Cleidocranial dysplasia(CCD)is a rare autosomal dominant disorder mainly characterized by skeletal and dental abnormali-ties.It is caused by the runt-related transcription factor-2(Runx2)mutations.In this paper,a case of CCD syndrome is reported.The proband and his family were examined by the proband's verification method for general condition,oral specialty and genetic examination.A new nonsense mutation exon7 c.1078C＞T,p.Gln360*heterozygous variant(Q360X)was verified,the relationship between Runx2 mutation and CCD phenotype was analyzed.

Cleidocranial dysplasia(CCD)is a rare autosomal dominant disorder mainly characterized by skeletal and dental abnormali-ties.It is caused by the runt-related transcription factor-2(Runx2)mutations.In this paper,a case of CCD syndrome is reported.The proband and his family were examined by the proband's verification method for general condition,oral specialty and genetic examination.A new nonsense mutation exon7 c.1078C＞T,p.Gln360*heterozygous variant(Q360X)was verified,the relationship between Runx2 mutation and CCD phenotype was analyzed.

Glioblastoma(GBM)is a widely occurring and highly invasive central nervous system tumor.Its occurrence and development are closely related to multiple molecular mechanisms,making treatment and prognosis challenging.Integrin α7(ITGA7)is a potential marker for glioblastoma stem cells,and its high expression is associated with poor prognosis in various solid tumor patients.In recent years,research on the pathogenesis of GBM involving ITGA7 has increased.This review summarizes recent studies on the role of ITGA7 in promoting GBM progression,including GBM cell biology,angiogenesis,signaling pathways,and the tumor microenvironment,with the aim of providing references for further understanding the mechanisms of GBM occurrence and development and the exploration of therapeutic targets.

Glioblastoma(GBM)is a widely occurring and highly invasive central nervous system tumor.Its occurrence and development are closely related to multiple molecular mechanisms,making treatment and prognosis challenging.Integrin α7(ITGA7)is a potential marker for glioblastoma stem cells,and its high expression is associated with poor prognosis in various solid tumor patients.In recent years,research on the pathogenesis of GBM involving ITGA7 has increased.This review summarizes recent studies on the role of ITGA7 in promoting GBM progression,including GBM cell biology,angiogenesis,signaling pathways,and the tumor microenvironment,with the aim of providing references for further understanding the mechanisms of GBM occurrence and development and the exploration of therapeutic targets.

ObjectiveTo study the relationship between the exposure to two kinds of phthalate esters （PAEs） ［Di-N-butyl phthalate，（DBP） and Di-（2-ethylhexyl）phthalate （DEHP）］ and estrogen homeostasis in pregnant women. MethodsIn 2021， we classified the Jiading District of Shanghai into five geographical areas， east， west， south， north and central. A total of 151 pregnant women from each area were selected for questionnaire survey， with random urine samples during first， second， and third trimesters collected. A DBP metabolite ［Mono-N-butyl phthalate （MBP）］ and two DEHP metabolites ［Mono（2-ethylhexyl） phthalate （MEHP）， Mono（2-ethyl5-oxohexyl） phthalate， （MEOHP）］ and three estrogens ［estrone （E₁）， 17β -estradiol （E₂）， and estriol （E₃）］ in urine were determined by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry. After a natural logarithmic transformation of PAEs metabolite levels and estrogen concentration， multivariable linear regression was used to control potential confounders and determine the relationship between PAEs metabolite levels and estrogen concentration. ResultsThe detection rates of three PAEs metabolites in urine of pregnant women were more than 98%. The median corrected concentrations of MBP， MEHP and MEOHP were 5.18， 0.59 and 4.23 mg·kg^-1， respectively. During the whole pregnancy， MEOHP was positively correlated with E₁ （β=0.450， 95%CI： 0.057‒0.844）， and MBP was positively correlated with E₃ （β=0.250， 95%CI： 0.034‒0.465）. Stratified by trimesters， MBP was positively correlated with E₃ in the first trimester （β=0.428， 95%CI： 0.103‒0.752）. MEOHP was positively correlated with E₁ in the second trimester （β=0.734， 95%CI： 0.130‒0.752）， and had a possitive trend with E₁ in the third trimester （β=0.744， 95%CI： -0.140‒1.629）. In addition， MEHP had a negative correlation with E₁ in the second trimester （β=-0.498， 95%CI： -1.063‒0.066）. MEOHP had a positive correlation trend with E₂ （β=0.628， 95%CI： -0.101‒1.356） in the third trimester. ConclusionPAEs exposure may interfere with estrogen homeostasis during pregnancy and differs by trimesters. Given the cross-sectional nature of this study， it warrants further study to validate the findings.

To investigate the temporal trend of antibiotic use among children in Shanghai from 2017 to 2020. The stratified cluster sampling method was used to establish a dynamic cohort of healthy children based on primary schools in Changning District, Shanghai. In the cohort, there were 282 children from 2017, 287 children from 2018, 294 from 2019 and 301 from 2020. A total of 700 children aged 7-11 years were included in the study. The basic information and antibiotic use of children were investigated by questionnaire every year, and their height and weight were measured at the same time. Chi-square test was used to analyze the difference of antibiotic use rate in each year and generalized estimation equation was used to analyze the temporal trend of antibiotic use. The results showed that the use rates of all antibiotics, cephalosporins, azithromycin and other antibiotics (including penicillin, lincomycin, quinolones, etc.) of children between 2017 and 2020 were 15.6%, 10.5%, 2.7%, and 2.4%, respectively. In 2017, 2018, 2019, and 2020, there were significant differences for the use rates of total antibiotics and other antibiotics in children ( P=0.033, P=0.040), and there were no significant differences for the use rates of cephalosporins and azithromycin ( P=0.274, P=0.455). After adjusting for children′s basic characteristics, the generalized estimation equation showed that the annual use rate of all antibiotics, cephalosporins, and other antibiotics decreased over time.

To investigate the temporal trend of antibiotic use among children in Shanghai from 2017 to 2020. The stratified cluster sampling method was used to establish a dynamic cohort of healthy children based on primary schools in Changning District, Shanghai. In the cohort, there were 282 children from 2017, 287 children from 2018, 294 from 2019 and 301 from 2020. A total of 700 children aged 7-11 years were included in the study. The basic information and antibiotic use of children were investigated by questionnaire every year, and their height and weight were measured at the same time. Chi-square test was used to analyze the difference of antibiotic use rate in each year and generalized estimation equation was used to analyze the temporal trend of antibiotic use. The results showed that the use rates of all antibiotics, cephalosporins, azithromycin and other antibiotics (including penicillin, lincomycin, quinolones, etc.) of children between 2017 and 2020 were 15.6%, 10.5%, 2.7%, and 2.4%, respectively. In 2017, 2018, 2019, and 2020, there were significant differences for the use rates of total antibiotics and other antibiotics in children ( P=0.033, P=0.040), and there were no significant differences for the use rates of cephalosporins and azithromycin ( P=0.274, P=0.455). After adjusting for children′s basic characteristics, the generalized estimation equation showed that the annual use rate of all antibiotics, cephalosporins, and other antibiotics decreased over time.

Objective:To systematically evaluate the risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI).Methods:Randomized controlled trials of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2, 2019). The patients who were treated with a VEGFR-TKI were enrolled into the trial group, and those who received placebo or another VEGFR-TKI were enrolled into the control group. The outcomes included the incidence of serious gastrointestinal events. The Jadad scoring method was used to assess the quality of included studies. The Review Manager 5.3 software was used for direct meta-analysis on the risk of severe gastrointestinal events. Stata 13.0 software and linear mixed model based on frequency framework were used for network meta-analysis on severe gastrointestinal events at the highest risk. The results were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 38 studies were included in the analysis, all of which were high-quality studies (Jadad score 4-7), comprising a total of 15 217 patients (9 130 in the trial group and 6 087 in the control group). The results of direct meta-analysis showed that the risks of severe diarrhea, severe anorexia, and severe nausea in the trial group were higher than those in the control group respectively, and the differences were statistically significant [6.8% (602/8 894) vs. 0.7% (49/6 584), RR=6.62 (95 %CI: 5.00-8.76), P<0.001; 2.5% (201/7 937) vs. 0.7% (41/5 831), RR=2.14 (95 %CI: 1.40-3.25), P<0.001; 1.5% (92/6 343) vs. 0.4% (21/4 870), RR=1.95 (95 %CI: 1.23-3.12), P=0.005]; the risk of severe diarrhea was the highest [6.8% (602/8 894)]. There was no significant difference in the risk of severe vomiting and severe abdominal pain compared with the control group [1.4% (79/5 788) vs. 0.7% (32/4 428), RR=1.49 (95 %CI: 0.90-2.47), P=0.120; 1.7% (82/4 766) vs. 1.1% (40/3 628), RR=1.35 (95 %CI: 0.84-2.16), P=0.210]. The results of network meta-analysis on risk of severe diarrhea events showed that the relative risks of severe diarrhea caused by varieties of VEGFR-TKI were axitinib>anlotinib>cabozantinib≈vandetanib≈sunitinib≈lenvatinib≈sorafenib≈pazopanib>regorafenib>fruquintinib>apatinib in the order. Conclusion:The application of VEGFR-TKIs, especially axitinib, can increase the risk of severe diarrhea in patients with tumors, which deserves clinical attention and vigilance.

Objective:To systematically evaluate the risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI).Methods:Randomized controlled trials of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2, 2019). The patients who were treated with a VEGFR-TKI were enrolled into the trial group, and those who received placebo or another VEGFR-TKI were enrolled into the control group. The outcomes included the incidence of serious gastrointestinal events. The Jadad scoring method was used to assess the quality of included studies. The Review Manager 5.3 software was used for direct meta-analysis on the risk of severe gastrointestinal events. Stata 13.0 software and linear mixed model based on frequency framework were used for network meta-analysis on severe gastrointestinal events at the highest risk. The results were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 38 studies were included in the analysis, all of which were high-quality studies (Jadad score 4-7), comprising a total of 15 217 patients (9 130 in the trial group and 6 087 in the control group). The results of direct meta-analysis showed that the risks of severe diarrhea, severe anorexia, and severe nausea in the trial group were higher than those in the control group respectively, and the differences were statistically significant [6.8% (602/8 894) vs. 0.7% (49/6 584), RR=6.62 (95 %CI: 5.00-8.76), P<0.001; 2.5% (201/7 937) vs. 0.7% (41/5 831), RR=2.14 (95 %CI: 1.40-3.25), P<0.001; 1.5% (92/6 343) vs. 0.4% (21/4 870), RR=1.95 (95 %CI: 1.23-3.12), P=0.005]; the risk of severe diarrhea was the highest [6.8% (602/8 894)]. There was no significant difference in the risk of severe vomiting and severe abdominal pain compared with the control group [1.4% (79/5 788) vs. 0.7% (32/4 428), RR=1.49 (95 %CI: 0.90-2.47), P=0.120; 1.7% (82/4 766) vs. 1.1% (40/3 628), RR=1.35 (95 %CI: 0.84-2.16), P=0.210]. The results of network meta-analysis on risk of severe diarrhea events showed that the relative risks of severe diarrhea caused by varieties of VEGFR-TKI were axitinib>anlotinib>cabozantinib≈vandetanib≈sunitinib≈lenvatinib≈sorafenib≈pazopanib>regorafenib>fruquintinib>apatinib in the order. Conclusion:The application of VEGFR-TKIs, especially axitinib, can increase the risk of severe diarrhea in patients with tumors, which deserves clinical attention and vigilance.

Objective:To explore the protective effect of vitamin D in acute liver failure through a mouse model.Methods:Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1β, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test.Results:Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1β, and NLRP-3 mRNA expression ( P < 0.05), and increased macrophages quantitation ( P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury ( P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise ( P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues ( P < 0.05). Conclusion:Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.