Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.
Osteoporosis is prevalent in postmenopausal women. The underlying reason is mainly estrogen deficiency, but recent studies have indicated that osteoporosis is also associated with iron accumulation after menopause. It has been confirmed that some methods of decreasing iron accumulation can improve the abnormal bone metabolism associated with postmenopausal osteoporosis. However, the mechanism of iron accumulation-induced osteoporosis is still unclear. Iron accumulation may inhibit the canonical Wnt/β-catenin pathway via oxidative stress, leading to osteoporosis by decreasing bone formation and increasing bone resorption via the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-B ligand (RANKL)/receptor activator of nuclear factor kappa-B (RANK) system. In addition to oxidative stress, iron accumulation also has been reported to inhibit either osteoblastogenesis or osteoblastic function as well as to stimulate either osteoclastogenesis or osteoclastic function directly. Furthermore, serum ferritin has been widely used for the prediction of bone status, and nontraumatic measurement of iron content by magnetic resonance imaging may be a promising early indicator of postmenopausal osteoporosis.
Tumor-associated macrophages (TAMs) of the M2 phenotype are frequently associated with cancer progression. Invasive cancer cells undergoing epithelial-mesenchymal transition (EMT) have a selective advantage as TAM activators. Cyclin D1b is a highly oncogenic splice variant of cyclin D1. We previously reported that cyclin D1b enhances the invasiveness of breast cancer cells by inducing EMT. However, the role of cyclin D1b in inducing macrophage differentiation toward tumor-associated macrophage-like cells remains unknown. This study aimed to explore the relationship between breast cancer cells overexpressing cyclin D1b and TAMs.
Mouse breast cancer 4T1 cells were transfected with cyclin D1b variant and co-cultured with macrophage cells in a Transwell coculture system. The expression of characteristic cytokines in differentiated macrophages was detected using qRT-PCR, ELISA and zymography assay. Tumor-associated macrophage distribution in a transplanted tumor was detected by immunofluorescence staining. The proliferation and migration ability of breast cancer cells was detected using the cell counting kit-8 (CCK-8) assay, wound healing assay, Transwell invasion assay, and lung metastasis assay. Expression levels of mRNAs were detected by qRT-PCR. Protein expression levels were detected by Western blotting. The integrated analyses of The Cancer Genome Atlas (TCGA) datasets and bioinformatics methods were adopted to discover gene expression, gene coexpression, and overall survival in patients with breast cancer.
After co-culture with breast cancer cells overexpressing cyclin D1b, RAW264.7 macrophages were differentiated into an M2 phenotype. Moreover, differentiated M2-like macrophages promoted the proliferation and migration of breast cancer cells in turn. Notably, these macrophages facilitated the migration of breast cancer cells in vivo. Further investigations indicated that differentiated M2-like macrophages induced EMT of breast cancer cells accompanied with upregulation of TGF-β1 and integrin β3 expression.
Breast cancer cells transfected with cyclin D1b can induce the differentiation of macrophages into a tumor-associated macrophage-like phenotype, which promotes tumor metastasis in vitro and in vivo.
The main characteristics of diabetic nephropathy (DN) at the early stage are abnormal angiogenesis of glomerular endothelial cells (GECs) and macrophage infiltration. Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand, advanced glycation end products (AGEs). Catalpol, an iridoid glucoside extracted from Rehmannia glutinosa, has been found to ameliorate vascular inflammation, reduce endothelial permeability, and protect against endothelial damage in diabetic milieu. However, little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.
Mouse GECs (mGECs) and RAW 264.7 macrophages were treated with different concentrations of AGEs (0, 50, 100, 200 and 400 µg/mL) for different time (0, 6, 12, 24 and 48 h) to determine the optimal concentration of AGEs and treatment time. Cells were treated with catalpol (10 µmol/L), GB1107 (1 µmol/L, galectin-3 inhibitor), PX-478 (50 µmol/L, HIF-1α inhibitor), adenovirus-green fluorescent protein (Ad-GFP) [3×107 plaque-forming unit (PFU)/mL] or Ad-galectin-3-GFP (2×108 PFU/mL), which was followed by incubation with 50 µg/mL AGEs. The levels of galectin-3, vascular endothelial growth factor A (VEGFA) and pro-angiogenic factors angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), tunica interna endothelial cell kinase-2 (Tie-2) were detected by enzymelinked immunosorbent assay (ELISA). Cell counting kit-8 (CCK-8) assay was used to evaluate the proliferation of these cells. The expression levels of galectin-3, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, and hypoxia-inducible factor-1α (HIF-1α) in mGECs and those of galectin-3 and HIF-1α in RAW 264.7 macrophages were detected by Western blotting and immunofluorescence (IF) staining. The rat DN model was established. Catalpol (100 mg/kg) or GB1107 (10 mg/kg) was administered intragastrically once a day for 12 weeks. Ad-galectin-3-GFP (6×107 PFU/mL, 0.5 mL) or Ad-GFP (6×106 PFU/mL, 0.5 mL) was injected into the tail vein of rats 48 h before the sacrifice of the animals. The expression of galectin-3, VEGFR1, VEGFR2, and HIF-1α in renal cortices was analyzed by Western blotting. The expression of galectin-3, F4/80 (a macrophage biomarker), and CD34 (an endothelium biomarker) in renal cortices was detected by IF staining, and collagen accumulation by Masson staining.
The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50 µg/mL AGEs for 48 h than those in untreated cells. Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages. Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells. Catalpol could significantly decrease the levels of Ang-1, Ang-2 and Tie-2 released by AGEs-treated mGECs, which could be reversed by over-expression of galectin-3. Catalpol could significantly inhibit AGEs-induced expression of galectin-3, HIF-1α, VEGFR1, and VEGFR2 in mGECs. The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478. Moreover, catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages, which was weakened by PX-478. Additionally, catalpol significantly inhibited the expression of galectin-3, macrophage infiltration, collagen accumulation, and angiogenesis in the kidney of diabetic rats. Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol.
Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3. It could prevent the progression of diabetes-induced renal damage.
Metabolic disorders are regarded as hallmarks of multiple myeloma (MM) and are responsible for rapid cancer cell proliferation and tumor growth. However, the exact biological roles of metabolites in MM cells have not been fully explored. This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid (Lac) in the proliferation of myeloma cells and cell sensitivity to bortezomib (BTZ).
Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients. The CCK8 assay and flow cytometry were used to detect cell proliferation, apoptosis, and cell cycle changes. Western blotting was used to detect the potential mechanism and apoptosis- and cycle-related protein changes.
Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients. It was significantly correlated with Durie-Salmon Staging (DS Staging) and the International Staging System (ISS Staging) and the serum and urinary involved/uninvolved free light chain ratios. Patients with relatively high lactate levels had a poor treatment response. Moreover, in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells, which was accompanied by an increased proportion of S-phase cells. In addition, Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2 (NFkB2) and RelB.
Metabolic changes are important in MM cell proliferation and treatment response; lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.
The purpose of this study was to investigate the role of the unfolded protein response, specifically the inositol-requiring enzyme 1 (IRE1) signaling pathway, in hypoxia-induced autophagy in human umbilical venous endothelial cells (HUVECs).
The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting, qRT-PCR and confocal microscopy. Further, we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro. Finally, we examined the function of IRE1 in local blood vessels through animal models.
Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs. Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals.
Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.
Diabetic nephropathy is one of the most important microvascular complications of diabetes, which mainly refers to glomerular capillary sclerosis. Podocytes are an important part of glomerular capillaries. Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy. This study aimed to assess the protective mechanism of glycyrrhizic acid (GA) on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)/sucrose nonfermenting AMPK-related kinase (SNARK) signaling pathway.
SNARK siRNA was used to transfect podocytes. Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis. The expression levels of key pathway proteins (including TGF-β1, α-SMA, SITR1, AMPKα, LKB1, PGC-1α, NF-κB, IL-6, and TNF-α) were verified by Western blotting. The expression of inflammatory factors in podocytes was detected by ELISA.
We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors. However, after transfection of podocytes with SNARK siRNA, there was an increased expression of fibrosis-related factors and inflammation-related factors.
GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose, which is related to the AMPK signaling pathway. Meanwhile, knockdown of SNARK protein can inhibit the AMPK signaling pathway, aggravate fibrosis, and increase inflammation.
Cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) is one of the main causes of capillary leakage syndrome (CLS). This study aimed to establish a stable CLS model following the CA and cardiopulmonary resuscitation (CA-CPR) model in Sprague-Dawley (SD) rats.
We conducted a prospective, randomized, animal model study. All adult male SD rats were randomly divided into a normal group (group N), a sham operation group (group S), and a cardiopulmonary resuscitation group (group T). The SD rats of the three groups were all inserted with 24-G needles through their left femoral arteries and right femoral veins. In group S and group T, the endotracheal tube was intubated. In group T, CA induced by asphyxia (AACA) was caused by vecuronium bromide with the endotracheal tube obstructed for 8 min, and the rats were resuscitated with manual chest compression and mechanical ventilation. Preresuscitation and postresuscitation measurements, including basic vital signs (BVS), blood gas analysis (BG), routine complete blood count (CBC), wet-to-dry ratio of tissues (W/D), and the HE staining results after 6 h were evaluated.
In group T, the success rate of the CA-CPR model was 60% (18/30), and CLS occurred in 26.6% (8/30) of the rats. There were no significant differences in the baseline characteristics, including BVS, BG, and CBC, among the three groups (P>0.05). Compared with pre-asphyxia, there were significant differences in BVS, CBC, and BG, including temperature, oxygen saturation (SpO2), mean arterial pressure (MAP), central venous pressure (CVP), white blood cell count (WBC), hemoglobin, hematocrit, pH, pCO2, pO2, SO2, lactate (Lac), base excess (BE), and Na+ (P<0.05) after the return of spontaneous circulation (ROSC) in group T. At 6 h after ROSC in group T and at 6 h after surgery in groups N and S, there were significant differences in temperature, heart rate (HR), respiratory rate (RR), SpO2, MAP, CVP, WBC, pH, pCO2, Na+, and K+ among the three groups (P<0.05). Compared with the other two groups, the rats in group T showed a significantly increased W/D weight ratio (P<0.05). The HE-stained sections showed consistent severe lesions in the lung, small intestine, and brain tissues of the rats at 6 h after ROSC following AACA.
The CA-CPR model in SD rats induced by asphyxia could reproduce CLS with good stability and reproducibility.
Patients undergoing hematopoietic stem cell transplant (HSCT) need frequent transfusions, until their red blood cells (RBCs) and platelets start to recover. The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process. To date, there is no user-friendly tool to choose the right blood product for transfusion treatment, despite the number of guidelines and expert advice on the subject.
R/shiny is a powerful programming language for clinical data analysis and visualization. It can create interactive web applications that work in real-time. The web application named TSR was built using R programming, simplifying blood transfusion practice for ABO-incompatible HSCT with a one-click solution.
The TSR is divided into four main tabs. The home tab provides an overview of the application, while RBC, plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category. Unlike traditional methods that rely on treatment guidelines and specialist consensus, TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters, providing an innovative approach to improve transfusion support.
The present study highlights that the TSR enables real-time analysis, and promotes transfusion practice by offering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT. TSR has the potential to become a widely-utilized tool for transfusion services, providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.
This study aimed to establish a nomogram model to predict the mortality risk of patients with dangerous upper gastrointestinal bleeding (DUGIB), and identify high-risk patients who require emergent therapy.
From January 2020 to April 2022, the clinical data of 256 DUGIB patients who received treatments in the intensive care unit (ICU) were retrospectively collected from Renmin Hospital of Wuhan University (n=179) and the Eastern Campus of Renmin Hospital of Wuhan University (n=77). The 179 patients were treated as the training cohort, and 77 patients as the validation cohort. Logistic regression analysis was used to calculate the independent risk factors, and R packages were used to construct the nomogram model. The prediction accuracy and identification ability were evaluated by the receiver operating characteristic (ROC) curve, C index and calibration curve. The nomogram model was also simultaneously externally validated. Decision curve analysis (DCA) was then used to demonstrate the clinical value of the model.
Logistic regression analysis showed that hematemesis, urea nitrogen level, emergency endoscopy, AIMS65, Glasgow Blatchford score and Rockall score were all independent risk factors for DUGIB. The ROC curve analysis indicated the area under curve (AUC) of the training cohort was 0.980 (95%CI: 0.962–0.997), while the AUC of the validation cohort was 0.790 (95%CI:0.685–0.895). The calibration curves were tested for Hosmer-Lemeshow goodness of fit for both training and validation cohorts (P=0.778, P=0.516).
The developed nomogram is an effective tool for risk stratification, early identification and intervention for DUGIB patients.
This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells (CAR-T cells) versus chemotherapy plus donor lymphocyte infusion (chemo-DLI) for treating relapsed CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed. Twenty-two patients were treated with CAR-T cells (CAR-T group), and 21 with chemotherapy plus DLI (chemo-DLI group). The complete remission (CR) and minimal residual disease (MRD)-negative CR rates, leukemia-free survival (LFS) rate, overall survival (OS) rate, and incidence of acute graft-versus-host disease (aGVHD), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were compared between the two groups.
The CR and MRD-negative CR rates in the CAR-T group (77.3% and 61.5%) were significantly higher than those in the chemo-DLI group (38.1% and 23.8%) (P=0.008 and P=0.003). The 1- and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group: 54.5% and 50.0% vs. 9.5% and 4.8% (P=0.0001 and P=0.00004). The 1- and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1% and 54.5% vs. 19% and 9.5% (P=0.011 and P=0.003). Six patients (28.6%) with grade 2–4 aGVHD were identified in the chemo-DLI group. Two patients (9.1%) in the CAR-T group developed grade 1–2 aGVHD. Nineteen patients (86.4%) developed CRS in the CAR-T group, comprising grade 1–2 CRS in 13 patients (59.1%) and grade 3 CRS in 6 patients (27.3%). Two patients (9.1%) developed grade 1–2 ICANS.
Donor-derived anti-CD19 CAR-T-cell therapy may be better, safer, and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences. This study aimed to determine the deciding factors that drive students’ perceived advantages in class to improve precision education and the teaching model.
A mixed strategy of an existing flipped classroom (FC) and a case-based learning (CBL) model was conducted in a medical morphology curriculum for 575 postgraduate students. The subjective learning evaluation of the individuals (learning time, engagement, study interest and concentration, and professional integration) was collected and analyzed after FC-CBL model learning.
The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model. Students felt more engaged by instructors in person and benefited in terms of time-saving, flexible arrangements, and professional improvement. Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories: 1) advancing a guideline of precision teaching according to individual characteristics; 2) revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course; 3) understanding the perceived advantages and their interfaces; and 4) barriers and/or improvement to implement the FC-CBL model in the Research Design class, such as a richer description of e-learning and hands-on practice.
Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.
This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in promoting the structural and functional recovery of the injured CNS.
A compressive SCI mouse model was utilized for this investigation. Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein, acrolein-induced inflammation-related factors, and macrophages at the injury site and within the CNS. Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway to study macrophage regulation. The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67 (GAD65/67), vesicular glutamate transporter 1 (VGLUT1), paw withdrawal response, and Basso Mouse Scale score. Nissl staining and Luxol Fast Blue (LFB) staining were performed to investigate the structural recovery of the injured CNS.
Hydralazine downregulated the levels of acrolein, IL-1β, and TNF-α in the spinal cord. The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway, leading to M2 macrophage polarization, which protected neurons against SCI-induced inflammation. Additionally, hydralazine promoted the structural recovery of the injured spinal cord area. Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression. Furthermore, hydralazine facilitated motor function recovery following SCI. Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.
Hydralazine, an acrolein scavenger, significantly mitigated SCI-induced inflammation and oxidative stress in vivo, modulated macrophage activation, and consequently promoted the structural and functional recovery of the injured CNS.
A high-fat, low-carbohydrate ketogenic diet has been used to treat malignant glioma, in which the Raf/MEK/ERK signaling pathway is overactivated. However, whether the Raf/MEK/ERK signaling pathway is involved in the therapeutic effect of ketone bodies remains unknown. In this study, we investigated the effects of a major ketone body, 3-hydroxybutyric acid (3-HBA), on the proliferation and metastasis of malignant glioblastoma cells and the underlying mechanism.
Two human malignant glioblastoma cell lines (U87 and U251) were treated with different concentrations of 3-HBA with or without the Raf inhibitor PAF C-16 for 24 h. Cell proliferation, cell cycle, cell invasion, and phospholipase D1 (PLD1) activity were determined. Protein and gene expression levels of Raf/MEK/ERK signaling pathway members were examined.
3-HBA significantly decreased cell proliferation, invasion, and intracellular PLD1 activity in both U87 and U251 glioblastoma cell lines. 3-HBA treatment significantly increased the proportion of cells in the G1 phase and decreased the proportion of cells in S phase in U87 cells. In the U251 line, the proportion of treated cells in S phase was increased and proportion of cells in G2 was decreased. 3-HBA treatment also significantly decreased the protein expression levels of Raf, MEK, p-MEK, ERK, p-ERK, and PLD1 while increasing p53 expression; an effect that was similar to treatment with the Raf inhibitor. Co-treatment of 3-HBA with the Raf inhibitor further enhanced the effects of the 3-HBA in both cell lines.
We confirmed that a ketogenic microenvironment can inhibit glioma cell proliferation and invasion by downregulating the expression of PLD1 through the Raf/MEK/ERK signaling pathway.
With the increasing application of vascular reconstruction in surgical procedures, allogeneic vessels are becoming more popular in clinical practice due to their abundant sources, precise diameter matching, improved histocompatibility, and higher long-term patency rate. This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions.
The study utilized a total of 150 Sprague-Dawley (SD) rats, with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups. The abdominal aorta of the rats was chosen as the subject of our research. The aorta in the experimental groups were randomly assigned to 4 groups: University of Wisconsin (UW) solution group, histidine-tryptophan-ketoglutarate (HTK) solution group, normal saline (NS) group, and sodium lactate Ringer’s solution (RS) group. Samples were subjected to examination after preservation periods of 1 day, 3 days, 5 days, 7 days, 14 days, 30 days, and 90 days. Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test. Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining.
The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%. Regarding the vascular skeleton structure, both the UW group and HTK group exhibited intact structures after 2 weeks of preservation, with slightly edematous collagen and elastic fibers, which was significantly better than that of the NS group and RS group. In terms of cell activity and contractile function, all preservation groups showed similar effects within 2 weeks. However, after 2 weeks, the UW group showed the most favorable preservation effect (P<0.05). In terms of vascular tension, different groups exhibited similar effects within 1 week. However, after 2 weeks, the UW group showed the best preservation effect (P<0.05).
All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation. However, after 2-week preservation, the UW solution was found to be the most suitable solution for the preservation of blood vessels.
This study aimed to explore the clinical efficiency of an improved transosseous pullout suture technique for arthroscopic repair of a meniscus root tear.
From January 2017 to January 2021, 53 patients with posterior meniscus root tears combined with anterior cruciate ligament (ACL) and/or posterior cruciate ligament (PCL) tears were collected. Totally, in 29 patients (group A), the 2.0 mm modified pullout tunnel method was used to suture the posterior meniscus root, while 24 patients (group B) were treated with the traditional 4.5 mm pullout tunnel method. In group A, 20 patients had lateral meniscus posterior root (LMPR) combined with ACL tears, 5 patients had LMPR combined with ACL and PCL tears, and 4 patients had medial meniscus posterior root (MMPR) combined with ACL tears. In group B, 19 patients had LMPR combined with ACL tears, 3 patients had LMPR combined with ACL and PCL tears, and 2 patients had MMPR combined with ACL tears. The improvement of the Lysholm and VAS scores and the incidence of complications in group A and group B before the operation, 1 month and 3 months after the operation, and after the final follow-up were compared.
Preoperative Lysholm score was 26.0±5.6 in group A and 26.7±5.8 in group B (P>0.05). One-month postoperative Lysholm score was 66.5±5.7 in group A and 54.3±2.4 in group B (P<0.001). Three-month postoperative Lysholm score was 81.1±7.2 in group A and 73.2±9.7 in group B (P<0.05). Lysholm scores after the final follow-up was 90.3±5.6 in group A and 90.0±5.0 in group B (P>0.05). Preoperative VAS score was 6.3±1.4 in group A and 6.3±1.2 in group B (P>0.05). One-month postoperative VAS score was 1.8±0.7 in group A and 2.4±0.9 in group B (P<0.05). Three-month postoperative VAS score was 0.7±0.6 in group A and 0.8±0.6 in group B (P>0.05). VAS score after the final follow-up was 0.2±0.4 in group A and 0.3±0.5 in group B (P>0.05).
The improved transosseous pullout suture technique using a smaller 2.0 mm bone tunnel can virtually eliminate the risk of conflict with other bone tunnels and facilitate the management of bone tunnels in multiple ligament injuries, while also diminishing suture abrasion caused by the windshield wiper effect. The technique achieves good clinical efficacy.
Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. LncRNA HLA complex group 27 (HCG27) plays a crucial role in various metabolic diseases. However, the relationship between lncRNA HCG27 and GDM is not clear. This study aimed to verify a competing endogenous RNA (ceRNA) interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1 (MAPK1) regulated by HCG27 in GDM.
LncRNA HCG27 and miR-378a-3p were detected by RT-qPCR. The expression of MAPK1 in umbilical vein endothelial cells (HUVECs) was detected by RT-qPCR and that in the placenta by Western blotting. To explore the relationship among lncRNA HCG27, miR-378a-3p, MAPK1 and the glucose uptake ability of HUVECs, vector HCG27, si-HCG27, miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p. The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay. Besides, glucose consumption by HUVECs was detected by the glucose assay kit.
HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells, while the expression of miR-378a-3p was significantly increased in GDM tissues, and the expression of MAPK1 was decreased in GDM tissues. This ceRNA interaction regulation axis was proved to affect the glucose uptake function of HUVECs. The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein. If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection, the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed. MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs, whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1. The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27. Besides, overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmitic acid-induced insulin resistance model of HUVECs to normal.
LncRNA HCG27 promotes glucose uptake of HUVECs by miR-378a-3p/MAPK1 pathway, which may provide potential therapeutic targets for GDM. Besides, the fetal umbilical cord blood and umbilical vein endothelial cells collected from pregnant women with GDM after delivery could be used to detect the presence of adverse molecular markers of metabolic memory, so as to provide guidance for predicting the risk of cardiovascular diseases and health screening of offspring.
Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis.
In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified.
EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance.
Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.
This study aimed to explore the existence of small extracellular vesicles (sEVs) in peri-urethral tissues and the role of abnormal expression of sEVs in the pathogenesis of female stress urinary incontinence (SUI).
sEVs were extracted from peri-urethral vaginal wall tissues using differential centrifugation and were observed by transmission electron microscopy (TEM). The number of sEVs and their protein contents were compared between SUI and control groups using nanoparticle tracking analysis (NTA) and bicinchoninic acid (BCA) protein assay. Fibroblasts were cultured separately with SUI (SsEVs group) and normal tissue sEVs (NsEVs group). Proliferation and migration of fibroblasts were compared between groups using CCK-8 and wound healing assays, respectively. Expression levels of collagen I and III were compared among blank control (BC), NsEVs, and SsEVs groups using real-time PCR. Protein mass spectrometry was used to test the differentially expressed proteins contained in sEVs between groups.
sEVs were extracted and found under the electron microscope. There were significantly more sEVs extracted from the SUI group compared to the normal group. Fibroblasts showed increased proliferative and decreased migratory abilities, and expressed more collagen in the SsEVs group compared to the NsEVs and BC groups. Protein spectrum analysis demonstrated several differentially expressed targets, including components of microfibrils, elastin polymer, and anti-inflammatory factors.
sEVs were detected in the peri-urethral tissues. SUI tissues expressed more sEVs than control. The abnormal expression of sEVs and their protein contents may contribute to the pathogenesis and progression of SUI.
The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone.
This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions.
Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0–7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0–7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study.
Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.
This study assessed the necessity of surgical re-staging in women with borderline ovarian tumors (BOTs) and evaluated the impact of complete surgical staging, lymphadenectomy, and omentectomy on disease recurrence and survival.
We retrospectively reviewed the medical records of patients with BOTs. A total of 901 patients were eligible for inclusion in the study, and we evaluated some of the variables and clinical/surgical characteristics of the cases. The effects of the type of surgical procedure, surgical staging, and complete or incomplete staging on recurrence were calculated. The rates of disease-free survival, overall survival, and recurrence were compared according to complete surgical staging. A Cox regression analysis was performed to identify potential prognostic factors, and survival curves were constructed using the Kaplan-Meier method.
The overall recurrence rate was 13.9%, and recurrence was comparable between the complete surgical staging group and the incomplete groups (P>0.05). The performance of complete surgical staging did not show an effect on long-term survival, and complete surgical staging, omentectomy, and lymphadenectomy had no effect on recurrence. In multivariate analyses, only radical surgery and adjuvant chemotherapy were risk factors for the recurrence of BOTs. Furthermore, we found that omentectomy led to a relatively low recurrence rate in patients with International Federation of Gynecology and Obstetrics (FIGO) stage > I (P=0.022).
Our results suggest that complete surgical staging should be considered a standard treatment for patients with advanced stage BOTs but not for those at FIGO stage I. It might be safe to reduce the scope of surgical procedures in patients with early-stage BOTs. However, it is not necessary to perform re-staging operations for BOTs with a macroscopically normal extra-ovarian appearance.
Polyphenols are complex compounds containing multiple phenolic hydroxyl groups. They are widely distributed in plants and have antioxidant activities. Whether the antioxidant activities of the cultivated varieties of Echinacea are similar to or better than those of the wild ones and the relationship between the accumulation of polyphenols and their antioxidant activities are still not clear.
Folin-Ciocalteu method, high performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric ion reducing antioxidant power (FRAP) assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6)-sulfonic acid (ABTS) radical scavenging assay, and Fe2+ chelating ability assay were used, respectively, to detect the total polyphenols and 5 kinds of caffeic acid derivatives (chicoric acid, caffeic acid, caftaric acid, chlorogenic acid, and 1,5-dicaffeoylquinic acid) in the roots, stems, leaves, and flowers, and the antioxidant activities of 3 varieties of Echinacea: E. purpurea L., cultivar E. purpurea ‘Aloha’, and E. purpurea ‘White Swan’.
E. purpurea L. had the highest contents of total polyphenols, 5 caffeic acid derivatives and antioxidant activities, followed by E. purpurea ‘White Swan’ and E. purpurea ‘Aloha’, respectively. E. purpurea ‘White Swan’ had the strongest ability to remove the DPPH, ABTS•+ and free radicals, and to chelate Fe2+; E. purpurea L. had the strongest ability to reduce FRAP. The correlation analyses revealed that the contents of total polyphenols and caffeic acid derivatives of E. purpurea L. and E. purpurea ‘White Swan’ were correlated with their antioxidant activities.
E. purpurea L. was the most appropriate material for the development of medicinal plants. E. purpurea ‘White Swan’ could be used as a substitute for E. purpurea L. in terms of its antioxidant activity.
The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30–92 years old.
A total of 6669 healthy Chinese men and 4494 healthy Chinese women aged 30–92 years old were assessed for their skeletal muscle mass and visceral fat area.
The results showed age-dependent decreases in the total skeletal muscle mass indexes in both men and women aged 40–92 years old as well as age-dependent increases in the visceral fat area in men aged 30–92 years old and in women aged 30–80 years old. Multivariate regression models showed that the total skeletal muscle mass index was positively associated with the body mass index and negatively associated with the age and visceral fat area in both sexes.
The loss of skeletal muscle mass becomes obvious at approximately 50 years of age, and the visceral fat area commences to increase at approximately 40 years of age in this Chinese population.
The authors examined the original data of their work and noticed misuse of images in fig. 1 and fig. 3 (as shown below on the upper panels, red box). The correct images are shown on the lower panels (red box). The authors sincerely apologize for the mistake and confirm the change does not affect the scientific conclusion of the published work.