OS and PFS of patients in the NACT group were markedly better than those in the control group. CONCLUSIONS: Neoadjuvant chemotherapy benefits patients with NSCLC (stage IIIA), and it is capable of effectively leading to pathological down-staging, elevating the R0 resection rate, significantly improving the survival of patients and considerably repressing the progression of the disease.

IgG Immunocomplexes Drive the Differentiation of a Novel Subset of Osteoclasts Independent of RANKL and Inflammatory Cytokines.

Potentiation of receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis by IgG immunocomplexes (ICs) is generally considered an important pathway leading to cartilage and bone destruction in rheumatoid arthritis (RA). However, whether IgG ICs possess pro-osteoclastogenic potential independent of RANKL and inflammatory cytokines is unclear. Here we demonstrate that by fully cross-linking human FcγRIIa (hFcγRIIa) or co-ligating hFcγRIIa and TLR4, IgG ICs alone could drive the differentiation of human blood monocytes into nuclear factor of activated T cells cytoplasmic 1 (NFATc1-negative nonclassical osteoclasts (NOCs). Surprisingly, IgG ICs could also overrule RANKL-induced classical osteoclast (COC) differentiation in vitro. In mouse model of collagen-induced arthritis, hFcγRIIa-transgenic, but not nontransgenic control, mice suffered from cartilage/bone destruction accompanied by the presence of NFATc1- NOCs lining the eroded cartilage surface in affected joints. Our results not only identify a novel subset of IC-induced NOCs but also provide a possible explanation for the uncoupling of FcγR-mediated cartilage destruction from RANKL-related bone erosion in autoinflammatory arthritis. © 2021 American Society for Bone and Mineral Research (ASBMR)..

Hyperoxia-induced miR-342-5p down-regulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3.

BACKGROUND AND PURPOSE: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation. EXPERIMENTAL APPROACH: Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O2 on postnatal days 1-7) and the BPD model (100% O2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis. KEY RESULTS: Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets. CONCLUSION AND IMPLICATIONS: These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD.

IFI30 as a prognostic biomarker and correlation with immune infiltrates in glioma.

BACKGROUND: Increased evidence indicates that the tumour microenvironment (TME) plays an essential role in the development, treatment and prognosis of glioma. High expression of interferon-gamma-inducible protein 30 (IFI30) is associated with the malignant phenotype, but the effect of IFI30 on the tumour immune microenvironment and its potential role in the carcinogenesis of glioma remain unknown. METHODS: The RNA sequencing (RNA-seq) data of 33 types of human cancer were obtained from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC). R software was used to perform analyses, such as the expression of IFI30 in pan-cancer, evaluation of IFI30 as a prognostic biomarker in glioma, the relationship between IFI30 expression and clinical characteristics, and immune checkpoint. TIMER was used to analyse the correlation of IFI30 expression level with immune cell infiltration, and also to conduct survival analysis for immune cells and IFI30 in low grade glioma (LGG). DAVID was used for Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway analysis of the genes similar to IFI30 in glioma. The differentially expressed genes (DEGs) between the high- and low-IFI30 expression groups were determined by DESeq2. Gene set enrichment analysis (GSEA) was then conducted to identify IFI30-related functional significance based on the hallmark gene set. RESULTS: Dysregulated expression of IFI30 was associated with human cancers. High IFI30 expression was associated with poor overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI). Univariate and multivariate analyses identified IFI30 as an independent predictor for glioma. Meanwhile, IFI30 overexpression significantly correlated with high-grade tumours, poor OS, and immune infiltration. In addition, IFI30-associated genes significantly enriched the hallmark tumour progression-related clusters and cancer pathways. CONCLUSIONS: IFI30 is a prognostic biomarker correlated with immune infiltrates and acts as an oncogene in glioma.