Objective To study the effect of dual stress on the behaviors and the expression of hippocampal let-7a and serotonin receptor 4(HTR4) in rats.Methods Newborn SD rats were randomly divided into dual stress group (DS,n=6) and control group (C,n=6).The DS rats were deprived of the mother care 6 hours per day from postnatal day 1 to 14 and then were exposed to chronic mild stress for 21 days from 10 weeks old,while the rats from C group received no experimental handle but husbandry care.Open field test,forced swimmiug test and sucrose consumption test were conducted to evaluate rats' depression-like behaviors at the age of thirteen weeks.The let-7a level in hippocampus was detected by real-time Polymerase Chain Reaction and the HTR4 protein level was measured by Western Blotting.Results In the open filed test,the rearing times of DS rats was shorter than that of C group((7.50±2.35) vs (19.00±5.73),P＜0.05).In the forced swimming test,the floating time of DS rats was longer than that of C group ((110.17 ± 1.72)s vs (70.33± 1.16)s,P＜ 0.05).In the sucrose c onsumption test,DS rats consumed less sucrose than rats from C group did((0.80±0.73) vs (0.52±0.26),P＜ 0.05).The protein level of hippocampal HTR-4 in DS group was lower than that of C group((1.44±0.38) vs (0.46±0.29),P＜0.01).The let-7a level in DS group was higher than that of C group((0.04±0.01) vs (1.58±0.27),P＜0.01).The Pearson correlation analysis revealed that the sucrose preference rate of rats were negatively and positively correlated with hippocampal let-7a and HTR4 level respectively(r=-0.653,P＜0.05; r=0.774,P＜0.01),and hippocampal let-7a level showed negative association with HTR4 protein level (r=-0.803,P＜0.01).Conclusion Dual stress can induce the depressive behaviors of rats and affect the expression of let-7a and HTR4 in hippocampus.Hippocampal HTR4 and let-7a might be involved in determining individual ability to experience pleasure in rats;and hippocampal let-7a may be involved in the regulation of HTR4 gene expression in rats.

Objective To evaluate the clinical efficacy of early diagnosis by contrast-enhanced ultrasound (CEUS) combined with mesenchymal stem cell (MSC) therapy in the treatment of biliary ischemia after liver transplantation. Methods Clinical data of 9 recipients presenting with biliary ischemia detected by CEUS within 4 weeks after liver transplantation and diagnosed with non-anastomotic biliary stricture (NAS) within postoperative 1 year were retrospectively analyzed. In the conventional treatment group, 4 recipients were treated with conventional treatment including liver protection, cholagogic therapy and interventional therapy. In MSC treatment group, 5 recipients received intravenous infusion of MSC at 1, 2, 4, 8, 12 and 16 weeks after biliary ischemia detected by CEUS on the basis of conventional therapy. The interventional treatment and clinical prognosis within 1 year after liver transplantation were analyzed between two groups. Results Two recipients in the MSC treatment group required interventional therapy, which was initially given at 7-9 months after liver transplantation for 1-2 times. All recipients in the conventional treatment group required interventional therapy, which was initially delivered at postoperative 1-3 months for 2-6 times, earlier than that in the MSC treatment group. Within 1 year following liver transplantation, diffuse bile duct injury occurred in 2 recipients in MSC treatment group, and no graft dysfunction was observed. In the conventional treatment group, all recipients developed diffuse bile duct injury, and 2 recipients presented with graft dysfunction. Conclusions Early diagnosis of biliary ischemia after liver transplantation by CEUS combined with MSC therapy may delay and reduce the requirement of interventional therapy for NAS, and also improve clinical prognosis of the recipients.

As the main cell type in mammalian cortex, cortical projection neurons play an important role in brain functions, including motor control, sensation and cognition.Projection neurons in the cerebral cortex include excitatory projection neurons and inhibitory projection neurons, of which excitatory projection neurons are the main type.Cortical excitatory projection neurons have various subtypes, and most of them have their own unique developmental rules and molecular markers.Studying the origin and classification of projection neurons in the cerebral cortex is helpful to understand the mechanisms of diseases related to abnormal projection neurons.This paper reviews the origin, classification and function of cortical projection neurons.

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50-60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, P<0.05). It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years, while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40. Compared with the patients elder than or equal to 40 years old (n=3289, 27.46%), the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases, 47.18%; P<0.001). However, there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453), and both of them were high. There was no significant association between the morbidity of breast diseases and cervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Objective To evaluate the role of tumor budding in the prognostic value of intrahepatic cholangiocarcinoma(ICC) after radical resection.Methods The clinicopathological data of patients undergoing radical resection for intrahepatic cholangiocarcinoma between 2011 and 2016 were retrospectively analyzed.The number of tumor budding was counted in a ×200 microscopic field (0.785mm2).Based on receiver operation curve (ROC),the number of tumor budding ≥ 15 was defined as high-grade group,and ＜ 15 was low-grade group.Multivariate analysis were performed on predictors of the tumor.Results Low-grade group was observed in 32 cases and high-grade group in 50.High-grade group appeared to develop tumors with higher CA199,poor differentiation,larger tumor diameter,advanced stage and high risks of lymphnode metastasis (respectively x2 =5.470,4.359,5.101,4.696,5.960,all P ＜ 0.05).Univariate analysis showed that tumor budding,CA199,differentiation,tumor diameter,T classification and lymphnode metastasis were related to the overall survival of patients with ICC (respectively x2 =11.704,4.876,5.056,5.152,8.442,16.725,all P ＜ 0.05).On multivariable analysis,high-grade group was a significant independent predictor of worse OS (HR =2.707 95％ CI 1.558-4.705,P ＜ 0.001).Conclusions High-grade tumor budding is an important negative prognostic factor for ICC.

Objective:To explore the mechanism and regulatory effects of melatonin on UVB-induced melanin synthesis in human immortalized keratinocytes (HaCaT), so as to provide a theoretical basis for the skin protection of melatonin.Methods:HaCaT cells were pretreated with 10 -5 mol/L melatonin and then irradiated with 80 mJ/cm 2UVB. The melanin content was detected by NaOH assay, the proportion of premature senescence cells was detected by β-galactosidase staining kit, and the protein expression levels of both p53 and tyrosinase (TYR) were detected by Western blot at 72 h after UVB exposure. After 12 h pretreatment of ATM/ATR inhibitor, p53 inhibitor and melatonin, the proportion of premature senescence and the change of melanin content in HaCaT cells were detected at 72 h after 80 mJ/cm 2 UVB irradiation. Results:Melatonin inhibited UVB-induced increases of melanin content ( t=56.65, 13.39, P<0.05) and TYR expression ( t=16.46, P<0.05) in HaCaT cells. Melatonin alleviated UVB-induced premature senescence ( t=7.139, P<0.05) and inhibited UVB-induced increase of p53 expression ( t=19.08, P<0.05) in HaCaT cells. In addition, ATM/ATR inhibitor, p53 inhibitor and melatonin all inhibited UVB-induced increase of melanin content in HaCaT cells. Conclusions:Melatonin inhibits TYR-mediated melanin synthesis by regulating p53-related premature senescence in HaCaT cells after UVB irradiation.

In this study,the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated.From March to August,2009,17618 women,from Wufeng area of Hubei province,China,were recruited to screen breast diseases by using breast infrared diagnostic apparatus.Other diagnostic methods,such as B-mode ultrasound,X-ray mammography,needle biopsy and pathological examination were,if necessary,used to further confirm the diagnosis.The screening showed that 5990 of 17618 cases (34.00％) had breast diseases,5843 (33.16％) had mammary gland hyperplasia,48 (0.27％) had breast fibroadenoma,ll (0.06％) had breast carcinoma,and 88 (0.50％) had other breast diseases.The peak morbidity of breast cancer was found in the women aged 50-0 ages.The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8,0.157％) in comparison with that in the subjects younger than 50 years old (n=3,0.024％) (u=2.327,P＜0.05).It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years,while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40.Compared with the patients elder than or equal to 40 years old (n=3289,27.46％),the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases,47.18％; P＜0.001).However,there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453),and both of them were high.There was no significant association between the morbidity of breast diseases and cervical cancer.Since the morbidity of breast diseases was higher among young women,more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with F-flurodeoxyglucose (F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.
Chronic Disease ; Colitis, Ulcerative/therapy* ; Crohn Disease/epidemiology* ; Diarrhea ; Homeodomain Proteins ; Humans ; Inflammatory Bowel Diseases ; Mesenchymal Stem Cells/cytology* ; MicroRNAs ; RNA, Long Noncoding ; Recurrence ; Umbilical Cord/cytology*