Objective:To investigate the alterations in the topological properties of gray matter and white matter dynamic and static functional brain networks in patients with major depressive disorder (MDD) and bipolar depression (BDD) using graph theory analysis, and to evaluate the potential of their combination as biomarkers for differential diagnosis between unipolar and bipolar depression.Methods:From March 2021 to April 2024, inpatients were recruited from the Department of Psychosomatic Medicine, Zhongda Hospital, Southeast University, including 132 patients with MDD, 84 patients with BDD, and 91 healthy controls (HCs). Resting-state structural and functional MRI data were collected, and dynamic and static functional brain networks of gray matter and white matter were constructed. Graph theory analysis was applied to calculate global and nodal network properties, differences in topological attributes among the three groups were compared by One-way analysis of covariance, and Turkey′s post hoc test was used for further pairwise comparison. The network topology attribute indicators with statistically significant inter-group differences were selected using the Least Absolute Shrinkage and Selection Operator regression (LASSO) for feature classification. The diagnostic performance of combined gray and white matter network features for distinguishing MDD from BDD was assessed using receiver operating characteristic (ROC) curves and a random forest model.Results:In the analysis of the static gray matter functional network, both MDD and BDD patients showed abnormal local topological properties. Compared with HCs, the MDD group exhibited abnormal betweenness centrality (BC) in the left inferior frontal gyrus, left precuneus, left ventromedial occipital cortex, right ventromedial occipital cortex, and right anterior thalamus ( t=-3.95-3.62, all P<0.05). The degree centrality (DC) of the left and right anterior thalamus was also abnormal in the MDD group ( t=3.78,4.14, both P<0.001), as was the nodal efficiency (Ne) of the left precuneus and bilateral anterior thalamus ( t=2.37, 3.61, 3.82, all P<0.05). Compared with HCs, the BDD group showed abnormalities in DC and Ne of the left precuneus ( t=-2.76, P=0.014; t=-3.01, P=0.007). In the analysis of the dynamic white matter functional network, both MDD and BDD patients demonstrated abnormal temporal variability of local topological properties. Compared with HCs, the MDD and BDD groups showed reduced BC temporal variability in the left superior corona radiata ( t=-2.39, P=0.047; t=-4.28, P<0.001), and there were significant differences in DC temporal variability in the right posterior limb of the internal capsule and lentiform nucleus ( t=2.65, P=0.021; t=3.49, P=0.001) in MDD group compared with HCs and BBD. The differential diagnosis model combining gray and white matter dynamic and static network topological features achieved an area under the ROC curve of 0.80. Conclusion:Both MDD and BDD exhibit altered topological properties in static gray matter functional networks and dynamic white matter functional networks. The combination of these features may aid in the differential diagnosis of MDD and BDD.

Objective:To investigate the alterations in the topological properties of gray matter and white matter dynamic and static functional brain networks in patients with major depressive disorder (MDD) and bipolar depression (BDD) using graph theory analysis, and to evaluate the potential of their combination as biomarkers for differential diagnosis between unipolar and bipolar depression.Methods:From March 2021 to April 2024, inpatients were recruited from the Department of Psychosomatic Medicine, Zhongda Hospital, Southeast University, including 132 patients with MDD, 84 patients with BDD, and 91 healthy controls (HCs). Resting-state structural and functional MRI data were collected, and dynamic and static functional brain networks of gray matter and white matter were constructed. Graph theory analysis was applied to calculate global and nodal network properties, differences in topological attributes among the three groups were compared by One-way analysis of covariance, and Turkey′s post hoc test was used for further pairwise comparison. The network topology attribute indicators with statistically significant inter-group differences were selected using the Least Absolute Shrinkage and Selection Operator regression (LASSO) for feature classification. The diagnostic performance of combined gray and white matter network features for distinguishing MDD from BDD was assessed using receiver operating characteristic (ROC) curves and a random forest model.Results:In the analysis of the static gray matter functional network, both MDD and BDD patients showed abnormal local topological properties. Compared with HCs, the MDD group exhibited abnormal betweenness centrality (BC) in the left inferior frontal gyrus, left precuneus, left ventromedial occipital cortex, right ventromedial occipital cortex, and right anterior thalamus ( t=-3.95-3.62, all P<0.05). The degree centrality (DC) of the left and right anterior thalamus was also abnormal in the MDD group ( t=3.78,4.14, both P<0.001), as was the nodal efficiency (Ne) of the left precuneus and bilateral anterior thalamus ( t=2.37, 3.61, 3.82, all P<0.05). Compared with HCs, the BDD group showed abnormalities in DC and Ne of the left precuneus ( t=-2.76, P=0.014; t=-3.01, P=0.007). In the analysis of the dynamic white matter functional network, both MDD and BDD patients demonstrated abnormal temporal variability of local topological properties. Compared with HCs, the MDD and BDD groups showed reduced BC temporal variability in the left superior corona radiata ( t=-2.39, P=0.047; t=-4.28, P<0.001), and there were significant differences in DC temporal variability in the right posterior limb of the internal capsule and lentiform nucleus ( t=2.65, P=0.021; t=3.49, P=0.001) in MDD group compared with HCs and BBD. The differential diagnosis model combining gray and white matter dynamic and static network topological features achieved an area under the ROC curve of 0.80. Conclusion:Both MDD and BDD exhibit altered topological properties in static gray matter functional networks and dynamic white matter functional networks. The combination of these features may aid in the differential diagnosis of MDD and BDD.

Objective To observe the effect of Yiaikang capsules on viral load, immunologic function and quality of life of patients with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS). Methods A prospective randomized controlled clinical study was conducted, 118 patients with HIV/AIDS admitted to Department of Integrated Traditional Chinese and Western Medicine of Qinghai Fourth People's Hospital from July 2015 to February 2017 were enrolled, and they were divided into two groups by random digital table method, 59 cases in each group. The control group received highly active anti-retroviral therapy (HAART); while the treatment in combined Chinese and western medicine group was additionally given Yiaikang capsules on the basis of the therapy in control group, 5 capsules (0.5 g per grain,) once and 3 times a day for 12 months. The differences of World Health Organization HIV quality of life scale (WHOQOL HIV-BREF) score, CD4+, CD8+T-lymphocyte and viral load levels were compared between the two groups. Results After treatment for 12 months, the results of WHOQOL HIV-BREF scores in two groups were reduced significantly compared with those before treatment (P ＜ 0.05), and the degree of decrease of WHOQOL HIV-BREF score in combined Chinese and western medicine group was slower than that in control group (82.57±8.76 vs. 70.53±9.45, P ＜ 0.05). The CD4+, CD8+levels in control group after treatment were of no significant change compared with those before treatment (P ＞ 0.05), but the viral load level was decreased significantly after treatment compared with that before treatment (log/mL: 3.57±0.82 vs. 3.89±1.32, P ＜ 0.05); the CD4+in combined Chinese and western medicine group after treatment was obviously higher compared with that before treatment (number/μL: 413.67±187.39 vs. 376.65±206.51), the viral load level was markedly lowered compared with that before treatment (log/mL: 3.14±0.76 vs. 3.81±1.27) and the level of CD4+was significantly higher in combined Chinese and western medicine group than that in control group (413.67±187.39 vs. 382.72±194.82), viral load level in combined Chinese and western medicine group was siginificantly lower that in the control group (3.14±0.76 vs. 3.57±0.82, P ＜ 0.05), but the number of CD8+in two groups after treatment was of no significant change (P ＞ 0.05). Conclusion Yiaikang capsules possibly may elevate the number of CD4+T-lymphocytes and decrease the level of viral load to improve the quality of life in patients with HIV/AIDS.

Objective To study the mechanisms of levofloxacin,thymopentin combined with decoction of four noble drugs for treatment of patients with severe pulmonary tuberculosis and offer a new therapeutic strategy for treatment of the disease.Methods A total of 100 patients with severe pulmonary tuberculosis admitted to Qinghai Fourth People's Hospital from November 2013 to January 2016 were enrolled,and they were divided into a research group (50 patients) and a control group (50 patients) by random number table.The patients in two groups were treated with 2HRZE/4HR standardized therapy program.The patients in the research group were additionally treated with levofloxacin (0.5 g orally taken,1 times a day),thymopentin (1 mg intravenous injection,once a day) combined with decoction of four noble drugs (ginseng 9 g,poria 9 g,atractylodes 9 g,and licorice 6 g,all the above ingredients were immersed in 400 mL water and boiled to 100 mL,one dose orally taken daily and it was equally divided into 2 parts,one part taken in the morning and the remaining part taken in the evening).Four months after treatment,the changes of indexes of immune functions [total lymphocyte count (LY),CD4+,CD8+,and CD4+/CD8+ ratio],blood coagulation indexes [prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),D-dimer,and plasma fibrinogen (Fib)],pulmonary function indexes [forced vital capacity (FVC),peak expiratory flow rate (PEF),forced expiratory maximum volume in 1 second (FEV1),and mean maximum expiratory flow (MMEF)] and blood gas analysis indexes [arterial partial pressure of carbon dioxide (PaCO2),arterial partial pressure of oxygen (PaO2),pulse oxygen saturation (SpO2),and oxygenation index (PaO2/FiO2)] and the therapeutic effects were observed in the two groups.Results After treatment,the CD8+,TT,PT,Fib,D-Dimer and PaCO2 of two groups were decreased significantly than those before treatment (all P ＜ 0.05);while the LY,CD4+,CD4+/CD8+ ratio,FEV1,FVC,PEF,MMEF,APTT,PaO2,SpO2 and PaO2/FiO2 of two groups were all increased significantly than those before treatment (all P ＜ 0.05).The changes of the study group were more obvious than those of the control group [LY (109/L):1.79 ± 0.19 vs.1.45 ± 0.16,CD4+:0.40 ± 0.03 vs.0.33 ± 0.03,CD8+:0.20 ± 0.01 vs.0.23 ± 0.02,CD4+/CD8+ ratio:2.10 ± 0.23 vs.1.67 ± 0.20,FEV1:0.269 ± 0.004 vs.0.198 ± 0.003,FVC:(3.78 ± 0.41)％ vs.(3.14 ± 0.39)％,PEF (L/s):3.68 ± 0.26 vs.3.05 ± 0.23,MMEF (L/s):0.96 ± 0.06 vs.0.74 ± 0.05,PaO2 (mmHg,1 mmHg =0.133 kPa):95.11 ± 7.68 vs.85.23 ± 7.01,PaCO2 (mmHg):31.76± 3.26 vs.46.28±4.36,SpO2:0.96±0.08 vs.0.91 ±0.07,PaO2/FiO2 (mmHg):310.58± 11.12 vs.285.01 ± 10.76,TT (s):15.64± 1.25 vs.18.82 ± 1.54,PT (s):12.69 ± 1.01 vs.14.28 ± 1.21,APTT (s):29.01 ± 2.02 vs.25.21 ± 1.80,Fib (mg/L):233.46 ± 15.61 vs.286.27 ± 18.14,D-Dimer (μg/L):210.88 ± 14.13 vs.256.39 ± 16.47,all P ＜ 0.05].After combined treatment,the sputum negative conversion rate [94％ (47/50) vs.60％ (30/50)],the total efficiency [88％ (44/50) vs.64％ (32/50)] and the focus absorption rate [86％ (43/50) vs.60％ (30/50)] of research group were significantly higher than those of the control group (all P ＜ 0.05).Conclusions The combination of levofloxacin,thymopentin and decoction of four noble drugs on the bases of 2HRZE/4HR standardized therapy for treatment of patients with severe pulmonayr tuberculosis can help to regulate acid-base balance,improve the hypoxia condition and lung function,elevate the immune function and increase the blood circulation in the body to improve clinical efficacy.

OBJECTIVE:To observe the efficacy and safety of levofloxacin and capreomycin combined with chemotherapy regi-men in the treatment of multi-drug resistant tuberculosis(MDR-TB). METHODS:84 MDR-TB patients were randomly divided in-to observation group (42 cases) and control group (42 cases). Observation group received 0.75 g Capreomycin sulfate for injec-tion,addint into 100 ml 0.9% Sodium chloride injection,intravenous infusion,once a day+0.4 g Levofloxacin hydrochloride tab-let,orally,once a day+0.2 g Protionamide tablet,orally,3 times a day+0.3 g Pasiniazid tablet,orally,3 times a day+0.5 g Pyra-zinamide tablet,orally,4 times a day. Control group received 0.4 g Amikacin sulfate injection,adding into 100 ml 0.9% Sodium chloride injection,once a day,intravenous infusion+0.3 g Ofloxacin tablet,orally,twice a day+Protionamide tablet (the same dose with observation group)+Pasiniazid tablet (the same dose with observation group)+Pyrazinamide tablet (the same dose with observation group). All patient were given 0.1 g Glucuronolactone tablet,orally,3 times a day. The treatment course for both group was 12 months. Sputum negative conversion rate,negative conversion time,symptom improvement time,lesion absorption and lung cavity closing,and cell immune indexes (CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+),IL-17 level before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The sputum negative conversion rate,ab-sorption rate,lung cavity closing and narrowing cases in research group after 3,6,9,12,18 months treatment were significantly higher than control group,sputum negative conversion time,symptom improvement time in observation group were significantly lower than control group,the differences were statistically significant(P<0.05). Before treatment,there were no significant differ-ences in CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+,IL-17 level in 2 groups(P>0.05). After treatment,CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+ in 2 groups were significantly lower than before,and observation group was lower than control group,IL-17 level was significantly higher than before,and observation group was higher than control group,the differences were statistically significant (P<0.05). And there was no significant difference in the incidence of adverse reactions in 2 groups (P>0.05). CON-CLUSIONS:Levofloxacin and capreomycin combined with chemotherapy in the treatment of MDR-TB,it can reduce T regulatory cells,increase IL-17 level,do not increase the incidence of adverse reactions.

Objective This study was aimed to investigate the association between integrity of long association fiber tracts changes and neuropsychological performance in patients with remitted geriatric depression (RGD).Methods Using the Mini Mental State Examination (MMSE),Auditory Verbal Learning Test (AVLT),Symbol Digit Modality Test (SDMT),Trail Making Test-A&B (TMT-A&B),Digit Span Test (DST) to collect general clinical data and neuropsychological data.14 patients with RGD and 19 healthy volunteers as control were recruited in this follow-up study.Subjects were scanned using a General Electric 1.5 Tesla scanner to acquire diffusion tensor imaging (DTI) images.Using the DTI studio software to calculate the fraction anisotropy (FA) value of region of interesting (ROI) in 13 RGD patients and 19 controls.Results (1) At baseline,RGD patients showed significant poorer performance in some specific domain of cognitive function,such as AVLT,SDMT,TMT A&B and DST than controls [RGD patients:5.93±2.56,25.00 ± 15.04,133.50 ±96.66,237.71 ± 138.42,11.79 ±2.08; controls:8.16 ± 1.83,34.95 ± 8.89,69.58 ± 27.92,139.74 ± 38.11,13.16 ± 1.74.At follow-up,the score of MMSE,AVLT,DST in RGD patients showed some degrees of decline (27.79 ±3.97,5.00 ±2.83,11.71 ±2.13,SDMT,TMT-A&B exhibited increased score 27.07 ± 15.78,70.43 ±25.52,157.71 ±36.92,but only the change of TMT-A and B was statistically significant (P =0.038,0.032).After follow-up,the RGD patients exhibited lower scores of DST than controls [(11.71 ±2.13) vs.(14.05 ±2.72),P ＜0.01].(2) At baseline,the FA value of left cingulate fasciculus (posterior) in RGD patients was lower than controls [(0.50 ± 0.08) vs.(0.57 ±0.05),P =0.015].At follow-up,the FA value of right frontooccipital fasciculus in RGD patients was lower compared to controls [(0.50 ± 0.03) vs.(0.54 ± 0.06),P =0.025],the FA value of corpus callosum (splenium) was decreased significantly in RGD patients [(0.83 ± 0.05) vs.(0.77 ± 0.06),P =0.013].In controls,the FA value of left cingulate fasciculus (middle) exhibited significant decrease [(0.60 ± 0.06) vs.(0.54 ± 0.06),P =0.011].(3) Correlation analysis showed that the decreased FA value of splenium of corpus callosum was negatively related to the increase of SDMT score (r =-0.617,P =0.025).Conclusions The findings suggest that the regional fiber connection change be closely related to cognitive impairment.The abnormality of integrity long white matter fiber bundle might be associated with impaired cognitive function in patients with RGD.

Objective This study was aimed to investigate the association between integrity of long association fiber tracts changes and neuropsychological performance in patients with remitted geriatric depression (RGD).Methods Using the Mini Mental State Examination (MMSE),Auditory Verbal Learning Test (AVLT),Symbol Digit Modality Test (SDMT),Trail Making Test-A&B (TMT-A&B),Digit Span Test (DST) to collect general clinical data and neuropsychological data.14 patients with RGD and 19 healthy volunteers as control were recruited in this follow-up study.Subjects were scanned using a General Electric 1.5 Tesla scanner to acquire diffusion tensor imaging (DTI) images.Using the DTI studio software to calculate the fraction anisotropy (FA) value of region of interesting (ROI) in 13 RGD patients and 19 controls.Results (1) At baseline,RGD patients showed significant poorer performance in some specific domain of cognitive function,such as AVLT,SDMT,TMT A&B and DST than controls [RGD patients:5.93±2.56,25.00 ± 15.04,133.50 ±96.66,237.71 ± 138.42,11.79 ±2.08; controls:8.16 ± 1.83,34.95 ± 8.89,69.58 ± 27.92,139.74 ± 38.11,13.16 ± 1.74.At follow-up,the score of MMSE,AVLT,DST in RGD patients showed some degrees of decline (27.79 ±3.97,5.00 ±2.83,11.71 ±2.13,SDMT,TMT-A&B exhibited increased score 27.07 ± 15.78,70.43 ±25.52,157.71 ±36.92,but only the change of TMT-A and B was statistically significant (P =0.038,0.032).After follow-up,the RGD patients exhibited lower scores of DST than controls [(11.71 ±2.13) vs.(14.05 ±2.72),P ＜0.01].(2) At baseline,the FA value of left cingulate fasciculus (posterior) in RGD patients was lower than controls [(0.50 ± 0.08) vs.(0.57 ±0.05),P =0.015].At follow-up,the FA value of right frontooccipital fasciculus in RGD patients was lower compared to controls [(0.50 ± 0.03) vs.(0.54 ± 0.06),P =0.025],the FA value of corpus callosum (splenium) was decreased significantly in RGD patients [(0.83 ± 0.05) vs.(0.77 ± 0.06),P =0.013].In controls,the FA value of left cingulate fasciculus (middle) exhibited significant decrease [(0.60 ± 0.06) vs.(0.54 ± 0.06),P =0.011].(3) Correlation analysis showed that the decreased FA value of splenium of corpus callosum was negatively related to the increase of SDMT score (r =-0.617,P =0.025).Conclusions The findings suggest that the regional fiber connection change be closely related to cognitive impairment.The abnormality of integrity long white matter fiber bundle might be associated with impaired cognitive function in patients with RGD.

Objective To explore the effect of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism,environmental factor and their interactions on antidepressant treatment.Methods 340 patients of major depressive disorder (MDD) who met the diagnosis criteria of MDD ( DSM-Ⅳ Axis Ⅰ) were recruited.280 patients of them were finished 12 weeks antidepressant treatment.The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 12 weeks antidepressant treatment.Childhood Trauma Questionnaire,28-item Short Form (CTQ-SF) and Life Events Scale (LES) were used to evaluate childhood adverse and life stress before onset.Genotyping of BDNF Val66Met polymorphism was detected by Illumina GoldenGate assays.Results Male patients proportion were significantly higher in non-remitters than remitters (P =0.008 ).After adjusting by gender, the frequencies of genotype and allele for the BDNF Val66Met polymorphism were no significant difference between remitters (AA: AG: GG = 28: 79: 40, A:G = 135:159 ) and non-remitters (AA: AG: GG = 29:81:23 ,A: G = 139:127 ) (P ＞0.05 ).There was no significant difference of CTQ scores and LES scores between the two groups (P＞0.05 ).The regression analysis showed that social intercourse problem and age were the risk factor for the severity of depression.The gender, HDRS baseline scores and mental disorder family history were associated with the efficacy of 12 weeks antidepressant.However,there was no significantly relationship between the interaction of BDNF Val66Met polymorphism and environment with the antidepressant treatment.Conclusion The older men with the mental disorder family history, severe depression symptom would be less-response to antidepressant treatment.However, BDNF Val66Met polymorphism, childhood trauma, life events stress and the interaction of BDNF Val66Met polymorphism and environment have no significantly effect on the 12 weeks antidepressant treatment.