Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective To investigate the clinical effectiveness of magnetic resonance spectroscopy (MRS) combined with sodium fluorescein(FL) in the treatment of high grade gliomas(HGG). Methods From August 2013 to 2015 November,the clinical data of 72 supratentorial HGG(WHO grade Ⅲ-Ⅳ) patients who had received surgical treatment in our hospital were retrospectively studied,among whom 43 cases received MRS combined with intra-perative FL navigation(observation group),and 29 cases only received conventional surgery(control group). Post-operative radiotherapy and chemotherapy were applied for more than 3 months. Routine enhanced MRI were performed 24-48 hours after the operation to investigate the extent of tumor resection. Six months after the operation,the quality of life of patients was evaluated by using the Karnofsky score,and 1-year postoperative survival rate and progression-free survival(PFS) were observed. Results Postoperative MRI showed that the rate of gross total resection(GTR) in observation group was significantly higher than that in control group(72.09%vs.51.72%;χ=23.88,P=0.001),and the GTR rate of WHO grade Ⅳ tumors was significantly higher than that of WHO grade Ⅲ tumors in observation group(92.86% vs.62.07%;χ=6.06,P=0.042). The postoperative Karnofsky score in the observation group was significantly higher than that in control group(μ=2.34,P=0.021). The mean time of follow-up was(16.4±2.4) months(8-21 months) and there was no statistical significant difference between observation group and control group in 1-year survival rate(74.07% vs.77.50%;χ=4.90,P=0.165) and PFS [(13.2±1.2) months vs.(12.7±2.0) months;χ=7.26,P=0.067]. In observation group,the PFS of WHO grade Ⅳ patients was significantly higher than that in control group [(14.2±0.3) months vs.(10.0±1.1) months;χ=11.03,P=0.031]. There was also no statistical significant difference between WHO grade Ⅳ tumors in two groups in terms of 1-year survival rate(71.43% vs.72.54%;χ=5.33,P=0.089),and there was no statistical significant difference between WHO grade Ⅲ tumors in two groups in 1-year survival rate(75.86% vs. 72.22%;χ=3.78,P=0.250) and in PFS [(13.7±1.4) months vs.(12.4±0.8) months;χ=4.85,P=0.083]. Conclusions MRS combined with intraoperative FL navigation technology can improve the resection rate and improve survival quality of patients,and there is no evidence that MRS combined with intraoperative FL navigation prolong the overall survival of patients with high-grade gliomas. Different outcome may be found with longer follow-up and increased simple size.

Objective To compare the intraoperative major metabolite level of preoperative proton magnetic resonance spectroscopy(H-MRS)and fluorescence intensity marked with fluorescein sodium(FLs)in glioblastoma(GBM)and thus provide an objective basis for fluorescence surgical treatment of GBM. Methods All newly diagnosed patients by plain and enhanced magnetic resonance imaging from the April 1,2014 to December 31,2015 were enrolled in this study.All of them receivedH-MRS and marked with FLs.The expression of Ki67 in tumor boundary were confirmed by postoperative pathology and determined by immunostaining assay.The relationship betweenH-MRS metabolite levels and tumor fluorescence intensity was analyzed. Results Totally 33 patients were included in the study.PreoperativeH-MRS revealed high-grade gliomas in 25 cases.The N-acetylaspartate(NAA)decreased significantly and choline(Cho)increased significantly in high-grade gliomas.The ratios of Cho/NAA,NAA/creatine(Cr),and Cho/Cr significantly differed in different tumor regions(P=0.02,P=0.01,and P=0.00,respectively).Surgical results were marked with FLs intraoperatively.Tissue fluorescence were clearly seen.There were 29 patients undergoing total resection and 4 cases undergoing subtotal resection.No acute encephalocele occured after operation,while 2 patients suffered from epilepsy.Postoperative pathology results included:28 cases were diagnosed as GBM(22 cases consistent withH-MRS diagnosis).The results of GBM fluorescence imaging included:the level of fluorescence intensity in tumor parenchyma was significantly higher than that in tumor boundary and peritumoral edema(P=0.01).The result ofH-MRS metabolite analysis included:The kurtosis of NAA and of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor parenchyma(P=0.01,P=0.02,and P=0.01).While there was no difference in the kurtosis of NAA,the kurtosis of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor boundary(P=0.02, P=0.00).In peritumoral edema,there was no significant different in kurtosis of NAA and of Cho and in the ratio of Cho/NAA(P=0.23,P=0.09,P=0.14).Immunohistochemistry in GBM tumor boundary showed different Ki67 expressions according to different fluorescence imaging(P=0.03). Conclusions The fluorescence intensity in GBM parenchyma is higher than that in other tumor regions,and there are different metabolic levels in different fluorescence intensity.The metabolic information marked by FLs and provided byH-MRS before operationis are important,and the correlation between them should be further investigated.

OBJECTIVETo investigate the role of Pim-3 abnomal expression in development of acute myeloid leukemia.

METHODSSemi-quantitative RT-PCR was used to detect the expression of Pim-3 in bone marrow of 47 newly diagnosed and untreated patients with acute myeloid leukemia (AML) and 18 patients with AML after treatment with chemotherapy. At the same time, the bone marrow of 10 cases of non-hematologic malignancies was used as normal control. The difference of the Pim-3 gene expression in bone marrows among the 3 groups was also compared.

RESULTSAccording to the RT-PCR detection results, the Pim-3 expression level in bone marrow of AML patients before chemotherapy were all significantly lower than those in patients with non-hematologic malignancies (P < 0.01). After chemotherapy, there were no significant differences of the Pim-3 expression level between the patients with acute myeloid leukemia and non-hematologic malignancies (P > 0.05), but the Pim-3 expression level was significantly lower in patients before chemotherapy as compared with that in patients post chemotherapy (P < 0.01). The comparison of Pim-3 expression before and after chemotherapy in remission group showed that Pim-3 expression levels before chemotherapy were all significantly lower than those after chemotherapy (P < 0.01), but there were no significant differences of Pim-3 expression levels between patients before and after chemotherapy in non-remission group (P > 0.05). The Pim-3 expression levels of non-remission patients after chemotherapy were all significantly lower than those of the remission patients after chemotherapy (P < 0.01).

CONCLUSIONPim-3 gene is abnormally expressed in the AML patients before and after chemotherapy, and this gene may be involved in the genesis and development of acute myeloid leukemia.

Antineoplastic Agents ; therapeutic use ; Bone Marrow ; metabolism ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism

OBJECTIVETo isolate, identify and culture human spermatogonial stem cells (SSC) and then obtain purified and enriched human SSCs for research and application.

METHODSWe detected the expression of CD90 in the human testis using the immunofluorescence technique and isolated human testicular spermatogenic cells by two-step enzymatic digestion, followed by differential plating and magnetic-activated cell sorting (MACS) with CD90 as an SSC marker. Then we identified the isolated CD90-positive spermatogenic cells by RT-PCR and immunocytochemistry, and meanwhile cocultured them with Sertoli cells in SG medium in vitro.

RESULTSThe isolated CD90-positive cells showed a relatively homogeneous characteristic in size and morphology and expressed the genes specific for human SSCs, with high expressions (90.5%) of GFRA1, GPR125, and UCHL1. After coculture with Sertoli cells in the SG medium for 2 weeks, the isolated CD90-positive cells maintained a good activity.

CONCLUSIONCD90 can be regarded as a speci- fic marker for human SSCs and used to obtain highly enriched human SSCs by differential plating and MACS. Furthermore, the isolated human SSCs can be cultured in SG medium in vitro.

Adult Stem Cells ; cytology ; Biomarkers ; metabolism ; Cell Separation ; methods ; Cell Shape ; Cell Size ; Coculture Techniques ; Glial Cell Line-Derived Neurotrophic Factor Receptors ; metabolism ; Humans ; Immunohistochemistry ; Male ; Receptors, G-Protein-Coupled ; metabolism ; Sertoli Cells ; Spermatogonia ; cytology ; Testis ; metabolism ; Thy-1 Antigens ; isolation & purification ; metabolism ; Ubiquitin Thiolesterase ; metabolism

BACKGROUNDSmall noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins. However, their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood. The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF.

METHODSThree groups of dogs were studied: adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing. The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction. Pathohistological and ultrastructural changes were tested by light and electron microscopy. Apoptosis index of myocytes was detected by TUNEL.

RESULTSSamples of atrial tissue showed the abnormal pathohistological and ultrastructural changes, the accelerated fibrosis, and apoptosis with aging and/or in AF dogs. Compared to the adult group, the expressions of microRNAs-21 and -29 were significantly increased, whereas the expressions of microRNAs-1 and -133 showed obvious downregulation tendency in the aged group. Compared to the aged group, the expressions of microRNAs-1, -21, and -29 was significantly increased in the old group in AF; contrastingly, the expressions of microRNA-133 showed obvious downregulation tendency.

CONCLUSIONThese multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.

Age Factors ; Animals ; Apoptosis ; Atrial Fibrillation ; etiology ; Atrial Remodeling ; Connective Tissue Growth Factor ; physiology ; Dogs ; Electrocardiography ; Fibrosis ; In Situ Nick-End Labeling ; MicroRNAs ; analysis ; physiology ; Myocardium ; pathology ; ultrastructure

OBJECTIVETo construct the recombinant plasmid pcDNA3.0-RGC32 and evaluate the effect of the response gene to complement-32 (RGC32) on cell cytoskeleton in vitro.

METHODSThe full-length cDNA of RGC32 was obtained by RT-PCR and inserted into the eukaryotic expression vector pcDNA3.0 to generate the recombinant plasmid pcDNA3.0-RGC32. After transfection of the recombinant plasmid into SW480 cells, the expression of RGC32 in the cells was detected by Western blotting. The cytoskeleton of SW480 cells was visualized before and after the transfection, and the changes in the cell migration ability was assessed by wound-healing assay.

RESULTSThe recombinant plasmid pcDNA3.0-RGC32 was successfully constructed. The expression of RGC32 was significantly increased in SW480 cells after transfection with pcDNA3.0-RGC32. Before the transfection, the microfilaments of SW480 cells were few and short without obvious polarity, but after the transfection, the microfilaments were increased and elongated with also an obvious polarity, and the invasive structures of lamellae and lamellipodia occurred. The migration ability of the cells was enhanced after transfection with pcDNA3.0-RGC32.

CONCLUSIONOverexpression of RGC32 can cause the reorganization of cytoskeleton and promotes the cell migration, which can be an important mechanism of RGC32 in promoting cancer metastasis.

Cell Cycle Proteins ; biosynthesis ; genetics ; Cell Line, Tumor ; Cell Movement ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Cytoskeleton ; chemistry ; metabolism ; Genetic Vectors ; Humans ; Muscle Proteins ; biosynthesis ; genetics ; Neoplasm Metastasis ; genetics ; Nerve Tissue Proteins ; biosynthesis ; genetics ; Plasmids ; genetics ; Recombinant Proteins ; biosynthesis ; genetics

BACKGROUNDNon-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platelet activation may play an important role in pathologic progress in lung cancer. In this study, we aimed to clarify the influence of activated platelets on lung cancer generation and growth, and the relationship among these functional and ultrastructural changes of platelets and the severity of pathogenetic condition in these patients with NSCLC.

METHODSOne hundred and thirty-six cases of patients with pathologically confirmed NSCLC were included in this study. Fifty-four healthy people were enrolled as controls. The change of ultra microstructure and activity of blood platelets were observed under the transmission and scanning electron microscope. Simultaneous determination of plasma granule membrane protein 140 (GMP-140) was made.

RESULTSTransmission electron microscopy showed remarkable changes of ultra microstructure of platelets in patients with NSCLC, including swelling, increase of a-granules, vesicles, and glycogenosome. Scanning electron microscopy showed many more surface processes and wrinkles on platelets in patients with NSCLC. The reference plasma levels of GMP-140 of healthy controls were (18.2 +/- 2.7) microg/L. The plasma levels of GMP-140 in patients with NSCLC were (47.8 +/- 12.3) microg/L, which were much higher than those of the controls. There was a medium positive correlation between plasma levels of GMP-140 and amount of a-granules (r = 0.514, P < 0.01) and a high positive correlation between plasma levels of GMP-140 and area of platelet (r = 0.84, P < 0.01) in patients with NSCLC. The Kaplan-Meier survival curve analysis showed significant shift to the left in patients with NSCLC whose a-granules per platelet were 19 or more compared to those 18 or less (Log rank statistic, chi(2) = 17.38, P < 0.01).

CONCLUSIONSThere are significant activated changes of ultra microstructure and increased activity of blood platelets in patients with NSCLC. These activated platelets may play an important role in the generation and growth of lung cancer. These changes can be used as a diagnostic index of severity, progression, and prognosis of NSCLC.

Adult ; Aged ; Blood Platelets ; ultrastructure ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; mortality ; ultrastructure ; Female ; Humans ; Male ; Microscopy, Electron, Transmission ; Middle Aged ; P-Selectin ; blood ; Survival Analysis