Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study.

BACKGROUND: Observational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders. METHODS: Using a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach. RESULTS: The study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241-4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260-2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above. CONCLUSION: Our MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.

CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-ß-catenin signalling pathway in serous ovarian cancer.

BACKGROUND: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. METHODS: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-ß-catenin signalling pathway. RESULTS: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-ß-catenin signalling pathway. CONCLUSIONS: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-ß-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.

Immune checkpoint inhibitors enhanced the antitumor efficacy of disitamab vedotin for patients with HER2-positive or HER2-low advanced or metastatic gastric cancer: a multicenter real-world study.

BACKGROUND: Novel ADC drugs provide a new therapeutic strategy for gastric cancer.The present study aimed to analyze the clinical efficacy and drug toxicities of disitamab vedotin (RC48) plus immune checkpoint inhibitors(ICIs) and RC48 as third-line therapies and beyond for advanced and metastatic gastric cancer patients. METHODS: This was an observational multicenter real-world study.From August 2021 to January 2022,patients with HER2-positive or HER2-low advanced and metastatic gastric cancer and failed from two or more lines of prior therapy were enrolled and treated with RC48 plus ICIs or RC48. In this study, progression free survival(PFS) was the primary end point. Other evaluation indicators were objective response rate(ORR),disease control rate(DCR),overall survival(OS) and drug toxicities. RESULTS: 45 patients were enrolled,of which 25 patients received RC48 plus ICIs,20 patients received RC48.Patients who received RC48 plus ICIs obtained better ORR (36.0% vs. 10.0%, P = 0.044) and DCR (80.0% vs. 50.0%, P = 0.034) compared with RC48,and simultaneously,the median PFS in RC48 plus ICIs group were superior to RC48 group(6.2 m vs. 3.9 m).The median OS was not reached.No statistically differences were found between HER2-positive and HER2-low group with respect to ORR (27.3% vs. 16.7%, P = 0.464),DCR (66.7% vs. 66.7%, P = 1.000),median PFS(5.7 m vs. 4.3 m, P = 0.299).The most common adverse events (AEs) were decreased white blood count,decreased neutrophil count,fatigue,hypoaesthesia and alopecia.Grade 3-4 AEs occurred in 7(35.0%) patients of RC48 group and 10(40.0%) patients of RC48 plus ICIs group,respectively. CONCLUSION: Compared with RC48 monotherapy, ICIs plus RC48 demonstrated superior third-line and beyond therapeutic efficacy for HER2-positive or HER2-low advanced and metastatic gastric cancer patients with manageable safety.

The correlation between blood-lipid ratio in the first trimester and large-for-gestational-age infants.

BACKGROUND: To investigate the correlation between maternal glucose and lipid metabolism indexes and blood-lipid ratio in the first trimester and large-for- gestational-age (LGA) infants. METHODS: Women in the first trimester of pregnancy who underwent regular obstetric examination in the obstetric outpatient department of the Affiliated Hospital of Chengde Medical College from June 2018 to March 2019 were included according to the standard. Basic information were collected based on questionnaires at the first visit of pregnant women, including early fasting blood glucose (FBG), fasting insulin (FINS), glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), apolipoprotein A1 (APO-A1), apolipoprotein B (APO-B), lipoprotein a (LP(a)), LDL/HDL, TG/HDL, TC/HDL, APO-B/APO-A1 ratio, birth weight of newborns, gestational age at delivery etc. RESULTS: A total of 418 cases were included for analysis. The incidence rate of LGA infants was 13.88%, and that of small-for-gestational-age (SGA) infants was 4.78%. Univariate analysis revealed that the age, pre-pregnancy body mass index (BMI), weight gain during pregnancy, APO-B/APO-A1 between LGA group and appropriate-for-gestational-age (AGA) group were significantly different (P < 0.05); multivariate stepwise logistic regression analysis indicated that the correlation between maternal age, pre-pregnancy BMI, weight gain during pregnancy, APO-B/APO-A1 level and LGA were statistically significant (P < 0.05); compared with the reference range of APO-B/APO-A1 of 0.46-0.65, values < 0.46 and > 0.65 were protective factor of LGA (P < 0.05). The receiver operating curve(ROC) indicated that the area under the curve (AUC)s for predicting LGA using maternal age, pre-pregnancy BMI, weight gain during pregnancy, and early pregnancy APO-B/APO-A1 were 0.585, 0.606, 0.637, 0.531, respectively. The AUC for a combined prediction model was 0.742, showing greater predictive value than any other factors individually. CONCLUSION: Maternal age, pre-pregnancy BMI, weight gain during pregnancy, and APO-B/APO-A1 levels in first trimester are significant factors influencing the occurrence of LGA infants, and the combination of the four factors would have certain predictive value for LGA.

Identification of the cuproptosis-related molecular subtypes and an immunotherapy prognostic model in hepatocellular carcinoma.

BACKGROUND: Cuproptosis, a newly discovered mode of cell death, has been less studied in hepatocellular carcinoma (HCC). Exploring the molecular characteristics of different subtypes of HCC based on cuproptosis-related genes (CRGs) is meaningful to HCC. In addition, immunotherapy plays a pivotal role in treating HCC. Exploring the sensitivity of immunotherapy and building predictive models are critical for HCC. METHODS: The 357 HCC samples from the TCGA database were classified into three subtypes, Cluster 1, Cluster 2, and Cluster 3, based on the expression levels of ten CRGs genes using consensus clustering. Six machine learning algorithms were used to build models that identified the three subtypes. The molecular features of the three subtypes were analyzed and compared from some perspectives. Moreover, based on the differentially expressed genes (DEGs) between Cluster 1 and Cluster 3, a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the efficacy of immunotherapy in the IMvigor210 cohort. RESULTS: Cluster 3 had the worst overall survival compared to Cluster 1 and Cluster 2 (P = 0.0048). The AUC of the Catboost model used to identify Cluster 3 was 0.959. Cluster 3 was significantly different from the other two subtypes in gene mutation, tumor mutation burden, tumor microenvironment, the expression of immune checkpoint inhibitor genes and N6-methyladenosine regulatory genes, and the sensitivity to sorafenib. We believe Cluster 3 is more sensitive to immunotherapy from the above analysis results. Therefore, based on the DEGs between Cluster 1 and Cluster 3, we obtained a 7-gene scoring prognostic model, which achieved meaningful results in predicting immunotherapy efficacy in the IMvigor210 cohort (P = 0.013). CONCLUSIONS: Our study provides new ideas for molecular characterization and immunotherapy of HCC from machine learning and bioinformatics. Moreover, we successfully constructed a prognostic model of immunotherapy.

Pharmacokinetic study of deufruquintinibs in rats by HPLC-MS/MS after oral administration.

A sensitive and specific high-performance liquid chromatography-tandem mass spectrometry method was established to quantitatively determine the pharmacokinetics of fruquintinib (HMPL-013) and its derivatives [deufruquintinib-3D (HMPL-013-3D), deufruquintinib-6D (HMPL-013-6D) and deufruquintinib-9D (HMPL-013-9D)] in rats. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The method established in this assay was successfully applied to a pharmacokinetic study of HMPL-013 and HMPL-013-Ds after oral administration. These results showed that HMPL-013-Ds had longer half-life and larger area under the plasma concentration-time curve than HMPL-013, especially HMPL-013-6D, which provides a significant basis for innovative ideas for drug structure transformation to reduce drug administration frequency and dosage.

α-Pinene Induces Apoptotic Cell Death via Caspase Activation in Human Ovarian Cancer Cells.

BACKGROUND The plant-derived terpenoid, alpha-pinene is a bicyclic monoterpene potentially useful for the treatment of various diseases which also includes cancer and its types. The present investigation is about finding the anticancer activity of the alpha-pinene extracted from the leaves of Boswellia dalzielii over the PA-1 cancer cells of the human ovary. MATERIAL AND METHODS The cytotoxic activity of the alpha-pinene was evaluated using MTT and LDH assays which indicated that alpha-pinene could induce cytotoxicity in cancer-causing cells in the ovary. The consequences of alpha-pinene on the cell sequence regulation were determined by the staining technique using propidium iodide (PI) followed with flow cytometry. RESULTS The cell cycle distribution analysis showed that alpha-pinene inhibit the cycle progression from G2 to M phase. In addition, apoptosis analysis is done through the double staining investigation using Annexin V-FITC/PI to analyze the controlled growth of alpha-pinene which is associated with the apoptosis. Caspase-3 a crucial enzyme involved in apoptosis was markedly increased in the a-pinene treated PA-1 cells. The apoptosis results reveal, that the cancer cells at the human ovary with alpha-pinene induces the significant populations of apoptotic cells. CONCLUSIONS Overall, alpha-pinene may exert anticancer effects in PA-1 cells by promoting cytotoxicity, suppression of cell sequence progression along with the programmed cell death.

Associations between dietary habits and bipolar disorder: a diet-wide mendelian randomization study.

Background: Diet/nutrition is critically important in the pathogenesis, progression, and treatment outcomes of various mental disorders. Current research predominantly focuses on the role of diet in the development and treatment of depression, with less attention given to the relationship between diet and Bipolar Disorder (BD). Method: We employed Mendelian Randomization (MR) to investigate the relationship between 28 dietary habits and BD. An analysis was conducted using publicly available genome-wide association study data from the UK Biobank dataset. Various dietary habits were analyzed as exposures with BD as the outcome, mainly using the Inverse Variance Weighted (IVW) method. Results: Intake of non-oily fish and sponge pudding both have a positive association with BD. Oily fish, dried fruit, apples, salt, and cooked vegetables intake also appeared potentially risky for BD, although the possibility of false positives cannot be ruled out. Sensitivity analysis further confirmed the robustness of these findings. Conclusion: Our research provides evidence of a relationship between various dietary habits and BD. It underscores the need for careful dietary management and balance to reduce the risk of BD, suggesting caution with dietary preferences for fish and sponge pudding. Furthermore, more detailed studies are needed to further understand the potential impacts of high-sugar and high-protein diets on BD development.

Seasonal patterns in Chinese population: Validating the seasonal pattern assessment questionnaire and exploring associations with psychiatric diagnoses and biological rhythms.

Seasonal patterns (SP) exert a notable influence on the course and prognosis of patients with affective disorders, serving as a specifier in diagnosis. However, there is limited exploration of seasonality among psychotic patients, and the distinctions in seasonality among psychiatric patients remain unclear. In this study, we enrolled 198 psychiatric patients with anxiety and depressive disorders (A&D), bipolar disorder (BD), and schizophrenia (SZ), as well as healthy college students. Online questionnaires, including the Seasonal Pattern Assessment Questionnaire (SPAQ) for seasonality, the Morningness and Eveningness Questionnaire-5 (MEQ-5) for chronotypes, and the Pittsburgh Sleep Quality Index (PSQI), were administered. The validity and reliability of the Chinese version of the SPAQ were thoroughly analyzed, revealing a Cronbach's alpha of 0.896 with a two-factor structure. Results indicated that higher seasonality was correlated with poorer sleep quality and a more delayed chronotype (p < 0.05). Significant monthly variations were particularly evident in BD, specifically in mood, appetite, weight, social activities, and sleep dimensions (p < 0.001). In summary, the Chinese version of SPAQ is validated, demonstrating moderate correlations between seasonality, chronotype, and sleep quality. BD patients exhibited the strongest seasonality, while mood disorder patients displayed more delayed chronotypes than SZ.

Balance and knee extensibility evaluation of hemiplegic gait using an inertial body sensor network.

BACKGROUND: Most hemiplegic patients have difficulties in their balance and posture control while walking because of the asymmetrical posture and the abnormal body balance. The assessment of rehabilitation of hemiplegic gait is usually made by doctors using clinical scale, but it is difficult and could not be used frequently. It is therefore needed to quantitatively analyze the characteristics of hemiplegic gait. Thus the assessment would be simple, and real-time evaluation of rehabilitation could be carried out. METHODS: Twenty subjects (ten hemiplegic patients, ten normal subjects) were recruited. The subjects walked straight for five meters at their self-selected comfortable speed towards a target line on the floor.Xsens MTx motion trackers were used for acquiring gestures of body segments to estimate knee joint angles and identify gait cycles. A practical method for data acquisition that does not need to obtain accurate distances between a knee joint and its corresponding sensors is presented. RESULTS: The results showed that there were significant differences between the two groups in the three nominated angle amplitudes. The mean values of balance level of each parameter in hemiplegic gait and normal gait were: 0.21 versus 0.01, 0.18 versus 0.03, and 0.92 versus 0.03, respectively. The mean values of added angles of each parameter in hemiplegic gait and normal gait were: 74.64 versus 91.31, -76.48 versus -132.4, and 6.77 versus 35.74. CONCLUSIONS: It was concluded that the wearable bio-motion acquisition platform provided a practical approach that was effective in discriminating gait symptoms between hemiplegic and asymptomatic subjects. The extensibility of hemiplegic patients' lower limbs was significantly lower than that of normal subjects, and the hemiplegic gait had worse balance level compared with normal gait. The effect of rehabilitation training of hemiplegic gait could be quantitatively analyzed.

Sample entropy characteristics of movement for four foot types based on plantar centre of pressure during stance phase.

BACKGROUND: Motion characteristics of CoP (Centre of Pressure, the point of application of the resultant ground reaction force acting on the plate) are useful for foot type characteristics detection. To date, only few studies have investigated the nonlinear characteristics of CoP velocity and acceleration during the stance phase. The aim of this study is to investigate whether CoP regularity is different among four foot types (normal foot, pes valgus, hallux valgus and pes cavus); this might be useful for classification and diagnosis of foot injuries and diseases. To meet this goal, sample entropy, a measure of time-series regularity, was used to quantify the CoP regularity of four foot types. METHODS: One hundred and sixty five subjects that had the same foot type bilaterally (48 subjects with healthy feet, 22 with pes valgus, 47 with hallux valgus, and 48 with pes cavus) were recruited for this study. A Footscan® system was used to collect CoP data when each subject walked at normal and steady speed. The velocity and acceleration in medial-lateral (ML) and anterior-posterior (AP) directions, and resultant velocity and acceleration were derived from CoP. The sample entropy is the negative natural logarithm of the conditional probability that a subseries of length m that matches pointwise within a tolerance r also matches at the next point. This was used to quantify variables of CoP velocity and acceleration of four foot types. The parameters r (the tolerance) and m (the matching length) for sample entropy calculation have been determined by an optimal method. RESULTS: It has been found that in order to analyze all CoP parameters of velocity and acceleration during the stance phase of walking gait, for each variable there is a different optimal r value. On the contrary, the value m=4 is optimal for all variables.Sample entropies of both velocity and acceleration in AP direction were highly correlated with their corresponding resultant variables for r>0.91. The sample entropy of the velocity in AP direction was moderately correlated with the one of the acceleration in the same direction (r≥0.673), as well as with the resultant acceleration (r≥0.660). The sample entropy of resultant velocity was moderately correlated with the one of the acceleration in AP direction, as well as with the resultant acceleration (for the both r≥0.689). Moderate correlations were found between variables for the left foot and their corresponding variables for the right foot.Sample entropies of AP velocity, resultant velocity, AP acceleration, and resultant acceleration of the right foot as well as AP velocity and resultant velocity of the left foot were, respectively, significantly different among the four foot types. CONCLUSIONS: It can be concluded that the sample entropy of AP velocity (or the resultant velocity) of the left foot, ML velocity, resultant velocity, ML acceleration and resultant acceleration could serve for evaluation of foot types or selection of appropriate footwear.

Synthesis of mesoporous Cu/Mg/Fe layered double hydroxide and its adsorption performance for arsenate in aqueous solutions.

The mesoporous Cu/Mg/Fe layered double hydroxide (Cu/Mg/Fe-LDH) with carbonate intercalation was synthesized and used for the removal of arsenate from aqueous solutions. The Cu/Mg/Fe-LDH was characterized by Fourier transform infrared spectrometry, X-ray diffraction crystallography, scanning electron microscopy, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller. Effects of various physico-chemical parameters such as pH, adsorbent dosage, contact time and initial arsenate concentration on the adsorption of arsenate onto Cu/Mg/Fe-LDH were investigated. Results showed that it was efficient for the removal of arsenate, and the removal efficiency of arsenate increased with the increment of the adsorbent dosage, while the arsenate adsorption capacity decreased with increase of initial pH from 3 to 11. The adsorption isotherms can be well described by the Langmuir model with R2 > 0.99. Its adsorption kinetics followed the pseudo second-order kinetic model. Coexisting ions such as HPO4(2-), CO3(2-), SO4(2-) and NO3(-) could compete with arsenate for adsorption sites on the Cu/Mg/Fe-LDH. The adsorption of arsenate on the adsorbent can be mainly attributed to the ion exchange process. It was found that the synthesized Cu/Mg/Fe-LDH can reduce the arsenate concentration down to a final level of < 10 microg/L under the experimental conditions, and makes it a potential material for the decontamination of arsenate polluted water.

Ginsenoside Rg1/ADSCs supplemented with hyaluronic acid as the matrix improves rabbit temporomandibular joint osteoarthrosis.

OBJECTIVE: To investigate whether and how ginsenoside Rg1/ADSCs supplemented with hyaluronic acid as the matrix can improve rabbit temporomandibular joint osteoarthrosis. METHOD: Isolate and culture adipose stem cells, measure the activity of differentiated chondrocytes by MTT assay and expression of type II collagen in these cells by immunohistochemistry, in order to evaluate the effect of ginsenoside Rg1 on adipose stem cell proliferation and differentiation into chondrocytes.32 New Zealand white rabbits were randomly divided into four groups: blank group, model group, control group and experimental group, 8 in each group. Osteoarthritis model was established by intra-articular injection of papain. Two weeks after successful model building, medication was given for the rabbits in control group and experimental group. 0.6 mL ginsenoside Rg1/ ADSCs suspension was injected into superior joint space for the rabbits in control group, once a week; 0.6 mL ginsenoside Rg1/ ADSCs complex was injected for the rabbits in experimental group, once a week. RESULTS: Ginsenoside Rg1 can promote ADSCs-derived chondrocytes' activity and expression of type II collagen. Scanning electron microscopy histology images showed cartilage lesions of the experimental group was significantly improved in comparison with control group. CONCLUSION: Ginsenoside Rg1 can promote ADSCs differentiate into chondrocytes, and Ginsenoside Rg1/ADSCs supplemented with hyaluronic acid as the matrix can significantly improve rabbit temporomandibular joint osteoarthrosis.

Real-world effectiveness and safety of RC48-ADC alone or in combination with PD-1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study.

INTRODUCTION: Previous RC48 (Disitamab Vedotin) studies established that the safety and efficacy of RC48-antibody-drug conjugate (ADC), either alone or combined with toripalimab, for metastatic urothelial carcinoma (mUC) patients exhibiting human epidermal growth factor receptor 2 (HER2)-positive or even HER2-negative status after standard chemotherapy failure. METHODS: With locally advanced or metastatic urothelial carcinoma (la/mUC), patients who received RC48-ADC monotherapy or a combination with programmed cell death protein 1 (PD-1) inhibitors between August 2021 and October 2022 were enrolled in this retrospective observational study to evaluate the real-world antitumor effectiveness and safety. RESULTS: Among the 38 enrolled patients (29 males; median age 67.5 years [38-93]), 8 received RC48-ADC monotherapy, while 30 received combination therapy. Initially, 63.2% (24/38) of the patients had received ≥1 line of prior treatment, and 63.2% (24/38) had visceral metastasis. UC of the bladder represented the majority type in 68.4% (26/38) of cases. By the data cutoff in March 2023, the overall objective response rate (ORR) was 63.2% (95% CI, 47.1%-79.2%), with a disease control rate (DCR) of 89.5% (95% CI, 79.3%-99.7%). Median follow-up time was 10.6 months. The median progression-free survival (PFS) was 8.2 months (95% CI, 5.9-10.5), with a 6-month PFS rate of 63.2% and a 12-month PFS rate of 34.1%. Median overall survival (OS) was not reached, with a 12-month OS rate of 76.7%. The median duration of response was 7.3 months (95% CI, 4.6-10.0) among 24 patients evaluated as partial response (PR). The most common treatment-related adverse events (TRAEs) included anemia (71.1%), anorexia (57.9%), asthenia (52.6%), hypoesthesia (52.6%), bone marrow suppression (47.4%), alopecia (47.4%), nausea (44.7%), proteinuria (36.8%), vomiting (34.2%), and hypoalbuminemia (31.6%). No patient experienced TRAEs of Grade ≥3. One patient had an immune-related adverse event (irAE) of rash related to toripalimab. CONCLUSIONS: Both as monotherapy and in combination with PD-1 inhibitors, RC48-ADC exhibits promising effectiveness and manageable safety profile for mUC patients in real-world settings.

Exploration and implementation of a pre-impact fall recognition method based on an inertial body sensor network.

The unintentional injuries due to falls in elderly people give rise to a multitude of health and economic problems due to the growing aging population. The use of early pre-impact fall alarm and self-protective control could greatly reduce fall injuries. This paper aimed to explore and implement a pre-impact fall recognition/alarm method for free-direction fall activities based on understanding of the pre-impact lead time of falls and the angle of body postural stability using an inertial body sensor network. Eight healthy Asian adult subjects were arranged to perform three kinds of daily living activities and three kinds of fall activities. Nine MTx sensor modules were used to measure the body segmental kinematic characteristics of each subject for pre-impact fall recognition/alarm. Our analysis of the kinematic features of human body segments showed that the chest was the optimal sensor placement for an early pre-impact recognition/alarm (i.e., prediction/alarm of a fall event before it happens) and post-fall detection (i.e., detection of a fall event after it already happened). Furthermore, by comparative analysis of threshold levels for acceleration and angular rate, two acceleration thresholds were determined for early pre-impact alarm (7 m/s/s) and post-fall detection (20 m/s/s) under experimental conditions. The critical angles of postural stability of torso segment in three kinds of fall activities (forward, sideway and backward fall) were determined as 23.9 ± 3.3, 49.9 ± 4.1 and 9.9 ± 2.5 degrees, respectively, and the relative average pre-impact lead times were 329 ± 21, 265 ± 35 and 257 ± 36 ms. The results implied that among the three fall activities the sideway fall was associated with the largest postural stability angle and the forward fall was associated with the longest time to adjust body angle to avoid the fall; the backward fall was the most difficult to avoid among the three kinds of fall events due to the toughest combination of shortest lead time and smallest angle of postural stability which made it difficult for the self-protective control mechanism to adjust the body in time to avoid falling down.

A low-cost body inertial-sensing network for practical gait discrimination of hemiplegia patients.

Gait analysis is widely used in detecting human walking disorders. Current gait analysis methods like video- or optical-based systems are expensive and cause invasion of human privacy. This article presents a self-developed low-cost body inertial-sensing network, which contains a base station, three wearable inertial measurement nodes, and the affiliated wireless communication protocol, for practical gait discrimination between hemiplegia patients and asymptomatic subjects. Every sensing node contains one three-axis accelerometer, one three-axis magnetometer, and one three-axis gyroscope. Seven hemiplegia patients (all were abnormal on the right side) and 7 asymptomatic subjects were examined. The three measurement nodes were attached on the thigh, the shank, and the dorsum of the foot, respectively (all on the right side of the body). A new method, which does not need to obtain accurate positions of the sensors, was used to calculate angles of knee flexion/extension and foot in the gait cycle. The angle amplitudes of initial contact, toe off, and knee flexion/extension were extracted. The results showed that there were significant differences between the two groups in the three angle amplitudes examined (-0.52±0.98° versus 6.94±2.63°, 28.33±11.66° versus 47.34±7.90°, and 26.85±8.6° versus 50.91±6.60°, respectively). It was concluded that the body inertial-sensing network platform provided a practical approach for wearable biomotion acquisition and was effective for discriminating gait symptoms between hemiplegia and asymptomatic subjects.

[Effects of Xinjierkang on two kidney one clip-induced hypertension and target organ injury in rats].

OBJECTIVE: To investigate the effects of Xinjierkang on two kidney one clip -induced hypertension and target organ injury in rats. METHODS: Two kidney one clip-induced hypertension rats model was established. Rats were divided into control group, model group, Xinjierkang group, and fosinopril group. At the end of 8th w, the hemodynamics indexes were recorded. The cardiac hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes of heart, aorta and kidney were investigated by HE and/or Van Gieson stain. RESULTS: Compared with control group, the heart systolic and diastolic function were impaired, the heart weight index, cardiomyocytes cross section area (CSA), cardiac collagen deposition, vascular remodeling index and glomerulus area were increased markedly in model group rats. Administration of Xinjierkang and fosinopril markedly ameliorated hemodynamic indexes, inhibited the elevation of HW/BW ratio, CSA of cardiomyocytes, vascular remodeling index and glomerulus hypertrophy, decreased collagen deposition in heart. CONCLUSION: Xinjierkang has protective effects against two kidney one clip-induced hemodynamic impairment, cardiovascular remodeling and glomerulus hypertrophy in rats.

[Effects of a compound Chinese medicine Xinji' erkang on isoproterenol-induced ventricular remodeling in mice].

OBJECTIVE: To investigate the effects of Xinji' erkang (XJEK), a compound Chinese herbal medicine, on isoproterenol-induced ventricular remodeling in mice. METHODS: Isoproterenol was given subcutaneously (1 mg/kg, twice per day for 7 d) to induce ventricular remodeling in mice. Mice were divided into normal control group, model group, XJEK low-, medium- and high- dose groups, XJEK water layer group, XJEK n-butanol layer group and metoprolol group. All drugs were given by intragastric administration. At the end of the 7th day, the hearts of the rats were weighted, and myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW). The histological changes were observed by hemotoxylin-eosin and Van Gieson staining. Colorimetric method was used to determine the content of hydroxyproline in heart, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum. RESULTS: Compared with the isoproterenol injection only, XJEK potently inhibited cardiomyocyte hypertrophy and the increase of hydroxyproline content in heart (P<0.01), improved cardiac pathology change, inhibited the decrease of SOD activity and the increase of MDA content in serum (P<0.01). XJEK water layer also inhibited the increase of cardiomyocyte hypertrophy (P<0.01) while XJEK n-butanol layer inhibited cardiomyocyte hypertrophy and fibrosis (P<0.01). CONCLUSION: XJEK possesses protective effects against isoproterenol-induced ventricular remodeling in mice, which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body. XJEK water layer and XJEK n-butanol layer attenuated ventricular remodeling without significant oxidative stress state changing, which indicates that a non-antioxidative stress mechanism may exist.

Utilization of 3D Laser Scanning for Stability Evaluation and Deformation Monitoring of Landslides.

Three-dimensional laser scanning technology can comprehensively and accurately monitor slope deformation. To conduct deformation monitoring and stability evaluation of the Changzhou Shunguoshan landslide, in this paper, the causes of the Changzhou Shunguoshan landslide were analyzed. Consequently, 3D laser scanning technology and the traditional monitoring methods such as data from the total station were compared. The point cloud data provides big data support for landslide deformation monitoring and landslide stability early warning. Meanwhile, the landslide stability was evaluated by analogy with existing studies on slope deformation monitoring data. Results show that the three-dimensional laser scanning monitoring data is similar to the total station monitoring data. The overall deformation of the Shunguoshan landslide is no more than ± 0.0015 m; the deformation of the Liyang slope is less than ±0.09 m, which is far less than the analog slope deformation monitoring data. The slope construction and monitoring process are in a stable state.

Identification and exploration of the pyroptosis-related molecular subtypes of breast cancer by bioinformatics and machine learning.

OBJECTIVES: To classify breast cancer (BRCA) according to the expression of pyroptosis-related genes and explore their molecular characteristics. METHODS: Nonnegative matrix factorization (NMF) was used for subtype classification based on 21 pyroptosis-related genes in the TCGA database. Survival analysis and t-distributed stochastic neighbor embedding (t-SNE) analysis were conducted to assess the NMF results' performance. XGBoost, CatBoost, logistic regression, neural network, random forest, and support vector machine were utilized to perform supervised machine learning and construct prediction models. Genetic mutations, tumor mutational burden, immune infiltration, methylation, and drug sensitivity were analyzed to explore the molecular signatures of different subtypes. Lasso, RF, and Cox regression were operated to construct a prognostic model based on differentially expressed genes. RESULTS: BRCA patients were divided into two subtypes (named Cluster1 and Cluster2). Survival analysis (P = 0.02) and t-SNE analysis demonstrated that Cluster1 and Cluster2 were well classified. The XGBoost model achieved reliable predictions on both training and validation sets. Regarding molecular characteristics, Cluster1 had higher TMB, immune cell infiltration, and m6A methylation-related gene expression than Cluster2. There was also a statistically significant difference between the two subtypes concerning drug susceptibility. Finally, a 5-gene prognostic model was constructed using Lasso, RF, and Cox regression and validated in the GEO database. CONCLUSION: Our study may provide new insights from bioinformatics and machine learning for exploring pyroptosis-related subtypes and their respective molecular signatures in BRCA. In addition, our models may be helpful for the treatment and prognosis of BRCA.