NONO promotes gallbladder cancer cell proliferation by enhancing oncogenic RNA splicing of DLG1 through interaction with IGF2BP3/RBM14.

Gallbladder cancer (GBC) is a highly malignant and rapidly progressing tumor of the human biliary system, and there is an urgent need to develop new therapeutic targets and modalities. Non-POU domain-containing octamer-binding protein (NONO) is an RNA-binding protein involved in the regulation of transcription, mRNA splicing, and DNA repair. NONO expression is elevated in multiple tumors and can act as an oncogene to promote tumor progression. Here, we found that NONO was highly expressed in GBC and promoted tumor cells growth. The dysregulation of RNA splicing is a molecular feature of almost all tumor types. Accordingly, mRNA-seq and RIP-seq analysis showed that NONO promoted exon6 skipping in DLG1, forming two isomers (DLG1-FL and DLG1-S). Furthermore, lower Percent-Spliced-In (PSI) values of DLG1 were detected in tumor tissue relative to the paraneoplastic tissue, and were associated with poor patient prognosis. Moreover, DLG1-S and DLG1-FL act as tumor promoters and tumor suppressors, respectively, by regulating the YAP1/JUN pathway. N6-methyladenosine (m6A) is the most common and abundant RNA modification involved in alternative splicing processes. We identified an m6A reader, IGF2BP3, which synergizes with NONO to promote exon6 skipping in DLG1 in an m6A-dependent manner. Furthermore, IP/MS results showed that RBM14 was bound to NONO and interfered with NONO-mediated exon6 skipping of DLG1. In addition, IGF2BP3 disrupted the binding of RBM14 to NONO. Overall, our data elucidate the molecular mechanism by which NONO promotes DLG1 exon skipping, providing a basis for new therapeutic targets in GBC treatment.

Intracranial aneurysm rupture risk in northern China: a retrospective case-control study.

Background: Rupture of intracranial aneurysms (IAs) can cause subarachnoid hemorrhage (SAH), which leads to severe neurological dysfunction and even death. Exploring the risk factors for IA rupture and taking preventive measures accordingly can reduce or prevent the occurrence of SAH. Currently, there is still no consensus on the detrimental factors for IA rupture. Thus, our study aimed to investigate the risk factors of IA rupture in a population of northern China. Methods: We systematically collected the demographic features, medical history, and imaging data of aneurysms from patients with ruptured and unruptured IAs (UIAs) who attended the Department of Neurosurgery at the Second Hospital of Hebei Medical University from 2014 to 2019. All cases had been diagnosed by digital subtraction angiography. We excluded patients with SAH resulting from injuries, as well as those with vascular dissection and incomplete data. Finally, 1,214 patients including 616 with ruptured IAs and 598 with UIAs were collected for further analysis. A case-control study was conducted, in which multivariable logistic regression was used to analyze the risk factors for IA rupture. Results: Our multivariable logistic regression showed that anterior cerebral artery [odds ratio (OR) =2.413; 95% confidence interval (CI): 1.235-4.718], anterior communicating artery (OR =3.952; 95% CI: 2.601-6.006), posterior communicating artery (OR =2.385; 95% CI: 1.790-3.177), and anterior circulation branches (OR =3.493; 95% CI: 1.422-8.581) were risk factors for IA rupture, whereas patients with a history of cerebral infarction (OR =0.395; 95% CI: 0.247-0.631) and those with IAs located in the internal carotid artery (OR =0.403; 95% CI: 0.292-0.557) were less likely to have IA rupture. Conclusions: IAs at specific locations are prone to rupture. These IAs should be paid particular attention and preventive measures should be taken to reduce or prevent their rupture.

Application Value of Target Calyx Pretreatment Technique for Treating Complete Staghorn Calculi by Endoscopic Combined Intrarenal Surgery / 中国微创外科杂志

Objective To investigate the safety and efficacy of target calyx pretreatment technique in the treatment of complete staghorn calculi by endoscopic combined intrarenal surgery(ECIRS).Methods Clinical data of 21 patients with complete staghorn calculus treated by ECIRS from October 2019 to September 2021 in our hospital were retrospectively analyzed.There were 8 cases in the left side and 12 cases in the right side.One case of bilateral kidney calculus was given right side treatment in the first stage.The stone density was(1101±185)HU.The operation was performed by two surgeons.Under general anesthesia,the patient was placed in an oblique supine lithotomy position.The target calyx was designed according to preoperative imaging examination.The stone in the target calyx was broken up by flexible ureteroscope in advance to expose the papillary dome.Percutanous nephrostomy of the target calyx was performed,and F18 or F20 percutaneous work access was established under surveillance by using flexible ureteoscope and ultrasound.Results The operation was successfully accomplished in one stage in all the 21 cases.The mean operation time was(121.8±21.2)min,the postoperative hemoglobin reduction was(9.38±4.36)g/L,the postoperative hospital stay was(4.4±1.4)d,and the postoperative stone free rate(SFR)was 85.7％(18/21).A total of 6 patients had postoperative complications,including 1 case of bleeding requiring blood transfusion,3 cases of fever,1 case of hydrothorax,and 1 case of postoperative pain in the operative area requiring analgesic treatment.Conclusion For complete staghorn calculus,using flexible ureteroscope to pretreat stones of target calices and then puncturing to establish percutaneous renal working channel can significantly increase the success rate of surgery and the immediate postoperative stone free rate,reduce the number of percutaneous renal channels,and improve the safety of surgery.

A cooperative construction strategy for multi-parameter spatial variant random fields and its application in groundwater pollution risk assessment.

The spatial variability of hydrogeological parameters is a significant source of uncertainty in groundwater numerical modeling and has a certain risk impact on the prediction of pollutant migration and transformation. Current research has focused on the effects of single-parameter spatial variant random fields or utilizing random sampling methods to randomly combine multiple-parameter spatial variant random fields while ignoring the correlation between parameters. This paper proposes an innovative concept of associated random variables to construct multi-parameter synergistic spatial variant random fields, ensuring both the spatial variability and inherent correlation of the parameters. A hypothetical case was constructed, and the Monte Carlo sampling experiment based on computer simulation was used to assess groundwater pollution risks with multiple associated parameters. The results show that hydraulic conductivity and porosity are the main sensitive parameters. The associated random variable allows for the representation of positive correlation, negative correlation, and no correlation between the hydraulic conductivity and porosity. The pollutant mass concentrations in each observation well conform to the generalized extreme value distribution, and the pollution risks of each water well as well as the concentration distribution intervals of pollutants with different probabilities can be obtained. The influence of associated parameters on the cumulative risk of contaminants in observation wells and pollution degree range is only related to their mathematical distribution and is independent of correlations between parameters. This study addresses the issues of spatial variability and inherent correlation of hydrogeological parameters, which are of great significance for groundwater pollution risk assessment and the promotion of sustainable water quality management of groundwater resources.

Nicorandil Exerts Anticonvulsant Effects in Pentylenetetrazol-Induced Seizures and Maximal-Electroshock-Induced Seizures by Downregulating Excitability in Hippocampal Pyramidal Neurons.

N-(2-hydroxyethyl) nicotinamide nitrate (nicorandil), a nitrate that activates adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, is generally used in the treatment of angina and offers long-term cardioprotective effects. It has been reported that several KATP channel openers can effectively alleviate the symptoms of seizure. The purpose of this study was to investigate the improvement in seizures induced by nicorandil. In this study, seizure tests were used to evaluate the effect of different doses of nicorandil by analysing seizure incidence, including minimal clonic seizure and generalised tonic-clonic seizure. We used a maximal electroshock seizure (MES) model, a metrazol maximal seizure (MMS) model and a chronic pentylenetetrazol (PTZ)-induced seizure model to evaluate the effect of nicorandil in improving seizures. Each mouse in the MES model was given an electric shock, while those in the nicorandil group received 0.5, 1, 2, 3 and 6 mg/kg of nicorandil by intraperitoneal injection, respectively. In the MMS model, the mice in the PTZ group and the nicorandil group were injected subcutaneously with PTZ (90 mg/kg), and the mice in the nicorandil group were injected intraperitoneally with 1, 3 and 5 mg/kg nicorandil, respectively. In the chronic PTZ-induced seizure model, the mice in the PTZ group and the nicorandil group were injected intraperitoneally with PTZ (40 mg/kg), and the mice in the nicorandil group were each given 1 and 3 mg/kg of PTZ at a volume of 200 nL. Brain slices containing the hippocampus were prepared, and cell-attached recording was used to record the spontaneous firing of pyramidal neurons in the hippocampal CA1 region. Nicorandil (i.p.) significantly increased both the maximum electroconvulsive protection rate in the MES model and the seizure latency in the MMS model. Nicorandil infused directly onto the hippocampal CA1 region via an implanted cannula relieved symptoms in chronic PTZ-induced seizures. The excitability of pyramidal neurons in the hippocampal CA1 region of the mice was significantly increased after both the acute and chronic administration of PTZ. To a certain extent, nicorandil reversed the increase in both firing frequency and proportion of burst spikes caused by PTZ (P < 0.05). Our results suggest that nicorandil functions by downregulating the excitability of pyramidal neurons in the hippocampal CA1 region of mice and is a potential candidate for the treatment of seizures.

Predictors of unprovoked seizures in intracerebral hemorrhages.

BACKGROUND: Seizures are a common complication of intracerebral hemorrhage (ICH). We aimed to identify predictors of unprovoked seizures (US) after ICH in a Chinese cohort. METHODS: We retrospectively included patients with ICH admitted in the Second Hospital of Hebei Medical University between November 2018 and December 2020. Incidence and risk factors of US were identified with univariate and then multiple Cox regression analysis. We used χ2 test to compare incidence of US between groups with or without prophylactic anti-seizure medications (ASM) in patients with craniotomy. RESULTS: A total of 488 patients were included in the cohort, 58 (11.9%) patients developed US within 3 years after ICH. Analysis on the 362 patients without prophylactic ASM showed that craniotomy (HR 8.35, 95% CI 3.80-18.31) and acute symptomatic seizures (ASS) (HR 13.76, 95% CI 3.56-53.17) are independent predictors of US. No significant effect of prophylactic ASM use was found on incidence of US in ICH patients with craniotomy (P = 0.369). CONCLUSIONS: Craniotomy and acute symptomatic seizures were independent predictors for unprovoked seizures after ICH, suggesting that more attention should be paid for such patients during follow-up. Whether prophylactic ASM treatment benefits ICH patients underwent craniotomy remains uncertain.

Clinical value of complete lateral position endoscopic combined intra-renal surgery in treatment of staghorn kidney calculi / 中国医师进修杂志

Objective:To assess the safety and feasibility of complete lateral position endoscopic combined intra-renal surgery (ECIRS) in treatment of staghorn kidney calculi.Methods:The clinical data of 105 patients with staghorn kidney calculi from March 2016 to July 2022 in the First Hospital of Shanxi Medical University were retrospectively analyzed. Among them, 55 patients were treated with lateral position percutaneous nephrolithotomy (PCNL) (PCNL group), and 50 patients were treated with complete lateral position ECIRS (ECIRS group). The operative time, removal time of double J-tube, postoperative hospital stay, postoperative hemoglobin decrease value, operative complications (using Clavien-Dindo grading criteria), additional postoperative intervention and calculi free rate were compared between two groups.Results:Both groups of patients were successfully operated. The operative time, postoperative hemoglobin decrease value and rate of additional postoperative intervention in ECIRS group were significantly lower than those in PCNL group: (98.3 ± 19.1) min vs. (103.4 ± 16.5) min, (9.34 ± 3.04) g/L vs. (12.55 ± 4.75) g/L and 8.00% (4/50) vs. 21.82% (12/55), the calculi free rate was significantly higher than that in PCNL group: 90.00% (45/50) vs. 74.55% (41/55), and there were no statistical differences ( P<0.05 or <0.01); there were no statistical differences in the removal time of double J-tube, postoperative hospital stay, incidence of Clavien-Dindo≥ grade Ⅱ operative complications between two groups ( P>0.05). Conclusion:The complete lateral position ECIRS is a safe and effective treatment for staghorn kidney calculi, and is a good complement to the ECIRS technique because of its high stone free rate in phase Ⅰ, low complication incidence and easy dissemination.

Guillain-Barré Syndrome in Northern China: A Retrospective Analysis of 294 Patients from 2015 to 2020.

Objectives: Acute motor axonal neuropathy (AMAN) was first reported to be the main subtype of Guillain−Barré syndrome (GBS) in northern China in the 1990s. About 30 years has passed, and it is unknown whether the disease spectrum has changed over time in northern China. We aimed to study the epidemiological, clinical, and electrophysiological features of GBS in northern China in recent years. Methods: We retrospectively analyzed the medical records of GBS patients admitted to the Second Hospital of Hebei Medical University in northern China from 2015 to 2020. Results: A total of 294 patients with GBS were enrolled, with median age 53 years and 60.5% of participants being male, and a high incidence in summer and autumn. AMAN was still the predominant subtype in northern China (40.1%). The AMAN patients had shorter time to nadir, longer hospitalization time, and a more severe HFGS score at discharge than acute inflammatory demyelinating polyneuropathies (AIDP) (p < 0.05). With SPSS multivariable logistic regression analysis, we found the GBS disability score (at admission), dysphagia, and dysautonomia were independent risk factors for GBS patients requiring MV (p < 0.05). In comparison with other regions, the proportion of AMAN in northern China (40.1%) was higher than in eastern (35%) and southern (19%) China. Conclusions: AMAN is still the predominant subtype in northern China after 30 years, but there have been changes over time in the GBS spectrum since the 1990s. There are regional differences in GBS in China.

A construction strategy for conservative adaptive Kriging surrogate model with application in the optimal design of contaminated groundwater extraction-treatment.

When the simulation-optimization model to optimize the groundwater extraction-treatment schemes is used, the construction of a surrogate model for the numerical simulation model has become an effective means to overcome the large calculation load of repeatedly calling the numerical model. However, there are still some problems in using the surrogate model, such as large training sample size, low accuracy, and poor optimization results. In this paper, a conservative adaptive Kriging surrogate model (CAKSM) was proposed by coupling the Kriging surrogate model, optimal solution adaptive sampling method (OSAS), and conservative prediction idea. Firstly, an initial Kriging surrogate model (IKSM) was built for the numerical simulation model of groundwater flow and solute transport. Then, the IKSM was coupled with the optimization model to construct the adaptive Kriging surrogate model (AKSM) by using OSAS. A safety margin was added to the AKSM to build the CAKSM. Finally, the simulation-optimization models based on IKSM, AKSM, and CAKSM were solved by the genetic algorithm, respectively. The results showed that the IKSM could well substitute for the simulation model. The AKSM significantly improved the approximation degree between the surrogate model and the simulation model at the optimal solution by supplementing a small number of new samples. CAKSM could effectively constrain the pollutant mass concentrations within the controlled value, improving the reliability of the optimization scheme. The optimal extraction wells based on different surrogate models were all well 5, well 6, and well 9. They were concentrated in the middle and lower reaches of the contaminated plume's central axis. The sequence for the remediation effects by different surrogate models from high to low was as follows: CAKSM, AKSM, and IKSM. The risk rate of the optimal remediation scheme from the hydraulic conductivity random fields was as high as 12.12%, and the risks were mainly located upstream of the pollution plume's central axis.

"Olfactory three-needle" acupuncture enhances synaptic function in Aß1-42-induced Alzheimer's disease via activating PI3K/AKT/GSK-3ß signaling pathway.

Synaptic dysfunction and neuronal loss are related to cognitive impairment of Alzheimer's disease. Recent evidence indicates that regulating the phosphatidylinositol 3-Kinase (PI3K)/AKT/GSK-3ß pathway is a therapeutic strategy for improving synaptic plasticity in Alzheimer's disease. Here, we investigated "olfactory three-needle" effects on synaptic function and the PI3K/AKT/GSK-3ß signaling pathway in ß-amyloid1-42 (Aß1-42)-induced Alzheimer's disease rats. A three-needle olfactory bulb insertion for 28 days alleviated Aß1-42-induced Alzheimer's disease rats' cognitive impairment as assessed by performance in the Morris water maze test. Furthermore, the three-needle electrode inhibited neuro-apoptosis and neuro-inflammation. It significantly upregulated the protein expression of postsynaptic density protein 95, synaptophysin, and GAP43, indicating a protective effect on hippocampal synaptic plasticity. Additionally, the activation level of PI3K/AKT signaling and the phosphorylation inactivation of GSK-3ß were significantly enhanced by the "olfactory three-needle". Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents.

Anti-Tumor Effects of Astaxanthin by Inhibition of the Expression of STAT3 in Prostate Cancer.

Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3.

"Olfactory Three-Needle" Enhances Spatial Learning and Memory Ability in SAMP8 Mice.

As one of the most important therapies in complementary and alternative medicine, acupuncture has been used in the treatment of Alzheimer's disease (AD). Acupuncture of "olfactory three-needle" manipulation can improve the cognitive ability of AD patients. However, the mechanism of "olfactory three-needle" in AD remains largely unknown. Here, we identified that the "olfactory three-needle" therapy and eugenol olfactory stimulation both reduced the deposition of ß-amyloid (Aß) protein and increased the expression of synaptophysin (SYP), but only the "olfactory three-needle" enhanced the spatial learning and memory ability of SAMP8. Remarkably, the "olfactory three-needle" inhibited the phosphorylation of p38MAPK and the excessive activation of microglia (MG) in the hippocampus. Our study demonstrates that the "olfactory three-needle" enhances spatial learning and memory ability by inhibiting the phosphorylation of p38MAPK and the excessive activation of MG to reduce the neuroinflammatory response and neurotoxicity of Aß and promote synaptic regeneration, but it was not completely consistent with the stimulation of the olfactory system.

The manufacture and application of novel evaluating tool for renal vascular anatomy : the system of individualized reno-vasculature evaluation for nephrectomy / 中华泌尿外科杂志

Objective To explore the clinical feasibility and effectiveness of novel preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy for retroperitoneoscopic radical nephrectomy (RLRN).Methods Two-hundred and fifty one consecutive patients who underwent RLRN for renal tumours from September 2016 to March 2018 were enrolled prospectively,including 154 males (61.4％) and 97 females (38.6％),aged 26 to 84 years with the mean age of 58.7 and mean BMI of 25.8 kg/m2.The tumors were all isolated with the mean size of 5.4 cm.According to presence or absence of vascular correlation events (VCE) and nephrectomy times under endoscope (NTE),all the cases were divided into two groups:the common group (VCE,NTE ＜ 60 min)and the difficult group (no VCE,NTE ≥ 60 min).With the help of preoperative three-dimensional reconstruction,the specific and crucial arteriovenous anatomical features were recorded,which consist of side,count,spatial configuration and density of the vessel to be processed.After univariable analysis,muhivariable analysis with logistic regression was performed for the selected risk factors.Individualized renovasculature evaluation for nephrectomy were established,when the value of risk factors were assigned separately according to its correlation and clinical practice.Results There was no statistical significance between common group and difficult group in the aspects of gender,age,BMI,maximum diameter of the tumor,R.E.N.A.L.score and PADUA score.There were statistical significance between common group and difficult group in the aspects of N (number of total vessels),D (vascular anomalies density),C (3Dconformation),S (sides) of pending renal vessels (x2 =125.700,102.014,97.090,12.603,P ＜0.05).The correlation of N,D,C were closely related (standardized regression coefficient were 0.742,0.664,0.324,P ＜ 0.05),but S was not significant (P ＞ 0.05).SIREN was preliminarily established as a preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy.Of the 5 components of SIREN,N,D were scored on 1 to 3 points,C was scored on 0 to 3 points,E was scored on 0 to 1 point,and S was not scored but showed in terms of L or R.All of these constitute the assessment content with a full score of 10 points except S suffixed by L or R instead of scores.There was a statistically significant difference during low (2-3 points),middle (4-6 points),and high (7-10 points) groups (x2 =126.927,P ＜ 0.05) according to the comparisons between low and middle,low and high,as well as middle and high (x2 =90.997,7.195,91.679,P ＜ 0.05).Conclusions In virtue of the renal vascular scoring system named after SIREN by 3d reconstructing,the spatial structure information of the renal vascular system can be obtained accurately and expressed directly before operation,the difficulty of vascular treatment can be predicted,the preoperative planning can be optimized,and the accurate quantitative evaluation of renal vascular anatomical structure can be achieved to further improve the surgical safety and efficiency.

The manufacture and application of novel evaluating tool for renal vascular anatomy: the system of individualized reno-vasculature evaluation for nephrectomy / 中华泌尿外科杂志

Objective@#To explore the clinical feasibility and effectiveness of novel preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy for retroperitoneoscopic radical nephrectomy (RLRN).@*Methods@#Two-hundred and fifty one consecutive patients who underwent RLRN for renal tumours from September 2016 to March 2018 were enrolled prospectively, including 154 males (61.4%) and 97 females (38.6%), aged 26 to 84 years with the mean age of 58.7 and mean BMI of 25.8 kg/m2. The tumors were all isolated with the mean size of 5.4 cm. According to presence or absence of vascular correlation events (VCE) and nephrectomy times under endoscope (NTE), all the cases were divided into two groups: the common group (VCE, NTE <60 min) and the difficult group (no VCE, NTE ≥60 min). With the help of preoperative three-dimensional reconstruction, the specific and crucial arteriovenous anatomical features were recorded, which consist of side, count, spatial configuration and density of the vessel to be processed. After univariable analysis, multivariable analysis with logistic regression was performed for the selected risk factors. Individualized reno-vasculature evaluation for nephrectomy were established, when the value of risk factors were assigned separately according to its correlation and clinical practice.@*Results@#There was no statistical significance between common group and difficult group in the aspects of gender, age, BMI, maximum diameter of the tumor, R. E.N.A.L. score and PADUA score. There were statistical significance between common group and difficult group in the aspects of N (number of total vessels), D (vascular anomalies density), C (3D conformation), S (sides) of pending renal vessels (χ2=125.700, 102.014, 97.090, 12.603, P<0.05). The correlation of N, D, C were closely related (standardized regression coefficient were 0.742, 0.664, 0.324, P<0.05), but S was not significant (P>0.05). SIREN was preliminarily established as a preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy. Of the 5 components of SIREN, N, D were scored on 1 to 3 points, C was scored on 0 to 3 points, E was scored on 0 to 1 point, and S was not scored but showed in terms of L or R. All of these constitute the assessment content with a full score of 10 points except S suffixed by L or R instead of scores. There was a statistically significant difference during low (2-3 points), middle (4-6 points), and high (7-10 points) groups (χ2=126.927, P<0.05) according to the comparisons between low and middle, low and high, as well as middle and high (χ2=90.997, 7.195, 91.679, P<0.05).@*Conclusions@#In virtue of the renal vascular scoring system named after SIREN by 3d reconstructing, the spatial structure information of the renal vascular system can be obtained accurately and expressed directly before operation, the difficulty of vascular treatment can be predicted, the preoperative planning can be optimized, and the accurate quantitative evaluation of renal vascular anatomical structure can be achieved to further improve the surgical safety and efficiency.

The application of full-size three-dimensional printing model combined with three-dimensional digital demonstration in facilitating patient's preoperative understanding of laparoscopic partial nephrectomy / 中华泌尿外科杂志

Objective To evaluate the feasibility and effectiveness of full-size three-dimensional individual printed model (3D-IPM) for improving the patient's understanding of laparoscopic partial nephrectomy (LPN) preoperatively.Methods Between June 2015 and June 2016,37 patients with cT1 renal tumors underwent retroperitoneal LPN.The 3D individual digital models (3D-IDMs) were created using 3D medical image reconstructing and guiding system (3D-MIRGS) and the full-size 3D-IPMs were fabricated correspondingly.For each patient and his/her closest accompanying immediate family member (CAIFM),two preoperative conversations with a single surgeon were held by using patient's CT films,the entity of 3D-IPM combined with 3D-IDM demonstration separately.The preoperative levels of comprehension to the renal anatomy,mass characteristics,the upcoming PN procedure,potential complication risks and postoperative prognosis were evaluated using a self-made scoring questionnaire in the patient and CAIFM groups.Results All the fabrications of full-size 3D-IPMs were technically successful.Both in patient and CAIFM groups,the total preoperative comprehending score (total-PCS) elevated significantly by presenting 3D-IPM combined with 3D-IDM demonstration than CT films (42.7 vs.31.5 in patient group,P ＜ 0.05;44.6 vs.33.1 in CAIFM group,P ＜ 0.05).Sub-PCSs in all 5 aspects also showed a uniformed climbing pattern with the assistance of 3D-IPM combined with 3D-IDM demonstration rather than CT films.Conclusion The application of 3D-IPM combined with 3D-IDM demonstration can improve the preoperative comprehension of the patient and CAIFM to LPN with more intuitionistic and verisimilar presentation.

Age-related alterations in the metabolic profile in the hippocampus of the senescence-accelerated mouse prone 8: a spontaneous Alzheimer's disease mouse model.

Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD.

1483 cases of paternity test with STR loci mutation / 法医学杂志

OBJECTIVE@#To observe and analyze the mutation phenomenon of 17 STR loci of PowerPlex 18D Kit in paternity test of Yunnan population.@*METHODS@#The DNA was extracted by Chelex-100 method. The PowerPlex 18D Kit was used to test 1,483 cases and their conclusions of paternity tests were verified.@*RESULTS@#In the 1,483 cases, 1,047 were parental triplet and 436 were uniparental diad. A total of 2,530 times of meiosis was observed. One STR locus mutation was observed in 24 cases. And 11 mutation loci were found in the 17 STR loci.@*CONCLUSION@#STR loci mutation is a common phenomenon. We should collect the data of STR loci mutation, choose other good polymorphism, low mutation rate of genetic markers, to ensure that the results are accurate and reliable.

Repetitive transcranial magnetic stimulation applications normalized prefrontal dysfunctions and cognitive-related metabolic profiling in aged mice.

Chronic high-frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has recently received increasing interests as a therapeutic procedure for neurodegenerative diseases. To identify the metabolism mechanism underlying the improving effects of rTMS, we observed that high frequency (25Hz) rTMS for 14 days could reverse the decline of the performance of the passive avoidance task in aged mice. We further investigated the metabolite profiles in the prefrontal cortex (PFC) in those mice and found that rTMS could also reverse the metabolic abnormalities of gamma-aminobutyric acid, N-acetyl aspartic, and cholesterol levels to the degree similar to the young mice. These data suggested that the rTMS could ameliorate the age-related cognitive impairment and improving the metabolic profiles in PFC, and potentially can be used to improve cognitive decline in the elderly.

Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice.

Autophagy is responsible for the degradation of long-lived proteins and damaged organelles intracellular, even extracellular,and autophagy is proved to have relationship with Alzheimer's disease (AD) and aging. The senescence accelerated mouse prone 8 (SAMP8) was a non-genetically modified mice widely used as a rodent model of aging and senile dementia. However, little was known about the age-related changes of autophagy in the brain of SAMP8 mice. To better understand the precise relationship between aging, autophagy and neurodegeneration, we explored the time course of cognitive ability, ubiquitin-positive inclusions, ultrastructure of neurons and detected the expression of LC3 and Beclin 1 protein in different brain regions of 2, 7 and 12-month-old SAMP8 and SAMR1 mice. We found that 7 and 12-month-old SAMP8 mice presented cognitive decline and ubiquitinated proteins enhanced. In the hippocampal neurons of 12-month-old SAMP8 mice, lots of dense clumps and autophagic vacuoles were found in the cytoplasm and axons. The LC3-II expression showed an increase in hippocampus and cortex of 7 and 12-month-old SAMP8 mice. The expression of Beclin 1 displayed a significant increase in 7 months old and a decline in 12 months old mice. Based on these data, we suggest that the autophagic activity maybe increase reactively at the beginning of AD and then showed a decline with aging, and the pathological changes of 12-month-old SAMP8 mice are more similar to the late-onset AD in the perspective of autophagy.