CRISPR/Cas9 System with Dual gRNAs Synergically Inhibit Hepatitis B Virus Replication.

BACKGROUND: In recent years, a gene-editing technology known as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has been developed and is progressively advancing into clinical trials. While current antiviral therapies are unable to eliminate the Hepatitis B virus (HBV), it stands as a prime target for the CRISPR/Cas9 technology. The objective of this study was to enhance the efficacy of CRISPR/Cas9 in suppressing HBV replication, lowering HBsAg and HBeAg levels, and eliminating covalently closed circular DNA (cccDNA). METHODS: To enhance the anti-HBV effectiveness of CRISPR/Cas9, our study delved into a dual-guide RNA (gRNA) strategy. After evaluating the antiviral activities of multiple gRNAs that effectively impeded HBV replication, we identified three specific gRNAs-namely 10, 4, and 21. These gRNAs were selected for their targeting of distinct yet conserved regions within the HBV genome. RESULTS: In HBV-stable cell lines, namely HepAD38, and HBV infection models of HepG2-NTCP cells, our investigation revealed that the co-application of gRNA-10 with either gRNA-4 or gRNA-21 within the CRISPR/Cas9 system demonstrated heightened efficacy in impeding HBV replication, reducing the levels of HBsAg, HBeAg, and cccDNA levels, along with a more pronounced promotion of HBsAg clearance when compared to the use of a single gRNA. CONCLUSIONS: The CRISPR/Cas9 system employing dual gRNAs has proven highly effective in both suppressing HBV replication and facilitating HBsAg clearance. This promising outcome suggests that it holds potential to emerge as a novel approach for achieving the functional cure of patients with HBV infection.

Validation of gait analysis using smartphones: Reliability and validity.

Objective: This study aims to validate the reliability and validity of gait analysis using smartphones in a controlled environment. Methods: Thirty healthy adults attached smartphones to the waist and thigh, while an inertial measurement unit was fixed at the shank as a reference device; each participant was asked to walk six gait cycles at self-selected low, normal, and high speeds. Thirty-five cerebral small vessel disease patients were recruited to attach the smartphone to the thigh, performing single-task (ST), cognitive dual-task (DT1), and physical dual-task walking (DT2) to obtain gait parameters. Results: The results from the healthy group indicate that, regardless of whether attached to the thigh or waist, the smartphones calculated gait parameters with good reliability (ICC2,1 > 0.75) across three different walking speeds. There were no significant differences in the gait parameters between the smartphone attached to the thigh and the IMU across all three walking speeds (P > 0.05). However, significant differences were observed between the smartphone at the waist and the IMU during the stance phase, swing phase, stance time, and stride length at high speeds (P < 0.05). At the same time, measurements of other gait parameters were similar (P > 0.05). Patients demonstrated significant differences in the cadence, stride time, stance phase, swing phase, stance time, stride length, and walking speed between ST and DT1 (P < 0.05). Significant differences were observed in the stance phase, swing phase, stride length, and walking speed between ST and DT2 (P < 0.05). Conclusions: This study demonstrates the feasibility of using built-in smartphone sensors for gait analysis in a controlled environment.

[A study of cognitive impairment quantitative assessment method based on gait characteristics].

Alzheimer's disease (AD) is a common and serious form of elderly dementia, but early detection and treatment of mild cognitive impairment can help slow down the progression of dementia. Recent studies have shown that there is a relationship between overall cognitive function and motor function and gait abnormalities. We recruited 302 cases from the Rehabilitation Hospital Affiliated to National Rehabilitation Aids Research Center and included 193 of them according to the screening criteria, including 137 patients with MCI and 56 healthy controls (HC). The gait parameters of the participants were collected during performing single-task (free walking) and dual-task (counting backwards from 100) using a wearable device. By taking gait parameters such as gait cycle, kinematics parameters, time-space parameters as the focus of the study, using recursive feature elimination (RFE) to select important features, and taking the subject's MoCA score as the response variable, a machine learning model based on quantitative evaluation of cognitive level of gait features was established. The results showed that temporal and spatial parameters of toe-off and heel strike had important clinical significance as markers to evaluate cognitive level, indicating important clinical application value in preventing or delaying the occurrence of AD in the future.

[Effect of Bushen Huoxue（） recipe on autophagy of ovariectomized rat chondrocytes based on Akt/mTOR signaling pathway].

OBJECTIVE: To investigate whether Bushen Huoxue recipe can protect articular cartilage by regulating Akt/mTOR signaling pathway to promote the autophagy of chondrocytes in ovariectomized rats. METHODS: Among 30 SPF 12-week-old female SD rats weighing （247.0±7.0） g, 6 were randomly selected as the blank control group, and the remaining rats were randomly divided into model group, BSHXR-L group, BSHXR-M group and BSHXR-H group, with 6 rats in each group. The protective effect of Bushen Huoxue recipe on articular cartilage injury in rats was determined by visual observation score, muscovine O-solid green staining and immunohistochemistry. The expression of autophagy related proteins was detected by Western-blot, and the relative expression of Akt, mTOR and downstream autophagy genes was detected by qPCR. RESULTS: After modeling, BSHXR （L, M, H） groups could alleviate the histological damage of cartilage. Immunohistochemistry showed that the expression of Collagen-Ⅱand Aggrecan gradually increased, and the expression of MMP-13 gradually decreased, and the differences between BSHXR-M and BSHXR-H groups and model group were statistically significant （P<0.05）. The results of Western-blot showed that the autophagy pathway proteins p-Akt/Akt and p-mTOR/mTOR were inhibited in the BSHXR（L, M, H） groups, and the expressions of downstream proteins Beclin-1 and LC3Ⅱwere gradually increased, while p62 was gradually decreased, showing a dose effect. QPCR results showed that BSHXR（L, M, H） groups could promote the relative expression of Beclin-1 and LC3ⅡmRNA, and inhibit the relative expression of p62, Akt, mTOR mRNA, and the differences were statistically significant compared with model group （P<0.05）. CONCLUSION: Bushen Huoxue recipe can enhance the cartilage autophagy response by inhibiting the Akt/mTOR signaling pathway, and then protect the cartilage.

Integrated analysis of potential biomarkers associated with diabetic periodontitis development based on bioinformatics: An observational study.

Based on the importance of chronic inflammation in the pathogenesis of periodontitis and diabetes, the bidirectional relationship between these 2 diseases has been widely confirmed. However, the molecular mechanisms of bidirectional relationship still need to be studied further. In this study, gene expression profile data for diabetes and periodontitis were obtained from Gene Expression Omnibus (GEO) database. Integrative analytical platform were constructed, including common differentially expressed genes (cDEGs), Gene Ontology-Kyoto Encyclopedia of Genes and Genomes (GO-KEGG), and protein-protein interaction. Hub genes and essential modules were detected via Cytoscape. Key hub genes and signaling pathway that mediate chronic inflammation were validated by qPCR and Western blot. Eleven cDEGs were identified. Function analysis showed that cDEGs plays an important role in inflammatory response, cytokine receptor binding, TNF signaling pathway. As hub genes, CXCR4, IL1B, IL6, CXCL2, and MMP9 were detected based on the protein-protein interactions network. IL1B, CXCR4 mRNA were up-regulated in gingivitis samples compared with normal tissues (P < .05). Western blot indicated that the levels of TNF were enhanced in gingivitis of type 2 diabetes compared with normal tissues (P < .01). Hub gene and TNF signaling pathway are helpful to elucidate the molecular mechanism of the bidirectional relationship between periodontitis and diabetes.

Effectiveness of nursing interventions for management of children with bronchial asthma: A systematic review and meta-analysis.

AIM: Nursing interventions include the preventive care that can support and guide the nurse's effort to provide asthma interventions for children. Hence, this review was done to assess the effectiveness of nursing interventions for management of childhood asthma. METHODS: We conducted a search in Medline, the Cochrane library, EMBASE, ScienceDirect and Google Scholar from 1964 until April 2022. Meta-analysis was done using a random-effects model and pooled weighted mean difference (WMD) or standardized mean difference (SMD) and/or risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: Fourteen studies were analysed. The pooled RR was 0.49 for emergency visits (95% CI: 0.32 to 0.77) and 0.46 for hospitalizations (95% CI: 0.27 to 0.79). The pooled WMD was -1.20 for number of days with symptoms (95% CI: -3.50 to 1.11), -0.98 for number of nights with symptoms (95% CI: -2.94 to 0.98) and -0.69 for frequency of asthma attacks (95% CI: -1.19 to -0.20). The pooled SMD was 0.39 for quality of life (95% CI: 0.11 to 0.66) and 0.58 for asthma control (95% CI: -0.29 to 1.46). CONCLUSION: Nursing interventions were relatively effective in improving the quality of life and reducing asthma related emergencies, acute attacks and hospitalization amongst childhood asthma patients.

Proto-Oncogene FAM50A Can Regulate the Immune Microenvironment and Development of Hepatocellular Carcinoma In Vitro and In Vivo.

Hepatocellular carcinoma (HCC) is a vital global health problem. The characteristics are high morbidity, high mortality, difficulty in early diagnosis and insensitivity to chemotherapy. The main therapeutic schemes for treating HCC mainly include Tyrosine kinase inhibitors represented by sorafenib and lenvatinib. In recent years, immunotherapy for HCC has also achieved certain results. However, a great number of patients failed to benefit from systemic therapies. FAM50A belongs to the FAM50 family and can be used as a DNA-binding protein or transcription factor. It may take part in the splicing of RNA precursors. In studies of cancer, FAM50A has been demonstrated to participate in the progression of myeloid breast cancer and chronic lymphocytic leukemia. However, the effect of FAM50A on HCC is still unknown. In this study, we have demonstrated the cancer-promoting effects and diagnostic value of FAM50A in HCC using multiple databases and surgical samples. We identified the role of FAM50A in the tumor immune microenvironment (TIME) and immunotherapy efficacy in HCC. We also proved the effects of FAM50A on the malignancy of HCC in vitro and in vivo. In conclusion, we confirmed that FAM50A is an important proto-oncogene in HCC. FAM50A acts as a diagnostic marker, immunomodulator and therapeutic target for HCC.

CHINAT-CD4 Score Predicts Transplant-Free Survival in Patients with Acute-on-Chronic Liver Failure.

Aim: The early prognosis evaluation of acute-on-chronic liver failure (ACLF) is important to decrease its mortality. We aimed to develop a new score to accurately predict the outcome of patients with ACLF. Methods: A derivation set of 408 patients with hepatitis B virus-related ACLF (HBV-ACLF) based on the Asian Pacific Association for the Study of the Liver criteria is used to develop a prognostic score that was validated in 209 patients with HBV-ACLF and 195 patients with non-HBV-ACLF. Results: Seven factors were significantly related to the 28-day mortality and constituted a new score (CHINAT-CD4 = 0.320 × ln (creatinine) + 0.668 × hepatic encephalopathy score + 0.745 × ln (international normalized ratio) + 0.476 × ln (neutrophil) + 0.251 × ln (aspartate aminotransferase) + 0.411 × ln (total bilirubin) - 0.605 × ln (CD4+ T cells count)). The C-indices of the new score for the 28-/90-day mortality (0.810/0.806) outperformed those of the other seven scores (p≤0.05). The results were confirmed in a validation set (0.798/793 for HBV-ACLF; 0.790/0.788 for non-HBV-ACLF). The novel score based on CD4+ T cell count showed high predictive performance for the 28-/90-day mortality of ACLF. Conclusion: The novel score based on CD4+ T cell count can accurately predict the 28-/90-day mortality for patients with ACLF.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Comprehensive analysis of the cuproptosis-related model to predict prognosis and indicate tumor immune infiltration in lung adenocarcinoma.

Background: Cuproptosis is a novel form of programmed cell death termed as Cu-dependent cytotoxicity. However, the roles of cuproptosis-associated genes (CAGs) in lung adenocarcinoma (LUAD) have not been explored comprehensively. Methods: We obtained CAGs and utilized consensus molecular clustering by "non-negative matrix factorization (NMF)" to stratify LUAD patients in TCGA (N = 511), GSE13213 (N = 117), and GSE31210 (N = 226) cohorts. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in tumor microenvironment (TME). The risk score based on CAGs was calculated to predict patients' survival outcomes. Results: We identified three cuproptosis-associated clusters with different clinicopathological characteristics. We found that the cuproptosis-associated cluster with the worst survival rates exhibited a high enrichment of activated CD4/8+ T cells. In addition, we found that the cuproptosis-associated risk score could be used for patients' prognosis prediction and provide new insights in immunotherapy of LUAD patients. Eventually, we constructed a nomogram-integrated cuproptosis-associated risk score with clinicopathological factors to predict overall survival in LUAD patients, with 1-, 3-, and 5-year area under curves (AUCs) being 0.771, 0.754, and 0.722, respectively, all of which were higher than those of the TNM stage. Conclusions: In this study, we uncovered the biological function of CAGs in the TME and its correlations with clinicopathological parameters and patients' prognosis in LUAD. These findings could provide new angles for immunotherapy of LUAD patients.

Diagnostic accuracy of multi-component spatial-temporal gait parameters in older adults with amnestic mild cognitive impairment.

Objective: This study aimed to develop a diagnostic model of multi-kinematic parameters for patients with amnestic mild cognitive impairment (aMCI). Method: In this cross-sectional study, 94 older adults were included (33 cognitively normal, CN; and 61 aMCI). We conducted neuropsychological battery tests, such as global cognition and cognitive domains, and collected gait parameters by an inertial-sensor gait analysis system. Multivariable regression models were used to identify the potential diagnostic variables for aMCI. Receiver operating characteristic (ROC) curves were applied to assess the diagnostic accuracy of kinematic parameters in discriminating aMCI from healthy subjects. Results: Multivariable regression showed that multi-kinematic parameters were the potential diagnostic variables for aMCI. The multi-kinematic parameter model, developed using Timed Up and Go (TUG) time, stride length, toe-off/heel stride angles, one-leg standing (OLS) time, and braking force, showed areas under ROC (AUC), 0.96 [95% confidence interval (CI), 0.905-0.857]; sensitivity, 0.90; and specificity, 0.91. In contrast, a single kinematic parameter's sensitivity was 0.26-0.95 and specificity was 0.21-0.90. Notably, the separating capacity of multi-kinematic parameters was highly similar to Montreal Cognitive Assessment (MoCA; AUC: 0.96 vs. 0.95). Compared to cognitive domain tests, the separating ability was comparable to Auditory Verbal Learning Test (AVLT) and Boston Naming Test (BNT; AUC: 0.96 vs. 0.97; AUC: 0.96 vs. 0.94). Conclusion: We developed one diagnostic model of multi-kinematic parameters for patients with aMCI in Foshan.

Development and Validation of a Non-invasive Model to Predict Liver Histological Lesions in Chronic Hepatitis B Patients With Persistently Normal Alanine Aminotransferase and Detectable Viremia.

Background: A critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA. Methods: 398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set (n = 256) and validation set (n = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set. Results: 132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index ≤ 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index ≥ 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%). Conclusion: The SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.

Neuronal calcium sensor 2 is key to moulting and oocyte development in the brown planthopper, Nilaparvata lugens.

Intracellular calcium (Ca2+ ) is vital for signal transduction in many cellular events. Several Ca2+ -binding proteins mediate the transduction of intracellular calcium signals. The EF-hand motifs containing neuronal calcium sensor (NCS) proteins are mainly expressed in the nervous system, where they have important roles in the regulation of a variety of neuronal functions. NCS1 has four EF-hand motifs and well-defined neuronal development functions in a variety of eukaryotes. However, NCS2 has only been identified in invertebrates such as insects and nematodes thus far. The functions of NCS2 remain largely unknown. Here, we identified an orthologous NCS2 in the hemipteran Nilaparvata lugens. Based on qRT-PCR, this gene was found to be primarily expressed in the brain. Knockdown of NCS2 in each nymphal instar by RNA interference led to lethality and caused aggradation and disordered arrangement of lipid droplets in the ovaries and testes of adults, which were associated with the absence of mature oocytes in female ovaries and reduction of spermiation in male adults. Our findings revealed a novel function for NCS2 as a regulator in development and reproduction and suggested that this protein had an important role in modulating lipid droplet remodelling in ovary and testis of N. lugens adults.

High Fall Risk Associated With Memory Deficit and Brain Lobes Atrophy Among Elderly With Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease.

Objectives: This study aimed to primarily examine the association between memory deficit and increased fall risk, second, explore the underlying neuroanatomical linkage of this association in the elderly with aMCI and mild AD. Methods: In this cross-sectional study, a total of 103 older adults were included (55 cognitively normal, CN; 48 cognitive impairment, CI, elderly with aMCI, and mild AD). Memory was assessed by the Auditory Verbal Learning Test (AVLT). Fall risk was evaluated by the Timed Up and Go (TUG) Test, heel strike angles, and stride speed, which were collected by an inertial-sensor-based wearable instrument (the JiBuEn™ gait analysis system). Brain volumes were full-automatic segmented and quantified using AccuBrain® v1.2 from three-dimensional T1-weighted (3D T1W) MR images. Multivariable regression analysis was used to examine the extent of the association between memory deficit and fall risk, the association of brain volumes with memory, and fall risk. Age, sex, education, BMI, and HAMD scores were adjusted. Sensitivity analysis was conducted. Results: Compared to CN, participants with aMCI and mild AD had poorer cognitive performance (p < 0.001), longer TUG time (p = 0.018), and smaller hippocampus and medial temporal volumes (p = 0.037 and 0.029). In the CI group, compared to good short delayed memory (SDM) performance (AVLT > 5), the elderly with bad SDM performance (AVLT ≤ 3) had longer TUG time, smaller heel strike angles, and slower stride speed. Multivariable regression analysis showed that elderly with poor memory had higher fall risk than relative good memory performance among cognitive impairment elderly. The TUG time increased by 2.1 s, 95% CI, 0.54∼3.67; left heel strike angle reduced by 3.22°, 95% CI, -6.05 to -0.39; and stride speed reduced by 0.09 m/s, 95% CI, -0.19 to -0.00 for the poor memory elderly among the CI group, but not found the association in CN group. In addition, serious medial temporal atrophy (MTA), small volumes of the frontal lobe and occipital lobe were associated with long TUG time and small heel strike angles; small volumes of the temporal lobe, frontal lobe, and parietal lobe were associated with slow stride speed. Conclusion: Our findings suggested that memory deficit was associated with increased fall risk in the elderly with aMCI and mild AD. The association might be mediated by the atrophy of medial temporal, frontal, and parietal lobes. Additionally, increased fall risk, tested by TUG time, heel stride angles, and stride speed, might be objective and convenient kinematics markers for dynamic monitoring of both memory function and fall risk.

CPR Gene Contributes to Integument Function and Ovary Development in a Rice Planthopper.

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is an essential enzyme that transfers electrons from NADPH to cytochrome P450 monooxygenases. CPR is involved in cuticular hydrocarbon (CHC) synthesis in insects and is vital for insect development and survival. Here, we clarify the physiological function of a CPR gene in Nilaparvata lugens, an important rice pest, by using RNA interference. CPR gene knockdown leads to the functional loss of waterproofing and water retention in the integument of female adults, which causes significantly reduced body weight and a lethal phenotype. Scanning electron microscopy shows that the lipid layer on the outermost surface of the abdominal cuticle becomes thin in dsCPR-injected adults. Furthermore, CHC profile analysis reveals that CPR knockdown significantly decreases the contents of CHCs with a carbon chain length ≥ C27 in adult females. Moreover, we find that CPR knockdown generates a deficient phenotype in ovaries with deformed oocytes and a complete failure of egg-laying. These findings suggest that CPR plays multiple functional roles in CHC biosynthesis and embryo development in insects.

Effects of Golden Plaster on Knee Osteoarthritis: A Multicenter Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Golden plaster is the preferred and most commonly used in China for pain reduction in patients with knee osteoarthritis (OA). However, there was no evidence-based medical evidence about its effect in relieving pain of knee OA patients. Here, a multicenter randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of golden plaster for the improvement of pain relief and function's obstacle in patients with knee OA. METHODS: 320 patients with knee OA were enrolled at four hospitals and randomly divided into the treatment group and the control group with 160 subjects in each group. Patients in treatment group were treated with golden plaster, and those in control group with placebo plaster. The study cycle in both groups was 21 days. Patient visits were documented before treatment and 7-, 14-, and 21-day follow-ups after treatment. The outcomes included VAS score, WOMAC score, and adverse events. RESULTS: Compared to the control group, the VAS score in the treatment group was significantly decreased after treatment with golden plaster for 7 days, 14 days, and 21 days. Compared to the control group, the WOMAC score in the treatment group was significantly decreased 14 days and 21 days. The incidence rate of adverse events had no statistical difference between both the groups. CONCLUSIONS: In conclusion, our study, for the first time by carrying on the double-blind and placebo-controlled randomized trial, showed that golden plaster can effectively alleviate the pain of knee and improve the physical function in the patients with knee OA. This trial is registered with ChiCTR-TRC-13003418.

Pathological Gait Signatures of Post-stroke Dementia With Toe-Off and Heel-to-Ground Angles Discriminate From Alzheimer's Disease.

Given the limited power of neuropsychological tests, there is a need for a simple, reliable means, such as gait, to identify mild dementia and its subtypes. However, gait characteristics of patients with post-stroke dementia (PSD) and Alzheimer's disease (AD) are unclear. We sought to describe their gait signatures and to explore gait parameters distinguishing PSD from post-stroke non-dementia (PSND) and patients with AD. We divided 3-month post-stroke patients into PSND and PSD groups based on the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the activity of daily living (ADL). Thirty-one patients with AD and thirty-two healthy controls (HCs) were also recruited. Ten gait parameters in one single and two dual-task gait tests (counting-backward or naming-animals while walking) were compared among the groups, with adjustment for baseline demographic covariates and the MMSE score. The area under the receiver operating characteristic curve (AUC) was used to identify parameters discriminating PSD from individuals with PSND and AD. Patients with PSD and patients with AD showed impaired stride length, velocity, stride time, and cadence while patients with PSD had altered stance and swing phase proportions (all p ≤ 0.01, post hoc). Patients with AD had smaller toe-off (ToA) and heel-to-ground angles (HtA) (p ≤ 0.01) than HCs in dual-task gait tests. Individuals with PSD had a shorter stride length, slower velocity, and altered stance and swing phase percentages in all tests (p ≤ 0.01), but a higher coefficient of variation of stride length (CoVSL) and time (CoVST) only in the naming animals-task gait test (p ≤ 0.001) than individuals with PSND. ToA and HtA in the naming animals-task gait test were smaller in individuals with AD than those with PSD (p ≤ 0.01). Statistical significance persisted after adjusting for demographic covariates, but not for MMSE. The pace and the percentage of stance or swing phase in all tests, CoVST in the dual-task paradigm, and CoVSL only in the naming animals-task gait test (moderate accuracy, AUC > 0.700, p ≤ 0.01) could distinguish PSD from PSND. Furthermore, the ToA and HtA in the naming animals-task gait paradigm discriminated AD from PSD (moderate accuracy, AUC > 0.700, p ≤ 0.01). Thus, specific gait characteristics could allow early identification of PSD and may allow non-invasive discrimination between PSD and AD, or even other subtypes of dementia.

Effect of repetitive transcranial magnetic stimulation on patients with severe depression: a study protocol for systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Depression is characterised by easy recurrence, high disability and high burden, and antidepressant therapy is the standard treatment. However, its treatment effect on patients with severe depressive disorder has been unsatisfactory. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS), as a neurotherapy, can effectively mitigate the severity of depressive symptoms. Yet, more evidence is still required for TMS to treat severe depression. This study will be the first systematic review of the efficacy and tolerability of TMS for treating severe depression. We expect it to guide future clinical practice of TMS for the treatment of psychiatric disorders. METHODS AND ANALYSIS: We will search for the randomised controlled trial (RCT) involving rTMS for treating depression in eight electronic databases, including PubMed, Web of Science, EMBASE, the Cochrane Library and Wanfang Database, from publication up to September 2021. We will define Improvement in depressive symptoms, the difference between pretreatment (baseline) and post-treatment as the primary outcomes. The difference between pretreatment and post-treatment changes in resting state fMRI will be regarded as the secondary outcomes. Quality assessment of the included articles will be independently performed according to the Cochrane Risk of Bias tool. ETHICS AND DISSEMINATION: Ethical approval is not essential because there is no need to collect individual patient data. And this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42020211460.