As a promising manufacturing technology, three-dimensional (3D) printing technology is widely used in the medical field. In the treatment of osteoarticular defects, the emergence of 3D printing technology provides a new option for the reconstruction of functional articular surfaces. At present, 3D printing technology has been used in clinical applications such as models, patient-specific instruments (PSIs), and customized implants to treat joint defects caused by trauma, sports injury, and tumors. This review summarizes the application status of 3D printing technology in the treatment of osteoarticular defects and discusses its advantages, disadvantages, and possible future research strategies.
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Emerging evidence suggests that synaptic dysfunction is associated with the onset and progression of AD. Interestingly, Ginkgo biloba extract (EGb) is one of the most frequently investigated herbal medicines for enhancing cognition and alleviating neurodegenerative dementia. This study aimed to investigate the effect and the mechanism of EGb on AD-like synaptic disorders.
Scopolamine (SCO)-induced rats were used to mimic AD-like memory deficits. Morris water maze test and fear conditioning test were conducted to evaluate the memory status of rats in response to different treatments. Then, the synapse alterations were assessed by Golgi staining, and Western blotting was conducted to assess the protein expression of PSD95, GluN2B, synapsin-1, and synaptophysin. Reverse transcription quantitative polymerase chain reaction was applied to detect the mRNA expression of PSD95 and the levels of miR-1-3p/miR-206-3p.
EGb supplement alleviated the learning and memory deficits induced by SCO in behavioral experiments. Moreover, EGb treatment attenuated synaptic damage elicited by SCO, manifested as increased dendritic spine density and the proportion of mushroom-type spines in hippocampal neurons. Further investigation indicated that EGb rescued the expression of synaptic-related proteins, especially PSD95, and decreased the levels of miR-1-3p/miR-206-3p in the rat hippocampus.
The application of EGb effectively treats SCO-induced memory impairments probably by suppressing miR-1-3p/miR-206-3p and elevating the expression of PSD95.
Cerebral ischemia/reperfusion (I/R) is a potential factor for lethal injury, and currently lacks effective remedies. Bauhinia championii extracts (BCEs) have been reported to exhibit anti-oxidative and anti-hypoxia properties. The current work aimed to study whether BCE could alleviate neuronal injury caused by I/R.
To investigate the protective effects of BCE, oxygen-glucose deprivation/reperfusion (OGD/R) was applied to the HT22 cell line in vitro and to a cerebral I/R mouse model in vivo.
Under OGD/R, the survival of HT22 cells was significantly prolonged after treatment with BCE. In vivo, BCE significantly reduced the infarct area and decreased neuronal apoptosis caused by I/R. It was further found that OGD/R could trigger endoplasmic reticulum (ER) stress and induce ER stress-mediated neuronal apoptosis in vivo and in vitro, while BCE could effectively alleviate ER stress and neuronal apoptosis.
These results suggested that BCE exhibits neuroprotective effects by reducing ER stress-mediated apoptosis after cerebral I/R injury. BCE may therefore be an effective therapeutic regimen against cerebral I/R damage.
Cell division cyclin 25 homolog C (Cdc25C) is a tumor-associated antigen candidate gene, and this may be used as an effective target in cancer treatment. The present study aims to evaluate the lysis effect of cytotoxic T lymphocytes (CTLs) induced by dendritic cell line DC2.4 overexpressing Cdc25C, and the feasibility of Cdc25C as a component in hepatoma immunotherapy.
The mouse Cdc25C gene was ligated into a lentiviral vector, and transfected into DC2.4 cells. The DC2.4 cell phenotype and cytokine secretion were determined by flow cytometry and ELISA, respectively. CD8+ T cells were sorted from the spleens of C57BL/6 mice using a magnetic bead sorting kit obtained from Miltenyi Biotech, Germany, and co-cultured with DC2.4 cells for one week as effector cells. Then, IL-2, granzyme B and perforin were detected in the CTL culture medium by ELISA. Next, time-resolved fluorescence immunoassay was used to detect the immune killing effect of Cdc25C-specific CTLs on target cells. Meanwhile, the effect of blocking MHC-I sites on target cells with a monoclonal anti-MHC-I antibody was evaluated.
The results revealed that Cdc25C could be stably overexpressed in DC2.4 cells by LV-Cdc25C infection. DC2.4 cells transfected with LV-Cdc25C secreted more IL-6, IL-12, TNF-α and IFN-γ, and had higher expression levels of CD40, CD86, CCR7 and MHC-II than unaltered DC2.4 cells. The elevated Cdc25C in dendritic cells also further increased the secretion of IL-2, granzyme B and perforin to elicit Cdc25C-specific CTLs, and induced the higher cytotoxicity in Hepa1-6 cell lines (P<0.05), but this had no effect on the target cells when MHC-I monoclonal antibodies were blocked.
DC2.4 cells transfected with LV-Cdc25C can induce specific CTLs, and result in a strong cellular immune response. The dendritic cells that overexpress Cdc25C may be useful for hepatoma immunotherapy.
Melatonin has been reported to suppress inflammation and alleviate liver fibrosis, but its effect on autophagy in liver fibrosis has not been studied. This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell (HSC)-T6 cell line.
The model was established in rats through carbon tetrachloride treatment, and melatonin was administered at three doses (2.5, 5.0, and 10.0 mg/kg). Haematoxylin and eosin staining and Van Gieson’s staining were performed to examine the pathological changes of liver. The expression of alpha-smooth muscle actin (α-SMA) and Beclin1 in liver tissues was detected by immunohistochemical staining. The protein levels of α-SMA, Beclin1 and LC3 in the animal model were detected by Western blot analysis, and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR (qRT-PCR) in the animal model. HSC-T6 cells were activated by platelet-derived growth factor-BB (PDGF-BB). The expression of α-SMA, Beclin1 and collagen I was detected by Western blot analysis, and the gene expression of Beclin1 and LC3 was detected by qRT-PCR.
Melatonin reduced the expression of α-SMA, Beclin1 and LC3 in liver tissues. In addition, melatonin inhibited the activation of HSC-T6 cells and the expression of α-SMA, Beclin1 and LC3 in these cells. These results revealed that melatonin could inhibit autophagy and HSC activation.
Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.
Ticagrelor is a widely used anti-platelet drug. However, the mechanisms by which ticagrelor protects against sepsis-induced acute kidney injury (AKI) have not been clearly demonstrated. We designed this study to explore the protective effect of ticagrelor on sepsis-induced AKI and to explore the underlying mechanisms.
C57BL6J mice received oral ticagrelor (20 mg/kg and 50 mg/kg) for 7 days, and then caecal ligation and puncture (CLP) were performed. An adenosine receptor antagonist, CGS15943, was administered (10 mg/kg, intraperitoneal injection) to block the adenosine pathway 2 h before CLP. After 24 h, serum creatinine levels were measured. Periodic acid-Schiff (PAS) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were employed to analyze pathological changes and cell apoptosis. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and mRNA expression of tissue TNF-α and IL-1β were detected. Western blotting analysis was used to determine AKT and mammalian target of rapamycin (mTOR) protein expression in the kidney.
PAS staining showed less swelling of renal tubules, and TUNEL staining revealed less cell apoptosis in the ticagrelor group than in the CLP group. Serum creatinine levels were significantly lower in the ticagrelor group than in the CLP group. Moreover, significantly lower serum and kidney levels of TNF-α and IL-1β were observed in the ticagrelor group. CGS15943 blocked the effects of ticagrelor. Western blotting analysis showed increased phosphorylation of AKT and mTOR in the kidneys of the 50 mg/kg ticagrelor group. The adenosine receptor antagonist inhibited the activation of AKT and mTOR.
This study demonstrates that the protective effect of ticagrelor on sepsis-induced AKI depends on adenosine receptor activation and the subsequent increase of AKT and mTOR phosphorylation.
Nonalcoholic fatty liver disease (NAFLD) is a common cause of clinical liver dysfunction and an important prepathological change of liver cirrhosis. Central obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome are the major risk factors for NAFLD. Sitagliptin (Sig) is a novel hypoglycemic agent that improves blood glucose levels by increasing the level of active incretin. Sig has been shown to prevent the development of fatty livers in mice on a fructose-rich diet. The purpose of this study was to observe the efficacy of Sig on NAFLD in type 2 diabetic mice.
The diet-induced obesity mouse model was established, and the diabetic mice were screened by an intraperitoneal glucose tolerance trial. The mice were randomly divided into four groups for 8 weeks of intervention: high-fat diet (HFD) group, Sig group, metformin (Met) group, and Sig+Met group. After the intervention, the liver function indexes as well as the blood glucose and blood lipid levels of the mice were measured. In addition, the wet weight of the liver was measured; the pathological sections of the liver tissues were stained to observe the hepatocyte fatty degeneration, inflammation, necrosis, and fibrosis; and the hepatic histological injury was recorded as the NAFLD activity score (NAS).
Compared with the normal control group, the body weight, liver weight, blood glucose level, insulin resistance (IR), blood lipid level, and transaminase level of the mice in the HFD group were significantly increased, showing typical metabolic syndrome. After treatment with Sig and/or Met, the mice gained less weight, had lower levels of blood glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and transaminase, and had improved IR compared with the HFD group. The liver pathological NASs in the Sig group (P=0.01), Met group (P=0.028), and Sig+Met group (P<0.001) were lower than those in the HFD group (P<0.05), suggesting that the use of the two drugs alone or in combination can improve the state of liver inflammation. In terms of fibrosis, there was no fibrosis in the control group but there was significant fibrosis in the HFD group (P<0.001). There was no significant difference between the drug intervention groups and the HFD group, indicating that the drug therapy (Sig and/or Met) did not significantly improve the pre-existing fibrosis.
Our experiment proved that Sig can improve NAFLD, including improvement of the serum transaminase level, hepatic pathological inflammation level, and hepatocyte adiposis, suggesting that Sig may play a role by improving glucose and lipid metabolism, reducing the body weight and liver weight, improving insulin sensitivity, and inhibiting fatty liver inflammation. Sig may be a new direction for the treatment of patients with a nonalcoholic fatty liver and diabetes, delaying the progression of NAFLD.
Gestational diabetes mellitus (GDM) and gestational weight gain (GWG) are important risk factors that are known to affect offspring growth, but these outcomes are inconsistent and it remains unknown if both risk factors have a synergetic effect on early childhood growth. The present study aimed to conduct offspring body mass index-for-age Z-scores (BMIZ) trajectories and to evaluate the independent and interactive effect of the status of GDM and excessive GWG on the risks of overweight/obesity from birth to 24 months of age.
A total of 7949 mother-child pairs were enrolled in this study. The weight and length of children were measured at birth, 6, 12, and 24 months of age to calculate BMIZ.
The status of GDM was positively associated with offspring BMIZ and risk of macrosomia at birth but was not associated with offspring BMIZ or the risks of overweight/obesity at 6, 12, and 24 months of age. In contrast, excessive GWG was positively linked to offspring BMIZ, the stable high BMIZ trajectory pattern, and risks of overweight/obesity in the first 24 months of age. These two risk factors also had a significant synergistic effect on macrosomia at birth, but the interactive effect was only significant in boys during the follow-up years in the sex-stratified analyses.
The maternal GWG was a more pronounced predictor than GDM with relation to BMIZ and risk of overweight/obesity in early childhood. The interactive effect between these risk factors on offspring overweight/obesity may vary by sex.
The influential factors of chemotherapy-induced myelosuppression in esophageal cancer in central China are unclear. This study aimed to investigate the effect of commonly used chemotherapy regimens on the incidence of myelosuppression in clinical treatment of esophageal cancer.
In this retrospective study, 624 patients with esophageal cancer who received six different chemotherapy regimens between 2013 and 2020 at our institute were included. Chemotherapy consisted of lobaplatin, 5-fluorouracil (5-F), lobaplatin and 5-F, nedaplatin, nedaplatin and paclitaxel (PTX), cisplatin and PTX. Multivariable logistic regression analysis was used to explore the risk of myelosuppression among the six different chemotherapy regimens.
Compared with lobaplatin group, the incidence of myelosuppression in patients treated with chemotherapy regimens of lobaplatin and 5-F, nedaplatin, nedaplatin and PTX and cisplatin and PTX were significantly ameliorated. The dose of lobaplatin was significantly reduced (P=0.007) when lobaplatin was combined with 5-F, and the combination could significantly reduce the risk of myelosuppression (P=0.022). Furthermore, chemotherapeutic regimens, the dose of platinum, hemoglobin and uric acid levels, age, sex, total bilirubin and immune-enhancing drugs were found to be strong predictors of developing myelosuppression.
Targeted preventive interventions that enhance immune function, reduce uric acid levels and choose combined medication during chemotherapy should be implemented for high-risk patients to reduce the occurrence of myelosuppression. In addition, the dose of lobaplatin should be adjusted when combined with other chemotherapy drugs to reduce the incidence of myelosuppression.
Increasing evidence has indicated that there is a correlation between Fusobacterium nucleatum (F. nucleatum) abundance and poor prognosis of colorectal cancer (CRC). Furthermore, tumor metastasis plays a decisive role in the prognosis of CRC patients. Therefore, it was hypothesized that the abundance of F. nucleatum in CRC tissues affects the tumor metastasis.
In the present study, F. nucleatum DNA obtained from 141 resected CRC samples was quantified by qPCR to determine whether there were differences in F. nucleatum abundance between groups with and without CRC metastasis.
The results revealed that F. nucleatum was more abundant in CRC patients with metastasis, and CRC tissues enriched with F. nucleatum had a higher risk of lymph node metastasis and distant metastasis. The receiver operating characteristic curve indicated that F. nucleatum in CRC tissues could be used as an indicator for CRC metastasis, to some extent. Furthermore, the in vitro experiments (electron microscopy, and migration and invasion trials) revealed that F. nucleatum was a highly invasive bacterial strain, and could significantly enhance the invasion and migration capacity of SW480 and SW620 cells. In addition, a meta-analysis comprehensively indicated a slight correlation between F. nucleatum abundance and advanced CRC stage (RR=1.17, 95% CI: 1.00–1.37, P=0.04, random effect).
There is a correlation between F. nucleatum abundance and CRC metastasis, and F. nucleatum may serve as a metastasis biomarker for CRC patients.
Patients undergoing liver transplantation for hepatocellular carcinoma (HCC) within the Milan criteria have an excellent outcome. We developed a program to analyze and prove that the Milan criteria can be expanded safely and effectively.
We retrospectively reviewed 117 HCC patients treated with liver transplantation between January 2013 and December 2017. Patients were grouped according to the Milan criteria, the University of California, San Francisco (UCSF) criteria, Up-to-seven criteria and Hangzhou criteria. Tumor-free and overall survival rates were investigated with a Kaplan-Meier analysis. Multivariable regression Cox models produced survival estimates for the patients that exceeded the Milan criteria.
The 1-year, 3-year and 5-year overall survival rates of patients fulfilling the Milan criteria (n=44) were 100%, 87.5% and 78.9%, respectively. Compared with the Milan criteria, the UCSF criteria (n=50), Up-to-seven criteria (n=51) and Hangzhou criteria (n=86) provided an expansion of 13.6%, 15.9% and 95.9%, respectively. The 1-year, 3-year and 5-year overall survival rates of patients fulfilling UCSF criteria, Up-to-seven criteria and Hangzhou criteria were 96.0%, 84.9%, 76.9%; 96.1%, 85.2%, 77.6% and 97.7%, 83.9%, 66.7%, respectively (P>0.05). Multifactor Cox regression showed that tumor diameter and microvascular invasion were independent risk factors for survival in patients that exceeded the Milan criteria.
Compared with the Milan criteria, the Hangzhou criteria can safely expand the scope of liver transplantation for HCC to a certain extent. By contrast, the UCSF criteria and Up-to-seven criteria result in a limited number of patients which need further expansion. Tumor diameter and microvascular invasion were the independent risk factors for survival in patients that exceeded the Milan criteria.
Coronavirus disease 2019 (COVID-19) has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide. Among the infected patients, there is a high prevalence of COVID-19-related cardiovascular injuries. However, the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear. The COVID-19 pandemic also has exacerbated the mental health burden of humans. Considering the close association between neuroimmune interactions and cardiovascular disease, this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease. It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage. Specifically, the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal (HPA) axis, sympathovagal imbalance, and endothelial dysfunction, which lead to an increased risk of developing cardiovascular injury during COVID-19. Therefore, during the prevention and treatment of cardiovascular complications in COVID-19 patients, particular attention should be given to relieve the mental health burden of these patients.
To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older.
This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression.
Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P<0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P<0.001] and a significantly lower probability of survival (P<0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203–17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19.
The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.
The goal of this study was to develop a decellularized tendon scaffold (DTS) and repopulate it with adipose-derived stem cells (ADSCs) assisted by low air pressure (LP).
The porcine superficial flexor tendons were processed into the DTSs using a combination of physical, chemical, and enzymatic treatments. The effectiveness of decellularization was verified by histological analysis and DNA quantification. The properties of the DTSs were evaluated by quantitative analysis of biochemical characterization, porosimetry, in vitro biocompatibility assessment, and biomechanical testing. Subsequently, the ADSCs-DTS complexes were constructed via cell injection assisted by LP or under atmospheric pressure. The differences in cell distribution, biomechanical properties, and the total DNA content were compared by histological analysis, biomechanical testing, and DNA quantification, respectively.
Histological analysis confirmed that no cells or condensed nuclear materials were retained within the DTSs with widened interfibrillar space. The decellularization treatment resulted in a significant decrease in the content of DNA and glycosaminoglycans, and a significant increase in the porosity. The DTSs were cytocompatible in vitro and did not show reduced collagen content and inferior biomechanical properties compared with the fresh-frozen tendons. The assistance of LP promoted the broader distribution of cells into the adjacent interfibrillar space and cell proliferation in DTSs. The biomechanical properties of the scaffolds were not significantly affected by the recellularization treatments.
A novel LP-assisted approach for the construction of cells-DTS complex was established, which could be a methodological foundation for further bioreactor and in vitro studies.
This study aimed to investigate the correlation between the surface area ratio of medial tibial plateau (MTP) to lateral tibial plateau (LTP) and the mechanical tibiofemoral angle (mTFA).
Lower limb computed tomography (CT) images were collected at our hospital. Then, the original CT data were analyzed and reconstructed using medical image processing software. The proximal and distal centres of the femur and tibia were marked. The surface areas of MTP and LTP were identified using image processing software. GraphPad Prism 8.0.2 was used to perform the statistical analysis.
The surface area ratio of MTP to LTP was significantly correlated with the mTFA in all patients (P<0.0001), male group (P<0.0001), female group (P<0.0001), varus group (P<0.0001), and valgus group (P=0.002). Furthermore, the surface area of MTP and LTP was significantly greater in the male group than in the female group (P<0.0001). There was significant difference in the surface area of the MTP between the varus and valgus groups (P<0.0001). Significant difference was also observed in the surface area ratio of MTP to LTP between the varus and valgus groups (P<0.0001).
The surface area ratio of MTP to LTP was correlated with the mTFA. Within a certain range, the smaller the mTFA, the greater the surface area ratio of MTP to LTP. For patients undergoing total knee arthroplasty, of whom the surface area of the MTP was basically equal to that of the LTP, it is recommended that the osteotomy should be performed in accordance with mechanical alignment standards, and that a symmetrical tibial plateau prosthesis should be used. For patients whose surface area of MTP is significantly greater than that of the LTP, it is recommended that the osteotomy should be performed in accordance with kinematic alignment standards, and that an anatomical tibial plateau prosthesis should be used.
Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It’s known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker.
Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis.
Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis.
MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.
The present study aimed to develop an autophagy-related gene prognostic prediction model to provide survival risk prediction for head and neck squamous cell carcinoma (HNSCC) patients.
The K-mean cluster analysis was performed on HNSCC samples based on the expression values of 210 autophagy-related genes for candidate signature gene selection. LASSO Cox regression analysis was generated using the potential genes and the risk score was calculated from the prognosis model. The risk score was processed as an independent prognostic indicator to construct the nomogram model. The immune status including immune cell infiltration ratio and checkpoints of patients with HNSCC in high- and low-risk groups was also explored.
LASSO Cox regression analysis was performed on the selected autophagy-related genes. According to the lambda value corresponding to the number of different genes in the LASSO Cox analysis, six genes (GABARAPL2, SAR1A, ST13, GAPDH, FADD and LAMP1) were finally chosen. The risk score based on the genes was generated, which was an independent prognostic marker for HNSCC. The prognostic prediction model (nomogram) was further optimized by the independent prognostic factors (risk score), which can better predict the prognosis and survival of patients. With the risk score and prognosis model, eight types of immune cells and six key immune checkpoints (CTLA4, PD1, IDO1, TDO2, LAG3, TIGIT) displayed expression specificity.
This study identified several potential prognostic biomarkers and established an autophagy-related prognostic prediction model for HNSCC, which provides a valuable reference for future clinical research.
Abdominal aortic balloon occlusion (AABO) is a vascular intervention method that has been widely used in the treatment of severe placenta accreta spectrum (PAS). The aim of this study was to investigate the benefits, potential risks, and characteristics of AABO combined with tourniquet binding of the lower uterine segment (LUS) in treatment of pregnant women with PAS.
In this study, 64 pregnant women with PAS scores greater than 5 were enrolled as research subjects and divided into two groups. Group A (n=34) underwent normal operative procedures including tourniquet binding of the LUS. Group B (n=30) underwent AABO combined with tourniquet binding of the LUS. General clinical characteristics, ultrasonography PAS score, intraoperative blood loss (IBL), blood loss within 24 h after surgery (24-h BL), postoperative complications, and neonatal data of the two groups were retrospectively reviewed. The influencing factors of IBL for the two groups were analyzed.
The amounts of IBL, 24-h BL, total input red blood cell, and the incidence of disseminated intravascular coagulation were significantly lower in group B than in group A (P<0.05), and this difference was even more significant in the subgroup of placenta percreta (PAS scores ≥10). Further multivariate linear analysis showed that the combined therapy of AABO and tourniquet could independently predict lower IBL than normal operative procedures did (P=0.001).
AABO combined with tourniquet binding of the LUS could improve the outcomes of pregnant women with severe PAS and reduce serious peripartum complications of AABO.
The purpose of the study was to evaluate the efficiency of the supine roll test (SRT) and alternative positional tests (APTs) including the bow and lean test (BLT), pseudo-spontaneous nystagmus (PSN), and lying down nystagmus (LDN) to identify the affected side in horizontal canal benign paroxysmal positional vertigo (HC-BPPV).
In our prospective study, we performed a testing profile (PSN, BLT, LDN, SRT) on 59 HC-BPPV patients using videonystagmography. We compared the accuracy and sensitivity of these tests in HC-BPPV lateralization. Data from 30 healthy patients were collected as the control group.
When performing positional tests, the elicited nystagmus coinciding with Ewald’s second law was defined as a “positive response”. In 44 patients with geotropic nystagmus, the rates of positive response in LDN, PSN, and BLT were 22/44 (50%), 19/44 (43%), and 18/44 (41%), respectively, while in 15 patients with apogeotropic nystagmus, the positive response rates of these three tests were 10/15 (66.7%), 9/15 (60%), and 4/15 (27.00%), respectively. The sensitivity of LDN (54.38%) was higher than that of PSN (47.37%) and BLT (38.60%) but lower than that of SRT (89.47%). Notably, the accuracy rate of PSN (71.8%) was higher than that of the other APTs. In 6 patients with symmetrical nysgtamus during the roll test, 5 patients showed a positive response in both LDN and BLT (83.34%), whereas 4 patients showed a positive response in PSN (66.67%).
All positional tests are helpful for determining the affected side of HC-BPPV, but SRT carries the highest accuracy of lateralization followed by PSN.
To explore the anti-inflammatory effects and mechanisms of action of thymol in Aspergillus fumigatus (A. fumigatus) keratitis.
The minimum inhibitory concentration of thymol against A. fumigatus was detected. To characterize the anti-inflammatory effects of thymol, mouse corneas and human corneal epithelial cells were pretreated with thymol or dimethyl sulfoxide (DMSO) before infection with A. fumigatus spores. Slit-lamp microscopy, immunohistochemistry, myeloperoxidase detection, quantitative real-time polymerase chain reaction, and Western blotting were used to assess infection. Neutrophil and macrophage recruitment, in addition to the secretion of LOX-1 and IL-1β, were quantified to evaluate the relative contribution of thymol to the inflammatory response.
We confirmed that the growth of A. fumigatus was directly inhibited by thymol. In contrast with the DMSO group, there was a lower degree of inflammation in the mouse corneas of the thymol-pretreated group. This was characterized by significantly lower clinical scores, less inflammatory cell infiltration, and lower expression of LOX-1 and IL-1β. Similarly, in vitro experiments indicated that the production of LOX-1 and IL-1β was significantly inhibited after thymol treatment, in contrast with the DMSO-pretreated group.
Our findings demonstrate that thymol exerted a direct fungistatic activity on A. fumigatus. Furthermore, thymol played a protective role in fungal keratitis by inhibiting LOX-1/IL-1β signaling pathway and reducing the recruitment of neutrophils and macrophages.
Melanoblasts are the cell source of regeneration for pigment restoration. The ability to differentiate into mature melanocytes is the essential feature of melanoblasts in depigmentation diseases. Cold atmospheric plasma is an ionized gas with near-room temperature and highly reactive species that has been shown to induce stem cell differentiation. The aim of the study was to explore the effect of cold atmospheric plasma on the differentiation of melanoblast progenitor cells.
In this study, melanoblasts were exposed to the plasma jet and the cell morphology was observed. The cell cycle and cell proliferation were detected. Furthermore, the cell immunofluorescence and the detection of melanin particle and nitric oxide were carried out to investigate the differentiation of melanoblast progenitor cells.
Cells that were treated with the plasma had longer and more synaptic structures, and the G1 phase of cell cycle was prolonged in the treated group. More melanin synthesis-related proteins and melanin particles were produced after plasma treatment. Nitric oxide was one of the active components generated by the plasma jet, and the nitric oxide content in the cell culture medium of the treated group increased.
These results indicate that an increase in nitric oxide production caused by a plasma jet can promote cell differentiation. The application of plasma provides an innovative strategy for the treatment of depigmentation diseases.
This study aimed to assess the feasibility and usefulness of transabdominal color Doppler flow imaging (CDFI) technology and the high-definition flow imaging (HDFI) technique in detecting fetal pulmonary veins (PVs) in the first trimester (11–13+6 weeks).
From December 2018 to October 2019, 328 pregnant women with 328 normal singleton fetuses (crown-rump length: 45–84 mm) who had undergone CDFI and HDFI scans for fetal heart and vessel examination were enrolled in this study. The cases were divided into three groups according to the gestational age: group A, 11+0 −11+6 weeks; group B, 12+0 −12+6 weeks; and group C, 13+0 −13+6 weeks. Baseline sonograms and CDFI and HDFI images were analyzed by two senior radiologists independently and blindly. The abilities of CDFI and HDFI to display PVs were compared.
Successful PV display rates via CDFI and HDFI were 2.3% and 68.2% (P<0.01), 22.4% and 82.4% (P<0.01), 41.5% and 91.2% (P<0.01) for group A, group B, and group C, respectively. The total successful display rates for the two methods were 28.9% (CDFI) and 84.8% (HDFI) (P<0.01).
The HDFI technique is more valuable than CDFI for detecting PVs in early pregnancy (11–13+6 weeks). HDFI can detect at least one PV in all cases and may be used to detect pulmonary venous anomalies early.
The influence of the coronary artery anatomy on the prognosis of patients receiving an arterial switch operation (ASO) is currently controversial, and the risk factors for this operation may change in more complicated patients. This study aimed to investigate the influence of coronary artery anomalies on the in-hospital and post-discharge outcomes of ASO in patients with transposition of the great arteries (TGA) and Taussig-Bing anomaly (TBA).
We retrospectively reviewed 206 patients who underwent ASO from January 2007 to December 2019. The median age at operation was 33 [interquartile range (IQR): 20–71] days. Median follow-up time was 7.2 years (IQR: 4.0–10.3 years).
Coronary anomalies were present in 86 patients (41.7%), with 9 (4.4%) of them having a single coronary artery. Additional coronary features included intramural courses in 5 (2.4%) patients, ostial stenosis in 1 (0.5%) patient, and accessory coronary artery orifices in 5 (2.4%) patients. There were 32 (15.5%) in-hospital deaths and 8 (4.6%) post-discharge deaths, yielding an overall survival of 81.3%, 80.7% and 79.9% at 1, 5 and 10 years, respectively. Mortality due to ASO has been drastically decreased since 2013. Patients with a single coronary artery had higher rate of in-hospital mortality, but this finding was not statistically significant. The earlier surgical era (OR: 2.756) and a longer cardiopulmonary bypass time (OR: 2.336) were significantly associated with in-hospital mortality, while coronary patterns were not. An intramural coronary artery (HR: 10.034) and a patient age of older than 1 year at the time of ASO (HR: 9.706) were independent predictors of post-discharge mortality.
ASO remains the procedure of choice for TGA with coronary anomalies with acceptable in-hospital and post-discharge outcomes in terms of overall survival and freedom of reoperation. However, intramural coronary artery is an independent risk factor for post-discharge mortality. Timely surgery within the 1st year of life helps improve overall midterm survival of ASO.
Isocitrate dehydrogenase gene (IDH) mutations are associated with tumor angiogenesis and therefore play an important role in glioma management. This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume (3D-BRAVO) sequence and dynamic contrast-enhanced (DCE) MRI in differentiating IDH1 status in gliomas.
Forty-four glioma patients [16 with IDH1 mutant-type (IDH1-MT), 28 with IDH1 wild-type (IDH1-WT)] were retrospectively analyzed. A blood vessel entering a tumor was defined as an intratumoral vessel; a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel. Combined vessels were defined as the sum of the intratumoral and peritumoral vessels. DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter.
Intratumoral, peritumoral, and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas, and the range of area under curves (AUCs) was 0.816–0.855. For DCE-derived parameters, cerebral blood volume, cerebral blood flow, mean transit time, and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas, and the range of AUCs was 0.703–0.756. Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas (AUC: 0.855, sensitivity: 0.857, specificity: 0.812, P<0.001).
The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.
Hepatitis B virus (HBV) infection, which has been recognized as an international public health challenge, has caused significant morbidity for the entire world. This research focused on patients with HBV in China to examine health utilization and expenses.
Patients hospitalized with HBV from 2017 to 2019 in tertiary hospitals in Hubei, a province located in central China, were selected as the study population. Healthcare information was collected from the provincial inpatient electronic system database. Univariate and regression analyses were performed to describe the basic situation of healthcare services and determine the influencing indicators of inpatient service expenditure.
A total of 367 381 cases of HBV infection were identified in the study area. Most of these cases were patients who were married (90.2%) and males (63%). With the great efforts by the universal coverage of the basic medical insurance (BMI) in China, the increasing rate of inpatient hospitalization for HBV was 3.5 times higher than that of the total inpatient health service cases in the study area. The average age of this group was 52.84±14.10 years and 11.1% of patients paid for their own medical expenditures without insurance. The average length of stay (LOS) was 11.10 days, and the average cost per patient was 15 712.05 RMB. Both values were higher than the average level in study area. Gender, marital status, career, payment type, and kind of hospitals significantly influenced healthcare utilization. Males and the elderly might incur higher healthcare costs than their counterparts.
The BMI operated by government has played a role in the utilization release of health services for HBV carriers. However, researchers must pay more attention to the continuing increase in the medical expenses of this group.
Ovarian cancer (OC) is one of the most common and most lethal gynecological malignancies. OC has an age-dependent incidence and occurs more commonly in females older than 50 years old. Most OC patients are diagnosed at an advanced stage and have a poor prognosis. Germline mutations in the BRCA1 DNA repair associated gene (BRCA1) and the BRCA2 DNA repair associated gene (BRCA2) account for 20%–25% of epithelial ovarian cancer (EOC). BRCA1 germline mutations are more common in Chinese EOC patients.
This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient. Whole-exome sequencing was performed on two EOC patients and an unaffected individual. Variant validation was also performed in all available members by Sanger sequencing.
A heterozygous splice site variant, c.4358-2A>G in the BRCA1 gene, was identified. Bioinformatic analysis showed that the variant may change the splicing machinery.
The BRCA1 splice site variant, c.4358-2A>G was identified as the likely genetic cause for EOC, and may also be associated with the increased risk of rectal adenocarcinoma in the family. The findings were beneficial for genetic counseling, helpful for cancer prevention in other family members, and may facilitate therapy decision-making in the future to reduce cancer lethality.