Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.

Chimeric antigen receptor T-cells, known as CAR-T cells, represent a promising breakthrough in the realm of adoptive cell therapy. These T-cells are genetically engineered to carry chimeric antigen receptors that specifically target tumors. They have achieved notable success in the treatment of blood-related cancers, breathing new life into this field of medical research. However, numerous obstacles limit chimeric antigen receptors T-cell therapy's efficacy, such as it cannot survive in the body long. It is prone to fatigue and exhaustion, leading to difficult tumor elimination and repeated recurrence, affecting solid tumors and hematological malignancies. The challenges posed by solid tumors, especially in the context of the complex solid-tumor microenvironment, require specific strategies. This review outlines recent advancements in improving chimeric antigen receptors T-cell therapy by focusing on the chimeric antigen receptors protein, modifying T-cells, and optimizing the interaction between T-cells and other components within the tumor microenvironment. This article aims to provide an extensive summary of the latest discoveries regarding CAR-T cell therapy, encompassing its application across various types of human cancers. Moreover, it will delve into the obstacles that have emerged in recent times, offering insights into the challenges faced by this innovative approach. Finally, it highlights novel therapeutic options in treating hematological and solid malignancies with chimeric antigen receptors T-cell therapies.

Recent Advancement in Inhaled Nano-drug Delivery for Pulmonary, Nasal, and Nose-to-brain Diseases.

Pulmonary, nasal, and nose-to-brain diseases involve clinical approaches, such as bronchodilators, inhaled steroids, oxygen therapy, antibiotics, antihistamines, nasal steroids, decongestants, intranasal drug delivery, neurostimulation, and surgery to treat patients. However, systemic medicines have serious adverse effects, necessitating the development of inhaled formulations that allow precise drug delivery to the airways with minimum systemic drug exposure. Particle size, surface charge, biocompatibility, drug capacity, and mucoadhesive are unique chemical and physical features that must be considered for pulmonary and nasal delivery routes due to anatomical and permeability considerations. The traditional management of numerous chronic diseases has a variety of drawbacks. As a result, targeted medicine delivery systems that employ nanotechnology enhancer drug efficiency and optimize the overall outcome are created. The pulmonary route is one of the most essential targeted drug delivery systems because it allows the administering of drugs locally and systemically to the lungs, nasal cavity, and brain. Furthermore, the lungs' beneficial characteristics, such as their ability to inhibit first-pass metabolism and their thin epithelial layer, help treat several health complications. The potential to serve as noninvasive self-administration delivery sites of the lung and nasal routes is discussed in this script. New methods for treating respiratory and some systemic diseases with inhalation have been explored and highlight particular attention to using specialized nanocarriers for delivering various drugs via the nasal and pulmonary pathways. The design and development of inhaled nanomedicine for pulmonary, nasal, and respiratory medicine applications is a potential approach for clinical translation.

Construction and application of prone position ventilation management scheme for severe COVID-19 patients.

Background: Prone position ventilation (PPV) can significantly improve oxygenation index and blood oxygen saturation in most (70%-80%) patients with acute respiratory distress syndrome. However, although PPV is not an invasive procedure, there are many potential PPV-related complications, such as nerve compression, crush injury, venous stasis (e.g., facial oedema), pressure sores, retinal damage, vomiting, and arrhythmia, with an incidence of up to 56.9%. Nursing managers have focused on reducing the occurrence of PPV-related complications and improving safety. Objective: To construct a prone ventilation management scheme for patients with severe coronavirus disease 2019 (COVID-19) and analyse its application effect. Methods: Based on a previous evidence-based study combined with the COVID-19 Diagnosis and Treatment Protocol (Trial Edition 9), a prone ventilation management protocol for severe COVID-19 was formulated and applied to COVID-19 patients in the intensive care unit of a designated hospital. A prospective self-control study was used to compare changes in the oxygenation index and other outcome indicators before and after the intervention. Results: The oxygenation index of patients after intervention (321.22 ± 19.77 mmHg) was significantly higher (p < 0.05) than before intervention (151.59 ± 35.49 mmHg). The difference in oxygenation index in different prone position ventilation durations was statistically significant (p < 0.05). Nursing quality evaluation indicators showed that the implementation rate of gastric residual volume assessment was 100% and the incidence of occupational exposure and cross-infection was 0%; the incidences of pressure ulcers, drug extravasation, and facial oedema were 13.64% (3/22), 4.54% (1/22), and 4.54% (1/22), respectively. The incidence of unplanned extubation, aspiration, and falls/falls was 0%.

Effects of menthol on thirst during surgery patients fasting: A systematic review and meta-analysis of randomized controlled studies.

AIMS: We aim to analyse the effect of menthol on thirst intensity and thirst comfort in surgical patients. BACKGROUND: Menthol has achieved good results in quenching thirst in patients in intensive care units, but its safety and reliability in perioperative fasting patients are unknown. DESIGN: A systematic review with meta-analysis of intervention studies was performed. DATA SOURCES: We used Chinese and English databases from their dates of inception to May 2022. Literature was retrieved from PubMed, Web of Science, Cochrane Library, Embase, CINHAL, SinoMed, CNKI, Wanfang and VIP database. REVIEW METHODS: Two reviewers independently examined the records according to the eligibility criteria and extracted the data of each included study. RESULTS: A total of seven studies were identified in this review, which included 537 surgical patients. Overall, menthol reduced thirst intensity in surgical patients and decreased thirst discomfort. Further subgroup analysis revealed that the menthol intervention significantly improved thirst intensity in surgical patients during preoperative and postoperative fasting periods. The Egger's tests showed no significant bias (p = 0.113 and 0.553, thirst intensity and thirst discomfort, respectively). CONCLUSION: Menthol intervention effectively improved thirst intensity and thirst discomfort during fasting in surgical patients, but more large-scale, multicentre randomized controlled trials are required to confirm these findings further.

Association between red cell distribution width-to-platelet ratio and short-term and long-term mortality risk in patients with acute ischemic stroke.

BACKGROUND: The objective of this study was to evaluate the association between red cell distribution width/platelet ratio (RPR) and 30-day and 1-year mortality in acute ischemic stroke (AIS). METHODS: Data for the retrospective cohort study were collected from the Medical Information Mart for Intensive Care (MIMIC) III database. RPR was divided into two groups: RPR ≤ 0.11 and RPR > 0.11. The study outcomes were 30-day mortality and 1-year mortality from AIS. Cox proportional hazard models were utilized to assess the association between RPR and mortality. Subgroup analyses were applied based on age, tissue-type plasminogen activator (IV-tPA), endovascular treatment, and myocardial infarction. RESULTS: A total of 1,358 patients were included in the study. Short- and long-term mortality occurred in 375 (27.61%) and 560 (41.24%) AIS patients, respectively. A high RPR was significantly associated with increased 30-day [hazard ratio (HR): 1.45, 95% confidence interval (CI): 1.10 to 1.92, P = 0.009] and 1-year mortality (HR: 1.54, 95%CI: 1.23 to 1.93, P < 0.001) in AIS patients. Meanwhile, RPR was found to be significantly related to 30-day mortality in AIS patients aged < 65 years (HR: 2.19, 95% CI: 1.17 to 4.10, P = 0.014), without IV-tPA use (HR: 1.42, 95% CI: 1.05 to 1.90, P = 0.021), without using endovascular treatment (HR: 1.45, 95% CI: 1.08 to 1.94, P = 0.012), and without myocardial infarction (HR: 1.54, 95% CI: 1.13 to 2.10, P = 0.006). Additionally, RPR was associated with 1-year mortality in AIS patients aged < 65 years (HR: 2.54, 95% CI: 1.56 to 4.14, P < 0.001), aged ≥ 65 years (HR: 1.38, 95% CI: 1.06 to 1.19, P = 0.015), with (HR: 1.46, 95% CI: 1.15 to 1.85, P = 0.002) and without using IV-tPA (HR: 2.30, 95% CI: 1.03 to 5.11, P = 0.041), without using endovascular treatment (HR: 1.56, 95% CI: 1.23 to 1.96, P < 0.001), and without myocardial infarction (HR: 1.68, 95% CI: 1.31 to 2.15, P < 0.001). CONCLUSION: Elevated RPR is associated with a high risk of short-term and long-term mortality in AIS.

Effect of different pressure balloon dilation combined with prying reduction and bone graft fixation in the treatment of thoracolumbar fractures and the risk factors of postoperative re-fracture / 中国综合临床

Objective:To investigate the effect of different pressure balloon dilation combined with prying reduction and bone graft fixation in the treatment of thoracolumbar fractures and the risk factors of postoperative re-fracture.Methods:One hundred cases of thoracolumbar fracture patients admitted to Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province from March 2019 to June 2021 were selected. Prospective randomized controlled study method was used and random number table method was used to divide them into three groups: incomplete expansion group (33 cases), moderate expansion group (33 cases) and complete expansion group (34 cases). All the 3 groups were treated with balloon dilation combined with prying reduction and bone graft fixation. The pressure of balloon dilation in incomplete dilation group, moderate dilation group and complete dilation group was 100 psi, 150 psi and no more than 200 psi respectively, and the volume of balloon dilation was 0.5∶1, 1∶1 and 1.5∶1 respectively. The operation time, intraoperative bleeding volume, postoperative drainage volume, vertebral anterior margin recovery rate and hospital stay, as well as local Cobb angle, visual analog scale (VAS) and Oswestry disability index (ODI) scores before and after operation were compared among the three groups. According to the follow-up of whether there is re-fracture after surgery, the clinical data of the re-fracture group and the non re-fracture group were compared, and the risk factors of the re-fracture after surgery were analyzed. The measurement data with normal distribution was expressed as: independent sample t-test was used for comparison between two groups, one-way ANOVA or repeated measurement ANOVA was used for comparison between three groups, and SNK-q test was used for comparison between two groups. Counting data were expressed in cases or cases (%), and compared between groups by χ 2 Inspection. Logistic regression was used to analyze the risk factors of refracture after thoracolumbar fracture. Results:There was no significant difference in operation time, intraoperative blood loss and postoperative drainage volume among the three groups ( P=0.096, 0.328 and 0.344, respectively). The recovery rate of vertebral anterior edge height in moderate expansion group was higher than that in incomplete expansion group and complete expansion group ((84.15±4.21)% vs (70.18±7.44)%, (75.94±6.56)%), and the hospitalization time was shorter than that in incomplete expansion group and complete expansion group ((10.38±2.35) d vs (15.18±3.44), (14.59±2.48) d) (all P<0.001). Before treatment, there was no significant difference in Cobb angle, VAS and ODI scores among the three groups (all P>0.05). After treatment, the Cobb angle, VAS and ODI scores of patients in the three groups were lower than those before treatment, and the moderate expansion group were lower than those in the incomplete expansion group and the complete expansion group ((14.08±2.15) ° vs (16.48±4.85) °, (15.06±3.45) °, (1.81±0.53)% vs (2.25±0.41), (2.31±0.42), (18.16±2.18)% vs (20.48±4.85), (20.01±4.45) points) (all P<0.001). 100 patients were followed up until the fracture was healed. They were divided into re-fracture group (15 cases) and non re-fracture group (85 cases) according to whether there was re-fracture after operation. The results of multifactor logistic regression analysis showed that body mass index and bone mineral density were protective factors for patients with thoracolumbar fracture after operation (odds ratio was 0.66 and 0.15 respectively, 95% confidence interval: 0.51~0.86, 0.05~0.42, P values were 0.006 and <0.001 respectively), The old wedge-shaped change of the vertebral body and the abnormal structure of the lumbar spine are the risk factors for postoperative re-fracture (odds ratio 4.22 and 6.36, 95% confidence interval 1.14-15.56 and 1.43-28.21, respectively, P values were 0.027 and 0.015). Conclusions:In the treatment of thoracolumbar fracture with prying reduction and bone grafting fixation, the effect of balloon expansion pressure of 150 psi is better. Body mass index (BMI) and bone mineral density (BMD) were protective factors for postoperative re-fracture of patients with thoracolumbar fracture. Old wedge-shaped change of vertebral body and abnormal lumbar structure are risk factors for postoperative re-fracture.

Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through A β/Kv2.1/microglial NLRP3/neuronal tau axis / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

Working memory deficits in Parkinson's disease mouse model / 中国药理学与毒理学杂志

OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.

Ligustroflavone mediates the resistance of non-small cell lung cancer to osimertinib by arresting G1/S phase / 药学学报

Natural products are an important source for the development of antitumor lead compounds, but the pharmacological effects and regulatory mechanisms of natural products in osimertinib resistance in non-small cell lung cancer (NSCLC) are not well understood. The natural product ligustroflavone was used as the research object to analyze its efficacy in osimertinib-resistant NSCLC cells by cell proliferation assay and cell cycle detection. The potential targets of ligustroflavone in osimertinib-resistant NSCLC cells were screened by public databases and bioinformatics, molecular docking and microscale thermophoresis were used to identify the interaction between privet and target molecules. Western blot was used to detect the effect of privet on the target molecules and their downstream pathways. Ligustroflavone reduced the proliferation of osimertinib-resistant NSCLC cells, and could arrest the cell cycle. Cyclin-dependent kinase 6 (CDK6) was the potential target of ligustroflavone in osimertinib-resistant NSCLC cells. Ligustroflavone inhibited the activation of CDK6-Rb axis. Together, ligustroflavone could regulate osimertinib resistance in NSCLC cells by binding cell cyclin-related molecules. This study provides a theoretical basis for the targeted drug resistance of NSCLC with natural products, and also provides a new idea for the development of clinical drug combination.

Measurement of the Thermic Effect of Food in a Chinese Mixed Diet in Young People / 生物医学与环境科学（英文）

OBJECTIVE@#To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people.@*METHODS@#During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF.@*RESULTS@#Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%.@*CONCLUSION@#The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.

Neurocircuitry of Predatory Hunting / 神经科学通报·英文版

Predatory hunting is an important type of innate behavior evolutionarily conserved across the animal kingdom. It is typically composed of a set of sequential actions, including prey search, pursuit, attack, and consumption. This behavior is subject to control by the nervous system. Early studies used toads as a model to probe the neuroethology of hunting, which led to the proposal of a sensory-triggered release mechanism for hunting actions. More recent studies have used genetically-trackable zebrafish and rodents and have made breakthrough discoveries in the neuroethology and neurocircuits underlying this behavior. Here, we review the sophisticated neurocircuitry involved in hunting and summarize the detailed mechanism for the circuitry to encode various aspects of hunting neuroethology, including sensory processing, sensorimotor transformation, motivation, and sequential encoding of hunting actions. We also discuss the overlapping brain circuits for hunting and feeding and point out the limitations of current studies. We propose that hunting is an ideal behavioral paradigm in which to study the neuroethology of motivated behaviors, which may shed new light on epidemic disorders, including binge-eating, obesity, and obsessive-compulsive disorders.

Tailoring Dirac Fermions by In-Situ Tunable High-Order Moiré Pattern in Graphene-Monolayer Xenon Heterostructure.

We report an experimental study of a high-order moiré pattern formed in graphene-monolayer xenon heterostructure. The moiré period is in situ tuned from few nanometers to +∞, by adjusting the lattice constant of the xenon monolayer through annealing. Using angle-resolved photoemission spectroscopy, we observe that Dirac node replicas move closer and finally overlap with a gap opening, as the moiré pattern expands to +∞ and evolves into a Kekulé distortion. A moiré Hamiltonian coupling Dirac fermions from different valleys explains experimental results and indicates narrow moiré band. Our Letter demonstrates a platform to study continuous evolution of the moiré pattern, and provides an unprecedented approach for tailoring Dirac fermions with tunable intervalley coupling.

Effect of elevated fasting blood glucose level on the 1-year mortality and sequelae in hospitalized COVID-19 patients: A bidirectional cohort study.

To observe the predictive effect of fasting blood glucose (FBG) level on the prognosis, clinical sequelae, and pulmonary absorption in hospitalized coronavirus disease 2019 (COVID-19) patients with and without a history of diabetes, respectively, and to evaluate the correlation between the dynamic changes of FBG and poor prognosis. In this bidirectional cohort study, we enrolled 2545 hospitalized COVID-19 patients (439 diabetics and 2106 without a diabetic history) and followed up for 1 year. The patients were divided according to the level of admission FBG. The dynamic changes of FBG were compared between the survival and the death cases. The prediction effect of FBG on 1-year mortality and sequelae was analyzed. The 1-year all cause mortality rate and in-hospital mortality rate of COVID-19 patients were J-curve correlated with FBG (p < 0.001 for both in the nondiabetic history group, p = 0.004 and p = 0.01 in the diabetic history group). FBG ≥ 7.0 mmol/L had a higher risk of developing sequelae (p = 0.025) and have slower recovery of abnormal lung scans (p < 0.001) in patients who denied a history of diabetes. Multivariable Cox regression analysis showed that FBG ≥ 7.0 mmol/L was an independent risk factor for the mortality of COVID-19 regardless of the presence or deny a history of diabetes (hazard atio [HR] = 10.63, 95% confidence interval [CI]: 7.15-15.83, p < 0.001; HR = 3.9, 95% CI: 1.56-9.77, p = 0.004, respectively). Our study shows that FBG ≥ 7.0 mmol/L can be a predictive factor of 1-year all-cause mortality in COVID-19 patients, independent of diabetes history. FBG ≥ 7.0 mmol/L has an advantage in predicting the severity, clinical sequelae, and pulmonary absorption in COVID-19 patients without a history of diabetes. Early detection, timely treatment, and strict control of blood glucose when finding hyperglycemia in COVID-19 patients (with or without diabetes) are critical for their prognosis.

Deep learning algorithms for magnetic resonance imaging of inflammatory sacroiliitis in axial spondyloarthritis.

OBJECTIVE: The aim of this study was to develop a deep learning algorithm for detection of active inflammatory sacroiliitis in short tau inversion recovery (STIR) sequence MRI. METHODS: A total of 326 participants with axial SpA, and 63 participants with non-specific back pain (NSBP) were recruited. STIR MRI of the SI joints was performed and clinical data were collected. Region of interests (ROIs) were drawn outlining bone marrow oedema, a reliable marker of active inflammation, which formed the ground truth masks from which 'fake-colour' images were derived. Both the original and fake-colour images were randomly allocated into either the training and validation dataset or the testing dataset. Attention U-net was used for the development of deep learning algorithms. As a comparison, an independent radiologist and rheumatologist, blinded to the ground truth masks, were tasked with identifying bone marrow oedema in the MRI scans. RESULTS: Inflammatory sacroiliitis was identified in 1398 MR images from 228 participants. No inflammation was found in 3944 MRI scans from 161 participants. The mean sensitivity of the algorithms derived from the original dataset and fake-colour image dataset were 0.86 (0.02) and 0.90 (0.01), respectively. The mean specificity of the algorithms derived from the original and the fake-colour image datasets were 0.92 (0.02) and 0.93 (0.01), respectively. The mean testing dice coefficients were 0.48 (0.27) for the original dataset and 0.51 (0.25) for the fake-colour image dataset. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the algorithms using the original dataset and the fake-colour image dataset were 0.92 and 0.96, respectively. The sensitivity and specificity of the algorithms were comparable with the interpretation by a radiologist, but outperformed that of the rheumatologist. CONCLUSION: An MRI deep learning algorithm was developed for detection of inflammatory sacroiliitis in axial SpA.

Effects of Postmortem Hemolysis and Ultrafiltration on Creatinine Detection Results / 法医学杂志

OBJECTIVES@#To investigate the interference of postmortem hemolysis on the detection of creatinine and whether ultrafiltration can reduce the interference.@*METHODS@#A total of 33 non-hemolyzed whole blood samples from the left heart were collected. Hemolyzed samples with 4 hemoglobin mass concentration gradients H1-H4 were artificially prepared. Ultrafiltration was performed on each hemolyzed sample. Creatinine concentrations in non-hemolyzed serum (baseline serum), hemolyzed samples and ultrafiltrate were detected. Bias (B), Pearson correlation and receiver operator characteristic (ROC) of baseline creatinine concentration between before and after ultrafiltration were analyzed.@*RESULTS@#As the hemoglobin mass concentration increased, B of the hemolyzed samples in the H1-H4 groups gradually increased, the |B| was 2.41(0.82, 8.25)-51.31(41.79, 188.25), reaching a maximum of 589.06%, and there was no statistically significant between the creatinine concentration and the baseline creatinine concentration (P=0.472 7, r=0.129 5). After ultrafiltration of hemolyzed samples, the interference of creatinine concentration in ultrafiltrate was significantly reduced, the |B| was 5.32(2.26, 9.22)-21.74(20.06, 25.58), reaching a maximum of 32.14%, and there was a positive correlation with baseline creatinine concentration (P<0.05, r=0.918 2). In the hemolyzed samples of H3 and H4 groups, there were 7 false-positive samples and 1 false-negative sample; in the ultrafiltrate samples, there were no false-positive sample and 1 false-negative sample. ROC analysis results showed the hemolyzed samples were lack of diagnostic value (P=0.117 5).@*CONCLUSIONS@#The postmortem hemolysis significantly interferes creatinine detection results of blood samples, ultrafiltration can reduce hemolysis-induced interference in postmortem creatinine detection.

Research Progress of Exosomal microRNA in Cardiovascular Disease and Its Forensic Application Prospects / 法医学杂志

Exosomal microRNAs (miRNAs) are miRNAs that are mediated by exosomes to achieve cell-to-cell communication, and they are widespread in organisms. In recent years, the key role of the multiple biological functions of exosomal miRNAs in the occurrence and development of cardiovascular diseases has been confirmed by a large number of studies, which has become a hot spot in clinical and basic research. Sudden cardiac death caused by cardiovascular disease is one of the important contents in forensic medical identification. This article introduces the research progress of cardiovascular disease prediction, treatment and prognosis on exosomal miRNA. The prospects of the application in forensic medical identification are discussed.

The abnormalities of free uroflow curve in female patients with detrusor underactivity and their clinical significance / 中华泌尿外科杂志

Objective:To explore the features of free uroflow(FF) curve patterns in female patients with detrusor underactivity(DU) and their clinical significance.Methods:Data of 275 adult female patients with lower urinary tract symptoms(LUTS) underwent urodynamic studies(UDS) at urology center of our hospital from June 2014 to June 2016 were analyzed retrospectively. The uroflow curve patterns of patients with DU were classified and analyzed in the context of parameters of FF, cystometry (CM), and pressure-flow study(PFS). The prevalence of each abnormal uroflow curve pattern in DU patients were calculated and compared with those in non-DU patients.Results:No bell-shaped curve was found in 141 patients with DU. The abnormal curve patterns can be divided into 5 types: Type Ⅰ (bell-shaped curve with saw tooth) in 20 cases (14.2%), Type Ⅱ (box-like curve) in 34 cases (24.1%), Type Ⅲ (triangle curve with decreasing slop) in 62 cases(43.9%), Type Ⅳ (triangle curve with increasing slop) in 4 cases (4.3%), Type Ⅴ (tide-wave curve)in 19 cases (13.5%). Maximum flow rate of free uroflow(Q max.FF) of type Ⅰ [(28.4±9.7) ml/s] was significantly greater than that of type Ⅱ, Ⅲ and Ⅴ[(17.0±4.1), (15.8±5.4) and (12.9±6.4) ml/s, P<0.05]. Flow time of free uroflow(FT.FF) of type Ⅲ and Ⅴ [(43.7±17.2) and (50.1±28.9)s] were significantly longer than that of type Ⅰ and Ⅱ [(18.5±7.3)s and (27.2±9.7)s, P<0.05]. Post voided residual > 50ml was noted in 19 cases (30.6%) of type Ⅲ, 7 cases (36.8%) of type Ⅴ, 1 case (2.9%) of type Ⅱ and no one in type Ⅰ and Ⅳ. Abnormal manifestations in cystometry mainly included bladder hypersensitivity, detrusor overactivity, and stress urinary incontinence. Detrusor pressure at Q max (Pdet.Q max) of type Ⅴ [(7.4±5.0) cmH 2O] was significantly lower than that of type Ⅰ, Ⅱ, Ⅲ [(11.8±6.7), (12.0±5.3), (12.1±5.0) cmH 2O, P<0.05]. Among 134 cases of non-DU, there were type Ⅰ curves in 88 cases (65.7%), type Ⅱ curves in 4 cases (2.9%), type Ⅲ curves in 15 cases (11.2%), type Ⅳ curves in 1 cases (0.7%), type Ⅴ curves in 7 cases (5.2%). And normal bell-shaped curves in 19 cases(14.2%). The prevalence of type Ⅱ, Ⅲ and Ⅴ in DU patients was significantly higher than that in the non DU patients ( P<0.05). Conclusions:This study reveals that the characteristics of reduced detrusor contractility and duration, prolonged bladder emptying or incomplete emptying can be reflected in the patterns of free uroflow curve in female patients with DU. The abnormalities of these free uroflow curve patterns, especially type Ⅱ, Ⅲ and Ⅴ will be helpful in preliminarily screening DU in females.

Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.

Isolation, identification and electrophysiological activity of BmK M2 from Buthus martensii Karsch venom / 中国药科大学学报

@#This study aimed to isolate and identify novel toxin peptides targeting voltage-gated sodium channels (VGSGs) from the venom of the Buthus martensii Karsch (BmK) scorpion. Using G50-gel filtration, HPLC, peptide fingerprinting and amino acid sequencing, a novel sodium channel modulator, BmK M2, was identified from BMK scorpion. BmK M2 is a relatively abundant long chain polypeptide toxin in BmK scorpion venom with a molecular weight of 7 235.59, consisting of 64 amino acids and 4 pairs of disulfide bonds.Sequence alignment showed that the amino acid sequence of BmK M2 had high sequence and structural similarity to that of the discovered sodium channel toxins of BmK M1, BmK M3 and BmK M9, etc.BmK M2 is a potential new sodium channel modulator.Electrophysiological results revealed that BmK M2 can significantly enhance the activation, delay the steady-state inactivation and closed-state inactivation of Nav1.7, but has no activity on Nav1.8.BmK M2 can be used as a novel peptide probe for the study of the structure and function of Nav1.7 and the development of drugs targeting Nav1.7.

One-year mortality and consequences of COVID-19 in cancer patients: A cohort study.

The 1-year mortality and health consequences of COVID-19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID-19 patients with cancer were compared with 498 non-cancer COVID-19 patients and 498 non-COVID cancer patients. The 1-year all-cause mortality and hospital mortality rates in Cancer COVID-19 Cohort (30% and 20%) were significantly higher than those in COVID-19 Cohort (9% and 8%, both P < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12-month all-cause post-discharge mortality rate in survival discharged Cancer COVID-19 Cohort (8%) was higher than that in COVID-19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID-19 Cohort (23%, 26/114) is similar to that in COVID-19 Cohort (30%, 130/432, P = .13). The 1-year all-cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID-19 patients with cancer showed a high rate of in-hospital mortality and 1-year all-cause mortality, but the 12-month all-cause post-discharge mortality rate in survival discharged cancer COVID-19 patients was similar to that in Cancer Cohort. Comparing to COVID-19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID-19 Cancer Cohort. Different tumor subtypes had different effects on COVID-19. But if cancer patients with COVID-19 manage to survive their COVID-19 infections, then long-term mortality appears to be similar to the cancer patients without COVID-19, and their long-term clinical sequelae were similar to the COVID-19 patients without cancer.