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.

Objective: To understand the unhealthy listening habits and related factors hearing on impairment among primary and middle school students in Jilin Province, so as to provide a scientific basis for the prevention of hearing impairment in children and adolescents. Methods: From September to November 2021, a stratified cluster random sampling method was employed to select 12 847 primary and middle school students in nine cities of Jilin Province who use headphones for more than 0.5 hours daily for a questionnaire survey. Data on unhealthy listening habits, lifestyle habits and hearing impairment were collected. The data were analyzed using the χ 2 test and Logistic regression. Results: Totally 1 702 students(13.25%) experienced hearing impairment within the last month. There were statistical differences between the sexes with the average daily headphone use, the times of using headphones ≥1 h every day for one week use in all environment or noisy environment ( χ 2=47.86, 57.60, 66.31, P <0.01). Logistic regression analysis results showed that factors related to the occurrence of hearing impairment among primary and secondary school students included:average daily headphone use of 1-2 h and more than 2 h ( OR=1.74, 95%CI =1.60-1.90; OR=1.73, 95%CI =1.59-1.90), times of using headphones ≥1 h every day for one week were 1-2 times and >2 times ( OR=1.71, 95%CI =1.59- 1.84 ; OR=1.83, 95%CI =1.71-1.97), the times of using headphones≥1 h every day for one week being 1-2 times and >2 times in noisy environment per week ( OR=1.48, 95%CI =1.40-1.56; OR=1.72, 95%CI =1.61-1.86), economic underdevelopment ( OR=1.85, 95%CI =1.76-1.96), boarding （OR=1.78, 95%CI =1.69-1.89), single parent family ( OR=1.72, 95%CI =1.60- 1.87 ), daily activity duration less than 1 h ( OR=1.71, 95%CI =1.63-1.81), sedentary behavior duration more than 6 h per day ( OR=1.88, 95%CI =1.79-1.98) ( P <0.05). Conclusions The behavior of ear protection among primary and middle school students in Jilin Province needs to be enhanced, focusing on students in economically underdeveloped areas, boarding schools and single parent families. It is necessary to guide primary and middle school students to improve their bad ear habits, increase outdoor activities and reduce the time of sitting.

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.

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 investigate the changes of exam scores of retrained peritoneal dialysis (PD) operators (patients, family members, or nannies) with an internal of one year during COVID-19 epidemic and provide basis for targeted training.Methods:It was a cross-sectional survey study. The maintenance PD patients who participated in two trainings with an interval of one year during COVID-19 epidemic from November 1, 2019 to February 28, 2021 in Department of Nephrology in Peking University People's Hospital were enrolled. During COVID-19 epidemic, retraining was extended from once every six months to once a year. The clinical data were collected, the self-designed training exam score table including theoretical knowledge and operational skills assessment was used to investigate the exam scores of two trainings, and the total exam scores and sub-item scores of PD operators before and after one year were compared. Logistic regression analysis was used to analyze the associated factors of the reduction of exam scores.Results:A total of 59 patients were enrolled, with 35 males (59.32%), age of (58.41±14.52) years, and dialysis duration of 42 (12, 84) months. There were 54 patients (91.53%) operating by themselves, 22 operators (37.29%) having college degree or above, and 35 operators (59.32%) having decreased exam scores. The total exam scores were 83.17±7.90 and 80.61±8.20 before and after one year, respectively ( t=2.732, P=0.008). In the six contents of itemized scoring, compared with one year ago, the exam scores of complication treatment ( t=4.928, P<0.001) and self-monitoring ( t=3.222, P=0.002) were significantly decreased. There was no statistically significant difference in the exam scores of environment and hygiene, dialysate replacement operation, exit nursing and diet before and after one year (all P>0.05). The total exam scores in patients with dialysis duration <12 months and 36-60 months after one year were significantly lower than before one year ( t=2.309, P=0.041; t=3.086, P=0.009). There was no statistically significant difference in the exam scores of PD operators with dialysis duration of 12-<36 months and >60 months before and after one year (both P>0.05). Logistic regression analysis showed that dialysis duration was an independent associated factor of exam scores reduction (dialysis duration 36-60 months/>60 months, OR=6.233, 95% CI 1.035-37.529, P=0.046). Conclusions:During COVID-19 epidemic, the reduced frequency of retraining reduces the training exam scores of PD operators, especially in patients with dialysis duration of 36-60 months. The weak points are focused on complication management and self-monitoring. Training should be strengthened for key patients and key contents if regular retraining is not possible due to special circumstances.

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.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.