Application of ultrasonography in diagnosis and treatment of children with congenital muscular torticollis.

Congenital muscular torticollis (CMT) is a more common childcare disease, which belongs to muscle-skeletal system diseases, and is more common in newborns. The disease is mainly due to congenital contracture due to chest locks, which leads to asymmetric head and neck. For such diseases, clear diagnosis and treatment in the early days is an important way to improve the prognosis of children. Compared with X-ray film, CT, and MRI, ultrasound examination has the advantages of low examination cost, short time, and no exposure to radiation during the examination. Moreover, ultrasound examination can provide an objective basis for the clinical diagnosis and prognosis evaluation of CMT children. This article reviews the latest research progress of conventional ultrasound, color Doppler ultrasound, and ultrasound elastography in the clinical diagnosis of CMT children and assisting in the formulation of treatment plans.

Neutrophil-derived PAD4 induces citrullination of CKMT1 exacerbates mucosal inflammation in inflammatory bowel disease.

Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in infection and inflammatory diseases by facilitating the formation of neutrophil extracellular traps (NETs). However, the substrates of PAD4 and its exact role in inflammatory bowel disease (IBD) remain unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) and substrate citrullination mapping to decipher the role of PAD4 in intestinal inflammation associated with IBD. Our results demonstrated that PAD4 deficiency alleviated colonic inflammation and restored intestinal barrier function in a dextran sulfate sodium (DSS)-induced colitis mouse model. scRNA-seq analysis revealed significant alterations in intestinal cell populations, with reduced neutrophil numbers and changes in epithelial subsets upon PAD4 deletion. Gene expression analysis highlighted pathways related to inflammation and epithelial cell function. Furthermore, we found that neutrophil-derived extracellular vesicles (EVs) carrying PAD4 were secreted into intestinal epithelial cells (IECs). Within IECs, PAD4 citrullinates mitochondrial creatine kinase 1 (CKMT1) at the R242 site, leading to reduced CKMT1 protein stability via the autophagy pathway. This action compromises mitochondrial homeostasis, impairs intestinal barrier integrity, and induces IECs apoptosis. IEC-specific depletion of CKMT1 exacerbated intestinal inflammation and apoptosis in mice with colitis. Clinical analysis of IBD patients revealed elevated levels of PAD4, increased CKMT1 citrullination, and decreased CKMT1 expression. In summary, our findings highlight the crucial role of PAD4 in IBD, where it modulates IECs plasticity via CKMT1 citrullination, suggesting that PAD4 may be a potential therapeutic target for IBD.

Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysis.

BACKGROUND: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. METHODS: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10-8) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures. FINDINGS: Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases. INTERPRETATION: The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases. FUNDING: Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

Mycobacterium tuberculosis PE_PGRS45 (Rv2615c) Promotes Recombinant Mycobacteria Intracellular Survival via Regulation of Innate Immunity, and Inhibition of Cell Apoptosis.

Tuberculosis (TB), a bacterial infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is a significant global public health problem. Mycobacterium tuberculosis expresses a unique family of PE_PGRS proteins that have been implicated in pathogenesis. Despite numerous studies, the functions of most PE_PGRS proteins in the pathogenesis of mycobacterium infections remain unclear. PE_PGRS45 (Rv2615c) is only found in pathogenic mycobacteria. In this study, we successfully constructed a recombinant Mycobacterium smegmatis (M. smegmatis) strain which heterologously expresses the PE_PGRS45 protein. We found that overexpression of this cell wall-associated protein enhanced bacterial viability under stress in vitro and cell survival in macrophages. MS_PE_PGRS45 decreased the secretion of pro-inflammatory cytokines such as IL-1ß, IL-6, IL-12p40, and TNF-α. We also found that MS_PE_PGRS45 increased the expression of the anti-inflammatory cytokine IL-10 and altered macrophage-mediated immune responses. Furthermore, PE_PGRS45 enhanced the survival rate of M. smegmatis in macrophages by inhibiting cell apoptosis. Collectively, our findings show that PE_PGRS45 is a virulent factor actively involved in the interaction with the host macrophage.

Sponsorship bias in published pharmacoeconomic evaluations of national reimbursement negotiation drugs in China: a systematic review.

BACKGROUND: China's National Reimbursement Drug List (NRDL) has become the primary route for drug reimbursement in China. More recently, the authority has made pharmacoeconomic evaluation an integral part of the application for NRDL inclusion. The underlying financial conflict of interests (FCOI) of pharmacoeconomic evaluations, however, has the potential to influence evidence generated and thus subsequent decision-making yet remains poorly understood. METHODS: We searched for studies published between January 2012 and January 2022 on the 174 drugs added to the 2017-2020 NRDLs after successful negotiation. We categorised the study's FCOI status into no funding, industry funding, non-profit funding and multiple fundings based on authors' disclosure and assessed the reporting quality of included studies using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. We compiled descriptive statistics of funding types and study outcomes using t-tests and χ2 tests and conducted multivariate regression analysis. RESULTS: We identified 378 records and our final sample included 92 pharmacoeconomic evaluations, among which 69.6% were conducted with at least one funding source. More than half (57.6%) of the evaluations reached favourable conclusions towards the intervention drug and 12.6% reached a dominant result of the intervention drug over the comparison from model simulation. The reporting quality of included studies ranged from 19 to 25 (on a scale of 28), with an average of 22.3. The statistical tests indicated that industry-funded studies were significantly more likely to conclude that the intervention therapy was economical (p<0.01) and had a significantly higher proportion of resulting target drug economically dominated the comparison drug (p<0.05). CONCLUSION: The study revealed that FCOI bias is common in published pharmacoeconomic evaluations conducted in Chinese settings and could significantly influence the study's economical results and conclusions through various mechanisms. Multifaceted efforts are needed to improve transparency, comparability and reporting standardisation.

The quality and reliability of TikTok videos on non-alcoholic fatty liver disease: a propensity score matching analysis.

Background: Lifestyle modification is the cornerstone of non-alcoholic fatty liver disease (NAFLD) prevention and treatment. Short video platforms can facilitate easier access to health information for patients, thereby influencing lifestyle changes. An increasing number of individuals rely on online platforms to acquire health-related information about NAFLD. However, the quality of information regarding NAFLD on these platforms remains unclear. Objective: This study aimed to investigate the quality of information about NAFLD on TikTok. Methods: A total of 497 videos were retrieved from TikTok. The basic video information, including the video source, was extracted. Two independent raters evaluated the quality and reliability of the videos using the Global Quality Score system and a modified DISCERN tool. Propensity score matching (PSM) was used to compare video quality across sources. Results: NAFLD-related videos on TikTok were divided into three groups according to the uploader: health professionals, medical institutions, and science bloggers. Overall, the quality of NAFLD videos on TikTok was not satisfactory. Before PSM, there were no significant differences in video quality or content between the three groups. After PSM, the quality of NAFLD videos from health professionals was significantly better than the videos created by other groups. Besides, the videos of health professionals outperformed those of medical institutions and science bloggers in terms of the definition of disease, risk factors, and treatment, but were inferior to those of medical institutions considering the symptoms and tests of NAFLD. Conclusion: The quality of NAFLD-related videos on TikTok needs improvement. Compared with videos created by science bloggers and medical institutions, videos from health professionals may provide accurate guidance on the treatment and prevention of NAFLD.

Adiposity as a risk factor for inflammatory bowel disease and the mediating effect of metabolic and inflammatory status: A population-based cohort study.

BACKGROUND: To examine whether general and abdominal adiposity was a risk factor for the new-onset of inflammatory bowel disease (IBD) and the potential mediating effect of metabolic and inflammation status. METHODS: A total of 492,998 individuals free of IBD recruited from 2006 to 2010 in the UK Biobank were included in our study, with ongoing follow-up linking to the health-related outcome. Multivariable Cox regression models were used to evaluate the associations between general adiposity (body mass index) and abdominal adiposity (waist circumference) and the subsequent risk of IBD and its subtype. We also investigated the potential mediating effects of metabolic and inflammation status by carrying out exploratory mediation analyses. RESULTS: During a median follow-up of 12.5 years, we documented 2954 incident IBD cases (915 Crohn's disease [CD] and 2039 ulcerative colitis). After adjustment for important confounders, body mass index (hazard ratio [HR] highest quintile [Q5] vs. lowest quintile [Q1] = 1.18, 95% confidence interval [CI] 1.04-1.32; P-trend = 0.006) and waist circumference (HR Q5 vs. Q1  = 1.30, 95% CI 1.14-1.49; P-trend <0.001) showed a positive association with the risk of IBD. The associations were partially mediated by metabolic status (24%; 15%), C-reactive protein (36%; 19%) and inflammation score (82%; 46%). CONCLUSIONS: Adiposity bore a risk factor for incident IBD, whereas unhealthy metabolism, especially inflammation, seemed to be an important intermediate condition between the association. Our findings provide evidence for possible mechanisms relating adiposity to IBD from an epidemiological perspective, and experimental studies are needed for further demonstration.

Macrophage-derived exosomes promote intestinal mucosal barrier dysfunction in inflammatory bowel disease by regulating TMIGD1 via mircroRNA-223.

BACKGROUND & AIM: Exosomes are effective mediators of cell-to-cell interactions and transport several regulatory molecules, including microRNAs (miRNAs), involved in diverse fundamental biological processes. The role of macrophage-derived exosomes in the development of inflammatory bowel disease (IBD) has not been previously reported. This study investigated specific miRNAs in macrophage-derived exosomes in IBD and their molecular mechanism. METHODS: A dextran sulfate sodium (DSS)-induced IBD mouse model was established. The culture supernatant of murine bone marrow-derived macrophages (BMDMs) cultured with or without lipopolysaccharide (LPS) was used for isolating exosomes, which were subjected to miRNA sequencing. Lentiviruses were used to alter miRNA expression and investigate the role of macrophage-derived exosomal miRNAs. Both mouse and human organoids were co-cultured with macrophages in a Transwell system to model cellular IBD in vitro. RESULTS: LPS-induced macrophages released exosomes containing various miRNAs and exacerbated IBD. Based on miRNA sequencing of macrophage-derived exosomes, miR-223 was selected for further analysis. Exosomes with upregulated miR-223 expression contributed to the exacerbation of intestinal barrier dysfunction in vivo, which was further verified using both mouse and human colon organoids. Furthermore, time-dependent analysis of the mRNAs in DSS-induced colitis mouse tissue and miR-223 target gene prediction were performed to select the candidate gene, resulting in the identification of the barrier-related factor Tmigd1. CONCLUSION: Macrophage-derived exosomal miR-223 has a novel role in the progression of DSS-induced colitis by inducing intestinal barrier dysfunction through the inhibition of TMIGD1.

Endoscopic management of pancreatic fluid collections with disconnected pancreatic duct syndrome.

Disconnected pancreatic duct syndrome (DPDS) is an important and common complication of acute necrotizing pancreatitis. Endoscopic approach has been established as the first-line treatment for pancreatic fluid collections (PFCs) with less invasion and satisfactory outcome. However, the presence of DPDS significantly complicates the management of PFC; besides, there is no standardized treatment for DPDS. The diagnosis of DPDS presents the first step of management, which can be preliminarily established by imaging methods including contrast-enhanced computed tomography, ERCP, magnetic resonance cholangiopancreatography (MRCP), and EUS. Historically, ERCP is considered as the gold standard for the diagnosis of DPDS, and secretin-enhanced MRCP is recommended as an appropriate diagnostic method in existing guidelines. With the development of endoscopic techniques and accessories, the endoscopic approach, mainly including transpapillary and transmural drainage, has been developed as the preferred treatment over percutaneous drainage and surgery for the management of PFC with DPDS. Many studies concerning various endoscopic treatment strategies have been published, especially in the recent 5 years. Nonetheless, existing current literature has reported inconsistent and confusing results. In this article, the latest evidence is summarized to explore the optimal endoscopic management of PFC with DPDS.

Machine learning prognosis model based on patient-reported outcomes for chronic heart failure patients after discharge.

BACKGROUND: Patient-reported outcomes (PROs) can be obtained outside hospitals and are of great significance for evaluation of patients with chronic heart failure (CHF). The aim of this study was to establish a prediction model using PROs for out-of-hospital patients. METHODS: CHF-PRO were collected in 941 patients with CHF from a prospective cohort. Primary endpoints were all-cause mortality, HF hospitalization, and major adverse cardiovascular events (MACEs). To establish prognosis models during the two years follow-up, six machine learning methods were used, including logistic regression, random forest classifier, extreme gradient boosting (XGBoost), light gradient boosting machine, naive bayes, and multilayer perceptron. Models were established in four steps, namely, using general information as predictors, using four domains of CHF-PRO, using both of them and adjusting the parameters. The discrimination and calibration were then estimated. Further analyze were performed for the best model. The top prediction variables were further assessed. The Shapley additive explanations (SHAP) method was used to explain black boxes of the models. Moreover, a self-made web-based risk calculator was established to facilitate the clinical application. RESULTS: CHF-PRO showed strong prediction value and improved the performance of the models. Among the approaches, XGBoost of the parameter adjustment model had the highest prediction performance with an area under the curve of 0.754 (95% CI: 0.737 to 0.761) for death, 0.718 (95% CI: 0.717 to 0.721) for HF rehospitalization and 0.670 (95% CI: 0.595 to 0.710) for MACEs. The four domains of CHF-PRO, especially the physical domain, showed the most significant impact on the prediction of outcomes. CONCLUSION: CHF-PRO showed strong prediction value in the models. The XGBoost models using variables based on CHF-PRO and the patient's general information provide prognostic assessment for patients with CHF. The self-made web-based risk calculator can be conveniently used to predict the prognosis for patients after discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/index.aspx ; Unique identifier: ChiCTR2100043337.

A Nucleus Accumbens Tac1 Neural Circuit Regulates Avoidance Responses to Aversive Stimuli.

Neural circuits that control aversion are essential for motivational regulation and survival in animals. The nucleus accumbens (NAc) plays an important role in predicting aversive events and translating motivations into actions. However, the NAc circuits that mediate aversive behaviors remain elusive. Here, we report that tachykinin precursor 1 (Tac1) neurons in the NAc medial shell regulate avoidance responses to aversive stimuli. We show that NAcTac1 neurons project to the lateral hypothalamic area (LH) and that the NAcTac1→LH pathway contributes to avoidance responses. Moreover, the medial prefrontal cortex (mPFC) sends excitatory inputs to the NAc, and this circuit is involved in the regulation of avoidance responses to aversive stimuli. Overall, our study reveals a discrete NAc Tac1 circuit that senses aversive stimuli and drives avoidance behaviors.

Bacterial Community Composition and Isolation of Actinobacteria from the Soil of Flaming Mountain in Xinjiang, China.

In this work, bacterial community composition and actinobacteria resources were explored in extremely hot and hyper-arid areas of Flaming Mountain. This was achieved through a combination of PCR amplicon sequencing of bacterial 16S rRNA gene and cultivation-dependent isolation and characterization efforts. According to the high-throughput sequencing results and soil characteristics, 11 kinds of media were firstly designed to isolate actinobacteria, following the screening and identification of related strains. The results showed that a total of 2994 operational taxonomic units (OTUs) were obtained, involving 22 phyla, 77 orders and 121 genera. Among them, actinobacteria with the relative abundance of 8% ranked third, accounting for 33 genera and 47 species. A total of 132 strains distributed by eight families and 11 genera of actinobacteria were isolated from 11 media, of which six strains were potential new species. Furthermore, the functional characteristics of isolated strains were preliminarily evaluated. The results showed that the obtained strains generally had tolerance against heat, salt and alkali. Fifty-two strains had antibacterial activity, 69 strains could produce hydrolases, and 12.4% of the strains had quorum sensing inhibitory activity. The present study has laid a solid foundation for further understanding the bacterial diversity and exploiting actinobacteria resources in the Flaming Mountain area.

The Reliability and Quality of Short Videos as a Source of Dietary Guidance for Inflammatory Bowel Disease: Cross-sectional Study.

BACKGROUND: Dietary management is considered a potential adjunctive treatment for inflammatory bowel disease (IBD). Short-video sharing platforms have enabled patients to obtain dietary advice more conveniently. However, accessing useful resources while avoiding misinformation is not an easy task for most patients. OBJECTIVE: This study aimed to evaluate the quality of the information in IBD diet-related videos on Chinese short-video sharing platforms. METHODS: We collected and extracted information from a total of 125 video samples related to the IBD diet on the 3 Chinese short-video sharing platforms with the most users: TikTok, Bilibili, and Kwai. Two independent physicians evaluated each video in terms of content comprehensiveness, quality (rated by Global Quality Score), and reliability (rated by a modified DISCERN tool). Finally, comparative analyses of the videos from different sources were conducted. RESULTS: The videos were classified into 6 groups based on the identity of the uploaders, which included 3 kinds of medical professionals (ie, gastroenterologists, nongastroenterologists, and clinical nutritionists) and 3 types of non-medical professionals (ie, nonprofit organizations, individual science communicators, and IBD patients). The overall quality of the videos was poor. Further group comparisons demonstrated that videos from medical professionals were more instructive in terms of content comprehensiveness, quality, and reliability than those from non-medical professionals. Moreover, IBD diet-related recommendations from clinical nutritionists and gastroenterologists were of better quality than those from nongastroenterologists, while recommendations from nonprofit organizations did not seem to be superior to other groups of uploaders. CONCLUSIONS: The overall quality of the information in IBD diet-related videos is unsatisfactory and varies significantly depending on the source. Videos from medical professionals, especially clinical nutritionists and gastroenterologists, may provide dietary guidance with higher quality for IBD patients.