CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

Exploiting Photoinduced Atom Transfer Radical Polymerizations with Boron-Dopant and Nitrogen-Defect Synergy in Carbon Nitride Nanosheets.

Graphitic carbon nitrides (g-C3N4) possess various benefits as heterogeneous photocatalysts, including tunable bandgaps, scalability, and chemical robustness. However, their efficacy and ongoing advancement are hindered by challenges like limited charge-carrier separation rates, insufficient driving force for photocatalysis, small specific surface area, and inadequate absorption of visible light. In this study, boron dopants and nitrogen defects synergy are introduced into bulk g-C3N4 through the calcination of a blend of nitrogen-defective g-C3N4 and NaBH4 under inert conditions, resulting in the formation of BCN nanosheets characterized by abundant porosity and increased specific surface area. These BCN nanosheets promote intermolecular single electron transfer to the radical initiator, maintaining radical intermediates at a low concentration for better control of photoinduced atom transfer radical polymerization (photo-ATRP). Consequently, this method yields polymers with low dispersity and tailorable molecular weights under mild blue light illumination, outperforming previous reports on bulk g-C3N4. The heterogeneity of BCN enables easy separation and efficient reuse in subsequent polymerization processes. This study effectively showcases a simple method to alter the electronic and band structures of g-C3N4 with simultaneously introducing dopants and defects, leading to high-performance photo-ATRP and providing valuable insights for designing efficient photocatalytic systems for solar energy harvesting.

Evaluation of Early Psychological Interventions in Patients with Intracranial Aneurysm Embolism: A Nursing Business Process Reengineering Perspective.

Objective: This study examines the impact of early psychological intervention for patients undergoing nursing process modification through a business process reengineering (BPR) approach in preventing intracranial aneurysm embolism. Methods: A randomized controlled trial (RCT) design was employed in this study. A randomized method was utilized to allocate a total of 201 cases into two distinct groups. 10 patients experiencing delirium and coma due to drug sedation were excluded from the analysis. Consequently, the final distribution included 96 cases in the nursing group and 95 cases in the routine group. Results: In the nursing group, waiting time, nursing staff working hours, and hospital stay were significantly lower compared to the routine group (t = 50.916, 28.893, 4.298, P < .05). No substantial difference in actual running time between the groups was observed (t=0.289, P > .05). Scores for physical pain, psychological well-being, material life status, and social function were notably higher in the nursing group than in the routine group (t=19.109, 20.658, 21.165, 24.014, P < .05). Post-intervention, SAS and SDS scores in the nursing group were significantly lower than those in the routine group (t=21.910, 25.808, P < .05). The complication rate in the nursing group (1.04%) was significantly lower than that in the routine group (8.42%) (χ2=5.791, P < .05). Furthermore, nursing staff job satisfaction (92.71%) was significantly higher than that in the routine group (78.13%) (χ2=7.449, P < .05). Conclusions: The modification of the nursing process demonstrates a positive impact on efficiency and quality of care, ensuring patient safety and meeting patient needs without altering surgical techniques. The findings highlight substantial enhancements and effectiveness of nursing process, providing strong support for the broad implementation of these interventions.

A Pneumatic Particle-Blocking Variable-Stiffness Actuator.

In order to improve the stiffness of flexible robots, this paper proposes a variable-stiffness elastic actuator. The actuator integrates the working principles of a pneumatic drive, wedge structure, and particle blockage. The anti-tensile stiffness of the actuator is nonlinearly negatively correlated with the air pressure because of the structural and material properties. The anti-compressive stiffness and lateral stiffness increase nonlinearly as air pressure increases, being 3 and 121 times greater at 0.17 MPa compared to 0 MPa, respectively. Beyond 0.17 MPa, the two stiffnesses of the actuator experience incremental growth due to wedge resistance forces.

An antagonistic variable-stiffness pneumatic flexible joint.

This paper develops an antagonistic variable-stiffness pneumatic flexible joint in which two groups of artificial muscles are symmetrically distributed on both sides of the elastic thin plate. The elastic thin plate restricts the axial movement of the joint. Therefore, the joint can achieve single-dimensional and bidirectional bending by controlling the air pressure value of the pneumatic artificial muscle. Two variable stiffness elastic dampers are also symmetrically installed on both sides of the elastic thin plate, using a positive-pressure driving method to achieve real-time posture maintenance function of the joint based on particle-blockage, wedge structure, and antagonistic effect. The mathematical models for the bending angle and stiffness of flexible joints were established, and relevant experiments were conducted. When the air pressure of the pneumatic artificial muscle is 0.32 MPa, the joint bending angle reaches 62.7°. When the bending angle is 60° and the air pressure of the variable-stiffness elastic damper is 0.5 MPa, the stiffness in the bending direction of the flexible joint with the variable-stiffness elastic damper is 6.9 times that of the flexible joint without the variable-stiffness elastic damper, and the stiffness in the reverse bending direction is 10.3 times that of the flexible joint without the variable-stiffness elastic damper under the same conditions.

A genome-wide association study of escitalopram treatment outcomes in patients with major depressive disorder.

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression.

Epigallocatechin gallate suppresses mitotic clonal expansion and adipogenic differentiation of preadipocytes through impeding JAK2/STAT3-mediated transcriptional cascades.

BACKGROUND: Mitotic clonal expansion (MCE) is a prerequisite for preadipocyte differentiation and adipogenesis. Epigallocatechin gallate (EGCG) has been shown to inhibit preadipocyte differentiation. However, the exact molecular mechanisms are still elusive. PURPOSE: This study investigated whether EGCG could inhibit adipogenesis and lipid accumulation by regulating the cell cycle in the MCE phase of adipogenesis and its underlying molecular mechanisms. METHOD: 3T3-L1 preadipocytes were induced to differentiate by a differentiation cocktail (DMI) and were treated with EGCG (25-100 µM) for 9, 18, and 24 h to examine the effect on MCE, or eight days to examine the effect on terminal differentiation. C57BL/6 mice were fed a high-fat diet (HFD) for three months to induce obesity and were given EGCG (50 or 100 mg/kg) daily by gavage. RESULTS: We showed that EGCG significantly inhibited terminal adipogenesis and lipid accumulation in 3T3-L1 cells and decreased expressions of PPARγ, C/EBPα, and FASN. Notably, at the MCE phase, EGCG regulated the cell cycle in sequential order, induced G0/G1 arrest at 18 h, and inhibited the G2/M phase at 24 h upon DMI treatment. Meanwhile, EGCG regulated the expressions of cell cycle regulators (cyclin D1, cyclin E1, CDK4, CDK6, cyclin B1, cyclin B2, p16, and p27), and decreased C/EBPß, PPARγ, and C/EBPα expressions at MCE. Mechanistic studies using STAT3 agonist Colivelin and antagonist C188-9 revealed that EGCG-induced cell cycle arrest in the MCE phase and terminal adipocyte differentiation was mediated by the inhibition of JAK2/STAT3 signaling cascades and STAT3 (Tyr705) nuclear translocation. Furthermore, EGCG significantly protected mice from HFD-induced obesity, reduced body weight and lipid accumulations in adipose tissues, reduced hyperlipidemia and leptin levels, and improved glucose intolerance and insulin sensitivity. Moreover, RNA sequencing (RNA-seq) analysis showed that the cell cycle changes in epididymal white adipose tissue (eWAT) were significantly enriched upon EGCG treatment. We further verified that EGCG treatment significantly reduced expressions of adipogenic factors, cell cycle regulators, and p-STAT3 in eWAT. CONCLUSION: EGCG inhibits MCE, resulting in the inhibition of early and terminal adipocyte differentiation and lipid accumulation, which were mediated by inhibiting p-STAT3 nucleus translocation and activation.

miR-4645-5p regulates malignant biological behavior of esophageal cancer cells by targeting MUC16 / 国际检验医学杂志

Objective To investigate the effect of microRNA(miR)-4645-5p on the proliferation,invasion and epithelial-mesenchymal transition of esophageal cancer cells by targeting mucin 16(MUC16)and its mo-lecular mechanism.Methods The expression of miR-4645-5p in esophageal cancer tissues was analyzed online by TCGA database.The expression level of miR-4645-5p in esophageal cancer cell lines was analyzed by fluo-rescent real-time fluorescence quantitative polymerase chain reaction(qPCR).KYSE-30 cells were transfected with miR-4645-5p mimic and negative control mimic by lipofection technology,and were divided into miR-4645-5p group and control mimic group.The proliferation ability,migration ability and invasion ability of transfected KYSE-30 cells were analyzed by CCK-8 method,scratch test and Transwell test respectively.The target gene of miR-4645-5p was predicted by the bioinformatics website,and the binding of miR-4645-5p to the target gene was detected by the dual-luciferase reporter gene assay.The expression level of MUC16 mR-NA was detected by qPCR,and the protein expression levels of MUC16,transcription factor-1(ZEB-1),zonal atresia protein(ZO-1),tight junction protein-1(Claudin-1)and α-smooth muscle actin(α-SMA)were detected by Western blotting.Results The expression level of miR-4645-5p in esophageal cancer tissues was signifi-cantly lower than that in adjacent tissues(P＜0.01).Compared with HET-1 A,the expression of miR-4645-5p was lower in esophageal cancer cell lines(P＜0.05).After overexpression of miR-4645-5p,the proliferation a-bility of KYSE-30 cells was significantly reduced(P＜0.05),the migration ability was significantly reduced(P＜0.01)and the invasion ability was significantly reduced(P＜0.01).miR-4645-5p targeted and negatively regulated the expression of MUC16 mRNA(P＜0.01).After overexpression of miR-4645-5p,the protein ex-pression levels of MUC16,ZEB-1 and α-SMA were all down-regulated,and the protein expression levels of ZO-1 and Claudin-1 were up-regulated.Conclusion miR-4645-5p regulates the malignant biological behavior of esophageal cancer KYSE-30 cells by targeting MUC16.

Fluid-Structure Interaction Simulation of Carotid Plaque / 医用生物力学

Objective To propose a two-way fluid-structure interaction (FSI) method based on real patients with carotid artery stenosis, and analyze the hemodynamic parameters of carotid plaques with different types at the lesion as well as deformation and stress changes of the plaque itself. Methods Three-dimensional ( 3D) modeling was performed based on computed tomography angiography ( CTA) data of patients with moderate carotid artery stenosis. The carotid artery wall model and plaque model were separated, and transient fluid structure coupling calculation was performed. The situation from early stage of carotid atherosclerosis to formation of the plaque was simulated. The plaque types were divided into thickened plaques, lipid plaques, mixed plaques and calcified plaques, among which thickened plaques were regarded as non-plaque conditions for representing the thickening of vascular intima-media. The stenotic carotid arteries with different plaque types were compared and analyzed. Results The plaques with different types had little effect on the overall blood flow, but the wall shear stress of lipid plaques at the lesion was lower than that of other plaques. With thickened plaques as a control, concurrence of the plaque would inhibit artery expansion, and lipid plaques were the most obvious. Calcified plaques had the highest average plaque structure stress, while lipid plaques had the lowest average plaque structure stress. Conclusions The method proposed in this study can analyze fluid area and solid area at the same time. The results can contribute to better understanding the influence of different plaque types on carotid artery diseases.

Identification and biological characterization of a Streptococcus parasuis strain / 中华微生物学和免疫学杂志

Objective:To identify a strain isolated from the cerebrospinal fluid of a patient and to investigate its biological characteristics.Methods:The strain was analyzed by several methods including Gram staining, biochemical identification, 16S rRNA and recN gene sequencing, average nucleotide identity (ANI), antibiotic susceptibility testing and detection of drug resistance and virulence genes. Results:The strain was Gram-positive cocci and formed α-hemolytic colonies on the blood plate. It was identified as Streptococcus parasuis by 16S rRNA, recN gene and whole-genome sequencing. It was sensitive to multiple antibiotics and carried the genes encoding a variety of virulence factors such as adhesion. Conclusions:Streptococcus parasuis could cause human infection and be identified by whole-genome sequencing.

High preoperative neutrophile-lymphocyte ratio predicts poor prognosis of patients undergoing radical cystectomy for nonurothelial carcinoma of the bladder / 现代泌尿外科杂志

【Objective】 To investigate the predictive value of high preoperative neutrophile-lymphocyte ratio (NLR) for the prognosis of nonurothelial carcinoma of the bladder (NUBC) after radical cystectomy (RC). 【Methods】 Clinical and follow-up data of NUBC patients undergoing RC during Jan.2005 and Dec.2020 were collected. The optimal cut-off value of NLR was determined with the receiver operating characteristic (ROC) curve. The survival curve was drawn with Kaplan-Meier method to compare the differences in cancer specific survival (CSS) and overall survival (OS) between the high-NLR and low-NLR groups. The independent risk factors of CSS and OS were screened with Cox proportional hazard regression model. 【Results】 Of the 62 eligible cases,34 (54.8%) were diagnosed with adenocarcinoma,17 (27.4%) with squamous cell carcinoma, 6 (9.7%) with small cell carcinoma and 5 (8.1%) with sarcoma. Kaplan-Meier analysis results showed high NLR was associated with poor CSS (P=0.001) and OS (P<0.001). Cox regression results indicated that high NLR (HR=2.42, 95%CI: 1.12-5.23, P=0.025) and advanced pathologic tumor stage (HR=3.21, 95%CI:1.53-6.74,P=0.002) were independent risk factors of unfavorable CSS. Similarly, high NLR (HR=2.75, 95%CI: 1.35-5.56, P=0.005) and advanced pathologic tumor stage (HR=2.81, 95%CI:1.43-5.57, P=0.003) were independent risk factors of unfavorable OS. 【Conclusion】 As an independent risk factor of unfavorable CSS and OS in NUBC patients undergoing RC, high preoperative NLR is of great value in the prediction of long-term prognosis and may help to optimize individualized treatment.

Current status of lymph node dissection in pyloric-preserving gastrectomy for early gastric cancer / 中华胃肠外科杂志

With the gradual increase in the diagnosis rate of early gastric cancer, clinicians must consider prevention of gastric anatomical structure and physiological function while ensuring the radical treatment of the tumor. Pylorus-preserving gastrectomy is a function- preserving operation that preserves the pylorus, inferior pyloric vessel, and the vagus nerve in patients with early middle gastric cancer. One of the major controversies at present is the thoroughness of limited lymph node dissection for pyloric-preserving gastrectomy. Various studies have reported that the lymph node metastasis rate of early middle gastric cancer was low, especially in the suprapyloric region, inferior pylorus and the upper pancreatic region. Partial lymph node dissection is required for vascular and neurological protection, which is also safe and feasible in studies reported by major centers. Many clinical studies have been carried out in Japan and Korea, and postoperative follow-up has gradually increased evidence, providing the basis for the safety of lymph node dissection. In large case studies comparing pylorus- preserving gastrectomy with traditional distal gastrectomy, the incidence of postoperative morbidity, such as dumping syndrome, bile reflux esophagitis, weight loss, and malnutrition is low. Sentinel lymph node navigation technology is gradually applied to the diagnosis and treatment of early gastric cancer, and its clinical application value still needs further research.

Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR).@*METHODS@#Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting.@*RESULTS@#Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.@*CONCLUSION@#Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.

Molecular characterization of Staphylococcus aureus ST6 and ST7 isolates from food-borne illness outbreaks / 中华预防医学杂志

Objective: To analyze the Staphylococcal enterotoxins, Staphylococcal enterotoxin genes, drug resistance and molecular typing of 41 Staphylococcus aureus isolates from 2 food-borne illness outbreaks on 21 August and 27 September 2020 in Guangzhou. Methods: A total of 41 Staphylococcus aureus isolates from 2 outbreaks were analyzed by multilocus sequence typing (MLST) and spa typing. The Staphylococcal enterotoxins typing and the Staphylococcal enterotoxin genes of the isolates were analyzed by ELISA and PCR, respectively. The antimicrobial susceptibility of the isolates was performed by disc diffusion. 21 Staphylococcus aureus isolates were characterized using whole genome sequencing (WGS). Based on the whole genome single nucleotide polymorphism (SNP), the phylogenetic tree was constructed by Snippy. Results: 41 Staphylococcus aureus isolates were divided into 2 types by MLST and spa typing: ST6-t701 and ST7-t091. 2 ST7-t091 isolates were identified as methicillin-resistant Staphylococcus aureus (MRSA). 25 ST7-t091 isolates and 14 ST6-t701 isolates were methicillin-sensitive Staphylococcus aureus (MSSA), and were resistant to 7 and 6 antibiotics, respectively. All isolates were positive for sea by PCR. WGS revealed all 21 isolates carried scn, sak, sea, hla, hld, hlgA, hlgB, hlgC, lukD virulence genes. The results showed the isolates contained an immune evasion cluster type D which located in bacteriophage ϕSa3. The SNP phylogenetic tree showed 2 MRSA ST7-t091 were constituted a separate clade from the 12 MSSA ST7-t091 isolates and 7 ST6-t701 isolates showed high similarity to each other. Conclusion: Base on the results of phylogenetic analysis, the 2 food-borne illness outbreaks occurred on 21 August and 27 September 2020 are caused by the combination of the MRSA ST7-t091 strain and the MSSA ST7-t091 strain, and the MSSA ST6-t701 strain, respectively. All isolates have high level of antibiotic resistance and carry high virulent genes.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells / 生物医学与环境科学（英文）

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

MiR-663a Inhibits Radiation-Induced Epithelium-to-Mesenchymal Transition by Targeting TGF-β1 / 生物医学与环境科学（英文）

Objective@#miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT).@*Methods@#TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified.@*Results@#Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation.@*Conclusion@#Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.

Progress on femorotibial mechanical axis of total knee arthroplasty / 中国骨伤

Femorotibial mechanical axis (FTMA) is one of important factors influencing clinical effect after total knee arthroplasty (TKA). It is generally believed that the range of lower limb alignment after TKA is controlled within neutral FTMA ± 3 °, which has more advantages in improving joint function, prolonging prosthesis survival rate and reducing revision rate, and obtain better clinical results. Therefore, neutral FTMA is also considered to be the gold standard for TKA. However, with the application of computer-assisted surgery and other technologies, the alignment of FTMA is more accurate than before, but the clinical effect after surgery has not significantly improved. Some scholars have begun to question the necessity of neutral alignment of FTMA, and proposed alignment methods such as kinematics and retained residual deformity, which could achieve better clinical effects. In recent years, it has been reported that FTMA might not be the most important factor influencing postoperative clinical effects, and it is suggested that the arrangement and measurement of lower limbs and the effects on adjacent joint functions could affect clinical effect after TKA. The paper reviews neutral FTMA alignment is still an important factor for success of TKA. After a thorough evaluation according to the patient's condition, it should be appropriately applied in the case of neutral FTMA alignment; the operator should explore other factors which affect clinical outcome after TKA, and improve it to achieve the best therapeutic effect.

Geospatial analysis of severe road traffic accidents in Singapore in 2013-2014

INTRODUCTION@#Injury is a significant cause of mortality and morbidity. We aimed to investigate which areas in Singapore have a significantly higher incidence of road traffic accidents (RTA) resulting in severe injuries (Tier 1), which is defined as an Injury Severity Score (ISS) greater than 15, and to develop a spatiotemporal model.@*METHODS@#Data was obtained from the National Trauma Registry. The RTA locations were geomapped onto the Singapore map, and spatial statistical techniques were used to identify hotspots with the Getis-Ord Gi* algorithm.@*RESULTS@#From 1 January 2013 to 31 December 2014, there were 35,673 people who were injured as a result of RTAs and 976 Tier 1 RTA victims. A total of 920 people were included in the geospatial analysis. Another 56 were involved in RTAs that did not occur within Singapore or had missing location data and thus were not included. 745 (81.0%) were discharged alive, whereas 175 (19.0%) did not survive to discharge (median ISS 38.00, interquartile range 30.00-48.00). Most of the Tier 1 RTA victims were motorcycle riders (50.1%, n = 461), pedestrians (21.8%, n = 201) and cyclists (9.9%, n = 91). The majority were male and aged 20-40 years, and there was a peak occurrence at 0600-0759 hours. Nine hotspots were identified (p < 0.01).@*CONCLUSION@#Information from studying hotspots of RTAs, especially those resulting in severe injuries, can be used by multiple agencies to direct resources efficiently.

Effects of noise, bright light and mechanical stimulation on sleep, blood-brain barrier and cognitive function in septic rats / 中华危重病急救医学

Objective:To evaluate the effects of noise, bright light and mechanical stimulation on sleep, blood-brain barrier and cognitive function in septic rats.Methods:Forty male Sprague-Dawley (SD) rats were selected and intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) was used to establish sepsis model. 0, 30, 45, 60, 75 dB noise stimulation or 0, 50, 100, 200, 400 Lux light stimulation were given to rats (all n = 4). The serum levels of cortisol and melatonin, and the cerebral content of Evans blue (EB) were measured 96 hours after the stimulation to determine the optimal intensity of intervention. The other 40 SD rats were randomly divided into control group (Con group), LPS group, noise intervention group (LPS+60 dB group), 200 Lux light intervention group (LPS+200 Lux group) and mechanical stimulation group (LPS+MS group), with 8 rats in each group. The open fields test and fear conditioning test were used to evaluate the exploratory behavior and cognitive function 96 hours after corresponding stimulation. The enzyme linked immunosorbent assay (ELISA) was used to detect cerebral level of interleukin-6 (IL-6) and serum levels of cortisol and melatonin. The blood-brain barrier integrity was assessed by EB staining. The protein levels of ZO-1, Claudin-5 and caspase-3 in the hippocampus were detected by Western blotting to assess the blood-brain barrier integrity and neuronal apoptosis. Results:Compared with 0 dB group or 0 Lux group, the serum melatonin concentration in 60 dB group and 200 Lux group were significantly reduced, while the serum cortisol concentration and cerebral EB content were significantly increased. Therefore, 60 dB noise and 200 Lux light were selected in the subsequent experiments. Compared with Con group, the horizontal score and vertical score in the open field test in LPS group were significantly decreased. There were no significant differences in the proportion of freezing time, the cerebral contents of EB and IL-6, the serum levels of melatonin and cortisol, and the hippocampal expressions of ZO-1, Claudin-5 and caspase-3. Compared with LPS group, the horizontal score, vertical score and the percentage of freezing time in LPS+60 dB group, LPS+200 Lux group and LPS+MS group were significantly reduced [horizontal score: 73.8±9.7, 80.3±9.4, 64.5±8.3 vs. 103.6±15.5; vertical score: 9.4±1.7, 11.2±1.9, 6.8±0.9 vs. 15.9±2.8; the percentage of freezing time: (45.3±4.7)%, (53.3±5.8)%, (42.1±5.1)% vs. (66.1±6.3)%], the serum level of melatonin was significantly decreased (ng/L: 53.62±6.20, 44.25±6.41, 45.33±5.84 vs. 74.39±7.54), the serum level of cortisol was significantly increased (nmol/L: 818.34±95.53, 710.04±65.41, 989.73±91.63 vs. 398.82±72.59), the levels of EB, IL-6 in the brain tissue were significantly increased [EB (μg/g): 2.80±0.35, 2.38±0.31, 3.24±0.42 vs. 1.59±0.26; IL-6 (ng/g): 31.56±4.11, 26.69±3.75, 37.47±4.56 vs. 16.28±2.69], the expressions of ZO-1 and Claudin-5 were significantly decreased (ZO-1/β-actin: 0.37±0.04, 0.32±0.05, 0.24±0.04 vs. 0.80±0.09; Claudin-5/β-actin: 0.62±0.08, 0.47±0.06, 0.35±0.05 vs. 0.97±0.20), and the expression of cleaved caspase-3 was significantly increased (caspase-3/β-actin: 0.56±0.06, 0.39±0.04, 0.72±0.12 vs. 0.20±0.03), with statistically significant differences (all P < 0.05). Conclusion:60 dB noise, 200 Lux light or mechanical stimulation for 96 hours could inhibit the secretion of serum melatonin, promote the secretion of cortisol, and activate neuroinflammation in septic rats, and lead to neuronal apoptosis in hippocampus and hyper-permeability of blood-brain barrier, which in turn could cause sleep disturbance and cognitive impairment.

Epidemiological characteristics of novel coronavirus confirmed cases and asymptomatic infected patients in Guangzhou / 中华微生物学和免疫学杂志

Objective:To analyze the epidemiological characteristics of novel coronavirus positive cases including confirmed cases with clinical symptoms and asymptomatic infected cases in Guangzhou.Methods:Epidemiological data were collected on the nucleic acid positive cases of COVID-19 in Guangzhou from January to September 2020. The epidemiological characteristics, the distribution of time intervals between the confirmed/isolation date and the date of the first positive detection were analyzed, at last the influencing factors for the confirmed cases and asymptomatic infected persons were discussed.Results:From January 7 to September 4 in 2020, a total of 1 097 nucleic acid positive cases were identified, including 658 confirmed cases (59.98%) and 439 asymptomatic infected cases (40.02%). Among the 658 confirmed cases, the median age was 42 years old, the cases indicated two significant peaks. one of the peaks was related to the imported and associated cases from Hubei province, and the other peak was connected with individuals from overseas. In terms of 439 asymptomatic infected cases, the median age was 32 years old. There were two stages in these cases. The first stage followed the second peak of confirmed cases, and the second stage overlapped with the confirmed cases in Guangzhou when the epidemic was in a period of normal prevention and control, mainly related to imported cases from abroad. The asymptomatic infected persons accounted for 57.32% in all the imported infected cases. In both of asymptomatic and symptomatic cases, the positive rate of pharyngeal swabs was higher than that of nasopharyngeal swabs and anal swabs. There were statistically significant differences in age, source of infection and gender composition between confirmed cases and asymptomatic infected persons ( P<0.05). Older age groups were more likely to have clinical symptoms, with ≥40 years being the risk factor for confirmed cases (OR=2.334, P=0.001), and 20-39 years less likely to have clinical symptoms (OR=0.620, P=0.047), compared with the 0-19 years old group. Compared with those infected in China, those infected abroad were less likely to develop clinical symptoms and became confirmed cases (OR=0.723, P=0.013). Women were more likely to have clinical symptoms than men (OR=1.574, P=0.001). Conclusions:At present, asymptomatic infected persons and confirmed patients with clinical symptoms co-existed, and the number of asymptomatic infected patients was higher than that of confirmed cases in Guangzhou. High age, domestic infection and female may be risk factors for confirmed cases. It was of great value to further explore these underlying mechanisms for the prevention and treatment of the COVID-19.