DCC in the cerebral cortex is required for cognitive functions in mouse.

Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between deleted in colorectal cancer (DCC) and SZ. Previous study has shown a lowered expression of DCC in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of DCC statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of DCC in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI). Critically, the defective sensorimotor gating could be restored by olanzapine, an antipsychotic drug. Furthermore, we found that the levels of p-AKT and p-GSK3α/ß were decreased, which was responsible for impaired PPI in the DCC-deficient mice. Finally, the DCC-deficient mice also displayed reduced spine density of pyramidal neurons and disturbed delta-oscillations. Our data, for the first time, identified and explored downstream substrates and signaling pathway of DCC which supports the hypothesis that DCC is a SZ-related risky gene and when defective, may promote SZ-like pathogenesis and behavioral phenotypes in mice.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

Optimal shrinkage denoising breaks the noise floor in high-resolution diffusion MRI.

The spatial resolution attainable in diffusion magnetic resonance (MR) imaging is inherently limited by noise. The weaker signal associated with a smaller voxel size, especially at a high level of diffusion sensitization, is often buried under the noise floor owing to the non-Gaussian nature of the MR magnitude signal. Here, we show how the noise floor can be suppressed remarkably via optimal shrinkage of singular values associated with noise in complex-valued k-space data from multiple receiver channels. We explore and compare different low-rank signal matrix recovery strategies to utilize the inherently redundant information from multiple channels. In combination with background phase removal, the optimal strategy reduces the noise floor by 11 times. Our framework enables imaging with substantially improved resolution for precise characterization of tissue microstructure and white matter pathways without relying on expensive hardware upgrades and time-consuming acquisition repetitions, outperforming other related denoising methods.

Application of computer-aided detection for NCCN-based follow-up recommendation in subsolid nodules: Effect on inter-observer agreement.

RATIONALE AND OBJECTIVES: Computer-aided detection (CAD) of pulmonary nodules reduces the impact of observer variability, improving the reliability and reproducibility of nodule assessments in clinical practice. Therefore, this study aimed to assess the impact of CAD on inter-observer agreement in the follow-up management of subsolid nodules. MATERIALS AND METHODS: A dataset comprising 60 subsolid nodule cases was constructed based on the National Cancer Center lung cancer screening data. Five observers independently assessed all low-dose computed tomography scans and assigned follow-up management strategies to each case according to the National Comprehensive Cancer Network (NCCN) guidelines, using both manual measurements and CAD assistance. The linearly weighted Cohen's kappa test was used to measure agreement between paired observers. Agreement among multiple observers was evaluated using the Fleiss kappa statistic. RESULTS: The agreement of the five observers for NCCN follow-up management categorization was moderate when measured manually, with a Fleiss kappa score of 0.437. Utilizing CAD led to a notable enhancement in agreement, achieving a substantial consensus with a Fleiss kappa value of 0.623. After using CAD, the proportion of major and substantial management discrepancies decreased from 27.5% to 15.8% and 4.8% to 1.5%, respectively (p < 0.01). In 23 lung cancer cases presenting as part-solid nodules, CAD significantly elevates the average sensitivity in detecting lung cancer cases presenting as part-solid nodules (overall sensitivity, 82.6% vs. 92.2%; p < 0.05). CONCLUSION: The application of CAD significantly improves inter-observer agreement in the follow-up management strategy for subsolid nodules. It also demonstrates the potential to reduce substantial management discrepancies and increase detection sensitivity in lung cancer cases presenting as part-solid nodules.

Application of combined preoperative indocyanine green lymphography and ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer.

BACKGROUND: This study aimed to investigate the value of preoperative indocyanine green (ICG) lymphography combined with ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer. METHODS: A total of 29 patients who were admitted to the breast surgery department of our hospital from July 2019 to May 2021 were included in this study. All patients received preoperative reverse lymphography and ultrasonography for low-pressure vein in lymphedema surgery. Three arm circumferences were measured before surgery, 6 months after surgery, and 12 months after surgery for comparison with the healthy limb at the same time. RESULTS: Arm circumference at 12 months after surgery was significantly different from those at the preoperative period and 6 months after surgery (P < 0.05). However, this parameter after surgery was still significantly higher than that of the healthy limb (P < 0.05). CONCLUSIONS: The application of preoperative ICG lymphography combined with ultrasonography for low-pressure vein localization before surgery can greatly shorten operation duration by reducing the number of ineffective incisions and improving the probability of vein-lymphatic vessel matching, while ensuring the postoperative efficacy for patients.

Application of brain-computer interface technology based on electroencephalogram in upper limb motor function rehabilitation of stroke patients / 中国组织工程研究

BACKGROUND:Current rehabilitation programs are effective in treating post-stroke sequelae,but the treatment cycle is long and the labor cost is high.Brain-computer interface technology can be used for the treatment of post-stroke patients by extracting signals from the brain's neural activity through special equipment and converting this signal into commands that can be recognized by a computer. OBJECTIVE:To analyze and summarize the application of brain-computer interface technology in the upper limb motor function rehabilitation of stroke patients in recent years and to explore the clinical value of brain-computer interface technology in the upper limb function rehabilitation of stroke patients. METHODS:CNKI and PubMed were retrieved for relevant literature published from 2000 to 2022.The keywords were"stroke,electroencephalogram,brain-computer interface,upper limb,virtual reality technology,functional electrical stimulation,exoskeleton"in Chinese and"stroke,brain-computer interface,computer assistance,upper limb,virtual reality technology,functional electrical stimulation,exoskeleton"in English. RESULTS AND CONCLUSION:The brain-computer interface has shown promise for the restoration of upper limb motor function in stroke patients and has been shown to produce results that are unattainable with conventional treatments,and is well worth further research and promotion,but the mechanisms have not been fully elucidated.Also the ability to accurately decode all degrees of freedom of upper limb movements to provide flexible and natural control remains a challenge from the perspective of brain-computer interface systems that capture electroencephalogram signals from patients.Future research should focus on clarifying the specific neural mechanisms by which brain-computer interface technology facilitates upper limb motor recovery after stroke and identifying rehabilitation options such as brain-computer interfaces combined with external devices to facilitate upper limb motor function recovery in stroke patients.

Discussion on the Mechanism of Jianpi Xiaoai Prescription in the Treatment of Colorectal Cancer Based on UPLC-Q-TOF-MS Combined with Network Pharmacology and Experimental Verification / 中国中医药信息杂志

Objective To explore the active components of Jianpi Xiaoai Prescription and its mechanism in the treatment of colorectal cancer(CRC).Methods UPLC-Q-TOF-MS technology was used to identify the chemical components of Jianpi Xiaoai Prescription;Active components and target proteins were screened through TCMSP and SwissTargetPrediction databases;STRING database was used for protein interaction analysis;The GeneCards database was used to screen CRC-related targets;DAVID database was used for GO and KEGG pathway enrichment analysis;Molecular docking verification of main active components and key targets was conducted.A rat model of CRC was constructed,and the effect of Jianpi Xiaoai Prescription on key targets of CRC-related pathways in rats was verified by Western blot.Results Totally 35 active components of Jianpi Xiaoai Prescription,617 potential targets,and 325 intersected with CRC-related targets were obtained.The enrichment analysis of active component targets showed that the main enrichments were PI3K-Akt signaling pathway,EGFR tyrosine kinase inhibitors signaling pathway,T cell receptor signaling pathway,VEGF signaling pathway and other related pathways.13 key active components and 6 key proteins of EGFR,SRC,CA2,CA12,CYP19A1 and MAPK3 were obtained in Jianpi Xiaoai Prescription.The results of Western blot experiments showed that Jianpi Xiaoai Prescription could significantly reduce the protein expression levels of SRC and EGFR in rat CRC samples.Conclusion The active component in Jianpi Xiaoai Prescription may exert anti CRC cell proliferation,invasion,and metastasis effects by regulating EGFR,SRC with multiple targets and pathways.

Causal Association Between Omega-3 Fatty Acids and Risk of Breast Cancer: A Mendelian Randomization Study / 肿瘤防治研究

Objective To explore the causal relationship between Omega-3 fatty acids and the risk of breast cancer via Mendelian randomization analysis. Methods Analysis was conducted on data from genome-wide association studies (GWASs) on Omega-3 fatty acids and breast cancer. The selected instrumental variables (IVs) comprised genetic loci associated with Omega-3 fatty acids. Various Mendelian randomization analysis methods, including inverse-variance weighted (IVW) method, MR–Egger regression analysis, weighted median, simple models, and weighted models, were used to evaluate the causal relationship between Omega-3 fatty acids and the risk of breast cancer. Results A total of 47 single-nucleotide polymorphisms strongly associated with Omega-3 fatty acids were selected as IVs. The analysis methods, including IVW method, revealed no causal relationship between Omega-3 fatty acids and the risk of breast cancer (P>0.05). Analysis methods, such as MR-Egger regression analysis, did not detect significant gene-level pleiotropy (P=0.319), which indicates the high sensitivity and robustness of analysis results. Conclusion The findings of this study suggest the absence of a causal relationship between Omega-3 fatty acids and the risk of breast cancer.

Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.

The apolipoprotein E ɛ4 allele (APOE4) is universally acknowledged as the most potent genetic risk factor for Alzheimer's disease (AD). APOE4 promotes the initiation and progression of AD. Although the underlying mechanisms are unclearly understood, differences in lipid-bound affinity among the three APOE isoforms may constitute the basis. The protein APOE4 isoform has a high affinity with triglycerides and cholesterol. A distinction in lipid metabolism extensively impacts neurons, microglia, and astrocytes. APOE4 carriers exhibit phenotypic differences from non-carriers in clinical examinations and respond differently to multiple treatments. Therefore, we hypothesized that phenotypic classification of AD patients according to the status of APOE4 carrier will help specify research and promote its use in diagnosing and treating AD. Recent reviews have mainly evaluated the differences between APOE4 allele carriers and non-carriers from gene to protein structures, clinical features, neuroimaging, pathology, the neural network, and the response to various treatments, and have provided the feasibility of phenotypic group classification based on APOE4 carrier status. This review will facilitate the application of APOE phenomics concept in clinical practice and promote further medical research on AD.

Ultrasound-guided extracorporeal shock wave lithotripsy with minimal x-ray exposure prevented genitourinary tract injury patients with urolithiasis in Taiwan.

BACKGROUND: This study investigated the use of ultrasound-guided extracorporeal shock wave lithotripsy (ESWL) to break stones in the genitourinary tract and prevent genitourinary injury. Our goals were to achieve accurate focusing and minimal X-ray exposure for the benefit of the patients. METHODS: The LiteMed LM-9200 lithotripter with ultrasonography and fluoroscopy was used for two different procedures: autoaimed and autoperiodical. These procedures enabled dual focusing on stone localization and tracking. RESULTS: Out of 108 patients who underwent autoperiodical procedures, 29 had no gross hematuria. Among the 335 patients who received autoaimed procedures, 194 had no gross hematuria. The average duration of X-ray exposure during autoperiodical and autoaimed procedures was 120 and 50 s, respectively. CONCLUSION: The ultrasound-guided ESWL with minimal X-ray exposure was found to be useful in treating genitourinary upper-tract urolithiasis in the autoaimed procedure. Patients who underwent the autoaimed procedure experienced less gross hematuria compared to those who underwent the autoperiodical procedure.

Influenza vaccination is associated with lower risk of renal cell carcinoma among chronic kidney disease patients: a population-based cohort study.

Background: Chronic kidney disease (CKD) patients possess a higher risk for renal cell carcinoma (RCC) possibly because of related underlying inflammation and immune dysregulation. In the current population-based cohort study, we evaluate the effects of influenza vaccination on RCC among CKD patients. Methods: We analysed the vaccinated and unvaccinated CKD patients (≥55 years of age) identified from the Taiwan National Health Insurance Database. Propensity score matching was used to reduce the selection bias. Subgroup analyses based on comorbid conditions, dialysis status and vaccinated dosages were also conducted. Results: The incidence of RCC decreased significantly in the vaccinated compared with unvaccinated group {unadjusted hazard ratio [HR] 0.50 [95% confidence interval (CI) 0.31-0.81], P < .01; adjusted HR 0.46 [95% CI 0.28-0.75], P < .01}. Such protective effects of influenza vaccination were noted significantly among those ≥75 years of age [unadjusted HR 0.29 (95% CI 0.12-0.74), P < .01; adjusted HR 0.22 (95% CI 0.08-0.58), P < .01]. A reverse association was noted between the total number of vaccinations and RCC events in both unadjusted and adjusted models. The Kaplan-Meier estimates of the RCC events showed significantly higher free survival rates in the vaccinated as compared with the unvaccinated patients (logrank P = .005). Conclusion: This population-based cohort study found a significant inverse relationship between influenza vaccination and the risk of RCC in CKD patients and the protective effects were more prominent in patients >75 years of age. A possible relation exists between the total number of vaccinations and RCC events. Future randomized clinical and basic studies will be needed to prove these findings and underlying pathophysiological mechanisms.

Enabling brain-wide mapping of directed functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression.

Layer-dependent functional magnetic resonance imaging (fMRI) offers a compelling avenue for investigating directed functional connectivity (FC). To construct a comprehensive map of brain-wide directed FC, several technical criteria must be met, including sub-mm spatial resolution, adequate temporal resolution, functional sensitivity, global brain coverage, and high spatial specificity. Although gradient echo (GE)-based echo planar imaging (EPI) is commonly used for rapid fMRI acquisition, it faces significant challenges due to the draining-vein effect, particularly when utilizing blood oxygen level-dependent (BOLD) contrast. In this study, we mitigated this effect by incorporating velocity-nulling (VN) gradients into a GE-BOLD fMRI sequence, opting for a 3T magnetic field strength over 7T. We also integrated several advanced techniques, such as simultaneous multi-slice (SMS) acceleration and NORDIC denoising, to enhance temporal resolution, spatial coverage, and signal sensitivity. Collectively, the VN fMRI method exhibited notable spatial specificity, as evidenced by the identification of double-peak activation patterns within the primary motor cortex (M1) during a finger-tapping task. Additionally, the technique demonstrated BOLD sensitivity in the lateral geniculate nucleus (LGN). Furthermore, our VN fMRI technique displayed superior robustness when compared to conventional fMRI approaches across participants. Our findings of directed FC elucidate several layer-specific functional relationships between different brain regions and align closely with existing literature. Given the widespread availability of 3T scanners, this technical advancement has the potential for significant impact across multiple domains of neuroscience research.

Mei-Gin Formula Ameliorates Obesity through Lipolysis, Fatty Oxidation, and Thermogenesis in High-Fat Diet-Induced Obese Rats.

Obesity is a metabolic dysfunction characterized by excessive body fat deposition as a consequence of an energy imbalance. Novel therapeutic strategies have emerged that are safe and have comparatively low side effects for obesity treatment. Functional foods and nutraceuticals have recently received a great deal of attention because of their components with the properties of antimetabolic syndrome. Based on our previous in vitro and in vivo investigations on anti-adipogenesis activity and improved body fat accumulation in serials, the combination of three ingredients (including bainiku-ekisu, black garlic, and Mesona procumbens Hemsl), comprising the Mei-Gin formula (MGF), was eventually selected as a novel inhibitor that exhibited preventive effects against obesity. Herein, we verify the anti-obesity effects of MGF in obese rats induced by a high-fat diet and discuss the potential molecular mechanisms underlying obesity development. Oral administration of MGF significantly suppressed the final body weight, weight change, energy and water intake, subcutaneous and visceral fat mass, liver weight, hepatic total lipids and triglycerides (TG), and serum levels of TG, triglycerides (TC), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (AST), uric acid, and ketone bodies and augmented fecal total lipids, TG, and cholesterol excretion in the high-dose MGF-supplemented groups. Furthermore, the corresponding lipid metabolic pathways revealed that MGF supplementation effectively increased lipolysis and fatty acid oxidation gene expression and attenuated fatty acid synthesis gene expression in the white adipose tissue (WAT) and liver and it also increased mitochondrial activation and thermogenic gene expression in the brown adipose tissue (BAT) of rats with obesity induced by a high-fat diet (HFD). These results demonstrate that the intake of MGF can be beneficial for the suppression of HFD-induced obesity in rats through the lipolysis, fatty oxidation, and thermogenesis pathway. In conclusion, these results demonstrate the anti-obesity efficacy of MGF in vivo and suggest that MGF may act as a potential therapeutic agent against obesity.

Rationale for white skin roll flap in unilateral cleft lip repair: A retrospective anthropometric measurement analysis.

BACKGROUND: Although the "white skin roll" of the lip is often considered a line, it is better defined as the subunit between the vermilion border and the upper lip horizontal groove. In many unilateral cleft lip repair techniques, this structure is approximated between both sides of the cleft without restoration. This study aimed to analyze the white skin roll height in patients with unilateral cleft lip. METHODS: This retrospective cohort study included 134 consecutive infants with unilateral cleft lip aged 3-6 months who underwent lip repair in a single institution between January 2019 and July 2021. White skin roll heights at the peak of the Cupid's bow on the non-cleft side (CPHIR), cleft medial element (CPHIL), and cleft lateral element (CPHIL') were measured, and differences in their averages were analyzed. RESULTS: The mean height was 1.70 ± 0.30 mm at CPHIR, 0.98 ± 0.33 mm at CPHIL, and 1.28 ± 0.32 mm at CPHIL.' The mean difference in height between CPHIR-CPHIL, CPHIR-CPHIL,' and CPHIL-CPHIL' groups was significant for each paired sample (p < 0.01). No difference was found between the complete and incomplete clefts or left and right clefts (p > 0.01). CONCLUSIONS: A significantly reduced mean height of the white skin roll was present more markedly on the cleft medial element than on the cleft lateral element. Therefore, we strongly support using a white skin roll flap on the cleft lateral element for unilateral cleft lip repair, embracing the concepts of subunits and lip contour lines.

Effects of enriched environment on the expression of ß-amyloid and transport-related proteins LRP1 and RAGE in chronic sleep-deprived mice.

Sleep plays an important role in the learning process and memory consolidation, and sleep deprivation (SD) leads to inadequate memory consolidation and plays an important role in brain development and plasticity. SD increases ß-amyloid levels while impairing cognitive function. We explored the effect of enriched environment (EE) on ß-amyloid and transporter protein LRP1 and receptor for advanced glycosylation end-products (RAGE) expression in chronic sleep deprived mice. We randomly divided mice into four groups (n = 10), the standard environment group (Ctrl group), the sleep deprivation group (SD group), the enriched environment intervention group (EE group), and the sleep deprivation plus environmental enrichment intervention group (SD + EE group). A modified multi-platform SD model was used to sleep deprive the mice for 19 h per day. Five hours of EE intervention was performed daily in the EE group and the SD + EE group, respectively. The behavioral measurements of mice were performed by Y-maze method and new object recognition; the expression levels of Aß1-42, LRP1, and RAGE in prefrontal cortex and hippocampus of mice were measured by immunofluorescence; the expression levels of LRP1 and RAGE in prefrontal cortex and hippocampus were detected by Western blot. The results showed that EE could effectively ameliorate the effects of SD on cognitive impairment, reduce SD induced Aß deposition, and decrease the expression of RAGE, while increase the expression of LRP1.

Moxibustion modulates working memory in patients with amnestic mild cognitive impairment: a functional magnetic resonance imaging study.

OBJECTIVE: To investigate the correlation between changes in brain activity associated with working memory and assessment scales of memory scores in amnestic mild cognitive impairment (aMCI) before and after moxibustion therapy. METHODS: aMCI patients were randomized into the moxibustion treatment (MT) group and the placebo moxibustion (PM) group. Each group received either moxibustion therapy or a placebo moxibustion for eight weeks. Neuropsychological performance and functional brain responses to a working memory task were assessed at baseline and at the end of treatment. Memory function was evaluated individually by the Rivermead behavioral memory test (RBMT), and working memory was assessed by the N-back task. RESULTS: Compared with the PM group, RBMT score changes were significant ( < 0.05). In the MT group, the accuracy of the N-back texts increased compared with those before the intervention. After moxibustion intervention, the right insula, postcentral gyrus, precentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, calcarine sulcus, posterior cingulate gyrus, middle frontal gyrus and anterior frontal gyrus were significantly activated (= 0.01, Cluster-level Family-Wise Error = 0.05). Pearson correlation analysis showed that the insula, lingual gyrus and posterior cingulate gyrus were associated with changes in N-back score. Spearman correlation analysis showed that the postcentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, and posterior cingulate gyrus were correlated with RBMT score changes. CONCLUSION: Moxibustion treatment improved memory in aMCI patients and was associated with the activation of the brain region of the insula, lingual gyrus, posterior cingulate gyrus, postcentral gyrus, superior temporal gyrus, and thalamus, which may be an important mechanism by which moxibustion improves the memory function.

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China.

BACKGROUND: Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China. METHODS: A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL. RESULTS: A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3-93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2-84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons. CONCLUSIONS: Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.

Pteropine orthoreoviruses use cell surface heparan sulphate as an attachment receptor.

Pteropine orthoreoviruses (PRVs) are an emerging group of fusogenic, bat-borne viruses from the Orthoreovirus genus. Since the isolation of PRV from a patient with acute respiratory tract infections in 2006, the zoonotic potential of PRV has been further highlighted following subsequent isolation of PRV species from patients in Malaysia, Hong Kong and Indonesia. However, the entry mechanism of PRV is currently unknown. In this study, we investigated the role of previously identified mammalian orthoreovirus (MRV) receptors, sialic acid and junctional adhesion molecule-1 for PRV infection. However, none of these receptors played a significant role in PRV infection, suggesting PRV uses a distinct entry receptor from MRV. Given its broad tissue tropism, we hypothesized that PRV may use a receptor that is widely expressed in all cell types, heparan sulphate (HS). Enzymatic removal of cell surface HS by heparinase treatment and genetic ablation of HS biosynthesis genes, SLC35B2, exostosin-1, N-deacetylase/N-sulfotransferase I and beta-1,3-glucuronyltransferase 3, significantly reduced infection with multiple genetically distinct PRV species. Replication kinetic of PRV3M in HS knockout cells revealed that HS plays a crucial role in the early phase of PRV infection. Mechanistic studies demonstrated that HS is an essential host-factor for PRV attachment and internalization into cells. To our knowledge, this is the first report on the use of HS as an attachment receptor by PRVs.

Feasibility and Toxicity of Interval-Compressed Chemotherapy in Asian Children and Young Adults with Sarcoma.

Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1200-2200 mg/m2) (VDC) alternating with a regimen of ifosfamide (9000 mg/m2) and etoposide (500 mg/m2) (IE), with filgrastim (5-10 mcg/kg/day) between cycles. Carboplatin (800 mg/m2) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15-24 days. Median nadirs (IQR) were neutrophil count, 134 (30-396) × 106/L at day 11 (10-12), recovery by day 15 (14-17) and platelet count, 35 (23-83) × 109/L at day 11 (10-13), recovery by day 17 (14-21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.