ATP5PO levels regulate enteric nervous system development in zebrafish, linking Hirschsprung disease to Down Syndrome.

Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the absence of enteric nervous system (ENS) in the distal region of the intestine. Down Syndrome (DS) patients have a >50-fold higher risk of developing HSCR than the general population, suggesting that overexpression of human chromosome 21 (Hsa21) genes contribute to HSCR etiology. However, identification of responsible genes remains challenging. Here, we describe a genetic screening of potential candidate genes located on Hsa21, using the zebrafish. Candidate genes were located in the DS-HSCR susceptibility region, expressed in the human intestine, were known potential biomarkers for DS prenatal diagnosis, and were present in the zebrafish genome. With this approach, four genes were selected: RCAN1, ITSN1, ATP5PO and SUMO3. However, only overexpression of ATP5PO, coding for a component of the mitochondrial ATPase, led to significant reduction of ENS cells. Paradoxically, in vitro studies showed that overexpression of ATP5PO led to a reduction of ATP5PO protein levels. Impaired neuronal differentiation and reduced mitochondrial ATP production, were also detected in vitro, after overexpression of ATP5PO in a neuroblastoma cell line. Finally, epistasis was observed between ATP5PO and ret, the most important HSCR gene. Taken together, our results identify ATP5PO as the gene responsible for the increased risk of HSCR in DS patients in particular if RET variants are also present, and show that a balanced expression of ATP5PO is required for normal ENS development.

Meta-analysis of the effect of whole-body vibration training on the improvement of limb function in patients with Parkinson's disease.

OBJECTIVE: This study aimed to systematically evaluate the effect of whole-body vibration (WBV) training on the improvement of limb function in patients with Parkinson's disease (PD). MATERIALS AND METHODS: An electronic search was performed on the databases, including PubMed, Web of Science, Scopus, SCI-hub, ScienceDirect, Embase, IEEE, Medline, Wiley, ClinicaIKey, CNKI, Wanfang, VIP database, Chinese Medical Association, and CBM Database from inception to May 2022 to collect randomized controlled studies on whole-body vibration training for patients with Parkinson's disease. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature, then used ReviewManager 5.4 software for quantitative statistical analysis, including heterogeneity test, sensitivity analysis, risk of bias assessment, combined outcome index effect size and effect size inspection. RESULTS: A total of 9 studies were included in the meta-analysis, including 346 patients, 174 patients in the control group and 172 patients in the observation group. Meta-analysis results showed that, compared with conventional physical therapy or drug therapy alone, whole-body vibration reduced the Unified Parkinson's Disease Rating Scale (UPDRSIII) score and significantly improved the motor function of patients with Parkinson's disease [MD=-2.39, 95% CI (-4.41, -0.37), Z=2.14 (p=0.23)]. Moreover, whole-body vibration significantly improved the walking stability of Parkinson's patients [MD=-1.96, 95% CI (-2.71-1.21), Z=1.17 (p=0.03)]. However, its improvement in balance ability [MD=-0.06, 95% CI (-0.77, 0.65), Z=1.07 (p=0.19)] and daily living ability [MD=0.03, 95% CI (-1.68, 0.74), Z=0.24 (p=0.87)] of patients, it was not t statistically significant. CONCLUSIONS: Compared with conventional therapy, WBV has certain advantages in improving the balance function and gait performance of PD patients, but the effect on balance ability and daily living ability is not significant. Thus, more high-quality research is required for further verification.

[Establishment and preliminary application of organoids in ovarian cancer].

Objective: To explore the establishment and application of ovarian cancer organoids. Methods: Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 µmol/L (5, 10, 20, 40, 80 µmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC50) in different organoids. Results: (1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC50 of (29.5±15.8) µmol/L. Moreover, IC50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) µmol/L vs (24.0±12.1) µmol/L; t=3.429, P=0.022]. Conclusions: Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.

[Six cases of acute toilet cleaners].

The oral toilet cleaners poisoning can result in devastating gastrointestinal tract injuries with the risk of perforation and/or hemorrhage, and sometimes potentially fatal systemic complications and sequelas. It should be given positive treatment. In this paper, six cases of acute toilet cleaners poisoning were analyzed, and the clinical characteristics and treatment effect were summarized, so as to improve the understanding, diagnosis and treatment level of the disease.

[Oncologic outcomes of early stage cervical cancer performed operation by different laparoscopic surgical procedures: analysis of clinical data from mutiple centers].

Objective: To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy. Methods: From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study. Results: There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively (P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions: The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.

Finite-temperature scaling of trace distance discord near criticality in spin diamond structure.

In this work we explore the quantum correlation quantified by trace distance discord as a measure to analyze the quantum critical behaviors in the Ising-XXZ diamond structure at finite temperatures. It is found that the first-order derivative of the trace distance discord exhibits a maximum around the critical point at finite temperatures. By analyzing the finite-temperature scaling behavior, we show that such a quantum correlation can detect exactly the quantum phase transitions from the entan-gled state in ferrimagnetic phase to an unentangled state in ferrimagnetic phase or to an unentangled state in ferromagnetic phase. The results also indicate that the above two kinds of transitions can be distinguished by the different finite-temperature scaling behaviors. Moreover, we find that the trace distance discord, in contrast to other typical quantum correlations (e.g., concurrence, quantum discord and Hellinger distance), may be more reliable to exactly spotlight the critical points of this model at finite temperatures under certain situations.

[The attentional bias of emotion in medical workers of emergency department in one hospital and it's relationship with mood state].

Objective: To study the characteristics of attentional bias to emotional stimulus in medical workers of emergency department and explore the relationship between the emotional Stroop effect and mood states, thus providing a reference to the assessment and intervention of emergency medical workers' mental health. Methods: Two kinds of emotional Stroop tasks with words and pictures and the Profile of Mood States (POMS) were administered to thirty-six medical workers of emergency department and thirty-six medical workers of other departments. Results: The reaction time to negative and positive words and pictures were all higher than the reaction time to neutral stimulus, thus showing the significant Stroop effect in medical workers. The Stroop effect to negative emotional stimulus in medical workers of emergency department was significantly smaller than that in medical workers of other departments, while the difference of Stroop effect to positive stimulus was not significant between the two groups. Correlation analyses revealed that the correlations between Stroop effect size to positive pictures and tension and angry of POMS were all negatively significant (r value was -0.314 and -0.330 respectively) , and the correlation between Stroop effect size to negative pictures and fatigue was negatively significant (r=-0.303) . Conclusions: There is a significant emotional Stroop effect in medical workers. Although the ability of anti-interference to emotional stimulus in medical workers of emergency department was better than medical workers of the other departments, the long-term avoidance to negative emotional stimulus was still has a negative effect on the mood states of individuals.

Microsatellite markers reveal genetic divergence among wild and cultured populations of Chinese sucker Myxocyprinus asiaticus.

Studies of genetic diversity and genetic population structure are critical for the conservation and management of endangered species. The Chinese sucker Myxocyprinus asiaticus is a vulnerable monotypic species in China, which is at a risk of decline owing to fluctuations in effective population size and other demographic and environmental factors. We screened 11 microsatellite loci in 214 individuals to assess genetic differentiation in both wild and cultured populations. The single extant wild population had a higher number of alleles (13) than the cultured populations (average 7.3). High levels of genetic diversity, expressed as observed and expected heterozygosity (HO = 0.771, HE = 0.748, respectively), were found in both wild and cultured populations. We also report significant differentiation among wild and cultured populations (global FST = 0.023, P < 0.001). Both STRUCTURE analysis and neighbor-joining tree revealed three moderately divergent primary genetic clusters: the wild Yangtze population and the Sichuan population were each identified as an individual cluster, with the remaining populations clustered together. Twenty-two samples collected from the Yangtze River were assigned to the cultured population, demonstrating the efficacy of artificial propagation to avoid drastic reduction in the population size of M. asiaticus. These genetic data support the endangered status of the M. asiaticus and have implications for conservation management planning.

Lowering the high rate of caesarean delivery in China: an experience from Shanghai.

OBJECTIVE: To examine the trends of caesarean delivery (CD) after an intervention to lower the high rate of CD at a Chinese maternity hospital. DESIGN: Retrospective cohort study. SETTING: A large tertiary obstetric centre in Shanghai, China, from 2007 to 2014. SAMPLE: 81 459 nulliparous women who delivered a term singleton infant. METHODS: Logistic regression was used to calculate the odds of CD while adjusting for confounders. MAIN OUTCOME MEASURE: Rate of CD before and after the intervention. RESULTS: The rate of CD decreased from 51.5% in 2008 to 36.1% in 2014, mostly due to a reduction in non-indicated antepartum CD from 27.9% in 2010 to 11.9% in 2014. After adjustment, a period effect remained with delivery between 2011 and 2014 associated with a 31% reduction in the odds of CD compared with delivery between 2007 and 2010 [odds ratio (OR): 0.69, 95% CI: 0.66-0.71)] and a 33% reduction in the odds of antepartum CD (OR: 0.67, 95% CI: 0.64-0.69). The frequencies of perinatal mortality (0.5 versus 0.4/1000), hypoxic ischaemic encephalopathy (0.9 versus 1.2/1000), meconium aspiration syndrome (0.5/1000), birth trauma (0.6/1000), respiratory distress syndrome (0.5% versus 0.4%) and necrotising enterocolitis (0.9 versus 0.6/1000) were similar. The frequency of neonatal infection increased slightly (0.6% versus 0.8%), although this could be explained by other factors. CONCLUSIONS: A marked reduction in CD has occurred at an urban tertiary care centre as a result of efforts to reduce the high rate of caesarean delivery. No notable differences in neonatal outcomes were observed. TWEETABLE ABSTRACT: High rates of caesarean delivery can be lowered without increases in neonatal morbidity and mortality.

Renormalization-group approach to quantum Fisher information in an XY model with staggered Dzyaloshinskii-Moriya interaction.

We investigate the quantum Fisher information and quantum phase transitions of an XY spin chain with staggered Dzyaloshinskii-Moriya interaction using the quantum renormalization-group method. The quantum Fisher information, its first-derivatives, and the finite-size scaling behaviors are rigorously calculated respectively. The singularity of the derivatives at the phase transition point as a function of lattice size is carefully discussed and it is revealed that the scaling exponent for quantum Fisher information at the critical point can be used to describe the correlation length of this model, addressing the substantial role of staggered Dzyaloshinskii-Moriya interaction in modulating quantum phase transitions.

Placental NRP1 and VEGF expression in pre-eclamptic women and in a homocysteine-treated mouse model of pre-eclampsia.

OBJECTIVES: To investigate the expression levels of neuropilin 1 (NRP1) and vascular endothelial growth factor (VEGF) in the placentas of women with pre-eclampsia (PE), determine whether homocysteine (Hcy) contributes to the development of PE in mice, and detect alterations in placental NRP1 and VEGF in Hcy-treated mice. STUDY DESIGN: Placental tissue samples were obtained from 16 patients with and without PE. Using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, the expression levels of NRP1 and VEGF in PE and control placental tissues were examined. Immunohistochemical (IHC) assay was used to detect the localization of NRP1 and VEGF proteins. Pregnant mice were treated with DL-Hcy on embryonic day 7.5. The symptoms of the treated mice were examined. The expression levels of Ddah1, Ddah2, eNos, Cbs and Cse were determined by quantitative RT-PCR to study the possible mechanism of hyperhomocysteinemia (HHcy). Nrp1 and Vegf expression levels in the placentas of treated mice were measured by quantitative RT-PCR, western blot analysis and IHC. RESULTS: NRP1 and VEGF were expressed at lower levels in women with PE compared with control women. The immunoreactivity of NRP1 was detected in villous trophoblast cells and villous capillary endothelial cells (ECs). Immunoreactive VEGF was observed mainly in vascular ECs within the villi. The pregnant mice treated with DL-Hcy showed PE-like symptoms such as higher systolic blood pressure and proteinuria in late pregnancy. Compared with the control mice, Ddah1, Ddah2 and eNos mRNA were expressed at lower levels, and Cbs and Cse mRNA were expressed at significantly higher levels in the placentas of the Hcy-treated group. Expression levels of Nrp1 and Vegf in mice placentas were decreased in the Hcy-treated group. CONCLUSIONS: DL-Hcy can induce PE-like symptoms in mice. Both placental NRP1 and VEGF were expressed at lower levels in women with PE and Hcy-treated mice, which may contribute to endothelial damage.

Propofol induces apoptosis and inhibits the proliferation of rat embryonic neural stem cells via gamma-aminobutyric acid type A receptor.

We investigated the effect of propofol on the proliferation and viability of rat embryonic neural stem cells (rENSCs) and the potential mechanisms involved. rENSCs were isolated and cultured in vitro and treated with 1, 10, or 50 µM propofol, while the control group was treated with 0.1 µM dimethyl sulfoxide. The effect of propofol on the proliferation and viability of rENSCs was examined by proliferation and apoptosis assays. Real-time polymerase chain reaction was employed to analyze the mRNA expression of checkpoint kinase 1 (Chk1) and p53 in rENSCs exposed to propofol. Immunoprecipitation assay and western blotting analysis were performed to analyze the effect of propofol on Chk1 and p53 activity. The gamma-aminobutyric acid type A (GABAA) receptor antagonist securinine was added to the rENSCs before being treated with propofol to investigate the role of the GABAA receptor in propofol-triggered effects on rENSCs. rENSCs specifically expressing nestin protein were successfully isolated and cultured for experiments. The inhibitory effect of propofol on rENSCs increased dose-dependently. The percentage of apoptotic cells increased to 11.7% and the activity of Chk1 and p53 enhanced after treatment with 50 µM propofol. However, addition of securinine abrogated propofol-induced apoptosis and activation of Chk1. The GABAA receptor mediates propofol-induced apoptosis and proliferation inhibition of rENSCs, possibly by modulating the Chk1/p53 signaling pathway.

Agonist of farnesoid X receptor protects against bile acid induced damage and oxidative stress in mouse placenta--a study on maternal cholestasis model.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder, which is characterized by raised serum bile acid level and potential adverse fetal outcome. Farnesoid X receptor (FXR), also known as a bile acid receptor, was found to be expressed in placenta with low level. Whether activation of FXR by specific agonists could regulate the pathogenesis of ICP is still unclear. METHODS: A model of maternal cholestasis was induced by administration of 17α-ethynylestradiol (E2) in pregnant mice for 6 days. We explored the regulatory effect of WAY-362450 (W450), a highly selective and potent FXR agonist on placenta. RESULTS: In this study, we demonstrated that administration of E2 increased bile acid levels in mouse serum, liver and amniotic fluid. Bile acid levels were significantly decreased after W450 treatment. W450 protected against the impairment of placentas induced by E2, including severe intracellular edema and apoptosis of trophoblasts. Moreover, W450 significantly induced the expressions of FXR target bile acid transport gene ATP-binding cassette, sub-family B (MDR/TAP), member 11 (Abcb11;Bsep) in placenta. W450 could also attenuate placental oxidative stress and increase the expressions of antioxidant enzymes Prdx1 and Prdx3. DISCUSSION AND CONCLUSION: In conclusion, our data demonstrated that FXR agonist W450 modulated bile acid balance and protected against placental oxidative stress. Thus, our results support that potent FXR agonists might represent promising drugs for the treatment of ICP.

Utilization of International Association of Diabetes and Pregnancy Study Groups criteria vs. a two-step approach to screening for gestational diabetes mellitus in Chinese women with twin pregnancies.

AIM: To evaluate prevalence and pregnancy outcomes using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria and screening protocol vs. a standard two-step screening approach for gestational diabetes mellitus in Chinese twin pregnancies. METHODS: A retrospective cohort study for pregnancies during 2007-2013 was performed in a tertiary hospital in Shanghai, China. Data were abstracted from the medical records of twin pregnancies delivered at the hospital. During the period 2007-2011, this hospital used a two-step approach with a 50 g screening with a cut-off value of ≥ 7.8 mmol/l followed by a 100 g diagnostic oral glucose tolerance test (OGTT) utilizing Carpenter-Coustan criteria. In 2012-2013, the hospital switched to the IADPSG protocol of universal 75 g OGTT. RESULTS: Among 1461 twin pregnancies, 643 were screened utilizing IADPSG criteria and 818 using the two-step protocol. Gestational diabetes mellitus was diagnosed more frequently in the IADPSG group than in the two-step group [20.4% and 7.0%, respectively; adjusted odds ratio (aOR) = 3.22; 95% confidence interval (CI) = 2.30-4.52]. During the IADPSG period, the incidence of pre-eclampsia was 38% lower in non-gestational diabetes mellitus affected pregnancies compared with the two-step period (aOR = 0.62; 95% CI = 0.44-0.87). We observed no significant differences in most perinatal outcomes between the two groups. CONCLUSION: Compared with a standard two-step approach to screening and diagnosis, the IADPSG screening method resulted in a three-fold increase in the incidence of gestational diabetes mellitus in twin pregnancies, with a 38% lower risk of pre-eclampsia but no significant difference in most perinatal outcomes in non-gestational diabetes mellitus affected pregnancies.

A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency.

A 15-year-old Chinese male with infantile-onset hypotonia, developmental delay, ptosis, and oculogyric episodes presented with a history of chronic diarrhoea since the age of 5 years. At presentation, he had an exacerbation of diarrhoeal symptoms resulting in dehydration and malnutrition with a concurrent severe chest infection. In view of his infantile-onset hypotonia, oculogyric crises, and protracted diarrhoea, an autonomic disturbance related to neurotransmitters was suspected. Urine organic acid profiling was compatible with aromatic L-amino acid decarboxylase deficiency. The diagnosis was confirmed based on cerebrospinal fluid analysis and genetic mutation analysis. The patient was treated with a combination of bromocriptine, selegiline, and pyridoxine; a satisfactory reduction in diarrhoea ensued. Our report highlights the importance of urine organic acid screening in infantile-onset hypotonia, especially when accompanied by oculogyric crises, and severe diarrhoea which could manifest as a result of autonomic disturbance.