Oncolytic activity of a coxsackievirus B3 strain in human endometrial cancer cell lines.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological malignancies globally. Although progress has been made in surgical and other adjuvant therapies, there is still a great need to develop new approaches to further reduce the incidence and mortality of EC. Oncolytic virotherapy offers a novel promising option of cancer treatment and has demonstrated good efficacy in preclinical models and clinical trials. However, only few oncolytic viruses have been tested for EC treatment. In this study, the potential of an oncolytic coxsackievirus B3 (CV-B3) strain 2035A (CV-B3/2035A) was investigated as a novel biotherapeutic agent against EC. METHODS: Human EC cell lines (Ishikawa, HEC-1-A and HEC-1-B) were infected with CV-B3/2035A, and viral replication and cytotoxic effects were evaluated in vitro. CV-B3/2035A-induced oncolysis was also investigated in nude mice bearing EC xenografts in vivo and in patient-derived EC samples ex vivo. RESULTS: Human EC cell lines expressing different levels of CAR and DAF were all susceptible to infection by CV-B3/2035A and supported efficient viral replication in vitro. In the EC xenograft/nude mouse model, both intratumoral and intravenous administrations of CV-B3-2035A exerted significant therapeutic effects against pre-established EC tumors without causing significant treatment-related toxicity and mortality in nude mice. Moreover, CV-B3/2035A treatment resulted in decreased viability of patient-derived EC samples ex vivo. CONCLUSIONS: CV-B3/2035A showed oncolytic activity in human EC cell lines both in vitro and in vivo as well as in patient-derived EC samples ex vivo and thus could be used as an alternative virotherapy agent for the treatment of EC.

Sputum signatures for invasive pulmonary aspergillosis in patients with underlying respiratory diseases (SPARED): study protocol for a prospective diagnostic trial.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied. METHODS: This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ2 test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models. DISCUSSION: We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD. TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.

Compound Formulas of Traditional Chinese Medicine for the Common Cold: Systematic Review of Randomized, Placebo-controlled Trials.

CONTEXT: The common cold is one of the most frequent acute illnesses of the respiratory tract, affecting all age groups. The compound formulas of traditional Chinese medicine (TCM) are frequently used to treat the common cold in China and other parts of the world. Until now, however, the efficacy and safety of compound formulas of TCM for the common cold, studied in comparison with placebos, have not been systematically reviewed. OBJECTIVES: This literature review intended to assess existing evidence of the effectiveness and safety of compound formulas of TCM for the common cold. DESIGN: Randomized, controlled trials (RCTs) comparing compound formulas of TCM with placebos in treating the common cold were included, regardless of publication status. The research team searched the Cochrane Library, PubMed, Embase, the Chinese Biomedical Literature Database, the Chinese Scientific and Technological Periodical Database, the Chinese National Knowledge Infrastructure and the Wangfang Database from their inceptions to December 2013. The team also searched Web sites listing ongoing trials and contacted experts in the field and relevant pharmaceutical companies to locate unpublished materials. OUTCOME MEASURES: Two review authors independently extracted data and assessed the methodological quality of included studies, using the Cochrane risk of bias tool. MAIN RESULTS: A total of 6 randomized, double-blind, placebo-controlled trials involving 1502 participants were included. Most trials had a low risk of bias. Five were conducted in mainland China and 1 in Hong Kong; 5 were multicenter clinical trials and 1 was a single-center trial; 4 were published in Chinese and 2 were published in English. Compound formulas of TCM were superior to placebos in reducing disease symptoms, inducing recovery from a TCM syndrome, and increasing quality of life. In addition, the formulas were superior in shortening the duration of the main symptoms, the amount of time for a decline in temperature of at least 0.5°C to occur, and the duration of any fever. The team did not perform a summary meta-analysis due to clinical heterogeneity. No serious adverse event (AE) occurred in either the treatment or the control groups. CONCLUSIONS: This systematic review indicated that compound formulas of TCM, compared with placebo, can provide benefits to patients with the common cold, with no serious side effects having been identified in the included trials. However, due to the small number of included studies and of participants and the unclear risk of some biases in the included studies, more high-quality, large-scale RCTs are still warranted to clarify fully the effectiveness and safety of compound formulas of TCM in treating the common cold.

Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

Objective: To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Methods: We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. Results: We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Conclusion: Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.

Associations of lactate dehydrogenase with risk of renal outcomes and cardiovascular mortality in individuals with diabetic kidney disease.

OBJECTIVE: This study aimed to investigate the role of the lactate dehydrogenase (LDH) in the development of end-stage renal disease (ESRD) and the cardiovascular mortality in individuals with diabetic kidney disease (DKD). METHODS: Two cohorts were recruited in this study. We explored the correlation between LDH and renal injury in individuals with DKD in using a Cohort 1. Additionally, we validated this correlation in the NHANES database and further investigated its association with the risk of cardiovascular mortality in Cohort 2 which also comprised individuals with DKD. RESULTS: In cohort 1, multivariate Cox regression analysis demonstrated that individuals in DKD with higher LDH were independently associated with an increased risk of ESRD compared to those with lower LDH (HR = 2.11; 95 % CI, 1.07-4.16). In cohort 2, linear regression models showed that LDH affects the level of albumin-creatinine ratio (ACR) (ß = 2.95, P = 0.001). Additionally, multivariate Cox regression analysis results showed that an increase in LDH per 1-standard deviation (SD) was associated with a 27 % increased risk of cardiovascular mortality (HR = 1.27; 95 % CI, 1.09-1.48). CONCLUSIONS: LDH levels are associated with renal injury and progression to ESRD, as well as being an independent risk factor for cardiovascular in individuals with DKD.

Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes.

Background: Obesity often initiates or coexists with metabolic abnormalities. This study aimed to investigate the pathological characteristics and the independent or mutual relations of obesity and metabolic abnormalities with end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) and associated diabetic kidney disease (DKD). Methods: A total of 495 Chinese patients with T2D and biopsy-confirmed DKD between 2003 and 2020 were enrolled in this retrospective study. The metabolic phenotypes were based on the body weight index (BMI)-based categories (obesity, BMI ≥ 25.0 kg/m2) and metabolic status (metabolically unhealthy status, ≥ 1 criterion National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) excluding waist circumference and hyperglycemia) and were categorized into four types: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO). The pathological findings were defined by the Renal Pathology Society classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) for ESKD. Results: There are 56 (11.3%) MHNO patients, 28 (5.7%) MHO patients, 176 (35.6%) MUNO patients, and 235 (47.5%) MUO patients. The high prevalence of the Kimmelstiel-Wilson nodule and severe mesangial expansion were associated with obesity, whereas severe IFTA was related to metabolically unhealthy status. In the multivariate analysis, the adjusted HR (aHR) was 2.09 [95% confidence interval (CI) 0.99-4.88] in the MHO group, 2.16 (95% CI 1.20-3.88) in the MUNO group, and 2.31 (95% CI 1.27-4.20) in the MUO group compared with the MHNO group. Furthermore, the presence of obesity was insignificantly associated with ESKD compared with non-obese patients (aHR 1.22, 95% CI 0.88-1.68), while the metabolically unhealthy status was significantly associated with ESKD compared to the metabolically healthy status in the multivariate analysis (aHR 1.69, 95% CI 1.10-2.60). Conclusion: Obesity itself was insignificantly associated with ESKD; however, adding a metabolically unhealthy status to obesity increased the risk for progression to ESKD in T2D and biopsy-proven DKD.

[The current situation of children neglect and its influencing factors for rural children aged 0 - 6 years in Chongqing].

OBJECTIVE: To learn the current situation of children neglect and its influencing factors among children aged from 0 - 6 years in rural Chongqing. METHODS: Scales and evaluation methods in the "Chinese rural child neglected evaluation model" were used in this study. The investigation was conducted by using multistage stratified cluster sampling method in December 2010, and 822 rural children aged 0 to 6 years of three districts in Chongqing were randomly select for the survey, with neglect rate and the neglect degree to describe their neglect status, using logistic regression analysis to analyze factors affecting children neglect. RESULTS: The total neglect rate and the neglect degree in the rural children were 35.64% (293/822) and 49.69 ± 6.45, respectively. The neglect degree in boys was higher than that of girls (boys: 50.23 ± 6.40 vs girls: 49.09 ± 6.47, P < 0.05). Further, Our data demonstrated both the neglect rate and the neglect degrees in children whose parents away from home were higher than that of the children whose parents stayed with them (neglect rate: 40.48% (202/499) vs 28.17% (91/323), P < 0.05; neglect degree: 50.64 ± 6.29 vs 48.23 ± 6.44, P < 0.05). Based on multivariate unconditional logistic regression analysis, the determinants of children neglect were: parents were away from home (OR = 1.61, 95%CI: 1.17 - 2.21), single mother and remarried family (OR = 1.39, 95%CI: 1.10 - 1.76), maternal occupation(OR = 0.81, 95%CI: 0.73 - 0.90), estrangement relationship between children and their mothers (OR = 1.42, 95%CI: 1.02 - 1.97). CONCLUSION: The neglect situation of rural children is serious in Chongqing, and the main factors are parents away from home, single mother and remarried family, maternal occupation, and estrangement relationship between children and their mothers.

[The situation of children neglect between left-behind children and living-with-parents children in rural areas of two western provinces of China].

OBJECTIVE: To understand the children neglect situation of left-behind children (children who do not grow up with their parents) and non-left-behind children in China's western rural and its influencing factors. METHODS: Scales and evaluation methods in the "Chinese rural child neglected evaluation model" were used in this study. The investigation was conducted by using multistage stratified cluster sampling method; three countries were sampled randomly in Shanxi and Chongqing in November 2010, respectively. And, in every county, children from rural area aged from zero to six were randomly selected, with neglect rate and degree to describe their neglected status, using logistic regression analysis to analyze factors affecting the neglect rate. RESULTS: Among 1568 subjects (859 left-behind and 709 living-with-parents), the total neglect rates were 29.78% (467/1568), and the total neglect degrees were 48.51 ± 6.49; the neglect rates for left-behind ones and living-with parents ones were 34.34% (295/859) and 24.26% (172/709) (P < 0.05); the neglect degree were 49.59 ± 6.54 and 47.19 ± 6.18 (P < 0.05). The neglect degree among left-behind ones and living-with parents ones between 0 to 2 years old were 48.59 ± 6.33 and 45.78 ± 5.94 (P < 0.05); in 3 to 6 years old group, which were 50.43 ± 6.60 and 48.25 ± 6.16(P < 0.05). The degrees in boy's group of these two kinds of children were 49.83 ± 6.67, 47.36 ± 6.28(P < 0.05) and girl's were 49.32 ± 6.38, 47.01 ± 6.08 (P < 0.05). On the other side, the neglect rate of left-behind and non-left-behind children between 0 to 2 years old were 39.33% (153/389) and 18.54% (56/302) (P < 0.05). The rates of boy's group were 34.91% (162/464) and 25.13% (94/374) (P < 0.05), and girl's were 33.67% (133/395) and 23.28% (78/335) (P < 0.05). Results showed that if the left-behind child's father was with lower education background, and the child and his mother feel stranger to each other, which led to the conclusion there was more chance for them to be neglected (OR values were 1.29 and 1.55, P < 0.05). If the non-neglected child's father was farmer or migrant worker and the relationship between the mother and father was poor, then there was more chance for them to be neglected (OR values were 0.85 and 1.92, P < 0.05). CONCLUSION: The situation of children neglect in the western rural regions in China is serious. Both the neglect rate and degree among left-behind children are higher than those living-with-parents children. The influencing factors of neglect rate are different in the two groups.

Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases.

BACKGROUND: Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-ß-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. METHODS: Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. RESULTS: The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2  = 19.83, P   <  0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2  = 24.65, P  < 0.001), and fungal culture (33% [84/253]) ( χ2  = 29.38, P  < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher's exact P  = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2  = 5.52, P  = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P  = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2  = 0.89, P  = 0.345) to and lower sensitivity (63% [24/38]) ( χ2  = 4.14, P  = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2  = 6.95, P  = 0.008), BDG ( χ2  = 10.43, P  = 0.001), and fungal culture ( χ2  = 12.70, P  < 0.001). CONCLUSIONS: Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

A SCID mouse-human lung xenograft model of varicella-zoster virus infection.

Varicella pneumonia is one of the most serious, potentially life-threatening complications of primary varicella-zoster virus (VZV) infection in adults and immunocompromised individuals. However, studies on the lung pathogenesis of VZV infection as well as development and testing of antivirals have long been hindered by limited access to clinical samples and a lack of suitable animal models. In this study, we report for the first time the use of human lung xenografts in SCID mice for investigating VZV infection. Human fetal lung tissues grafted under the kidney capsule of SCID mice rapidly grew and developed mature structures closely resembling normal human lung. Following infection, VZV replicated and spread efficiently in human lung xenografts, where the virus targeted both alveolar epithelial and mesenchymal cells, and resulted in formation of large viral lesions. VZV particles were readily detected in the nuclei and cytoplasm of infected lung cells by electron microscopy. Additionally, VZV infection resulted in a robust pro-inflammatory cytokine response in human lung xenografts. In conclusion, infecting human lung xenografts in SCID mice provides a useful, biological relevant tool for future mechanistic studies on VZV lung pathogenesis, and may potentially facilitate the evaluation of new antiviral therapies for VZV lung infection.

Outer nuclear membrane fusion of adjacent nuclei in varicella-zoster virus-induced syncytia.

Syncytia formation has been considered important for cell-to-cell spread and pathogenesis of many viruses. As a syncytium forms, individual nuclei often congregate together, allowing close contact of nuclear membranes and possibly fusion to occur. However, there is currently no reported evidence of nuclear membrane fusion between adjacent nuclei in wild-type virus-induced syncytia. Varicella-zoster virus (VZV) is one typical syncytia-inducing virus that causes chickenpox and shingles in humans. Here, we report, for the first time, an interesting observation of apparent fusion of the outer nuclear membranes from juxtaposed nuclei that comprise VZV syncytia both in ARPE-19 human epithelial cells in vitro and in human skin xenografts in the SCID-hu mouse model in vivo. This work reveals a novel aspect of VZV-related cytopathic effect in the context of multinucleated syncytia. Additionally, the information provided by this study could be helpful for future studies on interactions of viruses with host cell nuclei.

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization.

Varicella-zoster virus (VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues, however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 kDa viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.

Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model.

Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1ß, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/ß, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1ß, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/ß, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner.

Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.

Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release.

The development of multifunctional nanocarrier with each unit functioning at the correct time and location is a challenge for clinical applications. With this in mind, a type of intelligent mesoporous silica nanocarrier (PGFMSN) is proposed for matrix metalloprotease 2 (MMP 2)-triggered tumor targeting and release by integrating programmed packing and MMP 2-degradable gelatin. Mesoporous silica nanoparticles (MSN) are first functionalized with folic acid (FA) as a target ligand to improve cell uptake. Then gelatin is introduced onto FA-MSN via temperature-induced gelation, where gelatin layer blocks drugs inside the mesopores and protects the targeting ligand. To prolong blood-circulation lifetime, PEG is further decorated to obtain PGFMSN. All units are programmatically incorporated in a simple way and coordinated in an optimal fashion. Cells, multicellular spheroids and in vivo results demonstrate that PGFMSN is shielded against nonspecific uptake. After circulating to tumor tissue, the up-regulated MMP-2 hydrolyzes gelatin layer to deshield PEG and switch on the function of FA, which facilitate the selective uptake by tumor cells through folate-receptor-mediated endocytosis. Meanwhile, the packaged drug is released due to the shedding of gelatin layer. It is shown that doxorubicin (DOX)-loaded exhibits superior tumor targeting, drug internalization, cytotoxicity, and antitumor efficacy over free DOX, non-PEGylated and non-targeted nanoparticles, which provides potential applications for targeted cancer therapy.

[Analysis on the current situation of neglected rural children aged 0 - 6 years and its impact factors in the western areas of China].

OBJECTIVE: To learn the current neglected situation and its impact factors on rural children in two provinces in Western China. METHODS: The investigation was conducted by using multistage stratified cluster sampling method in some parts of the Shanxi province and the city of Chongqing. RESULTS: 1488 subjects, aged from 0 to 6, were recruited in the present study. Results showed that the total prevalence rates of neglected rural children in the two research sites were 31.59% and 48.32 respectively. No significant difference was found on the prevalence of neglected for boys and girls (χ(2) = 0.86, U = 1.51, P > 0.05). The degrees of negligence in the older children showed a significant increase than in the younger children (χ(2) = 13.36, F = 33.45, P < 0.05). The prevalence and degree of negligence in families with three generations were lower than that of a single-parent families and remarried families (H = 10.03, F = 2.83, P < 0.05). The one-child-families were significantly lower than multiple children families, both in terms of prevalence and degree of negligence. Our data demonstrated the degrees of negligence in children whose parents were away from home, were higher than the children whose parents stayed with them (χ(2) = 30.30, U = 6.76, P < 0.05). The degree of negligence in Shanxi was lower than that in Chongqing (χ(2) = 9.42, U = 8.40, P < 0.05). Based on multivariate non-conditional logistic regression analysis, the determinants of stunting among the stranded children were as follows: parents were away from home (OR = 1.54, 95%CI: 1.20 - 1.97); structure of the family (OR = 1.38, 95%CI: 1.16 - 1.65); father's occupation (OR = 0.87, 95%CI: 0.78 - 0.97); schooling of the children's mother (OR = 1.27, 95%CI: 1.07 - 1.52); relationship between children and their fathers (OR = 1.43, 95%CI: 1.07 - 1.91) etc. CONCLUSION: The situation of negligence in children living in the rural areas, were serious in Shanxi and Chongqing provinces, which called for the strengthening on the publicity and education of the issue. School and the society should also pay more attention to this problem.

[Analysis of 112 postnasal drip syndrome's ambulatory treatment].

OBJECTIVE: Discuss the clinical features and the disease curing methods for the chronic cough caused by postnasal drip syndrome. METHOD: One hundred and twelve patients who were diagnosed with postnasal drip syndrome were given systemic cure such as giving antibiotics, adopt a decongestant, part system using decongestion and glucocorticoid, improving the sticky film cilium function. RESULT: All above follow-up of one hundred and twelve example patients three months. With subjectivity, if symptoms improve action appraises an index, cough of ninety-nine cases had different improve. Thirteen cases did not feel their symptom improve obviously. Have efficiency amounting to 88%. CONCLUSION: Although the cause of postnasal drip syndrome is complicated. Cough is an important clinical feature of postnasal drip syndrome. It will get ideal therapeutic efficacy if cured by systemic medication.