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.

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).

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.

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.

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.

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.

[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.

Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3.

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism. Methods: A double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon's signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson's correlation analysis. Results: After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = - 0.831, p = 0.02). Conclusion: The treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

Non-synonymous substitution of evolutionarily conserved residue in Tau class glutathione transferases alters structural and catalytic features.

Plant-specific tau glutathione transferases (GSTs) are basically involved in catalysing γ-glutathione (GSH)-dependent conjugation reactions with pesticides and herbicides, which play an important role in the detoxification of pollutants. Given the lack of systematic biochemical and structural information on tau GSTs, the study of their mediated defence mechanisms against toxic compounds has been greatly hindered. Here, we reveal the importance of the Ile residue closely interacting with GSH for the structural stability and catalytic function of GST. Evolutionary conservation analysis indicated that the crucial G-site Ile55 in the SbGSTU6 was converted to Thr53 of SbGSTU7. The comparative biochemical data on SbGSTU6, SbGSTU7 and their mutants showed that the substitution of Ile by Thr caused significant decrease in the affinity and catalytic efficiency of the GSTs. The unfavourable structural flexibility and pKa distribution of the active cavity residues were also demonstrated. Crystallography studies and molecular dynamics simulations showed that the conversion resulted in the hydrogen bond recombination with GSH and conformational rearrangement of GST active cavity, in which the Ile residue was more conducive to the formation of enzyme substrate complexes. The extensive biochemical and structural data not only reveal the critical role of the conserved G-site Ile residue in catalysing GSH-conjugate reactions but also provide valuable resources for the development of GST engineering in analytical and agricultural biotechnology.

Clinical Features and Natural History in a Cohort of Chinese Patients with RPE65-Associated Inherited Retinal Dystrophy.

RPE65-associated inherited retinal dystrophy (RPE65-IRD) is an early-onset retinal degeneration. The aim of this study was to describe the clinical features and natural course of this disease in a Chinese patient cohort with RPE65 biallelic variants. Thirty patients from 29 unrelated families with biallelic disease-causing RPE65 variants underwent full ophthalmic examinations. Thirteen were followed up over time. An additional 57 Chinese cases from 49 families were retrieved from the literature to analyze the relationship between best-corrected visual acuity (BCVA) and age. Our 30 patients presented age-dependent phenotypic characteristics. Multiple white dots were a clinical feature of young patients, while maculopathy, epiretinal membrane, and bone spicules were common in adult patients. Among the 84 patients, BCVA declined with age in a nonlinear, positive-acceleration relationship (p < 0.001). All patients older than 40 years met the WHO standard for low vision. Longitudinal observation revealed a slower visual acuity loss in patients younger than 20 years than those in their third or fourth decade of life. Our study detailed the clinical features and natural course of disease in Chinese patients with RPE65-IRD. Our results indicated that these patients have a relatively stable BCVA in childhood and adolescence, but eyesight deteriorates rapidly in the third decade of life. These findings may facilitate the implementation of gene therapy in China.

Doxorubicin-induced novel circRNA_0004674 facilitates osteosarcoma progression and chemoresistance by upregulating MCL1 through miR-142-5p.

Accumulating evidence has shown that circular RNA (circRNA) dysregulation is involved in various types of cancer, including osteosarcoma (OS). Nevertheless, the role and mechanism of circRNAs in OS progression and chemoresistance remain elusive. We found that a novel doxorubicin-induced circular RNA, hsa_circ_0004674, screened by whole total transcriptome RNA sequencing in our previous study, was upregulated in OS chemoresistant cell lines and tissues and also connected with patients' poor prognosis. Circ_0004674 knockdown remarkably suppressed OS cell chemoresistance, proliferation, migration, invasion, OS tumor growth, and enhanced cell cycle arrest and apoptosis in vitro and in vivo through control the expression of the antiapoptotic protein MCL1, a member of the Bcl-2 gene family. Further online bioinformatics analysis revealed that miR-142-5p had potential binding sites that can bind circ_0004674 and the 3'UTR of MCL1 mRNA. Moreover, the expression and function of miR-142-5p were conversely correlated with circ_0004674 in vitro. RIP, pull-down, luciferase assay, and RNA FISH demonstrated that circ_0004674 could compete with MCL1 for miR-142-5p binding to counteract miR-142-5p-mediated repression of MCL1 at the post-transcriptional level. To sum up, our study sheds light on the critical role of the oncogenic circ_0004674/miR-142-5p/MCL1 axis in OS progression and chemoresistance, providing a novel potential target for OS therapy.

Distribution of IOP and its relationship with refractive error and other factors: the Anyang University Students Eye Study.

AIM: To investigate the distribution of intraocular pressure (IOP) and its relationship with refractive error and other factors in university students from Anyang, China. METHODS: A university-based study was conducted. Subjects were invited to complete ophthalmic examinations, including visual acuity, noncontact tonometry (NCT), cycloplegic autorefraction, and ocular biometry. Univariable and multivariable analyses were used to evaluate the associations between IOP and other factors. Only data from right eyes were used in analysis. RESULTS: A total of 7720 subjects aged 16 to 26 years old were included, and 2834 (36.4%) of the participants were male. The mean IOP of the right eye for all subjects was 15.52±3.20 mm Hg (95%CI: 15.45, 15.59). Using multivariate linear regression analysis, IOP was found to correlate significantly with younger age (P<0.001; standardized regression coefficient ß, -0.061; regression coefficient ß, -0.139; 95%CI: -0.18, -0.09), higher myopic refractive error (P=0.044; standardized ß, -0.060; regression coefficient ß, -0.770; 95%CI: -0.15, -0.002), higher central corneal thickness (P<0.001; standardized ß, 0.450; regression coefficient ß, 0.044; 95%CI: 0.04, 0.05), and shorter axial length (AL; P<0.001; standardized ß, -0.061; regression coefficient ß, -0.163; 95%CI: -0.25, -0.07). CONCLUSION: This study described the normal distribution of IOP. In Chinese university students aged 16-26y, higher IOP is associated with younger age, higher myopic refractive error, higher thickness of the central cornea, and shorter AL.

Effect of body stature on refraction and ocular biometry in Chinese young adults: The Anyang University Students Eye Study.

CLINICAL RELEVANCE: Large-scale data on the association between body stature with biometry parameters and refraction in young adults facilitates an understanding of myopia development. Taller persons have eyes with more negative refractions, longer axial lengths, deeper anterior chambers, flatter corneas, and higher axial length-corneal radius ratio. BACKGROUND: To determine the relationship between body stature with ocular biometry and refraction in young adults. METHODS: This was a cross-sectional university-based study of 16- to 26-year-old students in China. Cycloplegic refraction and corneal curvature were measured using an autorefractor. Ocular parameters, including axial length, anterior chamber depth and lens thickness, were measured using a Lenstar LS900. Data on height and weight were acquired from an annual standardised physical examination and body mass index was calculated. RESULTS: Of 7,971 participants examined in the school clinics, 5,657 (71.0 per cent) were available in the analysis. After adjusting for age, gender, parental myopia, time outdoors, near work and weight, each centimetre of height increase was associated with more negative refraction of -0.023-D, a 0.032-mm increase in axial length, a 0.003-mm increase in anterior chamber depth, a 0.008-mm increase in corneal curvature, and a 0.001 increase in axial length-corneal radius ratio. With regard to weight, a 1-kg heavier person was more likely to have less negative refraction of 0.011-D, a 0.001-mm increase in anterior chamber depth and a 0.002-mm increase in corneal curvature. A similar pattern of significant associations was also found in body mass index. CONCLUSION: Taller, young adults tended to have longer eyes, deeper anterior chambers, flatter corneas, higher axial length-corneal radius ratio, and more negative refraction, adjusted for potential confounders. In contrast, heavier and higher body mass index persons are more hyperopic. The differences in stature may partially explain the variation in refraction and ocular biometric parameters.

Six Visual Rating Scales as A Biomarker for Monitoring Atrophied Brain Volume in Parkinson's Disease.

The focus of our investigation was to determine the feasibility of using six visual rating scales as whole-brain imaging markers for monitoring atrophied brain volume in Parkinson's disease (PD). This was a prospective cross-sectional single-center observational study. A total of 98 PD patients were enrolled and underwent an MRI scan and a battery of neuropsychological evaluations. The brain volume was calculated using the online resource MRICloud. Brain atrophy was rated based on six visual rating scales. Correlation analysis was performed between visual rating scores and brain volume and clinical features. We found a significant negative correlation between the total scores of visual rating scores and quantitative brain volume, indicating that six visual rating scales reliably reflect whole brain atrophy in PD. Multiple linear regression-based analyses indicated severer non-motor symptoms were significantly associated with higher scores on the visual rating scales. Furthermore, we performed sample size calculations to evaluate the superiority of visual rating scales; the result show that using total scores of visual rating scales as an outcome measure, sample sizes for differentiating cognition injury require significantly fewer subjects (n = 177) compared with using total brain volume (n = 2524). Our data support the use of the total visual rating scores rather than quantitative brain volume as a biomarker for monitoring cerebral atrophy.

The Advances of the Structure and Function of Indoleamine 2, 3- dioxygenase 1 and Its Inhibitors.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is the only rate-limiting enzyme outside the liver that catalyzes the oxidation and cracking of indole rings in the tryptophan along the kynurenine pathway (KP). The overactivation of IDO1 is closely related to the pathogenesis of various human immune and neurological diseases. As an important target for the treatment of many human serious diseases, including malignant tumors, the development of IDO1 inhibitors is of great practical significance. In this work, the structure and function of IDO1 both are summarized from the aspects of the signal pathway, catalytic mechanism, structural biology, and so on. Moreover, the current development status of IDO1 inhibitors is also systematically reviewed, which provides assistance for anti-cancer drug design based on the structure of receptors.

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.

Comparative study of pronator teres branch transfer and brachialis motor branch transfer to the anterior interosseous nerve to treat lower brachial plexus injury in rats.

Distal nerve transfer is used to treat lower brachial plexus palsy, but outcome series on these transfer procedures following lower plexus injuries are sparse. The objective of this study is to compare treatment outcomes after nerve transfer using the brachialis motor branch (BMB) versus that using the pronator teres motor branch (PTMB). One hundred twenty adult rats with C8T1 nerve root avulsion were randomly divided into three groups (40 each): A: BMB transfer to the anterior interosseous nerve (AIN), B: PTMB transfer to the AIN, and C: no repair. Electrophysiological examination result, muscle tension test result, muscle weight and muscle fiber cross-sectional area of the flexor digitorum profundus and flexor pollicis longus, and number of myelinated nerve fibers in the AIN were compared among the groups to evaluate the treatment outcome. Nerve regeneration and muscle recovery in group B was better than those in group A at 4 and 8 weeks postoperatively (P < 0.05). There was no significant difference in the myelinated nerve fibers in groups A and B at 12 and 16 weeks postoperatively. The rats in group B showed greater and more significant improvement in other measured values than those in group A (P < 0.05). In conclusion, the PTMB seems a better donor nerve than the BMB for distal nerve transfer to treat lower brachial plexus injury according to the electrophysiological and histological examination in this rat study.

An Overview of Computational Tools of Nucleic Acid Binding Site Prediction for Site-specific Proteins and Nucleases.

Understanding the interaction mechanism of proteins and nucleic acids is one of the most fundamental problems for genome editing with engineered nucleases. Due to some limitations of experimental investigations, computational methods have played an important role in obtaining the knowledge of protein-nucleic acid interaction. Over the past few years, dozens of computational tools have been used for identification of nucleic acid binding site for site-specific proteins and design of site-specific nucleases because of their significant advantages in genome editing. Here, we review existing widely-used computational tools for target prediction of site-specific proteins as well as off-target prediction of site-specific nucleases. This article provides a list of on-line prediction tools according to their features followed by the description of computational methods used by these tools, which range from various sequence mapping algorithms (like Bowtie, FetchGWI and BLAST) to different machine learning methods (such as Support Vector Machine, hidden Markov models, Random Forest, elastic network and deep neural networks). We also make suggestions on the further development in improving the accuracy of prediction methods. This survey will provide a reference guide for computational biologists working in the field of genome editing.