[Diagnostic value of optical imaging combined with indocyanine green-guided sentinel lymph node biopsy in gastric cancer: a meta-analysis].

Objective: To systematically evaluate the diagnostic value of optical imaging combined with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy in gastric cancer, and to identify potential factors that would influence diagnostic accuracy. Methods: Study was carried out by searching the electronic database of PubMed, Embase, Medline, Web of Science, and the Cochrane Library with keywords as "gastric/stomach" and "cancer/carcinoma/tumor/tumour/adenocarcinoma/neoplasm" and "sentinel lymph node" and "near-infrared/NIR or fluorescent imaging" and "indocyanine green/ICG" . Literature inclusion criteria: (1) gastric cancer clinical stage was cT0-3; (2) clinical stage determined by at least 2 kinds of imaging modalities; (3) optical imaging (near-infrared or fluorescence imaging) combined with ICG-guided SLN biopsy; (4) prospective study to predict lymph node metastasis; (5) intraoperative or postoperative pathology for all lymph nodes removed; (6) patients number in the literature >10 cases. Exclusion criteria: (1) patients with a history of ICG allergy or chemoradiotherapy; (2) previous history of endoscopic mucosal resection or endoscopic submucosal dissection; (3) patients with a variety of gastrointestinal tumor; (4) case reports, conference abstracts, clinical guidelines, editorials, reviews, meta-analysis and correspondence letters; (5) in vitro or animal experiments; (6) insufficient diagnostic efficacy data. The meta-analysis was performed in the Stata12.0 software using the "bivariate mixed-effects model" combined with the "midas" command to pool the data. Information such as true positive value, false positive value, false negative value, and true negative value of each included articles were extracted. The literature quality assessment map was drawn to describe the overall quality of the articles; the heterogeneity analysis was performed with the forest map, with P<0.01 considered as statistical significance; the funnel plot was used to describe publication bias, with P<0.1 considered as statistically significant. Area under curve (AUC) of summary receiver operator characteristic (SROC) was used to describe the diagnostic accuracy and the AUC closer to 1 indicated higher diagnostic accuracy. If there was heterogeneity (I(2)>50%) among studies, regression analysis and subgroup analysis were performed. P<0.05 was considered as statistically significant. Results: A total of 15 studies (1020 patients) were included. The optical imaging contained near-infrared (NIR) and fluorescent imaging (FI). The diagnostic value of optical imaging combined with ICG-guided SLN biopsy in gastric cancer was as follows: the pooled sensitivity (Sen) was 0.95 (95% CI: 0.82 to 0.99), specificity (Spe) was 1.00 (95% CI: 0.92 to 1.00), positive likelihood ratio (PLR) was 30.39 (95% CI: 9.14 to 101.06), negative likelihood ratio (NLR) was 0.05 (95% CI:0.01 to 0.20), diagnostic odds ratio (DOR) was 225.54 (95% CI: 88.81 to 572.77), AUC was 1.00 (95% CI: 0.99 to 1.00), threshold value was sensitivity=0.95 (95% CI: 0.82 to 0.99) and specificity=1.00 (95% CI: 0.92 to 1.00). Deeks method revealed DOR funnel plot of SLN biopsy was not asymmetrical obviously with significant difference (P=0.01), which indicated remarkable publishing bias. Meta-subgroup analysis showed that compared to FI, NIR imaging had higher sensitivity (0.98 vs. 0.73); compared to 0 minutes, optical imaging performed 20 minutes after ICG injection had higher sensitivity (0.98 vs. 0.70); compared to mean detected number of SLN of 4, mean detected number≥4 had higher sensitivity (0.96 vs. 0.68); compared to HE stain, immunohistochemistry + HE had higher sensitivity (0.99 vs. 0.84); compared to subserous injection of ICG, submucosa injection of ICG had higher sensitivity (0.98 vs. 0.40); compared to injection of 5 g/L ICG, 0.5 g/L and 0.05 g/L had higher sensitivity (0.98 vs. 0.83); compared to cT2-3 tumor, early stage (cT1) tumor had higher sensitivity (0.96 vs. 0.72); compared to ≤ enrolled 26 cases in the study, > 26 cases had higher sensitivity (0.96 vs. 0.65); compared to papers before 2010, papers after 2010 had higher sensitivity (0.97 vs. 0.81); whose differences were all significant. Sensitivity differences between mean tumor diameter of ≤30 cm and >30 cm, open surgery and laparoscopic surgery, lymph node regional dissection and retrieved dissection were not significant (all P>0.05). Conclusions: Optical imaging combined with ICG-guided SLN biopsy is clinically feasible, and especially suitable for early gastric cancer. However, the ICG being used in current studies may be overdosed. Higher sensitivity may be achieved from NIR imaging when compared with FI method.

[Practice of parenting and related factors on children aged 0-5 in the urban areas of China].

Objective: To characterize the relations between the practice of parenting and associated factors on children (0-5 years old) in urban areas of China, in order to provide evidence for promoting the early development of children and to provide positive guidance and service programs on parenting. Methods: A total of 4 515 parents from 15 cities (14 provinces) were surveyed with a self-administered questionnaire. Parenting and Family Adjustment Scales (PAFAS) was used, including parameters as: consistency and coercive parenting, positive encouragement, parent-child relationship and parental emotion adjustment, family relationship and parental teamwork aspects, etc. Both single factor analysis and multiple linear regression were used to examine the associations between parenting practice, individual, parental and family factors. Results: The mean score of PAFAS was 21.00 (15.00-28.00), associated with factors as children's age, only-child family, premature delivery, father's education level, confidence on parenting, problems regarding the parental mood, annual family income, family structure and behavior on seeking professional help, etc. Results showed that there were big differences on the practice of parenting in China and influenced by variety of factors. Conclusions: The general situation of parenting was well, in the urban areas of China. The practice of parenting was associated with a series of individual, parental and family factors. Programs on improving the parenting skills and promoting the early development of children, should be highlighted.

Modeling cell-in-cell structure into its biological significance.

Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of 'entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintaining homeostasis, aberrant cell-in-cell process contributes to the etiopathology in humans. Indeed, cell-in-cell is observed in many pathological processes of human diseases. In this review, we intend to discuss the biological models of cell-in-cell structures under physiological and pathological status.

Rapid reuptake of granzyme B leads to emperitosis: an apoptotic cell-in-cell death of immune killer cells inside tumor cells.

A cell-in-cell process refers to the invasion of one living cell into another homotypic or heterotypic cell. Different from non-apoptotic death processes of internalized cells termed entosis or cannibalism, we previously reported an apoptotic cell-in-cell death occurring during heterotypic cell-in-cell formation. In this study, we further demonstrated that the apoptotic cell-in-cell death occurred only in internalized immune killer cells expressing granzyme B (GzmB). Vacuole wrapping around the internalized cells inside the target cells was the common hallmark during the early stage of all cell-in-cell processes, which resulted in the accumulation of reactive oxygen species and subsequent mitochondrial injury of encapsulated killer or non-cytotoxic immune cells. However, internalized killer cells mediated rapid bubbling of the vacuoles with the subsequent degranulation of GzmB inside the vacuole of the target cells and underwent the reuptake of GzmB by killer cells themselves. The confinement of GzmB inside the vacuole surpassed the lysosome-mediated cell death occurring in heterotypic or homotypic entosis processes, resulting in a GzmB-triggered caspase-dependent apoptotic cell-in-cell death of internalized killer cells. On the contrary, internalized killer cells from GzmB-deficient mice underwent a typical non-apoptotic entotic cell-in-cell death similar to that of non-cytotoxic immune cells or tumor cells. Our results thus demonstrated the critical involvement of immune cells with cytotoxic property in apoptotic cell-in-cell death, which we termed as emperitosis taken from emperipolesis and apoptosis. Whereas entosis or cannibalism may serve as a feed-on mechanism to exacerbate and nourish tumor cells, emperitosis of immune killer cells inside tumor cells may serve as an in-cell danger sensation model to prevent the killing of target cells from inside, implying a unique mechanism for tumor cells to escape from immune surveillance.