Objective : To explore the mechanism of hippocampal corticotropin-releasing hormone ( CRH) receptor type 1 ( CRHR1 ) in chronic stress-induced learning and memory impairment in early aged mice． Methods: C57BL /6J mice aged 12 －14 months were divided into two groups according to gender，and then divided into wild type (WT) group and hippocampal CRHR1 conditional gene knockout (KN) group according to genotype．Mice in each group were randomly divided into control group and stress group，and the stress group was subjected to chronic unpredictable stress ( CUS ) for 30 days． Genotyping of mice was performed using polymerase chain reaction ( PCR) ，agarose gel electrophoresis and real-time fluorescence quantitative PCR (RT-qPCR) ．The new object rec- ognition experiment and Morris Water maze measured learning and memory ability．Golgi-Cox staining was used to observe damage to hippocampal neuronal dendrites． The protein expressions of target protein of rapamycin (mTOR) ，p-mTOR (Ser2448) ，ribosomal protein S6 kinase ( p70S6K) and p-p70S6K ( Thr389 / Thr412 ) were detected by Western blot．Serum levels of corticotropin releasing hormone ( CRH) were measured by ELISA. Results : Compared to mice without chronic stress，the cognitive coefficient of WT stress groups decreased after chron- ic stress，and the difference was statistically significant (P ＜0. 05) ，while there was no significant difference in cognitive coefficient of KN stress groups before and after chronic stress．Compared with the WT stress group，the escape latency of the WT control group was shortened (P＜0. 05) ，and the number of crossing the platform and tar- get quadrant increased (P ＜0. 01) ，and there was no significant difference in the KN groups above． Compared with the WT control group，the WT stress group had a significant reduction in the neuronal complexity in the hipp- ocampal CA1，CA3 and DG regions (P ＜0. 05) and significant reductions in the expression of p-mTOR and p- p70S6K in the hippocampus (P＜0. 05) ．There was no significant difference in the expression of p-mTOR between the KN stress group and the KN control group (P＞0. 05) ，except that the expression of p-mTOR in the hippocam- pus of the female group decreased (P＜0. 05) ．In addition，the serum level of CRH in the stress group was higher than that in the control group (P＜0. 01) ． Conclusion Hippocampal CRHR1 regulates learning and memory im- pairment and neuronal dendrite damage in early aged mice induced by chronic stress．The mechanism may be that high levels of CRH induced by chronic stress cannot bind to CRHR1 receptor，thereby enhancing the expression of down-regulated mTOR / p70S6K signaling pathway.

ObjectiveTo observe the apoptosis induced by paeoniflorin （PF） in non-small cell lung cancer （NSCLC） cells and explore its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the inhibition rates of H1299， H292 and A549 cells with different concentrations of PF （2.5， 5， 10， 20， 25 µmol·L^-1）， and to screen suitable concentrations of PF and experimental cells. The inhibitory effect of PF on lung cancer cells was detected by clone formation assay. The effect of PF on cell apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide （PI） double staining. With the right concentration of drugs， levels of apoptosis-associated protein B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3 and Caspase-3 were detected by Western blot. At the same time， the molecular expressions of hypoxia inducible factor -1α （HIF-1α） and Hippo signaling pathway were determined. ResultCompared with the blank group， PF significantly inhibited the growth of H1299， H292 and A549 cells of human lung cancer （P<0.01）. PF significantly induced apoptosis in A549 cells （P<0.01）， decreased the Bcl-2/Bax ratio （P<0.01）， and significantly increased the cleaved Caspase-3 expression （P<0.01）. Compared with those in the blank group， the expression levels of HIF-1α， transcriptional coactivator with PDZ-binding motif （TAZ）， large tumor suppressor 1 （LATS1）， Mps one binding 1 （MOB1） and Yes-associated protein （YAP） in A549 cells of the PF treatment group were significantly decreased （P<0.01）， while the expressions of p-LATS1， p-MOB1 and p-YAP were significantly increased （P<0.01）. At the same time， there was no significant effect on the expression levels of phosphorylated mammalian Ste20-like kinase 1 （p-MST1） and MST1， which did not reach a statistical difference. ConclusionAll data demonstrated that PF showed an anti-tumor effect by improving hypoxic conditions and inhibiting the abnormally activated Hippo signaling pathway， thereby inducing and promoting apoptosis in non-small cell lung cancer.

Objective To investigate the difference of CT features of gastrointestinal stromal tumors(GIST),neurogenic tumors,and leiomyomas in stomach.Methods A retrospective analysis was performed on clinical and CT features from 312 cases of GIST,21 cases of neurogenic tumors,and 35 cases of leiomyomas in stomach.Results GIST were most commonly found in the body of stomach and exhibited large tumor sizes and late onset.CT showed GIST predominantly showed intraluminal and mixed growth pattern with irregular or round shapes and uneven density,and cystic degeneration and calcification were frequently observed.The CT values of GIST in the arterial phase and the degree of arterial enhancement were higher,with light to moderate arterial phase enhancement and moderate to marked venous phase enhancement.Gastric leiomyomas had smaller tumor sizes and presented mainly in the cardia,gastric fundus,and lesser curvature of gastric body.CT showed the intraluminal growth pattern,primarily in round shapes with uniform density,lower incidence of cystic degeneration and calcification,both the arterial and venous phase CT values and the extent of enhancement in these phases were lower,showed no or slight enhancement during the arterial phase and light to moderate enhancement during the venous phase.Gastric neurogenic tumors were predominantly located in the gastric body and antrum.CT showed the tumors demonstrated extraluminal and mixed growth patterns,most with oval-shaped appearace,uniform density and the venous phase CT values and the degree of enhancement were higher,with light to moderate arterial enhancement and moderate to marked venous enhancement.Conclusion GIST,neurogenic tumors,and leiomyomas in stomach can be differentiated based on their distinct CT features.Accurate recognition of these features aids in the differential diagnosis of these kinds of tumors.

Objective:To investigate the prognostic value of serum suppressor of cytokine signaling 3 (SOCS3) and thioredoxin-interacting protein (TXNIP) levels in transcatheter arterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) .Methods:A total of 107 HCC patients who underwent TACE treatment in Wuhan Hanyang Hospital from December 2019 to July 2021 were selected as the observation objects. According to the situation after TACE treatment, the patients were divided into poor prognosis group ( n=47) and good prognosis group ( n=60). Serum SOCS3 and TXNIP levels were detected by enzyme-linked immunosorbent assay, the prognostic factors were analyzed by logistic regression. The predictive value of serum SOCS3 and TXNIP levels before treatment for TACE treatment prognosis in patients with HCC was analyzed by receiver operator characteristic (ROC) curve. Results:There were no statistically significant differences between good prognosis group and poor prognosis group in age ( χ2=0.56, P=0.453), gender ( χ2=0.06, P=0.800), tumor size ( χ2=1.46, P=0.227), Child-Pugh grade ( χ2=0.26, P=0.608), tumor number ( χ2=0.77, P=0.382), cirrhosis ( χ2=0.03, P=0.860), TACE times ( χ2=0.16, P=0.691), alpha-fetoprotein level before treatment ( χ2=0.79, P=0.374), and hepatitis B surface antigen ( χ2=0.58, P=0.446). The proportion of TNM stage Ⅲ patients in the poor prognosis group (57.45%, 27/47) was higher than that in the good prognosis group (25.00%, 15/60), with a statistically significant difference ( χ2=11.64, P=0.001). The serum levels of SOCS3 and TXNIP in the good prognosis group before treatment were (114.34±20.39) and (45.64±6.41) pg/ml, respectively, while those in the poor prognosis group were (82.83±15.97) and (34.82±6.36) pg/ml, respectively, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=8.71, P<0.001; t=8.70, P<0.001). After treatment, the serum SOCS3 and TXNIP levels in the good prognosis group were (139.65±24.32) and (64.75±7.58) pg/ml, respectively, while those in the poor prognosis group were (92.41±16.15) and (41.74±7.23) pg/ml, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=11.48, P<0.001; t=15.90, P<0.001). Serum SOCS3 and TXNIP levels in both groups were significantly higher after treatment than before (all P<0.05). Multivariate analysis showed that TNM stage ( OR=2.53, 95% CI: 1.27-5.02, P=0.008) was an independent risk factor for prognosis in HCC patients after TACE treatment, SOCS3 ( OR=0.65, 95% CI: 0.44-0.96, P=0.031) and TXNIP ( OR=0.57, 95% CI: 0.36-0.89, P=0.014) were independent protective factors for prognosis in HCC patients after TACE treatment. ROC curve analysis showed that the sensitivity and specificity of the combined detection of serum SOCS3 and TXNIP before treatment in predicting prognosis of TACE treatment in HCC patients were 81% and 92%, respectively, the area under the curve was 0.92 (95% CI: 0.85-0.96) . Conclusion:The low levels of serum SOCS3 and TXNIP before TACE treatment in HCC patients may indicate poor prognosis after TACE treatment. The combined detection of the two has certain predictive value for judging the prognosis of HCC patients after TACE treatment.

Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.

Objective:To evaluate the fetal adrenal gland volume (AGV) and corrected adrenal gland volume (cAGV) in intrauterine growth restriction (IUGR) fetuses and observe their associations with the adverse perinatal outcomes.Methods:From February 2021 to August 2022, 32 IUGR fetuses who underwent fetal ultrasound examination in the Second Xiangya Hospital of Central South University were prospectively selected as the IUGR group, and 32 normal fetuses matched for gestational age during the same period were selected as the control group. Three-dimensional ultrasound was used to obtain fetal adrenal volume images, and the virtual organ computer-aided analysis (VOCAL) was used to measure AGV, then the cAGV was calculated. The values of AGV and cAGV were appropriately compared between the IUGR and the control groups. The pregnancy outcomes were noted. Multiple logistic regression analysis was employed to evaluate the relationship between the cAGV and adverse perinatal outcomes in IUGR fetus, with maternal age and the CPR included as covariates to control for confounding factors.Results:A total of 32 fetuses with IUGR and 32 controls were involved in this prospective study. There was no significant difference in the AGV between these two groups ( P=0.417). The cAGV of the IUGR fetus was substantially larger than that of the normal fetus ( P=0.034). In the multivariate logistic regression analysis, after adjusting for maternal age and fetal CPR, the fetal cAGV was noticeably associated with the fetal distress (adjusted OR=0.005, 95% CI=0.000-0.587, P=0.029) and the total adverse perinatal outcomes (adjusted OR=0.014, 95% CI=0.000-0.475, P=0.018). Conclusions:The value of cAGV is increased in the IUGR fetuses and associated with adverse perinatal outcomes. The evaluation of fetal AGV could be beneficial to monitoring and managing IUGR fetuses.

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a₂b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.
Humans ; Quality of Life ; Cross-Sectional Studies ; Cardiovascular Diseases/complications* ; Stress, Psychological

OBJECTIVE To prepare anemoside B4 （AB4） and programmed cell death ligand 1 （PDL1） siRNA （siP） co- delivered cRGD-modified targeting liposomes （AB4/siP-c-L）， and to study the cellular uptake in vitro. METHODS The cRGD- modified AB4-loaded targeted liposomes （AB4-c-L） were prepared by ethanol injection. AB4-c-L was mixed with 20 nmol/L siP in the same volume and AB4/siP-c-L was obtained through electrostatic adsorption. The particle size， Zeta potential， morphology， encapsulation efficiency and drug content， in vitro release behavior and serum stability of AB4/siP-c-L were investigated by laser scattering particle size tester， transmission electron microscopy， ultrafiltration centrifugation， dialysis and agar-gel electrophoresis block test. Cellular uptake of AB4/siP-c-L by Lewis lung cancer cells LLC and its intracellular localization were evaluated by flow cytometry and confocal laser scan technique. RESULTS The average particle size of AB4/siP-c-L was （187.4±3.1） nm， and the Zeta potential was （33.5±1.4） mV. AB4/siP-c-L was spheroidal in shape. The encapsulation efficiency and content of AB4 were （95.2±0.4） % and （1.0±0.2） mg/mL， respectively. AB4/siP-c-L could better package siP， and exhibited good serum stability， obvious pH sensitivity and sustained release property. The uptake rate of AB4/siP-c-L by LLC cells was significantly higher than that of free drug， and was able to accumulate in cytoplasm. CONCLUSIONS AB4/siP-c-L can effectively realize the co-loading of AB4 and gene drug siP， which has certain in vitro targeting to LLC cells.

OBJECTIVE To Establish a liquid chromatography-mass spectrometry analysis method to comprehensively and quickly identify the chemical components in Gleditsiae Fructus Abnormalis. METHODS The ultra-high liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) was applied for the composition analysis of Gleditsiae Fructus Abnormalis extract; its mobile phase was 0.1% formic acid(A)-acetonitrile(B) with gradient elution at a flow rate of 0.3 mL·min-1. Accurate ion mass and secondary fragmentation information were obtained in negative ion mode, combined with databases and standard reference for structure elucidation. RESULTS A total of 78 compounds(32 flavonoids, 15 phenolic acids, 22 lignans and 9 chemical constituents of monoterpenoid acids) with 14 potential new compounds were screened. CONCLUSION This study comprehensively analyzes the chemical composition of Gleditsiae Fructus Abnormalis, and provides a basis for the investigation of the pharmacodynamic basis and quality standards of this drug.

【Objective】 To investigate the control rate of blood glucose and its influencing factors in type 2 diabetes mellitus patients in Yulin area. 【Methods】 We selected the adult type 2 diabetes patients who visited our hospital from May 2020 to December 2021 as the subjects. Then we collected their basic information (gender, age, household income, type of medical insurance payment, education level, and duration of disease), measured their height and weight, calculated their body mass index (BMI), detected HbA1c, and measured their subcutaneous and visceral fat. The Chi-square test and multivariate Logistic regression methods were used to analyze the influencing factors. 【Results】 The total attainment rate of HbA1c (HbA1c<7%) among 877 adults with type 2 diabetes was 13.34%. The Chi-square test showed that statistical differences in the attainment rate of HbA1c among different ages, family annual income, type of medical insurance, and duration of disease. Further unconditional multivariate Logistic regression analysis model results showed that the HbA1c attainment rate in 18-44 years old group was 0.418 times higher than that in ≥60 years old group (95% CI=0.219-0.799, P=0.008). The HbA1c compliance rate of patients with employees’ medical insurance was 1.744 times that those with residents’ medical insurance (95% CI=1.131-2.782, P=0.013). The HbA1c attainment rate of diabetic patients with an annual family income of 30 000 yuan to 100 000 yuan was 1.873 times (95% CI=1.074-3.266, P=0.027), and with an annual family income of more than 100 000 yuan was 2.649 (95% CI=1.299-5.404, P=0.007) times than that of diabetic patients with less than 30 000 yuan. 【Conclusion】 The blood glucose control rate in adults with type 2 diabetes mellitus in Yulin area is lower compared with the level of the nation and other regions. Age, annual household income, and type of medical insurance payment are independent influencing factors.