Background:Zinc finger protein of cerebellum 2(ZIC2)is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system.Previous studies have reported that ZIC2 is widely upregulated in a variety of tumors. Methods:Oncomine database was used to evaluate the expression levels of ZIC2 in hepatocellular car-cinoma(HCC)and normal liver tissues.Quantitative real-time polymerase chain reaction and immu-nohistochemistry were conducted to validate the results from the database.Cox regression analysis and survival curves were performed to assess the survival effect of ZIC2 in HCC. Results:Increased expression of ZIC2 was detected in HCC tissues compared with normal liver tissues.In addition,patients with high ZIC2 levels had a poor prognosis.Multivariate analysis showed that clinical stage(T or M classification)and ZIC2 levels were independent prognostic factors for overall survival.Moreover,a subgroup analysis revealed that patients with moderate or poor grade tumors,T1-2 tumors,N0 tumors,early American Joint Committee on Cancer(AJCC)stage,and old age were more likely to present with overexpression of ZIC2.To conclude,ZIC2 is upregulated in HCC and associated with the histology and survival of HCC patients. Conclusions:The expression status of ZIC2 may serve as an independent prognostic marker of HCC.

Fluorine is an important element widely present in nature, and moderate intake can prevent dental caries and promote bone development. However, long-term excessive intake can lead to fluorosis, damaging tissues or organs such as teeth, bones, heart muscle, and blood vessels. Bone marrow mesenchymal stem cells (BMSCs) play an important role in the repair process of bone injury due to their excellent multi-directional differentiation potential. Therefore, studying BMSCs is of great value in the treatment of fluorosis caused by fluoride poisoning. This article summarize the progress on the effect of fluoride on BMSCs, providing new ideas for the study of the pathogenesis and clinical treatment of fluorosis.

OBJECTIVE To investigate the anti-tumor effects of the components of Ganoderma lucidum(Gc) based on the two-dimensional(2D) and three-dimensional(3D) culture of colorectal cancer HCT116 cells. METHODS The chemical compositional of the three components was identified by UPLC-Q-TOF-MS. An in vitro 3D culture model of HCT116 cells was established by using Matrigel as the matrix material, and the effects of Gc1, Gc2, Gc3, and 5-fluorouracil(5-FU) on the proliferation of HCT116 cells in 2D and 3D culture models were evaluated, and the effects of Gc3 on cell-cycle, apoptosis, drug resistance, lipid metabolism, and 5-FU's anti-tumor activity were evaluated. Cell viability was detected by CCK-8 assay. mRNA expression level of the cells was analyzed by Real-time PCR. Proteins expression level of the cells was analyzed by Western blotting. HPLC was used to detect the content of 5-FU in cells. RESULTS A total of 76, 69, and 17 compounds were identified from Gc1, Gc2, and Gc3, respectively. Compared with 2D culture, the proliferation rate of HCT116 cells was decreased in the 3D culture model, and the expression of cell cycle-promoters CDK2, CDK4, CDK6, and fatty acid synthesizer FASN, SREBP1 were significantly down-regulated. On the contrary, the expression of cell cycle-suppressor p21, p27, and lipid droplet breakdown proteins ATGL and drug resistance gene ITGB1, CDH1, ABCB1, and ABCC1 mRNA were significantly up-regulated. Gc1, Gc2, Gc3 and 5-FU inhibited the proliferation of both 2D and 3D cultured HCT116 cells in a dose dependent manner after incubation for 48 h, and the inhibitory effect of Gc3 was significantly stronger than Gc1 and Gc2. Gc3 could not only reduce the expression of CDK2, CDK4, Bcl-xl, ATGL, and LC3B proteins, but also increase the expression of p21, p27, Bax, Cleaved caspase-3, and Cleaved PARP1 proteins, and overexpression of LC3B or ATGL attenuated Gc3-induced cytotoxicity in 3D cultured HCT116 cells. In addition, Gc3 significantly inhibited the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA, and increased the intracellular 5-FU content, and enhanced the anti-tumor activity. CONCLUSION Gc3 significantly inhibit the proliferation of 3D-cultured HCT116 cells by inhibiting cell autophagy and lipid droplet breakdown, and enhance the anti-cancer activity of 5-FU by inhibiting the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA.

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women’s Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.

Objective:To label mesenchymal stem cells (MSCs) with 89Zr-oxine complex, and assess its characteristics of PET imaging in systemic lupus erythematosus (SLE) model (MRL/lpr mice). Methods:SLE mice were screened by 18F-FDG PET imaging. 89Zr-oxine was prepared and used for labeling MSCs (10 6 MSCs and 1 MBq 89Zr-oxine). 89Zr-oxine-labeled MSCs (0.2 MBq) were injected into MRL/lpr mice and BALB/c mice (each n=5) via tail vein at a dose of 1.2×10 6 cells per mouse, and followed with microPET imaging in vivo at 2 h, 6 h, 1 d, 3 d, 7 d, 10 d and 14 d after injection. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used to analyze the data. Results:MSCs was successfully labeled with 89Zr-oxine, with the labeling efficiency of 20% and cell viability >90%. MicroPET imaging showed that MSCs were mainly distributed in lungs and the liver sites at 2 h after injection. The number of MSCs homing to kidneys of MRL/lpr mice ( n=5) increased significantly 24 h after the injection, and the renal uptake of MSCs in MRL/lpr mice was much higher than that in BALB/c mice ((8.28±1.27) vs (4.33±0.94) %ID/g; t=3.54, P=0.024). The renal uptake increased firstly and then decreased and then leveled off, indicating MSCs homing to kidneys. Conclusions:A method for 89Zr-oxine labeling of MSCs is successfully established. 89Zr-labeled MSCs can home to kidneys of SLE mice. PET imaging of 89Zr-labeled MSCs can be effectively used to explore the in vivo distribution and migration behavior of transplanted MSCs during the treatment of diseases such as SLE.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.