[Estimation of COVID-19 incidence in Shanghai under optimized epidemic prevention and control strategies].

Objective: To quantitatively estimate the incidence of COVID-19 in different backgrounds, including vaccination coverage, non-pharmacological interventions (NPIs) measures, home quarantine willingness and international arrivals, and the demands of healthcare resource in Shanghai in the context of optimized epidemic prevention and control strategies. Methods: Based on the natural history of 2019-nCoV, local vaccination coverage and NPI performance, an age-structured Susceptible-Exposed-Infections-Removed (SEIR) epidemic dynamic model was established for the estimation of the incidence of COVID-19 and demand of hospital beds in Shanghai by using the data on December 1, 2022 as the basis. Results: Based on current vaccination coverage, it is estimated that 180 184 COVID-19 cases would need treatment in hospitals in Shanghai within 100 days. When the booster vaccination coverage reaches an ideal level, the number of the cases needing hospitalization would decrease by 73.20%. School closure or school closure plus workplace closure could reduce the peak demand of regular beds by 24.04% or 37.73%, respectively, compared with the situation without NPI. Increased willingness of home quarantine could reduce the number of daily new cases and delay incidence peak of COVID-19. The number of international arrivals has little impact on the development of the epidemic. Conclusions: According to the epidemiological characteristics of COVID-19 and the actual situation of vaccination in Shanghai, the incidence of COVID-19 and health resource demand might be reduced by increasing vaccination coverage and early implementation of NPI.

[Observational study on perioperative outcomes of pelvic exenteration].

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.

Broadband photoresponse arising from photo-bolometric effect in quasi-one-dimensional Ta2Ni3Se8.

In this paper, we report the synthesis of high-quality Ta2Ni3Se8crystals free of noble or toxic elements and the fabrication and testing of photodetectors on the wire samples. A broadband photoresponse from 405 nm to 1550 nm is observed, along with performance parameters including relatively high photoresponsivity (10 mA W-1) and specific detectivity (3.5 × 107Jones) and comparably short response time (τrise= 433 ms,τdecay= 372 ms) for 1064 nm, 0.5 V bias and 1.352 mW mm-2. Through extensive measurement and analysis, it is determined that the dominant mechanism for photocurrent generation is the photo-bolometric effect, which is believed to be responsible for the very broad spectral detection capability. More importantly, the pronounced response to 1310 nm and 1550 nm wavelengths manifests its promising applications in optical communications. Considering the quasi-one-dimensional structure with layered texture, the potential to build nanodevices on Ta2Ni3Se8makes it even more important in future electronic and optoelectronic applications.

[A model analysis on the knowledge-attitude-practice of children guardians in Jiangxi, Shanghai and Qinghai].

Objective: To understand the knowledge attitude and practice (KAP) on vaccination among children's parents in Jiangxi, Shanghai, and Qinghai and explore the factors influencing KAP. Methods: The study selected two counties/districts in Jiangxi, Shanghai, and Qinghai, respectively, by stratified sampling and used a unified questionnaire to investigate the parental KAP of vaccination. A structural equation model (SEM) was used to explore factors influencing parental KAP, as well as the relationship between knowledge and behavior. Results: Of the 760 valid questionnaires, the knowledge of vaccination among children's parents was better, and the vaccination knowledge of parents in Qinghai and Shanghai were slightly better than those in Jiangxi. Parents mainly obtained vaccination knowledge through medical staff and vaccination manuals. The fitting degree of SEM was relatively good; the root mean square error of approximation of the model is 0.033. The higher the parents' education level, the better their knowledge of vaccination (ß̂=0.082). Parental vaccination knowledge could influence whether the vaccinated children stay for half an hour in the clinics (ß̂=0.541). It could also impact whether parents giving up vaccinating their children in the face of media reports about the adverse effects of vaccinations (ß̂=0.515). Conclusions: The knowledge of vaccination among the parents in Jiangxi, Shanghai, and Qinghai was quite good. Moreover, we should pay more attention to the mass media programs and vaccination knowledge among parents with low or middle education backgrounds. Vaccination knowledge can be disseminated through medical staff, vaccination manuals, or mobile applications.

[Research and application of assessment tools for Residents' Nutrition Literacy].

Nutrition literacy is an important part of health literacy, as well as an significant factor to enhance the quality of population, improving the nutritional status of residents and preventing nutrition-related diseases. In 2010, China developed an evaluation tool for health literacy and began to monitor residents' health literacy. So far, eight national surveys on health literacy have been completed, providing an important basis for health promotion intervention strategies and related policies. However, in health literacy evaluation system, there is neither evaluation content of nutrition literacy, nor evaluation tools. In order to achieve the goals of "national nutrition plan (2017-2030)"and evaluate the implementation effect, it is urgent to carry out the assessment and monitoring of nutrition literacy. According to the nutritional characteristics of different populaitons, this research organizes national experts in related fields, following the principles of scientificity, conciseness and generality and through the scientific formulation procedures to construct the nutrition literacy assessment tools for different populations. This assessment tool can enhance the pertinence and scientificity of nutrition education and improve nutrition development strategy. The establishment of the nutrition literacy assessment tool is the premise of gradually establishing the nutrition literacy assessment system of the residents, and also lays a solid foundation for further conducting the national nutrition literacy evaluation work.

[Establishment of nutrition literacy core items for Chinese people].

Objective: To establish core items of nutrition literacy for general population in China. Methods: The framework system and preliminary items of nutrition literacy were established through literature review and experts' consultation. Content validity test was used to determine the nutrition literacy item. Thirteen experts in the field of human nutrition, health education and nutrition and diseases were invited to score the importance of each nutrition literacy item via Email. The judgment basis and familiarity of experts towards the items, active coefficient, and content validity were analyzed to generate the final list of nutrition literacy items. Results: 92.3% of questionnaires in two rounds were collected.The active coefficient of experts was satisfied and the authority coefficient was 0.96.In the content validity evaluation, the correlation I-CVI value of each item was above 0.83 and the κ value was above 0.74. The evaluation result was excellent.After the second round of expert consultation, all selected items met the inclusion criteria. We identified the final list of nutrition literacy items consisting of three scales (knowledge and concepts, lifestyles and dietary behaviors, and basic skills), ten subscales (basic nutrition philosophy, food classification and nutrition knowledge, healthy weight, eating behavior and culture, balanced diet, exercise health, food assessment, nutrition information acquisition and decision, nutrition safety, and weight management)with 25 items in total. Conclusions: The framework system and core items of nutrition literacy are established for Chinese people based on the content validity evaluation. The experts involved in the consultation process present a performance with good representativeness, enthusiasm and authority, and the content validity evaluation result is satisfied.

[Influence of dietary patterns on type 2 diabetes mellitus in local residents aged 40 years and above in Songjiang district, Shanghai].

Objective: To evaluate the association between dietary pattern and type 2 diabetes mellitus (T2DM) in local residents aged 40 years and above in Songjiang district of Shanghai. Methods: Data was obtained from the baseline investigation of Shanghai Peak-Plan cohort. According to inclusion and exclusion criteria, we selected people with T2DM as the case group, and people without T2DM as controls, matched with gender, age and alcohol intake status. Dietary patterns were established by factor analysis. Conditional logistic regression model (CLRM) was used to explore the relationship between different dietary patterns and T2DM, as well as the association between multiplicative interactions of dietary patterns and T2DM. Results: We used factor analysis to obtain six dietary patterns: including meat, desserts-coarse cereals, condiment-egg, beverage, cereals-tubers and fruit-vegetable. Data from multivariate condition logistic regression suggested that condiment-egg patterns as (OR=0.543, 95%CI: 0.377-0.781), beverage (OR=0.590, 95%CI: 0.409-0.852), cereals-tubers (OR=0.592, 95%CI: 0.414-0.848), fruit-vegetable (OR=0.604, 95%CI: 0.417-0.876) were associated with the reduced risks for T2DM. After analyzing the multiplicative interactions between dietary patterns, there were three interaction items associated with T2DM with statistical significances: the multiplicative interaction between meat pattern and condiments-egg pattern was related with the increased risk for T2MD, and the multiplicative interactions between cereal-tubers pattern, meat pattern between cereal-tubers pattern and fruit-vegetable pattern were related with the reduced risks for T2MD. Conclusions: In the six dietary pattern under study, cereals-tubers pattern undwr studly, fruit-vegetable pattern might be more practical in preventing T2DM. In addition, the dietary pattern with cereals and potatos as the main ingredients, appropriate meat and reduced condiment intake might also play positive roles in reducing the risk for T2DM.

MiR-29 inhibits neuronal apoptosis in rats with cerebral infarction through regulating Akt signaling pathway.

OBJECTIVE: The aim of this study was to explore the influence of micro ribonucleic acid (miR)-29 on neuronal apoptosis in rats with cerebral infarction by regulating the protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: Sham group (n=12), Model group (n=12), and Inhibitor group (n=12). Common carotid artery, external carotid artery, and internal carotid artery were only exposed in the Sham group. However, the ischemia-reperfusion model was established by the suture method in the other two groups. After modeling, artificial cerebrospinal fluid was injected into the lateral ventricle in the rats of the Sham and Model groups. Similarly, miR-29 inhibitor was injected into the lateral ventricle in the rats of the Inhibitor group. At 24 h postoperatively, the sampling was performed. Zea-Longa score was used to evaluate the neurological deficit of rats. Meanwhile, the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in cerebral tissues were detected via immunohistochemistry. The protein expression levels of Akt and phosphorylated Akt (p-Akt) were determined using Western blotting. Furthermore, the expression of miR-29 and cell apoptosis were detected via quantitative Polymerase Chain Reaction (qPCR) and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. RESULTS: Compared with Sham group, Model, and Inhibitor groups had substantially raised the Zea-Longa scores (p<0.05). The Zea-Longa score in the Model group was markedly lower than that of the Inhibitor group (p<0.05). The positive expression level of Bax was remarkably upregulated (p<0.05). However, the positive expression level of Bcl-2 declined dramatically in both Model group and Inhibitor group when compared with the Sham group (p<0.05). Besides, the Model group exhibited significantly lower positive expression level of Bax and higher positive expression level of Bcl-2 than the Inhibitor group (p<0.05). The relative protein expression level of p-Akt markedly increased in the Model and Inhibitor groups when compared with the Sham group (p<0.05). However, it was considerably higher in the Model group than that of the Inhibitor group (p<0.05). In comparison with the Sham group, both Model group and Inhibitor group exerted substantially elevated expression level of miR-29 (p<0.05). The relative expression level of miR-29 in the Model group was significantly upregulated when compared with the Inhibitor group (p<0.05). The apoptosis rate of cells in both Model group and Inhibitor group was markedly higher than that of the Sham group (p<0.05). Furthermore, the Model group showed remarkably lower apoptosis rate than the Inhibitor group (p<0.05). CONCLUSIONS: MiR-29 inhibits neuronal apoptosis in cerebral infarction rats by upregulating the Akt signaling pathway, thereby serving as a protector.

Correction: Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Following publication of this article, the authors noted that the bands of Na-K ATPase in Figure S1B were mislabelled when selecting representative blots, and were erroneously duplicated from GluA2. However, the data analysis was still made with the correct immunoblots. The Supplementary Information file has now been updated to include the corrected Figure S1 with the correct western blot bands of Na-K ATPase.The authors would like to apologise for this error and the inconvenience this may have caused. This has been corrected in both the PDF and HTML versions of the article.

[Related factors of sarcopenia in hospitalized elderly patients with coronary heart disease].

Objective: To explore the incidence and clinical characteristics of sarcopenia in hospitalized elderly patients with coronary heart disease and search for the related factors. Methods: This study was a single-center observational study. According to the inclusion criteria, elderly patients hospitalized with coronary heart disease from Peking Union Medical College Hospital between December 2017 and December 2018 were enrolled. The patients were divided into sarcopenic group and non-sarcopenic group according to the diagnostic criteria of the Asian Working Group for Sarcopenia. Activities of daily living of the patients were assessed (including ADL and IADL) . Comorbidity of the patients was evaluated by the Charlson comorbidity index (CCI). Long-term medication use of the patients was recorded to assesse whether there was polypharmacy. The nutritional status of the patients was examined by the mini nutritional assessment-short form (MNA-SF). The full tandem stance time of the patients was evaluated. The history of falls over the previous year, urinary incontinence, and living conditions of the patients were also recorded. Multivariate logistic regression was used to analyze the related factors for sarcopenia of elderly patients with coronary heart disease. Results: A total of 364 patients were enrolled in the study. The patients were aged 65-96 (74.6±6.5) years and there were 218 (59.9%) male patients. There were 264 cases of stable coronary heart disease and 100 cases of acute coronary syndrome. The median number of long-term used medication was 7. One hundred and fifty-two (41.8%) patients were complicated with type 2 diabetes, 38 (10.4%) patients were complicated with anxiety/depression, and 98 (26.9%) patients had the history of falls over the previous year. Eighty-two (22.5%) patients were complicated with urinary incontinence, 12 patients (3.3%) were complicated with malnutrition and 33 patients (9.2%) were living alone. There were 81 (22.3%) sarcopenic patients and 283 (77.7%) non-sarcopenic patients among all the hospitalized elderly patients with coronary heart disease. The sarcopenic patients were more older, with lower body mass index(BMI)(both P<0.001), higher CCI and more long-term used medication (both P<0.05), higher proportions of malnutrition, urinary incontinence, history of falls, and living alone (all P<0.05) compared to non-sarcopenic patients. ADL and IADL scores of sarcopenic patients were significantly lower than those of non-sarcopenic patients (both P<0.001). There was also a higher proportion of unable to accomplish full tandem stance among sarcopenic patients compared to non-sarcopenic patients (P<0.001). Moreover, higher hs-CRP level (P=0.047) , lower albumin level (P=0.004) and significantly lower prealbumin level (P<0.001) were observed in sarcopenic patients compared to non-sarcopenic patients. Stepwise multivariate binomial logistic regression analysis revealed that male (OR=5.036, 95%CI 1.782-14.230, P=0.002), low BMI (OR=0.883, 95%CI 0.796-0.980, P=0.019), as well as low prealbumin level (OR=0.990, 95%CI 0.980-1.000, P=0.045) were related factors for sarcopenia among elderly patients with coronary heart disease. Conclusions: Sarcopenia is a geriatric condition commonly seen in hospitalized elderly patients with coronary heart disease. Male, low BMI, and low prealbumin level were the factors related to sarcopenia for older adults with coronary heart disease.

[A cross-sectional study on the association between frailty and muscular performances in hospitalized elder patients with coronary artery disease].

Objective: To explore the association between frailty and muscle performances of hospitalized elder adults with coronary artery disease. Methods: A total of 122 hospitalized patients aged 65-85 years old with coronary artery disease from Department of Geriatrics and Cardiology, Peking Union Medical College Hospital between December 2017 and March 2018 were enrolled in the study. A comprehensive geriatric assessment was performed to evaluate existing comorbidity and geriatric syndromes of the patients. Frailty was assessed using the Clinical Fraity Scale. The patients were classified as frail and non-frail, according to the scale. Muscle performances were assessed using grip strength, gait speed, etc. Whole body and appendicular skeletal muscle mass was detected with bioelectrical impedance analysis in patients with reduced grip strength or slowed gait speed. Appendicular skeletal muscle index (ASMI) was calculated. Results: Among all subjects, 28 were with frailty (23.0%) and 94 were without (77.0%). The frail patients were older [(76.7±5.4) years vs. (72.2±5.6)years], had higher Charlson comorbidity index [2.0(1.0,2.75)vs. 1.0(0,2.0)], and higher proportion of malnutrition (14.29% vs. 1.06%), urinary incontinence (39.29% vs. 15.96%), using walking-aid (28.57% vs. 6.38%), and more kinds of taken drugs (8.1±3.0 vs. 6.6±2.7), than the non-frail patients. Prealbumin levels [(207.8±60.0)mg/L vs.(234.3±45.4)mg/L] were lower, and highly sensitive C-reactive protein levels [(5.89±9.57)mg/L vs.(1.89±2.49)mg/L] were higher in the frail patients than in the non-frail patients (all P<0.05). Compared with non-frail patients, the frail patients had poorer grip strength [(19.67±7)kg vs.(29.23±8.29)kg] and slower gait speed [(0.54±0.2)m/s vs.(0.91±0.22)m/s] (all P<0.001). Spearman rank correlation analyses showed that grip strength was positively correlated with the appendicular skeletal muscle mass(r=0.811), whole body skeletal muscle mass(r=0.74) and the ASMI (r=0.783), respectively. Conclusions: The incidence of frailty among hospitalized older adults with coronary artery disease is high. Poor muscle performances were common in these patients. Assessment of frailty and muscle performances can help to evaluate the overall function of older adults with cardiovascular disease in a comprehensive way.

[The study of making decision in the timing of delivery for patients of placenta previa through dynamic monitoring the length of cervical canal by perineal ultrasound].

Objective: To investigate the value of dynamic monitoring of cervical canal length by transperineal ultrasonography in the decision-making of the timing of delivery in patients with complete placenta previa, then to provide clinical guidance for complete termination of placenta. Methods: A total of 130 patients with complete placenta previa from 28 weeks to 30 weeks of gestation between January 2014 and October 2017 in Jiaxing Maternal and Child Health Hospital were selected. There were 66 patients in the experimental group and 64 in the control group, closely monitor the patient's vital signs, abdominal pain, abdominal distension, vaginal bleeding and fetal intrauterine conditions. In the experimental group, the length of the cervical canal was monitored by perineal ultrasonography at 2 hours and 12 hours after admission. This led to termination of the pregnancy. The control group was instructed to terminate the timing of pregnancy based on the patient's abdominal pain relief symptoms and vaginal bleeding. Compare the maternal and fetal outcomes of both groups. Results: The length of the cervical canal was (31.3±1.3) mm when the experimental group was admitted to the hospital, and the length of the cervical canal after the use of the retention drugs 2 h and 12 h was (32.1±0.4) mm and (32.2±0.4) mm, respectively.Compared with the length of the cervix at the time of admission. There was no significant change in the length of the cervical canal after the application of the retention drug 2 and 12 h(all P>0.05). The delivery week of 11 patients in the experimental group did not exceed 34 weeks, and 28 cases in the control group, and there was significant difference between the two groups. Compared with the control group, the difference of birth rate did not exceed 34 weeks, birth weight and hospitalization time decreased significantly (all P<0.05). However, there was no significant difference in maternal outcomes between the two groups. Conclusion: Through monitoring the length of the cervical canal by perineal ultrasound can make a better decision for the patients of complete placenta previa to chose the time of delivery.

Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.

Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC). CUS also enhanced GluN2B-mediated NMDA currents and extrasynaptic responses that were induced by bursts of high-frequency stimulation, which may be associated with the loss of astrocytes and low expression of glutamate transporter-1 (GLT-1). The blockade of GLT-1 in the mPFC was sufficient to induce depressive-like behavior and cause similar molecular changes. Selective GluN2B antagonist, DAPK1 knockdown by adeno-associated virus-mediated short-hairpin RNA or a pharmacological inhibitor, and the uncoupling of DAPK1 from the NMDAR GluN2B subunit produced rapid antidepressant-like effects and reversed CUS-induced alterations in the mPFC. The inhibition of DAPK1 and its interaction with GluN2B subunit in the mPFC also rescued CUS-induced depressive-like behavior 7 days after treatment. A selective GluN2B antagonist did not have rewarding effects in the conditioned place preference paradigm. Altogether, our findings suggest that the DAPK1 interaction with the NMDAR GluN2B subunit acts as a critical component in the pathophysiology of depression and is a potential target for new antidepressant treatments.

Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness. The involvement of PKMζ in the antidepressant effects of conventional antidepressants and ketamine were also investigated. We found that chronic stress decreased the expression of PKMζ in the mPFC and hippocampus but not in the orbitofrontal cortex. Overexpression of PKMζ in mPFC prevented the depressive-like and anxiety-like behaviors induced by CUS, and reversed helplessness behaviors. Inhibition of PKMζ in mPFC by expressing a PKMζ dominant-negative mutant induced depressive-like behaviors after subthreshold unpredictable stress and increased learned helplessness behavior. Furthermore, stress-induced deficits in synaptic proteins and decreases in dendritic density and the frequency of miniature excitatory postsynaptic currents in the mPFC were prevented by PKMζ overexpression and potentiated by PKMζ inhibition in subthreshold stress rats. The antidepressants fluoxetine, desipramine and ketamine increased PKMζ expression in mPFC and PKMζ mediated the antidepressant effects of ketamine. These findings identify PKMζ in mPFC as a critical mediator of depressive-like behavior and antidepressant response, providing a potential therapeutic target in developing novel antidepressants.

[Prognostic factors and model of primary liver cancer treated with transcatheter arterial chemoembolization combined with radiofrequency ablation].

Objective: To investigate the prognostic factors of primary liver cancer treated with transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA), and then to establish a prognostic model. Methods: Clinicopathological and follow-up data of 145 patients who underwent TACE combined with RFA from January 2010 to December 2012 were retrospectively analyzed. Univariate and multivariate survival analyses were performed using the Cox proportional hazards model, and the prognostic model was established. Results: The 1, 2, and 3-year survival rates were 92.6%, 81.4% and 66.2%, respectively. The 3-year recurrence and metastasis rate was 64.8%.Multivariate analysis showed that female cases and higher serum albumin levels were the protective factors for the 3-year overall and relapse-free survival of patients(P<0.05 for all). High levels of alpha-fetoprotein (AFP), alanine aminotransferase (ALT), total bilirubin (TBIL), portal vein thrombosis and higher Child Pugh stages were the independent risk factors for the 3-year overall survival(P<0.05 for all). High levels of AFP, TBIL, portal vein thrombosis and advanced stages of BCLC staging (B and C) were the independent risk factors for tumor recurrence and metastasis(P<0.05 for all). The predictive model established based on the multivariate analysis showed good sensitivity and specificity. The area under ROC curve were higher than 0.90. Conclusions: The prognosis of liver cancer patients treated with TACE combined with RFA is affected by various clinicopathological factors. The systematic evaluation of the relevant factors before treatment may help to select proper patients and improve prognosis.

[Risk factors and prognosis of neurological complications in patients with infective endocarditis].

OBJECTIVE: To identify risk factors of neurological complications (NC) in left-sided infective endocarditis (IE) and to assess its impact on the outcome and cardiac surgery. METHODS: Clinical data, NC, treatment and outcome of patients with definite left-sided IE admitted to our hospital during 2001-2012 were retrospectively analyzed. RESULTS: A total of 308 patients with age of (45.3±15.9) years were enrolled. Among them, 65 (21.1%) experienced at least one NC. Independent risk factors associated with NC were large vegetation (HR=1.681, 95%CI 1.013-2.788, P=0.044), non-neurologic embolism (HR=1.820, 95%CI 1.068-3.100, P=0.028), mitral valve involvement (HR=1.888, 95%CI 1.089-3.274, P=0.024), Staphylococcus aureus infection (HR=2.054, 95%CI 1.097-3.846, P=0.044), and uncontrolled infection (HR=4.680, 95%CI 2.563-8.546, P<0.001). During a median follow-up for 17 months, 70 (22.7%) patients died. NC had a negative impact on long-term outcome (HR=2.292, 95%CI 1.274-4.122, P=0.006). Valve replacement surgery was performed in 156(50.6%)patients, which was associated with a lower rate of 1-year IE-related death (HR=0.160, 95%CI 0.063-0.405, P<0.001). Among patients with NC, valve replacement surgery was associated with lower rates of in-hospital mortality and 1-year IE-related mortality (14.8% vs 5.3%, 18.5% vs 73.7%, respectively, P<0.001). CONCLUSIONS: Independent risk factors of NC include large vegetation, non-neurologic embolism, mitral valve involvement, Staphylococcus aureus infection, and uncontrolled infection. Neurologic complications link to the poor prognosis in patients with left-sided IE. Valve surgery is considered as a safe procedure and improves the survival.

[Efficacy and mechanism of local delivery of rapamycin and rapamycin-loaded poly(lactic-co-glycolic) acid nanoparticles on coronary restenosis of injury-stenosis model of minipigs].

OBJECTIVE: To determine whether intramural administration of rapamycin (RPM)-loaded polylactic-polyglycolic acid (PLGA) nanoparticles (NPs) can reduce intimal thickening and affect the mRNA expressions of matrix metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-2 and p27(kipl) in a coronary injury-stenosis model of minipigs. METHODS: Twenty eight minipigs were randomly separated into four groups: saline group (n=7), blank PLGA NPs group (5.0 mg/ml)(n=7), RPM group (1.0 mg/ml)(n=7), and RPM-PLGA NPs(5.0 mg/ml)group (n=7), respectively. Different treatments were intracoronary locally delivered via a Dispatch™ catheter for 10 minutes. Serial angiography was performed pre-and post-modeling 30 days and the percent stenosis degree was assessed. Hematoxylin-Eosin (HE) staining, Weigert's resorcin fuchsin staining and picric acid-sirius red staining were used for morphometric analysis. Immunohistochemistry was performed to assess the levels of proliferating cell nuclear antigen (PCNA), MMP-2, and TIMP-2 at early and late time points, respectively. The expression of p27(kip1) mRNA was detected by in situ hybridization staining. RESULTS: Data from 21 minipigs had been collected at the end of the experiment with 6, 4, 5, and 6 from the former mentioned 4 groups, respectively. For the instant injury index, there was no significant difference among the four groups. The percent stenosis degree of RPM-PLGA NPs group was significantly lower than that of the other three groups respectively (all P< 0.05). The neointima area, net external elastic lamina area to external elastic laminal area ratio, and proliferative index of RPM-PLGA NPs group were significantly less than those of the other three groups, with all the P values less than 0.05. The mean value of integral optical density of p27(kip1)mRNA expression of RPM-PLGA group was 0.35 ± 0.06, higher than that of blank PLGA NPs group (0.12 ± 0.05, P< 0.01), saline group (0.16 ± 0.03, P< 0.05), and RPM group (0.15 ± 0.03, P< 0.05), respectively. The MMP-2/TIMP-2 ratio and the positive expression index of PCNA in RPM-PLGA group were lower than that of the other groups (P< 0.05). CONCLUSIONS: Locally delivered rapamycin-loaded PLGA NPs significantly reduces MMP-2/TIMP-2 ratio and PCNA expression, increases p27(kip1) mRNA expression and significantly relieves percent stenosis degree and shows excellent acute procedural results in the minipig interventional coronary artery oversized balloon injury model. The results from minipig model further support that this approach could be a potential clinical procedure for vascular proliferative disease.

Effects of cetuximab combined with afatinib on the expression of KDR and AQP1 in lung cancer.

In this study, we examined the effect of cetuximab (epidermal growth factor receptor monoclonal antibody) combined with afatinib (epidermal growth factor receptorand human epidermal growth factor receptor 2 tyrosine kinase irreversible inhibitor) on the apoptosis of A549 cells and on kinase domain receptor (KDR) and aquaporin 1 (AQP1) expression in A549 cells. A549 cells were cultured in RPMI-1640 and then divided into 4 groups: control group, 1-nM cetuximab group, 25-µM afatinib group, and 1-nM cetuximab + 25-µM afatinib group. After incubation for 48 h, the cell inhibition rate, cell cycle distribution, and invasive ability of A549 cells before and after treatment were examined using MTT, flow cytometry, and transwell assays, respectively. Gene and protein expression levels of KDR and AQP1 were detected by reverse transcription-polymerase chain reaction and western blot analysis. Cetuximab and afatinib significantly inhibited A549 cell growth. Their combination produced greater growth inhibition (P < 0.01). Cetuximab and afatinib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P < 0.01). Compared with monotherapy, cetuximab in combination with afatinib induced G1 phase arrest and downregulated the gene and protein expression of KDR and AQP1 (P < 0.05). Cetuximab in combination with afatinib synergistically inhibited the growth and migration of cells and downregulated the gene and protein expression of KDR and AQP1, indicating that a combination of cetuximab and afatinib is a potential strategy for lung cancer therapy.

Effects of kinase insert domain receptor (KDR) gene silencing on the sensitivity of A549 cells to erlotinib.

We investigated the effects of kinase insert domain receptor (KDR) gene silencing on the proliferation of A549 cells and their sensitivity to erlotinib. A KDR small interfering RNA (siRNA) sequence was designed and synthesized; then, it was transfected into A549 cells using Lipofectamine(TM) 2000. KDR mRNA and protein expression after KDR gene silencing was detected by reverse transcription polymerase chain reaction and western blotting; the A549 cell cycle was detected by flow cytometry. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay were performed to determine the sensitivity of A549 cells to erlotinib after KDR gene silencing. After 48h of KDR gene silencing, there was a significant decrease in KDR gene and protein expression (P < 0.05). The A549 cell cycle was arrested at the G0/G1 phase, and the number of cells in the S phase decreased; the difference was statistically significant (P < 0.05). In the KDR gene silencing group, the sensitivity of A549 cells to erlotinib was significantly enhanced (P < 0.05). KDR siRNA can significantly silence the KDR gene in A549 cells, inhibit the proliferation of A549 cells, and enhance their sensitivity to erlotinib.