Objective:This study aims to analyze the gamma band effective connectivity characteristics of the prefrontal-striatal circuitry in bipolar disorder patients with and without a history of manic episodes, as well as in major depressive disorder patients, during the recognition of positive emotional faces, this study aims to identify unique neurophysiological features that may aid in the early detection of bipolar disorder.Methods:This retrospective study collected clinical data and magnetoencephalography (MEG) imaging data from patients performing a positive emotional face recognition task at the Affiliated Brain Hospital of Nanjing Medical University from May 2009 to December 2019. The study included 75 patients with major depressive disorder and 29 patients with bipolar disorder in a depressive episode (rBD group). Concurrently, 39 age-and gender-matched healthy controls (HC group) were recruited. After a follow-up period of at least 5 years, 23 out of the 75 patients with major depressive disorder converted to bipolar disorder (ctBD group), while the remaining 52 who did not convert maintained a diagnosis of major depressive disorder.Results:There were statistically significant differences in gamma-band effective connectivity in the prefrontal-striatal circuit when recognizing positive emotional faces among the converted to bipolar disorder (ctBD), raw bipolar disorder, major depressive disorder, and HC groups ( H=9.04, 10.30, 8.30, 13.43, 14.38, 12.62, 9.82, 8.94, 24.62, 7.89, 18.53, 9.97, 9.58, 12.79, P<0.05). The ctBD group, rBD group, and major depressive group all showed reduction in effective connectivity from the right orbital inferior frontal gyrus (ORBinf.R) to the left orbital inferior frontal gyrus (ORBinf.L) [ Z=-1.98, -3.38, -2.88], from the right orbital inferior frontal gyrus to the right ventral striatum (VS.R) ( Z=-2.05, -2.76, -2.11; P<0.05) and from the left ventral striatum (VS.L) to the left orbital middle frontal gyrus (ORBmid.L) ( Z=-2.76, -1.98, -2.43; P<0.05). Among the disease groups, the ctBD group showed significantly enhanced effective connectivity strength compared to the major depressive group from the right amygdala (AMYG.R) to the left orbital inferior frontal gyrus(0.04(0.03, 0.08)), from the right amygdala to the left ventral striatum(0.05(0.03, 0.09)), and from the right ventral striatum to the right anterior cingulate and paracingulate gyri (ACG.R) (0.04(0.02, 0.08)) ( Z=4.17, 3.70, 3.35; P<0.001).The ctBD group also exhibited enhanced effective connectivity compared to the rBD group from ORBinf.R to the ACG.R, fron the AMYG.R to the ORBinf.L, from the AMYG.R to the VS.L, and from the VS.R to the ACG.R ( Z=2.05, 4.61, 3.60, 3.04; P<0.05).The rBD group demonstrated reduced effective connectivity compared to the major depressive disorder group from the right orbital middle frontal gyrus(ORBmid.R) to the left anterior cingulate and paracingulate gyri (ACG.L), ORBinf.R to the ACG.R and from the ORBinf.R to the AMYG.R ( Z=-2.12, -2.40, -2.22; P<0.05). Conclusion:There are significant differences in the gamma-band effective connectivity characteristics of the prefrontal-striatal pathway when recognizing positive emotional faces between patients with bipolar disorder in depressive episodes and those with depression, as well as differences between bipolar depressed patients with and without a history of manic episodes.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective:This study aims to analyze the gamma band effective connectivity characteristics of the prefrontal-striatal circuitry in bipolar disorder patients with and without a history of manic episodes, as well as in major depressive disorder patients, during the recognition of positive emotional faces, this study aims to identify unique neurophysiological features that may aid in the early detection of bipolar disorder.Methods:This retrospective study collected clinical data and magnetoencephalography (MEG) imaging data from patients performing a positive emotional face recognition task at the Affiliated Brain Hospital of Nanjing Medical University from May 2009 to December 2019. The study included 75 patients with major depressive disorder and 29 patients with bipolar disorder in a depressive episode (rBD group). Concurrently, 39 age-and gender-matched healthy controls (HC group) were recruited. After a follow-up period of at least 5 years, 23 out of the 75 patients with major depressive disorder converted to bipolar disorder (ctBD group), while the remaining 52 who did not convert maintained a diagnosis of major depressive disorder.Results:There were statistically significant differences in gamma-band effective connectivity in the prefrontal-striatal circuit when recognizing positive emotional faces among the converted to bipolar disorder (ctBD), raw bipolar disorder, major depressive disorder, and HC groups ( H=9.04, 10.30, 8.30, 13.43, 14.38, 12.62, 9.82, 8.94, 24.62, 7.89, 18.53, 9.97, 9.58, 12.79, P<0.05). The ctBD group, rBD group, and major depressive group all showed reduction in effective connectivity from the right orbital inferior frontal gyrus (ORBinf.R) to the left orbital inferior frontal gyrus (ORBinf.L) [ Z=-1.98, -3.38, -2.88], from the right orbital inferior frontal gyrus to the right ventral striatum (VS.R) ( Z=-2.05, -2.76, -2.11; P<0.05) and from the left ventral striatum (VS.L) to the left orbital middle frontal gyrus (ORBmid.L) ( Z=-2.76, -1.98, -2.43; P<0.05). Among the disease groups, the ctBD group showed significantly enhanced effective connectivity strength compared to the major depressive group from the right amygdala (AMYG.R) to the left orbital inferior frontal gyrus(0.04(0.03, 0.08)), from the right amygdala to the left ventral striatum(0.05(0.03, 0.09)), and from the right ventral striatum to the right anterior cingulate and paracingulate gyri (ACG.R) (0.04(0.02, 0.08)) ( Z=4.17, 3.70, 3.35; P<0.001).The ctBD group also exhibited enhanced effective connectivity compared to the rBD group from ORBinf.R to the ACG.R, fron the AMYG.R to the ORBinf.L, from the AMYG.R to the VS.L, and from the VS.R to the ACG.R ( Z=2.05, 4.61, 3.60, 3.04; P<0.05).The rBD group demonstrated reduced effective connectivity compared to the major depressive disorder group from the right orbital middle frontal gyrus(ORBmid.R) to the left anterior cingulate and paracingulate gyri (ACG.L), ORBinf.R to the ACG.R and from the ORBinf.R to the AMYG.R ( Z=-2.12, -2.40, -2.22; P<0.05). Conclusion:There are significant differences in the gamma-band effective connectivity characteristics of the prefrontal-striatal pathway when recognizing positive emotional faces between patients with bipolar disorder in depressive episodes and those with depression, as well as differences between bipolar depressed patients with and without a history of manic episodes.

Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To observe the therapeutic effect of quercetin (QUE) on triggering receptor expressed on myeloid cells (TREM-1) activated macrophage inflammation and lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice, and explore its possible mechanism.Methods:In vitro cell experiment: The primary peritoneal macrophages of mice were collected by intraperitoneal injection of 3% calcium mercaptan acetate. The collected cells were divided into blank control group, dimethylsulfoxide (DMSO) vehicle group, TREM-1 agonist group (10 μg/ml), QUE group (10 μmol/L) and TREM-1 agonist + QUE group (cells were pretreated with 10 μmol/L QUE for 30 min before adding agonist). Enzyme linked immunosorbent assay (ELISA) was used to detect the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in the culture supernatant of primary macrophages; To observe the effect of QUE on LPS-induced TREM-1 protein levels, macrophages were divided into: normal control group, LPS group (100 ng/ml) and LPS+ QUE treatment group [macrophages were pretreated with 10 μmol/L QUE for 2 hours, and then incubated with LPS (100 ng/ml) for 16 hours]. Western blot was used to detect the expression of TREM-1 protein. In animal experiments: 80 male C57BL/6 mice were randomly divided into 4 groups (20 in each group): normal control group, ALI model group, QUE group and QUE treatment group (LPS+ QUE). In the ALI model group, the ALI model was established by intratracheal injection of 5 mg/kg LPS; The mouse ALI model was established by intratracheal injection of LPS 5 mg/kg in the QUE treatment group, and then intraperitoneal injection of 15 mg/kg QUE. The control group was given the same amount of normal saline intratracheal followed by intraperitoneal injection of DMSO, and the QUE group was given the same amount of normal saline intratracheal followed by intraperitoneal injection of 15 mg/kg QUE. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue in each group; Inflammatory cells including IL-1β, TNF- α and IL-6 in bronchoalveolar lavage fluid (BLAF) of mice in each group were counted ; The expression of TREM-1 mRNA and protein in lung tissue of mice in each group was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot. Results:In vitro cell experiment: the secretion of IL-1β, TNF-α and IL-6 in the supernatant of primary macrophages in TREM-1 agonist group was higher than those in DMSO vehicle group, while the secretion of IL-1β, TNF-αand IL-6 in the supernatant of primary macrophages in TREM-1 agonist + QUE group were lower than that of TREM-1 agonist group (all P<0.001). The expression of TREM-1 protein in LPS group was higher than that in control group ( P<0.05), while the expression of TREM-1 protein in LPS + QUE group was lower than that in LPS group ( P<0.05). Animal experiments showed that compared with the control group, the ALI model group had higher lung pathological injury score, more total cells, macrophages and neutrophils in BALF and increased TNF-α, IL-6, IL-1β content (all P<0.001). The above indexes in QUE group were lower than those in ALI model group (all P<0.001). The results of qRT-PCR and Western blot showed that compared with the control group, the expression of TREM-1 mRNA and protein in the lung tissue of ALI model group was increased, while the expression of TREM-1 mRNA and protein in the lung tissue of QUE group was lower than that of ALI model group (all P<0.05). Conclusions:Quercetin can inhibit TREM-1 activation, reduce macrophage inflammatory response and LPS induced acute lung injury in mice.

Objective:This study aims to examine the incidence and risk factors of violent behaviors in community-dwelling unmedicated patients with severe mental disorders in Shenzhen.Methods:The baseline and follow-up data of unmedicated patients with severe mental disorders were collected from the Information Management System of Mental Health Prevention and Control in Shenzhen. The incidence of violent behaviors in unmedicated patients was described. The influencing factors of violent behaviors were analyzed using logistic regression model.Results:A total of 3 163 patients were included. The incidence of violent behaviors was 9.1% (288/3 163) in 2019. Multivariate logistic regression analysis showed that having an acute illness onset ( OR=1.589, 95 %CI 1.181-2.139) was the risk factor of violent behaviors, while having cohabitants ( OR=0.596, 95 %CI 0.410-0.867), being diagnosed as mental retardation comorbid with psychotic disorders ( OR=0.432, 95 %CI 0.199-0.938), having application for carers allowances ( OR=0.440, 95 %CI 0.319-0.606), and participating in family doctor services ( OR=0.642, 95 %CI 0.492-0.838) and community face-to-face interviews during 2019 ( OR (1-2 times vs. 0 times)=0.633, 95 %CI 0.466-0.861; OR (3-4 times vs. 0 times)=0.546, 95 %CI 0.368-0.811) were the protective factors. Conclusions:The incidence of violent behaviors is high in unmedicated patients with severe mental disorders with acute illness onset. The improvement of comprehensive level of community mental health services and the development of targeted intervention measures would help to reduce the occurrence of violent behaviors among unmedicated patients with severe mental disorders in the community.

" Medical prevention integration" is the practical need of the construction of healthy China and the focus of the construction of medical consortium in the future. Taking the practice of four chronic disease specific medical prevention centers of Wenling County medical consortium as an example, the authors analyzed their practices and experience in coordinating county advantageous resources, establishing organizational structure, and implementing chronic disease specific prevention and control based on informatization. The " medical prevention integration" system constructed by this mode optimized chronic disease service content, improved service capacity and service quality, and achieved in improving satisfaction. This mode could improve the effect and satisfaction of chronic disease management, improve the prevention and treatment efficiency of chronic diseases, and practice the whole cycle health management of chronic diseases.

Objective:This study aims to examine the incidence and risk factors of violent behaviors in community-dwelling unmedicated patients with severe mental disorders in Shenzhen.Methods:The baseline and follow-up data of unmedicated patients with severe mental disorders were collected from the Information Management System of Mental Health Prevention and Control in Shenzhen. The incidence of violent behaviors in unmedicated patients was described. The influencing factors of violent behaviors were analyzed using logistic regression model.Results:A total of 3 163 patients were included. The incidence of violent behaviors was 9.1% (288/3 163) in 2019. Multivariate logistic regression analysis showed that having an acute illness onset ( OR=1.589, 95 %CI 1.181-2.139) was the risk factor of violent behaviors, while having cohabitants ( OR=0.596, 95 %CI 0.410-0.867), being diagnosed as mental retardation comorbid with psychotic disorders ( OR=0.432, 95 %CI 0.199-0.938), having application for carers allowances ( OR=0.440, 95 %CI 0.319-0.606), and participating in family doctor services ( OR=0.642, 95 %CI 0.492-0.838) and community face-to-face interviews during 2019 ( OR (1-2 times vs. 0 times)=0.633, 95 %CI 0.466-0.861; OR (3-4 times vs. 0 times)=0.546, 95 %CI 0.368-0.811) were the protective factors. Conclusions:The incidence of violent behaviors is high in unmedicated patients with severe mental disorders with acute illness onset. The improvement of comprehensive level of community mental health services and the development of targeted intervention measures would help to reduce the occurrence of violent behaviors among unmedicated patients with severe mental disorders in the community.

Objective: To explore the value of index of microcirculatory resistance (IMR) for early prediction of periprocedural myocardial injury (PMI) in patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) after PCI. Methods: It was a prospective study. One hundred and sixty-four patients who had single coronary lesion were consecutively enrolled from May 2014 to December 2017 at Nanjing Hospital affiliated to Nanjing Medical University. According to clinical manifestation, patients were divided into SAP group (n=81) and ACS group (n=83). IMR was determined by thermal dilution with pressure guide wire. Basic clinical characteristics, coronary angiographic results, PCI procedural details, IMR after PCI, ΔIMR (IMR=post-PCI-IMR pre-PCI), levels of myocardial biomarkers before and after PCI were compared between the two groups. Multivariate logistic regression was used to analyze the relation of PMI with IMR and ΔIMR, and the predictive ability was evaluated by receiver operating characteristic (ROC). Results: The levels of total cholesterol and low density lipoprotein cholesterol were significantly higher in ACS group than in SAP group (P<0.05), other clinical data at baseline were similar between the two groups (P>0.05). Quantitative coronary angiography (QCA) results and PCI related data were also similar between the two groups before PCI (P>0.05). Values of mean transit time (Tmn) of intracoronary injection with room temperature saline, post-PCI IMR and ΔIMR were significantly higher in ACS group than in SAP group after PCI (P<0.05). Plasma creatine kinase isoenzyme-MB difference (ΔCK-MB) (ΔCK-MB=CK-MB post-PCI-CK-MB pre-PCI) and cardiac troponin-I (cTnI) difference (ΔcTnI=cTnI post-PCI-cTnI pre-PCI) were significantly larger in ACS group than in SAP group (P<0.05). Multivariate logistic regression analysis showed that coronary artery disease (CHD) type (SAP and ACS) (OR=1.301, 95%CI 1.083-1.562), age (OR=1.007, 95%CI 1.000-1.013), ΔIMR (OR=1.009, 95%CI 1.000-1.017) and post-PCI IMR (OR=1.008, 95%CI 1.001-1.014) were independent predictors of PMI (P<0.05). The area under the ROC curve (AUC) of ΔIMR was 0.763 to predict PMI (P<0.05), the optimum cut-off value of ΔIMR was 5.485 with 70.0% sensitivity and 77.4% specificity. ΔIMR was positively correlated with ΔcTnI (r=0.592, P<0.05). Conclusions ΔIMR serves as an early predictor of PMI in CHD patients after PCI. As compared with SAP patients, ACS patients are more likely to develop PMI.