ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective To explore the diagnostic value of 18F-fluorodeoxyglucose(FDG)PET/CT in primary pulmonary enteric adenocarcinoma.Methods The clinical and imaging data of 9 patients with primary pulmonary enteric adenocarcinoma who under-went 18F-FDG PET/CT examination were retrospectively analyzed,including lesion distribution,morphology,maximum standardized uptake value(SUVmax),clinical symptoms and signs,gastroscopy finding,puncture pathological results,and serum tumor markers[carbohydrate antigen 72-4(CA72-4),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),carcinoembryonic antigen(CEA),carbo-hydrate antigen 199(CA199)].Results Pathological examination confirmed a diagnosis of primary pulmonary enteric adenocarcinoma after excluding gastrointestinal primary tumors through clinical evaluation.In all nine patients,18F-FDG PET/CT examination did not reveal any evidence of digestive system malignancies,and gastrointestinal microscopy was negative.Primary lesions were observed as masses or nodular types in 6 cases(5 in the left lung and 1 in the right lung),while 3 cases exhibited diffuse bilateral pulmonary involvement(manifested as multiple patchy opacities,nodules,ground-glass opacities,and consolidations).All pulmonary primary lesions showed increased 18F-FDG uptake,with SUVmax ranging from 2.7 to 12.8,mean 8.6±3.7.The six masses-or nodular-type primary lesions showed maximum diameters ranging from 2.1 to 10.5 cm,mean(5.23±3.06)cm.Four cases demonstrated hilar and mediastinal lymph node metastases,intrapulmonary metastases,and distant metastases,while 1 case showed only distant metastasis.Elevated levels of serum tumor markers were observed as follows:CA72-4 in 7 cases(10-273.3 U/mL),CEA in 7 cases(5-147.4 ng/mL),CA199 in 6 cases(31.22-4 364 U/mL),and CYFRA21-1 in 5 cases(8.31-99.7 ng/mL).Conclusion When pathological biopsy of a pulmonary lesion suggests primary pulmonary enteric adenocarcinoma after excluding gastrointestinal primary tumors,and 18F-FDG PET/CT shows no gastrointestinal masses,this may support the diagnosis of primary pulmonary enteric adenocarcinoma.

Objective To investigate the expression of NOP2/Sun RNA methyltransferase family member 2(NSUN2)and protein arginine methyltransferase 5(PRMT5)in retinoblastoma(Rb)tissue and their correlation with the survival prognosis of Rb patients.Methods From February 2019 to February 2021,84 patients with Rb(Rb group)were selected from Beijing Anzhen Hospital Affiliated to Capital Medical University Nanchong Hospital,and 50 normal retinal tissues were used as control group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the levels of NSUN2 mRNA and PRMT5 mRNA in retinal tissues.Kaplan-Meier curve was used to analyze the effect of NSUN2 mRNA and PRMT5 mRNA on the prognosis of Rb patients.COX regression analysis was used to analyze the factors affecting the prognosis of Rb.Results The expression of NSUN2 mRNA(3.11±0.42)and PRMT5 mRNA(2.84±0.39)in Rb cancer tissues were higher than that in the control group(0.80±0.23,0.76±0.20),and the differences were statistically significant(t=35.935,35.033,all P<0.001).The expression of NSUN2 mRNA and PRMT5 mRNA in Rb cancer tissues with tumor diameter≥20mm,undifferentiated and ⅡRC stage D～E were higher than that in tumor diameter<20mm,differentiated tissues and ⅡRC stage A～C cancer tissues,and the differences were statistically significant(t=18.297,141.770,16.693;18.663,139.144,39.947,均P<0.001).The 3-year progression-free survival rate in the high expression group of NSUN2 mRNA was lower than that in the low expression group(60.00%vs 88.64%).The 3-year progression-free survival rate in the high expression group of PRMT5 mRNA was lower than that in the low expression group(56.10%vs 93.02%)(Log rank χ2=13.440,19.501,all P<0.001).Undifferentiated type,ⅡRC stage D-E stage,NSUN2 mRNA high,PRMT5 mRNA high were risk factors affecting the prognosis of Rb patients(Waldχ2=5.923～7.161,all P<0.001).Conclusion The expression of NSUN2 mRNA and PRMT5 mRNA in Rb tissues is increased,which is related to the maximum diameter of tumor,pathological classification and ⅡRC stage,and can be used as a tumor marker to evaluate the survival prognosis of Rb.

Objective To investigate the value of gemstone spectral CT multiparameter for risk assessment in acute pulmonary embolism(APE).Methods A total of 83 patients diagnosed with APE were categorized into three groups based on the European Society of Cardiology(ESC)guidelines:high-risk group(n=23),medium-high-risk group(n=29),and medium-low-risk group(n=31).The spectral CT multiparameters for each group were subsequently analyzed and compared.The predictive value of the region of interest perfusion defect iodine group value(ROI vPD),whole lung mean perfusion iodine group value(vMeanIP),and lung perfusion defect volume ratio(rPDvol)in high-risk APE patients were assessed using receiver operating characteristic(ROC)curves.Pearson correlation was employed to analyze the correlation of gemstone spectral CT multiparameter with pulmonary artery obstruction index(PAOI)and right ventricle/left ventricle diameter ratio(rRVD/LVD).Results Whole lung minimum perfusion iodine group value(vMinIP),whole lung maximum perfusion iodine group value(vMaxIP),vMeanIP,rPDvol and right ventricle/left ventricle volume ratio(rRVV/LVV)exhibited significant differences across all groups.The area under the curve(AUC)for ROI vPD,vMeanIP,and rPDvol in high-risk APE patients were 0.792,0.831,and 0.884,respectively.The sensitivity and specificity for ROI vPD(≤0.3),vMeanIP(≤1.1),and rPDvol(≥23.7％)were recorded at 95.7％and 60.0％,78.3％and 75.0％,as well as 91.3％and 75.0％,respectively.Simultaneously,the gemstone spectral CT multiparameter exhibited correlations with PAOI and rRVD/LVD.Conclusion The gemstone spectral CT multiparameter can be utilized to evaluate the severity and progression of patients with APE.

Objective To explore the current status and influencing factors of returning to work among breast cancer patients by Meta-analysis.Methods Literatures studies on the current status and influencing factors of returning to work among breast cancer patients were systematically searched in databases.The literature was sorted,screened and evaluated,and a total of 15 articles were included,involving 3975 breast cancer patients after surgery.Results After Meta-analysis,the return-to-work rate among breast cancer patients was 48.49％.Age,treatment method,social support,surgical method,and self-efficacy were influencing factors.Conclusion Clinically,early evaluation and intervention should be carried out for patients with relevant factors to improve the quality of life after breast cancer surgery and improve the level of patients' readiness to return to work.

Objective:To analyze and confirm the ambiguous results of HLA-DRB1 genotyping in one case.Methods:HLA genotyping was performed on a sample of hematopoietic stem cell donor using Illumina MiSeq-based next-generation sequencing(NGS).The ambiguous results of HLA-DRB1 locus were further analyzed and confirmed through PacBio SMRT third-generation sequencing.Results:The Illumina MiSeq-based NGS typing results suggested the presence of a new HLA-DRB1*11 allele(DRB1*11:NEW,12:01)in the specimen,with a mismatch of G＞A located in the 40th residue of exon 1 compared with the nearest allele DRB1*11:01:01:03.However,due to the long sequence of intron 1,this observed mutation site was so far away from the near heterozygous sites that no reads could cover this gap.Therefore,it was impossible to determine which consensus the mutation site was located in,and the NGS-based genotyping results were obtained from the random allocation by the software,which was ambiguous and unreliable.In order to confirm the results,the long-read third generation sequencing technology based on PacBio was applied to genotype the DRB1 locus.The results showed that the DRB1 typing was HLA-DRB1*11:01,12:10.E1-40A was actually located in the allele HLA-DRB1*12:XX,which was exactly matched with HLA-DRB1*12:10.Conclusion:For some new alleles suggested by NGS,especially the ambiguous ones that are far away from other heterozygous sites,it is necessary to analyze and confirm them by other methods such as the third-generation long-read sequencing technology to obtain reliable results.

Objective To investigate the expression of NOP2/Sun RNA methyltransferase family member 2(NSUN2)and protein arginine methyltransferase 5(PRMT5)in retinoblastoma(Rb)tissue and their correlation with the survival prognosis of Rb patients.Methods From February 2019 to February 2021,84 patients with Rb(Rb group)were selected from Beijing Anzhen Hospital Affiliated to Capital Medical University Nanchong Hospital,and 50 normal retinal tissues were used as control group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the levels of NSUN2 mRNA and PRMT5 mRNA in retinal tissues.Kaplan-Meier curve was used to analyze the effect of NSUN2 mRNA and PRMT5 mRNA on the prognosis of Rb patients.COX regression analysis was used to analyze the factors affecting the prognosis of Rb.Results The expression of NSUN2 mRNA(3.11±0.42)and PRMT5 mRNA(2.84±0.39)in Rb cancer tissues were higher than that in the control group(0.80±0.23,0.76±0.20),and the differences were statistically significant(t=35.935,35.033,all P<0.001).The expression of NSUN2 mRNA and PRMT5 mRNA in Rb cancer tissues with tumor diameter≥20mm,undifferentiated and ⅡRC stage D～E were higher than that in tumor diameter<20mm,differentiated tissues and ⅡRC stage A～C cancer tissues,and the differences were statistically significant(t=18.297,141.770,16.693;18.663,139.144,39.947,均P<0.001).The 3-year progression-free survival rate in the high expression group of NSUN2 mRNA was lower than that in the low expression group(60.00%vs 88.64%).The 3-year progression-free survival rate in the high expression group of PRMT5 mRNA was lower than that in the low expression group(56.10%vs 93.02%)(Log rank χ2=13.440,19.501,all P<0.001).Undifferentiated type,ⅡRC stage D-E stage,NSUN2 mRNA high,PRMT5 mRNA high were risk factors affecting the prognosis of Rb patients(Waldχ2=5.923～7.161,all P<0.001).Conclusion The expression of NSUN2 mRNA and PRMT5 mRNA in Rb tissues is increased,which is related to the maximum diameter of tumor,pathological classification and ⅡRC stage,and can be used as a tumor marker to evaluate the survival prognosis of Rb.

OBJECTIVE To explore the relationship between levels of peripheral blood interleukin(IL)-6,IL-18,IL-1β,tumor necrosis factor(TNF-α),procalcitonin(PCT),C-reactive protein(CRP)and vascular cell adhesion molecule-1(VCAM-1)and disease condition and prognosis in children with Mycoplasma pneumoniae pneumonia(MPP),and to construct a prediction model.METHODS A total of 196 children with MPP admitted to Dazhou Central Hospital in Sichuan Province from Jan.2022 to Jan.2024 were selected as the MPP group and were divided into the mild group(n=124)and the severe group(n=72)according to the clinical pulmonary infection score(CPIS),and 200 healthy children who participated in physical examination in the hospital during the same period were selected as the healthy group.All 196 children with MPP received relevant treatments and were divided into a poor prognosis group(n=40)and a good prognosis group(n=156)according to their prognosis.The levels of peripheral blood IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 were measured in all the subjects,the risk factors affecting the disease condition and prognosis of children with MPP were analyzed,the prediction model was constructed,and the receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated to evaluate the predictive effect of the constructed prediction model.RESULTS Peripheral blood IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 levels in the MPP group were higher than those in the healthy group(P＜0.05).The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in peripheral blood were significantly higher in the severe group than those in the mild group(P＜0.05).IL-6(OR=1.203),IL-18(OR=1.072),IL-1β(OR=4.060),TNF-α(OR=1.264),PCT(OR=3.132),CRP(OR=1.546)and VCAM-1(OR=1.009)were risk factors for severe condition in MPP children(P＜0.05).The prediction model constructed for the devel-opment of severe illness in MPP children was as follows:Logit(P)=-67.522+0.185×IL-6+0.069×IL-18+1.401×IL-1β+0.234×TNF-α+1.142×PCT+0.436×CRP+0.009 ×VCAM-1.The AUC of the prediction model for predicting severe conditions in MPP children was 0.985.The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in peripheral blood in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).IL-6(OR=1.083,95％CI:1.024-1.145,P=0.005),TNF-α(OR=1.083,95％CI:1.002-1.172,P=0.046)and VCAM-1(OR=1.029,95％CI:1.015-1.044,P＜0.001)were risk factors for poor prognosis in MPP children.The prediction model established for poor prognosis in children with MPP was as follows:logit(P)=-31.557+0.080×IL-6+0.080×TNF-α+0.029×VCAM-1.The AUC of the prediction model for predicting poor prognosis in MPP children was 0.979.CONCLUSIONS The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in pe-ripheral blood are closely related to the severity of illness in children with MPP.The prediction model constructed on the basis of the above indicators predicts the risk of severe disease in children with MPP,and the prediction model constructed on the basis of IL-6,TNF-α and VCAM-1 predicts the risk of poor prognosis in children with MPP.

Objective To explore the diagnostic value of 18F-fluorodeoxyglucose(FDG)PET/CT in primary pulmonary enteric adenocarcinoma.Methods The clinical and imaging data of 9 patients with primary pulmonary enteric adenocarcinoma who under-went 18F-FDG PET/CT examination were retrospectively analyzed,including lesion distribution,morphology,maximum standardized uptake value(SUVmax),clinical symptoms and signs,gastroscopy finding,puncture pathological results,and serum tumor markers[carbohydrate antigen 72-4(CA72-4),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),carcinoembryonic antigen(CEA),carbo-hydrate antigen 199(CA199)].Results Pathological examination confirmed a diagnosis of primary pulmonary enteric adenocarcinoma after excluding gastrointestinal primary tumors through clinical evaluation.In all nine patients,18F-FDG PET/CT examination did not reveal any evidence of digestive system malignancies,and gastrointestinal microscopy was negative.Primary lesions were observed as masses or nodular types in 6 cases(5 in the left lung and 1 in the right lung),while 3 cases exhibited diffuse bilateral pulmonary involvement(manifested as multiple patchy opacities,nodules,ground-glass opacities,and consolidations).All pulmonary primary lesions showed increased 18F-FDG uptake,with SUVmax ranging from 2.7 to 12.8,mean 8.6±3.7.The six masses-or nodular-type primary lesions showed maximum diameters ranging from 2.1 to 10.5 cm,mean(5.23±3.06)cm.Four cases demonstrated hilar and mediastinal lymph node metastases,intrapulmonary metastases,and distant metastases,while 1 case showed only distant metastasis.Elevated levels of serum tumor markers were observed as follows:CA72-4 in 7 cases(10-273.3 U/mL),CEA in 7 cases(5-147.4 ng/mL),CA199 in 6 cases(31.22-4 364 U/mL),and CYFRA21-1 in 5 cases(8.31-99.7 ng/mL).Conclusion When pathological biopsy of a pulmonary lesion suggests primary pulmonary enteric adenocarcinoma after excluding gastrointestinal primary tumors,and 18F-FDG PET/CT shows no gastrointestinal masses,this may support the diagnosis of primary pulmonary enteric adenocarcinoma.