Case-problem-based learning of pathophysiology based on inquiry-based learning and process management / 中华医学教育探索杂志

Based on the teaching concept of constructivism, this study aims to promote independent inquiry-based learning and clinical thinking among students and establish the guiding ideology of "full participation, process control, in-depth discussion, and expansion of thinking". A blending learning model was adopted with offline inquiry-based group learning and in-class defense and comment, as well as online teacher-student interaction and supervision to promote learning. Case-problem-based learning (CPBL) of pathophysiology was carried out among the medical students in the class of 2017, and process management was strengthened to effectively manage the two key links of data retrieval and group discussion. The analysis of 176 teaching evaluations collected at the end of the semester show that in terms of the overall evaluation of CPBL teaching, 162 students (92.05%) had high evaluation on teaching objectives, organization, cases, and personal gains and held a very or relatively favorable attitude. There were more negative feedbacks on "appropriate time allocation"; 21 students (11.93%) held a relatively or very disapproving attitude, and 149 students (84.66%) "felt very tired". In terms of teaching effect evaluation, 150 students (85.23%) strongly or relatively agreed that CPBL teaching may help to understand professional knowledge, stimulate learning enthusiasm and initiative, improve problem solving ability, emphasize clinical practice to cultivate clinical thinking, supervise and promote learning, and enhance team cooperation and teacher-student communication. In terms of the evaluation of teachers, 167 students (94.89%) thought that teachers were rigorous, responsible, and enthusiastic in teaching, attached importance to process management, and did well in effective guidance and thinking inspiration (strongly or relatively agree). The above results suggest that the CPBL teaching reform of pathophysiology based on process management can effectively promote in-depth inquiry-based independent learning and the cultivation of clinical thinking and improve teaching effectiveness, but further improvement is needed for teaching arrangement and time allocation.

Cerebral blood flow autoregulation and cerebrovascular reactivity in patients with cerebral small vessel disease and depression / 中国医师进修杂志

Objective:To investigate the cerebral blood flow autoregulation and cerebrovascular reactivity in patients with cerebral small vessel disease (SVD) and depression.Methods:Eighty patients who were treated in Dalian Municipal Central Hospital Affiliated with Dalian University of Technology from May 2020 to may 2021 were selected and divided into observation group and control group according to the existence of depression. Transcranial Doppler sonography combined with standing and lying position test, breath holding test and breath exchange test were used to observe the "w" wave slope, the "w" wave slope, the "w" wave velocity and the "w" wave velocity cerebral blood flow velocity difference, breath holding index, pulsation index (PI) change rate before and after breath holding, resistance index (RI) change rate before and after breath holding, mean velocity (Vm), PI, RI change rate before and after breath exchange. The correlation between depression score and blood flow index was analyzed.Results:There were 38 and 29 patients occurred "w" wave in the control group and observation group respectively, and the rate were 95.0% (38/40) and 72.5% (29/40) respectively ( χ2 = 7.44, P = 0.006). The slope of "w" descending branch of Vm and the slope of "w" ascending branch of Vm in the observation group were smaller than those of the control group respectively: (1.26 ± 0.23) cm/s vs. (2.45 ± 1.00) cm/s, (1.38 ± 0.71) cm/s vs. (2.56 ± 0.77) cm/s, the difference of which had statistical meanings ( P<0.05). The difference of cerebral blood flow velocity of Vm after different positions in the observation group was higher than that in the control group significantly: (7.20 ± 3.07) cm/s vs. (2.93 ± 1.46) cm/s ( P<0.05). The breath holding index PI change rate, RI change rate before and after breath holding test in the observation group were lower than those in the control group statistically: (0.88 ± 0.33)% vs. (1.49 ± 0.27)%, (14.42 ± 9.31)% vs. (21.51 ± 8.79)%, (11.07 ± 1.70)% vs. (15.31 ± 6.73)% ( P<0.05). The change rates of Vm, PI and RI in the observation group before and after ventilation were lower than those in the control group ( P<0.05). There was a negative correlation between depression score and "w" wave slope (Vm), breath holding index, Vm change rate before and after ventilation, and a positive correlation between depression score and cerebral blood flow velocity difference (Vm) in supine and upright position with statistical meanings ( P<0.05). Conclusions:Depression could lead to the decline of cerebral blood flow autoregulation and cerebrovascular reactivity in patients with SVD. And with the aggravation of depression, the decline of cerebral blood flow autoregulation and cerebrovascular reactivity in patients with SVD is more serious.

LDHA inhibitor combined with targeted drugs synergistically inhibit the proliferation of fumarate hydratase-deficient renal cell carcinoma cells / 现代泌尿外科杂志

【Objective】 To explore the therapeutic effects of lactate dehydrogenase A (LDHA) inhibitor and targeted drugs on fumarate-hydratase-deficient renal cell carcinoma (FH-d RCC). 【Methods】 RNA-sequencing was used to detect the mRNA expression in FH-d RCC tissues, which was further validated with real-time fluorescence quantitative PCR and immunohistochemistry. Human-derived FH-d RCC cell line UOK262 and murine-derived FH-d RCC cell line FH1-/-CL19 (CL19) were treated with LDHA inhibitor [(R)-GNE-140] and listed kidney cancer targeted drugs (Axitinib, Cabozantinib, Sunitinib, Sorafenib, Pazopanib, Everolimus) respectively, and then treated with LHDA inhibitor in combination with the targeted drugs to observe the alteration of cell proliferation. The combination index (CI) of different dose groups of the combination drugs were analyzed with CompuSyn software to determine the optimal combination regimen. 【Results】 LDHA inhibitor and targeted drugs, including Cabozantinib, Sorafenib and Sunitinib, had a significant inhibitory effect on the proliferation of FH-d RCC cells, and the combination of Cabozantinib and Sorafenib or Pazopanib had a significant anti-tumor effect. 【Conclusion】 LDHA inhibitor combined with targeted drugs can significantly inhibit the growth of FH-d RCC cells, indicating that LDHA may be a potential therapeutic target of FH-d RCC.

Evaluation of the efficacy of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension using pulmonary perfusion tomography imaging / 中华核医学与分子影像杂志

Objective:To evaluate the efficacy of balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) using 99Tc m-macroaggregated albumin (MAA) pulmonary perfusion tomography imaging. Methods:Twenty-five patients (4 males, 21 females; age (56.5±12.3) years) with CTEPH who underwent BPA from January 2017 to April 2020 in Beijing Chaoyang Hospital, Capital Medical University were enrolled retrospectively. Effect of BPA on the improvement of pulmonary lobe/pulmonary segment perfusion was analyzed, and the proportions of improved and unimproved pulmonary lobe/pulmonary segment perfusion by BPA were calculated. The percentages of perfusion defect scores (PPDs%) of lung perfusion tomography imaging before BPA and after 4-6 times BPA were compared and analyzed (paired t test). The correlations between PPDs% and mean pulmonary artery pressure (mPAP) before BPA and after BPA were analyzed respectively, and the correlation between decreased percentage of PPDs% and decreased percentage of mPAP after BPA were also analyzed (Pearson correlation analysis). Results:Among 150 lobes of 25 patients, 96.00%(144/150) lobes showed perfusion abnormalities before BPA. After BPA, 11.11%(16/144) showed complete improvement, 57.64%(83/144) showed partial improvement, and 31.25%(45/144) showed no improvement. Among 450 pulmonary segments of 25 patients, 62.44%(281/450) showed perfusion abnormalities before BPA. After BPA, 30.60%(86/281), 37.37%(105/281), 32.03%(90/281) showed complete, partial and no improvement, respectively. The post-BPA PPDs% was significantly lower than that of pre-BPA ((39.08±10.88)% vs (57.88±10.46)%; t=10.40, P<0.001). The post-BPA mPAP was significantly lower than that of pre-BPA ((32.36±10.57) vs (49.08±10.23) mmHg; 1 mmHg=0.133 kPa; t=10.25, P<0.001). There was no significant correlation between PPDs% and mPAP either before BPA ( r=0.01, P=0.953) or after BPA ( r=0.27, P=0.199), but there was a positive correlation between the changes of PPDs% and mPAP ( r=0.40, P=0.045). Conclusions:BPA can significantly improve the pulmonary perfusion and reduce mPAP in CTEPH patients. Pulmonary perfusion tomography imaging can be used to evaluate the efficacy of BPA in CTEPH.

Effect of three tongue needles acupoints Lianquan (CV23) and Hegu (LI4) combined with swallowing training on the quality of life of laryngeal cancer patients with dysphagia after surgery.

OBJECTIVE: To evaluate the effect of acupuncture therapies administered in combination with swallowing training on the quality of life of laryngeal cancer patients with dysphagia after surgery. METHODS: Seventy-one postoperative patients with laryngeal cancer participated in this study. The patients diagnosed with swallowing dysfunction by video fluoroscopic swallowing examination (VFSE) were randomly divided into experimental group (n = 36) and control group (n = 35). Patients in both groups were provided swallowing training and rehabilitation consultation. Patients in the experimental group were additionally provided with acupuncture therapies. All patients were evaluated using VFSE and MD Anderson dysphagia inventory (MDADI) and Quality of Life Questionnaire-core 30 (QLQ-c30) score immediately after surgery and three months later. RESULTS: The effective rate of 97.1% (n = 35) and the complete remission rate of 36.1% (n = 13) in the experimental group were higher than those in the control group of 60% (n = 21) and 14.3% (n = 5) (P < 0.01). The scores of VFSE, MDADI and QLQ-c 30 in the experimental group and the control group at three months after therapies were significantly improved compared with those before therapies (P < 0.05). The scores of VFSE, MDADI and QLQ-c30 in the experimental group at three months after therapies were significantly improved compared with the control group. The improvement in the intervention group was significantly better than that in the control group. There were no adverse reactions in two groups. CONCLUSIONS: Acupuncture therapies combined with swallowing training can improve the swallowing function and the quality of life of laryngeal cancer patients with dysphagia after surgery.

Indolethylamine-N-Methyltransferase Inhibits Proliferation and Promotes Apoptosis of Human Prostate Cancer Cells: A Mechanistic Exploration.

Indolethylamine-N-methyltransferase (INMT) is a methyltransferase downregulated in lung cancer, meningioma, and prostate cancer; however, its role and mechanism in prostate cancer remain unclear. By analyzing The Cancer Genome Atlas (TCGA)-PRAD, we found that the expression of INMT in prostate cancer was lower than that of adjacent non-cancerous prostate tissues and was significantly correlated with lymph node metastasis Gleason score, PSA expression, and survival. Combined with the GSE46602 cohorts for pathway enrichment analysis, we found that INMT was involved in regulating the MAPK, TGFß, and Wnt signaling pathways. After overexpression of INMT in prostate cancer cell lines 22Rv1 and PC-3, we found an effect of INMT on these tumor signal pathways; overexpression of INMT inhibited the proliferation of prostate cancer cells and promoted apoptosis. Using the ESTIMATE algorithm, we found that with the increase of INMT expression, immune and stromal scores in the tumor microenvironment increased, immune response intensity increased, and tumor purity decreased. The difference in INMT expression affected the proportion of several immune cells. According to PRISM and CTRP2.0, the potential therapeutic agents associated with the INMT expression subgroup in TCGA were predicted. The area under the curve (AUC) values of 26 compounds positively correlated with the expression of INMT, while the AUC values of 14 compounds were negatively correlated with the expression of INMT. These findings suggest that INMT may affect prostate cancer's occurrence, development, and drug sensitivity via various tumor signaling pathways and tumor microenvironments.

Amentoflavone attenuates Listeria monocytogenes pathogenicity through an LLO-dependent mechanism.

BACKGROUND AND PURPOSE: L. monocytogenes remain a leading cause of foodborne infection. Listeriolysin O (LLO), an indispensable virulence determinant involved in diverse pathogenic mechanisms of L. monocytogenes infection, represents a promising therapeutic target. In this study, we sought to identify an effective inhibitor of LLO pore formation and its mechanism of action in the treatment of L. monocytogenes infection. EXPERIMENTAL APPROACH: Haemolysis assays were carried out to screen an effective LLO inhibitor. The interaction between candidate and LLO was investigated using surface plasmon resonance and molecular docking. The effect of candidate on LLO-mediated cytotoxicity, barrier disruption and immune response were investigated. Finally, the in vivo effect of candidate on mice challenged with L. monocytogenes was examined. KEY RESULTS: Amentoflavone, a natural flavone present in traditional Chinese herbs, effectively inhibited LLO pore formation by engaging the residues Lys93, Asp416, Tyr469 and Lys505 in LLO. Amentoflavone dose-dependently reduced L. monocytogenes-induced cell injury in an LLO-dependent manner. In the Caco-2 monolayer model, amentoflavone maintained the integrity of the epithelial barrier exposed to LLO. Amentoflavone inhibited the inflammatory response evoked by L. monocytogenes in an LLO-dependent manner, and inhibition was attributed to ability to block perforation-associated K+ efflux and Ca2+ influx. In the mouse infection model, amentoflavone treatment significantly reduced bacterial burden and pathological lesions in target organs, with a significant increase in survival rate. CONCLUSIONS AND IMPLICATIONS: Amentoflavone reduced the pathogenicity of L. monocytogenes by specifically inhibiting LLO pore formation, and this may represent a potential treatment for L. monocytogenes infection.

Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit / 中华神经科杂志

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma with PD-L1 negativity in transplanted liver tissue / 中华器官移植杂志

Objective:To explore the safety and efficacy of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma with PD-L1 negativity in transplanted liver tissue.Methods:From May 2020 to December 2020, retrospective analysis was performed for 3 cases of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma recipients with PD-L1 negative in transplanted liver tissue.Three recipients with extrahepatic recurrence progressed after first/second-line targeted drug therapy.Camrelizumab was given as salvage therapy after normal tissue of ransplanted liver was confirmed as negative for PD-L1 by immunohistochemistry.The safety and efficacy of treatment were observed by monitoring the changes in the levels of alanine aminotransferase, aspartate aminotransferase and bilirubin, the occurrence of complications and the outcome of treatment before and after dosing.Results:During a follow-up period of 1.5 to 15.5 months, no recipients showed acute rejection symptoms such as sharp elevations of transaminase and bilirubin.Headache ( n=1), vomiting ( n=1) and fatigue & hypertension ( n=1) became relieved after treatment.As of February 28, 2022, there were one survivor and two deaths.The fatal causes were tumor progression ( n=1) and thoracic aortic rupture due to esophageal perforation ( n=1). The survival time of recipients was (11-15.5) months and the progression-free survival time (4-6) months. Conclusions:For extrahepatic recurrent hepatocellular carcinoma with PD-L1-negative liver transplantation in normal liver tissue, camrelizumab salvage therapy can control tumor progression to a certain extent and prolong the survival time of recipients.

Correlation analysis between SUV index in 18F-FDG PET/CT imaging and invasiveness of early lung adenocarcinoma / 中华核医学与分子影像杂志

Objective:To investigate the correlation between the SUV index (SUV max of the lesion/SUV mean of the liver) in 18F-FDG PET/CT imaging and the invasiveness of early lung adenocarcinoma presenting as ground-glass nodule (GGN). Methods:From January 2012 to March 2020, 167 GGN patients (49 males, 118 females; age: (61.5±9.0) years) with early lung adenocarcinoma who underwent PET/CT imaging in Changzhou First People′s Hospital were retrospectively enrolled. The image parameters including the GGN number, location, type, edge, shape, abnormal bronchus sign, vacuole sign, pleural depression, vessel convergence sign, GGN diameter ( DGGN), solid component diameter ( Dsolid), consolidation to tumor ratio (CTR, Dsolid/ DGGN), CT values (CT value of ground-glass opacity (CT GGO), CT value of lung parenchyma (CT LP), ΔCT GGO-LP (CT GGO-CT LP)) and SUV index were analyzed. Single and multivariate logistic regressions were used to analyze the correlation between SUV index and infiltration. The generalized additive model was used for curve fitting, and the piece-wise regression model was used to further explain the nonlinearity. Results:In 189 GGNs, invasive adenocarcinoma accounted for 85.2% (161/189). Single logistic regression showed that the GGN number, type, shape, edge, abnormal bronchus sign, pleural depression, vessel convergence sign, DGGN, Dsolid, CTR, CT GGO, ΔCT GGO-LP and SUV index were related factors of infiltration (odds ratio ( OR) values: 0.396-224.083, P<0.001 or P<0.05). After fully adjusting for confounding factors, SUV index was significantly correlated with increased risk of invasion ( OR=2.162 (95% CI: 1.191-3.923), P=0.011). Curve fitting showed that the SUV index was non-linearly related to the risk of infiltration, and the risk of infiltration increased significantly only when the SUV index was greater than 0.43 ( OR=3.509 (95% CI: 1.429-8.620), P=0.006). The correlation between SUV index and infiltration had no interaction between age, vacuoles, pleural depression and CTR subgroups (all P>0.05). Conclusions:SUV index is an independent factor related to the invasiveness of early lung adenocarcinoma. The higher the SUV index, the greater the risk of invasion; but the two are not simply linearly correlated.

Assessment of left ventricular diastolic dyssynchrony and its influencing factors early after acute myocardial infarction by SPECT gated myocardial perfusion imaging: an experimental study / 中华核医学与分子影像杂志

Objective:To evaluate the left ventricular diastolic dyssynchrony (LVDD) and its influencing factors early after acute myocardial infarction (AMI) using phase analysis of SPECT gated myocardial perfusion imaging (GMPI).Methods:Bama miniature swines ( n=16) were subjected to establish AMI models. GMPI was performed before and 1 d after AMI to obtain the extent of myocardial perfusion defect (Extent, %) and left ventricular systolic dyssynchrony (LVSD)/LVDD parameters, namely the phase histogram bandwidth (PBW) and phase standard deviation (PSD). Meanwhile, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early to late peak mitral diastolic flow (E/A) were obtained by echocardiography. Independent-sample t test, paired t test and Pearson correlation analysis were used to analyze the data. Results:Sixteen AMI swines were successfully created. Compared to baseline, Extent, LVEDV and LVESV significantly increased on 1 d after AMI ( t values: -11.14, -4.55, -6.12, all P<0.001), while LVEF and E/A significantly decreased ( t values: 10.16, 2.18, P<0.001, P=0.046). GMPI showed that the LVDD parameters PBW and PSD increased significantly on 1 d after AMI when compared to those at baseline((142.25±72.06)° vs (33.06±8.98)°, (56.15±26.71)° vs (12.51±5.13)°; t values: -6.11, -6.60, both P<0.001). There were significant differences between LVSD parameters and LVDD parameters (PBW: (109.06±62.40)° vs (142.25±72.06)°, PSD: (44.40±25.61)° vs (56.15±26.71)°; t values: -2.73, -2.20, P values: 0.016, 0.044). LVDD parameters PBW, PSD were negatively correlated with E/A after AMI ( r values: -0.569, -0.566, P values: 0.021, 0.022), and positively correlated with the Extent ( r values: 0.717, 0.634, P values: 0.002, 0.008). The phase analysis of SPECT GMPI to evaluate LVDD showed good intra-observer and inter-observe reproducibility (intraclass correlation coefficient (ICC): 0.953-0.984, all P<0.001). Conclusions:LVDD occurs early on 1 d after AMI, and can reflect left ventricular diastolic dysfunction. The Extent is correlated with LVDD significantly. Phase analysis of SPECT GMPI is an accurate method to evaluate LVDD and left ventricular diastolic function.

Correlation between lesion volume ratio and cognitive function in ischemic leukoaraiosis / 中国医师进修杂志

Objective:To investigate the relationship between the volume ratio of ischemic leukoaraiosis (LA) and cognitive level and arterial perfusion.Methods:Fifty-four patients, who was hospitalized in Dalian Central Hospital and diagnosed as LA clinically during the time of March to December in 2012, were selected to collect the information of the volume ratio of white matter disease, MoCa score and the average flow rate of carotid artery. The correlation between the volume ratio of white matter disease and MoCa score, cognitive impairment and the average flow rate of carotid artery were analyzed.Results:The volume ratio of LA lesions was negatively correlated with MOCA score ( r = -0.59, P<0.01); the volume ratio of LA lesions was negatively correlated with the mean flow rate of internal carotid artery ( r = -0.37, P<0.01). Quantity order of the area under receiver operating characteristic (ROC) curve of MoCA cognitive subgroup was as following: delayed memory (1.000)> visual space/executive function (0.970) = abstract force (0.970)> language ability (0.960)> attention (0.888). Conclusions:The larger the volume ratio of leukopathy in LA patients, the more serious the cognitive impairment, especially the cognitive impairment of impairment of memory delay, visual space/executive function, abstract ability and language ability.

Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension / 中华内科杂志

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Association of inflammatory markers and thromboinflammatory factors before and after thrombolytic intervention with functional outcomes in elderly patients with acute cerebral infarction / 中华老年医学杂志

Objective:To explore the association of inflammatory markers and thromboinflammatory factors before and after thrombolytic intervention with functional outcomes in elderly patients with acute cerebral infarction.Methods:392 patients with acute cerebral infarction admitted to our hospital were randomly selected as study subjects and divided into an observation group(196 cases)treated with arterial thrombolytic therapy and a control group(196 cases)treated with intravenous thrombolysis.Functional outcomes of patients were assessed 72 hours after thrombolysis using the activities of daily living(ADL)scale and, based on the results, patients were divided into a poor functional outcome group and a good functional outcome group.Inflammatory markers such as neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)and thromboinflammatory factors such as monocyte chemoattractant protein-1(MCP-1), tissue plasminogen activator(t-PA), soluble CD40 ligand(sCD40L)and P-selectin before and after thrombolysis were measured.The relationship of these inflammatory markers and thromboinflammatory factors before thrombolysis with functional outcomes 72 hours after thrombolysis was analyzed.Results:NLR and PLR levels in the two groups after thrombolysis were significantly lower than those before thrombolysis(all P<0.05); Their levels in the observation group were lower than those in the control group(all P<0.05). After thrombolysis, MCP-1 levels in both groups were significantly higher and t-PA, sCD40L, P-selectin levels were significantly lower than pre-thrombolysis levels(all P<0.05); After thrombolysis, the observation group had better results than the control group(all P<0.05). Correlation analysis showed that NLR, PLR, MCP-1 and t-PA were positively correlated with NIHSS score( r=0.336, 0.264, 0.483, 0.549, all P<0.05). NLR, PLR, MCP-1, t-PA and sCD40L levels were significantly lower and P-selectin levels were significantly higher in the good functional outcome group than in the poor functional outcome group both before and 72 hours after thrombolysis( t=13.850, 18.208, 23.636, 22.371, 59.868, 96.646, 378.112, 141.213, 131.160, 110.039, 10.716, 11.108, P<0.05 for all). Logistic regression analysis showed that abnormal levels of NLR, PLR, MCP-1 and t-PA before and after thrombolysis were risk factors for adverse outcomes with thrombolytic intervention( P<0.05). ROC curves showed that the levels of NLR, PLR, MCP-1, t-PA, sCD40L and P-selectin before thrombolysis had a certain predictive value for the risk of adverse functional outcomes with thrombolysis. Conclusions:The levels of these inflammatory markers and thromboinflammatory factors before and after thrombolytic intervention have varying degrees of correlation with functional outcomes in elderly patients with acute cerebral infarction.

Molecular engineering of transketolase from Escherichia coli and tartaric semialdehyde biosynthesis / 生物工程学报

Transketolase (EC 2.2.1.1, TK) is a thiamine diphosphate-dependent enzyme that catalyzes the transfer of a two-carbon hydroxyacetyl unit with reversible C-C bond cleavage and formation. It is widely used in the production of chemicals, drug precursors, and asymmetric synthesis by cascade enzyme catalysis. In this paper, the activity of transketolase TKTA from Escherichia coli K12 on non-phosphorylated substrates was enhanced through site-directed saturation mutation and combined mutation. On this basis, the synthesis of tartaric semialdehyde was explored. The results showed that the optimal reaction temperature and pH of TKTA_M (R358I/H461S/R520Q) were 32 ℃ and 7.0, respectively. The specific activity on d-glyceraldehyde was (6.57±0.14) U/mg, which was 9.25 times higher than that of the wild type ((0.71±0.02) U/mg). Based on the characterization of TKTA_M, tartaric acid semialdehyde was synthesized with 50 mmol/L 5-keto-d-gluconate and 50 mmol/L non-phosphorylated ethanolaldehyde. The final yield of tartaric acid semialdehyde was 3.71 g with a molar conversion rate of 55.34%. Hence, the results may facilitate the preparation of l-(+)-tartaric acid from biomass, and provide an example for transketolase-catalyzed non-phosphorylated substrates.

TACR2 is associated with the immune microenvironment and inhibits migration and proliferation via the Wnt/ß-catenin signaling pathway in prostate cancer.

BACKGROUND: The tachykinin receptor 2 (TACR2) is encoded by the tachykinin receptor correlation gene. Recent microarray analysis for prostate cancer suggests that TACR2 expression is associated with clinical phenotype and disease-free survival among patients with prostate cancer. RESULTS: TACR2 protein levels were lower in prostate cancer tissues than in adjacent normal prostate tissue. TACR2 expression significantly correlated with clinical stage, Gleason scores, and survival outcomes. TACR2 expression positively correlated with mast cells and negatively correlated with M2 macrophages. Overexpression of TACR2 promoted the migration and proliferation of prostate cancer cells by regulating the Wnt signaling pathway. CONCLUSIONS: The TACR2-Wnt/ß-catenin signaling pathway is critical in prostate cancer. TACR2 may affect tumor cells' occurrence and development by changing the content of immune cells in the tumor microenvironment. These findings suggest that TACR2 may be a candidate molecular biomarker for prostate cancer therapy.

Long non-coding RNAs correlate with genomic stability in prostate cancer: A clinical outcome and survival analysis.

BACKGROUND: Long non-coding RNAs (lncRNAs) participate in the regulation of genomic stability. Understanding their biological functions can help us identify the mechanisms of the occurrence and progression of cancers and can provide theoretical guidance and the basis for treatment. RESULTS: Based on the mutation hypothesis, we proposed a computational framework to identify genomic instability-related lncRNAs. Based on the differentially-expressed lncRNAs (DElncRNAs), we constructed a genomic instability-derived lncRNA signature (GILncSig) to calculate and stratify outcomes in patients with prostate cancer. It is an independent predictor of overall survival. The area under the curve = 0.805. This value may be more significant than the classic prognostic markers TP53 and Speckle-type POZ protein (SPOP) in terms of outcome prediction. CONCLUSIONS: In summary, we conducted a computation approach and resource for mining genome instability-related lncRNAs. It may turn out to be highly significant for genomic instability and customized decision-making for patients with prostate cancer. It also may lead to effective methods and resources to study the molecular mechanism of genomic instability-related lncRNAs.

Efficient Anticancer Effect on Choroidal Melanoma Cells Induced by Tanshinone IIA Photosensitization.

Tanshinone IIA (TanIIA) has multiple biological functions and already been clinically used to treat many cardiovascular diseases. TanIIA is a photoactive molecule and can be excited by light to generate 3 TanIIA*. Generation of 3 TanIIA* by TanIIA photosensitization indicates that TanIIA may serve as a photosensitizer to bring photodynamic damage to organisms. Therefore, human choroidal melanoma MUM-2B cell was chosen as a superficial tumor model and the photodynamic effect of TanIIA on tumor cells was evaluated in this study. The results showed that TanIIA photosensitization could generate singlet oxygen in noncellular system. MTT, clone formation and wound-healing assays showed that the survival and migration of MUM-2B cells could be efficiently inhibited by TanIIA photosensitization. And then, laser confocal microscope and flow cytometry were used to try to elucidate related mechanism. It was found that TanIIA could pass through cellular membrane and preferably accumulate in nucleus. TanIIA photosensitization could efficiently induce cell apoptosis and necrosis, increase intracellular ROS levels, decrease mitochondria membrane potential, and lead to cell cycle arrest in G2/M phase. Our findings indicate that TanIIA photosensitization can exert remarkable toxicity on choroidal melanoma cells.

Analysis of sonography videourodynamic studies in characteristics of patients with female bladder outlet obstruction / 中华泌尿外科杂志

In this study, sonography video urodynamic studies (SVUDS), which combined synchronically urodynamic studies with trans-perineal and trans-abdominal sonography, were used to detect female bladder outlet obstruction (FBOO). The dynamic changes of urethra and surrounding pelvic floor structure during storage and voiding phase were observed by SVUDS and the causes of FBOO were analyzed. And the findings were as follows: 13 patients showed organ prolapse, there was an urethral angulation deformity during urination; 5 cases had abnormal urination as the urethral opening was not good in the middle of urination period; 4 cases had urethral stricture, as the proximal end of the obstruction dilated during urination, and the obstruction site showed no relaxation; 1 case had primary bladder neck obstruction with an incomplete opening of the bladder neck during urination; 3 cases had idiopathic bladder outlet obstruction and the sphincter of bladder neck and urethra opened well during urination.

Value of 18F-FDG PET/CT metabolic parameters of primary lesions for predicting occult lymph node metastasis in non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To investigate the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT metabolic parameters for occult lymph node metastasis (OLM) in non-small cell lung cancer (NSCLC). Methods:A total of 183 patients (72 males, 111 females; age (61.5±8.4) years) who underwent 18F-FDG PET/CT and preoperatively diagnosed with clinical N0 stage (cN0) in Third Affiliated Hospital of Soochow University from January 2013 to December 2018 were retrospectively enrolled. All patients underwent anatomical pulmonary resection with systematic lymph node dissections within 3 weeks after 18F-FDG PET/CT examinations. According to the presence or absence of lymph node metastasis, patients were divided into OLM positive (OLM+ ) group and OLM negative (OLM-) group. Parameters of primary lesions, such as the maximum diameter (D max), tumor sites, morphological features, maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), metabolic total volume (MTV), total lesion glycolysis (TLG), tumor SUV max to liver SUV mean (TLR max), tumor TLG to liver SUV mean (TLR TLG) were analyzed. Mann-Whitney U test and χ2 test were used to compare the parameters between groups. Multivariable logistic regression was used to analyze the independent risk factors for OLM. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of different parameters. Results:Among 183 patients, 25 (13.7%, 25/183) of them were diagnosed as OLM. In OLM+ group, 46 lymph nodes were pathologically positive for metastasis, including 15 N1 disease and 31 N2 disease. D max (2.9(2.3, 3.7) vs 2.3(1.7, 2.8) cm), lobulation ((76.0%(19/25) vs 37.3%(59/158)), SUV max (11.1(7.9, 17.7) vs 4.7(2.3, 9.2)), TLG (41.5(10.2, 91.1) vs 15.6(6.5, 23.8) ml), TLR max (4.7(3.5, 7.6) vs 2.1(0.9, 4.0)) and TLR TLG (18.1(5.0, 44.3) vs 6.1(3.0, 11.4) ml) of the primary lesions in OLM+ group were significantly higher than those in OLM-group ( z values: from -4.709 to -3.247, χ2=13.190, all P<0.05). Multivariable logistic regression analysis showed that TLR max (odds ratio ( OR)=15.145, 95% CI: 3.381-67.830, P<0.001) and D max ( OR=3.220, 95% CI: 1.192-8.701, P=0.021) were independent risk factors for OLM. TLR max yielded the highest area under curve (AUC; AUC=0.794) with the threshold of 3.12, and the sensitivity, specificity, accuracy, positive predictive value and negative predictive value for predicting OLM were 92.0%(23/25), 63.3%(100/158), 67.2%(123/183), 28.4%(23/81) and 98.0%(100/102), respectively. Conclusions:TLR max of tumor is the independent risk factor for OLM in NSCLC patients. TLR max can sensitively predict OLM preoperatively in patients with NSCLC.