New non- and less-invasive techniques have been developed to overcome the procedural and operator related burden of the fractional flow reserve (FFR) for the assessment of potentially significant stenosis in the coronary arteries. Virtual FFR-techniques can obviate the need for the additional flow or pressure wires as used for FFR measurements. This review provides an overview of the developments and validation of the virtual FFR-algorithms, states the challenges, discusses the upcoming clinical trials, and postulates the future role of virtual FFR in the clinical practice.
Diabetes and its complications reduce quality of life and are life-limiting. At present, diabetes treatment consists of hypoglycemic agents to control blood glucose and the use of insulin-sensitizing drugs to overcome insulin resistance. In diabetes, autophagy is impaired and thus there is poor intracellular environment homeostasis. Pancreatic β-cells and insulin target tissues are protected by enhancing autophagy. Autophagy decreases β-cell apoptosis, promotes β-cell proliferation, and alleviates insulin resistance. Autophagy in diabetes is regulated by the mammalian target of rapamycin (mTOR)/adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) pathway and others. Autophagy enhancers can likely be used as a treatment for diabetes and its complications. This review examines the evidence linking autophagy to diabetes.
Acute lung injury (ALI) is an acute clinical syndrome characterized by uncontrolled inflammation response, which causes high mortality and poor prognosis. The present study determined the protective effect and underlying mechanism of Periplaneta americana extract (PAE) against lipopolysaccharide (LPS)-induced ALI.
The viability of MH-S cells was measured by MTT. ALI was induced in BALB/c mice by intranasal administration of LPS (5 mg/kg), and the pathological changes, oxidative stress, myeloperoxidase activity, lactate dehydrogenase activity, inflammatory cytokine expression, edema formation, and signal pathway activation in lung tissues and bronchoalveolar lavage fluid (BALF) were examined by H&E staining, MDA, SOD and CAT assays, MPO assay, ELISA, wet/dry analysis, immunofluorescence staining and Western blotting, respectively.
The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α, IL-6 and IL-1β by suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells. Furthermore, PAE suppressed the neutrophil infiltration, permeability increase, pathological changes, cellular damage and death, pro-inflammatory cytokines expression, and oxidative stress upregulation, which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice.
PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties, which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways.
Little is known about the role of microRNA-29a-3p (miR-29a-3p) in inflammation-related pyroptosis, especially in drug-induced acute liver failure (DIALF). This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms.
Thioacetamide (TAA)- and acetaminophen (APAP)-induced ALF mouse models were established, and human samples were collected. The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, or immunochemical staining in miR-29a-3p knock-in transgenic mouse (MIR29A(KI/KI)) DIALF models. In addition, RNA sequencing was conducted to explore the mechanisms.
MiR-29a-3p levels were decreased in TAA- and APAP-induced DIALF models. MiR-29a-3p prevented DIALF caused by TAA and APAP. RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis, and the inhibition was dependent on activation of the PI3K/AKT pathway. In addition, miR-29a-3p levels were reduced, and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients.
The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF. MiR-29a-3p may be a promising therapeutic target for DIALF.
The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism.
A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining.
After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated.
HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.
We previously reported that mutations in inner mitochondrial membrane peptidase 2-like (Immp2l) increase infarct volume, enhance superoxide production, and suppress mitochondrial respiration after transient cerebral focal ischemia and reperfusion injury. The present study investigated the impact of heterozygous Immp2l mutation on mitochondria function after ischemia and reperfusion injury in mice.
Mice were subjected to middle cerebral artery occlusion for 1 h followed by 0, 1, 5, and 24 h of reperfusion. The effects of Immp2l+/− on mitochondrial membrane potential, mitochondrial respiratory complex III activity, caspase-3, and apoptosis-inducing factor (AIF) translocation were examined.
Immp2l+/− increased ischemic brain damage and the number of TUNEL-positive cells compared with wild-type mice. Immp2l+/− led to mitochondrial damage, mitochondrial membrane potential depolarization, mitochondrial respiratory complex III activity suppression, caspase-3 activation, and AIF nuclear translocation.
The adverse impact of Immp2l+/− on the brain after ischemia and reperfusion might be related to mitochondrial damage that involves depolarization of the mitochondrial membrane potential, inhibition of the mitochondrial respiratory complex III, and activation of mitochondria-mediated cell death pathways. These results suggest that patients with stroke carrying Immp2l+/− might have worse and more severe infarcts, followed by a worse prognosis than those without Immp2l mutations.
This study aimed to determine whether lipopolysaccharide (LPS) induces the loss of corneal nerve fibers in cultured trigeminal ganglion (TG) cells, and the underlying mechanism of LPS-induced TG neurite damage.
TG neurons were isolated from C57BL/6 mice, and the cell viability and purity were maintained for up to 7 days. Then, they were treated with LPS (1 µg/mL) or the autophagy regulator (autophibib and rapamycin) alone or in combination for 48 h, and the length of neurites in TG cells was examined by the immunofluorescence staining of the neuron-specific protein β3-tubulin. Afterwards, the molecular mechanisms by which LPS induces TG neuron damage were explored.
The immunofluorescence staining revealed that the average length of neurites in TG cells significantly decreased after LPS treatment. Importantly, LPS induced the impairment of autophagic flux in TG cells, which was evidenced by the increase in the accumulation of LC3 and p62 proteins. The pharmacological inhibition of autophagy by autophinib dramatically reduced the length of TG neurites. However, the rapamycin-induced activation of autophagy significantly lessened the effect of LPS on the degeneration of TG neurites.
LPS-induced autophagy inhibition contributes to the loss of TG neurites.
Vitamin D (VD) deficiency was reported to contribute to the progression of Crohn’s disease (CD) and affect the prognosis of CD patients. This study investigated the role of serum VD, body mass index (BMI), and tumor necrosis factor alpha (TNF-α) in the diagnosis of Crohn’s disease.
CD patients (n=76) and healthy subjects (n=76) were enrolled between May 2019 and December 2020. The serum 25-hydroxyvitamin D [25(OH)D] levels, BMI, and TNF-α levels, together with other biochemical parameters, were assessed before treatment. The diagnostic efficacy of the single and joint detection of serum 25(OH)D, BMI, and TNF-α was determined using receiver operating characteristic (ROC) curves.
The levels of 25(OH) D, BMI, and nutritional indicators, including hemoglobin, total protein, albumin, and high-density lipoprotein cholesterol, were much lower, and the TNF-α levels were much higher in the CD patients than in the healthy subjects (P<0.05 for all). The areas under the ROC curve for the single detection of 25(OH)D, BMI, and TNF-α were 0.887, 0.896, and 0.838, respectively, with the optimal cutoff values being 20.64 ng/mL, 19.77 kg/m2, and 6.85 fmol/mL, respectively. The diagnostic efficacy of the joint detection of 25(OH)D, BMI, and TNF-α was the highest, with an area under the ROC curve of 0.988 (95%CI: 0.968–1.000).
The joint detection of 25(OH)D, TNF-α, and BMI showed high sensitivity, specificity, and accuracy in CD diagnosis; thus, it would be effective for the diagnosis of CD in clinical practice.
There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis (OA). Tetrandrine (Tet) has been approved and used to treat rheumatoid arthritis for several decades, but its effect on OA has not been investigated. Herein, we explored the effect of Tet on OA and its underlying mechanism.
OA was induced using destabilization of the medial meniscus (DMM) in C57BL/6J mice. The animals were randomly divided into sham, DMM, Tet, celecoxib (CXB), and indomethacin (INDO) groups. Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence. Pathological staining, OARSI scores, micro-computed tomography and behavior tests were performed to evaluate the effects of Tet.
Tet remarkably alleviated cartilage injury in the knee joint, limited bone remodeling in the subchondral bone, and delayed progression of OA. Tet also significantly relieved joint pain and maintained function. Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase (COX)-2 but not COX-1 (P<0.01). Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa.
We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice, thus reducing inflammation and improving OA without obvious gastric adverse events. These results provide a scientific basis for the clinical application of Tet in the treatment of OA.
Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As “non-traditional” risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.
The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated.
(1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor’s BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202–0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045–0.747) and P<0.05, OR (95% CI): 0.114 (0.014–0.948), respectively].
The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor’s age, BMI and pre-existing hypertension.
Liver transplantation is a current treatment option for hepatocellular carcinoma (HCC). The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation, including locoregional recurrence, distant metastasis, and in-hospital mortality, in HCC patients with concurrent hepatitis B infection, hepatitis C infection, or alcoholic cirrhosis.
This retrospective cohort study included HCC patients (n=2391) from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection, co-infection with hepatitis B and C, or alcoholic cirrhosis of the liver between 2005 and 2014. Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.
Liver cirrhosis was due to alcohol in 10.5% of patients, hepatitis B in 6.6%, hepatitis C in 10.8%, and combined hepatitis B and C infection in 24.3%. Distant metastasis was found in 16.7% of patients infected with hepatitis B and 9% of hepatitis C patients. Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.
After liver transplantation, patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis. Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.
Cuproptosis is a novel cell death pathway that was newly discovered in early 2022. However, cuproptosis is still in its infancy in many respects and warrants further research in hepatocellular carcinoma (HCC). This study aimed to analyze the mechanism of cuprptosis in HCC.
Herein, the tumor microenvironment infiltration landscape of molecular subtypes was illustrated using GSVA, ssGSEA, TIMER, CIBERSORT, and ESTIMATE algorithms based on the expression profile of cuproptosis-related genes (CRGs) from TCGA and GEO databases. Then, the least absolute shrinkage and selection operator regression method was applied to construct a cuproptosis signature to quantify the cuproptosis profile of HCC. Further, we explored the expression of three hub CRGs in cell lines and clinical patient tissues of HCC by Western blotting, qRT-PCR and immunohistochemistry. Finally, we examined the function of dihydrolipoamide S-acetyltransferase (DLAT) in cuproptosis in HCC by loss-of-function strategy, Western blotting and CCK8 assay.
Three distinct molecular subtypes were identified. Cluster 2 had the greatest infiltration of immune cells with best prognosis. The cuproptosis signature was indicative of tumor subtype, immunity, and prognosis for HCC, and specifically, a low cuproptosis score foreshadowed good prognosis. DLAT was highly expressed in liver cancer cell lines and HCC tissues and positively correlated with clinical stage and grade. We also found that potent copper ionophore elesclomol could induce cuproptosis in a copper-dependent manner. Selective Cu++ chelator ammonium tetrathiomolybdate and downregulating DLAT expression by siRNA could effectively inhibit cuproptosis.
Cuproptosis and DLAT as a promising biomarker could help to determine the prognosis of HCC and may offer novel insights for effective treatment.
This study aimed to explore the value of M701, targeting epithelial cell adhesion molecule (EpCAM) and CD3, in the immunotherapy of ovarian cancer ascites by the in vitro assay.
The expression of EpCAM in ovarian cancer tissues was analyzed by databases. The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry. The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay. The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens. Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.
The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue. The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites. The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells. M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites. M701 could mediate the binding of CD3+ T cells to EpCAM+ tumor cells and induce T cell activation in a dose-dependent manner.
M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites, which had a promising application in immunotherapy for patients with ovarian cancer ascites.
To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer.
Patient information was extracted from the Surveillance, Epidemiology, and Results database. Patients diagnosed with early cervical cancer of stage T1a, T1b, and T2a (American Joint Committee on Cancer, 7th edition) from 1998 to 2015 were included in this study after propensity score matching. Overall survival (OS) was analyzed using the Kaplan-Meier method.
Among the 4964 patients included in the study, 1080 patients were identified as having positive lymph nodes (N1), and 3884 patients were identified as having negative lymph nodes (N0). Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group (P<0.001) and N0 group (P<0.001). In the subgroup analysis, similar results were found in patients with positive lymph nodes of stage T1a (100.0% vs. 61.1%), T1b (84.1% vs. 64.3%), and T2a (74.4% vs. 63.8%). In patients with T1b1 and T2a1, primary surgery resulted in longer OS than primary radiation, but not in patients with T1b2 and T2a2. In multivariate analysis, the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients (HRN1=2.522, 95% CI=1.919–3.054, PN1<0.001; HRN0=1.895, 95% CI=1.689–2.126, PN0<0.001).
In early cervical cancer stage T1a, T1b1, and T2a1, primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.
Cisplatin (CDDP)-based chemotherapy is a first-line, drug regimen for muscle-invasive bladder cancer (BC) and metastatic bladder cancer. Clinically, resistance to CDDP restricts the clinical benefit of some bladder cancer patients. AT-rich interaction domain 1A (ARID1A) gene mutation occurs frequently in bladder cancer; however, the role of CDDP sensitivity in BC has not been studied.
We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology. IC50 determination, flow cytometry analysis of apoptosis, and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A. qRT-PCR, Western blotting, RNA interference, bioinformatic analysis, and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.
It was found that ARID1A inactivation was associated with CDDP resistance in BC cells. Mechanically, loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3 (EIF4A3) through epigenetic regulation. Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399 (circ0008399), a novel circular RNA (circRNA) identified in our previous study, which, to some extent, showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells. Importantly, EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.
Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.
This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins.
A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment.
The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions.
The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.
This study examined humanin expression in rat ovarian tissue, its cellular localization, and its correlation with rat age under physiological conditions.
A total of 40 Sprague-Dawley rats of various ages (2, 12, 30, and 60 days old and 1 year old) were grouped by age. Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group. In addition, Western blotting and Real-time quantitative reverse transcription PCR (qRT-PCR) techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.
The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues. In addition, cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes, interstitial cells, granulosa cells and theca cells in all levels of follicles after the primary follicles, and in the corpus luteum. The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats (P>0.05), whereas the levels of humanin expression in the ovarian tissues of 30-day-old, 60-day-old, and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats (P<0.05). The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats (P<0.01), whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.
This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues. Moreover, the level of humanin expression was highest in the ovarian tissues of 12-day-old rats, and it subsequently decreased with age. The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging. The effect of humanin on ovarian function is worthy of further study in the future.
Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children. Toll-like receptors (TLRs) have been reported to be associated with response to steroid treatment in children with INS. Nevertheless, the correlation between TLR genes and the progression of INS has not yet been clarified. The present study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in TLR2, TLR4, and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.
A total of 183 pediatric inpatients with INS were included and given standard steroid therapy. Based on their clinical response to steroids, the patients were classified into three groups: steroid-sensitive nephrotic syndrome (SSNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS). A total of 100 healthy children were employed as controls. The blood genome DNA was extracted from each participant. Six SNPs (rs11536889, rs1927914, rs7869402, rs11536891, rs352140, and rs3804099) in TLR2, TLR4, and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.
Among the 183 patients with INS, 89 (48.6%) had SSNS, 73 (39.9%) had SDNS, and 21 (11.5%) had SRNS. No significant difference was found in the genotype distribution between healthy children and patients with INS. However, the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS. Compared with patients with the C allele and CC genotype, patients with the T allele and CT genotype had an increased risk of SRNS.
TLR4 rs7869402 affected the steroid response in Chinese children with INS. It might be a predictor for the early detection of SRNS in this population.
This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) for Autism Spectrum Disorder (ASD) screening in the presence of developmental surveillance.
All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules (GDS). Spearman’s correlation coefficients and Kappa values were obtained. Taking GDS as a reference assessment, the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic (ROC) curves. The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).
In total, 150 children aged 12–42 months with ASD were enrolled. The developmental quotients of the CNBS-R2016 were correlated with those of the GDS (r=0.62–0.94). The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays (Kappa=0.73–0.89), except for Fine Motor. There was a significant difference between the proportions of Fine Motor, delays detected by the CNBS-R2016 and GDS (86.0% vs. 77.3%). With GDS as a standard, the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor, which was 0.70. In addition, the positive rate of ASD was 100.0% and 93.5% when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used, respectively.
The CNBS-R2016 performed well in developmental assessment and screening for children with ASD, especially by Communication Warning Behaviors subscale. Therefore, the CNBS-R2016 is worthy of clinical application in children with ASD in China.
Oral lichen planus (OLP) is one of the most common oral mucosa diseases, and is mainly mediated by T lymphocytes. The metabolic reprogramming of activated T cells has been shown to transform from oxidative phosphorylation to aerobic glycolysis. The present study investigated the serum levels of glycolysis-related molecules (lactate dehydrogenase, LDH; pyruvic acid, PA; lactic acid, LAC) in OLP, and the correlation with OLP activity was assessed using the reticular, atrophic and erosive lesion (RAE) scoring system.
Univariate and multivariate linear regression functions based on scikit-learn were designed to predict the RAE scores in OLP patients, and the performance of these two machine learning functions was compared.
The results revealed that the serum levels of PA and LAC were upregulated in erosive OLP (EOLP) patients, when compared to healthy volunteers. Furthermore, the LDH and LAC levels were significantly higher in the EOLP group than in the nonerosive OLP (NEOLP) group. All glycolysis-related molecules were positively correlated to the RAE scores. Among these, LAC had a strong correlation. The univariate function that involved the LAC level and the multivariate function that involved all glycolysis-related molecules presented comparable prediction accuracy and stability, but the latter was more time-consuming.
It can be concluded that the serum LAC level can be a user-friendly biomarker to monitor the OLP activity, based on the univariate function developed in the present study. The intervention of the glycolytic pathway may provide a potential therapeutic strategy.
In this study, we aimed to assess the characteristics of the P3 component from an event-related potential (ERP) that was induced by visual acuity (VA) processing. Furthermore, we sought to provide electrophysiological evidence for the objective evaluation of VA.
We recruited 32 participants with myopia-related ametropia. They reported no other ocular diseases and had an uncorrected VA of 4.0 in both eyes. We used the block letter “E” at different visual angles and orientations as the graphic stimuli. The oddball paradigm, consisting of 4 modules, was used for ERP analysis. The standard stimuli of each module were identical, with a visual angle of 1°15′. The visual angles of the target stimuli were 1°15′, 55′, 24′, and 15′. The VA test was performed on each eye separately for all participants, and all characteristics of the P3 component were analyzed.
There was no significant difference in the P3 peak letencies between the target stimulation angle 1°15′ group and the 55′ group, or between the target stimulation angle 24′ group and the 15′ group. There was a significant difference in the P3 peak letencies between the target stimulation angle 1°15′ group and the 24′ group as well as the 15′ group. There was a significant difference in the P3 peak letencies between the target stimulation angle 55′ group and the 24′ group as well as the 15′ group. No significant differences were observed in the P3 amplitude between modules.
In the oddball paradigm, P3 elicitation indicated a cognitive response to the target stimuli. These data showed that the characteristics of P3 can be used as an objective evaluation of VA.
This study aimed to compare the postoperative analgesia and recovery of ultrasound-guided erector spinae plane block combined with serratus anterior plane block (ESPB combined with SAPB) versus thoracic paravertebral block (PVB) after thoracoscopic surgery.
Ninety-two patients who underwent video-assisted thoracoscopic surgery (VATS) were randomly divided into group S (n=46) and group P (n=46). After anesthesia induction, the same anesthesiologist performed ultrasound-guided ESPB at T5 and T7 levels combined with SAPB at the level of the fifth rib in the midaxillary line in group S and ultrasound-guided PVB at T5 and T7 levels in group P. Patients in both groups were given 40 mL of 0.4% ropivacaine. Eighty-six patients completed the study (group S, n=44; group P, n=42). The morphine consumption, visual analogue scale (VAS) scores at rest and coughing, and frequency of remedial analgesia were recorded at 1, 2, 4, 8, and 24 h postoperatively. Pulmonary function parameters were recorded at 1, 4, and 24 h postoperatively, and the quality of recovery (QoR)-15 score at 24 h postoperatively. The adverse effects, duration of chest tube drainage and length of stay were also recorded.
The morphine consumption at postoperative 4 and 8 h and the incidence of ipsilateral shoulder pain (ISP) were significantly lower in group S than in group P. The QoR-15 questionnaire score at postoperative 24 h was significantly lower in group P than in group S (P<0.05). The morphine consumption was lower at 24 h postoperatively in group S than in group P, with no significant difference found yet. The morphine consumption at other observed times, VAS scores, pulmonary function parameters, frequency of remedial analgesia, duration of chest tube drainage, length of stay, and incidence of other adverse events were comparable between group S and group P.
Ultrasound-guided ESPB combined with SAPB is non-inferior to PVB in terms of morphine consumption at postoperative 24 h and postoperative recovery. But, this approach can significantly reduce morphine consumption in the early postoperative period (0–8 h) after thoracoscopy with lower incidence of ISP. It is a simpler and safer operation.
Fibroblast activation protein (FAP) has been widely studied and exploited for its clinical applications. One of the difficulties in interpreting reports of FAP-targeted theranostics is due to the lack of accurate controls, making the results less specific and less confirmative. This study aimed to establish a pair of cell lines, in which one highly expresses FAP (HT1080-hFAP) and the other has no detectable FAP (HT1080-vec) as control, to accurately evaluate the specificity of the FAP-targeted theranostics in vitro and in vivo.
The cell lines of the experimental group (HT1080-hFAP) and no-load group (HT1080-vec) were obtained by molecular construction of the recombinant plasmid pIRES-hFAP. The expression of hFAP in HT1080 cells was detected by PCR, Western blotting and flow cytometry. CCK-8, Matrigel transwell invasion assay, scratch test, flow cytometry and immunofluorescence were used to verify the physiological function of FAP. The activities of human dipeptidyl peptidase (DPP) and human endopeptidase (EP) were detected by ELISA in HT1080-hFAP cells. PET imaging was performed in bilateral tumor-bearing nude mice models to evaluate the specificity of FAP.
RT-PCR and Western blotting demonstrated the mRNA and protein expression of hFAP in HT1080-hFAP cells but not in HT1080-vec cells. Flow cytometry confirmed that nearly 95% of the HT1080-hFAP cells were FAP positive. The engineered hFAP on HT1080 cells had its ability to retain enzymatic activities and a variety of biological functions, including internalization, proliferation-, migration-, and invasion-promoting activities. The HT1080-hFAP xenografted tumors in nude mice bound and took up 68GA-FAPI-04 with superior selectivity. High image contrast and tumor-organ ratio were obtained by PET imaging. The HT1080-hFAP tumor retained the radiotracer for at least 60 min.
This pair of HT1080 cell lines was successfully established, making it feasible for accurate evaluation and visualization of therapeutic and diagnostic agents targeting the hFAP.