Causal relationship between gut microbiota and gastric cancer: A two­sample Mendelian randomization analysis.

The gut microbiota is associated with GC; however, the causal association between the gut microbiota and GC remains to be determined. The aim of the present study was to investigate the causal association between gut microbiota and gastric cancer (GC) from the perspective of Mendelian randomization (MR). The present study performed MR analysis using summary statistics from a genome-wide association study of the gut microbiome and GC. Inverse-variance weighted, MR-Egger and weighted median methods were used to investigate the causal relationship between gut microbiota and GC. Heterogeneity tests were performed using Cochrane's Q statistic. Horizontal polytropy was detected using Mendelian Randomization Pleiotropy RESidual Sum and Outlier were eliminated. Estimates from MR indicated that nine gut microorganism remained stable with regard to acceptance of heterogeneity and sensitivity methods. Among them, the genera Prevotella 7, Roseburia and Ruminococcaceae UCG014 were associated with an increased risk of GC; by contrast, the family Enterobacteriaceae, the genera Allisonella, Lachnospiraceae FCS020, Ruminococcaceae UCG004 and Ruminococcaceae UCG009, and the order Enterobacteriales decreased the risk of GC development. The present study demonstrated the potential importance of modulating the abundance of gut microbiota for the prevention and treatment of GC.

Repetitive peripheral magnetic stimulation combined with transcranial magnetic stimulation in rehabilitation of upper extremity hemiparesis following stroke: a pilot study.

OBJECTIVE: To investigate the effect of combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation on upper extremity function in subacute stroke patients. DESIGN: Pilot study. SUBJECTS: Subacute stroke patients. METHODS: Included patients were randomized into 3 groups: a central-associated peripheral stimulation (CPS) group, a central-stimulation-only (CS) group, and a control (C) group. The CPS group underwent a new paired associative stimulation (combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation), the CS group underwent repetitive transcranial magnetic stimulation, and the C group underwent sham stimulation. All 3 groups received physiotherapy after the stimulation or sham stimulation. The treatment comprised 20 once-daily sessions. Primary outcome was the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score, and secondary outcomes were the Barthel Index and Comprehensive Functional Assessment scores, and neurophysiological assessments were mainly short-interval intracortical inhibition. A 3-group (CPS, CS, C) × 2-time (before, after intervention) repeated measures analysis of variance was conducted to determine whether changes in scores were significantly different between the 3 groups. RESULTS: A total of 45 patients were included in the analysis. Between-group comparisons on the FMA-UE demonstrated a significant improvement (group × time interaction, F2,42 = 4.86; p = 0.013; C vs CS, p = 0.020; C vs CPS, p = 0.016; CS vs CPS, p = 0.955). Correlation analysis did not find any substantial positive correlation between changes in FMA-UE and short-interval intracortical inhibition variables (C, r = -0.196, p = 0.483; CS, r = -0.169, p = 0.546; CPS, r = -0.424, p = 0.115). CONCLUSION: This study suggests that the real-stimulus (CS and CPS) groups had better outcomes than the control (C) group. In addition, the CPS group showed a better trend in clinical and neurophysiological assessments compared with the CS group.

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a malignant clonal disease involving hematopoietic stem cells that is characterized by myeloid cell proliferation in bone marrow and peripheral blood, and the presence of the Philadelphia (Ph) chromosome with BCR-ABL fusion gene. Treatment of CML has dramatically improved since the advent of tyrosine kinase inhibitors (TKI). However, there are a small subset of CML patients who develop resistance to TKI. Mutations in the ABL kinase domain (KD) are currently recognized as the leading cause of TKI resistance in CML. In this review, we discuss the concept of resistance and summarize recent advances exploring the mechanisms underlying CML resistance. Overcoming TKI resistance appears to be the most successful approach to reduce the burden of leukemia and enhance cures for CML. Advances in new strategies to combat drug resistance may rapidly change the management of TKI-resistant CML and expand the prospects for available therapies.

Predictors of long-term decannulation in patients with disorders of consciousness.

Purpose: The predictors of tracheostomy decannulation in patients with disorders of consciousness (DOC) are not comprehensively understood, making prognosis difficult. The primary objective of this study was to identify predictors of tracheostomy decannulation in patients with disorders of consciousness (DOC). The secondary aim was to evaluate the feasibility and safety of the modified Evans blue dye test (MEBDT) in tracheostomized DOC patients. Methods: This retrospective study included all patients with disorders of consciousness (DOC) who underwent tracheostomy and were admitted between January 2016 and September 2022. Age, sex, etiology, initial Glasgow coma scale (GCS), initial Coma Recovery Scale-Revised (CRS-R), diagnosis of unresponsive wakefulness syndrome (UWS) or minimal consciousness state (MCS), MEBDT, initial modified Rankin scale (mRS), and initial Functional Oral Intake Scale (FOIS) were collected upon study enrollment. The relationship between clinical characteristics and cannulation status was investigated through a Cox regression model. Results: A total of 141 patients were included in the study. The average age of these patients was 52.5 ± 16.7 years, with 42 (29.8%) being women. During the study period, 86 subjects (61%) underwent successful decannulation. Univariate analysis revealed that decannulated patients exhibited a significantly better conscious state compared to those without decannulation (CRS-R: p < 0.001; GCS: p = 0.023; MCS vs. UWS: p < 0.001). Additionally, a negative modified Evans blue dye test (MEBDT) result was significantly associated with tracheostomy decannulation (p < 0.001). In the multivariate analysis, successful decannulation was associated with a higher level of consciousness (MCS vs. UWS, p < 0.001, HR = 6.694) and a negative MEBDT result (negative vs. positive, p = 0.006, HR = 1.873). The Kaplan-Meier analysis further demonstrated that MEBDT-negative patients and those in the MCS category had a higher probability of decannulation at 12 months (p < 0.001). Conclusion: The findings of this study indicate that a negative MEBDT result and a higher level of consciousness can serve as predictive factors for successful tracheostomy decannulation in DOC patients.

Transcriptome Responses to Different Environments in Intertidal Zones in the Peanut Worm Sipunculus nudus.

The peanut worm (Sipunculus nudus) is an important intertidal species worldwide. Species living in the same aquaculture area might suffer different environmental impacts. To increase knowledge of the molecular mechanisms underlying the response to environmental fluctuations, we performed a transcriptome analysis of S. nudus from different intertidal zones using a combination of the SMRT platform and the Illumina sequencing platform. (1) A total of 105,259 unigenes were assembled, and 23,063 unigenes were perfectly annotated. The results of the PacBio Iso-Seq and IIIumina RNA-Seq enriched the genetic database of S. nudus. (2) A total of 830 DEGs were detected in S. nudus from the different groups. In particular, 33 DEGs had differential expression in the top nine KEGG pathways related to pathogens, protein synthesis, and cellular immune response and signaling. The results indicate that S. nudus from different zones experience different environmental stresses. (3) Several DEGs (HSPA1, NFKBIA, eEF1A, etc.) in pathways related to pathogens (influenza A, legionellosis, measles, and toxoplasmosis) had higher expression in groups M and L. HSPA1 was clearly enriched in most of the pathways, followed by NFKBIA. The results show that the peanut worms from the M and L tidal flats might have suffered more severe environmental conditions. (4) Some DEGs (MKP, MRAS, and HSPB1) were upregulated in peanut worms from the H tidal flat, and these DEGs were mainly involved in the MAPK signaling pathway. These results indicate that the MAPK pathway may play a vital role in the immune response of the peanut worm to the effects of different intertidal flats. This study provides a valuable starting point for further studies to elucidate the molecular basis of the response to different environmental stresses in S. nudus.

Theta-burst transcranial magnetic stimulation for dysphagia patients during recovery stage of stroke: a randomized controlled trial.

BACKGROUND: The Theta-burst Transcranial Magnetic Stimulation (TBS) is an emerging modality of Repetitive Transcranial Magnetic Stimulation (rTMS). However, the efficacy of TBS on post-stroke recovery-stage patients with dysphagia remains unclear. AIM: To investigate the effect of intermittent theta burst stimulation (iTBS) and continuous theta burst stimulation (cTBS) in post-stroke dysphagia patients within the recovery stage. DESIGN: Randomized controlled double blinded trial. SETTING: Inpatient. POPULATION: Ninety patients with dysphagia after stroke within 1 to 6 months. METHODS: Patients were divided into the supratentorial group and the brainstem group, and both of groups were further divided into three subgroups, including the sham subgroups, the iTBS subgroups, and the cTBS subgroups. Each of subgroups received 30 min of traditional swallowing rehabilitation treatment every day for 4 weeks. In addition, the iTBS subgroups received iTBS over the cortex of the suprahyoid muscles on the affected hemisphere, the cTBS subgroups received cTBS on the unaffected hemisphere, and the sham subgroups received sham stimulation on unilateral hemisphere. Standardized swallowing assessment (SSA), Oral Motor Function Scale (OMFS) and fiberoptic endoscopic examination of swallowing (FEES) were assessed before and after treatments. RESULTS: In the supratentorial group, compared with the sham and cTBS subgroups, the iTBS subgroups showed significant improvement in SSA, OMFS, vocal folds movement, laryngeal sensation, and Rosenbek Penetration-Aspiration Scale (PAS) (P<0.05). In the brainstem group, compared with the sham subgroup, the iTBS subgroup significantly improved SSA, OMFS, Yale Pharyngeal Residue Severity Rating Scale (YPR-SRS) and PAS (P<0.05), and the cTBS subgroup significantly improved SSA, YPR-SRS and PAS (P<0.05). CONCLUSIONS: This study demonstrated that iTBS might be an effective stimulation pattern to improve the overall swallowing function whether in supratentorial stroke patients or brainstem stroke patients. CLINICAL REHABILITATION IMPACT: iTBS seems to be a promising approach for rehabilitation of overall swallowing function in post-stroke patients.

Effect and safety of C7 neurotomy at the intervertebral foramen in patients with chronic poststroke aphasia: a multicentre, randomised, controlled study protocol.

INTRODUCTION: Aphasia affects many stroke survivors; therefore, effective treatments are urgently needed. Preliminary clinical findings have suggested an association between contralateral C7-C7 cross nerve transfer and recovery from chronic aphasia. Randomised controlled trials supporting the efficacy of C7 neurotomy (NC7) are lacking. This study will explore the efficacy of NC7 at the intervertebral foramen for improving chronic poststroke aphasia. METHODS AND ANALYSIS: This study protocol reports a multicentre, randomised, assessor-blinded active-controlled trial. A total of 50 patients with chronic poststroke aphasia for over 1 year and with a aphasia quotient calculated by Western Aphasia Battery Aphasia Quotient (WAB-AQ) score below 93.8 will be recruited. Participants will be randomly assigned to 1 of 2 groups (25 individuals each) to receive NC7 plus intensive speech and language therapy (iSLT), or iSLT alone programme. The primary outcome is the change in Boston Naming Test score from baseline to the first follow-up after NC7 plus 3 weeks of iSLT or iSLT alone. The secondary outcomes include the changes in the WAB-AQ, Communication Activities of Daily Living-3, International Classification of Functioning, Disability and Health (ICF) speech language function, Barthel Index, Stroke Aphasic Depression Questionnaire-hospital version and sensorimotor assessments. The study will also collect functional imaging outcomes of naming and semantic violation tasks through functional MRI and electroencephalogram to evaluate the intervention-induced neuroplasticity. ETHICS AND DISSEMINATION: This study was approved by the institutional review boards of Huashan Hospital, Fudan University, and all participating institutions. The study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200057180.

Association between motoric cognitive risk syndrome and future falls among Chinese community-dwelling elderly: A nationwide cohort study.

BACKGROUND: Motoric Cognitive Risk syndrome (MCR), known as the predementia stage, is characterized by both subjective cognitive complaint (SCC) and slow gait. This study aimed to investigate the causal relationship between MCR, its components, and falls. METHODS: Participants aged ≥ 60 years were selected from China Health and Retirement Longitudinal Study. SCC was determined by participants' responses to the question "How would you rate your memory at present?" with "poor" being the indicative answer. Slow gait was defined as one standard deviation or more below age- and gender-appropriate mean values of gait speed. MCR was identified when both SCC and slow gait were presented. Future falls were investigated by the question "have you fallen down during follow-up until wave 4 in 2018?" Logistic regression analysis was performed to test the longitudinal association of MCR, its components and future falls during the following 3 years. RESULTS: Of 3748 samples in this study, the prevalence of MCR, SCC, and slow gait was 5.92%, 33.06%, and 15.21%, respectively. MCR increased the risk of falls during the following 3 years by 66.7% compared to non-MCR after controlling for covariates. In the fully adjusted models, with the healthy group as reference, MCR (OR = 1.519, 95%CI = 1.086-2.126) and SCC (OR = 1.241, 95%CI = 1.018-1.513), but not slow gait, increased the risk of future falls. CONCLUSIONS: MCR independently predicts future falls risk in the following 3 years. Measuring MCR can be a pragmatic tool for early identification of falls risk.

Identification of the novel HLA-C*01:02:86 allele in a Chinese individual.

HLA-C*01:02:86 has one synonymous nucleotide C > T change from HLA-C*01:02:01:01 at nucleotide 879 (residue 269 Proline).

Altered Spontaneous Brain Activity in Poststroke Aphasia: A Resting-State fMRI Study.

PURPOSE: Brain areas frequently implicated in language recovery after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying language restoration are still largely unclear. METHODS AND MATERIALS: In the present study, we investigated the brain function in 15 patients with poststroke aphasia and 30 matched control subjects by combining the regional homogeneity (ReHo) and amplitudes of low-frequency fluctuation (ALFF) analysis methods based on resting-state fMRI. RESULTS: Compared to the control subjects, the patients with aphasia exhibited increased ReHo and ALFF values in the ipsilateral perilesional areas and increased ReHo in the contralesional right middle frontal gyrus. CONCLUSIONS: The increased spontaneous brain activity in patients with poststroke aphasia during the recovery period, specifically in the ipsilateral perilesional regions and the homologous language regions of the right hemisphere, has potential implications for the treatment of patients with aphasia.

Phylogenetic analysis of Arthrospira strains from Ordos based on 16S rRNA.

To study the growth rate of different Arthrospira strains, three species of Arthrospira from Ordos alkaline lake, labeled as sp.DD, sp.ER, sp.FB, one species of Arthrospira from Hasu Sea in Hohhot, labeled as sp.HS, another purified strain labeled as sp.QD donated by the Ocean University of China had been collected. The first four need to be further isolated and purified in culture. The growth curves of all strains were plotted. Subsequently, 16S rRNA sequences were amplified and sequenced in an attempt to study taxonomic relationships. The results showed that the growth rate was increased in the first 9 days, and sp.DD had the highest growth rate. Analysis of the sequencing results revealed that sp.HS had 99.79% homology with Arthrospira platensis strain Sp-2, sp.DD had 99.69% homology with Arthrospira platensis FACHB834, sp.QD had 99.54% homology with Arthrospira platensis F3S, sp.ER had 99.79% homology with Arthrospira erdosensis 'Inner Mongolia', sp.FB had 99.74% homology with Arthrospira erdosensis 'Inner Mongolia'. Phylogenetic analysis indicated that sp.HS was closely related to Arthrospira platensis strain Sp-2; sp.DD and sp.QD had a close genetic relationship; sp.ER and sp.FB had a close genetic relationship. In conclusion, these findings provide a theoretical basis for the further development and reproduction of dominant algae species in Inner Mongolia through biological analysis of Arthrospira.

Effects of lactoferrin on intestinal flora of metabolic disorder mice.

To study the mechanism of lactoferrin (LF) regulating metabolic disorders in nutritionally obese mice through intestinal microflora. Twenty-one male C57BL/6 mice were randomly divided into 3 groups: control group, model group and LF treatment group. The mice in control group were fed with maintenance diet and drank freely. The mice in model group were fed with high fat diet and drank freely. The mice in LF treatment group were fed with high fat diet and drinking water containing 2% LF freely. Body weight was recorded every week. Visceral fat ratio was measured at week 12. Blood glucose and serum lipid level were detected by automatic biochemical analyzer. The gut microbiota of mice was examined using 16 s rRNA sequencing method. LF treatment significantly reduced the levels of visceral adipose ratio, blood glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol (LDL-C) in high-fat diet mice (p < 0.05). It can be seen that drinking water with 2% LF had a significant impact on metabolic disorders. At the same time, the Firmicutes/Bacteroidetes ratio(F/B) of LF treated mice was decreased. The abundance of Deferribacteres, Oscillibacter, Butyricicoccus, Acinetobacter and Mucispirillum in LF treatment group were significantly decreased, and the abundance of Dubosiella was significantly increased (p < 0.05). In the LF-treated group, the expression levels of glucose metabolism genes in gut microbiota were increased, and the expression levels of pyruvate metabolism genes were decreased. It can be seen that metabolic disorders were related to intestinal flora. In conclusion, LF regulates metabolic disorders by regulating intestinal flora.

Detection of an HLA-C*01 variant, HLA-C*01:212, in a Chinese individual.

HLA-C*01:212 differs from HLA-C*01:02:01:01 by two non-synonmous nucleotide changes at positions 368 and 379 in exon 3.

Identification of the novel allele HLA-B*13:157 by sequence-based typing.

HLA-B*13:157 has one nucleotide change from HLA-B*13:02:01:01 at nucleotide 323 changing Tyrosine to Phenylalanine at residue 84.

A novel HLA-C allele, HLA-C*15:244.

HLA-C*15:244 has one nucleotide change from HLA-C*15:05:01:01 at nucleotide 308 changing Arginine to Glutamine at residue 79.

Characterization of the novel allele HLA-B*35:251:02.

HLA-B*35:251:02 has one nucleotide change from HLA-B*35:22:01:01 at nucleotide 363 changing Serine to Arginine at residue 97.

Recognition of the HLA-A*11:398 allele in a Chinese patient and his sister.

HLA-A*11:398 has one nonsynonymous nucleotide change from HLA-A*11:01:01:01 at nucleotide 709, changing Isoleucine 213 to Valine.

Identification of the novel HLA-A*02:981 allele by sequencing-based typing.

One nucleotide replacement at position 728 of HLA-A*02:07:01 results in a novel allele, HLA-A*02:981.

Recognization of the HLA-A*24:516 allele in a Chinese patient and his daughter.

HLA-A*24:516 has one nucleotide change from HLA-A*24:02:01:01 at nucleotide 194 where Alanine (41) is changed to Glycine.