The latest edition of the WHO classification of the central nervous system was published in 2021. This review summarizes the major revisions to the classification of anterior pituitary tumors. The most important revision involves preferring the terminology of pituitary neuroendocrine tumor (PitNET), even though the terminology of pituitary adenoma (PA) still can be used according to this WHO classification compared to the previous one. Moreover, immunohistochemistry (IHC) examination of pituitary-specific transcription factors (TFs), including PIT1, TPIT, SF-1, GATA2/3, and ERα, is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups. However, TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages, which includes unclassified plurihormonal (PH) tumors and null cell (NC) tumors in this edition. The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors. However, due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA, the application of this new classification system in practice should be further evaluated and validated. Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery, this classification system offers no additional help for neurosurgeons in clinical practice, especially in determining the treatment strategies. Therefore, it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis, as well as pathological diagnosis, thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.
Few studies have investigated the differences in outcomes between primary and repeat surgery for a craniopharyngioma in adults. As a result, a treatment concept for adult patients with a craniopharyngioma has not yet been established. The present study aimed to retrospectively analyze adult patients with craniopharyngioma to compare surgical outcomes between primary surgery and surgery for recurrence.
The demographic and clinical data of 68 adult patients with craniopharyngioma who had primary surgery (n=50) or surgery for recurrence (n=18) were retrospectively analyzed. In addition, the patients were followed up for an average of 38.6 months (range: 1–133 months).
The cohorts of patients undergoing primary surgery or repeat surgery did not differ preoperatively in terms of demographic data, or radiological tumor features. However, patients with recurrent craniopharyngioma had significantly more pituitary hormone deficits and hypothalamo-pituitary disorders before surgery compared with patients with newly diagnosed craniopharyngioma. The success rate of complete resection in primary surgery was 53.2%. Even after repeat surgery, a satisfactory rate of complete resection of 35.7% was achieved. Operative morbidity was increased neither in patients with repeat surgery compared with those with primary surgery (postoperative bleeding P=0.560; meningitis P=1.000; CSF leak P=0.666; visual disturbance P=0.717) nor in patients with complete resection compared with those with partial resection. We found no difference in recurrence-free survival between initial surgery and repeat surgery (P=0.733). The recurrence rate was significantly lower after complete resection (6.9%) than after partial resection (47.8%; P<0.001).
Attempting complete resection is justified for not only those with newly diagnosed craniopharyngioma but also for those with recurrent craniopharyngioma. However, the surgeon must settle for less than total resection if postoperative morbidity is anticipated.
Pituitary adenomas (PAs) can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation. Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo. However, the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear.
Target gene prediction and transcriptomic profiling of invasive vs. noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14. For cellular analyses of miRNA functions, two mouse PA cell lines (AtT20 and TtT/GF) were transfected with miR-149-3p and miR-149-5p, respectively. The effects of miR-149 (3p and 5p) on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays, scratch migration assays, and invasion assays.
A significant downregulation of miRNA-149 was observed in invasive vs. noninvasive PA (0.32 vs. 0.09, P<0.0001). In AtT-20 and TtT/GF mouse PAs cells, transfection of mimic miRNA-149 (3p and 5p) caused a significantly reduced cell proliferation and matrigel invasion, whilst the effect on cell migration was less pronounced. Both strands of miRNA-149 (3p and 5p) markedly reduced protein levels of ADAM12 and MMP-14 by at least 40% in both cell lines.
This study proved that the invasiveness of PA cells is, at least partly, regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.
To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma.
The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS) for different indications in our department since 2011 was retrospectively analyzed.
The most common indication was the ineffectiveness of oral medication (41.1%), followed by the personal willingness of the patient (35.5%), and 20.6% of the patients were young women with clear tumor boundaries. The pseudocapsule was not observed in 63 cases (58.9%), incomplete pseudocapsule was observed in 26 cases (24.3%), and complete pseudocapsule in 18 cases (16.8%). A total of 97 patients (90.7%) obtained 1-year post-operation remission. According to the relative location of the adenoma and pituitary gland on the MRI scan, 46 patients were classified into a central type, 59 a lateral type, and 2 a supra-pituitary type. Two patients developed hypogonadism, one patient developed hypocortisolism, and one patient developed post-operative hypothyroidism. Two patients were administrated with hormone replacement treatment, and the treatment was stopped within one week. There was no permanent hypopituitarism. Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma.
ETTS was an effective treatment for pituitary microprolactinomas. This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation. Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.
In this study, we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS).
Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021. Based on the results of the endocrinological evaluation and MRI examinations before and after surgery, the fluctuation of pituitary function and the extent of resection were analyzed. Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual.
Among the 144 patients with pituitary macroadenomas, 72 (50.0%) were female and 72 (50.0%) were male, the median age was 50 years, 26 (18.1%) had invasiveness grade 0, 46 (31.9%) had grade I, 57 (39.6%) had grade II, and 15 (10.4%) had grade III according to Lu’s classification method. Based on observation during surgery, 37 cases (25.7%) had no pseudocapsule, 54 cases (37.5%) had incomplete pseudocapsule, and 53 cases (36.8%) had intact pseudocapsule. In addition, 91 (63.2%) patients had total resection, 39 (27.1%) had subtotal resection, and 14 (9.7%) had partial resection. As for anterior pituitary function, 13 of 19 hypothyroid patients had recovery after surgery, with a remission rate of 68.4%. Eighteen of the 26 decreased cortisol patients got back to normal, with a remission rate of 69.2%. A total of 27 of 51 patients with hypogonadism improved, with a remission rate of 52.9%. Univariate and multivariate analyses indicated that gender, tumor size, and invasiveness were predictors of postoperative residual in patients (P<0.05).
The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas. Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.
Dental biofilm is the initiating factor of oral diseases, such as periodontitis and caries. Orthodontic treatment could alter the microbiome structure balance, and increase the risk of such diseases. Furthermore, fixed appliances can induce temporary changes in the microbiome community, and the changes that clear aligners bring are smaller by comparison. Temporary anchorage devices (TADs) are skeletal anchorages that are widely used in orthodontic treatment. Microorganisms affect the occurrence and development of inflammation surrounding TADs. At present, existing researches have verified the existence of plaque biofilm on the surface of TADs, but the formation of plaque biofilm and plaque composition under different stable conditions have not been fully understood. The development of high-throughput sequencing, molecular biology experiments, and metabonomics have provided new research ideas to solve this problem. They can become an effective means to explore the microbiome surrounding TADs.
With the deepening of China’s health-care reform, an integrated delivery system has gradually emerged with the function of improving the efficiency of the health-care delivery system. For China’s integrated delivery system, a medical consortium plays an important role in integrating public hospitals and primary care facilities. The first medical consortium policy issued after the COVID-19 pandemic apparently placed hope on accelerating the implementation of a medical consortium and tiered health-care delivery system. This paper illustrates the possible future pathway of China’s medical consortium through retrospection of the 10-year process, changes of the series of policies, and characteristics of the policy issued in 2020. We considered that a fully integrated medical consortium would be a major phenomenon in China's medical industry, which would lead to the formation of a dualistic care pattern in China.
The aim of this study was to explore the effect of norepinephrine (NE) on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.
Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks. Thirteen healthy New Zealand white rabbits were randomly selected as controls. After atherosclerosis induction, standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery. Contrast-enhanced ultrasound (CEUS) was performed at baseline and during intravenous injection of NE. The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity.
The serum nitric oxide (NO) level in atherosclerotic rabbits was higher than that in healthy rabbits (299.6±152 vs. 136.5±49.5, P<0.001). The infusion of NE induced a significant increase in the systolic blood pressure (112±14 mmHg vs. 84±9 mmHg, P=0.016) and a significant decrease in the enhanced intensity in renal cortex (17.78±2.07 dB vs. 21.19±2.03 dB, P<0.001) and renal medulla (14.87±1.82 dB vs. 17.14±1.89 dB, P<0.001) during CEUS. However, the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline.
NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis, partly by reducing the serum NO level.
This study aimed to develop a nomogram to predict the overall survival (OS) of patients with acinar-predominant adenocarcinoma (APA).
Data from patients with APA obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2008 and 2016 were used. Significant prognostic factors were incorporated to construct a nomogram for predicting the 1-, 3-, and 5-year OS in these patients. The discrimination and calibration abilities of the nomogram were assessed using a C-index and calibration curves, respectively.
A total of 2242 patients with APA were randomly divided into a training cohort (n=1576) and validation cohort (n=666). The independent prognostic factors for OS incorporated into the nomogram included marital status, age, gender, differentiation grade, T stage, N stage, and M stage. The nomogram showed good prediction capability, as indicated by the C-index [0.713, 95% confidence interval (CI): 0.705–0.721 in the training cohort, and 0.662, 95% CI: 0.649–0.775 in the validation cohort]. The calibration curves demonstrated that the 1-, 3-, and 5-year OS probabilities were consistent between the observed and predicted outcome frequencies. Patients were divided into the high-risk and low-risk groups with the former showing significantly worse survival than the latter (P<0.001).
Using the SEER database, a nomogram was established to predict the 1-, 3-, and 5-year OS of patients with APA and was superior to the tumor size, lymph node, and metastasis staging system in terms of evaluating long-term prognosis.
T cell receptor-associated transmembrane adaptor 1 (TRAT1) is one of the hub genes regulating T cell receptors (TCRs). Herein, the roles of TRAT1 in the prognosis and immune microenvironment of non-small cell lung cancer (NSCLC) were investigated.
The expression and prognosis values of TRAT1 in NSCLC, and the relationship between TRAT1 expression levels and cancer immune cell infiltration was identified via the TIMER, UALCAN, TISIDB, and other databases. The mechanism of TRAT1 in NSCLC was analyzed using gene set enrichment analysis (GSEA).
The expression level of TRAT1 was decreased in NSCLC tissues. Low TRAT1 expression was associated with shorter overall survival of patients with NSCLC and was related to gender, smoking, and tumor grade. TRAT1 was involved in regulating immune response, TCR signaling pathway, PI3K/AKT, and other processes. TRAT1 expression levels were positively correlated with immune cell infiltration in NSCLC.
Down-regulation of TRAT1 expression was associated with an unfavorable prognosis and immune infiltration of NSCLC.
Current commercially available immunological tests cannot be used for discriminating active tuberculosis (TB) from latent TB infection. To evaluate the value of biomarker candidates in the diagnosis of active TB, this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) between patients with active TB and individuals with latent TB infection by transcriptome sequencing.
The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis (Mtb) antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome sequencing. Selected candidate genes were evaluated in cohorts consisting of 110 patients with TB, 30 individuals with latent TB infections, and 50 healthy controls by quantitative real-time RT-PCR. Receiver operating characteristic (ROC) curve analysis was performed to calculate the diagnostic value of the biomarker candidates.
Among the differentially expressed genes in PBMCs without Mtb antigen stimulation, interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) had the highest area under curve (AUC) value (0.918, 95% CI: 0.852–0.984, P<0.0001) in discriminating patients with active TB from individuals with latent TB infection, with a sensitivity of 91.86% and a specificity of 84.00%. In Mtb antigen-stimulated PBMCs, orosomucoid 1 (ORM1) had a high AUC value (0.833, 95% CI: 0.752–0.915, P<0.0001), with a sensitivity of 81.94% and a specificity of 70.00%.
IFIT3 and ORM1 might be potential biomarkers for discriminating active TB from latent TB infection.
Hyperglycemia-induced inflammation and subsequent endothelial injuries ultimately lead to the pathogenesis of cardiovascular diseases associated with high mortality, such as atherosclerosis. Maslinic acid (MA) is a phytochemical with anti-inflammatory activity. However, it remains unknown whether it can inhibit diabetes-associated cardiovascular inflammation. The present study aimed to determine the effect of MA on high glucose-induced endothelial inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanism.
HUVECs were treated with high glucose to induce inflammation and apoptosis. Apoptosis was determined by flow cytometry. CCK-8 assay was used to examine cell viability. Production levels of cytokines were detected by quantitative realtime PCR (qPCR) and ELISA. Protein expression levels and signaling pathways activation were detected by Western blotting. RNA immunoprecipitation and qPCR were used to determine the N6-methyladenosine (m6A) levels of target mRNAs.
MA promoted the recruitment of RNA demethylase ALKBH5 to TXNIP mRNA, and subsequently enhanced its m6A demethylation. By this means, MA decreased the stability of TXNIP mRNA and downregulated its expression level. Subsequently, reactive oxygen species (ROS) and production of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1β, were inhibited. And high glucose-induced apoptosis in HUVECs was inhibited by MA.
MA ameliorates high glucose-induced endothelial inflammation and injury, serving as a new potential therapeutic application for protecting against diabetes-associated atherosclerosis and other inflammatory diseases.
Due to the rarity of angioimmunoblastic T-cell lymphoma (AITL), very limited data concerning its incidence patterns and prognostic factors are available. This study aimed to explore the incidence, characteristics, survival outcomes, and prognostic factors of AITL.
Age-adjusted incidence and temporal trends were calculated based on 1247 AITL patients from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-13 database. A total of 1525 AITL patients from the SEER-18 database and 43 patients from our single center were included for survival analysis and nomogram construction.
The age-adjusted incidence for overall cohort was 0.123 [95% confidence interval (CI), 0.117–0.131) per 100 000 during 1992–2017. The overall incidence increased steeply at the rate of 15.3% (95%CI 11.0%–19.8%, P<0.001) per year during 1992–2004, but remained stable during 2004–2017 (P=0.200). Similar incidence trends were observed in age, sex, and stage subgroups. The final nomograms consisted of four variables: age at diagnosis, sex, Ann Arbor stage, and primary site. The concordance index (C-index) of the nomogram for 5-year overall survival prediction was 0.717, 0.690 and 0.820 in the training cohort, validation cohort-1 and cohort-2, respectively. Regarding the disease-specific survival (DSS), the nomogram also demonstrated a good discrimination level, with the C-index for predicting the probability of DSS at 5 years of 0.716, 0.682 and 0.813 for the three cohorts, respectively. The calibration displayed good concordance between the nomogram-predicted and actual observed outcomes.
The age-adjusted incidence for AITL was low during 1992–2017. The incidence continuously increased during 1992–2004, but remained stable during 2004–2017. The nomograms as proposed may provide a favorable and accurate prognostic survival prediction in AITL.
MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases. HypoxamiRs (miR-210 and miR-21) play an important role in hypoxia and in inflammation-associated hypoxia. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that would potentiate many pathological complications, including hemolytic anemia. This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients.
This work was designed to analyze the circulating levels of↱ the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α (HIF-α) in SLE/hemolytic anemia patients. SLE activity was evaluated for all patients by SLE Disease Activity Index (SLEDAI). Clinical manifestations/complications and serological/hematological investigations were reported. HIF-α concentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR.
The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients. A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded. Among the associated-disease complications, hypertension, arthritis, oral ulcers, and serositis were associated with a high circulating miR-210 expression, while the occurrence of renal disorders was associated with the increased miR-21 expression. Furthermore, the HIF-α level was remarkably elevated in SLE/hemolytic anemia patients. A high positive correlation was recorded between the HIF-α concentration and miR-210/miR-21 expression levels. The occurrence of oral ulcers, arthritis, and hypertension was associated with the increased HIF-α concentration. On the other hand, SLEDAI and white blood cell count were positively correlated with miR-21/ miR-210. The erythrocyte sedimentation rate was positively correlated with miR-21.
The dysregulation of the circulating miR-210/miR-210/HIF-1α levels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases.
This study aimed to investigate the effect of combretastatin A4 phosphate (CA4P) on proliferation, migration, and capillary tube formation of human umbilical vein endothelial cells (HUVECs) and the efficacy of transcatheter arterial embolization combined with CA4P in the treatment of rabbit VX2 liver tumor.
The effects of different concentrations of CA4P on proliferation, migration and capillary tube formation of HUVECs were investigated by cell proliferation assay, wound healing assay and capillary tube formation assay, respectively. Thirty-two rabbits implanted with liver VX2 tumors were randomly divided into 4 groups. After catheterization of the left hepatic artery, the infusion was performed using normal saline (group A), CA4P aqueous solution (group B), lipiodol and polyvinyl alcohol particles (group C), and CA4P lipiodol emulsion and polyvinyl alcohol particles (group D), respectively. Half of the animals in each group were euthanized for immunohistochemical analysis to evaluate microvessel density (MVD) at 3 days post-treatment. The other half were examined by MRI and histology to evaluate tumor growth and necrosis at 7 days post-treatment.
CA4P could inhibit the proliferation, migration, and tube formation of HUVECs in cell experiments. After interventional treatment, the level of MVD in group D was lower than that in group C (P<0.01). The tumor volume in group C or D was lower than that in group A or B (P<0.01). The tumor necrosis rate was higher in group D than in the other groups.
The study suggests that CA4P could inhibit the proliferation, migration, and capillary tube formation of HUVECs, and transcatheter arterial embolization combined with CA4P could inhibit the growth of VX2 tumor and obviously induce tumor necrosis.
Thyroid hormones (THs) regulate multiple physiological activities in the liver, including cellular metabolism, differentiation, and cell growth, and play important roles in the pathogenesis of hepatocellular carcinoma (HCC). Thyroid peroxidase (TPO) is a key molecule involved in the THs synthesis and signaling pathway. As an epigenetic modification, DNA methylation has a critical role in tumorigenesis with diagnostic potential. However, the connection between THs and DNA methylation has been rarely investigated.
The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning, and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays, and evaluated their clinical implications.
We identified that the methylation of the TPO promoter was downregulated in the HCC tissues (P<0.0001) with a mean difference ranging from 18.5% to 22.3%. This methylation pattern correlated with several clinical factors, including a multi-satellite tumor, fibrous capsule, and the presence of tumor thrombus. The receiver operator characteristic (ROC) curve analysis further confirmed that the percent methylated reference (PMR) values for TPO were predictive of the tumor [the area under the curve (AUC) ranged from 0.755 to 0.818] and the thrombosis in the HCC patients (the AUC ranged from 0.706 to 0.777).
These findings demonstrated that epigenetic alterations of TPO, as indicated by the PMR values, were a potential biomarker for HCC patients with tumor thrombosis.
Anastomotic leakage (AL) is one of the serious complications after anterior resection for rectal cancer. Defunctioning stoma (DS) is one of the most widely used approaches to prevent it; however, the effect of DS on the occurrence of AL remains controversial. This study aimed to investigate risk factors of AL and assess the effect of DS after anterior resection for rectal cancer patients.
A retrospective analysis was conducted for the data of 1840 patients who underwent anterior resection for rectal cancer from January 2014 to December 2019.
The results showed the overall AL incidence was 7.5%. Multivariate analyses revealed that males [odds ratio (OR) 1.562] and T3–T4 stage (OR 1.729) were independent risk factors for all patients. After propensity score matching analysis, the AL incidence was 14.1% in the group with no DS and 6.4% in the DS group (P<0.001). The clinical AL (grade B + grade C) incidence was 12.4% in no DS group and 4.6% in the DS group (P<0.001).
The study suggested that males and T3–T4 stage were independent risk factors of AL. In addition, DS could reduce the rate of symptomatic AL.
The aim of this study was to examine the effects of photodynamic therapy (PDT) on the expression of Nav1.7 in spinal dorsal root ganglion (DRG) neurons.
The primary DRG neurons from newborn SD rats were cultured. The cells were identified by neuron-specific enolase immunofluorescence staining. DRG neurons were divided into four groups: control group, photosensitizer group, laser group, and PDT group. The cell viability was detected by a cell counting kit-8 (CCK8) assay. qRT-PCR and Western blotting were used to determine the mRNA and protein expression levels of Nav1.7 in DRG neurons.
The purity of the cultured primary DRG neurons was greater than 90%. Compared with the control group, no significant change was found in the cell viability of the photosensitizer group, while the viability in the laser group and the PDT group was significantly reduced. The mRNA and protein expression levels of Nav1.7 were significantly greater in the laser group and the PDT group than in the control group. At the same time, the mRNA and protein expression levels of Nav1.7 were greater in the laser group than in the PDT group.
Both laser and PDT could upregulate the expression of Nav1.7 in DRG neurons, and the promoting effect might be related to the pain induced by clinical treatment. This study provides a research basis for the use of laser and PDT to treat pain. A better understanding of the relationship between Nav1.7 and PDT can help clinicians better manage PDT-related pain.
This study aims to investigate the expression, prognostic value, and function of kinesin superfamily 4A (KIF4A) in cervical cancer.
Cervical cancer cell lines (Hela and SiHa) and TCGA data were used for experimental and bioinformatic analyses. Overall survival (OS) and progression free survival (PFS) were compared between patients with high or low KIF4A expression. Copy number variation (CNV) and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered sites. The function of KIF4A was also explored based on transcriptome analysis and validated by experimental methods. Chemotherapeutic and immunotherapeutic benefits were inferred using multiple reference databases and algorithms.
Patients with high KIF4A expression had better OS and PFS. KIF4A could inhibit proliferation and migration and induce G1 arrest of cervical cancer cells. Higher CNV load was observed in patients with low KIF4A expression, while the group with low KIF4A expression displayed more significantly altered sites. A total of 13 genes were found to mutate more in the low KIF4A expression group, including NOTCH1 and PUM1. The analysis revealed that low KIF4A expression may indicate an immune escape phenotype, and patients in this group may benefit more from immunotherapy. With respect to chemotherapy, cisplatin and gemcitabine may respond better in patients with high KIF4A expression, while 5-fluorouracil etc. may be responded better in patients with low KIF4A expression
KIF4A is a tumor suppressor gene in cervical cancer, and it can be used as a prognostic and therapeutic biomarker in cervical cancer.
Runt-related transcription factor 1 (RUNX1) has been proven to be over-expressed and vital in many malignancies. However, its role in cervical cancer is still unclear.
Some online databases (Oncomine, GEPIA, UALCAN, LinkedOmics, and others) were used to explore the expression level, prognostic significance, and gene mutation characteristics of RUNX1 in cervical cancer. The protein levels of RUNX1 in cervical cancer were measured by immunohistochemistry (IHC). The functional changes of cervical cancer cells were measured in vitro after decreasing RUNX1.
Bioinformatic results revealed that RUNX1 was upregulated in cervical cancer compared to normal tissues. Moreover, over-expression of RUNX1 was significantly correlated with cervical cancer patients’ clinical parameters (e.g., individual cancer stages, patients’ age, nodal metastasis status, and others). Meanwhile, functional enrichment analysis of RUNX1-related genes indicated that RUNX1 was mainly involved in the epithelial-mesenchymal transition (EMT) process in cervical cancer. Furthermore, RUNX1 may be upregulated by hsamiR-616-5p and hsa-miR-766 identified by miRDB, TargetScan, and miRWalk. Finally, RUNX1 was upregulated in cervical cancer compared to normal tissues by IHC in collected cervical cancer samples. The invasion and migration abilities of cervical cancer cells were significantly reduced by repressing EMT after knocking down RUNX1 in vitro.
RUNX1 was highly expressed in cervical cancer, and upregulated RUNX1 could significantly promote the invasive abilities of cervical cancer cells by inducing EMT. Therefore, RUNX1 may be a potential biomarker for early diagnosis and targeted therapy of cervical cancer.
This study aimed to investigate the influence of different culture media on early embryonic cleavage kinetics using time-lapse analysis and to determine the possible relationships between energy substrates in culture media and the cleavage kinetics.
A total of 10 021 embryos from 1310 couples were cultured in time-lapse incubators. Embryos cultured in Vitrolife media were allocated to group I, and those in COOK media to group II. Embryo cleavage time points up to the 8-cell stage (t2–t8) were observed after pronuclei fading.
The baseline demographic features, in vitro fertilization indications, ovarian stimulation protocol, oocyte-cumulus complexes, fertilization rate, together with pregnancy and perinatal outcomes were similar (P>0.05) between groups I and II. According to the time-lapse analysis, all embryos in group I showed significantly faster cleavage speed than those in group II (P<0.05). Furthermore, there was better synchrony in division (s3) and a longer length of the third cell cycle duration (cc3) in group II. Interestingly, implanted embryos in group II showed faster cleavage speed than those in group I, especially at t4 and t7. The glucose contents and multiple major amino acids were similar between the two groups. Lactic and pyruvic acid contents were generally higher in group I than those in group II.
Because different commercial culture media may influence cleavage kinetics of embryos, it is essential for embryologists to take culture media into consideration in selecting a potential embryo when using a time-lapse system before implantation.
This study aimed to evaluate the ability of a digital fundus camera to observe the development of the anterior chamber angle (ACA) in premature infants.
Forty-eight eyes of preterm infants (n=48) were examined by a digital fundus camera to observe the development of the ACA. ACA grading was performed based on the visualization of the anterior chamber structures according to the Scheie Angle Depth Evaluating System.
ACA images from all 48 infants were successfully acquired using RetCam3. The corrected gestational age ranged from 30 weeks to 49 weeks, which covered the period from 2 months preterm to >2 months post-term. As the corrected gestational age increased, the corrected gestational age grading was significantly decreased. The mean corrected gestational ages of the infants corresponding to the ACA classification from grade IV to grade 0 were 32.75±1.89, 37.20±1.30, 39.75±2.38, 40.56±2.24, and 44.23±2.14 weeks, respectively, which were all significantly different (P<0.05). The regression analysis showed a linear correlation between the grading of the ACA and the corrected gestational age (R2=0.724, P=0.0001).
The ACA of a full-term newborn can be fully detected and evaluated by a digital fundus camera. For premature infants, part of the ACA is not visible physiologically; however, it should not be misdiagnosed as angle closure or a narrow angle.
To evaluate the feasibility of using gadopentetate dimeglumine (Gd-DTPA) for dual-energy computed tomography pulmonary angiography (CTPA).
Sixty-six patients were randomly divided into three groups and underwent CTPA. Group A had a turbo flash scan using an iohexol injection, Group B had a turbo flash scan using Gd-DTPA, and Group C had a dual-energy scan using Gd-DTPA. The original images of Group C were linearly blended with a blending factor of 0.5 or reconstructed at 40, 50, 60, 70, 80, 90, 100, and 110 keV, respectively. The groups were compared in terms of pulmonary artery CT value, image quality, and radiation dose.
The pulmonary artery CT values were significantly higher in Group C40keV than in Groups B and C, but lower than in Group A. There was no significant difference in the image noise of Groups C40keV, B, and C. Moreover, Group A had the largest beam hardening artifacts of the superior vena cava (SVC), followed by Groups B and C. Group C40keV showed better vascular branching than the other three groups, among which Group B was superior to Group A. The subjective score of the image quality of Groups A, B, and C showed no significant difference, but the score was significantly higher in Group C40keV than in Groups A and B. The radiation dose was significantly lower in Group B than in Groups A and C.
Gd-CTPA is recommended to patients who are unsuitable for receiving an iodine-based CTPA. Furthermore, a turbo flash scan could surpass a dual-energy scan without consideration for virtual monoenergetic imaging.
This cross-sectional study aimed to investigate the current attention and intervention of oncologists on oxaliplatin (OXA)-induced adverse reactions (ADRs).
In 31 provinces or administrative regions across China, 401 oncologists were surveyed through a self-designed questionnaire. The survey queried the basic information of respondents, clinical use of OXA, OXA-induced ADRs, and relative interventions. Chi-square tests and multiple logistic regression were used to explore the sociodemographic factors influencing the safety perception of OXA and the relevant interventions.
The survey showed that the age of respondents was mainly distributed between 30 and 40 years and the working period for most oncologists was no more than 5 years. Oncologists with long working years were more willing to conduct patient education and inquire about ADRs than those with short working years. The rate of ADRs reported by oncologists with intermediate professional titles was significantly higher than that reported by oncologists with junior and senior professional titles.
Our findings indicate that oncologists in mainland China are concerned about OXA-induced ADRs, but the reporting of ADRs still needs to be strengthened. Therefore, training and educational programs are urgently needed to improve the risk management of OXA-induced ADRs among oncologists.
In 2017, China launched a new round of medical reform (NMR) to address the inaccessibility of high-priced drugs for patients with serious diseases. This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies (mAbs), and the effective promotion policies after the NMR.
We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province, China. By interviewing hospital pharmacy experts, we identified the potential value of the current NMR in improving the access to therapeutic mAbs.
The average availability of 13 mAbs increased by 8.1% in the surveyed hospitals of Hubei province after the NMR. The median unit price of 10 mAbs dropped by 34.3%. The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident (56.2% reduction). The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs. However, the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs.
Not all current NMR policies play a positive role in promoting the accessibility of mAbs. To further improve the accessibility of mAbs in the future in China, it is therefore critical to increase the investment in independent research and development of high-quality mAbs, establish localized guidelines for the rational use of mAbs in clinical practice, and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders.