Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAc^CRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAc^CRH neurons during wakefulness and rewarding stimulation. Activation of NAc^CRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAc^CRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAc^CRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAc^CRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.
Animals ; Septal Nuclei/metabolism* ; Nucleus Accumbens/physiology* ; Corticotropin-Releasing Hormone/metabolism* ; Wakefulness/physiology* ; Neurons/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiology* ; Anxiety/physiopathology* ; Reward

The growth of solid tumors rely on angiogenesis to establish blood supply, and inducing neovascularization is a necessary condition for the growth of solid tumors. Anti-angiogenic therapies have been developed for tumors based on this theory. Although liver cancer is considered as a highly angiogenic tumor, the effectiveness of these drugs in anti-angiogenic therapies on liver cancer has not met expectations. In recent years, vessel co-option, as a long-standing but overlooked mechanism of vascularization of non-angiogenic tumors, has gradually attracted attention. Tumor tissue can promote its own growth by "hijacking" existing blood vessels in the para-carcinoma tissue instead of inducing angiogenesis, known as vessel co-option or vascular hijacking. Vessel co-option has been observed in a variety of tumors, both primary and metastatic, and is believed to be a key mechanism of anti-angiogenic resistance. The authors systematically examine the evidence, clinical prognosis, and molecular mechanisms of vessel co-option in liver cancer, and discuss its potential role in anti-angiogenic therapeutic resistance and alternative anti-tumor strategies for liver cancer.

Objective: To study the effect of Musashi-2 ( MSI2 ) overexpression on the imbalance of proliferation and apoptosis of human ovarian granulosa cell line (KGN) induced by dihydrotestosterone (DHT) ． Methods: The gene expression profiles of human ovarian granulosa cells ( GCs) in primary culture were statistically analyzed to screen the differentially expressed genes．pcDNA3. 1-MSI2 eukaryotic expression plasmid was constructed and transiently transfected into the KGN cells，and the overexpression effect of MSI2 was detected by Quantitative Real-time PCR (RT-qPCR) and Western blot．After overexpressing MSI2 in DHT induced KGN cells，MTT colorimetry and Edu staining were used to detect the proliferation of cells in each group，and flow cytometry ( FCM) was further used to detect the apoptosis of cells in each group. Results: The mRNA expression level of MSI2 gradually decreased during the primary culture of human ovarian GCs．And pcDNA3. 1-MSI2 was successfully constructed and transfected into KGN cells to improve the mRNA and protein expression levels of MSI2．Then MTT，EdU and FCM results showed that compared with the blank group，DHT induction could significantly reduce the proliferation rate and increase the apoptosis rate of KGN cells (P ＜0. 05) ．However，after MSI2 overexpression，the proliferation rate of KGN cells increased and the apoptosis rate decreased (P ＜0. 05) ，which were close to the blank group. Conclusion Overexpression of MSI2 can effectively alleviate the imbalance of proliferation and apoptosis of KGN cells induced by DHT，indicating that MSI2 plays an important role in GCs growth and follicle development.

To summarize the clinical manifestations of a case with 46, XY sex development disorder caused by myelin regulatory factor(MYRF) gene mutation and review the literature to deepen the specialists′ understanding of the clinical disease spectrum resulting from MYRF gene variations. The child had a female phenotype with mild masculinity, chromosome 46, XY, sex-determining region of Y gene(SRY gene) positive, laboratory tests were consistent with primary hypogonadism, ultrasound did not detect the gonads, but the residual reproductive tract was visible, and echocardiography suggested coarctation of the aorta, MYRF gene c. 2518C>T(p.R840*) heterozygous variant. The father did not carry this variant. The mother was untraceable, and genetic testing had not been completed. It was analyzed as pathogenic variation according to American College of Medical Genetics and Genomics(ACMG) guidelines. Sixteen cases of disorders of sex development caused by MYRF gene variation reported from 2018 to 2021 were reviewed, MYRF gene variants, 46, XY, and 46, XX individuals can be pathogenic, can affect the gonad and reproductive tract at the same time, and can also affect multiple systems. In this case, the patient presents with 46, XY sex development disorder due to MYRF gene mutation, accompanied by rare cardiovascular complications. When encountering 46, XY primary hypogonadism without well-developed Müllerian duct structures, this condition should be considered. Following confirmation, a comprehensive assessment of multi-organ function is necessary.

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

Objective: To describe the status of cognition about colorectal cancer and the screening and its relevant factors among first degree relatives of hereditary colorectal cancer patients in Guangzhou. Methods: Totally 274 subjects were investigated by a self-designed demographic questionnaire and the Chinese version of Cognitive Questionnaire for Colorectal Cancer and were analyzed by chisquare test, rank sum test and logistic regressive. Results: 60.2% (165/274) cases had a high level of cognition about colorectal cancer, 23.7% (65/274) had middle level of cognition about colorectal cancer and 16.0% (44/274) had a low level of cognition about colorectal cancer. Multivariate logistic regression analysis showed that age, sex, degree of education, marital status, family income, medical insurance and the number of cancer patients in his family were related factors (P<0.05). People who were young, female, highly educated, high family income, single, public/urban health insurance, commercial insurance and with more than 4 relatives suffering from colorectal cancer have higher cognitive level. Conclusions The level of cognition about colorectal cancer among first degree relatives of hereditary colorectal cancer patients was a little high. Medical staff should pay attention to relevant factors of health belief in subjects and develop targeted intervention to improve the level of cognition among these subjects and to promote their screening behavior.

Objective:To summarize the clinical manifestations of four patients with 46, XY disorders of sex development(46, XY DSD)due to doublesex and mab-3 related transcription factor 1(DMRT1)gene variant/haploinsufficiency, and to improve the understanding of clinicians for this disease.Methods:The medical history, physical examination, endocrine function assessment, gonadal pathology, and genetic data of 4 patients with 46, XY DSD were retrospectively collected.Results:A heterozygous new missense mutation in DMRT1 was found in one child. The chief complain was primary amenorrhoea at the age of 15 years, with the external masculinisation score(EMS)0. The DMRT1 haploinsufficiency was found in 3 cases, 1.2 Mb, 5.1 Mb, and 6.0 Mb fragments were deleted at the 9p, and one of 3 cases had 33.3 Mb repeats in the 5p. All patients visited doctor under 1 year. Two patients were raised as females, and one was raised as male. All chief complains were external genital abnormalities, EMS of them were 1, 0, and 5 respectively. Endocrine evaluation of 2 out of 4 children showed varying degrees of primary hypogonadism, and presented with complete gonadal dysgenesis. One patient showed a well function of Leydig cells and poorly function of Sertoil cells, and presented with mixed gonadal dysgenesis. One of 3 cases was diagnosed with gonadoblastoma at the age of 18 months. Patient No.4 didn′t agree with the gonadal biopsy. The chromosome karyotypes of 4 children were 46, XY.Conclusions:The visiting ages of 46, XY DSD patients caused by DMRT1 variation were older than those of patients caused by DMRT1 haploinsufficiency. The clinical manifestations are complex, and gonadal function can vary from normal to complete gonadal dysgenesis. Such patients are at high risk of gonadoblastoma and young onset. Gonadal biopsy should be performed as early as possible.

Objective? To investigate the health belief of colorectal cancer and its screening in relatives of patients with hereditary colorectal cancer,and to analyze its influencing factors. Methods? Totally 148 blood relatives of patients with hereditary colorectal cancer hospitalized in the Department of Colorectum of a Class ⅢGrade A hospital in Guangzhou from December 2016 to May 2018 were selected using convenient sampling, and investigated with the self-made general information questionnaire and Chinese Colorectal Cancer Health Belief Scale (CCCHBS). SPSS 20.0 was used for statistical analysis. Results? The colorectal cancer health belief of blood relatives of patients with hereditary colorectal cancer totaled (3.37±0.35) in which the perception and acceptance levels of screening benefits, health motives and self-efficacy of colorectal cancer were higher, while the perception levels of severity of colorectal cancer, barriers against colorectal screening and susceptibility were lower. Multivariate linear regression analysis revealed that household income per capita, educational background, with commercial medical insurance or not and the number of blood relatives with cancer were the influencing factors for health belief levels, which accounted for 41.9% of the total variance. Conclusions? The health belief in blood relatives of patients with hereditary colorectal cancer remain at a medium level. Medical and nursing workers should pay attention to the blood relatives of patients with hereditary colorectal cancer with lower educational background, lower household income and less blood relatives with cancer, take measures to improve their health belief levels, and facilitate colorectal cancer screening behaviors so as to prevent and control colorectal cancer in a better manner.

The laterodorsal tegmentum (LDT) is a brain structure involved in distinct behaviors including arousal, reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear. Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex (VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive (PV) GABAergic cells received preferential projections from local LDT neurons. With regard to the different subtypes of GABAergic cells, a considerable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatin-positive cells than to PV cells. Diverse inputs to the LDT on a system-wide level were revealed.