This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objective:To construct a acute myeloid leukemia(AML)cell line in which HOXA5 gene is stably knocked out by CRISPR-Cas9-mediated gene editing technique,so as to clarify the effect of HOXA5 gene knockout on the proliferation of AML cells,and preliminarily explore the role of HOXA5 gene in the pathogenesis of AML.Methods:The expression of HOXA5 in bone marrow mononuclear cells(BMMC)of non-tumor hematological patients and newly diagnosed AML patients was detected by quantitative real-time PCR(qRT-PCR)and Western blot,respectively.The AML cell line KO-HOXA5-THP-1 was constructed in which HOXA5 gene was knocked out by CRISPR-Cas9-Mediated gene editing technique,and the knockout of HOXA5 gene was verified by qRT-PCR and Western blot,and the cell proliferation was detected by CCK-8 assay.Results:Compared with non-tumor hematological patients,the levels of HOXA5 gene and protein in BMMC of newly diagnosed AML patients were significantly increased(P＜0.05).The stable HOXA5 knockout cell line can be obtained by CRISPR-Cas9-Mediated gene editing technique,and the proliferation ability of THP-1 cells with HOXA5 gene knockout was significantly decreased(P＜0.05).Conclusion:HOXA5 is highly expressed in AML cells,and knocking out HOXA5 can significantly affect the proliferation ability of AML cells,which provides a new potential therapeutic target for the precise treatment of AML.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity

Objective: Nutrition is closely related to the health of the elderly population. This study aimed to provide a comprehensive picture of the nutrition status of elderly Chinese and its related dietary, geographical, and socioeconomic factors. Methods: A total of 13,987 ≥ 60-year-old persons from the 2010-2013 Chinese National Nutrition and Health Survey were included to evaluate various aspects of malnutrition, including underweight, overweight or obesity, and micronutrient inadequacy. Results: Overall, the prevalence of obesity, overweight, and underweight was 12.4%, 34.8%, and 5.7%, respectively, with disparities both geographically and socioeconomically. The prevalence of underweight was higher among the older old (≥ 75 years), rural residents and those with low income, with low education status, and residing in undeveloped West areas. More than 75% of the elderly do not meet the Dietary Reference Intakes for vitamins A, B Conclusions Obesity epidemic, inadequacy of micronutrient intake, and high prevalence of underweight and anemia in susceptible older people are the major nutrition challenges for the rapidly aging population in China.
Age Factors ; Aged ; Aged, 80 and over ; China/epidemiology* ; Cross-Sectional Studies ; Diet/statistics & numerical data* ; Female ; Health Surveys ; Humans ; Male ; Malnutrition/etiology* ; Micronutrients/deficiency* ; Middle Aged ; Nutritional Status ; Overweight/etiology* ; Risk Factors ; Socioeconomic Factors ; Thinness/etiology*

Objective: To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years. Methods: Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties. Results: A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( : 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( s) (95% ) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted (95% ) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group. Conclusion Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.
Adult ; Aged ; China ; epidemiology ; Diabetes Mellitus ; chemically induced ; epidemiology ; Diet ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Selenium ; deficiency ; metabolism ; Soil ; chemistry

Objective To characterize the epidermal growth factor receptor (EGFR) gene in Schistosoma japonicum (SjEGFR gene) and investigate the role of the EGFR gene in regulating the growth, reproductive system, maturation and fecundity of S. japonicum. Methods Rapid amplification of cDNA ends (RACE) was performed to obtain the full length of the SjEGFR gene, and the SjEGFR gene expression was quantified in different developmental stages of S. japonicum using a quantitative real-time PCR (qPCR) assay. The tissue localization of the SjEGFR gene was detected in 22-day parasite using whole-mount in situ hybridization (WISH). Following RNA interference (RNAi)-induced knockdown of the SjEGFR gene, the worm length, pairing rate and worm burden of S. japonicum were measured, and the worm morphology was observed using optical microscopy and confocal microscopy. Results The SjEGFR gene was identified with a conserved tyrosine-kinase active site, and the SjEGFR gene expression was detected at various developmental stages in male and female parasites. WISH showed that the transcript of the SjEGFR gene was localized on the tegument and in the digestive organs of S. japonicum. RNAi-induced SjEGFR knockdown resulted in marked suppression of the worm growth, smaller size of male testicles that contained more immature spermatocytes, and apparent impairment of ovary and vitelline gland development. In addition, no eggs were found in the uterus of SjEGFR knocked-down female parasites, indicating the interruption of egg production. Conclusions Inhibition of SjEGFR expression may remarkably suppress the growth and maturation of S. japonicum, and interrupt the egg production.

Objective: To differentiate the inflow and outflow channels of gastric varices in cirrhotic portal hypertension patients using multi-slice spiral CT (MSCT), and to assess the relationship between calculable CT volume of gastric varices and the amount of tissue adhesive. Methods: 97 cases with cirrhotic gastric varices who were admitted from November 2013 to August 2017 were selected. The type and shape of gastric varices were observed before tissue glue injection treatment by MSCT. The correlation between CT volume of gastric varices and the amount of tissue adhesive was evaluated by Spearman rank correlation coefficient and Univariate linear regression analysis. Results: MSCT showed that Le, g type had the highest proportion (54.6%), followed by Le, g, Lg (20.6%). Le, Lg and Lgf type accounted for 17.5%, and 5.2%, respectively, while Lgf+b accounted for 2.1%. On MSCT, varices of the gastric fundus were in the direction from bottom to top, and 75% of the fundus had a large curved side varices combined with gastric and renal shunt. Under the gastroscopy, varices in the small curved side of the gastric fundus from near to far were formless. In addition, varices in the large curved side of the gastric fundus when observed from different angles to the direction of blood flow (reverse gastroscope) were 72.7% (near and far) or 20.5 % (far and near). There was a positive correlation between CT volume (R = 0.97, P < 0.001) and the amount of tissue adhesive (Y₁ = 0.35 + 0.65X1, Univariate linear regression equation; ρ = 0.89, P < 0.001, Spearman correlation analysis). Conclusion MSCT can recognize the vascular shape and inflow and outflow channels of gastric varices. A positive correlation between CT volume and the amount of tissue adhesive, suggested that the CT volume measurement before treatment could be used as one of the method to predict the amount of tissue adhesive.

ObjectiveThe mechanism of paraquat poisoning (PQP) inducing acute lung injury is not clear. Nuclear factor erythroid 2-related factor 2 (Nrf2 )-antioxidant response element (ARE) is found to be a most important endogenous antioxidant defense pathway. This study aimed to explore the protective effect of 5- amino salicylic acid (5-ASA) against PQP-induced acute lung injury by activating the Nrf2-ARE pathway.MethodsEighty healthy adult male SD rats were randomly divided into four groups: blank control, 5-ASA control, PQP, and 5-ASA treatment. The animals in the PQP and 5-ASA treatment groups were injected with paraquat at 20 mg/kg into the left abdominal cavity for construction of the PQP model and those in the blank and 5-ASA control groups with isotonic saline at 1 mL. At 2 hours after modeling, the rats in the 5-ASA control and 5-ASA treatment groups received gavage of 5-ASA 75 at mg/kg for 3 successive days. At 1 and 3 days after observation, all the rats were sacrificed and the lower lobe of the right lung harvested for HE staining and observation of pathologic changes in the lung tissue. Meanwhile the left lung tissue was collected for determination of the expressions of Nrf2 and HO-1 proteins by Western blot.ResultsBehavioral changes were observed in the rats of the PQP and 5-ASA treatment groups, but less obvious in the latter. The alveolar wall capillaries of the rats in the PQP group were expanded and congested significantly, with widened alveolar septa and infiltration of a large number of inflammatory cells at 1 and 3 days, even severer at 3 days. The rats of the 5-ASA treatment group showed obviously reduced edema and the inflammatory cell infiltration at the corresponding time points as compared the PQP group. The lung tissue pathology scores were significantly higher in the 5-ASA treatment and PQP groups than in the blank control at 1 day (0.66±0.10 and 0.61±0.04 vs 0.18±0.05, P<0.05) and at 3 days (0.74±0.08 and 0.49±0.08 vs 0.16±0.02, P<0.05), but markedly lower in the 5-ASA treatment than in the PQP group (P<0.05). Both the expressions of Nrf2 and HO-1 proteins were remarkably higher in the 5-ASA control, PQP and 5-ASA treatment groups than in the blank control at 1 and 3 days (P<0.05), and so were they in the 5-ASA treatment than in the PQP group (P<0.05).Conclusion5-ASA can effectively reduce PQP-induced acute lung injury, which may be related to its up-regulation of the Nrf2 expression.