Relationships Among Serological Indicators and In Vitro High-Throughput Drug Sensitivity Screening Results in Patients with Hepatocellular Carcinoma.

AIM: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC). METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50. RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators. CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.

Adsorption of HF and H2S on α-Al2O3 (0001) Surfaces: A DFT Study.

Ex-service SF6 adsorbents in SF6 gas-insulated electric equipment contain many toxic substances. Inside, HF and H2S are two typical toxic gases. Based on the first principle, the interaction process between HF/H2S and α-Al2O3 (0001) surfaces was calculated using the density functional theory (DFT). The results showed that the adsorption of HF on α-Al2O3 (0001) is stronger than that of H2S. Under the five adsorption sites, the adsorption effect of HF-H and HF-F was similar. At O-2 site, the adsorption energy of H2S-H adsorption configuration is significantly higher than that of the other four sites. The density of states (DOS) indicated that new peaks appeared after adsorption. The DOS and partial density of states (PDOS) indicated that the adsorption of HF and H2S occurs via chemical adsorption. The DOS and PDOS shifted to the right when the S atom was approaching, proving that the system shifts to instability. Compared with the energy gap of α-Al2O3 (0001), HF and H2S adsorption systems decreased significantly. The energy gap of the HF adsorption system was 1.173 eV larger than that of the H2S system and the geometry was relatively stable, which is consistent with the DOS and PDOS adsorption calculation results. Thus, the adsorption of HF and H2S on α-Al2O3 (0001) surfaces was clearly different. The findings of this study may provide theoretical guidance for the adsorption of other gases or developing a new adsorbent.

Application of transvaginal three-dimensional power Doppler ultrasound in benign and malignant endometrial diseases.

To investigate the value of transvaginal three-dimensional (3D) power Doppler ultrasound in the diagnosis of benign and malignant endometrial diseases.A total of 144 patients with endometrial thickness ≥4 mm were enrolled. Endometrial thickness was measured by transvaginal 3D B-mode ultrasound, while blood signals were detected by 3D power Doppler ultrasound. Endometrial volume (EV), vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI) were calculated. All histopathological diagnoses of endometrium were obtained.There were 86 benign and 58 malignant cases. There were statistically significant differences between two groups in endometrial thickness [1.50 (1.30, 1.80) vs 2.30 (1.80, 3.20), P < .001], EV [10.62 (7.14, 17.36) vs 28.94 (9.59, 67.96), P < .001], VI [6.07 (3.61, 10.33) vs 12.01 (7.50, 19.87), P = .001], FI [27.42 (24.45, 31.33) vs 32.98 (30.22, 35.40), P < .001], and VFI [1.58 (0.92, 3.32) vs 4.28 (2.24, 6.41), P < 0.001]. Sensitivity and specificity of endometrial thickness were relatively high [endometrial thickness (86.2%, 76.1%), EV (48.3%, 97.7%), VI (72.4%, 69.8%), FI (72.4%, 74.4%), and VFI (72.4%, 74.4%)]. There was no significant difference in any parameters of the endometrium between different stages (Ia, Ib, II, and above) or phases (G1, G2, and G3) of Ia phase of endometrial cancer (all P > .05).Transvaginal 3D power Doppler ultrasound is valuable in the differentiating benign and malignant endometrial lesions.

Electrophysiological phenotypes of synaptic transmission and neural network in hippocampal neurons of the α7-nAChR knockout mice.

It was reported that α7 nicotinic acetylcholine receptor (α7-nAChR) knockout (α7 KO) mice showed few functional phenotypes. The purpose of this study was to investigate the effect of α7 KO on the electrophysiological characteristics of hippocampus in mice. The effect of α7 KO on hippocampal CA3-CA1 synaptic transmission in mice was evaluated by standard extracellular field potential recordings. The electrophysiological phenotype of γ-aminobutyrate A receptors (GABAA-Rs) of single hippocampal neuron was detected by perforated patch-clamp recordings. The results showed that, the slope of field excitatory postsynaptic potential (fEPSP) and carbachol-induced theta oscillation were significantly decreased in the hippocampal CA1 neurons of α7 KO mice, compared with those of wild type mice. Under the treatment of GABAA-R agonist muscimol, the I-V curves of both the hippocampal CA1 and CA3 neurons of α7 KO mice shifted towards depolarizing direction obviously, compared with those of wild type mice. These results suggest that the hippocampal CA3-CA1 synaptic transmission in α7 KO mice was significantly impaired and GABAA-R maturation was significantly delayed, indicating that the deletion of α7-nAChR gene could significantly change the electrophysiological function of the hippocampus. The results may provide a new understanding of the role of α7-nAChR in hippocampal function and associated diseases.

[Interventional effects of metformin on senescence induced by D-galactose in middle-aged male mice].

OBJECTIVE: To investigate the effects of metformin (Met) on middle-aged male mice aging induced by D-galactose. METHODS: Fifty nine-month-old male ICR mice were fed in SPF experimental environment and fed freely with water. Subsequently, the mice were randomly divided into 5 groups(n=10): control group, model group, metformin low, medium and high dose groups(Met 50 mg/kg, Met 100 mg/kg, Met 200 mg/kg). The mice in different doses of Met group and model group were subcutaneously injected with D-galactose 100 mg/kg at the back of neck to induce senescence every day. At the same time, the mice were respectively treated with Met (50, 100, 200 mg/kg) or NS of equal volume by gavage. The control group was injected and gavage with equal volume NS. All treatments lasted for 8 weeks. During the study, the general condition, body weight, blood glucose,the activities of superoxide dismutase (SOD) and malonic dialdehyde (MDA) in serum and liver tissue of each mouse were tested, learning and memory ability were measured by Mirris water maze test, HE staining was used to observe the pathology of hippocampus in the mice. RESULTS: Met 200 mg/kg per day could reduce body weight (P＜0.05). Met intervention had no effect on normal fasting blood glucose in model rats. Compared with model group, the daily dose of Met 50, 100, 200 mg/kg could significantly increase SOD activity in serum and liver tissues of model mice (P＜0.05) and decrease MDA content in serum of model mice (P＜0.05), and improve most of the indicators of learning and memory ability of Morris water maze test (P＜0.05). HE staining showed that the neurons with nuclear condensation and deep staining were obviously decreased in the dentate gyrus of hippocampus. Met intervention has dose-dependent effects on most indicators. CONCLUSION: Long-term treatment of Met can delay the aging process of middle-aged male mice induced by D-galactose, which may be related to reducing the weight of mice and enhancing the body's antioxidant level.

A Simple Method to Differentiate Atrioventricular Node Reentrant Tachycardia from Orthodromic Reciprocating Tachycardia.

Discrimination between atrioventricular node reentry tachycardia (AVNRT) and orthodromic reciprocating tachycardia (ORT) during an electrophysiological study is sometimes challenging. This study aimed to investigate if the difference in the local VA (ventricle-atrium) interval during ventricular entrainment pacing and during tachycardia (DVA, defined as the shortest local VA interval of coronary sinus [CS] during entrainment minus the shortest local VA interval of CS during tachycardia) was different in patients with AVNRT and patients with ORT.Diagnoses of AVNRT or ORT through a concealed accessory pathway (AP) were made according to conventional electrophysiological criteria and ablation results. Entrainment by right ventricular (RV) pacing was performed in each patient before ablation and patients with successful entrainment were included in the study. The DVA was compared between patients with AVNRT and patients with ORT. The DVA in patients with AVNRT was significantly longer than that in patients with ORT (120 ± 20 versus 5.7 ± 9; P < 0.001). In each patient with AVNRT of slow-fast type, fast-slow type, and slow-slow type, the DVA was more than 48 ms. In each patient with ORT using a left free wall accessory pathway (AP), right free wall AP, and septal AP, the DVA was less than 20 ms.DVA was found to be a rapid, useful test in distinguishing patients with AVNRT from those with ORT.

Ultrasonographic characteristics of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma.

This study was designed to explore differences in the ultrasonographic characteristics of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). This study included 35 cases of MTC and 96 cases of PTC that were surgically and pathologically confirmed. Preoperative ultrasound images were retrospectively reviewed by two physicians (with 5 years' experience in thyroid ultrasound) under the premise of unknown pathological results. Various ultrasonic features of nodules were assessed objectively. The clinical features of components were determined by other physicians. Age, sex, unilateral or bilateral involvement of thyroid gland, lesion size, margin, shape, echogenicity, calcification, intranodular blood flow, cervical lymph node, and tumor node metastasis (TNM) stage were compared between MTC and PTC groups. Age, sex, involvement of the thyroid gland, margin, and calcification were similar for the MTC and PTC groups. Compared with the PTC group, the lesion size in the MTC group was significantly larger (P < 0.001). A taller-than-wide shape (aspect ratio > 1) was significantly less likely in the MTC group than the PTC group (P < 0.001). A mixed echogenicity was significantly more common in the MTC group than the PTC group (P = 0.003). The MTC group had significantly enhanced intranodular blood flow (P < 0.001). The TNM stage of the MTC group was significantly higher than that of PTC group (P = 0.001). Medullary thyroid carcinomas differ significantly from PTCs in lesion size, shape, echogenicity, and intranodular blood flow.

Intracranial arterial fenestrations associated with arteriovenous malformations diagnosed by CT angiography.

BACKGROUND: Fenestrations involving aneurysms have been well documented. Only sporadic papers have been reported on fenestrations associated with AVMs (arteriovenous malformations) with few cases. Our study is to determine the rate of co-occurrence of fenestrations and AVMs and to analyze the possible relationship between them by CTA. METHODS: Between January 2006 and February 2012, the CTA data of 5,657 consecutive patients were retrospectively reviewed. RESULTS: A total of 12 cases (.21%) of fenestrations associated with AVMs were found. Of these, single-fenestrations were identified in 9 cases, and multifenestrations were found in 3 cases. Among 349 fenestrations, there were 15 cases of multifenestrations. The frequency of multifenestrations among fenestrated patients without AVMs was 3.6%. There was no significant difference in the incidence of AVMs in cases with and without fenestrations (3.4% and 2.7%), and there was no significant difference in the incidence of fenestration in cases with and without AVMs (7.7% and 6.1%, χ(2) = .643, P = .423). CONCLUSIONS: CTA may play a vital role in assessing the anomalies of co-occurring AVM and fenestration, with an incidence of .21%. The frequency of multifenestrations in fenestrated cases with AVMs was higher than those without AVMs, though there is no significant association between fenestrations and AVMs.

Basilar artery fenestration detected with CT angiography.

OBJECTIVES: To analyse the characteristics of basilar artery (BA) fenestrations and their coexistence with aneurysms and other anomalies in a massive cases by computed tomographic angiography (CTA). METHODS: A total of 5,657 sequential cerebral CTA images performed from January 2006 to February 2012 were reviewed. CTA images were obtained from the raw datasets by using volume rendering and maximal intensity projection reconstruction. RESULTS: One hundred and thirty-two (2.33 %) BA fenestrations were detected with CTA, and most common at the proximal segment (n = 124). BA fenestration-associated aneurysms were found in 34 cases and 7 located at the posterior circulation, and the frequency of posterior circulation aneurysms was significantly different in patients with and without BA fenestrations (P = 0.025). Other associated anomalies included arteriovenous malformation (n = 7) and moyamoya disease (n = 6). BA fenestrations were classified into Type I (74 cases), Type II (15 cases), Type III (41 cases) and Type IV (2 cases). A significant difference was observed between Types II + III associated with convex-lens-like and slit-like fenestrations (P = 0.008). CONCLUSIONS: BA fenestrations were found in 2.33 % with CTA. They were significantly more often associated with posterior circulation aneurysms than those without BA fenestration. The anterior inferior cerebral artery (AICA) tends to originate more often from convex-lens-like fenestration than slit-like. KEY POINTS: • Basilar artery fenestrations were found in 2.33 % of patients undergoing CT angiography. • Fenestrations were seen more often in the lower third with slit-like configurations. • No obvious relationship exists between basilar artery fenestration and aneurysm formation. • Basilar artery fenestrations perhaps predispose a patient to posterior circulation aneurysm formation. • The AICA tends to originate more often from convex-lens-like than slit-like fenestrations.

[Comparison of Southern blotting and Real-time PCR in measuring telomere shortening].

OBJECTIVE: To analyze and compare the performances of two telomere measurement methods (digoxigenin-labeled Southern blot and Real-time PCR) in cellular senescence research. METHODS: Genomic DNA extracted from normal human fibroblasts (2BS) of different population doublings (PDs) was used as test samples. The Southern blot and Real-time PCR methods for telomere measurements were optimized. The specificity and sensitivity of digoxigenin detection system were analyzed by dot blot. The two methods were respectively used to measure parallel samples to analyze and compare their resolution and accuracy. RESULTS: Digoxigenin-labeled Southern blot system could detect less than 1 µg of human genomic DNA, but the optimal sample size was around 4-5 µg when measuring telomeres. The resolution of the Southern blot method was around 150 bp while the Real-time PCR method 300-400 bp. The former could distinguish the difference of 2 PDs for 2BS cells while the latter could not distinguish the difference of less than 5 PDs. The measurement error of the repeated measurements for the Real-time PCR method was more than 10% which was bigger than that of the Southern blot method (2.5%, P<0.001). CONCLUSION: Digoxigenin-labeled Southern blot system is fully applicable to telomere measurement. The performance of the Southern blot method is better than that of the Real-time PCR method while the latter is convenient and high-throughput. In the study of cellular senescence, the appropriate method should be selected according to specific experiment.

[An in vitro study of the relationship between KiSS-1 expression and hepatoma carcinoma cell proliferation, adhesion, and invasion].

OBJECTIVE: To investigate the impact of expression of kisspeptin-1 (KiSS-1) metastasis-suppressor gene on the proliferative, adhesive and invasive abilities of human hepatocellular carcinoma (HCC) using an in vitro cell system. METHODS: The highly metastatic human hepatoma cell line MHCC97-H was transiently transfected with the pcDNA3.1/HisC vector expressing the KiSS-1 gene (experimental group) or the vector without the KisS-1 gene (blank control group). Untransfected cells served as the negative control group. Proliferative abilities of the three groups were assessed by flow cytometry and MTT assay. Adhesive abilities were assessed by MTT assays using matrigel and fibronectin. Invasive abilities and cell motility were assessed by chemoinvasion chamber assay using reconstituted matrigel and migration chamber assay using polycarbonate filters, respectively. RESULTS: The experimental group showed significantly lower adhesion capacity to matrigel (0.257+/-0.029) than either the blank control group (0.374+/-0.016; t=-7.90345, P less than 0.01) or the negative control group (0.394+/-0.031; t=-7.22752, P less than 0.01). Similarly, the experimental group showed significantly lower adhesion capacity to fibronectin (0.292+/-0.004) than either the blank control group (0.394+/-0.010; t=-20.93138, P less than 0.01) or the negative control group (0.412+/-0.023; t=-11.31371, P less than 0.01). The experimental group also showed significantly lower numbers of cells with invasive capacity (42.40+/-1.14) than either the blank control group (66+/-1.58; t=-27.0711, P less than 0.01) or the negative control group (67.80 +/- 1.92; t=-25.4, P less than 0.01). Similarly, the experimental group showed significantly lower numbers of cells with chemotactic movement (65.80+/-1.92) than either the blank control group (93.80+/-2.28; t=-30.11750, P less than 0.01) or the negative control group (96.40+/-2.07; t=-24.19142, P less than 0.01). The experimental group showed slightly, but not significantly, lower cell proliferation (0.644+/-0.027) than either the blank control group (0.669+/-0.022; t=-1.60371, P?>?0.05) or the negative control group (0.678+/-0.027; t=-1.97828, P?>?0.05). In addition, there were no obvious differences between the three groups in the amounts of cells arrested in either the G1 phase or the S phase. CONCLUSION: KiSS-1 overexpression suppresses the adhesion, invasion and motility, but not the proliferation, of hepatoma carcinoma cells in vitro. These findings imply that KiSS-1 might represent a promising new candidate for gene therapy against human hepatocellular carcinoma.

Ablation of right-sided accessory pathways with atrial insertion far from the tricuspid annulus using an electroanatomical mapping system.

BACKGROUND: It is difficult to ablate a right-sided accessory pathway (AP) with atrial insertion far from the tricuspid annulus (TA). We report our initial experience of ablating this rare AP by a 3-dimensional electroanatomical mapping system (CARTO). METHODS: From January of 2006 to April of 2008, 18 patients with right-sided APs who failed previous outside ablations were enrolled in this study. Retrograde AP conduction was mapped during pacing at the right ventricular apex by activation-mapping the right atrium (RA) using a 3-dimensional electroanatomical mapping system. AP atrial insertion was defined as the earliest retrograde atrial activations and successful ablation of the APs at this site. RESULTS: Among the 18 patients who had failed previous ablation, 10 patients (7 patients with right manifest APs and 3 patients with right conceal APs) had atrial insertions far from the TA. Of the 10 patients, the atrial insertions were found at the base of the RA appendage in 3 patients, at the high lateral RA in 5 patients, at the low lateral RA in other 2 patients. Ablation at the atrial insertions successfully abolished the AP conduction. The mean distance between the atrial insertion sites and the TA was 20.2 ± 2.7 mm. No patients reported recovered AP conduction or recurrent tachycardias after 6-month follow-up. CONCLUSIONS: The right-sided APs may have atrial insertion far from the TA. These uncommon variation of APs can be reliably identified and ablated using CARTO system.

Metabolic syndrome in patients with atrial fibrillation in the absence of structural heart disease from a tertiary hospital in China.

BACKGROUND: Metabolic syndrome (MetS) and atrial fibrillation (AF) are causally related. This study aimed to determine the prevalence of MetS in patients with AF in the absence of structural heart disease from a tertiary hospital in China. METHODS: In a single center, 741 inpatients with AF in the absence of structural heart disease prior to catheter ablation were retrospectively reviewed. Among them, 588 (79.4%) patients had paroxysmal AF. Subgroup analyses were performed in paroxysmal AF and persistent/permanent AF. RESULTS: MetS was found in 343 (46.3%) patients (200 males, 143 females); 0, 1, 2, 3, 4, 5 components of the MetS were found in 59 (8.0%), 140 (18.9%), 199 (26.9%), 203 (27.4%), 103 (13.9%) and 37 (5.0%) patients, respectively. The prevalences of overweight/obesity, high blood pressure, high glucose level, high triglyceride level and low high density lipoproteins cholesterol level were 53.8%, 47.6%, 23.2%, 40.6% and 72.1%, respectively. The prevalence of MetS was not significantly different between the paroxysmal AF group and the persistent/permanent AF group (44.6% vs 52.9%, P = 0.064). The five components of MetS except overweight/obesity (69.3% vs 49.8%, P < 0.001) were not significantly different between the aforementioned two groups. The left atrium diameter increased with the sum of the MetS components. The left atrium diameter in the MetS group was significantly higher than that in the non-MetS group both in patients with paroxysmal AF and in patients with persistent/permanent AF. CONCLUSIONS: The prevalence of MetS in patients with AF prior to catheter ablation is high. Further study and prevention are needed.

[Expression of survivin, p27 and PTEN in hepatocellular carcinoma and their clinical significances].

OBJECTIVE: To detect the expression of survivin protein, survivin mRNA, p27 protein, p27 mRNA and PTEN protein in hepatocellular carcinomas (HCC) and their clinical significances. METHODS: Tissue microarrays were constructed. The expression of survivin protein, p27 protein and PTEN protein were evaluated by immunohistochemical methods and in expression of survivin mRNA and p27 mRNA were evaluated by in stiu hybridization respectively in tumor tissues from 141 HCC patients, 128 samples of para-carcinoma liver tissues, 97 liver tissues far from the carcinomas and normal liver tissues from non HCC patients. The relationship of survivin, p27 and PTEN were investigated and a prediction model of HCC was constructed. RESULTS: The expressions of survivin protein (Ridit 95% CI = 0.689+/-0.048, P < 0.01), survivin mRNA (Ridit 95% CI = 0.690+/-0.049, P < 0.01) and p27 protein (Ridit 95% CI = 0.556+/-0.053, P < 0.05) in HCC tissues were significantly increased, while the expression of PTEN protein (Ridit 95% CI = 0.282+/-0.048) in HCC tissues was significantly reduced (P < 0.01). CONCLUSION: Overexpressions of survivin mRNA and p27 protein and reduced expression of PTEN protein might be a valuable marker to predict the presence of HCC.

[Effect of Yufeining on induced sputum interleukin-8 in patients with chronic obstructive pulmonary disease at the stable phase].

OBJECTIVE: To evaluate the effect of Yufeining, a traditional Chinese medicine, on induced sputum interleukin-8 (IL-8) in patients with chronic obstructive pulmonary disease (COPD) at the stable phase. METHODS: Thirty-six patients with COPD were divided into trial group (18 cases) and control group (18 cases) randomly. The trial group was treated with Yufeining pills taken orally for half a year; the control group was not given any medicine. Routine lung function was recorded before and after treatment. Total cell count (TCC), differential cell counts (DCCs) and IL-8 in induced sputum were determined at the baseline and 6 months later. RESULTS: The indices of lung function improved significantly after 6 months' treatment in trial group (P < 0.05); TCC and absolute neutrophil count decreased significantly compared with baseline in the trial group (P < 0.05); Sputum IL-8 concentration dropped significantly after 6 months' treatment, from a mean of 5.216 +/- 2.914 microg/L to 4.222 +/- 2.140 microg/L (P < 0.05). There were insignificant changes in the parameters in the control group between baseline and 6 months later. CONCLUSION: Yufeining could improve lung function, decrease sputum TCC, absolute neutrophil count and IL-8 concentration, and relieve airway inflammation in patients with COPD in the stable phase.