OBJECTIVE To explore the effect of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 （Nrf2）/ heme oxygenase-1 （HO-1）/nicotinamide adenine dinucleotide phosphate：quinone oxidoreductase 1 （NQO1） signaling pathway. METHODS The female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged， the successfully conceived rats were collected， and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group， metformin hydrochloride group （200 mg/kg metformin by gavage）， paeoniflorin low-， high-dose groups （45， 90 mg/kg paeoniflorin by gavage， respectively）， paeoniflorin+ML385 group （90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385）， with 12 rats in each group； in addition， another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline， once a day， for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose （FBG）， fasting insulin （FINS）， insulin resistance index （HOMA-IR）]， serum inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor- α （TNF- α）] and renal tissue oxidative stress indexes [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）] were detected； the pathological changes of renal tissue were observed， and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were detected. RESULTS Compared with the control group， the renal tissue lesions of the model group were obvious， including glomerular atrophy， edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration； the levels of FBG and FINS， HOMA-IR， the levels of IL-6 and TNF-α in serum， and the level of MDA in renal tissue were significantly increased （P＜0.05）， while the levels of SOD and GSH-Px and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were significantly decreased （P＜0.05）. Compared with the model group， the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced， the above quantitative indexes were significantly improved， and the improvement effect was better in high-dose group （P＜0.05）， while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes （P＜0.05）. CONCLUSIONS Paeoniflorin can improve the abnormal glucose metabolism， inflammation and oxidative stress damage of renal tissue in GDM rats， which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Aim The key genes for necroptosis in atherosclerosis were screened by bioinformatics methods and verified with the help of in vitro experiments to provide new strategies for the prevention and treatment of atherosclerosis from the perspective of necroptosis.Methods Genes related to atherosclerotic plaques were downloaded from GEO da-tabase,and genes related to necroptosis were downloaded from GeneCards database and intersected to obtain atherosclerotic necroptosis genes,and the mechanism of action and signalling pathways of the genes were further analysed by GO and KEGG enrichment analysis,and the protein-protein interaction(PPI)network was constructed and screened for key genes.Finally,macrophages were treated with oxidized low density lipoprotein(oa-LDL)at a final concentration of 100 mg/L,and the expression of key genes was detected by RT-PCR and Western blot.Results A total of 81 atherosclerotic nec-roptosis genes were obtained.GO and KEGG enrichment analyses revealed that they were mainly enriched in the positive regulation of endopeptidase activity,IκB kinase(IKK)/nuclear factor-KB(NF-κB)signalling,and autophagy signalling pathway.Five key genes including HSPA8,STAT3,HMOX1,SQSTM1 and FAS were obtained by using five computa-tional methods of Cytoscape software cytoHubba plug-in.Compared with the normal control group,the HMOX1 gene was highly expressed in THP-1 macrophages treated with ox-LDL(P＜0.05),while the expression of the HSPA8,STAT3,SQSTM1 and FAS genes showed no significant changes(P＞0.05);the HMOX1 and SQSTM1 genes were highly expressed in RAW264.7 macrophages treated with ox-LDL(P＜0.05),while HSPA8,STAT3 and FAS genes showed no significant changes(P＞0.05).The expression of HMOX1 protein in THP-1 macrophages was also increased.Conclusion HMOX1 may be the key gene of atherosclerotic necroptosis,and it is expected to become a new target for the prevention and treatment of atherosclerosis.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective : To investigate the expression and clinical significance of classic vascular endothelial growth factor A (VEGFA) and vasotropic mimicry factor matrix metalloproteinase 14 (MMP⁃14) in lung adenocarcinoma(LUAD) . Methods : The expression levels of MMP⁃14 and VEGFA genes and proteins in LUAD and their correlation with survival and prognosis were analyzed using TCGA and UALCAN databases . Serum of 69 patients with LUAD and 20 healthy subjects (control group) was collected , and the contents of MMP⁃14 and VEGFA were detected by ELISA and chemiluminescence , respectively , to analyze the correlation between the two and the clinicopathological features of tumors and their value in prediction and diagnosis of LUAD . Results: The levels of MMP⁃14 and VEGFA in LUAD tissues and serum were higher than those in control group . There were significant differences in serum VEGFA and MMP⁃14 expression levels among early stage group , advanced stage group and control group (P< 0. 001) . MMP⁃14 was higher in T3 /T4 stage than that in T1 /T2 stage (P = 0. 045) , higher in N2 /N3 stage than that in N0 /N1 stage (P = 0. 035) , and higher in the pleural metastasis group than that in the non⁃pleural metastasis group (P = 0. 034) . VEGFA level was higher in M 1 than M0 (P = 0. 025) . Elevated VEGFA level was a risk factor for LUAD (P = 0. 002) . The area under the curve (AUC) of MMP⁃14 , VEGFA and CEA alone was 0. 793 , 0. 849 and 0. 851 , respectively , and the AUC of the combined test was 0. 952 . The overall survival ( OS) and disease specific survival (DSS) of MMP⁃14 and VEGFA low expression group were longer than those of MMP⁃14 and VEGFA high expression group (P < 0. 05) . Conclusion High expression of MMP⁃14 and VEGFA in LUAD is associated with the growth , invasion and metastasis of LUAD , respectively , and has implications for survival prognosis determination .

BackgroundSuicide is one of the serious public health problems worldwide. The relationship between suicide and neutrophil-to-lymphocyte ratio （NLR） may vary in different regions and different age. It is necessary to further investigate the relationship between NLR and suicidal ideation in Chinese children and adolescents with depression. ObjectiveTo explore the correlation between NLR and suicidal ideation in children and adolescents with depression， so as to provide clues for exploring the biomarkers of suicide. MethodsA retrospective analysis of 536 children and adolescents with depression who were hospitalized in the Third People's Hospital of Fuyang from January 2020 to December 2022 and met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10） was performed. Patients were divided into two groups according to whether they reported suicidal ideation. Demographic data， discharge diagnosis， Hamilton Depression Scale-17 item （HAMD-17） score and hematological test data （neutrophil counts， lymphocyte counts） on the second day were collected from medical records. Receiver operating characteristic （ROC） curve was used to determine the optimal cut-off point of NLR for predicting suicidal ideation in children and adolescents with depression， and binary Logistic regression was used to analyze the risk factors for suicidal ideation. ResultsAmong the 536 patients， 429 cases （80.04%） had no suicidal ideation， and 107 cases （19.96%） had suicidal ideation. Compared with patients without suicidal ideation， the HAMD-17 score ［（25.28±8.86） vs. （21.21±8.46）， F=19.400， P<0.01］， neutrophil level ［（3.85±1.68）×10⁹/L vs. （3.15±1.14）×10⁹/L， Z=4.073， P<0.01］， and NLR level ［（1.96±1.50） vs. （1.52±0.71）， Z=3.532， P<0.01］ in the suicidal ideation patients were significantly higher. The optimal critical NLR value determined by the ROC curve was 1.52 （59.80% sensitivity， 58.50% specificity）， with an area under the curve of 0.610. Logistic regression analysis showed that the risk of suicidal ideation was 1.94 times higher in those with high NLR than in the low NLR after controlling for age， sex， age at onset， duration of illness， and HAMD-17 score （OR=1.940， 95% CI： 1.251~3.009， P=0.003）. ConclusionNLR may be a risk factor and potential biomarker influencing suicidal ideation in the children and adolescents with first-episode depression. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission （number， FY2020xg14）］

OBJECTIVE: To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia. METHODS: Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons. RESULTS: In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance. CONCLUSION Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Propofol/pharmacology* ; Sevoflurane/pharmacology* ; Zona Incerta ; Anesthesia, General ; GABAergic Neurons

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3⁺T cells were deficient in 124 cases (124/192, 66.31%). CD8⁺T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8⁺T cells were positively correlated with CD3⁺T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.
Adenocarcinoma/pathology* ; B7-H1 Antigen/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Humans ; Inflammation/pathology* ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Pancreatic Neoplasms/pathology* ; Prognosis ; Tumor Microenvironment

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China. METHODS: A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance. RESULTS: A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients' knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the "vaccine hesitancy" population and "vaccine acceptance" population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375-2.488; P-reference [P-Ref] < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126-2.318; P-Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024-2.203; P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376-3.894; P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759-4.280; P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438-0.784; P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer (OR = 0.408; 95% CI: 0.221-0.753; P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer (OR = 0.393; 95% CI: 0.307-0.504; P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy. CONCLUSION This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.
COVID-19 ; COVID-19 Vaccines ; China ; Cross-Sectional Studies ; Humans ; Intention ; Neoplasms ; Pandemics ; SARS-CoV-2 ; Vaccination Hesitancy