Epidemiological characteristics and influential factors of hand, foot and mouth disease (HFMD) reinfection in children in Anhui province.

Hand, foot and mouth disease (HFMD) is an acute contagious condition caused by a spectrum of human enteroviruses. HFMD reinfection is common in the absence of cross-protection from other virus subtypes. This study focused on reinfection in children in Anhui province, China between 2008 and 2013 using surveillance system data. We classified 8960 cases as reinfected, corresponding to a rate of 2·02%. The reinfection rate was higher in boys than in girls [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·21-1·32, P < 0·001], children aged < 3 years (OR 3·82, 95% CI 3·58-4·07, P < 0·001), and children living in rural areas (OR 1·09, 95% CI 1·04-1·14, P = 0·001). The reinfection rate in children who were originally infected with non-enterovirus A71 (non-EVA71) enteroviruses was higher than those infected with EVA71 (OR 1·36, 95% CI 1·02-1·80, P = 0·034). Influential factors of reinfection rate included annual incidence (ß coefficient = 0·715, P = 0·002) and the proportion of EVA71 in patients with mild HFMD (ß coefficient = -0·509, P = 0·018). These results demonstrate that boys aged <3 years, especially those in rural areas or regions with a lower EVA71 proportion are more prone to reinfection, and specific health education programmes should be developed to protect these susceptible populations.

Agrobacterium-mediated transformation of the ß-subunit gene in 7S globulin protein in soybean using RNAi technology.

The objective of this study was to use RNA interference (RNAi) to improve protein quality and decrease anti-nutritional effects in soybean. Agrobacterium tumefaciens-mediated transformation was conducted using RNAi and an expression vector containing the 7S globulin ß-subunit gene. The BAR gene was used as the selective marker and cotyledonary nodes of soybean genotype Jinong 27 were chosen as explant material. Regenerated plants were detected by molecular biology techniques. Transformation of the ß-subunit gene in the 7S protein was detected by PCR, Southern blot, and q-PCR. Positive plants (10 T0, and 6 T1, and 13 T2) were tested by PCR. Hybridization bands were detected by Southern blot analysis in two of the T1 transgenic plants. RNAi expression vectors containing the soybean 7S protein ß-subunit gene were successfully integrated into the genome of transgenic plants. qRT-PCR analysis in soybean seeds showed a clear decrease in expression of the soybean ß-subunit gene. The level of 7S protein ß-subunit expression in transgenic plants decreased by 77.5% as compared to that of the wild-type plants. This study has established a basis for the application of RNAi to improve the anti-nutritional effects of soybean.

Cutaneous metastasis from gastric cancer: Manifestation, diagnosis, treatment and prognosis.

INTRODUCTION: Cutaneous metastasis from gastric cancer is very rare. The understanding of this disease is incomplete. This situation delays its diagnosis and treatment, followed by poor prognosis. Here, we first report a study based on a network to improve the diagnosis, treatment and prognosis of cutaneous metastasis from gastric cancer. METHODS: A comprehensive search of PubMed was performed. All studies on cutaneous metastasis from gastric cancer were collected. The publication date was limited from 2000 to the present, and the language was limited to English. SPSS 26.0 was employed for statistical analysis. RESULTS: Seventy-two patients were included. The average patient age was 60.0 ± 16.0 years. In total, 72.2 % of the patients were male. The most common manifestation was nodular skin lesions (45.8 %). The metastases generally presented as multiple lesions (61.1 %). The most common metastasis location was the thoracoabdominal wall (56.9 %). 64.7 % of the patients simultaneously had extracutaneous metastases. Most of the tumors were poorly differentiated carcinomas (87.5 %), and 66.1 % had signet ring cells. 40.8 % of the cutaneous metastases presented as primary manifestations. Only 9.6 % had their diagnosis as soon as the cutaneous metastasis emerged. Systemic chemotherapy (65.6 %) was the most common treatment strategy, followed by radical surgery (12.5 %). The median overall survival was only 6 months. The median overall survival of 5 patients with resected tumors was 48 months. CONCLUSION: Cutaneous metastasis from gastric cancer usually manifests as an emerged nodule or erysipelas-like skin lesion. Resection of the cutaneous lesion could be helpful for patients with local metastases.

Lack of association between the haplotype GCC/ATA polymorphism in the IL-10 promoter and SLE risk: evidence from a meta-analysis.

Numerous studies have investigated the association between the interleukin (IL)-10 promoter haplotype GCC/ATA (at the - 1082, - 819 and - 592 positions of the IL-10 gene) polymorphism and systemic lupus erythematosus (SLE) risk, but the results were inconsistent. We performed the current meta-analysis to assess precisely the association by comparing the GCC haplotype with the ATA haplotype. A literature search was conducted using Pubmed and Web of Science databases. Twelve studies including 1765 cases and 2444 controls were included in this meta-analysis. The overall odds ratios (total and stratified by ethnicity: Asian or Caucasian) were 1.042 (95 % confidence interval [CI] 0.893-1.216; p = 0.599), 0.790 (95 % CI 0.528-1.182; p = 0.251), and 1.093 (95 % CI 0.919-1.300; p = 0.317), respectively. The results indicated that the GCC haplotype revealed no statistically significant association with SLE risk; thus, the haplotype GCC/ATA polymorphism of the IL-10 promoter is not likely to be involved in SLE susceptibility.

Attributable causes of cancer in China.

BACKGROUND: Most cancers are due to modifiable lifestyle and environmental risk factors, and are potentially preventable. No studies have provided a systematic quantitative assessment of the burden of cancer mortality and incidence attributable to known risk factors in China. METHODS: We calculated the proportions of cancer deaths and new cases attributable to known risk factors in China, based on the prevalence of exposure around 1990 and national data on cancer mortality and incidence for the year 2005. RESULTS: Chronic infection is the main risk factor for cancer in China, accounting for 29.4% of cancer deaths (31.7% in men and 25.3% in women), followed by tobacco smoking (22.6% with 32.7% in men and 5.0% in women), low fruit intake (13.0%), alcohol drinking (4.4%), low vegetable intake (3.6%) and occupational exposures (2.7%). The remaining factors, including environmental agents, physical inactivity, the use of exogenous hormones and reproductive factors are each responsible for <1.0%. CONCLUSIONS: Modifiable risk factors explain nearly 60% of cancer deaths in China, with a predominant role of chronic infection and tobacco smoking. Our findings could provide a basis for cancer prevention and control programs aimed at reducing cancer risk in other developing countries.

The efficiency and safety of immune checkpoint inhibitors for advanced biliary tract cancers based on gene profiles: A retrospectively controlled study.

Immune checkpoint inhibitors are potential agents to improve the survival of advanced biliary tract cancers (ABTCs). The current results are controversial because the predictors are imprecise. We present our primary experience with ABTCs based on gene landscape with exciting outcomes. ABTCs who were admitted to The First Affiliated Hospital of Henan University of Science and Technology from October 2019 to March 2021 were enrolled. They were divided into chemotherapy group or immunotherapy group according to the treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were response and toxicities. SSPS 16.0 was used for statistical analysis. A total of 33 patients were enrolled, including 25 in the chemotherapy group and 8 in the immunotherapy group. The median OS and PFS of the chemotherapy group were 2 and 4 months, respectively. The estimated median OS and PFS of immunotherapy were 10 + and 10 + months, respectively. The differences of OS and PFS between the 2 groups were significant (P = .000; P = .003). Stratified analysis showed that these differences were mainly from those patients with high expression of PD-L1 > 10%. The difference in the overall response was significant between 2 groups (χ2 = 9.275; P = .026). The difference in adverse events between the 2 groups was not significant. Immune checkpoint inhibitors were effective and safe for ABTCs with high expression of PD-L1. The threshold should be precise.

Kaempferol suppresses proliferation and induces apoptosis and DNA damage in human gallbladder cancer cells through the CDK4/CDK6/cyclin D1 pathway.

OBJECTIVE: Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear. MATERIALS AND METHODS: We found that kaempferol significantly inhibited the growth, invasion and migration, meanwhile induced apoptosis through cells arrested at G0/G1 phase of GBC cell lines, including GBC-SD and SGC996 cells in vitro. RESULTS: Kaempferol promoted the release of cytochrome C from the mitochondria to cytoplasm, the activation of c-caspase-3 and c-caspase-9 and increased the expression levels of pro-apoptotic factor Bax, meanwhile decreased the expression levels of anti-apoptotic factor Bcl-2. In addition, the expression levels of CDK4, CDK6 and cyclin D1, which are members of the CDK4/CDK6/cyclin D1 signaling pathway, were also decreased by kaempferol. Moreover, kaempferol could efficiently prevent tumor progression of GBC in the xenograft in vivo. CONCLUSIONS: Our results demonstrated that kaempferol suppressed GBC progression through activation of the CDK4/CDK6/cyclin D1 signaling pathway, suggesting that it might be a potential anti-tumor agent for clinical treatment of GBC.

[Survival status and influencing factors of HIV/AIDS cases in Liuzhou, 2008-2018].

Objective: To understand the duration of survival and related influencing factors of HIV/AIDS patients in Liuzhou city. Methods: Both life table method and Kaplan-Meier method were used to calculate the average survival time of HIV/AIDS patients aged ≥15 years reported in Liuzhou city from 2008 to 2018. Factors related to the duration of HIV/AIDS patients were analyzed by univariate and multivariate Cox regression models. Results: A total of 14 856 patients with HIV/AIDS were involved in this study and with the average duration of survival time as 98.74 (95%CI: 97.73-99.75) months. The cumulative survival rates of 1, 3, 5 and 10 years were 77.0%, 72.0%, 68.0%, 61.0% respectively. Results from the multivariate Cox proportional risk regression analysis showed that factors as sex, level of education, age when HIV infection was confirmed, occupation, route of transmission, source of samples, results of the first CD(4) test and antiviral treatment were all related to the duration of survival to the HIV/AIDS patients. Conclusions: Strategies involving early detection of HIV infection, improvement of the CD(4) initial detection rate and early antiviral treatment will help to significantly reduce the risk of death in HIV/AIDS population. Focus should be on male, middle-aged and elderly (over 41 years old), junior high school education or below farmers and migrant worker populations.

Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption.

To develop a new polypeptide delivery system, insulin nano-aggregates with sizes of 100-230nm were prepared by the salting out method with NaCl and encapsulated via the layer-by-layer (LbL) adsorption to provide the insulin nanoparticles shelled with two oppositely charged polyelectrolytes. Poly(alpha,beta-l-malic acid) (PMA) and water-soluble chitosan (WSC) as the weak polyelectrolytes with good biodegradability and biocompatibility in vivo were chosen to be the encapsulating materials of the LbL adsorption. In the preparation of the insulin nano-aggregates, the NaCl concentration and pH in the medium obviously affected yield and particle size of the insulin nano-aggregates. After eight adsorption cycles of the polyelectrolytes on the insulin nano-aggregates, the insulin-polyelectrolyte nanoparticles with the sizes of 100-250nm were obtained with about 20% insulin loss. The insulin release from the nanoparticles was mostly pH-dependent owing to sensitivity of the weak polyelectrolytes to pH. Insulin was hardly released from the nanoparticles in a medium at pH 4-5 while it could be released at pH 7.4, corresponding to the pH of the human blood and the body fluid. A burst effect was also observed although it could be reduced via increasing the polyelectrolyte layers of PMA and WSC assembled on insulin nano-aggregates.

Synthesis of a biodegradable tadpole-shaped polymer via the coupling reaction of polylactide onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and its properties as the new carrier of protein delivery system.

A new tadpole-shaped polymer was synthesized via the coupling reaction of poly(DL-lactide) (PLA) onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin (CDen) using N,N'-Dicyclohexycarbodiimide as the catalyst. The structures of CDenPLA as the products were characterized with infrared spectrometry, nuclear magnetic resonance and their molecular weights were determined by gel permeation chromatography. The tadpole-shaped polymer possessed both a hydrophilic head that could bind some residues on a protein and a hydrophobic polylactide tail so that it could be amphiphilic. Two methods, double emulsion (DE) and nanoprecipitation (NP), were employed to fabricate the polymeric nanoparticles into which the bovine serum albumin was loaded as a model protein. The nanoparticles with a hydrophobic core of the PLA segments covered with the hydrophilic corona layer of the cyclodextrin moiety could be formed from the copolymers using NP method as identified by 1HNMR. Influence of the preparation conditions on the nanoparticles size, encapsulation efficiency and release profile in vitro was investigated. The encapsulation efficiency of the BSA-loaded nanoparticles with the average diameter of 377 nm was 71.6% under an optimized condition. The structure maintenance in the nanoparticle preparation and release in vitro was also measured via sodium dodecyl sulfate polyacrylamide gel electrophoresis and circular dichroism spectrometry. The results showed that the new copolymer could load BSA effectively and BSA kept stable after it was released from the nanoparticles.

Prevalence and clinical significance of 15 autoantibodies in patients with new-onset systemic lupus erythematosus.

INTRODUCTION: It is necessary to assay multiple autoantibodies simultaneously in the same group of new-onset systemic lupus erythematosus (SLE) patient. AIM: To determine the prevalence and clinical significance of 15 autoantibodies in patients with new-onset SLE. METHODS: Twenty new-onset patients with SLE and 32 healthy individuals were enrolled in the present study. Serum levels of 15 autoantibodies were detected by enzyme linked immunosorbent assay. The clinical parameters of the patients were also recorded. RESULTS: The positive rate of anti-ssDNA was the highest (85%). The positive rates of anti-dsDNA, anti-ssDNA, AHA, anti-SSA, anti-SSB, anti-Sm, anti-U1RNP, AnuA, and rRNP were significantly higher in SLE patients than in nomal controls. In terms of clinical manifestation, there were significant associations of rRNP with photaesthesia and of AHA with nephritis. CONCLUSION: Clusters of autoantibodies were identified and associations of antibodies with symptoms were found in new-onset patients with SLE.

Endothelial monocyte-activating polypeptide II. A novel tumor-derived polypeptide that activates host-response mechanisms.

An important means by which tumor cells influence the vasculature is through the production of soluble mediators altering vascular properties. A approximately 22-kDa polypeptide was purified to homogeneity from conditioned medium of murine methylcholanthrene A (meth A) fibrosarcoma cells by ion-exchange chromatography and preparative sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE), based on its ability to induce tissue factor procoagulant activity in endothelial cells (ECs). The final product migrated as a broad band on reduced and nonreduced SDS-PAGE and had an unique amino-terminal sequence. This meth A-derived polypeptide modulated EC coagulant properties through the induction of tissue factor, induced monocyte migration and tissue factor expression, and was also chemotactic for granulocytes. Injection of the polypeptide into mouse footpads resulted in an inflammatory response with tissue swelling and polymorphonuclear leukocyte infiltration. The ability of this mediator to activate ECs and monocytes has led us to name it EMAP II (endothelial monocyte-activating polypeptide). EMAP II is distinct from a previously described approximately 40-kDa meth A-derived polypeptide termed EMAP I. Through its potential to activate host effector mechanisms, EMAP II could contribute to the biology of immunogenic tumors, such as the meth A fibrosarcoma.

A peptide derived from the amino terminus of endothelial-monocyte-activating polypeptide II modulates mononuclear and polymorphonuclear leukocyte functions, defines an apparently novel cellular interaction site, and induces an acute inflammatory response.

Endothelial-monocyte-activating polypeptide II (EMAP II) is a novel mediator isolated from conditioned medium of methylcholanthrene A-induced tumor cells which modulates properties of endothelial cells, mononuclear phagocytes (MPs), and polymorphonuclear leukocytes (PMNs) in vitro and induces an acute inflammatory response in vivo. A synthetic peptide comprising 15 residues from the N-terminal region (residues 6-20) was shown to induce directional migration of MPs and PMNs, with half-maximal effect at approximately 200-250 pM, whereas a peptide from the C terminus of EMAP II, as well as other irrelevant peptides, were without effect. Modulation of cellular phenotype by EMAP II-derived peptide was suggested by peptide-induced elevation of cytosolic free calcium concentration in fura-2-loaded MPs and PMNs and by stimulation of peroxidase release in PMNs. Consistent with these in vitro data, EMAP II-derived N-terminal peptide-albumin conjugates injected into the mouse footpad elicited inflammatory cell tissue infiltration, whereas albumin alone or EMAP II-derived C-terminal peptide conjugated to albumin incited little response. Binding of 125I-labeled EMAP II-derived peptide (residues 12-20) to MPs was saturable (Kd approximately 200 pM) and was blocked in a dose-dependent manner by the addition of intact EMAP II and unlabeled EMAP II-derived peptides (residues 6-20 and 12-20), whereas interleukin 1, tumor necrosis factor, formyl-methionyl-leucinyl-phenylalanine, or irrelevant peptides were without effect. Cross-linking of 125I-EMAP II-derived peptide (residues 12-20) by disuccinimidyl suberate to human MPs demonstrated a band, approximately 73 kDa, on reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 125I-EMAP II-derived peptide also demonstrated specific binding to human PMNs and murine RAW cells. These data indicate that the N-terminal region of EMAP II defines a biologically active locus of the molecule which interacts with target cells via a potentially novel cellular receptor.