DKPE-GraphSYN: a drug synergy prediction model based on joint dual kernel density estimation and positional encoding for graph representation.

Introduction: Synergistic medication, a crucial therapeutic strategy in cancer treatment, involves combining multiple drugs to enhance therapeutic effectiveness and mitigate side effects. Current research predominantly employs deep learning models for extracting features from cell line and cancer drug structure data. However, these methods often overlook the intricate nonlinear relationships within the data, neglecting the distribution characteristics and weighted probability densities of gene expression data in multi-dimensional space. It also fails to fully exploit the structural information of cancer drugs and the potential interactions between drug molecules. Methods: To overcome these challenges, we introduce an innovative end-to-end learning model specifically tailored for cancer drugs, named Dual Kernel Density and Positional Encoding (DKPE) for Graph Synergy Representation Network (DKPEGraphSYN). This model is engineered to refine the prediction of drug combination synergy effects in cancer. DKPE-GraphSYN utilizes Dual Kernel Density Estimation and Positional Encoding techniques to effectively capture the weighted probability density and spatial distribution information of gene expression, while exploring the interactions and potential relationships between cancer drug molecules via a graph neural network. Results: Experimental results show that our prediction model achieves significant performance enhancements in forecasting drug synergy effects on a comprehensive cancer drug and cell line synergy dataset, achieving an AUPR of 0.969 and an AUC of 0.976. Discussion: These results confirm our model's superior accuracy in predicting cancer drug combinations, providing a supportive method for clinical medication strategy in cancer.

Comparative Transcriptome Analysis Revealed Candidate Gene Modules Involved in Salt Stress Response in Sweet Basil and Overexpression of ObWRKY16 and ObPAL2 Enhanced Salt Tolerance of Transgenic Arabidopsis.

Sweet basil (Ocimum basilicum L.) is an important aromatic plant with high edibility and economic value, widely distributed in many regions of the tropics including the south of China. In recent years, environmental problems, especially soil salinization, have seriously restricted the planting and spread of sweet basil. However, the molecular mechanism of the salt stress response in sweet basil is still largely unknown. In this study, seed germination, seedling growth, and chlorophyll synthesis in sweet basil were inhibited under salt stress conditions. Through comparative transcriptome analysis, the gene modules involved in the metabolic processes, oxidative response, phytohormone signaling, cytoskeleton, and photosynthesis were screened out. In addition, the landscape of transcription factors during salt treatment in sweet basil was displayed as well. Moreover, the overexpression of the WRKY transcription factor-encoding gene, ObWRKY16, and the phenylalanine ammonia-lyase-encoding gene, ObPAL2, enhanced the seed germination, seedling growth, and survival rate, respectively, of transgenic Arabidopsis, suggesting that they might be important candidates for the creation of salt-tolerant sweet basil cultivars. Our data enrich the study on salt responses in sweet basil and provide essential gene resources for genetic improvements in sweet basil in the future.

MFSynDCP: multi-source feature collaborative interactive learning for drug combination synergy prediction.

Drug combination therapy is generally more effective than monotherapy in the field of cancer treatment. However, screening for effective synergistic combinations from a wide range of drug combinations is particularly important given the increase in the number of available drug classes and potential drug-drug interactions. Existing methods for predicting the synergistic effects of drug combinations primarily focus on extracting structural features of drug molecules and cell lines, but neglect the interaction mechanisms between cell lines and drug combinations. Consequently, there is a deficiency in comprehensive understanding of the synergistic effects of drug combinations. To address this issue, we propose a drug combination synergy prediction model based on multi-source feature interaction learning, named MFSynDCP, aiming to predict the synergistic effects of anti-tumor drug combinations. This model includes a graph aggregation module with an adaptive attention mechanism for learning drug interactions and a multi-source feature interaction learning controller for managing information transfer between different data sources, accommodating both drug and cell line features. Comparative studies with benchmark datasets demonstrate MFSynDCP's superiority over existing methods. Additionally, its adaptive attention mechanism graph aggregation module identifies drug chemical substructures crucial to the synergy mechanism. Overall, MFSynDCP is a robust tool for predicting synergistic drug combinations. The source code is available from GitHub at https://github.com/kkioplkg/MFSynDCP .

Physiological and clinical variables identify ARDS classes and therapeutic heterogeneity to glucocorticoids: a retrospective study.

OBJECTIVE: We aimed to identify new classes in acute respiratory distress syndrome (ARDS) using physiological and clinical variables and to explore heterogeneity in the effects of glucocorticoid therapy between classes. METHODS: Using the Medical Information Mart for Intensive Care-IV database, we identified patients with ARDS. Potential profile analysis was used to identify classes with physiological and clinical data as delineating variables. Baseline characteristics and clinical outcomes were compared between classes. The effect of glucocorticoid treatment was explored by stratifying by class and glucocorticoid treatment. RESULTS: From 2008 to 2019, 1104 patients with ARDS were enrolled in the study. The 2-class potential analysis model had the best fit (P < 0.0001), with 78% of patients falling into class 1 and 22% into class 2. Additional classes did not improve the model fit. Patients in class 2 had higher anion gap, lactate, creatinine, and glucose levels and lower residual base, blood pressure, and bicarbonate compared with class 1. In-hospital mortality and 28-day mortality were significantly higher among patients in class 2 than those in class 1 (P < 0.001). Heterogeneity of glucocorticoid treatment was observed, stratified by class and treatment, with no significant effect in class 1 (P = 0.496), increased mortality in class 2 (P = 0.001), and a significant interaction (P = 0.0381). In class 2, 28-day survival was significantly lower with glucocorticoid treatment compared with no hormone treatment (P = 0.001). CONCLUSION: We used clinical and physiological variables to identify two classes of non-COVID-19-associated ARDS with different baseline characteristics and clinical outcomes. The response to glucocorticoid therapy varied among different classes of patients.

Sphingosine Kinase 1 Acts as a Hypoxia-Upregulated Oncogene to Regulate Cell Invasion and Resistance to NK Cell Killing in Bladder Carcinoma Cells.

OBJECTIVE: Hypoxia facilitates an aggressive phenotype and immune evasion in solid tumors including bladder cancer (BC). Sphingosine kinase 1 (SphK1) is aberrantly expressed and correlated with poor prognosis in BC patients. However, its roles in hypoxia-evoked malignancies and immune evasion in BC remain elusive. METHODS: The expression of SphK1 in BC tissues was analysed using a bioinformatics database. BC cells were transfected with si-SphK1 or recombinant HIF-1α plasmids under hypoxic conditions. The mRNA level, activity and protein expression of SphK1 were determined. Transwell assay was performed to evaluate cell invasion. After co-culture with natural killer (NK) cells, NK cell cytotoxicity to BC cells was assessed. The involvement of sphingosine-1-phosphate (S1P)/HIF-1α signaling was analysed by ELISA, qRT-PCR and western blot. RESULTS: UALCAN and GEPIA database confirmed high expression of SphK1 in BC tissues. Moreover, hypoxia increased the expression and activity of SphK1. Loss of SphK1 inhibited hypoxia-induced cell invasion. IL-2 induced NK cell activation by secreting TNF-α and IFN-γ. Hypoxia antagonized NK cell activation-evoked cytotoxicity to BC cells. Intriguingly, SphK1 knockdown reversed hypoxia-induced cell resistance to NK cell killing. Mechanically, SphK1 loss inhibited hypoxia-activated the S1P/HIF-1α signaling. However, S1P addition reversed the inhibitory effects of SphK1 down-regulation on hypoxia-activated S1P/HIF-1α signaling. Notably, reactivating HIF-1α overturned the suppressive roles of SphK1 loss in decreasing hypoxia-induced cell invasion and resistance to NK cell cytotoxicity. CONCLUSIONS: Targeting SphK1 may inhibit hypoxia-evoked invasion and immune evasion via the S1P/HIF-1α signaling, indicating a promising therapeutic target for BC.

Segmentation of infected region in CT images of COVID-19 patients based on QC-HC U-net.

Since the outbreak of COVID-19 in 2019, the rapid spread of the epidemic has brought huge challenges to medical institutions. If the pathological region in the COVID-19 CT image can be automatically segmented, it will help doctors quickly determine the patient's infection, thereby speeding up the diagnosis process. To be able to automatically segment the infected area, we proposed a new network structure and named QC-HC U-Net. First, we combine residual connection and dense connection to form a new connection method and apply it to the encoder and the decoder. Second, we choose to add Hypercolumns in the decoder section. Compared with the benchmark 3D U-Net, the improved network can effectively avoid vanishing gradient while extracting more features. To improve the situation of insufficient data, resampling and data enhancement methods are selected in this paper to expand the datasets. We used 63 cases of MSD lung tumor data for training and testing, continuously verified to ensure the training effect of this model, and then selected 20 cases of public COVID-19 data for training and testing. Experimental results showed that in the segmentation of COVID-19, the specificity and sensitivity were 85.3% and 83.6%, respectively, and in the segmentation of MSD lung tumors, the specificity and sensitivity were 81.45% and 80.93%, respectively, without any fitting.

Construction of exchange integrated information chain management model leading by information nurse for large instrument and equipment in operating room.

BACKGROUND: This study aims to explore the information chain management model of large instrument and equipment inter-working in the operating room (OR) led by information nurses. METHODS: Through the chain management process of large instruments and equipment in the OR, which was based on information nurses, the management model of inter-working and integrating information chain was established, the key links were controlled, and the whole life cycle management of instruments and equipment from expected procurement to scrapping treatment was realized. Using the cluster sampling method, 1562 surgical patients were selected. Among these patients, 749 patients were assigned to the control group before the running mode, and 813 patients were assigned to the observation group after the running mode. The related indexes for large instrument and equipment management in the department before and after the running mode were compared. RESULTS: In the observation group, the average time of equipment registration was (22.05 ± 2.36), the cost was reduced by 2220 yuan/year, and the satisfaction rate of the nursing staff was 97.62%. These were significantly better, when compared to the control group (P < 0.05). Furthermore, the awareness rate of the whole staff for equipment repair application was 95.12%, and the arrival time of maintenance personnel and the examination and approval time of equipment management were greatly shortened (P < 0.05). CONCLUSION: The integrated management model of large instrument and equipment interworking in the OR based on chain flow realizes the whole life cycle management of instruments and equipment, which is essential to improve management efficiency.

Estimation of potential agricultural non-point source pollution for Baiyangdian Basin, China, under different environment protection policies.

To prevent and control non-point source pollution, many policies have been carried out by government in China. However, the effectiveness of these policies has rarely been evaluated. In this study, the potential and spatial distribution of agricultural non-point source pollution in the Baiyangdian Basin are reported. This investigation considers multiple parameters under various policies with county as a basic unit. The results for the potential pollution from chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN) and total phosphorus (TP) are 60.89×104, 3.93×104, 87.05×104 and 15.10×104 Mg, with corresponding intensities of 190, 12, 272 and 47 kg ha-1 for the Baiyangdian Basin in 2016. The highest pollution from COD is attributed to livestock and poultry breeding, whereas TN and TP are dominantly produced by rural domestic sources, and NH3-N is mostly derived from planting. Spatially, distribution of the counties producing larger non-point source pollution presented a northeast to southwest direction, consistent with the Taihang mountain alignment in the basin. The counties with high pollution intensities are mostly in the south and east of the basin. Agricultural non-point source pollution control and prevention policies contributed in pollution reduction. Compared with 2016, the total potential pollution of COD, NH3-N, TN and TP in 2020 decrease by 45.1%, 14.7%, 37.9% and 37.4%, respectively, whereas for an assumed future time (F2), the decreases are 59%, 51.4%, 56.2% and 55.7%, respectively. Prevention measures should focus on reducing pollution from livestock and poultry breeding as well as planting.

An unusual diagnosis of paravertebral lesions: mediastinal myelolipoma.

BACKGROUND: Mediastinal myelolipoma is extremely rare. It is a benign nonfunctioning tumor composed of hematopoietic tissue and mature fatty tissue. Although computed tomography and magnetic resonance imaging are effective in diagnosing mediastinal myelolipoma, a definitive diagnosis is difficult to establish for rare extra-adrenal myelolipomas by imaging alone. Such tumors are often misdiagnosed as malignant retropleural liposarcoma, denoting a poor prognosis. Case presentation: We herein describe a 72-year-old man with multiple bilateral paravertebral mediastinal myelolipomas and discuss the imaging findings and differential diagnoses. We used a computed tomography-guided core biopsy to attain a preoperative diagnosis. Using this technique, we avoided an unnecessary surgical procedure for the patient's asymptomatic and relatively small lesions. CONCLUSIONS: Instead of biopsy by lesion excision, we advocate conducting a precisely targeted, minimally invasive computed tomography-guided core biopsy to obtain a definitive preoperative diagnosis and thus avoid unnecessary surgery for mediastinal myelolipoma, a benign nonfunctioning tumor.

[Research progress of the role of postoperative pain in the development of postoperative cognitive dysfunction in geriatric patients].

Previous studies have shown that postoperative cognitive dysfunction (POCD) is related to multiple factors including age, postoperative trauma, inflammation, postoperative pain, and anesthesia, among which postoperative pain is thought to play an important role in the development of POCD. This review summarizes the recent findings in the study of the role of postoperative pain in the pathogenesis of POCD in light of nerve injuries, neural remodeling and stress, and the progress in the prevention and treatment of POCD in elderly patients. It is of vital important to assess the postoperative pain and formulate adequate analgesic regimens for effective prevention and management of POCD to protect the brain functions of elderly patients.

Downregulation of PDCD4 by miR-21 suppresses tumor transformation and proliferation in a nude mouse renal cancer model.

Programmed cell death 4 (PDCD4) is known to suppress neoplastic transformation, cell proliferation and metastasis, and to be downregulated by microRNA-21 (miR-21) in renal cell carcinoma (RCC) cell lines and tissues. The aim of the present study was to investigate the roles of and association between PDCD4 and miR-21 in a nude mouse renal cancer model. A total of 24 BALB/c male nude mice were randomly assigned into the following three groups: Negative control (NC; n=8), miR-21 inhibitor (n=8) and miR-21 mimic (n=8). Subsequently, renal cell adenocarcinoma 786-O cells were subcutaneously transplanted into the armpits of the mice, which were then injected daily with NC small interfering (si)RNA, precursor-miR-21 (mimic) or anti-miR-21 (inhibitor). Tumors were removed from the mice and weighed 16 days following 786-O cell transplantation. In addition, the expression of miR-21 and PDCD4 mRNA in cancer tissues was analyzed using reverse transcription-quantitative PCR. The expression of PDCD4 protein in cancer tissues was also examined using immunohistochemistry and western blotting. Furthermore, 786-O cells were transfected with PDCD4 siRNA or NC siRNA, and the effects of silencing PDCD4 on tumor cell growth, proliferation and invasion were investigated using soft agar colony formation, EdU cell proliferation assay and Transwell migration and invasion assays. Another 16 BALB/c male nude mice were randomly assigned into two groups as follows: NC (n=8) and PDCD4 siRNA (n=8). The 786-O cells were subcutaneously transplanted into the armpits of the mice, which were subsequently injected daily with NC siRNA or PDCD4 siRNA. The tumors were removed and weighed 16 days following transplantation. Compared with the NC group, tumor weight in the miR-21 mimic group was significantly increased. By contrast, tumor weight in the miR-21 inhibitor group was significantly decreased. Similar to the results observed in human renal cancer tissue and cell lines, miR-21 expression in the nude mouse renal cancer models was significantly upregulated in the miR-21 mimic group compared with the NC group, while it was significantly lower in the miR-21 inhibitor group. Furthermore, there was a significant reduction in PDCD4 protein levels in the miR-21 mimic group and a significant increase in the miR-21 inhibitor group compared with the NC, whereas PDCD4 mRNA expression was not significantly altered. In the EdU proliferation assay, the mean percentage of new cells that incorporated EdU was 28.6% in the NC siRNA group and significantly increased to 44.7% in PDCD4 siRNA transfected cells. In the soft agar colony formation assay, Transwell and migration and invasion assays, a significant increase in colony formation, migration and invasion capacity in PDCD4 siRNA-transfected cells was observed compared with the NC. Furthermore, compared with the NC group, tumor weight in the PDCD4 siRNA group was significantly increased. Similar to the results observed in human renal cancer tissue and cell lines, miR-21 promoted cancer cell hyperplasia and proliferation, and post-transcriptionally downregulated PDCD4 protein expression, in the nude mouse renal cancer model. The results of the present study and previous studies indicate that PDCD4 and miR-21 serve an important role in renal cancer. Thus, increasing PDCD4 expression or inhibiting miR-21 expression may constitute effective novel therapeutic strategies for the treatment of renal cancer.

MicroRNA-124 (MiR-124) Inhibits Cell Proliferation, Metastasis and Invasion in Colorectal Cancer by Downregulating Rho-Associated Protein Kinase 1(ROCK1).

BACKGROUND/AIMS: MiR-124 inhibits neoplastic transformation, cell proliferation, and metastasis and downregulates Rho-associated protein kinase (ROCK1) in Colorectal Cancer (CRC). The aim of this study was to further investigate the roles and interactions of ROCK1 and miR-124 and the effects of knockdown of ROCK1and MiR-124 in human Colorectal Cancer (CRC). METHODS: Three Colorectal cancer cell lines (HCT116, HT29 and SW620) and one Human Colonic Mucosa Epithelial cell line (NCM460) were studied. The protein expression of ROCK1 was examined by Western-blot and qRT-PCR were performed to examine the expression levels of ROCK1 mRNA and miR-124. Furthermore, We performed transfection of cancer cell line (SW620) with pre-miR-124(mimics), anti-miR-124(inhibitor), ROCK1 siRNA and the control, then observed the affects of ROCK1 protein expression by westen-blot, cell proliferation by EDU (5-ethynyl-2'deoxyuridine assay) and expression levels of ROCK1mRNA by qRT-PCR . A soft agar formation assay, Migration and invasion assays were used to determine the effect of regulation of miR-124 and ROCK1, and survivin on the transformation and invasion capability of colorectal cancer cell. RESULTS: MiR-124 expression was significantly downregulated in CRC cell lines compare to normal (P < 0.05). In contrast, ROCK1 protein expression was significantly increased in CRC cell lines compared to the normal (P < 0.05), whereas the gene (ROCK1mRNA) expression remained unaltered (P > 0.05). ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (P < 0.05). Cell proliferation, transformation and invasion of cells transfected with miR-124 inhibitor were significantly increased compared to those in normal controls (P<0.05). However, cell proliferation, transformation and invasion of cells transfected with ROCK1 siRNA were significantly decreased compared to control (P < 0.05). CONCLUSIONS: In conclusion, our results demonstrated that miR-124 not only promoted cancer cell hyperplasia and significantly associated with CRC metastasis and progression, but also downregulated ROCK1 protein expression. More importantly, increased ROCK1 expression or inhibited miR-124 expression may constitute effective new therapeutic strategies for the treatment of renal cancer in the future.

Variants on 8q24 and prostate cancer risk in Chinese population: a meta-analysis.

Previous studies have identified 8q24 as an important region to prostate cancer (PCa) susceptibility. The aim of this study was to investigate the role of six genetic variants on 8q24 (rs1447295, A; rs6983267, G; rs6983561, C; rs7837688, T; rs10090154, T and rs16901979, A) on PCa risk in Chinese population. Online electronic databases were searched to retrieve related articles concerning the association between 8q24 variants and PCa risk in men of Chinese population published between 2000 and 2014. Odds ratio (ORs) with its 95% correspondence interval (CI) were employed to assess the strength of association. Total eleven case-control studies were screened out, including 2624 PCa patients and 2438 healthy controls. Our results showed that three risk alleles of rs1447295 A (OR=1.35, 95% CI=1.19-1.53, P<0.00001), rs6983561 C (C vs. A: OR=1.41, 95% CI=1.21-1.63, P<0.00001) and rs10090154 T (T vs. C: OR=1.48, 95% CI=1.22-1.80, P<0.00001) on8q24 were significantly associated with PCa risk in Chinese population. Furthermore, genotypes of rs1447295, AA+AC; rs6983561, CC+AC and CC; rs10090154, TT+TC; and rs16901979, AA were associated with PCa as well (P<0.01). No association was found between rs6983267, rs7837688 and PCa risk. In conclusions, variants including rs1447295, rs6983561, rs10090154 and rs16901979 on 8q24 might be associated with PCa risk in Chinese population, indicating these four variations may contribute risk to this disease. This meta-analysis was the first study to assess the role of 8q24 variants on PCa risk in Chinese population.

[Efficacy of combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia with overactive bladder].

OBJECTIVE: To evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB). METHODS: We randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different RESULTS: Among the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse CONCLUSION: Combination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.

[Measurements of the concentration of atmospheric CO2 based on OP/FTIR method and infrared reflecting scanning Fourier transform spectrometry].

The present paper describes the observations and measurements of the infrared absorption spectra of CO2 on the Earth's surface with OP/FTIR method by employing a mid-infrared reflecting scanning Fourier transform spectrometry, which are the first results produced by the first prototype in China developed by the team of authors. This reflecting scanning Fourier transform spectrometry works in the spectral range 2 100-3 150 cm(-1) with a spectral resolution of 2 cm(-1). Method to measure the atmospheric molecules was described and mathematical proof and quantitative algorithms to retrieve molecular concentration were established. The related models were performed both by a direct method based on the Beer-Lambert Law and by a simulating-fitting method based on HITRAN database and the instrument functions. Concentrations of CO2 were retrieved by the two models. The results of observation and modeling analyses indicate that the concentrations have a distribution of 300-370 ppm, and show tendency that going with the variation of the environment they first decrease slowly and then increase rapidly during the observation period, and reached low points in the afternoon and during the sunset. The concentrations with measuring times retrieved by the direct method and by the simulating-fitting method agree with each other very well, with the correlation of all the data is up to 99.79%, and the relative error is no more than 2.00%. The precision for retrieving is relatively high. The results of this paper demonstrate that, in the field of detecting atmospheric compositions, OP/FTIR method performed by the Infrared reflecting scanning Fourier transform spectrometry is a feasible and effective technical approach, and either the direct method or the simulating-fitting method is capable of retrieving concentrations with high precision.

Relationship between PTEN and Livin expression and malignancy of renal cell carcinomas.

OBJECTIVES: This study focused on PTEN and Livin expression and associations with malignancy in human renal clear cell carcinomas (RCCC). METHODS: PTEN and Livin expression was assessed in 100 RCCC tissue samples, 50 paracarcinoma cases, and 20 normal renal tissue samples using the immunohistochemical Streptavidin proxidase (SP) method. The relationships between binding and corresponding biological characteristics, such as histological grade, lymph node metastases, and clinical stages were analyzed. RESULTS: Positive PTEN expression in RCCC was significantly lower than in renal tissue adjacent to carcinoma tissue and normal renal tissue (P<0.01). Livin expression in the renal tissue adjacent to the carcinoma and normal renal tissues exhibited only low levels, whereas overall Livin expression in RCCC was statistically significant (P<0.01). In RCCC, PTEN expression rate gradually decreased with an increase in clinical stage, whereas that of Livin increased to statistically significant levels (P<0.01), PTEN and Livin levels being negatively correlated (r=-0.395, P<0.01). CONCLUSIONS: PTEN and Livin are important in RCCC development. The two factors combined are expected to provide indices for estimating RCCC malignancy and progression levels, as well as references for RCCC diagnosis and treatment.

[Systematic reviews of mini-invasive surgery versus standard approaches for total knee arthroplasty].

OBJECTIVE: To conduct a systematic review to compare the early efficacies of minimally invasive surgery (MIS) versus conventional approaches in TKA (total knee arthroplasty). METHODS: Randomized controlled trials (RCTs) and clinical controlled trials (CCTs) were retrieved from the databases of MEDLINE (1996.6 - 2010.12), EMBASE (1996.6 - 2010.12), PubMed (1996 - 2010.12) and Cochrane Library (Issue 2, 2012). Journal of Orthopedics (from establishment to December 2010) and Orthopedic Journal of China (from establishment to December 2010) were manually searched. Both RCTs and CCTs were included. The data were extracted by two reviewers with designed extraction form RevMan 4.2.8 software for data analysis. The criteria were as follows: (1) operative duration and reduced blood loss; (2) VAS (visual analog scale) score; (3) faster recovery of ROM (range of movement); (4) quadriceps muscle strength; (5) component positioning malalignment; (6) tibiofemoral angle; (7) rate of complications. RESULTS: A total of 18 RCTs were included. Compared with the standard TKA procedure, the MIS group had a longer operative duration (WMD (weighted mean difference) 14.16, 95%CI (confidence interval) (12.61, 15.71)); reduced blood loss (WMD 8.31, 95%CI (6.16, 10.46)); lower VAS score at Days 3-5 post-operation (WMD 4.99, 95%CI (4.19, 5.78)); better Mean Knee Society scores at Week 6 post-operation (WMD 4.99, 95%CI (4.19, 5.78)), improvement in ROM occurred more rapidly at Month 3 post-TKA (WMD 14.59, 95%CI (8.39, 20.80)). Although the differences were not statistically significant, tibiofemoral angle was more precise in the standard group and the rate of component malalignment occurred more frequently in the MIS group (WMD 0.20, 95%CI (-0.12, 0.52)) (RR 1.57, 95%CI (0.88, 2.83)). CONCLUSION: MIS leads to a faster recovery than conventional surgery with a shorter operative duration, a reduced blood loss, a lower VAS score and a faster recovery of ROM and quadriceps muscle strength. However, the rates of component malalignment and complications occur more frequently in the MIS group. Potential benefits in long-term survival rate and functional improvement require further investigations.

Quantitation of HBV covalently closed circular DNA in micro formalin fixed paraffin-embedded liver tissue using rolling circle amplification in combination with real-time PCR.

BACKGROUND: The study aimed to develop an effective method to quantitate HBV covalently closed circular DNA (cccDNA) using small section of formalin fixed paraffin-embedded (FFPE) liver biopsy. METHODS: Plasmid-safe ATP-dependent DNase (PSAD)-treated samples were subjected to rolling circle amplification (RCA) prior to real-time PCR mediated by cccDNA-selective primers. Human beta-actin gene was used as a reference control. RESULTS: Compared to the classical method, i.e., PSAD digestion+real-time PCR, introduction of RCA increased the lower limit of detection for about 2 logs with good inter- and intra-assay reproducibility. HBV cccDNA was detected in 91.5% (119/130) of the FFPE samples. The cccDNA levels (copy/cell) between FFPE liver tissues and fresh frozen counterpart tissues were comparable. The median of cccDNA level in HBeAg-positive patients was higher than that in HBeAg-negative ones (52.60 vs. 31.25copies/cell, P<0.01). Intrahepatic cccDNA level was positively correlated with intrahepatic HBV total DNA level, but not obviously correlated with serum HBV DNA or alanine aminotransferase levels. CONCLUSIONS: The method could sensitively and specifically quantitate intrahepatic HBV cccDNA in micro FFPE liver biopsy tissue for evaluation of HBV replication status in the liver.

Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure.

OBJECTIVE: To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features. PATIENTS AND METHODS: Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54-1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant. CONCLUSIONS: Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.