Diagnostic accuracy of extended HPV DNA genotyping and its application for risk-based cervical cancer screening strategy.

OBJECTIVES: To evaluate the consistency of 14 high-risk HPVs (hr-HPVs) detection between extended HPV DNA genotyping and a well-validated partial HPV genotyping kit, and to explore the diagnostic accuracy of risk stratification strategy based on extended HPV genotyping for cervical cancer (CC) screening. METHODS: Baseline data from a clinical trial of recombinant HPV 9-valent vaccine in China was analyzed. All enrolled women aged 20-45 years received cervical cytology, HPV detection by extended and partial HPV genotyping kits. Those who met the indications would further receive colposcopy. The primary endpoints were cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+). RESULTS: A total of 8,000 women were enrolled between April 2020 and July 2020 and 83/33 cases were diagnosed as CIN2+/CIN3+. The overall agreement between the extended and partial HPV genotyping was 92.66 %. And the agreement further increased with the progression of lesions, which lead to similarly high sensitivity and negative predictive value of these kits. A stratified triage strategy of CC screening was constructed based on the immediate CIN2+/CIN3+ risk of specific HPV. Compared with the conventional HPV primary CC screening strategy, the risk-based strategy had higher specificity for CIN (CIN2+: 94.84 vs. 92.46 %, CIN3+: 96.05 vs. 91.92 %), and needed fewer colposcopies for detecting one cervical disease. CONCLUSIONS: Extended HPV genotyping had good agreement with a well-validated partial HPV genotyping CC primary screening kit in hr-HPV detection. Extended HPV genotyping could facilitate risk-based stratified management strategy and improve the diagnostic accuracy of primary CC screening.

The Significance of Human Papillomavirus Receptors Related Genetic Variants in Cervical Cancer Screening.

To investigate the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, from October 2016 to March 2020, a total of 3,066 women were recruited for a 3-year prospective population-based cervical cancer screening clinical trial. The primary endpoint was histological cervical intraepithelial neoplasia 2 and worse (CIN2+). Twenty-nine SNPs of HPV receptor associated genes on women with available cytology residual samples at baseline were detected using MALDI-TOF MS. Eligible data were available for 2,938 women. Rs16894821 (GG versus AA, OR =1.71 [1.08 to 2.69]) and rs724236 (TT versus AA, OR = 1.73 [1.14 to 2.62]) in SDC2 were significantly related to the HPV susceptibility. And rs2575712 (TT versus GG, OR = 2.78 [1.22 to 6.36]) in SDC2 was associated with increased HPV 16/18 susceptibility. Four SNPs (rs1047057 and rs10510097 in FGFR2 gene, rs2575735 in SDC2 gene, and rs878949 in HSPG2 gene) were significantly associated with persistent HPV infection. Importantly, the genotypes of rs16894821 under recessive model (GG versus AA/AG, OR = 2.40 [1.12 to 5.15]) in SDC2 and rs11199993 under dominant model (GC/CC versus GG, OR = 1.64 [1.01 to 2.68]) in FGFR2 were significantly associated with the disease progression. Finally, SNPs showed comparable efficacy in detecting CIN2+ for the women infected with non-HPV16/18 compared with cervical cytology (sensitivity: 0.51 [0.36 to 0.66] versus 0.44 [0.30 to 0.60], specificity: 0.96 [0.96 to 0.97] versus 0.98 [0.97 to 0.99], positive predictive value: 0.23 [0.15 to 0.33] versus 0.33 [0.22 to 0.47], and negative predictive value: 0.99 [0.98 to 0.99] versus 0.99 [0.98 to 0.99]). SNPs in HPV receptor related genes may influence HPV susceptibilities and clinical outcomes in Chinese women. IMPORTANCE Virus receptors are known to mediate virus attachment and further lead to virus infection of the host cells. In the current study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, and to explore the new triaging strategy for non-16/18 high-risk HPV infection.

A biodegradable and cofactor self-sufficient aptazyme nanoprobe for amplified imaging of low-abundance protein in living cells.

Despite the progress on the analysis of proteins either in vitro or in vivo, detection and imaging of low-abundance proteins in living cells still remains challenging. Herein, a novel biodegradable and cofactor self-sufficient DNAzyme nanoprobe has been deve-loped for catalytic imaging of protein in living cells with signal amplification capacity. This DNAzyme nanoprobe is constructed by assembling a DNAzyme subunit-containing aptamer hairpin (HP), another DNAzyme subunit strand (DS), and the molecular beacon (MB) substrate strand onto pH-sensitive ZnO@polydopamine nanorods (ZnO@PDA NRs) that work as DNAzyme cofactor suppliers. Such a nanoprobe can facilitate cellular uptake of DNA molecules and protection of them from nuclease degradation as well as release of them in cells by lysosomal acid-triggered dissolution of ZnO@PDA NRs into Zn2+ as DNAzyme cofactor. Upon recognition and binding with the intracellular protein target, the stem of HP is opened, after which the opened HP hybridizes with DS and generates activated DNAzymes. Each activated DNAzyme can catalyze the cleavage of many MB substrates through true enzymatic multiple turnovers, resulting in the separation of the quenched fluorophore/quencher pair labeled in MB and the generation of significantly amplified fluorescence. Using nucleolin (NCL) as a model protein, this nanoprobe enables the analysis of NCL with a detection limit of 1.8 pM, which are at least two orders of magnitude lower than that of non-catalytic imaging probe. Moreover, it could accurately distinguish tumor cells and normal cells by live cell NCL imaging. And the experimental results are also further verified by flow cytometry assays. The developed nanoprobe can be easily extended to detect other biomolecules by the change of their corresponding aptamer sequences, thus providing a promising tool for highly sensitive imaging of low-abundance biomolecules in living cells.

Particle exposure risk to a lavatory user after flushing a squat toilet.

Squat toilets are widely used in developing countries due to local customs and low costs. The flushing of a squat toilet can entrain strong airflow and produce aerosols. This investigation constructed a lavatory mock-up with a squat toilet. The flushing-induced airflow was both visualized and quantitatively measured by particle image velocimetry. The maximum height of the impacted airflow was identified by an ultrasonic anemometer. For inference of the particle emission rate, the toilet bowl was covered by an enclosed box for particle concentration measurement. The risks from skin contact of the deposited particles on the flushing button and the door handle and the possible inhalation of the released aerosols were evaluated. The results revealed that flushing a squat toilet can drive toilet plume to rise up to 0.9 m above the toilet bowl. A single flushing process can produce 0.29 million particles with diameters greater than 0.3 µm, among which 90% of the particles are submicron-sized. The flushing may cause particles to deposit on the flushing button and lavatory door handle as well as inhalation exposure even remaining in the lavatory for half a minute after flushing, especially for those lavatory users whose respiratory zones are below 1.0 m.

Hyperthermia synergistically enhances antitumor efficacy of PARP inhibitor through impacting homologous recombination repair and oxidative stress in vitro.

Tumors with homologous recombination (HR) deficiency are particularly responsive to PARP inhibitors, however strategies to improve the sensitivity of epithelial ovarian carcinoma (EOC) with sufficient HR abilities still need to be deeply explored. In the present study, we firstly validated that hyperthermia (HT) changed diverse genes and signal pathways related to HR and oxidative stress in HR proficient EOC cells. HT impaired HR efficiency through inhibiting Olaparib (Olap) induced RAD51 foci formation in EOC cells, which was independent of the expression level of RAD51. Combination therapy of HT and Olap synergistically induced oxidative stress and oxidative DNA damage of EOC cells. Furthermore, we revealed that HT and Olap synergistically aggravated double-strand breaks of DNA in EOC cells. Conclusively, our findings confirmed that HT could synergistically enhance HR proficient EOC cells' sensitivity to PARP inhibitor through impairing HR efficiency and increasing oxidative stress.

Clinical significance of extra-thyroid 99mTc-pertechnetate uptake before initial radioiodine therapy for differentiated thyroid carcinoma.

OBJECTIVE: To analyse the clinical characteristics of extra-thyroid 99mTc-pertechnetate uptake in order to explore the effect of the phenomenon on radioactive iodine (RAI) therapy for differentiated thyroid carcinoma (DTC) and its clinical significance. METHODS: This study retrospectively selected patients with DTC and extra-thyroid 99mTc-pertechnetate uptake. The clinical features, location, location count and extra-thyroid 99mTc-pertechnetate uptake distribution were analysed, combined with the uptake rate, stimulated thyroglobulin (sTg) level, post-therapy whole-body scan and curative effect. RESULTS: A total of 38 patients were enrolled in the study and 65 extra-thyroid 99mTc-pertechnetate foci were detected. Thirty-four patients showed abnormal 99mTc-pertechnetate uptake in the lymph nodes (26 of 38; 68.4%), lungs (four of 38; 10.5%) and bones (four of 38; 10.5%). The corresponding uptake rates were 0.2%, 0.2% and 0.8%, respectively. The uptake rate and sTg were significantly positively correlated (r = 0.36). 131I uptake was found in 36 patients at the 99mTc-pertechnetate uptake site. The number of iodine uptake foci was significantly higher than that of 99mTc-pertechnetate uptake foci. The sTg value and pathological staging significantly differed between the excellent and nonexcellent response groups (Z = -2.947 and Z = -2.348, respectively). CONCLUSION: Extra-thyroid 99mTc-pertechnetate uptake mostly indicated metastases with specific clinical features, which may have prognostic value for the judgment of iodine uptake function and the RAI therapy plan.

An aptamer-based four-color fluorometic method for simultaneous determination and imaging of alpha-fetoprotein, vascular endothelial growth factor-165, carcinoembryonic antigen and human epidermal growth factor receptor 2 in living cells.

The extraordinary fluorescence quenching capability of graphene oxide (GO) was coupled to the specific recognition capability of aptamers to design a four-color fluorescent nanoprobe for multiplexed detection and imaging of tumor-associated proteins in living cells. Specifically, alpha-fetoprotein (AFP), vascular endothelial growth factor-165 (VEGF165), carcinoembryonic antigen (CEA), and human epidermal growth factor receptor 2 (HER2) were detected. Due to strong π interaction, the fluorescence of labeled aptamers is quenched by GO. Four fluorophore-labeled aptamers that bind the tumor-associated proteins were adsorbed on GO to form the four-color nanoprobe with quenched fluorescence. The nanoprobes were internalized into cells via endocytosis, where the aptamer/GO nanoprobes bind the intracellular tumor-associated proteins. The aptamer-protein complexes thus formed detach from GO, and fluorescence recovers. Each analyte has its typical color (AFP: blue; VEGF165: green; CEA: yellow; HER2: red). As a result, simultaneous detection and imaging of multiple tumor-associated proteins in living cells were achieved. This nanoprobe has a fast response and is highly specific and biocompatible. The linear ranges for AFP, VEGF165, CEA, and HER2 are 0.8 nM-160 nM, 0.5 nM-100 nM, 1.0 nM-200 nM, and 1.2 nM-240 nM, respectively. Detection limits were 0.45 nM for AFP, 0.30 nM for VEGF165, 0.62 nM for CEA, and 0.96 nM for HER2. The probe allows for a fast distinction between tumor cells and normal cells via imaging. Graphical abstract Schematic presentation of the development of a four-color fluorometic method based on aptamer and graphene oxide for simultaneous detection and imaging of alpha-fetoprotein, vascular endothelial growth factor-165, carcinoembryonic antigen and human epidermal growth factor receptor 2 in living cells.

A peptide-based four-color fluorescent polydopamine nanoprobe for multiplexed sensing and imaging of proteases in living cells.

We develop a novel peptide-based four-color fluorescent polydopamine nanoprobe for multiplexed sensing and imaging of tumor-related proteases in living cells. This nanoprobe responds rapidly and selectively, enabling simultaneous and high-contrast imaging of multiple proteases in living cells. Furthermore, it could detect the changes of protease expression in living cells.

A gold nanoparticle-based four-color proximity immunoassay for one-step, multiplexed detection of protein biomarkers using ribonuclease H signal amplification.

A novel gold nanoparticle-based four-color fluorescence proximity immunoassay is developed for one-step, multiplexed detection of protein biomarkers using ribonuclease H signal amplification. This assay could detect proteins with detection limits down to pg mL-1 and a 5-log dynamic range. Furthermore, it is suitable for rapid, direct quantification of multiple proteins in biological samples.

Role of high mobility group A1 and body mass index in the prognosis of patients with breast cancer.

The high mobility group A1 (HMGA1) protein is associated with poor prognosis in patients with a wide range of cancers. However, the affect of HMGA1 on the risk of mortality from breast cancer (BC) has not been fully characterized. In the present retrospective multiple center study, the HMGA1 expression level was determined by performing immunohistochemistry on surgical tissue samples of 273 BC specimens from the Second Affiliated Hospital of Zhejiang University (Zhejiang, China) and 310 BCs from the National Engineering Center for Biochip (Shanghai, China). Kaplan-Meier analysis and Cox proportional hazard model were employed to analyze the survivability. HMGA1 expression was significantly associated with tumor histological degree and body mass index (BMI). However, HMGA1 expression showed no prognostic value in patients with BC. Combined evaluation of HMGA1 expression and high BMI (≥24 kg/m2) predicted worse overall survival of BC. Therefore, HMGA1 and BMI were considered to serve synergistic roles in the development and progression of BC, and combined evaluation of HMGA1 expression and high BMI may be an effective marker in predicting poor prognosis of BC patients.

Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer.

High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage II-III, low pathological grade and non-triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors.

Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma.

PURPOSE: To determine whether postoperative radioiodine (RAI) combined with radiofrequency ablation (RFA) is an effective, safe, and feasible method for elimination of excessive postsurgical thyroid remnant for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: We took a prospective study and treated 12 DTC patients (4 males, 8 females, age 20-78 years) who underwent thyroidectomy for RFA followed by 131 I ablation. The pretreatment requires iodine-free diet and thyroid hormone withdrawal for 3-4 week. All the patients showed the level of serum thyroid-stimulating hormone (TSH) <30 mU/L, and obvious thyroid remnant in 99m Technetium (99m Tc) imaging. Serum TSH level was determined 1 day before RFA and on days 1, 7, 14 after RFA, and 99m Tc imaging was performed on day 14 after RFA. Subsequently, the patients were given an oral dosage of 3700 MBq 131 I for remnant ablation, and posttreatment whole body scan was performed on day 5 after ablation. Efficacy evaluation was done 4-6 months after treatment. The changes of variants before and after RFA were analyzed using Wilcoxon signed rank sum test. RESULTS: Serum TSH was <30 µIU/ml (mean value 10.27 ± 6.16 µIU/ml) before RFA, and increased to more than 30 µIU/ml (34.73 ± 3.93 µIU/ml) 2 weeks later (P = 0.002, Wilcoxon rank sum test). The 99m Tc uptake ratio on day 14 postRFA was (0.31 ± 0.12)%, which is significantly lower than before RFA (0.80 ± 0.16)% (P = 0.002, Wilcoxon rank sum test). The success rate of thyroid remnant ablation was 91.7% (11/12), which was assessed 4-6 months after treatment. All patients reported neck discomfort and some are self-limiting, with no hoarseness, choking, or radiation thyroiditis symptoms. Five patients had puncture area pain, among which one patient had neck edema, which was relieved after prednisone treatment. CONCLUSION: Combined use of RAI therapy and radiofrequency ablation in treating excessive postsurgical thyroid remnant of DTC can be an effective approach and avoids re-operation. Long-term efficacy monitoring would further determine its feasibility.

Enhanced asymmetric transmission due to Fabry-Perot-like cavity.

In this paper, a three layered metamaterial composed of a ring-chain structure sandwiched between two layers of twisted sub-wavelength cut-wire arrays is proposed and investigated. The designed structure is optimized such that asymmetric transmission with an extremely broad bandwidth, sharp rejection stop-band and high transmittance is achieved. The physical mechanism is accounted for that the metallic layers form the Fabry-Perot-like resonance cavity, enhancing the polarization conversion efficiency between two orthogonal linearly polarized waves. To some extent, this approach offers a way to strengthen asymmetric transmission effect.

Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers.

PURPOSE: This study aims to address the hypothesis that the high-mobility group A2 (HMGA2), an oncofetal protein, relates to survivability and serves as a prognostic biomarker for colorectal cancer (CRC). EXPERIMENTAL DESIGN: This is a retroprospective multiple center study. The HMGA2 expression level was determined by performing immunohistochemistry on surgical tissue samples of 89 CRCs from a training set and 191 CRCs from a validation set. The Kaplan-Meier analysis and COX proportional hazard model were employed to analyze the survivability. RESULTS: Multivariate logistic analysis indicated that the expression of HMGA2 significantly correlates with distant metastasis in training set (odds ratio, OR = 3.53, 95% CI: 1.37-9.70) and validation set (OR = 6.38, 95% CI: 1.47-43.95). Survival analysis revealed that the overexpression of HMGA2 is significantly associated with poor survival of CRC patients (P < 0.05). The adjusted HRs for overall survival were 2.38 (95% CI: 1.30-4.34) and 2.14 (95% CI: 1.21-3.79) in training and validation sets, respectively. Further investigation revealed that HMGA2 delays the clearance of γ-H2AX in HCT-116 and SW480 cells post γ-irradiation, which supports our finding that CRC patients with HMAG2-positive staining in primary tumors had augmented the efficacy of adjuvant radiotherapy (HR = 0.18, 95% CI: 0.04-0.63). CONCLUSION: Overexpression of HMGA2 is associated with metastasis and unequivocally occurred in parallel with reduced survival rates of patients with CRC. Therefore, HMGA2 may potentially serve as a biomarker for predicting aggressive CRC with poor survivability and as an indicator for better response of radiotherapy.

[Effect of shensongyangxin capsule on myocardial remodeling and ventricular fibrillation threshold value in rat with coronary artery ligation].

OBJECTIVE: To study the effect of shensongyangxin capsule on myocardial remodeling and ventricular fibrillation characteristics in rat with coronary artery ligation. METHOD: Twenty-three male rats were randomly divided into sham-group (n = 5), model group (n = 6), anmiodarone group (n = 6) and shensongyangxin capsule group (n = 6). Drugs were administrated after modeling of 2 days, lasting four weeks. Two dimensional and Doppler images were acquired by a 15 MHz high-frequency linear ultrasound transducer at 4 weeks after operation, and chest was opened to detect ventricular fibrillation threshold value and persistent time. RESULT: After administration of four weeks, echocardiogram was detected. Compared with model group, shensongyangxin capsule group diastasis interventricular septum thickness (IVSTd) and left ventricle diameter (LVDd) were significiently different between them (1.20 +/- 0.49) vs (0.78 +/- 0.08) mm and (6.77 +/- 1.34) vs (7.95 +/- 0.92) mm, (P < 0.01 and 0.05); echocardiogram result had no difference in amiodarone and model groups (P > 0.05). LVMI measured by practicion was different between shensongyangxin capsule and model groups: (17.12 +/- 1.91) vs (18.95 +/- 1.41) g x m(-2), (P < 0.05), while amiodarone group had no difference compared with model group. Electrophysiology was used to detect ventricular fibrillation threshold value and 1-5, 6-10, 11-15 V three stages' ventricular fibrillation threshold persistent time were significiently different among each group (P < 0.01), 16-20 V stage's ventricular fibrillation persistent time were also different among each group (P <0.05). Sample "average ranks" showed ventricular fibrillation threshold value of amiodarone group and shensongyangxin capsule group were four times than model group; and amiodaron group had best effect of holding-back ventricular fibrillation persistent time. CONCLUSION: The coronary artery ligation can result in myocardial remodeling by increasing volume load, and at the same time influencing electrophysiology function of heart. Amiodaron elevated ventricular fibrillation threshold of heart, this effect maybe relate to influencing many ion channels of myocardial cellular membrane; shensongyangxin capsule also elevate ventricular fibrillation threshold of heart, this effect maybe also relate to influencing many ion channels of myocardial cellular membrane, and on the other hand this effect maybe relate to hold-back ventricular remodeling after coronary artery was ligated, accordingly improve electrophysiological base material of heart.

Epithelioid sarcoma: a case report with ultrastructural confirmation of myofibroblastic differentiation based on fibronexus junctions.

Epithelioid sarcoma is an uncommon but well-described malignancy, which is found predominantly in the soft tissues of the young and middle-aged, and which pursues an indolent to aggressive course. It shows a degree of both mesenchymal and epithelial differentiation. Myofibroblastic differentiation has been recorded in epithelioid sarcoma for some time, the evidence being based mainly on the presence of smooth-muscle-type myofilaments and, more recently, on alpha-smooth-muscle actin and muscle-specific actin immunostaining. Myofibroblastic differentiation based on the stricter criterion of the fibronectin fibril/fibronexus junction has not so far been demonstrated except for a single atypical case with spindle-cell morphology and a cytokeratin-negative immunophenotype. The authors describe a conventional epithelioid sarcoma showing myofibroblastic differentiation based on the presence of fibronectin fibrils and fibronexus junctions. The patient was a 35-year-old Chinese male with a tumor that initially developed on his left forefinger: it recurred, then metastasised first to the left arm and eventually to the scalp. Histologically, the tumors had the typical features of epithelioid sarcoma: by immunohistochemistry, cytokeratin, epithelial membrane antigen, and vimentin were positive. By electron microscopy, rough endoplasmic reticulum, intermediate filaments, peripheral myofilaments, and fibronexus junctions were observed. This is the first epithelioid sarcoma of conventional histological type to show myofibroblastic differentiation on the basis of the more stringent criterion of the fibronexus. The findings are discussed in relation to the unusually varied differentiation reported for this tumor.

Effect of Chinese drugs for supplementing Qi, nourishing Yin and activating blood circulation on myocardial perfusion in patients with acute myocardial infarction after revascularization.

OBJECTIVE: To observe the effects of Chinese drugs for supplementing qi, nourishing yin and activating blood circulation on the myocardial perfusion in acute myocardial infarction (AMI) patients after revascularization. METHODS: Eighty patients with anterior or inferior ventricular wall AMI, who had received revascularization by intravenous thrombolysis or coronary bypass, were randomized into the treated group and the control group equally, both treated with conventional Western medical treatment, but combined, respectively, with Xinyue Capsule (, XYC) plus Composite Salvia Tablet (CST) and placebo for 3 months. Dobutamine stress echocardiography (DSE) was performed 14 days and 3 months after revascularization, respectively on every patient to observe blood perfusion extent (b value), myocardial perfusion velocity (k value) and local blood fl ow volume (k x b) in left ventricular infarction-related vascular segments under stressed state. RESULTS: With 5 cases dropping out in the observation period (3 in the treated group and 2 in the control group), the trial was completed in 75 patients in total. The 14-day DSE shows that the b value and k x b value of left anterior ventricular wall mid segment and apex segment, and the k value of apex segment in patients with anterior wall AMI, as well as the b value and k x b of basal segment in patients with inferior wall AMI in the treated group were significantly higher than those in the control group (P<0.05 or P<0.01). The 3-month DSE shows that the b value of apex segment, k x b value of basal segment, mid segment and apex segment of left anterior ventricular wall in patients with anterior wall AMI as well as the b value and k x b value of basal segment of left inferior ventricular wall in patients with inferior wall AMI were all higher in the treated group than those in the control group, respectively (P<0.05). The comparison between 14-day DSE and 3-month DSE in the treated group showed that the b value of apex segment of left anterior ventricular wall in patients with anterior wall AMI and the k x b value of apex segment and mid segment of left inferior ventricular wall in patients with inferior wall AMI significantly increased along with the on-going treatment (P<0.05). CONCLUSION: Therapy with Chinese drugs for supplementing qi, nourishing yin and activating blood circulation in combination with conventional Western medical treatment could obviously improve the blood perfusion at the myocardial tissue level in infarction-related vascular segments.

[Application of immunohistochemistry-laser microdissection-PCR technique in detecting p53 gene mutation in paraffin sections of gastric cancer].

OBJECTIVE: To evaluate the application of immunohistochemistry-laser microdissection-polymerase chain reaction (IHC-LMD-PCR) technique in detecting p53 gene mutations using paraffin sections of advanced gastric cancers. METHODS: The expression of p53 protein in 41 paraffin-embedded advanced gastric cancer samples was assessed by immunohistochemistry. The p53-positive or negative carcinoma cells and normal foveolar cells far from the main tumor were then isolated by LMD. The DNA was extracted and p53 gene at exon 5 - 8 amplified by PCR. The products were then analyzed by single-strand conformation polymorphism (SSCP) and automated sequencing. RESULTS: p53 gene was successfully amplified in all the 41 specimens. Overexpression of p53 protein was noted in 11 cases. Mutations of p53 gene were found in 15 cases. Eight of the 11 p53-overexpressed cases had p53 gene mutations. On the other hand, p53 gene mutations were found in only 7 of the 30 p53 protein-negative cases. The presence of p53 gene mutations significantly correlated with p53 protein overexpression (P = 0.004). CONCLUSIONS: IHC-LMD-PCR technique can be successfully applied in paraffin sections of gastric cancers for the detection of p53 gene mutations. The results correlate well with overexpression of p53 protein.

[Effect of STAT3 phosphorylation and p53 expression on human epidermal non melanoma cutaneous tumors].

OBJECTIVE: To investigate the effect of stat3 phosphorylation and p53 expression on human epidermal non-melanoma cutaneous tumours. METHODS: Immunohistochemistry technique was employed to measure the expression of p-stat3 and p53 protein in skin tissue from 30 cases of skin squamous cell carcinoma (SCC), 20 cases of basal cell carcinoma (BCC), 20 cases of seborrhoeic keratosis (SK) and 20 normal subjects. RESULT: (1) p-stat3 protein was abnormally increased in SCC and BCC as compared with normal skin and SK. Expression of p-stat3 in SCC was also significantly higher than that in BCC. (2) Expression of p-stat3 was higher in poorly-differentiated cancers than that in well-differentiated cancers in SCC. The positive rate of p-stat3 expression was correlated with the depth of tumor invasion, but not with tumor size. (3) There was no p53 protein expression on normal skin and SK, it was significantly upregulated in SCC and BCC. In SCC, the intensity of p53 expression was associated with tumor differentiation. There was no correlation between the positive rate of p53 expression and the depth of tumor invasion, whereas the positive rate of p53 expression was correlated with the sun-exposure area. (4) There existed positive correlation between the expression intensity of p-stat3 and p53 in SCC (r=0.641, P<0.05). CONCLUSION: (1) The overexpression of p-stat3 may play an important role in the development of epidermal tumors. (2) The abnormal activation of stat3 may be related to metastatic potentials in SCC. (3) Both p53 gene and stat3 may contribute to the pathogenesis of skin SCC.