Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

[Study on drug properties of Arisaematis Rhizoma and Arisaema Cum Bile based on substance and energy metabolism in normal and cold/heat syndrome model rats].

This paper clarified the scientific connotation of the changes in cold and heat properties of Arisaematis Rhizoma and Arisaema Cum Bile through investigating the changes of substance and energy metabolism after drug intervention in the rats with normal and cold/heat syndrome, so as to improve the method of evaluating the drug properties of Chinese medicine. After one week of adaptive feeding, healthy male SD rats were randomly divided into three parts: normal rats, heat syndrome rat models, and cold syndrome rat models. Through ice water bath and oral euthyrox(120 µg·kg~(-1)), the models of cold syndrome and heat syndrome were induced, respectively. The models were made at 9:00 am. and administrated by gavage at 3:00 pm. every day. All administration groups were administrated with Arisaematis Rhizoma and Arisaema Cum Bile decoction, respectively, and the blank group was given the same dose of normal saline. After continuous administration for 15 d, the rats were anesthetized by chloral hydrate, blood was taken from abdominal aorta, and the hearts and livers were removed and stored at-80 ℃. The changes in the body weight and anal temperature of rats during administration were detected, and the liver coefficient of rats was detected after removing the liver. Enzyme-linked immunosorbent assay(ELISA) was adopted to detect the expression level of the indexes related to substance and energy metabolism in liver and heart of rat, and Western blot was used to detect the expression of key proteins in AMPK/mTOR signaling pathway for further verification. The results showed that Arisaematis Rhizoma enhanced the expression level of enzymes related to substance and energy metabolism in the normal and cold and heat syndrome rat models, and increased anal temperature, which exhibited warm(hot) drug property. Arisaema Cum Bile inhibited the level of substance and energy metabolism in rats, and reduced anal temperature, which showed cold(cool) drug property. Chinese Pharmacopoeia has recorded "Arisaematis Rhizoma has warm property and Arisaema Cum Bile has cool property", which is consistent with the phenomenon in this study. Therefore, it is feasible to evaluate the drug properties of Chinese medicine based on the substance and energy metabolism of normal and cold/heat syndrome model rats, which completes the method of evaluating drug properties of Chinese medicine.

A new BET inhibitor, 171, inhibits tumor growth through cell proliferation inhibition more than apoptosis induction.

The bromodomain and extra-terminal domain (BET) family of proteins, especially bromodomain-containing protein 4 (BRD4), has emerged as exciting anti-tumor targets due to their important roles in epigenetic regulation. Therefore, the discovery of BET inhibitors with promising anti-tumor efficacy will provide a novel approach to epigenetic anticancer therapy. Recently, we discovered the new BET inhibitor compound 171, which is derived from a polo-like kinase 1 (PLK1)-BRD4 dual inhibitor based on our previous research. Compound 171 was found to maintain BET inhibition ability without PLK1 inhibition, and there was no selectivity among BET family members. The in vitro and in vivo results both indicated that the overall anti-tumor activity of compound 171 was improved compared with the (+)-JQ-1 or OTX-015 BET inhibitors. Furthermore, we found that compound 171 could regulate the expression of cell cycle-regulating proteins including c-Myc and p21 and induce cell cycle arrest in the G0/G1 phase. However, compound 171 only has a quite limited effect on apoptosis, in considering that apoptosis was only observed at doses greater than 50 µM. To determine the mechanisms underlying cell death, proliferation activity assay was conducted. The results showed that compound 171 induced clear anti-proliferative effects at doses that no obvious apoptosis was induced, which indicated that the cell cycle arresting effect contributed mostly to its anti-tumor activity. The result of this study revealed the anti-tumor mechanism of compound 171, and laid a foundation for the combination therapy in clinical practice, if compound 171 or its series compounds become drug candidates in the future.

Analyzing the Interactions of mRNAs and ncRNAs to Predict Competing Endogenous RNA Networks in Osteosarcoma Chemo-Resistance.

Chemo-resistance is a huge obstacle encountered in the osteosarcoma (OS) treatment. Protein-coding mRNAs, as well as non-coding RNAs (ncRNAs), including long ncRNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA), have been demonstrated to play an essential role in the regulation of cancer biology. However, the comprehensive expression profile and competing endogenous RNA (ceRNA) regulatory network between mRNAs and ncRNAs in the OS chemo-resistance still remain unclear. In the current study, we developed whole-transcriptome sequencing (RNA sequencing [RNA-seq]) in the three paired multi-drug chemo-resistant and chemo-sensitive OS cell lines to comprehensively identify differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for mRNAs with significantly different expression. Then the ceRNA networks combining lncRNAs, circRNAs, miRNAs, and mRNAs were predicted and constructed on the basis of the authoritative miRanda and TargetScan databases combined with the widely accepted vital drug resistance-related genes and signal transduction pathways. In addition, two constructed ceRNA regulatory pathways, lncRNAMEG3/hsa-miR-200b-3p/AKT2 and hsa_circ_0001258/hsa-miR-744-3p/GSTM2, were randomly selected and validated by real-time qPCR, RNA immunoprecipitation (RIP), RNA pull-down assay, and dual luciferase reporter gene system. Taken together, our findings may provide new evidence for the underlying mechanism of OS chemo-resistance and uncover some novel targets for reversing it.

Adipocyte differentiation is regulated by mitochondrial trifunctional protein α-subunit via sirtuin 1.

Mitochondrial trifunctional protein α-subunit (MTPα) is involved in the fatty acid ß-oxidation (FAO) pathway. Two MTPα activities, 3-hydroxyacyl-CoA dehydrogenase and long-chain hydratase, have been linked with the occurrence and development of obesity and obesity-related disorders. These activities catalyze two steps in the FAO pathway (the second and third reactions). However, the role of MTPα in the pathogenesis of obesity has not been evaluated, and the functional role of MTPα in adipocyte differentiation has not been determined. Here, we analyzed the functional role of MTPα using in vitro and in vivo models of adipogenesis. MTPα expression was upregulated during the differentiation of 3T3-L1 preadipocyte cells into adipocytes. MTPα gene silencing stimulated peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT-enhancer-binding protein alpha(C/EBPα) expression, which promoted adipocyte differentiation. By contrast, MTPα overexpression blocked adipogenesis in 3T3-L1 cells. Further analysis showed that MTPα positively regulated sirtuin 1 (SIRT1). Injection of preadipocytes overexpressing MTPα into athymic mice significantly impaired de novo fat pad formation compared with that of the control, and furthermore MTPα knockdown enhances fat pad formation at a time point earlier than 5-week, such as week-2 and week-3, when the control fat pad is not fully developed. In summary, our data indicate that MTPα is a novel factor that negatively regulates adipocyte differentiation. We propose a pathway in which MTPα inhibits adipogenesis by promoting SIRT1 expression, which represses PPARγ and attenuates adipogenesis.

[Density Functional Theory Calculation and Raman Spectroscopy Studies of Organophosphorus Pesticides].

Organophosphorus pesticides were often used for prevention and control disease and insect of plant, and are acute toxic to human and livestock by anti-ache activity. The molecular geometry of three organophosphorus pesticides(dimethoate, trichlorfon and phosalone) were constructed on Gauss View3.07, and Density functional theory (DFT) was used to optimize and calculate the vibrational wavenumbers of three organophosphorus pesticides by B3LYP hybrid functional and 6-31G(d, p) basis set. The experimental spectra of three organophosphorus pesticides were compared with the theoretically calculated spectra and Surface-enhanced Raman Scattering spectra (SERS). The results indicated that the experimental spectra and theoretically calculated spectra of three organophosphorus pesticides have a very good match. The Raman peaks of three organophosphorus pesticides were roundly assigned between the range of 400～1 800 cm(-1), and the characteristics peaks of three organophosphorus pesticides were found. The Raman vibration peak of organophosphorus pesticide may appear similar characteristic peak. The pesticide contained PO is between 1 140 and 1 320 cm(-1), the pesticide contained PS is in the range 535～750 cm(-1), and the organophosphorus pesticide contained P­O­C is n the range 920～1 088 cm-1. The different characteristic peaks of three pesticides were found by the contrast of the surface enhanced Raman spectra. This shows that the SERS method can be used to identify the organophosphorus pesticide. The results can furnish a theoretical support for qualitative and quantitative analysis of organophosphorus pesticide.

Density Functional Theory Calculation and Raman Spectroscopy Studies of Carbamate Pesticides.

In order to obtain the molecular structure vibration information of carbamate pesticide, three carbamate pesticides (carbaryl, carbofuran and aldicarb) were optimized and calculated with B3LYP hybrid functional and 6-31G(d,p) basis set, and their experimental spectra were collected with the Raman spectrometer. The theoretically calculated spectra were compared with the experimental spectra carefully. The results indicated that the theoretically calculated spectra have a very good match with the experimental spectra. The vibrational peaks of three carbamate pesticides were assigned between the range of 400～3 200 cm-1, and the characteristic peaks of carbamate pesticide were found at 874, 1 014, 1 162 and 1 716 cm-1. The characteristic peaks of three carbamate pesticides were found by the contrast of the experimental spectra. The results can provide a theoretical basis for the detection of carbamate pesticide, and will be applied to the identification of carbamate pesticide residues in agricultural products.

CCAAT/enhancer-binding protein CEBP-2 controls fat consumption and fatty acid desaturation in Caenorhabditis elegans.

Mammalian CCAAT/enhancer-binding proteins (C/EBPs) are generally known as regulators in adipocyte differentiation. However, more understanding of the role of C/EBPs in lipid and glucose metabolism remains to be discovered. In this study, we verified the effect of CEBP-2, the homolog of CEBPs, on fat storage in Caenorhabditis elegans. Expressions of 85 genes that encode the major enzymes in energy metabolic pathways were then screened in cebp-2-deficient worms using a quantitative real-time polymerase chain reaction (QRT-PCR). Our data implied that loss of function of CEBP-2 displayed a low-fat phenotype in C. elegans owing to increased expression of ech-1.1 and decreased expression of fat-5. Our findings indicated that cebp-2 controls total body fat content by governing fatty acid mitochondrial ß-oxidation and desaturation in C. elegans. These data provide insights into how C/EBPs may affect lipid metabolism in mammals in addition to regulating adipocyte differentiation.

Freeze-thaw Caenorhabditis elegans freeze-thaw stress response is regulated by the insulin/IGF-1 receptor daf-2.

BACKGROUND: Adaption to cold temperatures, especially those below freezing, is essential for animal survival in cold environments. Freezing is also used for many medical, scientific, and industrial purposes. Natural freezing survival in animals has been extensively studied. However, the underlying mechanisms remain unclear. Previous studies demonstrated that animals survive in extremely cold weather by avoiding freezing or controlling the rate of ice-crystal formation in their bodies, which indicates that freezing survival is a passive thermodynamic process. RESULTS: Here, we showed that genetic programming actively promotes freezing survival in Caenorhabditis elegans. We found that daf-2, an insulin/IGF-1 receptor homologue, and loss-of-function enhanced survival during freeze-thaw stress, which required the transcription factor daf-16/FOXO and age-independent target genes. In particular, the freeze-thaw resistance of daf-2(rf) is highly allele-specific and has no correlation with lifespan, dauer formation, or hypoxia stress resistance. CONCLUSIONS: Our results reveal a new function for daf-2 signaling, and, most importantly, demonstrate that genetic programming contributes to freezing survival.

Molecular Dynamics Simulations of Ternary Complexes: Comparisons of LEAFY Protein Binding to Different DNA Motifs.

LEAFY (LFY) is a plant-specific transcription factor, with a variety of roles in different species. LFY contains a conserved DNA-binding domain (DBD) that determines its DNA-binding specificity. Recently, the structures of the dimeric LFY-DBD bound to different DNA motifs were successively solved by X-ray crystallography. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of DNA-bound LFY protein from angiosperms and the moss Physcomitrella patens, respectively. The comparison of stabilities of the two systems is consistent with the experimental data of binding affinities. The calculation of hydrogen bonds showed that position 312 in LFY determines the difference of DNA-binding specificity. By using principal component analysis (PCA) and free energy landscape (FEL) methods, the open-close conformational change of the dimerization interface was found to be important for the system stability. At the dimerization interface, the protein-protein interaction has multiple influences on the cooperative DNA binding of LFY. The following analysis of DNA structural parameters further revealed that the protein-protein interaction contributes varying roles according to the specific DNA-binding efficiency. We propose that the protein-protein interaction serves a dual function as a connector between LFY monomers and a regulator of DNA-binding specificity. It will improve the robustness and adaptivity of the LFY-DNA ternary structure. This study provides some new insights into the understanding of the dynamics and interaction mechanism of dimeric LFY-DBD bound to DNA at the atomic level.

Does a novel method of PICC insertion improve safety?

BACKGROUND: Placing a central venous access device via the internal jugular or subclavian vein entails significant risks to both patient and healthcare worker. PURPOSE: The purpose of this randomized, prospective study was to determine whether the accelerated Seldinger technique (AST) offers significant safety advantages over the modified Seldinger technique (MST) for peripherally inserted central catheter insertion. MATERIALS AND METHODS: Patients were randomly assigned to undergo introducer sheath insertion by means of either MST or AST. Primary outcome measures included time to completion of introducer sheath insertion, estimated blood loss, and success rate. Secondary outcome measures included vessel-to-air exposure events and unprotected sharps exposure. DISCUSSION: While both insertion methods proved equivalent for successful vessel cannulation, AST was significantly faster (P = 0.0048) and resulted in less blood loss (P = 0.0295) than MST. Additionally, AST resulted in significantly fewer vessel-to-air exposure events (P < 0.0001) and unprotected sharps exposures (P < 0.0001). Although this was a relatively small and unblinded study, the high degree of statistical significance of the study results suggests that, for both patients and healthcare workers, AST is faster and safer than MST for PICC peelable introducer sheath insertion.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3.

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).

Molecular dynamics simulations of wild type and mutants of human complement receptor 2 complexed with C3d.

The interaction between human complement receptor type 2 (CR2) and antigen-bound C3d can bridge the innate and adaptive immune systems. The recently determined structure of the CR2(SCR1-2):C3d complex has revealed the expected binding interface of CR2-C3d. In this article, wild type (WT) and three mutants of the new structure are studied by molecular dynamics (MD) simulations. The differently decreased structural stabilities of the mutants relative to WT are shown to be consistent with the experimental data, which can be explained by the different hydrogen bond patterns at the interfaces. It is also found that two clusters of residues (D36/E37/E39 and E160/D163/E166) in the acidic pocket of C3d are important for CR2-C3d interactions, which is in good agreement with previous mutagenesis study. In addition, functional dynamics and the conformational change of CR2 are explored by using domain cross-correlation map (DCCM), principal component analysis (PCA), and free energy landscape (FEL) methods. The conformational change mainly corresponds to the opening of a V-shaped structure of CR2, which is consistent with the previously reported high interdomain flexibility of CR2. We further suppose that the opening of a V-shaped structure of CR2 may favor the binding stability of CR2(SCR1-2):C3d. This study would provide some new insights into the understanding of the CR2-C3d interaction mechanism.

Combination of hsa_circ_0004674 and lncRNA OIP5­AS1 as a novel clinical biomarker used to predict prognosis in patients with osteosarcoma.

Osteosarcoma is a malignant tumor that predominantly occurs in children or adolescents under the age of 20 years old. Metastasis and chemotherapy resistance are two problems in the treatment of osteosarcoma, and the lack of definite biomarkers impairs the course of treatment. In recent years, non-coding RNA, as a biomarker of osteosarcoma, has become an area of research focus. The role of long non-coding RNAs (lncRNAs), such as lncRNA OIP5-AS1, and circular RNAs, such as hsa_circ_0004674, in osteosarcoma have previously been revealed, and the present study investigated their clinical significance. A total of 20 samples were collected from patients with osteosarcoma. The expression levels of lncRNA OIP5-AS1 and hsa_circ_0004674 were analyzed in tumor tissues and patient serum, and their associations with chemotherapy sensitivity, lung metastasis and prognosis were assessed. The results revealed that these two non-coding RNAs were significantly upregulated in the osteosarcoma tissues of patients compared with those in the adjacent tumor tissues. In addition, the expression levels of the two non-coding RNAs were increased in the serum of patients with osteosarcoma compared with those in patients with bone fractures (P<0.01). In patients with lung metastasis or chemotherapy resistance (tumor necrosis rate <90%), the expression levels of the two non-coding RNAs were similarly increased. By plotting the receiver operating characteristic curve, it was revealed that the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 was better than ALP or either non-coding RNA alone in predicting chemotherapy sensitivity and metastasis. Kaplan-Meier survival analysis showed that, in patients with osteosarcoma, higher expression of both non-coding RNAs was associated with worse survival time (log-rank test P=0.006). In conclusion, the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 may be used as a better biomarker than traditional biomarkers, such as ALP, in a clinical setting.

5G-based remote magnetically controlled capsule endoscopy for examination of the stomach and small bowel.

BACKGROUND AND AIMS: Remote endoscopy can improve diagnostic efficiency of gastrointestinal (GI) diseases for patients in remote areas. A novel remote magnetically controlled capsule endoscopy (MCE) system based on a 5G network was developed for real-time remote GI examinations. We aimed to evaluate the feasibility and safety of the 5G-based remote MCE for examination of the stomach and small bowel. METHODS: This was a prospective, nonrandomized, comparative study. Consecutive participants enrolled in the First People's Hospital of Yinchuan underwent remote MCE examinations performed by an endoscopist located in Changhai Hospital. Consecutive participants enrolled in Changhai Hospital underwent conventional MCE examinations performed by the same endoscopist. The main outcomes included the complete visualization rate of the stomach and small bowel, safety assessment and network latency time of remote MCE examinations. RESULTS: From March 2021 to June 2021, 20 participants in each group were enrolled. The complete visualization rate of the stomach and small bowel was 100% in both groups (p > 0.999) without any adverse event. The median network latency time of remote MCE group was 19.948 ms. Gastric examination time (8.96 vs. 8.92 min, p = 0.234), maneuverability (15.00 vs. 15.00, p = 0.317), image quality (1.00 vs. 1.00, p > 0.999) and diagnostic yields in the stomach and small bowel (55% vs. 30%, 5% vs. 0%, both p > 0.05) were comparable between remote and conventional MCE groups. All participants in remote MCE group considered remote MCE acceptable and necessary. CONCLUSIONS: 5G-based remote MCE was a feasible and safe method for viewing the stomach and small bowel.

Surgical robot-assisted tripod percutaneous reconstruction technique combined with bone cement filling technique for the treatment of acetabular metastasis.

Background: Acetabular metastasis is a type of metastatic bone cancer, and it mainly metastasizes from cancers such as lung cancer, breast cancer, and renal carcinoma. Acetabular metastasis often causes severe pain, pathological fractures, and hypercalcemia which may seriously affect the quality of life of acetabular metastasis patients. Due to the characteristics of acetabular metastasis, there is no most suitable treatment to address it. Therefore, our study aimed to investigate a novel treatment technique to relieve these symptoms. Methods: Our study explored a novel technique to reconstruct the stability of the acetabular structure. A surgical robot was used for accurate positioning and larger-bore cannulated screws were accurately inserted under the robot's guidance. Then, the lesion was curetted and bone cement was injected through a screw channel to further strengthen the structure and kill tumor cells. Results: A total of five acetabular metastasis patients received this novel treatment technique. The data relating to surgery were collected and analyzed. The results found that this novel technique can significantly reduce operation time, intraoperative bleeding, visual analogue score scores, Eastern Cooperative Oncology Group scores, and postoperative complications (e.g., infection, implant loosening, hip dislocation) after treatment. Follow-up time ranged from 3 months to 6 months, and the most recent follow-up results showed that all patients survived and no acetabular metastasis progressed in any of the patients after surgery. Conclusion: Surgical robot-assisted tripod percutaneous reconstruction combined with the bone cement filling technique may be a novel and suitable treatment in acetabular metastasis patients. Our study may provide new insights into the treatment of acetabular metastasis.

Altered brain white matter structural motor network in spinocerebellar ataxia type 3.

OBJECTIVES: Spinocerebellar ataxia type 3 is a disorder within the brain network. However, the relationship between the brain network and disease severity is still unclear. This study aims to investigate changes in the white matter (WM) structural motor network, both in preclinical and ataxic stages, and its relationship with disease severity. METHODS: For this study, 20 ataxic, 20 preclinical SCA3 patients, and 20 healthy controls were recruited and received MRI scans. Disease severity was quantified using the SARA and ICARS scores. The WM motor structural network was created using probabilistic fiber tracking and was analyzed using graph theory and network-based statistics at global, nodal, and edge levels. In addition, the correlations between network topological measures and disease duration or clinical scores were analyzed. RESULTS: Preclinical patients showed increasing assortativity of the motor network, altered subnetwork including 12 edges of 11 nodes, and 5 brain regions presenting reduced nodal strength. In ataxic patients assortativity of the motor network also increased, but global efficiency, global strength, and transitivity decreased. Ataxic patients showed a wider altered subnetwork and a higher number of reduced nodal strengths. A negative correlation between the transitivity of the motor network and SARA and ICARS scores was observed in ataxic patients. INTERPRETATION: Changes to the WM motor network in SCA3 start before ataxia onset, and WM motor network involvement increases with disease progression. Global network topological measures of the WM motor network appear to be a promising image biomarker for disease severity. This study provides new insights into the pathophysiology of disease in SCA3/MJD.

Prevalence and risk factors of stroke in China: a national serial cross-sectional study from 2003 to 2018.

Stroke imposes a substantial burden worldwide. With the rapid economic and lifestyle transition in China, trends of the prevalence of stroke across different geographic regions in China remain largely unknown. Capitalizing on the data in the National Health Services Surveys (NHSS), we assessed the prevalence and risk factors of stroke in China from 2003 to 2018. In this study, data from 2003, 2008, 2013, and 2018 NHSS were collected. Stroke cases were based on participants' self-report of a previous diagnosis by clinicians. We estimated the trends of stroke prevalence for the overall population and subgroups by age, sex, and socioeconomic factors, then compared across different geographic regions. We applied multivariable logistic regression to assess associations between stroke and risk factors. The number of participants aged 15 years or older were 154,077, 146,231, 230,067, and 212,318 in 2003, 2008, 2013, and 2018, respectively, among whom, 1435, 1996, 3781, and 6069 were stroke patients. The age and sex standardized prevalence per 100,000 individuals was 879 in 2003, 1100 in 2008, 1098 in 2013, and 1613 in 2018. Prevalence per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018, while urban areas had a stable trend from 1261 in 2003 to 1365 in 2018. Across geographic regions, the central region consistently had the highest prevalence, but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018 (P trend<0.001), surpassing the eastern region in 2013. Advanced age, male sex, rural area, central region, hypertension, diabetes, depression, low education and income level, retirement or unemployment, excessive physical activity, and unimproved sanitation facilities were significantly associated with stroke. In conclusion, the increasing prevalence of stroke in China was primarily driven by economically underdeveloped regions. It is important to develop targeted prevention programs in underdeveloped regions. Besides traditional risk factors, more attention should be paid to nontraditional risk factors to improve the prevention of stroke.

Endoscopic Ruler for varix size measurement: A multicenter pilot study.

BACKGROUND: We invented Endoscopic Ruler, a new endoscopic device to measure the size of varices in patients with cirrhosis and portal hypertension. AIM: To assess the feasibility and safety of Endoscopic Ruler, and evaluate the agreement on identifying large oesophageal varices (OV) between Endoscopic Ruler and the endoscopists, as well as the interobserver agreement on diagnosing large OV using Endoscopic Ruler. METHODS: We prospectively and consecutively enrolled patients with cirrhosis from 11 hospitals, all of whom got esophagogastroduodenoscopy (EGD) with Endoscopic Ruler. The primary study outcome was a successful measurement of the size of varices using Endoscopic Ruler. The secondary outcomes included adverse events, operation time, the agreement of identifying large OV between the objective measurement of Endoscopic Ruler and the empirical reading of endoscopists, together with the interobserver agreement on diagnosing large OV by Endoscopic Ruler. RESULTS: From November 2020 to April 2022, a total of 120 eligible patients with cirrhosis were recruited and all of them underwent EGD examinations with Endoscopic Ruler successfully without any adverse event. The median operation time of Endoscopic Ruler was 3.00 min [interquartile range (IQR): 3.00 min]. The kappa value between Endoscopic Ruler and the endoscopists while detecting large OV was 0.52, demonstrating a moderate agreement. The kappa value for diagnosing large OV using Endoscopic Ruler among the six independent observers was 0.77, demonstrating a substantial agreement. CONCLUSION: The data demonstrates that Endoscopic Ruler is feasible and safe for measuring the size of varices in patients with cirrhosis and portal hypertension. Endoscopic Ruler is potential to promote the clinical practice of the two-grade classification system of OV.