Toe stimulation improves tactile perception of the genitals.

The human body is represented in a topographic pattern in the primary somatosensory cortex (S1), and genital representation is displaced below the toe representation. However, the relationship between the representation of the genitals and toe in S1 remains unclear. In this study, tactile stimulation was applied to the big toe in healthy subjects to observe changes in tactile acuity in the unstimulated genital area, abdomen, and metacarpal dorsal. Then tactile stimulation was applied to the right abdomen and metacarpal dorsal to observe changes in tactile acuity in bilateral genitals. The results revealed that tactile stimulation of the big toe led to a reduction in the 2-point discrimination threshold (2PDT) not only in the stimulated big toe but also in the bilateral unstimulated genitals, whereas the bilateral abdomen and metacarpal dorsal threshold remained unchanged. On the other hand, tactile stimulation of the abdomen and metacarpal dorsal did not elicit 2-point discrimination threshold changes in the bilateral genitals. Cortical and subcortical mechanisms have been proposed to account for the findings. One explanation involves the intracortical interaction between 2 adjacent representations. Another possible explanation is that the information content of a specific body part is broadly distributed across the S1. Moreover, exploring the links between human behaviors and changes in the cerebral cortex is of significant importance.

Gastrointestinal symptoms of long COVID-19 related to the ectopic colonization of specific bacteria that move between the upper and lower alimentary tract and alterations in serum metabolites.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) outbreak, many COVID-19 variants have emerged, causing several waves of pandemics and many infections. Long COVID-19, or long-term sequelae after recovery from COVID-19, has aroused worldwide concern because it reduces patient quality of life after rehabilitation. We aimed to characterize the functional differential profile of the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. METHODS: We prospectively collected oral, fecal, and serum samples from 983 antibiotic-naïve patients with mild COVID-19 and performed a 3-month follow-up postdischarge. Forty-five fecal and saliva samples, and 25 paired serum samples were collected from patients with gastrointestinal symptoms of long COVID-19 at follow-up and from healthy controls, respectively. Eight fecal and saliva samples were collected without gastrointestinal symptoms of long COVID-19 at follow-up. Shotgun metagenomic sequencing of fecal samples and 2bRAD-M sequencing of saliva samples were performed on these paired samples. Two published COVID-19 gut microbiota cohorts were analyzed for comparison. Paired serum samples were analyzed using widely targeted metabolomics. RESULTS: Mild COVID-19 patients without gastrointestinal symptoms of long COVID-19 showed little difference in the gut and oral microbiota during hospitalization and at follow-up from healthy controls. The baseline and 3-month samples collected from patients with gastrointestinal symptoms associated with long COVID-19 showed significant differences, and ectopic colonization of the oral cavity by gut microbes including 27 common differentially abundant genera in the Proteobacteria phylum, was observed at the 3-month timepoint. Some of these bacteria, including Neisseria, Lautropia, and Agrobacterium, were highly related to differentially expressed serum metabolites with potential toxicity, such as 4-chlorophenylacetic acid, 5-sulfoxymethylfurfural, and estradiol valerate. CONCLUSIONS: Our study characterized the changes in and correlations between the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. Additionally, our findings reveal that ectopically colonized bacteria from the gut to the oral cavity could exist in long COVID-19 patients with gastrointestinal symptoms, with a strong correlation to some potential harmful metabolites in serum.

LINC01089 inhibits the progression of cervical cancer via inhibiting miR-27a-3p and increasing BTG2.

BACKGROUND: Increasing evidence confirms that long non-coding RNA (lncRNA) has a vital impact on the procession of cervical cancer (CC). The present study aimed to investigate the clinical significance of LINC01089 in CC, as well as explore its biological functions and potential molecular mechanisms. METHODS: A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to investigate the expression of LINC01089 and miR-27a-3p in CC cells and tissues. Analysis of the correlation between the expression level of LINC01089 and the clinical pathological parameters of CC was then conducted. The human CC cell lines HeLa and SiHa were utilized for transfection to establish a gain-of-function model and loss-of-function models. Western blotting and a qRT-PCR were performed to detect B-cell translocation gene-2 (BTG2) expression in CC cells. Cell counting kit (CCK)-8 and 5-bromo-2-deoxyuridine (BrdU) assays were performed to detect the proliferation of CC cells. The transwell method was employed to evaluate the migration and invasion of CC cells. The interactions between LINC01089 and miR-27a-3p were verified by bioinformatics, a dual luciferase reporter gene experiment and a RNA immunoprecipitation experiment, respectively. RESULTS: The expression of LINC01089 in CC was markedly down-regulated. The low expression of LINC01089 in CC was closely associated with a larger tumor size and positive lymph node metastasis. Moreover, overexpression of LINC01089 impeded the proliferation and metastasis of CC cells, whereas knockdown of LINC01089 had the opposite biological functions. In terms of mechanism, LINC01089 could sponge miR-27a-3p and indirectly up-regulate BTG2 expression. CONCLUSIONS: LINC01089, as a tumor suppressor, impedes the development of CC by targeting miR-27a-3p to up-regulate BTG2 expression.

Serum HBV RNA Dynamic and Drug Withdrawal Predictor Value in Patients With Chronic HBV Infection on Long-term Nucleos(t)ide Analogue (NA) Therapy.

AIMS: This study aimed to investigate the dynamic pattern of serum hepatitis B virus (HBV) RNA in chronic hepatitis B (CHB) patients on long-term nucleos(t)ide analogue (NA) therapy and evaluate predictor value of end-of-treatment (EOT) serum HBV RNA status on drug-withdrawal durability. METHODS: We carried out a real-life cohort study of 326 CHB patients on NA treatment between February 12, 2016 and February 21, 2018. Thirty of these patients discontinued NA treatment after enrollment, and were included in 2-year off-therapy follow-up. Serum HBV RNA levels were determined using the RNA simultaneous amplification testing method. RESULTS: Both serum HBV RNA and DNA levels declined significantly in long-term antiviral progress. When the treatment duration was longer than 3 years, the undetectable rates of HBV RNA and DNA were 55.10% and 97.0%, respectively. The serum HBV RNA-negative rate was 39.5%. The cumulative 2-year off-therapy viral and clinical relapse rate was 40.56%; 95% confidence interval (95% CI), 21.51-59.61 and 31.31%; 95% CI, 11.32-51.29 in all patients, respectively. Patients with EOT hepatitis B surface antigen (HBsAg)≤1000 IU/mL plus HBV RNA negativity had a relatively lower cumulative 2-year off-therapy viral relapse rate (23.01%; 95% CI, 0.17-45.99). EOT HBsAg≤1000 IU/mL plus HBV RNA negativity showed obvious superiority for the EOT HBsAg≤1000 IU/mL single in drug withdrawal durability prediction, with better specificity (18.18% vs. 72.73%, P=0.03), and the positive predictive value and negative predictive value were 76.92% and 47.06%, respectively. CONCLUSIONS: In the long-term antiviral process, both serum HBV RNA and DNA levels declined significantly. EOT serum HBV RNA negativity was not an independent drug withdrawal marker, but can complement the HBsAg titer to monitor drug withdrawal in CHB patients on long-term NA therapy.

Association of TBXA2R, P2Y12 and ADD1 genes polymorphisms with ischemic stroke susceptibility: A metaanalysis.

BACKGROUND: Ischemic stroke is a common cause of death and disability throughout the world. We aimed to evaluate the association between polymorphisms in TBXA2R (rs4523, rs768963, rs1131882), P2Y12 (rs204693), ADD1 (rs4961) and risk of ischemic stroke. METHODS: A comprehensive retrieval with the databases of Pubmed, Embase, CENTRAL, CNKI and Wan fang data was conducted. The deadline was February 1, 2019. Pooled ORs and 95% CIs were calculated by using the Z-test. Heterogeneity between the included studies was tested using the I2 method. Begg's funnel plot and Egger's linear regression were used to evaluate the publication bias. Software STATA 12.0 (StataCorp, College Station, TX, USA) was used for the meta-analysis and 26 studies with 5,776 cases and 8,025 controls were included. RESULTS: The results indicated significantly higher risk of ischemic stroke associated with TBXA2R variant rs768963 in all genetic models (C vs T: OR=1.27, 95% CI=1.13-1.42, P.

Correction to: Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection.

Following publication of the original article [1].

Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection.

BACKGROUND: As an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection. METHODS: A total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58) [corrected]. The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed. RESULTS: Serum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between 'HBeAg-negative immune reactive' phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only. CONCLUSION: During the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the 'HBeAg-negative reactive' phase.

Professor FU Wenbin's experience of "acupuncture-moxibustion-consolidation" holistic idea in treatment of laryngeal herpes zoster with vocal cord paralysis. / 符文彬教授整合思维"一针二灸三巩固"模式治疗喉带状疱疹伴声带麻痹的临床经验.

This paper introduces professor FU Wenbin's clinical experience in the treatment of laryngeal herpes zoster with vocal cord paralysis, using the holistic mode of treatment, in which, acupuncture, moxibustion and consolidation regimens are integrated. Regarding the core pathogenesis of the disease, the invaded exogenous toxic heat is transformed into fire that flows to the throat. Soothing liver and releasing heat is the general principle of treatment, guiding the entire process of treatment. For acupuncture regimen, the filiform needling is used and the acupoint prescription is composed of Baihui (GV 20), Yintang (GV 24+), Lianquan (CV 23), the four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]), the group points for conducting qi back to the primary (Zhongwan [CV 12], Xiawan [CV 10], Qihai [CV 6] and Guanyuan [CV 4]), as well as bilateral Fengchi (GB 20), Wangu (GB 12) and Yifeng (TE 17). Besides, the pricking technique is delivered to the posterior wall of the pharynx for soothing the liver, regulating the spirit, reducing the heat and benefiting the throat. For the moxibustion regimen, moxibustion is applied to Fengchi (GB 20), Feishu (BL 13), the four-flower points (bilateral Geshu [BL 17] and Danshu [BL 19]), Shenshu (BL 23) and Mingmen (GV 4), which nourishes the spleen and stomach and reduces the heat pathogen through the heating action of moxibustion specially. In the stage of consolidation, the bloodletting and cupping technique is used at Xinshu (BL 15), Ganshu (BL 18) and Jianjing (GB 21) to eliminate the liver stagnation and the intradermal needling is delivered to sustain the needling stimulation and consolidate the therapeutic effect.

Development of novel prognostic models based on dynamic changes in risk factors for hepatitis B associated acute-on-chronic liver failure:a 10-year retrospective study.

Background/Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality, and early prediction is critical to reduce the deaths of ACLF patients. To date, however, the prognostic accuracy of current models for ACLF is unsatisfactory, particularly, in patients with hepatitis B virus (HBV) infection. This study aims to develop novel prognostic models based on the dynamic changes in variables to predict the short-term mortality of HBV-associated ACLF (HBV-ACLF). Methods: A retrospective cohort study was conducted, with the population comprised in whom ACLF was confirmed.319 patients were enrolled and their clinical data were collected on Days 1 and 7 following hospital admission. Univariate and multivariate analyses were performed to identify risk factors for 28 and 90-day mortality. The dynamic alterations in the risk factors were further analyzed, and Days 1 and 7 prognostic models were constructed. Receiver operating characteristic (ROC) analysis were used to identify and compared the predictors of prognosis among our model. Results: Univariate and multivariate analyses revealed significant risk factors at Days 1 and 7, which when combined with the clinically important parameters, were used to establish the Days 1 and 7 prognostic models. For 28-day mortality, the predictive accuracy of the Day 1 prognostic model was significantly higher than that of the albumin-bilirubin (ALBI) model. For 90-day mortality, the predictive accuracy of the Days 1 and 7 prognostic models was significantly higher than that of the Model of End-Stage Liver Disease (MELD), MELD-sodium (MELD-Na), and ALBI prognostic models. Conclusions: The prognostic models established in this study were superior to the existing prognostic scoring systems to accurately predict short-term mortality, and therefore, could be potential novel prognostic tools for HBV-ACLF.

[Interaction between depression and insomnia under acupuncture treatment: a secondary analysis of a randomized controlled trial].

OBJECTIVE: To explore the interaction between emotional and insomnia symptom improvement in comorbid depression and insomnia patients treated with optimized acupuncture. METHODS: A secondary analysis was conducted on a multicenter randomized controlled trial of acupuncture treatment for comorbid depression and insomnia. One hundred and forty patients with comorbid depression and insomnia were randomly assigned to an optimized acupuncture group (70 cases, 8 cases dropped out) and a conventional acupuncture group (70 cases, 8 cases dropped out). The patients in the conventional acupuncture group were treated with acupuncture at Yintang (GV 24+), Baihui (GV 20), bilateral Hegu (LI 4) and Taichong (LR 3); the patients in the optimized acupuncture group were treated with additional acupuncture at bilateral Lieque (LU 7), Zhaohai (KI 6), and intradermal needling was applied alternately at bilateral Xinshu (BL 15) and Danshu (BL 19), Shenshu (BL 23) and Anmian (Extra). Both groups received treatments twice a week for six weeks. The Hamilton depression scale-24 (HAMD-24) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment for both groups. Mediation analysis was used to assess the mesomeric effect of PSQI and HAMD-24 emotional factors, and latent profile analysis categorized patients into subgroups based on HAMD-24 scores, followed by between-group efficacy comparisons. RESULTS: The indirect effect of the optimized acupuncture on improving depression emotions through PSQI was 3.052 (95%CI [1.407, 4.697]), accounting for 77.5% of the total effect. Conversely, the indirect effect of improving PSQI through the optimized protocol on depression emotions was 0.479 (95%CI [0.024, 0.935]), representing 14.8% of the total effect. Latent profile analysis identified 3 categories based on emotional and insomnia symptoms, and statistically significant differences in efficacy favoring the optimized acupuncture protocol over the conventional acupuncture protocol were observed only in the subgroup with relatively mild depression and insomnia symptoms (PSQI: 95%CI [-10.98, -5.44], P<0.001; HAMD-24: 95%CI [-12.31, -3.73], P =0.001). CONCLUSION: The optimized acupuncture protocol primarily improves insomnia symptoms and further improves depression emotions. Its efficacy advantages are more evident in patients with mild symptoms compared with the conventional acupuncture protocol.

Pirfenidone alleviates chronic pancreatitis via suppressing the activation of pancreatic stellate cells and the M1 polarization of macrophages.

In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.

NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke.

The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation.

Nifuroxazide Prevents Chikungunya Virus Infection Both In Vitro and In Vivo via Suppressing Viral Replication.

Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.

Subregions of the fusiform gyrus are differentially involved in the attentional mechanism supporting visual mental imagery in depression.

BACKGROUND: Impaired visual mental imagery is an important symptom of depression and has gradually become an intervention target for cognitive behavioral therapy. METHODS: Our study involved a total of 25 healthy controls (HC) and 23 individuals with moderate depressive symptoms (MD). This study explored the attentional mechanism supporting visual mental imagery impairments in depression using the Vividness of Visual Imagery Questionnaire (VVIQ), attentional network test (ANT), and resting-state functional magnetic resonance imaging (rs-fMRI). The intrinsic activity of attention-related regions relative to those supporting visual mental imagery was identified in depression patients. In addition, a meta-analysis was used to describe the cognitive function related to this intrinsic activity. RESULTS: The global correlation (GCOR) of the right anterior fusiform gyrus (FG) was decreased in depression patients. Attention-related areas were concentrated in the right posterior FG; the anterior and posterior functional connectivity (FC) of the FG was decreased in depression patients. Graph theoretic analysis showed that the degree of the right anterior FG was decreased, the degree of the anterior insula was increased, and the negative connection between these two regions was strengthened in depression patients. In addition, the degree of the right anterior FG, the FC between the subregions of the right FG, and the FC between the right anterior FG and insula were correlated with VVIQ scores; however, this correlation was not significant in depression patients. The meta-analysis suggested that the changes in the anterior FG in depressed patients may stem from difficulties of semantic memory retrieval. CONCLUSION: The changed intrinsic activity of subregions of the FG relative to the semantic memory retrieval may be associated with visual mental imagery impairments in depression.

Tunable valley splitting in two-dimensional CrBr3/VSe2van der Waals heterostructure under strains and electric fields.

Valleytronics opens up fascinating opportunities for using the valley degree of freedom in information storage and quantum computation. Here, based on the first-principles calculations, we investigate the effects of biaxial strains and electric fields on the magnetic, electronic, and valleytronic properties of two-dimensional CrBr3/VSe2van der Waals (vdW) heterostructure consisting of two ferromagnetic monolayers. An interlayer magnetic phase transition from parallel to antiparallel is found when a compressive strain exceeds-2%or a tensile strain exceeds 4% is applied, while the interlayer magnetic configuration remains parallel under perpendicular electric fields. The valley splitting in the conduction bands is significantly enhanced by a compressive strain or an electric field pointing from the VSe2to the CrBr3layer. Specifically, a large valley splitting about 30.8 meV is obtained in the system with antiparallel interlayer magnetic configurations under a compressive strain of-4%, which is more than three times that of pristine CrBr3/VSe2heterostructure. Our findings provide new insights into the future valleytronic applications for two-dimensional magnetic vdW heterostructures.

Mesenchymal Stem Cell Therapy for Huntington Disease: A Meta-Analysis.

Objective: Mesenchymal stem cell (MSC) therapy has been explored in Huntington disease (HD) as a potential therapeutic approach; however, a complete synthesis of these results is lacking. We conducted a meta-analysis to evaluate the effects of MSCs on HD. Method: Eligible studies published before November 2022 were screened from Embase, PubMed, Web of Science, Medline, and Cochrane in accordance with PRISMA guidelines. ClinicalTrial.gov and the World Health Organization International Clinical Trials Registry Platform were also searched for registered clinical trials. The outcomes in rodent studies evaluated included morphological changes (striatal volume and ventricular volume), motor function (rotarod test, wire hang test, grip strength test, limb-clasping test, apomorphine-induced rotation test, and neuromuscular electromyography activity), cognition (Morris water maze test), and body weight. Result: The initial search returned 362 records, of which 15 studies incorporating 346 HD rodents were eligible for meta-analysis. Larger striatal and smaller ventricular volumes were observed in MSC-treated animals compared to controls. MSCs transplanted before the occurrence of motor dysfunction rescued the motor incoordination of HD. Among different MSC sources, bone marrow mesenchymal stem cells were the most investigated cells and were effective in improving motor coordination. MSC therapy improved muscle strength, neuromuscular electromyography activity, cortex-related motor function, and striatum-related motor function, while cognition was not changed. The body weight of male HD rodents increased after MSC transplantation, while that of females was not affected. Conclusion: Meta-analysis showed a positive effect of MSCs on HD rodents overall, as reflected in morphological changes, motor coordination, muscle strength, neuromuscular electromyography activity, cortex-related motor function, and striatum-related motor function, while cognition was not changed by MSC therapy.

[Effects of electroacupuncture on the expression of serum exosomes and pro-inflammatory factors in spinal cord of rats with spinal cord injury].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the morphology and microstructure of spinal cord tissue, the expression of serum exosomes, and the pro-inflammatory factors interleukin (IL)-1ß and IL-6 in spinal cord of rats with spinal cord injury (SCI), so as to explore the underlying mechanism of EA in the treatment of SCI. METHODS: Twenty-four female Wistar rats were randomly divided into sham operation group, model group, EA group, EA+GW4869 group, with 6 rats in each group. The SCI model was established by impinging spinal cord at T10 with a hammer, while the vertebral lamina was only opened without impingement for rats in sham operation group. Rats in EA group received EA intervention at "Jiaji"(EX-B7) acupoints at bilateral T9 and T10 (0.4-0.6 mA, 100 Hz), 3 h after modeling, once a day, for 7 concecutive days. Besides the treatment as EA group, rats in the EA+GW4869 group received injection of exosome inhibitor GW4869(200 µL, 300 µg/mL) once every 2 days from the day before modeling. Motor function of hind limbs of rats was evaluated using BBB scores. The histopathological changes of spinal cord were observed under light mircoscope after H.E. staining. Microstructure of spinal cord was observed and extracted serum exosomes were identified by using transmission electron microscopy. The expression of exosome marker proteins in serum exosomes, the levels of IL-1ß and IL-6 in spinal cord were detected by Western blot. RESULTS: H.E. stanining showed severe tissue looseness, inflammatory cell infiltration, cellular hydropic degeneration in spinal cord of the model group, which were relatively milder in the EA and EA+GW4869 groups. Under transmission electron microscopy, there were nerve fiber disintegration, myelin sheath structure dispersion, axonal atrophy with submembrane edema and widened space, and mitochondrial swelling in spinal cord of rats in the model group, with the lesions in EA group milder than EA+GW4869 group, which were both moderate. Typical exosomes were detected by transmission electron microscope in the extracted serum of rats in each group after ultracentrifugation. Compared with the sham operation group, the motor function scores was significantly decreased (P<0.01), the expression of IL-6 and IL-1ß in the spinal cord was significantly increased (P<0.01), while the expression of serum exosome marker protein CD81 was slightly increased in rats of the model group. Compared with the model group, the motor function scores was significantly increased (P<0.01), the expression of IL-6 and IL-1ß in the spinal cord was significantly decreased (P<0.01) in rats of the EA and EA+GW4869 group, while the expression of serum CD81 protein was slightly increased in rats of the EA group. Compared with the EA+GW4869 group, the expression of IL-6 and IL-1ß in the spinal cord was significantly decreased (P<0.01), while the expression of serum CD81 protein was slightly increased in rats of the EA group. However, there was no significance in expression of CD81 between each group mentioned above. CONCLUSION: EA can promote the secretion of serum exosomes and inhibit the expression of pro-inflammatory cytokines IL-6 and IL-1ß, so as to improve the microenvironment of injured spinal cord and SCI.

Efficacy and safety of molnupiravir in patients with Omicron variant vaccine breakthrough COVID-19 infection: a randomized, controlled trial.

Introduction: Randomized, controlled trials of molnupiravir in real-world use during the Omicron wave are scarce. The frequency of hospitalization and death is low, so further research is needed to confirm the virological efficacy of molnupiravir. Methods: A single-center, randomized, controlled clinical trial was conducted, and 111 hospitalized coronavirus disease 2019 (COVID-19) patients were randomly assigned at a ratio of 1:1. Fifty-three patients in the molnupiravir group were administered 800 mg of molnupiravir twice daily for 5 days in addition to the standard therapy, and 58 patients in the control group only received the standard therapy in accordance with local guidelines. The antiviral effect and adverse events were evaluated during the follow-up. Results: The median viral clearance time in the molnupiravir group was significantly shorter than that in the control group (p = 0.003). Furthermore, patients who started molnupiravir therapy within 3 days had significantly shorter viral clearance time than the controls (p = 0.003). In the vaccinated subgroup, molnupiravir therapy was also associated with a shorter viral clearance time (p = 0.003). A total of three adverse events, which were minor, were reported in the molnupiravir group. One of the patients had mild liver function abnormalities, and all of them were resolved without intervention. However, the remission time was similar between the two tested groups. Conclusion: Molnupiravir exhibited good viral replication inhibitor efficacy in patients with Omicron variant vaccine breakthrough COVID-19 infection. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200059796].