Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Objective To construct a nonparametric proportional hazards (PH) model for mixed informative interval-censored failure time data for predicting the risks in heart transplantation surgeries. Methods Based on the complexity of mixed informative interval-censored failure time data, we considered the interdependent relationship between failure time process and observation time process, constructed a nonparametric proportional hazards (PH) model to describe the nonlinear relationship between the risk factors and heart transplant surgery risks and proposed a two-step sieve estimation maximum likelihood algorithm. An estimation equation was established to estimate frailty variables using the observation process model. I-spline and B-spline were used to approximate the unknown baseline hazard function and nonparametric function, respectively, to obtain the working likelihood function in the sieve space. The partial derivative of the model parameters was used to obtain the scoring equation. The maximum likelihood estimation of the parameters was obtained by solving the scoring equation, and a function curve of the impact of risk factors on the risk of heart transplantation surgery was drawn. Results Simulation experiment suggested that the estimated values obtained by the proposed method were consistent and asymptotically effective under various settings with good fitting effects. Analysis of heart transplant surgery data showed that the donor's age had a positive linear relationship with the surgical risk. The impact of the recipient's age at disease onset increased at first and then stabilized, but increased against at an older age. The donor-recipient age difference had a positive linear relationship with the surgical risk of heart transplantation. Conclusion The nonparametric PH model established in this study can be used for predicting the risks in heart transplantation surgery and exploring the functional relationship between the surgery risks and the risk factors.

Objective To observe the changes in functional connectivity(FC)of raphe nucleus in patients with first-episode depression complicated with suicidal ideation(SI).Methods Ninety-eight first-episode depression patients were prospectively enrolled and assigned into SI group(n=56)or non SI group(n=42)based on complicated with SI or not,while 47 healthy volunteers were recruited as control group.Resting-state functional MRI was performed.FC between dorsal raphe nucleus(DRN),median raphe nucleus(MRN)and the whole brain were analyzed and compared among 3 groups and between each 2 groups,and the correlations of FC of different brain regions with clinical data of SI group were explored.Results Compared with control group,FC between DRN and left cerebellum and left putamen in SI group and non SI group decreased(all P＜0.05),between MRN and right inferior temporal gyrus increased but between MRN and left inferior frontal gyrus,right superior occipital gyrus,left inferior parietal lobule,left putamen decreased(all P＜0.05).FC between DRN and left putamen in SI group was higher than that in non SI group(P＜0.05).FC between MRN and right central posterior gyrus of SI group increased compared with that in the rest 2 groups(both P＜0.05).FC between MRN and left putamen in SI group was positively correlated with body mass score of Hamilton depression scale-24(HAMD-24)(rs=0.297,P=0.026).Conclusion Abnormal changes of FC between raphe nucleus and cortex,also between raphe nucleus and subcortical area occurred,and FC between MRN and left putamen positively correlated with body mass score of HAMD-24 in patients with first-episode depression complicated with SI.

Objective To construct a nonparametric proportional hazards (PH) model for mixed informative interval-censored failure time data for predicting the risks in heart transplantation surgeries. Methods Based on the complexity of mixed informative interval-censored failure time data, we considered the interdependent relationship between failure time process and observation time process, constructed a nonparametric proportional hazards (PH) model to describe the nonlinear relationship between the risk factors and heart transplant surgery risks and proposed a two-step sieve estimation maximum likelihood algorithm. An estimation equation was established to estimate frailty variables using the observation process model. I-spline and B-spline were used to approximate the unknown baseline hazard function and nonparametric function, respectively, to obtain the working likelihood function in the sieve space. The partial derivative of the model parameters was used to obtain the scoring equation. The maximum likelihood estimation of the parameters was obtained by solving the scoring equation, and a function curve of the impact of risk factors on the risk of heart transplantation surgery was drawn. Results Simulation experiment suggested that the estimated values obtained by the proposed method were consistent and asymptotically effective under various settings with good fitting effects. Analysis of heart transplant surgery data showed that the donor's age had a positive linear relationship with the surgical risk. The impact of the recipient's age at disease onset increased at first and then stabilized, but increased against at an older age. The donor-recipient age difference had a positive linear relationship with the surgical risk of heart transplantation. Conclusion The nonparametric PH model established in this study can be used for predicting the risks in heart transplantation surgery and exploring the functional relationship between the surgery risks and the risk factors.

Objective:To investigate the abnormalities of gray matter volume (GMV) and the synergistic changes in different cerebral regions in the first-episode and early-onset depression (EOD) patients.Methods:A total of 60 patients with untreated EOD (EOD group) and 64 healthy controls (control group) matched for age, gender, and education underwent high-resolution T 1WI MR scans. Voxel-based morphometry was used to calculate the cerebral GMV. The difference in GMV between the two groups was compared with the t-test. Different brain regions were selected as seeds for structural covariation network (SCN) analysis. Spearman correlation model was used to analyze the correlation between the GMV in different cerebral regions and illness duration as well as the scores of Hamilton rating scale for depression (HAMD) 17 items in EOD group. Results:Compared to control group, the EOD group had significantly increased GMV in the right orbitofrontal cortex, right dorsolateral prefrontal cortex, right inferior parietal lobule, right superior parietal lobule and bilateral precuneus ( P<0.05, corrected by FDR). Based on the right orbitofrontal cortex and dorsolateral prefrontal cortex as seed regions, structural covariance analysis revealed that abnormal cooperative brain regions in EOD group, mainly distributed in the bilateral frontal lobe, parietal lobe, occipital lobe, temporal lobe, paralimbic system and cerebellum ( P<0.05, corrected by FDR). In EOD group, significant negative correlations were observed between the GMV in the right orbitofrontal cortex ( r=-0.314, P=0.015), the left precuneus ( r=-0.283, P=0.029), and illness duration. Significant positive correlations were observed between the GMV in the right dorsolateral prefrontal cortex and the scores of anxiety/somatization factor of HAMD17 ( r=0.331, P=0.010), the left precuneus and weight factor of HAMD17 ( r=0.255, P=0.049), respectively. Conclusions:Abnormal GMV changes are observed in some regions of the prefrontal and parietal lobule in patients with untreated EOD, accompanied by extensive covariant brain regions and additional structural connectivity. In addition, the abnormal GMV changes in some regions are associated with clinical features. Part of the prefrontal and parietal lobule may be the biomarkers to objectively evaluate abnormal brain structure in depression patients in the early stage.

Objective:To study the predictive value of superb microvascular imaging(SMI) in evaluating therapeutic efficacy of hepatic cancer treated by percutaneous radiofrequency ablation(PRFA).Methods:From Feb 2017 to Feb 2018, 55 patients (male: 31, female: 24, age range: 37-68 years, mean age: 56years) with 72 hepatic carcinoma lesions (length: 21.3-45.6 mm, average: 31.2 mm) were detected by SMI and contrast-enhanced CT(CECT)before PRFA. One month after treatment, more than two imaging examinations (CECT, CEMR, ultrasonic imaging) were used as the "gold standard" to evaluate the complete ablation rates. Consistency between the SMI grading and the arterial phase enhancement of CECT was analyzed by the Kappa-test.Results:Before PRFA, SMI showed 12 lesions (16.7%) to be in grade Ⅰ, 28 lesions (38.9%) in grade Ⅱ and 32 lesions (44.4%) in grade Ⅲ. The arterial phase of CECT showed 37 lesions (51.4%) to have no obvious enhancement and 35 lesions (48.6%) to have obvious enhancement. Consistency analysis showed that there was a high consistency between SMI and CECT(Kappa=0.861, P<0.001). The higher the SMI grading, the more obvious the enhancement on CECT. The complete ablation rates of the grade Ⅰ, grade Ⅱ and grade Ⅲ lesions were 100%(12/12), 92.9%(26/28) and 71.9%(23/32), respectively. The complete ablation rate of the lesions in grade Ⅲ was significantly lower than that in grade Ⅰ and grade Ⅱ (both P<0.05). Conclusion:SMI showed a good consistency with CECT in evaluating the blood flow signals of hepatic cancer, SMI grading could be used in predicting the therapeutic efficacy of hepatic cancer treated by PRFA.

OBJECTIVE: To investigate the protective effects of dexmedetomidine (DEX) against cerebral ischemia/reperfusion (I/R) injury in mice and its relation with mitochondrial fusion and fission. METHODS: Male ICR mice were randomly divided into sham-operated group, I/R group, I/R+DEX group and I/R+DEX+dorsomorphin group. Mouse models of cerebral I/R injury were established by modified thread occlusion of the middle cerebral artery. DEX (50 μg/kg) was injected intraperitoneally at 30 min before cerebral ischemia, which lasted for 1 h followed by reperfusion for 24 h. The neurobehavioral deficits of the mice were evaluated based on Longa's scores. The volume of cerebral infarction was detected by TTC staining. The changes in mitochondrial morphology of the brain cells were observed with transmission electron microscopy. Western blotting was performed to detect the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), mitochondrial fusion protein (Mfn2) and mitochondrial fission protein (p-Drp1) in the brain tissues. RESULTS: DEX pretreatment significantly reduced the neurobehavioral score and the percent volume of cerebral infarction in mice with cerebral I/R injury. Treatment with dorsomorphin (an AMPK inhibitor) in addition to DEX significantly increased the neurobehavioral score and the percent volume of cerebral infarction in the mouse models. Transmission electron microscopy showed that DEX obviously reduced mitochondrial damage caused by cerebral I/R injury and restored mitochondrial morphology of the brain cells, and such effects were abolished by dorsomorphin treatment. Western blotting showed that DEX pretreatment significantly increased the expressions of p-AMPK and Mfn2 protein and decreased the expression of p-Drp1 protein in the brain tissue of the mice, and these changes were also reversed by dorsomorphin treatment. CONCLUSIONS Preconditioning with DEX produces protective effects against cerebral I/R injury in mice possibly by activating AMPK signaling to regulate mitochondrial fusion and fission in the brain cells.
Animals ; Brain Ischemia ; Dexmedetomidine ; Male ; Mice ; Mice, Inbred ICR ; Mitochondrial Dynamics ; Reperfusion Injury

Objective: To evaluate the concordance of PD-L1 expression in various tissues using antibodies 28-8 and SP263 on their respective detection platforms. Methods: Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD-L1 expression using the two antibodies, 28-8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance. Results: For non-small cell lung carcinoma (NSCLC), the positive rate of PD-L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28-8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent. Conclusions The expression levels of 28-8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.

evaluate the concordance of PD?L1 expression in various tissues using antibodies 28?8 and SP263 on their respective detection platforms. Methods Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD?L1 expression using the two antibodies, 28?8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance. Results For non?small cell lung carcinoma (NSCLC), the positive rate of PD?L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28?8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent. Conclusions The expression levels of 28?8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.

OBJECTIVETo determine the frequency of spinocerebellar ataxia type 31 (SCA31) related mutations among patients from mainland China.

METHODSFor a cohort of molecularly unassigned patients comprised of 295 SCA patients (including 98 probands from families featuring autosomal dominant SCA and 197 sporadic cases) and 81 patients with hereditary spastic paraplegia (HSP) (including 23 probands from families with autosomal dominant HSP and 58 sporadic cases),TGGAA pentanucleotide expansion insertional mutation of the BEAN/TK2 gene was detected using repeat-primed PCR followed by capillary gel electrophoresis.

RESULTSNo TGGAA pentanucleotide insertion expansion in BEAN/TK2 gene was identified in the above cohort.

CONCLUSIONSCA31 is an extremely rare subtype of SCA and should not be included in routine genetic screening in mainland China.