Previous studies have demonstrated that exocytotic release from large dense cored vesicle(LDV)at structurally non-specialized areas within axon terminal of the medullary dorsal horn and it has been speculated that non-synaptic exocytosis from LDV may be a probable mechanism for neuropeptide release. This study provides the evidence that SP containing LDV can release their contents by exocytosis at non-synaptic sites of axon terminal within superficial dorsal horn of medulla oblongata in the rat with ultrastructural immunohistochemistry staining by an unilateral deafferentation. The results of this study confirmed previous hypothesis that SP and perhaps other peptides containing LDV release their contents by exocytosis at non-specialized sites and the significance of such release is discussed.

The ultrastructural localization of substance P (SP) immunoreactivity, especially the morphology, number and distribution of positive large granular vesicles (LGV) in SP axon terminals of the trigeminal subnucleus caudalis of the rat were studied by electron microscopic immunocytochemistry. This study revealed that SP immunoreactivity was mostly located in axon terminals and unmyelinated fibers. SP axon terminals contained both clear round vesicles and LGV. SP immunoreactivity was found in LGV, and on the surface of clear round vesicles and outer membrane of mitochondria. Positive LGV were spherical or oval in shape (60～120nm in diameter). The number of LGv was mostly 2～3 in a SP axon terminal. LGV often apposed to the axolemma or scattered in the centre of terminal. LGV were far from the presynaptic sites of the SP terminals which formed synapses. The number of LGV closed to the terminal membrane was significantly (P

Objective: This study aims to investigate the impact of individual and family factors on anxiety and loneliness of middle school students during quarantine in the COVID-19 pandemic and to provide reference for discussing the possible effective intervention paths in the stress process of public health emergencies. Methods: A total of 11 596 students from junior and high schools in Shanghai were selected to complete the questionnaire with the stratified random cluster sampling method. Generalized Anxiety Disorder(GAD-7) and UCLA Loneliness Scale, University of California at Los Angeles(ULS-6) were used for the survey. Results: The prevalence of anxiety and loneliness were 34.78% and 52.44% respectively. The rate of anxiety and loneliness in girls (36.13%, 54.62%) was higher than that of boys (33.44%, 50.28%)(χ 2=17.03, 21.82, P<0.05). Logistic regression analysis showed that graduates (OR=1.34, 95%CI=1.18-1.52), students ranking in the middle (OR=1.25, 95%CI=1.08-1.45) or in the bottom 25% (OR=1.76, 95%CI=1.50-2.05), non only children in the family (OR=1.25, 95%CI=1.09-1.43) and low socioeconomic status (OR=1.42, 95%CI=1.23-1.65) were associated with increased risk of moderate and severe level of anxiety(P<0.05). Girls(OR=1.20, 95%CI=1.12-1.30), graduates(OR=1.13, 95%CI=1.04-1.24), non residents(OR=1.20, 95%CI=1.09-1.33), lower level of grades(OR=1.72, 95%CI=1.55-1.91) and not living with parents(OR=1.32, 95%CI=1.18-1.48) were associated with increased risk of loneliness(P<0.05). Conclusion During the quarantine period caused by the COVID-19 pandemic, negative emotions such as anxiety and loneliness among adolescents need attention, especially females, graduates, only children and students with low rankings or low socioeconomic status.

As a normal physiological substance,D-galactose can induce a process similar to natural brain aging in vivo and in vitro when administered excessively,and thus it is widely used to induce brain aging models in China and abroad.The model of brain failure induced by D-galactose has the advantages of a short modeling time,low cost,and significant effect.However,the induction mechanisms are complex and diverse,and the relationships between the mechanisms are unclear,which limit the practical applications of the model.This article reviews the in vivo metabolism of D-galactose and the various mechanisms involved in the induction of brain aging,as well as the links between the mechanisms,to provide a reference for the application and development of this model and the in-depth study of brain aging.

Objective:To explore the clinical profile and prognostic features of relapsing polychondritis (RP) with nervous system involvement.Methods:The clinical data of 28 RP patients with nervous system involvement admitted to Peking Union Medical College Hospital from December 2005 to November 2019 were collected and analyzed.Results:The median age of the patients was 50 years and 57.1% (16/28) were men. Patients with central nervous system involvement accounted for 92.9% (26/28) of the total. Common manifestations included headache (69.2%, 18/26), cognitive impairment (38.5%, 10/26), and mental disorders (38.5%, 10/26); only two cases had peripheral nervous system damage. Brain magnetic resonance imaging revealed that subcortical (13/18) and cortical (8/18) tissues were most affected. Cerebrospinal fluid tests showed that the median white blood cell count was 55×10 6/L, while the protein level was also slighted elevated ((0.54±0.17) g/L). All patients were treated with glucocorticoids, and 85.7% (24/28) of patients with immunosuppressants; 27 patients showed optimistic responses to the treatment, while 24 had recurrent courses. Cognitive dysfunction was the most common residual symptom. Follow-up data of 16 patients were available with an average follow-up time of 3.3 years. Ten of the patients were in stable condition and three patients died. Conclusions:Nervous system damage, especially limbic encephalitis and meningitis may present in course of RP. However, it is a challenge to diagnose for the non-specific clinical manifestations. Treatment with corticosteroids and immunosuppressants can lead to a favorable response.

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

Objective:To establish high performance liquid chromatography (HPLC) wavelength switching method to simultaneously determine the contents of chlorogenic acid, hydroxysafflor yellow A, ferulic acid, Nicotiflorin, Osthole and columbianadin in Tongluo Zhibi Prescription.Methods:The column was XBridge C18 column (250 mm × 4.6 mm, 5 μm); the mobile phase was acetonitrile (A)-0.1% phosphate water (B); gradient eluted, with flow rate: 1 ml/min, column temperature: 30 °C, detection wavelength 330 nm (0-14 min detection of chlorogenic acid, 15-80 min detection of ferulic acid, Nicotiflorin, Osthole, and columbianadin), 403 nm (14-15 min detection of hydroxysafflower yellow pigment A).Results:Chlorogenic acid, hydroxyrhodopsin A, ferulic acid, kaempferol 3-O-rutinoside, serpentin, and dihydroeurobicarpus angelicus acid ester showed good linearity ( R2 ≥ 0.999 8) within 0.029 7-1.485 0, 0.030 0-1.500 0, 0.009 9-0.495 0, 0.017 5-0.875 0, 0.028 4-1.420 0, 0.013 7-0.685 0 μg, respectively. The precision, stability (24 h), repeatability relative standard deviation ( RSD) were all <2%. The average spiked recoveries were all in the range of 95%-105%, and the RSDs were all in the range of 0.32%-1.67%. In 10 batches of test samples of Tongluo Zhibi Prescription, the content of the above six components, including chlorogenic acid, was determined to be 0.221 60, 0.314 30, 0.085 10, 0.032 95, 0.043 87, 0.026 21 mg/g in the following order. Conclusion:The established HPLC wavelength switching method is fast, simple and accurate, which can be used for simultaneous determination of the content of the above six components in Tongluo Zhibi Prescription, which provides reference for quality monitoring and new dosage form research of Tongluo Zhibi Prescription.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

BackgroundAt least 77.0% of breast cancer patients will experience cancer-related fatigue. Hope level and resilience play as two important factors that have influence on cancer-related fatigue. Currently， most studies involve one single factor， either the level of hope or resilience， and explore its relationship with the cancer-related fatigue. Only limited studies explore the action mechanism behind with all three factors put together. ObjectiveTo investigate the mediating role of resilience between hope and cancer-related fatigue in patients with breast cancer， and to provide references for finding intervention targets for cancer-related fatigue in breast cancer patients. MethodsFrom March to October 2022， this study was conducted on the sample size of 324 hospitalized patients from three Grade-A tertiary hospitals in Shaanxi Province. These patients were over 18 years old and pathologically diagnosed as breast cancer. Hope level， resilience and cancer-related fatigue were assessed， respectively， using Adult Dispositional Hope Scale （ADHS）， Connor-Davidson Resilience Scale （CD-RISC-10） and Cancer Fatigue Scale （CFS）. Pearson Correlation Analysis was used to analyze the relationship between ADHS score， CD-RISC-10 score and CFS score. AMOS 22.0 was used to analyze the mediating effect of resilience between hope level and cancer-related fatigue in breast cancer patients. ResultsThe detection rate of cancer-related fatigue in patients with breast cancer was 88.58%. Scores of ADHS and CD-RISC-10 were negatively correlated with CFS score （r=-0.750， -0.809， P<0.01）. ADHS score was positively correlated with CD-RISC-10 score （r=0.901， P<0.01）. Resilience had a mediating effect between the hope level and cancer-related fatigue. The mediating effect value was -0.676（95% CI： -1.005~-0.347）， accounting for 81.90% of the total effect. ConclusionThe hope level of breast cancer patients can affect cancer-related fatigue directly as well as indirectly through resilience. Resilience plays a partial mediating role between hope level and cancer-related fatigue .