Immune Checkpoint Inhibitor-Associated Systemic Sclerosis in the Treatment of a Small Cell Lung Cancer Patient with Durvalumab: A Case Report.

As one of the key cancer treatment measures, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of various cancers, including malignancies previously thought to be untreatable. Immune checkpoint inhibitors work by targeting the dysfunctional immune system, to enhance cancer-cell killing by CD8-positive T cells. Despite the beneficial effects of ICIs, these treatments are also linked to a novel class of side effects, termed immune-related adverse events (irAEs). Immune-related adverse events can affect multiple organ systems, such as endocrine, neurological, gastroenteric, dermatologic, ocular, hepatic, renal, and rheumatic ones. While variable in severity, irAEs can be associated with significant morbidity, mortality, cessation of ICI treatment and can be potentially life-threatening sometimes. Among varieties of irAEs, dermatological manifestations are frequently reported, since they can be easily observed. Here, we present a case of a 74-year-old patient with widespread fibrosis of skin, eventually diagnosed as diffuse cutaneous systemic sclerosis after the treatment with durvalumab for small cell lung cancer (SCLC). Prompt recognition and treatment of immune-checkpoint inhibitors-associated systemic sclerosis may help enhance tolerance to ICIs and ensure better performance in treating tumors.

Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis.

Background: Necroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown. Methods: The data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes. Results: Necroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs. Conclusion: Our study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.

Construction and Validation of a m7G-Related Gene-Based Prognostic Model for Gastric Cancer.

Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. Chinese cases of GC account for about 40% of the global rate, with approximately 1.66 million people succumbing to the disease each year. Despite the progress made in the treatment of GC, most patients are diagnosed at an advanced stage due to the lack of obvious clinical symptoms in the early stages of GC, and their prognosis is still very poor. The m7G modification is one of the most common forms of base modification in post-transcriptional regulation, and it is widely distributed in the 5' cap region of tRNA, rRNA, and eukaryotic mRNA. Methods: RNA sequencing data of GC were downloaded from The Cancer Genome Atlas. The differentially expressed m7G-related genes in normal and tumour tissues were determined, and the expression and prognostic value of m7G-related genes were systematically analysed. We then built models using the selected m7G-related genes with the help of machine learning methods.The model was then validated for prognostic value by combining the receiver operating characteristic curve (ROC) and forest plots. The model was then validated on an external dataset. Finally, quantitative real-time PCR (qPCR) was performed to detect gene expression levels in clinical gastric cancer and paraneoplastic tissue. Results: The model is able to determine the prognosis of GC samples quantitatively and accurately. The ROC analysis of model has an AUC of 0.761 and 0.714 for the 3-year overall survival (OS) in the training and validation sets, respectively. We determined a correlation between risk scores and immune cell infiltration and concluded that immune cell infiltration affects the prognosis of GC patients. NUDT10, METTL1, NUDT4, GEMIN5, EIF4E1B, and DCPS were identified as prognostic hub genes and potential therapeutic agents were identified based on these genes. Conclusion: The m7G-related gene-based prognostic model showed good prognostic discrimination. Understanding how m7G modification affect the infiltration of the tumor microenvironment (TME) cells will enable us to better understand the TME's anti-tumor immune response, and hopefully guide more effective immunotherapy methods.

Optimization of extraction technology of Guizhi shaoyao zhimu decoction / 中国药房

OBJECTIVE To optimize the e xtraction technology of Guizhi shaoyao zhimu decoction （GSZD）. METHODS The contents of 9 components in GSZD were determined by HPLC ，such as ephedrine hydrochloride ，pseudoephedrine hydrochloride ， mangiferin，paeoniflorin，liquiritin，5-O-methylvisammioside，glycyrrhizic acid ，cinnamic acid ，6-gingerol. On the basis of single factor experiment ，taking material-liquid ratio ，extraction times and extraction time as inspection factors ，taking the contents of above 9 components and the yield of dry extract as evaluation indicators ，the analytic hierarchy process and entropy weight method were used to determine the composite weight of each index and calculate the comprehensive score ；the extraction technology parameters of GSZD were optimized by Box-Behnken response surface method ，and the validation tests were conducted. RESULTS The composite weight of the contents of ephedrine hydrochloride ，pseudoephedrine hydrochloride ，mangiferin，paeoniflorin， glycyrrhizin，5-O-methylvisa- midol ，glycyrrhizinate，cinnamic acid ，6-gingerol and the yield of dry extract were respectively 0.12，0.10，0.05，0.12，0.14，0.06，0.13，0.15，0.10，0.03. The optimal extraction technology of GSZD is that the ratio of material to liquid is 1 ∶ 14（g/mL），extraction is 2 times，and the extraction time is 3.0 h；average comprehensive score of the 3 verification tests was 95.879，and RSD was 0.50％（n＝3），the deviation from the predicted comprehensive score （94.328）was 1.64％. CONCLUSIONS In this study ，the optimal extraction technology of GSZD is determined.

Dental expenditure, progressivity and horizontal inequality in Chinese adults: based on the 4th National Oral Health Epidemiology Survey.

BACKGROUND: The financial burden of oral diseases is a growing concern as the medical expenses rise worldwide. The aim of this study was to investigate the dental expenditure, analyze its progressivity and horizontal inequality under the general health finance and insurance system, and identify the key social determinants of the inequality for Chinese adults. METHODS: A secondary analysis used the data of 13,464 adults from the 4th National Oral Health Epidemiological Survey (NOHES) in China was undertaken. The dental expenditure was collected and divided into out-of-pocket and health insurance payments. Horizontal inequality index and Kakwani index were used to analyze the horizontal inequality and progressivity, respectively. The decomposition model of the concentration index was set up to explore the associated socioeconomic determinants. RESULTS: The results showed that a mean dental expenditure per capita of Chinese adults was $20.55 (95% Confidence Interval-CI: 18.83,22.26). Among those who actually used dental service, the cost was $100.95 (95%CI: 93.22,108.68). Over 90% of dental spending was due to out-of-pocket expenses. For self-reported oral health, the horizontal inequality index was - 0.1391 and for the decayed tooth (DT), it was - 0.2252. For out-of-pocket payment, the Kakwani index was - 0.3154 and for health insurance payment it was - 0.1598. Income, residential location, educational attainment, oral hygiene practice, self-reported oral health, age difference were the main contributors to the inequality of dental expenditure. CONCLUSION: Dental expenditure for Chinese adults was at a lower level due to underutilization. The ratio of payments of dental expenditure and utilization was disproportional, whether it was out-of-pocket or insurance payment. Individuals who were more in need of oral care showed less demand for service or not required service in time. For future policy making on oral health, it is worth the effort to further promote the awareness of the importance of oral health and utilization of dental service.

Volar, Splitting, and Collapsed Type of Die-Punch Fracture Treated by Volar Locking Plate (VLP): A Retrospective Study.

OBJECTIVE: To compare the results of different types of die-punch fractures treated by volar locking plate (VLP). METHODS: Between January 2013 and February 2018, a total of 71 patients with die-punch fracture of distal radius were treated by VLP and their medical records were retrospectively reviewed. Of them, 18 were classified as volar type, 24 as splitting type, and 28 as collapsed type of fracture, based on the preoperative radiographs and CT scans. The minimum follow-up period was 12 months. Radiological parameters, wrist function, range of motion (ROM), and complications were evaluated and compared. Pearson chi-square test was used to assess the difference of gender distribution, injury side, dominance, mechanism, type and classification of fracture, and postoperative complications, when necessary (P < 0.05), followed by pairwise comparisons using partitions of chi-square test. Two-tailed P value <0.05 was considered as statistically significant. For pairwise comparisons, adjustment of statistical level as P < 0.017 (0.05/3) was used. SPSS 21.0 was used to perform all the analyses. RESULTS: The mean follow-up time was 14.5 months, and at the mean of postoperative 8 weeks all patients obtained bony union, without delayed or non-union. The grip strength was 26.6 ± 7.9 kg for patients in volar fracture group, 27.0 ± 9.4 kg in splitting group, and 26.2 ± 9.4 kg in collapsed group, without significant difference (P = 0.628).The disabilities of the arm, shoulder, and hand (DASH) (9.2 ± 10.0 for volar group, 8.8 ± 7.9 for splitting group, and 10.6 ± 8.7 for collapsed group) or Gartland-Werley score (5.1 ± 2.8 for volar group, 4.8 ± 3.2 for splitting group, and 6.4 ± 2.7 for collapsed group) either did not differ among the three groups (all P > 0.05). There was a poorer ROM in the group of collapsed fractures, but the difference was non-significant for any parameter (P > 0.05). As for radiographic parameters, we did not find any significant difference for volar tilt, radial inclination, radial height, and ulnar variance (all P > 0.05), except for articular step-off (P < 0.001). Pairwise comparisons showed a significantly greater step-off (1.2 mm vs 0.4 mm, 0.5 mm) and higher rate of total complications in group of collapsed fracture (39.3%), compared to either volar (10.5%) or splitting type (12.5%). CONCLUSIONS: The collapsed type of die-punch fracture posed a greater articular step-off and a higher rate of complications, especially secondary wrist osteoarthritis, which deserved more attention in clinical treatment.

Frequency and longitudinal clinical outcomes of Alzheimer's AT(N) biomarker profiles: A longitudinal study.

INTRODUCTION: We aimed to estimate the frequency of each AT(N) (ß-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.

Platelet-rich plasma injection for the treatment of chronic Achilles tendinopathy: A meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) is used as an alternative therapy to reduce pain and improve functional restoration in patients with Achilles tendinopathy (AT). We evaluated the current evidence for the efficacy of PRP as a treatment for chronic AT. METHODS: The PubMed, Embase, Web of Science, and The Cochrane Library databases were searched for articles on randomized controlled trials (RCTs) that compared the efficacy of PRP with that of with placebo injections plus eccentric training as treatment for AT. The articles were uploaded over the establishment of the databases to May 01, 2018. The Cochrane risk of bias (ROB) tool was used to assess methodological quality. Outcome measurements included the Victorian Institute of Sports Assessment-Achilles (VISA-A), visual analog scale (VAS) and Achilles tendon thickness. Statistical analysis was performed with RevMan 5.3.5 software. RESULTS: Five RCTs (n = 189) were included in this meta-analysis. Significant differences in the VISA-A were not observed between the PRP and placebo groups after 12 weeks [standardized mean difference (SMD) = 0.2, 95% confidence interval (95% CI): 0.36 to 0.76, I = 71%], 24 weeks (SMD = 0.77, 95% CI: -0.10-1.65, I = 85%) and 1 year (SMD = 0.83, 95% CI: -0.76-2.42, I = 72%) of treatment. However, PRP exhibited better efficacy than the placebo treatment after 6 weeks (SMD = 0.46, 95% CI: 0.15-0.77, I = 34%). Two studies included VAS scores and tendon thickness. VAS scores after 6 weeks (SMD = 1.35, 95% CI: -0.1.04-3.74, I = 93%) and 24 weeks (SMD = 1.48, 95% CI: -0.1.59-4.55, I = 95%) were not significantly different. However, VAS scores at the 12th week (SMD = 1.10, 95% CI: 0.53-1.68, I = 83%) and tendon thickness (SMD = 1.51, 95% CI: 0.39-2.63, I = 53%) were significantly different. CONCLUSION: PRP injection around the Achilles tendon is an option for the treatment of chronic AT. Limited evidence supports the conclusion that PRP is not superior to placebo treatment. These results still require verification by a large number of well designed, heterogeneous RCT studies.

Relationship of learning burnout and subjective well-being of military medical university students and the mediating role of psychological capital / 第二军医大学学报

Objective To explore the effect of learning burnout on subjective well-being of military medical university students and the mediating role of psychological capital. Methods The learning burnout questionnaire, well-being scale and psychological capital scale were used to survey 796 military medical university students. The correlation of subjective well-being and psychological capital with learning bornout was analyzed. A intermediary function equation was established and the mediating effect of psychological capital was tested. Results The subjective well-being score of military medical university students was 4.42±0.77, psychological capital scale score was 4.48±0.67, and learning burnout score was 2.45±0.69. The subjective well-being, psychological capital and learning burnout scores were different among different grades, the subjective well-being scale and psychological capital scale scores of freshmen were significantly higher, and the learning burnout score was significantly lower than those of the junior students (tsubjective well-being=12.45, P<0.01; tpsychological capital=6.01, P<0.01; and tlearning burnout=-13.96, P<0.01). The learning burnout was negatively related to the subjective well-being and the psychological capital (r=-0.539, P<0.01, and r=-0.721, P<0.01). The psychological capital was positively related to the subjective well-being (r=0.596, P<0.01). The psychological capital had a partial mediating effect between learning burnout and subjective well-being, and the proportion of the mediating effect of total effect was 57.90%. Conclusion The subjective well-being not only can directly predict learning burnout of the students in military medical universities, but also indirectly predict the learning burnout through psychological capital. Improving subjective well-being of military medical university students is helpful for alleviating the learning burnout, and the mediating role of psychological capital should be emphasized at the same time.

Training approaches of data literacy for teachers, undergraduates, scientific researchers and librarians / 中华医学图书情报杂志

After the connotation of data literacy was elaborated, the status quo of domestic and foreign data literacy education was described, the training approaches of data literacy for teachers, undergraduates, scientific researchers and librarians were analyzed, and their characteristics and differences were compared in order to provide reference and lessons for building the data literacy education system and implementing the data literacy education.

Domestic and foreign hospital assessment systems and their problems / 中华医学图书情报杂志

The aims, indexes, methods, results, data sources, advantages and disadvantages of 12 domestic and foreign hospital assessment systems were analyzed and the problems in current hospital assessment were described in order to provide reference and lessons for perfecting the domestic hospital assessment systems.

Domestic and foreign hospital assessment systems and their problems / 中华医学图书情报杂志

The aims, indexes, methods, results, data sources, advantages and disadvantages of 12 domestic and foreign hospital assessment systems were analyzed and the problems in current hospital assessment were described in order to provide reference and lessons for perfecting the domestic hospital assessment systems.

Comparison of AO Titanium Locking Plate and Screw Fixation versus Anterograde Intramedullary Fixation for Isolated Unstable Metacarpal and Phalangeal Fractures.

OBJECTIVE: This study aimed to compare the clinical and radiologic outcomes of AO titanium locking plate and screw (ATLPS) and anterograde intramedullary (AIM) fixation for treating unstable metacarpal and phalangeal fractures. METHODS: Adult patients with isolated fresh unstable metacarpal and phalangeal fractures who met the inclusion criteria were enrolled into this prospective study from July 2013. Patients were divided into ATLPS or AIM groups when they were admitted to our department after considering their work requirement, fracture complexity, and surgeon's experience and were then treated accordingly. Relevant demographic, clinical and preoperative clinical data were collected and analyzed. Clinical examination and radiograph evaluation were performed 1 week and 1, 3, and 6 months postoperatively. Outcome measures were visual analog scale (VAS) scores for pain, total range of motion (ROM) of the injured digit, Quick Disabilities of the Arm, Shoulder, and Hand scores (Quick-DASH) and grip strength (percentage of the contralateral corresponding digit). RESULTS: From July 2013 to September 2014, 76 patients were treated by AIM and 71 by ATLPS. Age, sex, time from injury to operation, dominant hand, injury mechanism, fracture location, fracture type and participant occupation were similar in both groups (P > 0.05). Operations were all performed well and followed by uneventful postoperative functional recoveries. At 3-month follow-up, all clinical outcomes were significantly better in the AIM than ATLPS group ( P < 0.05) except for VAS pain scores. However, at 6-month follow-up, the differences were no longer significant, indicating similar results for both types of fixation. Patients in the AIM group developed significantly more complications ( P = 0.037). Sick leave was significantly longer in the AIM group ( P = 0.02). CONCLUSIONS: AIM outperforms ATLPS in the treatment of unstable metacarpal and phalangeal fractures in the early, but not the later, postoperative period; the latter is associated with significantly more complications. Patients treated by ATLPS require shorter sick leave, which is of particular benefit to workers with specialized manual skills.

Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study.

BACKGROUND: Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes. METHODS: We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients. RESULTS: Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (ß = 0.364, P = 0.001) and maximum pressure (ß = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (ß = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (ß = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (ß = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (ß = 0.244, P = 0.014), and calluses over the course of the study. CONCLUSIONS: We should pay attention to the BMI, HbA1c, cholesterol, ABI, SCV, and NSS changes in the process of preventing high plantar pressure and ulceration. Some associated precautions may be taken with the appearance of infections, blisters, and calluses.

[Study on Extraction Methods of Characteristic Wavelength of Visible Near Infrared Spectroscopy Used for Sugar Content of Hetao Muskmelon].

Hetao muskmelon is a unique fruit in the hetao area of northwest china, which has been loved by consumers. Sugar content is the important indicator of measuring the quality and mature of muskmelons. This research uses Maya 2000 pro portable spectrometer and PR-101α portable digital refractometer to get spectrum and sugar content values of "jinhongbao" muskmelon, researches the effect of different extraction methods of characteristic wavelength (stepwise multiple linear regression (SMLR), interval partial least squares(iPLS), backward interval partial least squares (biPLS) and synergy interval partial least squares (siPLS)) on model accuracy and prediction results. The results show: using biPLS method on extraction of characteristic wavelength will the full spectrum evenly divided into 20 subintervals, the PLS factors of 14, when removing 8 subintervals, and choosing the wavelength variable numbers of 218, getting the biPLS model is best, RMSE of corresponding calibration and prediction models is 0.9961 and 1.18. So using the biPLS method of extraction on spectrum wavelength could extract effectively the characteristic wavelengths of melon sugar content, increase the ability of model prediction, and achieve rapid detecting of sugar content about muskmelons.

Contactin 1: A potential therapeutic target and biomarker in gastric cancer.

Despite advances in diagnosis and treatment, gastric cancer remains one of the most common malignant tumors worldwide, and early diagnosis remains a challenge. The lack of effective methods to detect these tumors early is a major factor contributing to the high mortality in patients with gastric cancer, who are typically diagnosed at an advanced stage. Additionally, the early detection of metastases and the curative treatment of gastric cancer are difficult to achieve, and the detailed mechanisms remain to be fully elucidated. Thus, the identification of valuable predictive biomarkers and therapeutic targets to improve the prognosis of patients with gastric cancer is becoming increasingly important. Contactin 1 (CNTN1), a cell adhesion molecule, is a glycosylphosphatidylinositol-anchored neuronal membrane protein that plays an important role in cancer progression. The expression of CNTN1 is upregulated in primary lesions, and its expression level correlates with tumor metastasis in cancer patients. The current evidence reveals that the functions of CNTN1 in the development and progression of cancer likely promote the invasion and metastasis of cancer cells via the VEGFC/FLT4 axis, the RHOA-dependent pathway, the Notch signaling pathway and the epithelial-mesenchymal transition progression. Therefore, CNTN1 may be a novel biomarker and a possible therapeutic target in cancer treatment in the near future.

MiR­214 promotes osteosarcoma tumor growth and metastasis by decreasing the expression of PTEN.

MicroRNAs (miRNAs) are a class of small non­coding RNAs, which function as critical gene regulators by targeting mRNAs for translational repression or degradation, and they are essential in cancer development and progression. Several previous studies have indicated that abnormal expression of miRNAs occurs frequently in human osteosarcoma (OS) tissues compared with that of adjacent normal tissues. In the present study, the role of miR­214 in the progression and metastasis of OS was investigated. The expression of miR­214 was frequently increased in OS tissues and cell lines. Inhibition of miR­214 in OS cell lines markedly suppressed cell proliferation, migration and invasion. Phosphatase and tensin homolog (PTEN) was identified as a direct target of miR­214, and ectopic expression of miR­214 inhibited PTEN by directly binding to its 3'­untranslated region. The expression of miR­214 negatively correlated with PTEN in OS tissues. Together, these data indicated that miR­214 acts as an oncogenic miRNA and may contribute to the progression, and metastasis of OS, suggesting that miR­214 may be a potential novel diagnostic and therapeutic target of OS.

Significances of contactin-1 expression in human gastric cancer and knockdown of contactin-1 expression inhibits invasion and metastasis of MKN45 gastric cancer cells.

PURPOSE: Contactin-1 (CNTN-1) has been shown to promote cancer metastasis. Previously, we have reported that the expression of CNTN-1 was upregulated in gastric cancer tissues compared with adjacent normal tissues. Here, we investigated the significance of CNTN-1 expression and its underlying mechanism of metastasis mediated by epithelial-mesenchymal transition (EMT) in gastric cancer. METHODS: The expressions of CNTN-1 and EMT-related proteins were assayed through immunohistochemical staining of pathological specimens from patients with gastric cancer. Other methods including reverse transcriptase polymerase chain reaction, Western blotting, stably transfected against CNTN-1 into MKN45 cells, migration and invasion assays in vitro and nude mouse tumorigenicity in vivo were also utilized. RESULTS: The results revealed that CNTN-1 expression was elevated and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with gastric cancer. Moreover, CNTN-1 expression might associate with invasive ability to some extent in gastric cancer cell lines KATO-Ш, SGC7901 and MKN45. Knockdown of CNTN-1 expression in MKN45 cells using short hairpin RNA (shRNA) had notable effects on cell migration and invasion, rather than proliferation in vitro and in vivo. Furthermore, suppression of CNTN-1 expression altered EMT through inhibition of transcription factor Slug, rather than Snail. CONCLUSION: Our study demonstrated that the elevated CNTN-1 expression closely correlated with cancer metastasis and patient survival, and its functions seemed to be important in migration and invasion of gastric cancer cells via EMT alteration probably mediated by inhibition of Slug. CNTN-1 may be a potential therapeutic target for gastric cancer.

Effects of Kupffer cell inactivation on graft survival and liver regeneration after partial liver transplantation in rats.

BACKGROUND: Gadolinium chloride (GdCl3) selectively inactivates Kupffer cells and protects against ischemia/reperfusion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplantation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process. METHODS: PLTx (30% partial liver transplantation) was performed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regeneration by PCNA staining and BrdU uptake, apoptosis by TUNEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting. RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine aminotransferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overexpression and STAT3 phosphorylation after PLTx in graft tissues. CONCLUSION: Kupffer cells may contribute to the liver regeneration after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.