Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo, but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (Gαq) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of Gαq to HTR2B was decreased after Ari treatment. Knockdown of Gαq not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and Gαq was found in that the mutation at amino acid 190 of Gαq reduced the efficacy of Ari. Thus, these results confirm that Gαq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.

ObjectiveTo investigate the effect of porcine large intestine-processed Dahuang （Radix et Rhizoma Rhei） on defecation in constipation model mice and the possible mechanism. MethodsFifty Kunming mice were randomized to blank group （n=10） and model group （n=40）. Loperamide suspension at the dose of 8 mg/（kg·d） was given by gavage for four consecutive days to establish a model of constipation. The 24 successfully modeled mice were randomly divided into model group， processed Dahuang group， lactulose group， raw Dahuang group， with six mice in each group. Moreover， six randomly selected mice were chosen as control group. Since the fifth day， 8 mg/（kg·d） of loperamide suspension by gavage was given to the model group， processed Dahuang group， raw Dahuang group， and lactulose group； two hours later， the processed and raw Dahuang groups were administered with 0.6 g/（kg·d） of processed and raw Dahuang suspension， respectively， while the lactulose group was given 0.6 g/（kg·d） of latulose suspension， and the blank group and the model group were given 0.2 ml/10 g of distilled water by gavage， all for four days. The general condition， body weight after the last gavage， number of fecal particles within six hours， fecal wet weight， fecal water content ratio， intestinal propulsion rate and colonic histology changes by HE staining of each group were detected. ResultsThe body weight of the mice in the raw Dahuang group was significantly lighter than that in the other groups （P＜0.05 or P＜0.01）. The number of fecal particles， fecal wet weight and intestinal propulsion rate of mice significantly decreased in the model group than in the blank group （P＜0.05 or P＜0.01）. Compared to those in the model group， the number of fecal particles and fecal wet weight in the processed Dahuang group， lactulose group and raw Dahuang group significantly increased， and the fecal water content ratio in the raw Dahuang group increased as well （P＜0.05 or P＜0.01）. Compared to those in the processed Dahuang group， the number of fecal particles and fecal wet weight in the raw Dahuang group decreased， while the fecal water content ratio increased （P＜0.05 or P＜0.01）， and the fecal water content ratio in the lactulose group increased significantly （P＜0.05）. The intestinal propulsion rate in the processed Dahuang group was higher than that in the model group， lactulose group and raw Dahuang group （P＜0.05 or P＜0.01）. Histopathological analysis showed that the colonic crypts and goblet cells in the blank group were normal and clear， and the colonic muscular layer was thicker. The colonic crypts of the mice in the model group were damaged， with reduced goblet cells to varying degrees and changed colonic muscularis. In the lactulose group and raw Dahuang group， part of the crypts were broken， and the goblet cells were damaged to varying degrees， while in the processed Dahuang group， still the colonic tissue structure of the mice was relatively clear， and the colonic crypts and goblet cells were relatively normal， with thickened muscular layer of the colon. ConclusionPorcine large intestine-processed Dahuang could improve defecation in constipation model mice， and reduce the drastic purgation function of raw Dahuang， for which the mechanism may be related to the protection of colon histopathological damage.

This article reported a case of kaposiform lymphangiomatosis (KLA) identified in the fetal stage and diagnosed at the neonatal stage. A routine ultrasound examination at 19 weeks of gestation showed multiple masses in the whole body of the fetus (involving neck, chest wall and armpit) complicated by pleural and peritoneal effusion. Shunting was performed to drain pleural effusion from the right chest in another hospital at 26 +5 weeks of gestation. The patient was born at 34 +3 weeks of gestation by cesarean section due to "intrauterine distress" and required invasive ventilator assisted ventilation support after birth because of respiratory distress. A large amount of hemorrhagic effusion was drained out during the shunting. Coagulation dysfunction and thrombocytopenia occurred on the 3rd day after birth and KLA was suspected. Empirical treatment with sirolimus turned out to be ineffective. Biopsy was taken on postnatal day 7. However, the patient died on the 12th day after birth due to respiratory and circulatory failure. Pathological findings obtained the day after death were consistent with the features of KLA. The diagnosis of KLA was confirmed based on the clinical manifestations and pathological results.

ObjectiveTo investigate the effect of macrophages (MCs) on the differentiation of mouse induced pluripotent stem cells (iPSCs) into hepatic progenitor cells (HPCs). MethodsA total of 24 C57BL/6N mice were used to obtain MCs by peritoneal irrigation, and the supernatant was collected to obtain the conditioned medium of MCs (MC-CDM). Activin A, bone morphogenetic protein 4, and fibroblast growth factor were used to induce the differentiation of mouse iPSCs into HPCs. The differentiation of HPCs were randomly divided into control group (normal medium) and experimental group (MC group; use of MC-CDM medium on day 5 of induction). Morphology, immunofluorescence assay, and Western blot were used to compare the morphology of HPCs and the expression of related proteins between the control group and the MC group. The t-test was used for comparison of continuous data between two groups. ResultsHPCs derived from iPSCs were established in vitro, and HPCs had the potential to differentiate into hepatocytes. Immunofluorescence assay showed that compared with the D12 control group, the D12 MC group had a significant increase in the protein expression of the HPC-specific protein CK19 (0.901±0.072 vs 0.686±0.097, t=-3.093, P＜0.05). Western blot showed that compared with the D12 control group, the D12 MC group had a significant increase in the protein expression of the HPC-related protein CK19 (1.922±0.103 vs 1.448±0.012, t =-7.881, P ＜005), as well as a significant increase in the protein expression of the autophagy-related protein LC3 (1.392±0.042 vs 1.101±0048, t =-5.978, P＜005). ConclusionMCs can promote the differentiation of mouse iPSCs into HPCs, possibly by increasing the autophagy level of HPCs.

Objective:To analyze the characteristics of prenatal MRI and postnatal CT images of fetal congenital mesoblastic nephroma (CMN).Methods:We retrospectively recruited three women with a singleton pregnancy suspected of having fetal CMN by prenatal imaging examination and confirmed by postpartum surgical resection and pathological examination at Guangzhou Women and Children Medical Center from August 2017 to April 2019. The prenatal MRI, postnatal CT, and pathological examination data were analyzed to summarize the image features of fetal CMN using descriptive statistical analysis.Results:(1) The total number of deliveries in the setting during the same period was 57 716, and the incidence of CMN was 0.005% (3/57 716). All the cases were male and born through cesarean section due to polyhydramnios for case 1 and 2 and sudden fetal distress, fetal pericardial effusion with enlarged mass in the third trimester for case 3. (2) Prenatal MRI examination found that the lesions in case 1 and 3 were located in the left kidney, and in the right kidney in case 2. The tumors in the three cases were all around with clear borders and hyperintense signal on T2-weighed imaging (T2WI). Iso-signal on T1WI was noted for case 1 and 2, a slightly hypointense signal on T1-weighed imaging (T1WI), and a hyperintense signal on diffused weighed imaging were noted for case 3. (3) Postnatal CT plain scan showed uniform density tumor in cases 1 and 2 with "packing sign" in CT enhancement. Non-uniform density, internal, larger and high-density bleeding tumor was found in case 3, and the CT enhancement manifested as nodular, non-uniform, and intratumoral bleeding. (4) Postoperative pathological examination revealed that cases 1 and 2 were classic types, and case 3 was cellular type.Conclusions:In this study, the prenatal MRI characteristic of CMN is a uniform signal, iso-signal on T1WI for classic type and non-uniform signal, and reduced signal on T1WI for cellular type. In classic type cases, postnatal CT enhancement showed a "packing sign." In contrast, in cellular type cases, the CT plain scan is manifested as non-uniform, intratumoral bleeding, and the enhancement pattern showed nodular and non-uniform enhancement. However, the results of this study is limited due to the small sample size and studies with larger sample size is needed in the future.

Objective To study the effect of multi-disciplinary team (MDT) management on the outcome in neonates with omphalocele.Method A retrospective non-randomized controlled clinical study was conducted.Neonates who were diagnosed as omphalocele and admitted to the surgical neonatal intensive care unit of the Guangzhou Women and Children Medical Center from December 2010 to December 2017 were collected.Because MDT was established in December 2014,infants were assigned into non-MDT group and MDT group according to their dates of admission.The characteristics and outcomes between non-MDT group and MDT group were compared using x2,t-test or rank-sum test.Multivariate analysis was performed by Logistic regression.Result A total of 91 neonates were included in the study,50 were in non-MDT group and 41 were in MDT group.The mortality in MDT group (2.4％,1/41) was lower than that in non-MDT group (18.0％,9/50),the difference was statistically significant (P ＜ 0.05).The median time of mechanical ventilation of giant omphalocele in non-MDT group (18.3 hours) was longer than that in MDT group (41.7 hours),the difference was also statistically significant (P ＜ 0.05).After adjusting for the associated confounding risk factors,the risk of death in non-MDT group was 54 times higher than that in MDTgroup (OR=54.19,95％CI2.64 ～1 113.49,P＜0.05).Conclusion There was significant association between the MDT management and the decreased risk of death of omphalocele.

Objective To explore the clinical characteristics of cardiotoxic reactions induced by nivolumab.Methods CNKI,VIP,Wanfang,PubMed,Web of Science and MEDLINE databases were searched up to September 2018.The literature containing cases on cardiotoxic reactions induced by nivolumab was collected,relevant information was extracted,and the clinical characteristics of cardiotoxic reactions induced by nivolumab were analyzed.Results A total of 22 patients enrolled in the study,including 13 males and 9 females,aged 35-80 years,of them,70.3％ (17 cases) patients were ＞ 60 years old.Primary diseases of the patients included malignant melanoma (9 patients),lung adenocarcinoma (6 patients),squamous cell carcinoma of lung (2 patients),type B3 thymoma (1 patient),non-small-cell lung cancer (1 patient),Merkel cell carcinoma (1 patient),uveal melanoma (1 patient),and clear cell renal cell carcinoma (1 patient).There were 6,1,1,and 4 patients with history of hypertension,cardiac pacemaker implantation,pseudo bundle branch block syndrome,and targeted therapy with tyrosine kinase inhibitor,respectively.Of the 22 patients,15 patients received nivolumab monotherapy,6 patients received combination therapy with nivolumab and ipilimumab,and one patient received 3 months' ipilimumab before nivolumab.There were 2 patients received nivolumab without reasonable dosage and frequency according to the specifications,and 10 patients with missing information of drug dosage and frequency.Cardiotoxic reactions appeared 47 times totally in the 22 patients,mainly including myocarditis (13 times),heart block (6 times),pericardial effusion (5 times),and etc.,and mainly performing as the clinical characteristics of pectoralgia,dyspnea,anhelation,and fatigue.Cardiotoxic reactions first appeared on the 4th day and lastly on the 327th day after the initial dose.After the appearance of cardiotoxic reactions,nivolumab were stopped immediately in 20 patients and after the reactions improved in 1 patient,while intermittent medication was conducted in another 1 patient.Of the 22 patients,17 received symptomatic treatments,4 received pacemaker implantation,18 received high-dose glucocorticoid shock therapy,and 6 received immunotherapy.Of the 22 patients,9 (40.9％) died,12 had improved symptoms,and 1 had unknown prognosis.Conclusions The cardiotoxic reactions induced by nivolumab were characterized by dispersed incubation period and higher mortality.The symptomatic treatments and high-dose glucocorticoid treatment have a certain positive effects.

Objective To investigate the prenatal imaging features of fetal congenital esophageal atresia and to further evaluate the value of MRI and ultrasound scan in the same condition.Methods This study recruited 12 singleton gravidas whose fetuses were initially suspected with congenital esophageal atresia by prenatal ultrasound scan and then confirmed by surgery and/or upper gastrointestinal angiography after birth at Guangzhou Women and Children's Medical Center from May 2011 to May 2017.Imaging features of prenatal MRI and ultrasonography of the 12 fetuses were retrospectively analyzed.Differences in imaging findings of these two methods were analyzed by Chi-square test.Results All 12 women received prenatal ultrasound examination and eight of them underwent MRI scan when fetal congenital esophageal atresia was suggested by ultrasound.Both ultrasound and MRI were capable of identifing polyhydramnios and absent or small stomach bubble (12/12 and 8/8,respectively).However,MRI was superior to ultrasound in detecting "pouch sign "/"oral filling sign" or poor filling of small intestine (7/8 vs 3/12 and 8/8 vs 0/12,x2 were 7.500 and 20.000,both P＜0.01).While,no statistical difference was shown in detecting curved tracheal between MRI and ultrasound (2/8 vs 0/12,x2=3.333,P=0.067).For Gross Ⅰ or Gross Ⅲ congenital esophageal atresia fetuses,no statistically significant difference was found in their imaging features (all P＞0.05).The total detection rates after 32 weeks of gestation of Gross Ⅰ and Gross Ⅲ cases were both 3/6.Conclusions Prenatal MRI is a vital supplement to ultrasound due to its high display rate of characterized features of congenital esophageal atresia.Thus,the combined use of ultrasound and MRI is of great importance for prenatal diagnosis of this fetal abnormality.

Objective To summarize the experience of perioperative management for repair of congenital diaphragmatic hernia (CDH) supported by extracorporeal membrane oxygenation (ECMO). Method Retrospective review was conducted for the clinical data of CDH patients who received surgical repair on ECMO from December 2016 to June 2018 in Guangzhou Women and Children's Medical Center. Result Four fetus with prenatal diagnosis of left-side CDH were transferred to our Center and received standardized perinatal management. Moderate-severe pulmonary hypoplasia was recognized after evaluation by fetal imaging. Four cases were initiated with veno-arterial ECMO at 3, 35, 41, 11 h of life, respectively. Repair of the diaphragmatic defect was performed within two weeks after cannulation of ECMO. Furthermore, activated clotting time goals were adjusted to 180～220 s, activated partial thromboplastin time were stabilized between 50～80 s, platelets count were maintained>100×109/L and hematocrit was kept>30％before the surgery. The surgeries of four patients were completed on the 0.9th, 0.5th, 3.6th, 5.1th day of life on ECMO, respectively. The defect was repaired by parachute patch. The operative time was 85～210 min. According to CDH Staging System defect size (A to D), there were two with defects at grade C and other two at grade D. Postoperative total volume of drainage was 215～1301 ml and ECMO duration was 3.0～39.3 d. Three of them survived during neonatal period, while one died. Conclusion Repair of CDH on ECMO is feasible and help to improve neonatal survival, especially for those with moderate-severe pulmonary hypoplasia.

Objective To explore the clinical characteristics of cardiotoxic reactions induced by nivolumab.Methods CNKI,VIP,Wanfang,PubMed,Web of Science and MEDLINE databases were searched up to September 2018.The literature containing cases on cardiotoxic reactions induced by nivolumab was collected,relevant information was extracted,and the clinical characteristics of cardiotoxic reactions induced by nivolumab were analyzed.Results A total of 22 patients enrolled in the study,including 13 males and 9 females,aged 35-80 years,of them,70.3％ (17 cases) patients were ＞ 60 years old.Primary diseases of the patients included malignant melanoma (9 patients),lung adenocarcinoma (6 patients),squamous cell carcinoma of lung (2 patients),type B3 thymoma (1 patient),non-small-cell lung cancer (1 patient),Merkel cell carcinoma (1 patient),uveal melanoma (1 patient),and clear cell renal cell carcinoma (1 patient).There were 6,1,1,and 4 patients with history of hypertension,cardiac pacemaker implantation,pseudo bundle branch block syndrome,and targeted therapy with tyrosine kinase inhibitor,respectively.Of the 22 patients,15 patients received nivolumab monotherapy,6 patients received combination therapy with nivolumab and ipilimumab,and one patient received 3 months' ipilimumab before nivolumab.There were 2 patients received nivolumab without reasonable dosage and frequency according to the specifications,and 10 patients with missing information of drug dosage and frequency.Cardiotoxic reactions appeared 47 times totally in the 22 patients,mainly including myocarditis (13 times),heart block (6 times),pericardial effusion (5 times),and etc.,and mainly performing as the clinical characteristics of pectoralgia,dyspnea,anhelation,and fatigue.Cardiotoxic reactions first appeared on the 4th day and lastly on the 327th day after the initial dose.After the appearance of cardiotoxic reactions,nivolumab were stopped immediately in 20 patients and after the reactions improved in 1 patient,while intermittent medication was conducted in another 1 patient.Of the 22 patients,17 received symptomatic treatments,4 received pacemaker implantation,18 received high-dose glucocorticoid shock therapy,and 6 received immunotherapy.Of the 22 patients,9 (40.9％) died,12 had improved symptoms,and 1 had unknown prognosis.Conclusions The cardiotoxic reactions induced by nivolumab were characterized by dispersed incubation period and higher mortality.The symptomatic treatments and high-dose glucocorticoid treatment have a certain positive effects.