ABSTRACT
Objective:To explore the relationship between macrophage infiltration in the coronary plaque and downstream myocardial perfusion in mice.Methods:The experimental group consisted of 20 ApoE knockout mice models of the coronary plaque established by feeding with cholesterol-rich diets, and the control group consisted of 20 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice.Adenosine stress myocardial contrast echocardiography was performed on all experimental animals to obtain the values of A, β and A×β of the left ventricular myocardium in anteroseptal and posterior walls both in the resting status and during adenosine stress. Concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using mouse enzyme-linked immunosorbent assay kits according to the manufacturer′s instructions. The degree of macrophage infiltration in the coronary plaque was evaluated by pathological immunohistochemistry staining and the correlations with the above indicators were analyzed.Results:There were no statistically significant differences in heart rate and left ventricular structural parameters between two groups (all P>0.05). The experimental group had a lower left ventricular ejection fraction( P=0.021), and higher weight and serum levels of triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, IL-6, and TNF-α than the control group (all P<0.05). The values of A, β and A × β of the left ventricular myocardium in anteroseptal and posterior walls in the experimental group were significantly lower than those in the control group during adenosine stress (all P<0.05). In the experimental group, the value of the macrophage infiltration found in the plaque of the left main coronary artery correlated positively with the level of serum TNF-α ( r=0.63, P=0.003) and negatively correlated with the values of A×β of the left ventricular myocardium in anteroseptal and posterior walls during adenosine stress ( r=-0.74, P<0.001; r=-0.72, P<0.001; respectively). Conclusions:Myocardial perfusion in ApoE knockout mice models of the coronary atherosclerosis was related with degree of macrophage infiltration in the coronary plaque, and macrophages may play a role by releasing inflammatory mediator TNF-α.
ABSTRACT
OBJECTIVE To evaluate the mode of pharmacists’ participation in multi-disciplinary diagnosis and treatment (MDT), as well as the effects of pharmacists’ participation. METHODS Retrieved from Cochrane Library, PubMed, Embase, CNKI, CBM and Wanfang database, experimental studies and observational studies on the effects of MDT with pharmacists on clinical outcomes of patients were collected. After data extraction and quality evaluation, the results of included studies were analyzed descriptively. RESULTS A total of 10 studies were included, among which 3 were randomized controlled trials (RCT), 2 were non-RCT, 4 were cohort and 1 was case-control study; there were 2 422 patients in total. In terms of effectiveness, tumor progression-free survival, glycosylated hemoglobin, re-admission rate and length of stay and other indexes were all improved significantly after pharmacists participated in MDT. In terms of safety, the incidence of major bleeding events was significantly decreased after pharmacists participated in MDT. In terms of economy, hospitalization costs and total outpatient expenses were improved significantly after pharmacists participated in MDT, but medical cost was not improved significantly. In terms of humanistic outcomes, there was controversy over the conclusion of patient compliance after pharmacists participated in MDT. CONCLUSIONS Pharmacists, based on their own pharmaceutical care skills and methods, actively participate in MDT throughout the process, improving the clinical outcomes of patients and enhancing the safety of medication. There are still controversies regarding economic and humanistic outcomes.
ABSTRACT
This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1β and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.
Subject(s)
Rats , Animals , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Caspase 3/genetics , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/metabolism , Plant Bark , Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/chemically induced , Inflammation/drug therapy , Cytokines/metabolism , Proto-Oncogene Proteins c-bcl-2 , ApoptosisABSTRACT
We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground. Etiologic diagnosis played a key role in this case. Systemic examinations ruled out systemic autoimmune diseases, tumors, and infections as the cause of scleritis and suggested that the disease was caused by a local delayed-type hypersensitivity (DTH) induced by ocular trauma and was non-infectious. Still, the right epididymitis was infectious. Both conditions were treated successfully using steroids and antibiotics, respectively. Thus, early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.
Subject(s)
Male , Humans , Child , Epididymitis/complications , Eye Injuries/complications , Wounds, Nonpenetrating/complications , Scleritis/etiology , FaceABSTRACT
Objective:To investigate the changes of left atrial structure and function in patients with apical hypertrophic cardiomyopathy (ApHCM) by three-dimensional (3D) echocardiography.Methods:From September 2020 to December 2022, 112 patients with ApHCM(ApHCM group) diagnosed at Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology and 41 age- and sex-matched normal controls(control group) were finally enrolled. In 'pure’ ApHCM patients, cardiac hypertrophy was confined to the apical segment below the papillary muscle. The wall thickness of apical and intermediate segments in 'mixed’ ApHCM patients increased, but the wall thickness of apical segment was the largest. Two-dimensional(2D) and 3D volume and strain parameters of left atrium were compared between control group and ApHCM group, 'pure’ and 'mixed’ ApHCM patients.The correlations between 2D and 3D volume and strain parameters of left atrium and intraclass correlation coefficient (ICC) of those parameters were analyzed. The ROC curve was performed to determine the cutoff values of 3D left atrial volume abnormalities in all subjects. Logistics regression analysis was performed to analyze the impact factors of the left atrial enlargement in patients with ApHCM.Results:Compared with the control group, 2D left atrial maximum volume index (2D LAVimax), 2D left atrial minimum volume index (2D LAVimin), 3D left atrial maximum volume index (3D LAVimax), 3D left atrial minimum volume index (3D LAVimin), and 3D left atrial presystolic volume index (3D LAVipreA) significantly increased in ApHCM group( Z=-6.54, -6.38, -6.98, -7.40, -6.96; all P<0.001). However, 2D left atrial ejection fraction (2D LAEF) ( Z=-3.75, P<0.001), 2D left atrial expansion index (2D LAEI) ( t=-4.15, P<0.001), 3D left atrial ejection fraction (3D LAEF) ( Z=-5.09, P<0.001), 3D left atrial expansion index (3D LAEI) ( t=-5.49, P<0.001), 2D left atrial reservoir strain (2D LASr) ( t=-12.03, P<0.001), 2D left atrial conduit strain (2D LAScd) ( t=7.91, P<0.001), 2D left atrial contractile strain (2D LASct) ( t=6.06, P<0.001), 3D left atrial reservoir strain (3D LASr) ( t=-9.23, P<0.001), 3D left atrial conduit strain (3D LAScd) ( t=7.12, P<0.001) and 3D left atrial contractile strain (3D LASct) ( t=4.78, P<0.001) significantly decreased in ApHCM group. Compared with the 'pure’ ApHCM group, 2D LAVimax, 3D LAVimax, 2D LAVimin, 3D LAVimin, 3D LAVipreA in patients with mixed ApHCM increased more significantly, while 2D LAEF, 2D LAEI and 2D LASr decreased more significantly. The measurements of left atrial volume and strain by 3D echocardiography were significantly correlated with 2D measurements ( P<0.05). The correlations between 2D LAVimax and 3D LAVimax, 2D LAVimin and 3D LAVimin, 2D LAEF and 3D LAEF, 2D LASr and 3D LASr, 2D LAEI and 3D LAEI ( r=0.91, 0.93, 0.72, 0.76, 0.57; all P<0.05) were more than moderate. The repeatability of 3D left atrial strain was lower than 2D results, while the repeatability of 3D left atrial volume was higher than 2D results. ROC curve analysis showed that 3D echocardiography parameters could identify left atrial volume abnormality in all subjects. The cutoff values of 3D LAVimax, 3D LAVimin, 3D LAVipreA in all subjects were 36 ml/m 2, 18 ml/m 2 and 27 ml/m 2, respectively. Multivariate binary logistic regression analyses showed that ratio of LV systolic obliteration to cavity was independent factor affecting left atrial enlargement in ApHCM patients( OR=1.20, P<0.001). Conclusions:Three-dimensional echocardiography is significant for the accurate evaluation of left atrial structural changes in patients with ApHCM. Ratio of left ventricular systolic obliteration to cavity was an independent impact factor of left atrial enlargement in ApHCM patients.
ABSTRACT
Objective:To evaluate the efficacy and safety of immediate intraoperative transapical beating-heart septal myectomy (TA-BSM) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and explored the clinical value of three-dimensional transesophageal echocardiography (3D-TEE) during the procedure of TA-BSM.Methods:One hundred and thirty-seven HOCM patients who underwent TA-BSM surgery in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2022 to March 2023 were selected.During the operation, 3D-TEE was used to locate the position of the myocardial circumcision system and navigate the range of myocardial circumcision. The interventricular septal thickness( IVST) and peak pressure gradient of the left ventricular outflow tract (LVOT-PG) were measured, and the degree of mitral systolic anterior motion (SAM) and mitral regurgitation (MR) were evaluated in HOCM patients before and after the operation. The range of the incisal margin was measured, and the number of resection knives and the weight of the removed myocardium were recorded.Results:TA-BSM under 3D-TEE navigation was successfully performed in 137 HOCM patients. The number of resection was 7(5, 9), and the weight of the removed myocardium was 5.6(3.4, 8.9)g. During the operation, there were no adverse events such as death, aortic valve injury, and iatrogenic interventricular septal perforation. Compared with those before the operation, the wall thickness of basal and middle segments of the anterior and posterior interventricular septum decreased significantly (all P<0.001), and LVOT-PG decreased significantly ( P<0.001). After TA-BSM, the number of patients with SAM≥3 decreased from 94 cases (68.6%) to 2 cases (1.5%), and the number of patients with MR≥3+ decreased from 86 cases (62.8%) to 9 cases (6.6%)(all P<0.001). For the patients with different degrees of ventricular septal hypertrophy (mild, moderate, and severe), the postoperative IVST and LVOT-PG were significantly lower than the preoperative values, and the degree of MR and SAM signs was relieved considerably. The length of the incisal margin, the weight of excised myocardium, and the number of resection in the group with extensive septal hypertrophy in all three regions were significantly higher than those in the group with localized interventricular septal hypertrophy in single or two areas (all P<0.05). Conclusions:3D-TEE can guide and monitor the process of TA-BSM myocardial resection in real-time. By accurately evaluating the IVST and the range and hemodynamic characteristics of HOCM patients, it can effectively relieve LVOTO and significantly reduce MR to ensure the safety and effectiveness of TA-BSM in HOCM patients with different degrees and ranges of hypertrophy.
ABSTRACT
Objective:To systematically review and evaluate the effect of intraoperative regional cerebral oxygen saturation (rSO 2) monitoring on perioperative neurocognitive disorders (PNDs) in elderly patients undergoing non-cardiac surgery. Methods:China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, China Science and Technology Journal Database, PubMed, Cochrane Library, Embase and Web of Science databases were searched from inception to October 2022 for randomized controlled trials involving the effects of intraoperative rSO 2 monitoring on PND in elderly patients underwent non-cardiac surgery. The primary outcome measure was the incidence of PND (1-7 days after surgery), and secondary outcome measures were intraoperative minimum rSO 2 (rSO 2min), intraoperative mean rSO 2 (rSO 2mean), maximum percentage of decrease (rSO 2% max) in rSO 2 from baseline (rSO 2baseline), and the Montreal Cognitive Assessment Scale was used to evaluate the quality of references that met the inclusion criteria, and data were extracted for meta-analysis using RevMan5.4 software. Results:Thirteen randomized controlled trials were enrolled, involving 1 134 patients with 557 patients in experimental group (anesthesia under rSO 2 monitoring) and 577 patients in control group. The results of meta-analysis showed that the incidence of PND was significantly lower in experimental group than in control group ( RR=0.32, 95% confidence interval [ CI] 0.25-0.41, P<0.001), the intraoperative rSO 2min was significantly higher in experimental group than in control group ( MD=7.46, 95% CI 5.05-9.86, P<0.001), and the intraoperative rSO 2mean was significantly higher in experimental group than in control group ( MD=5.49, 95% CI 3.97-7.02, P<0.001), the intraoperative rSO 2% max was significantly lower in experimental group than in control group ( MD=-6.55, 95% CI-9.03--4.07, P<0.001), and the postoperative Montreal Cognitive Assessment Scale score was significantly higher in experimental group than in control group ( MD=1.37, 95% CI 0.74-1.99, P<0.001). Conclusions:Intraoperative application of rSO 2 monitoring can reduce the occurrence of PND in elderly patients undergoing non-cardiac surgery.
ABSTRACT
Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O
ABSTRACT
INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.
Subject(s)
Cerebellar Neoplasms , Hydrocephalus , Medulloblastoma , Mutism , Cerebellar Neoplasms/epidemiology , Female , Fluorescein , Headache , Humans , Hydrocephalus/complications , Male , Medulloblastoma/complications , Medulloblastoma/diagnosis , Medulloblastoma/surgery , Mutism/etiology , Retrospective Studies , SodiumABSTRACT
VEXAS syndrome, an autoinflammatory syndrome due to a Ubiquitin Like Modifier Activating Enzyme 1 (UBA1) somatic mutation, has a high thrombotic burden. We report a case of a 69-year-old male that was diagnosed with VEXAS syndrome who developed venous thromboembolism (VTE). Review of literature of existing VEXAS syndrome cases showed a high thrombotic burden, with the reported incidence of VTE (36.4%) being markedly higher than arterial thrombosis (1.6%), with deep vein thrombosis being more common than pulmonary embolism. Somatic mutation in the UBA1 gene results in decreased ubiquitylation which is a key driver in the development of thrombosis in VEXAS syndrome, due to chronic inflammation and cytokine release from abnormal crosstalk between the intrinsic effector mechanism of innate immune cells, platelets and endothelium resulting in dysregulated haemostasis and endothelial dysfunction. Targeting endothelial dysfunction and reducing inflammatory milieu causing hypercoagulability with immunosuppressants and immunomodulatory agents, together with anticoagulation may be the strategy to prevent recurrent thrombotic events.
Subject(s)
Thrombosis , Venous Thromboembolism , Aged , Humans , Male , Mutation , Syndrome , Ubiquitin-Activating Enzymes/geneticsABSTRACT
Objective:To study the evaluation method of protein energy wasting (PEW) in maintenance hemodialysis patients.Methods:A total of 166 maintenance hemodialysis patients were selected. Their medical records, physical indicators, as well as NS2002, PG-SGA, and MUST nutrition scale scores were also collected. The patients were divided into PEW and non-PEW groups according to whether PEW occurred or not, and the differences in each index between the two groups were compared to analyze the diagnostic efficacy of each index and nutrition score scale results on the occurrence of PEW.Results:The differences in body mass, body mass index(BMI), body surface area, abdominal circumference, triceps skinfold thickness, upper arm circumference, and calf circumference between the PEW and non-PEW groups were statistically significant(all P<0.05). The diagnostic efficacy of a single physical index or nutrition score for PEW was limited. A simplified formula for the PEW risk was obtained by logistic model analysis. The formula had a sensitivity of 67.7% and a specificity of 94.4% for the diagnosis of PEW, as analyzed by the subject's working characteristic curve. Conclusions:Four indicators, including abdominal circumference, primary hand grip strength, BMI, and upper arm circumference, can be combined to comprehensively assess the presence of PEW to improve the diagnostic efficacy of the occurrence of malnutrition in maintenance hemodialysis patients.
ABSTRACT
Congenital heart disease (CHD) is the most frequent congenital malformation in children.With the improvement of the diagnosis and treatment of CHD, most children can survive to adulthood without suffering cardiovascular diseases.However, relevant research suggests that health-related quality of life (HRQOL) of some children with CHD after surgery still differs from that of healthy children of the same age.Based on a brief review of the concept of HRQOL, effective evaluation tools and the research status at home and abroad, disputes among relevant research conclusions in different countries or regions were discussed in this article.The influence of the child, family and diagnosis and treatment on postoperative HRQOL of children with CHD was analyzed.Approaches and response plans were put forward to improve postoperative HRQOL.In addition, the limitations of past research were pointed out, and suggestions were made on future research methods, tools and directions in this field.It′s hoped that this study can provide valuable information for CHD diagnosis and treatment and reference for follow-up research.
ABSTRACT
@#AIM: To explore the current situation of myopia among children and adolescents in Mengzi city and the possible influencing factors of myopia.METHODS: A multi-stage cluster sampling method was used to select students in 7 schools(2 primary schools, 2 junior high schools, 2 high schools, and 1 vocational high school)in Mengzi city, Yunnan Province in October 2019. A total of 1 837 students were selected for questionnaire surveys, and examination of distance visual acuity and noncycloplegic autorefraction. There were 1 622 valid questionnaires were finally collected after checking the integrity and rationality of the questionnaires. RESULTS: The prevalence of myopia among primary and secondary students in Mengzi city in 2019 was 61.34%. The prevalence of myopia in girls(71.36%)was higher than that in boys(50.45%), and the prevalence of myopia in Han nationality(70.19%)was higher than that in ethnic minorities(57.70%). With the grade growth, the prevalence of myopia showed an upward trend. Multivariate Logistic regression analysis showed that the risk factors of myopia were female(<i>OR</i>=2.308), Han nationality(<i>OR</i>=1.712), higher learning stage(junior high school: <i>OR</i>=1.579, high school: <i>OR</i>=5.538), the time of doing homework daily in the past 1wk(1-<2h: <i>OR</i>=1.456, 2-<3h: <i>OR</i>=1.514, ≥3h: <i>OR</i>=1.901), occasionally or never keep your eyes more than one foot away from a book while reading and writing(<i>OR</i>=1.741), insufficient sleep(<i>OR</i>=1.585), parental myopia(<i>OR</i>=2.191).CONCLUSION:The prevalence of myopia among primary and middle school students in Mengzi city is at a relatively high level. Female, Han nationality, higher learning stage, the time of doing homework daily in the past 1wk≥1h, occasionally or never keep your eyes more than one foot away from a book while reading and writing, insufficient sleep and parental myopia are all risk factors that can cause myopia.
ABSTRACT
Objective:To study the glypican 3 (GPC3) fluorescent probe imagings in hepatocellular carcinoma (HCC) tissues and to determine its prognostic value in HCC patients.Methods:The data of 87 patients who were treated at the Affiliated Hospital of Southwest Medical University from January 2019 to August 2020 were retrospectively analyzed. There were 75 males and 12 females, with the age of (56.1±11.9) years. The expressions of GPC3 were measured by immunohistochemistry and by the fluorescent probe. The results obtained by these two tests were compared. Patients were followed up for recurrence after hepatectomy. Univariate and multivariate Cox regression analyses were used to analyze factors influencing recurrence-free survival.Results:Detection of the GPC3 expression by GPC3 fluorescence probe was consistent with the results obtained by immunohistochemical studies ( Kappa=0.84, P<0.001). The positive rates of GPC3 fluorescent probe was 79.3%(69/87), compared with 80.4%(70/87) by immunohistochemistry studies, with no significant difference between the two groups ( P>0.05). The patients were then divided into the low differentiation group ( n=30) and the middle high differentiation group ( n=57) by the degrees of tumor differentiation. The fluorescence intensity in the low differentiation group was 134.4(128.0, 144.7) a. u. which was significantly different from the middle high differentiation group of 84.8(0, 108.5)a.u. ( Z=-7.52, P<0.001). The median fluorescence intensity of 87 patients with HCC was 108.6 a. u.. Multivariate Cox regression analysis showed that patients with a GPC3 fluorescence intensity ≥108.6 a. u. ( HR=2.07, 95% CI: 1.21-3.53, P=0.008) had a significant increased risk of recurrence after hepatectomy. Conclusion:The expressions of GPC3 in HCC were consistent between the studies by using either a GPC3 specific fluorescent probe or immunohistochemistry studies. A GPC3 fluorescence intensity ≥108.6 a. u. was a risk factor of recurrence after hepatectomy in patients with HCC.
ABSTRACT
Objective To look for a tissue paraffin embedding method that can replace xylene transparent agent. Methods The mixture of N-butanol and turpentine was used to replace the role of anhydrous ethanol and xylene in the process of conventional paraffin embedding. The brain, kidney, stomach, liver and duodenum of multiple cerebral infarction model rats were embedded in paraffin. Finally, the new dehydration procedure was evaluated according to the effect of paraffin section, HE staining and immunohistochemical result . Results The mixture of N-butanol and turpentine could replace not only the dehydration effect of anhydrous ethanol but also the transparency effect of xylene in the conventional paraffin embedding process. The tissue sections treated with the mixture of N-butanol and turpentine were smooth, and the tissue did not become brittle or hard; After HE staining, the nucleus and cytoplasm of the new dehydrated tissue were distinct, and the chromaticity, color and transparency of the tissue were not different from those of the conventional dehydration procedure; Immunohistochemical staining was performed on different tissues of rats, and the comparison result were no different from conventional embedded tissue immunohistochemical staining. Conclusion N-butanol combined with turpentine for tissue dehydration can not only avoid the toxic effect of xylene on human, but also reduce the tissue damage caused by excessive dehydration of anhydrous alcohol.
ABSTRACT
Caffeine and epigallocatechin-3-gallate (EGCG), which respectively, are the main functional extracts from coffee and green tea, and present protective effects against non-alcoholic fatty liver diseases (NAFLD). These two beverages and their functional extracts are highly recommended as potential treatments for obesity and NAFLD in clinics; however, their pharmacodynamic effects and pharmacological mechanisms in non-alcoholic steatohepatitis (NASH) remain unclear. Therefore, the aim of this study was to explore the commonality and specificity of the pharmacodynamic effects and pharmacological mechanisms of caffeine and EGCG on NASH mice, which were fed with a high-trans fatty acid/high-carbohydrate (HFHC) diet. C57BL/6J mice were fed a normal diet (control group) or an HFHC diet (HFHC group) for 24 weeks. HFHC group mice were additionally treated with caffeine (75 mg/kg) or EGCG (100 mg/kg) for 6 weeks, using obeticholic acid (OCA,10 mg/kg) as a positive control group. The pharmacological effects of the drugs, including effects on glucose and lipid metabolism and liver inflammation and fibrosis, were evaluated. Gene expression in liver tissue samples from the different groups were assessed. Both caffeine and EGCG significantly reduced the liver manifestations of NASH induced by HFHC. The pathological aspects of liver lipid deposition, inflammation, and liver fibrosis in both groups were strongly ameliorated. Of note, most indexes were strongly reversed in the caffeine group, although AST activity, fasting blood glucose, and the HOMA-IR index were improved in the ECGC group. There were 714 differentially expressed genes between the caffeine and HFHC groups and 268 differentially expressed genes between the EGCG and HFHC groups. Twenty and 17 NASH-related KEGG signaling pathways were enriched by caffeine and EGCG. This study confirmed that 75 mg/kg caffeine and 100 mg/kg EGCG could significantly improve liver lipid deposition, glucose metabolism, inflammation, and fibrosis in a mouse model of NASH induced by HFHC. The bioinformatics platform we built for caffeine and EGCG in NASH disease found that the two drugs may greatly overlap in improving the mechanism related to NASH inflammation. However, caffeine may have better potential in regulating glucose metabolism and EGCG may have better potential in regulating lipid metabolism.
ABSTRACT
Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways.
ABSTRACT
Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled patients with AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant treatment with intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m2 for adenocarcinoma) or nab-paclitaxel (260 mg/m2 for other subtypes) on day 1 of each 21-day cycle. Surgical resection was performed 4-5 weeks afterward. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor remaining at the time of surgery.Thirty-three patients were enrolled, of whom 13 (39.4%) had T3-4N2 stage IIIB disease. Thirty (90.9%) patients underwent resection and all except one (96.7%) achieved R0 resection. Twenty patients (60.6%) in the intention-to-treat population achieved an MPR, including 15 patients (45.5%) who achieved a pathological complete response (pCR). The MPR and pCR rates in the per-protocol population were 66.7% and 50.0%, respectively. The surgical complications included three cases of arrhythmias, one case of a prolonged air leak, and one case of chylothorax. The most common grade 3 treatment-related adverse event (TRAE) was anemia (2, [6.1%]). Severe TRAEs included one (3.0%) case of grade 3 peripheral neuropathy that resulted in surgical cancellation.Toripalimab plus platinum-based doublet chemotherapy yields a high MPR rate, manageable toxicity, and feasible resection in stage III NSCLC.Trial ClinicalTrials.gov (NCT04304248).
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Neoadjuvant TherapyABSTRACT
OBJECTIVE: Esophageal spindle cell squamous cell carcinoma (ESCSCC) is a distinct subtype of esophageal carcinoma with unique morphologic and clinicopathologic features. This study aimed to characterize the clinicopathologic manifestations and postoperative prognostic factors of ESCSCC. METHODS: In this study, 43 ESCSCC patients who underwent esophagectomy at Sun Yat-sen University Cancer Center between January 2001 and December 2014 were identified. 200 patients with conventional squamous cell carcinoma during the same period were sampled as a control. Hematoxylin and eosin-stained slides and available data were reviewed, and pertinent clinicopathologic features were retrospectively analyzed. RESULTS: Among the ESCSCC patients, the median age was 60.5 years, with a male-to-female ratio of 2.58:1. The five-year disease-free survival and cancer-specific survival rates were 51.6 and 55.5%, respectively. In the univariate analysis, drinking abuse, tumor size, macroscopic type, perineural invasion, pT, preoperative blood white blood cell count, preoperative blood neutrophil count, and preoperative blood neutrophil to lymphocyte ratio were significantly correlated with the cancer-specific survival and disease-free survival of the ESCSCC patients. The multivariate analysis showed that macroscopic type, perineural invasion, and preoperative blood neutrophil to lymphocyte ratio were independent prognostic factors for cancer-specific survival; macroscopic type, perineural invasion, tumor size, and pT were independent prognostic factors for disease-free survival. Moreover, the combined prognostic model for cancer-specific survival (including macroscopic type, perineural invasion, and preoperative blood neutrophil to lymphocyte ratio), the combined prognostic model for disease-free survival (including macroscopic type, perineural invasion, and tumor size) significantly stratified patients according to risk (low, intermediate, and high) to predict cancer-specific survival, disease-free survival, respectively. In terms of esophageal conventional squamous cell carcinoma cohort, there was no significant difference in long-term outcome when compared with ESCSCC. Though five independent prognostic variables (macroscopic type, perineural invasion, preoperative blood neutrophil to lymphocyte ratio, tumor size, and pT) were indentified in ESCSCC, univariate analysis demonstrated that perineural invasion, preoperative blood neutrophil to lymphocyte ratio were correlated with esophageal conventional squamous cell carcinoma on cancer-specific survival; whereas only perineural invasion on disease-free survival. CONCLUSIONS: The proposed two new prognostic models might aid in risk stratification and personalized management for patients with esophageal spindle cell squamous cell carcinoma who received radical surgery.
ABSTRACT
BACKGROUND: Visceral pleural invasion (VPI) with PL1 or PL2 increases the T classification from T1 to T2 in non-small cell lung cancers (NSCLCs) ≤ 3 cm. We proposed a modified T classification based on VPI to guide adjuvant therapy. RESEARCH QUESTION: Is it reasonable to upstage PL1-positive cases from T1 to T2 for NSCLCs ≤ 3 cm? STUDY DESIGN AND METHODS: In total, 1,055 patients with resected NSCLC were retrospectively included. Tumor sections were restained with hematoxylin and eosin stain and Victoria blue elastic stain for the elastic layer. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Subgroup analysis and a Cox proportional hazards model were used to further determine the impact of VPI on survival. RESULTS: The extent of VPI was diagnosed as PL0 in 824 patients, PL1 in 133 patients, and PL2 in 98 patients. The 5-year DFS rates of patients with PL0, PL1, and PL2 were 62.6%, 60.2%, and 28.8% (P < .01), whereas the corresponding 5-year OS rates were 78.6%, 74.4%, and 50.0% (P < .01), respectively. As predicted, the DFS and OS of patients with PL2 were much worse than those of patients with PL0 (P < .01) and PL1 (P < .01). However, both the DFS and OS of patients with PL0 and PL1 were comparable (DFS: P = .198; OS: P = .150). For node-negative cases, the DFS and OS of patients with PL0 and PL1 were also comparable (DFS: P = .468; OS: P = .388), but patients with PL2 had much worse DFS and OS than patients with PL0 (P < .01) and PL1 (P < .01). Multivariable analyses suggested that PL2, together with node positivity and poor cell differentiation, was an independent adverse prognostic factor. INTERPRETATION: In NSCLCs ≤ 3 cm, tumors with PL1 should remain defined as T1, not T2. Overtreatment by adjuvant chemotherapy in node-negative NSCLCs ≤ 3 cm might be avoided in PL1 cases.