Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Objective:To systematically evaluate the intervention effect of acceptance commitment therapy on anxiety disorder.Methods:The full-text databases of Web of Science Core Collection, MEDLINE, KCI-Korean Journal Database, SciELO Citation Index, SpringerLink, Pubmed, EMBASE, Cochrane Library, CNKI Wanfang and Weipu were searched and randomized controlled studies related to acceptance commitment therapy for patients with anxiety disorder were collected.All randomized controlled studies met the criterion were included.Meanwhile, the literature quality of the included literatures was evaluated.The outcome indicators such as anxiety index, psychological flexibility and quality of life index were selected, and RevMan 5.3 software was used to analyze the literature data that met the inclusion criteria.Results:A total of 12 studies with 1 062 patients were included, including 513 cases in ACT group and 549 cases in control group.Meta analysis showed that ACT can effectively reduce anxiety level of patients with anxiety disorder (MD=-0.58, 95% CI: -0.85- -0.32, P<0.001), anxiety level in follow-up period (MD=-0.42, 95% CI: -0.75- -0.08, P=0.01), improving psychological flexibility (MD=0.46, 95% CI: 0.24~0.68, P<0.001); In the study of CBT(cognitive behavioral therapy) as the control group, there was no significant difference between ACT group and control group, among which after intervention (MD =-0.06, 95% CI: -0.47- 0.36, P=0.79), follow-up period (MD = 0.17, 95% CI: -0.07-0.41, P=0.16) .In the study with the control group as the blank control, ACT can reduce the anxiety level of patients with anxiety disorder (MD =-0.76, 95% CI: -0.97- -0.56, P<0.001), and the difference is statistically significant.Excluding the non-blank control study, ACT can reduce the anxiety level of patients with anxiety disorder (MD =-0.82, 95% CI: -1.09--0.55, P<0.001) in the studies where the proportion of women is greater than or equal to 70%.In the study of 50%-70% females, ACT can reduce the anxiety level of patients with anxiety disorder (MD =-0.68, 95% CI: -1.09 --0.28, P=0.01). All the differences were statistically significant.There was no significant difference between ACT and the control group for quality of life(MD=0.24, 95% CI: -0.01-0.49, P=0.06). Conclusion:ACT has a certain effect on patients with anxiety disorder, which not only improves the anxiety level of patients, but also keeps the effect of anxiety improvement during the follow-up period, and the improvement of psychological flexibility has also been verified.The immediate and long-term efficacy of ACT is similar to that of CBT, which further improve the reliability of ACT curative effect.Gender difference has not been confirmed for the therapeutic effect.ACT has no obvious improvement on the quality of life, and the conclusion of this study needs more randomized controlled studies with large samples and high quality to verify it.

Objective: Abstract: Objective: To investigate the expression and significance of miR-138 and programmed cell death protein 1 (PD-1) in the patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: A total of 30 patients with HBV-related HCC, 20 with HBV-related cirrhosis (LC) and 30 with chronic hepatitis B (CHB) were recruited from Jiaozuo People′s Hospital. The blood samples from all patients and the peritoneal effusion samples from HCC and LC patients were collected. The levels of miR-138 and soluble PD-1 (sPD-1) in blood and peritoneal effusion samples were detected by real-time PCR and ELISA, respectively. The expressions of PD-1 in T lymphocytes were measured with flow cytometry and western blot. The targeting effect of miR-138 on the 3′-non-coding region (3′-UTR) of PD-1 gene was verified by the dual-luciferase reporter gene system. Results: The relative expression levels of miR-138 in the peritoneal effusion and plasma of HBV-related HCC patients were significantly lower than those in LC and CHB patients (P＜0.05). The serum sPD-1 levels and the expression levels of PD-1 in CD3 + T lymphocytes of HBV-related HCC patients were significantly higher than those in LC and CHB patients (P＜0.05). The relative expression levels of miR-138 were negatively correlated with serum sPD-1 levels and the expression levels of PD-1 in CD3 + T lymphocytes (P＜0.05). The dual-luciferase reporter gene system and western blot results demonstrated that there was a targeting relationship between miR-138 and the 3′-UTR of PD-1 gene. After miR-138 was transfected, the expression level of PD-1 was significantly down-regulated. Conclusion miR-138 participates in the development and progression of HBV-related HCC probably by targeting PD-1.

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult

Structure of biliary system is complex as well as various, making troubles for optimal surgical treatment of biliary disease. Remarkable imaging of biliary system helps surgeon evaluating patients and planning surgeries. There are several methods to obtain accurate anatomical information of biliary system, such as X-ray fluoroscopy, MRI and fluorescence-based imaging. Each has its own advantages and disadvantages. Combination of multi-model imaging technologies may improve visual result of anatomical information of biliary tract. More resolvable, legible, and sequential imaging technology of biliary system remains further study. This article reviews various cholangiography methods widely used in the clinical setting.

Gastric cancer is a serious malignancy that endangers human health. Increased rates of chemotherapy-resistant cancer have led to a decrease in the efficacy of treatment. Recent studies found that the presence of hypoxia in the tumor microenvironment was a notable cause of gastric cancer resistance to chemotherapy drugs. The abnormal structure and function of blood vessels in the tumor and the rapid proliferation of tumor cells increase the oxygen consumption of tumor cells, which results in tumor tissue hypox-ia. Hypoxic conditions make tumor cells more aggressive, more likely to metastasize and develop resistance to chemotherapy. In this paper, we have reviewed the progress of research into hypoxia-induced chemotherapeutic drug resistance in gastric cancer. The review has covered the causes of hypoxia and the characteristics of the hypoxic microenvironment in gastric cancer, the current situation and causes of hypoxia-induced chemotherapeutic drug resistance in gastric cancer, and the measures to overcome the hypoxia-induced re-sistance to chemotherapy drugs.

OBJECTIVE： To screen the active component， target and pathway of couplet medicine of “Bupleuri Radix- Atractylodis macrocephalea Rhizoma”， and to comprehensively explore its potential mechanism. METHODS： Based on the method of network pharmacology， main active componets and potential targets of  couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma” were retrieved from TCMSP， DRAR-CPI， Genecards and OMIM database. The active component-potential target network and interaction network of potential targets were established by Cytoscape 3.6.0 software. Five potential core targets were screened， and its affinity with active components were validated with molecule docking method. GO classified enrichment analysis and KEGG pathway enrichment analysis of potential targets were carried out to obtain key pathway so as to construct active component-potential target-key pathway network. RESULTS： Totally 17 active components and 47 active component-potential targets were obtained from couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma”. Five core targets were obtained， including AKT1， PRKCA， PRKCE， HRas， and PIK3CA. Five signaling pathways were involved， including MAPK pathway， PI3K/AKT pathway， RAS pathway， Estrogen pathway， BMP pathway. CONCLUSIONS： The couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma” not only act on multiple targets through multiple components for mammary hyperplasia， but also play a complex network regulation role through the interaction between potential targets.

Objective To investigate the prognostic influence factors of Solitaire stent thrombectomy in patients with acute anterior circulation macrovascular occlusion. Methods From March 2015 to March 2017,222 consecutive patients with acute anterior circulation macrovascular occlusion admitted to the Department of Neurosurgery,the 101stHospital of People′s Liberation Army and the Nanjing Jinling Hospital were enrolled retrospectively.They were all confirmed by DSA and were treated with Solitaire stent thrombectomy. According to the modified Rankin Scale(mRS) scores at 90 d after treatment,they were divided into a good prognosis group (0-2,n=120) and a poor prognosis group (3-6,n =102). The baseline data and clinical data of the two groups of patients were analyzed,including the risk factors for cardiocerebrovascular diseases,baseline National Institutes of Health Stroke Scale (NIHSS) score,occlusion sites (internal carotid artery or middle cerebral artery occlusion),collateral compensatory,onset to puncture time, operation time,onset to recanalization median time,recanalization status,preoperative Alberta stroke programme early CT score(ASPECTS),and symptomatic cerebral hemorrhage,and then further multivariate logistic regression analysis was conducted for the prognostic factors of patients. Results (1) The rate of good prognosis was 54.1% (120/222).There were no significant differences in patients′ age,NIHSS at admission,ASPECTS at admission,sex,hypertension,occlusion site,and rate of good collateral branches in both groups(all P<0.05).There were no significant differences in other baseline data (all P >0. 05). (2) Onset to puncture time and onset to successful recanalization median time of the patients in good prognosis group was lower than that of the poor prognosis group (182 [138,230]min vs.236[170,305]min, 237[175,269]min vs.288[223,367]min).The proportion of successful recanalization was higher than that of the poor prognosis group (98.3% [118/120] vs.78.4% [80/102]).The proportion of postoperative symptomatic intracerebral hemorrhage was lower than that of the poor prognosis group (2.5% [3/120] vs.21.6% [22/102]).There was significant difference between the two groups (all P <0.01). There was no significant difference in operative time between the two groups (P >0.05). (3)In the single factor analysis,the parameter of P <0.05 was used as an independent variable,and prognosis was used as a dependent variable,multivariate logistic regression analysis showed that the increased age (OR,1.096,95% CI 1.050-1.144),history of hypertension (OR,8.401,95% CI 2.960-23.845),increased baseline NIHSS score (OR,1.071,95% CI 1.007-1.138),prolonged onset to successful recanalization time (OR,1.019,95% CI 1.003-1.035),symptomatic intracerebral hemorrhage after procedure (OR,18.110,95% CI 4.656-70.434) were all the risk factors for poor prognosis(all P<0.05);higher ASPECTS score at admission(OR,0.641,95% CI 0.451-0.911) and successful recanalization (OR,0.127,95% CI 0.024-0.664) were all the protective factors of good prognosis (all P<0.05). Conclusions Higher ASPECTS at admission and successful recanalization were the protective factors of poor prognosis of Solitaire stent thrombectomy in patients with acute anterior circulation macrovascular occlusion.Increased age,history of hypertension,increased baseline NIHSS score,prolonged onset to successful recanalization time,and symptomatic intracerebral hemorrhage after procedure were the risk factors for poor prognosis of Solitaire stent thrombectomy in patients with acute anterior circulation macrovascular occlusion.