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Jun Mei Teng,1 Shuiqing Qin,2 Danyu Lu,1 Yefa Gu,3 Shi Jie Tang,3 Qiong Yan,1 Jiawei Yao,1 Chao Zhang1 1Laboratory Department, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Science and Education, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Psychiatry, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Danyu Lu, Laboratory Department, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86 13457087740, Email 297459717@qq.comPurpose: To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations.Patients and Methods: Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 *1, *2, and *3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression.Results: The study identified five CYP2C19 genotypes at the *2 and *3 loci, with the *3/*3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18– 60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age.Conclusion: In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.Keywords: CYP2C19 gene, valproic acid, blood drug concentration, Zhuang Chinese, Han Chinese

Background: Long ampullary stenoses and fibrotic distal biliary strictures are not infrequently encountered during endoscopic retrograde cholangiopancreatography (ERCP). Instead of balloon dilation and stenting, we propose that these strictures can be managed with sphincterotome stricturoplasty (SS) during the initial ERCP.Objective: To report our clinical experience with SS for benign distal biliary strictures.Design: Review on prospectively collected data.Patients: All (consecutive) patients who underwent ERCP and SS performed by the authors in a 12-month period. Long ampullary stenosis and/or distal biliary stricture is defined as significant narrowing of CBD from the level of duodenal wall into the common bile duct (CBD) after initial sphincterotomy. The upstream CBD is dilated. Despite adequate ES, contrast drainage is poor due to the downstream stricture. SS was performed using the same sphincterotome in slightly bowed position under endoscopic and fluoroscopic guidance. The cutting wire was placed parallel to the superior border within the stricture and incising the stenosis. In cases of relatively long strictures, during initial SS the majority of the cutting wire was inside the biliary opening. This differs from ES, where about one-third to one-half of the length of cutting wire is outside the ampulla.Measurements: Clinical data, hospital course, procedure-related complication rates, and outcomes were prospectively collected in a database.Results: During the study period, 308 ERCPs were performed. Benign and short (≤15 mm in length) distal biliary strictures were observed in 25 patients. Mean ± SD stricture length was 7.4 ± 3.0 mm. The presumed etiologies for these strictures were choledocholithiasis (n = 22) and postsphincterotomy stenosis (n = 3). There was no perforation, post-ERCP pancreatitis, postsphincterotomy bleeding, or cholangitis. To date, none of these patients who had SS have needed follow-up ERCP.Limitations: Single-operator experience, limited follow-up period.Conclusions: Compared with balloon stricturoplasty ± biliary stenting, SS is a simple and cost-effective alternative option in managing long ampullary stenosis and/or distal fibrotic biliary stricture during the initial ERCP. [ABSTRACT FROM AUTHOR]

Background: Studies have shown high-frequency, low-energy gastric electrical stimulation (GES) to be an effective management strategy for patients with medication refractory gastroparesis. However, placement of a permanent GES device requires surgery and has considerable cost considerations. More importantly, however, this mode of therapy may not be successful for all patients. Patients likely to benefit from such an invasive and expensive procedure could be selected on the basis of their response to temporary GES. Electrodes for the purpose of temporary GES usually are placed percutaneously or through a percutaneous endoscopic gastrostomy (PEG) tube (PEGStim). This study demonstrated an easier and less cumbersome placement of these electrodes endoscopically [1-3].Methods: The current case involved a 32-year-old man with diabetic gastroparesis. The endoscopic methods and protocol were approved by the Institutional Review Board at the University of Mississippi, Jackson, Mississippi. Informed consent was obtained before the procedure. Standard upper endoscopy was performed initially. A temporary cardiac pacing lead (Model 6414-200; Medtronic, Minneapolis, MN, USA) was used as the electrode. The video demonstrates an innovative technique of endoscopic placement of electrodes for temporary GES. The external stimulation device used was the standard GES device (Enterra; Medtronic).Results: Temporary GES produced a rapid and marked improvement in the patient's intractable symptoms, improvement in his health-related quality-of-life score, electrogastrography parameters, and gastric emptying. Although the temporary electrodes could have been removed easily by gentle traction in a counterclockwise direction, the patient desired that the electrodes be left in place until permanent electrode placement.Conclusion: For patients such as the man in the current case, who do not have a preexisting PEG tube, the authors demonstrated that endoscopic placement of electrodes is technically feasible. The reported patient likely will benefit from surgical placement of a permanent GES device. Thus, the authors propose ENDOStim as the preferred method for placement of electrodes for temporary GES. [ABSTRACT FROM AUTHOR]

A diagnosis of parathyroid hormone-related protein (PTH-rP)-secreting metastatic uterine epithelioid leiomyo-sarcoma was made in a 61-year-old woman with humoral hypercalcemia of malignancy. A primary uterine tumor had been removed 10 years previously, which had been associated with a short history of hypercalcemia. The original uterine tumor was diagnosed as a smooth muscle tumor of uncertain malignant potential. To the best of our knowledge, this is the first reported case of a PTH-rP-secreting uterine leiomyosarcoma. We demonstrate the dramatic changes in serum calcium, phosphorus, PTH, and PTH-rP levels after tumor resection. Extensive biochemical analysis and detailed immunohistochemical and ultrastructural characterization demonstrate several features of this tumor. [ABSTRACT FROM AUTHOR]

Objective: To determine the safety and proof of concept of a parcel-guided, repetitive Transcranial Magnetic Stimulation (rTMS) in patients who develop a heterogeneous array of symptoms, known collectively as post-concussive syndrome (PCS), following traumatic brain injury (TBI)., Methods: We performed a retrospective review of off-label, individualized, parcel-guided rTMS in 19 patients from December 2020 to May 2023. Patients had at least one instance of mild, moderate, or severe TBI and developed symptoms not present prior to injury. rTMS targets were identified based on machine learning connectomic software using functional connectivity anomaly matrices compared to healthy controls. EuroQol (EQ-5D), as a measurement of quality of life, and additional questionnaires dependent on individual's symptoms were submitted prior to, after, and during follow-up from rTMS., Results: Nineteen patients showed improvement in EQ-5D and Rivermead Post Concussion Symptoms Questionnaires - 3 after treatment and follow-up. For nine patients who developed depression, five (55%) attained response and remission based on the Beck Depression Inventory after treatment. Eight of ten patients with anxiety had a clinically significant reduction in Generalized Anxiety Disorder-7 scores during follow-up., Conclusion: Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies.

This article reported a case of an elderly female patient with diffuse lung lesions and multiple enlarged lymph nodes. In the early stages of diagnosis, many clues, obtained through cellular immunology and molecular biology tests on a variety of samples including blood and bronchoalveolar lavage fluid, pointed to the diagnosis of tuberculosis. At the same time, a peripheral lymph node biopsy was conducted, which led to the diagnosis of lymphoma coexisting with tuberculosis, a"dual-diagnosis". In the subsequent treatment, lymphoma therapy was actively pursued while the patient's tuberculosis infection was treated, with good results observed in the follow-up treatments. When diagnosing the disease, the differential diagnosis must be integrated into the overall disease process, and avoiding rigid adherence to a "unitary"diagnostic concept.

Introduction: Poor quality sleep has often been cited as a cause of lowered quality of life in patients with affective disorders such as major depressive disorder (MDD) and generalized anxiety disorder (GAD). As sleep and affective disorders are affected by multi-network interactions, we hypothesize that the modulation of the central executive network (CEN), salience, and default mode networks (DMNs) through individualized repetitive transcranial magnetic stimulation (rTMS) may improve sleep and quality of life., Methods: A retrospective analysis from 2020 to 2023 was conducted in patients with affective disorders at Cingulum Health. Multiple targets were selected based on anomalies detected from individual, functional connectivity networks from a machine-learning connectivity software. rTMS was conducted with accelerated continuous or intermittent theta burst stimulation (TBS) based on the anomaly detected. Pittsburgh Sleep Quality Index (PSQI), EuroQol (EQ5D), Beck's Depression Inventory (BDI), and the General Anxiety Disorder-7 (GAD-7) questionnaires were administered prior to, after, and at follow-up of rTMS., Results: Twenty-seven patients were identified, and the most common diagnoses were MDD (41%) or MDD with GAD (41%). All patients had at least one rTMS target in the CEN. The most common target (19 patients) was L8Av in the dorsolateral prefrontal cortex (dlPFC). Patients experienced significant improvements in sleep, quality of life, depressive, and anxiety symptoms after rTMS and during follow-up. Improvements in sleep correlated with quality of life at follow-up., Conclusion: This study suggests that personalized, parcel-guided rTMS is safe and may provide sustained improvements in sleep, quality of life, and affective symptoms for patients with affective disorders., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

N 6 -methyladenosine (m 6 A) RNA methylation is a prevalent RNA modification that significantly impacts RNA metabolism and cancer development. Maintaining the global m 6 A levels in cancer cells relies on RNA accessibility to methyltransferases and the availability of the methyl donor S-adenosylmethionine (SAM). Here, we reveal that death associated protein 3 (DAP3) plays a crucial role in preserving m 6 A levels through two distinct mechanisms. First, although DAP3 is not a component of the m 6 A writer complex, it directly binds to m 6 A target regions, thereby facilitating METTL3 binding. Second, DAP3 promotes MAT2A 's last intron splicing, increasing MAT2A protein, cellular SAM, and m 6 A levels. Silencing DAP3 hinders tumorigenesis, which can be rescued by MAT2A overexpression. This evidence suggests DAP3's role in tumorigenesis, partly through m 6 A regulation. Our findings unveil DAP3's complex role as an RNA-binding protein and tumor promoter, impacting RNA processing, splicing, and m 6 A modification in cancer transcriptomes., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: Hyperoxia has been suggested as a mechanism for secondary injury following adult traumatic brain injury (TBI), but its effects have not been well described in pediatric patients., Methods: Pediatric (≤18yo) TBI patients were identified in a prospective institutional registry from October 2008 to April 2022. The first, highest, and the Area Under the Curve (AUC) PaO2 in the first 24 hours were collected and calculated for each patient from arterial blood gas reports after admission to the ICU. Neurological outcome after 6 months was measured using dichotomized modified Rankin Scale (mRS) and Glasgow Outcome Scale - Extended (GOS-E). Multivariable logistic regression models were used to determine if the three measurements for hyperoxia predicted an unfavorable outcome after controlling for well-established clinical and imaging predictors of outcome., Results: We identified 98 pediatric patients with severe accidental TBI during the study period. Hyperoxia (PaO2 > 300 mmHg) occurred in 33% of the patients. The presence of elevated PaO2 values, determined by all three evaluations of hyperoxia, was not associated with unfavorable outcome after 6 months., Conclusion: Utilizing multiple methods to assess exposure, hyperoxia was present in a substantial number of patients with severe TBI but was not associated with an unfavorable outcome.

Background: The prevalence and disease course of inflammatory bowel disease (IBD) have evolved over the years. It is unknown how these factors have impacted all-cause mortality. Our study assesses IBD mortality trends in the United States over 20 years by age, sex, and race., Methods: We used the Centers for Disease Control Wide-Ranging OnLine Data for Epidemiologic Research database for multiple causes of death in Crohn's disease (CD) and ulcerative colitis (UC) from 1999 to 2020. Age-adjusted mortality rates (AAMR) and crude mortality rates per 100 000 population were obtained. Joinpoint Analysis Software was used for annual percentage change (APC) overall and by age, sex, and race (White and Black)., Results: Overall AAMR in CD and UC were 0.79 and 0.53, respectively. All-cause mortality was stable from 1999 to 2018. There was a significant rise in APC from 2018 to 2020 (CD vs. UC, +11.28 vs. +9.29). This rise was observed across both races, sexes, and ages ≥45 years in the last 2-4 years of the study. AAMR in females compared with males varied in CD (0.81 vs. 0.79) and UC (0.45 vs. 0.62). White adults had higher AAMR than Black adults in both CD (0.94 vs. 0.50) and UC (0.58 vs. 0.28). The crude mortality rate increased with age and was highest in those ≥85 years (CD vs. UC, 5.07 vs. 5.23)., Conclusions: All-cause mortality trends in IBD were stable until 2018 and rose between 2018 and 2020. Mortality rates were higher amongst the elderly and White adults. Females with CD and males with UC had higher mortality rates., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To report on the venous abnormalities of a patient with Sturge-Weber syndrome., Method: Case report., Patient: A 29-year-old woman with a history of Sturge-Weber syndrome since infancy was referred for evaluation of possible diffuse choroidal hemangioma. Multimodal imaging, including ultra-widefield fluorescein, indocyanine green, and optical coherence tomography angiography, was performed., Results: Dilated fundus examination was remarkable for increased cupping of the optic disk in the right eye, venous tortuosity, and marked dilation of the choroidal vessels. Ultra-widefield fluorescein angiography confirmed marked venous tortuosity and dilation, as well as anastomoses of the retinal veins ipsilateral to the port wine stain. Indocyanine green angiography revealed marked engorgement of the vortex veins and choroidal vasculature. Optical coherence tomography angiography revealed dilated vascular channels in the deep capillary plexus that were directly anastomosing to the superficial capillary plexus, but not the intermediate capillary plexus. Engorgement of the ampullae of the deep capillary plexus vortex system was also observed. The normal contralateral eye was used as comparison for all imaging studies., Conclusion: These findings support the notion of generalized venous hypertension state in adult eyes with Sturge-Weber syndrome and corroborate previous evidence that the deep capillary plexus acts as a venous outflow system., Competing Interests: B. Fortune: Heidelberg Engineering, GmbH (equipment support). The remaining authors have no conflicts of interest.

The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies.

Few studies investigate the impact of anterior-posterior excitation frequency on the time-domain vibrational response and injury risk of the lumbar spine in seated individuals. Firstly, this study utilised a previously developed finite element model of an upright seated human body on a rigid chair without a backrest to investigate the modes that affect the anterior-posterior vibrations of the seated body. Subsequently, transient dynamic analysis was employed to calculate the lumbar spine's time-domain responses (displacement, stress, and pressure) and risk factors under anteroposterior sinusoidal excitation at varying frequencies (1-8 Hz). Modal analysis suggested the frequencies significantly affecting the lumbar spine's vibration were notably at 4.7 Hz and 5.5 Hz. The transient analysis results and risk factor assessment indicated that the lumbar responses were most pronounced at 5 Hz. In addition, risk factor assessment showed that long-term exposure to 8 Hz vibration was associated with a greater risk of lumbar injury.

Progress toward single-molecule electronics relies on a thorough understanding of local physico-chemical processes and development of synthetic routines for controlled hetero-coupling. We demonstrate a structurally unexpected ring closure process for a homo-coupled 4,4'-bipicenyl, realized in on-surface synthesis. An initial covalent C-C coupling of 4-bromopicene locks at lower temperatures the position and geometrically shields part of 4,4'-bipicenyl. Employing this effect of shielding might offer a path toward controlled stepwise hetero-coupling. At higher temperatures, a thermally activated three-dimensional rotation upon hydrogen dissociation, a dehydrogenative roto-cyclization, lifts the surface-dimensionality restriction, and leads to the formation of a perylene. Thereby, the shielded molecular part becomes accessible again., (© 2024 Wiley-VCH GmbH.)

ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR) + macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1 high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The concept of functional localization within the brain and the associated risk of resecting these areas during removal of infiltrating tumors, such as diffuse gliomas, are well established in neurosurgery. Global efficiency (GE) is a graph theory concept that can be used to simulate connectome disruption following tumor resection. Structural connectivity graphs were created from diffusion tractography obtained from the brains of 80 healthy adults. These graphs were then used to simulate parcellation resection in every gross anatomical region of the cerebrum by identifying every possible combination of adjacent nodes in a graph and then measuring the drop in GE following nodal deletion. Progressive removal of brain parcellations led to patterns of GE decline that were reasonably predictable but had inter-subject differences. Additionally, as expected, there were deletion of some nodes that were worse than others. However, in each lobe examined in every subject, some deletion combinations were worse for GE than removing a greater number of nodes in a different region of the brain. Among certain patients, patterns of common nodes which exhibited worst GE upon removal were identified as "connectotypes". Given some evidence in the literature linking GE to certain aspects of neuro-cognitive abilities, investigating these connectotypes could potentially mitigate the impact of brain surgery on cognition., (© 2024. The Author(s).)

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD., Competing Interests: Dong‐Xu Chen is the editorial board members of Ibrain and a co‐author of this article, he has not been involved in the peer review process; all decisions are left to the editor‐in‐chief so as to minimize bias. The remaining authors declare no conflict of interest., (© 2024 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

Anti-tuberculosis drug-induced liver injury(ATB-DILI) is the most common adverse reaction during anti-tuberculosis therapy in tuberculosis patients. At present, the diagnosis of ATB-DILI is mainly based on traditional biomarkers such as transaminases, but these indicators have low specificity for liver toxicity, they cannot explain the mechanism of liver injury and the early onset of ATB-DILI. Based on the prediction of disease severity, treatment and prevention, this paper described the current potential biomarkers of ATB-DILI.

Objective: To investigate the influence of sacroiliac interosseous ligament tension and laxity on the biomechanics of the lumbar spine., Methods: A static analysis of a three-dimensional finite element model of the Lumbar-Pelvic is conducted to verify the model's effectiveness. Adjusting the sacroiliac ligament's elasticity modulus under a 10Nm lumbar flexion/extension moment, it simulates ligament tension/laxity to calculate vertebrae displacements, intervertebral disc stress and deformation, nucleus pulposus pressure, facet joint force, and ligament stress., Results: With the elastic modulus of the sacroiliac ligament changing by +50%, -50%, and -90%, the angular displacement of vertebra 3 in forward flexion changes by +1.64%, -4.84%, and -42.3%, and the line displacements change by +5.7%, -16.4%, and -144.9%, respectively; and the angular displacements in backward extension change by +0.2%, -0.6%, -5.9% and the line displacements change by +5.5%, -14.3%, and -125.8%. However, the angular displacement and center distance between adjacent vertebrae do not change, leading to no change in the maximum stress of the intervertebral disc and the maximum pressure in the nucleus pulposus. Flexion and extension directly affect the deformation and stress magnitude and distribution in the lumbar spine., Conclusions: While sacroiliac interosseous ligament laxity and tension have little effect on disc deformation and stress, and nucleus pulposus pressure, they reduce the stability of the lumbar-sacral vertebrae. In a forward flexion state, the lumbar ligaments bear a large load and are prone to laxity, thereby increasing the risk of lumbar injury., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A series of studies on the interventional diagnosis and treatment of tuberculosis(TB)were carried out by domestic and foreign researchers in 2023. The combination of minimally invasive interventional procedures with endoscopes, guidance, material acquisition techniques by multiple ways and multichannel and highly accurate laboratory testing techniques is becoming more and more widely practiced clinically, which has played an important role in the accurate diagnosis of problematic TB. Diagnostic procedures for pulmonary TB, tracheobronchial TB, mediastinal lymphatic TB and extrapulmonary TB included conventional flexible bronchoscopy and specific types of bronchoscopy(ultrathin bronchoscopy and endobronchial ultrasound), transbronchial needle aspiration biopsy, endobronchial ultrasound and virtual bronchoscopic navigation system-guided forceps biopsy, thoracoscopic cryobiopsy of pleura, percutaneous biopsy, and so on. The time to diagnosis has been significantly reduced and the diagnostic efficacy has been improved by the clinical specimen detection using either Gene Xpert MTB/RIF, Ultra, loop-mediated isothermal amplification, metagenomic next-generation sequencing, or nanopore sequencing, etc . Interventional therapy was focused on the following diseases: pulmonary TB with massive hemoptysis, tracheobronchial TB, pleural TB and TB-related fistulas. Interventional treatment of tracheobronchial TB mainly included the application of rigid bronchoscopy, bronchoscopic cold and thermal ablation treatment, endoscopic clamp, dilatations of narrow airway with balloon and stent placement, etc . The interventional treatment of pulmonary TB complicated by massive hemoptysis included endovascular embolization, coated stent placement, etc . Interventional treatment of pleural TB involved the application of thoracoscopy, endoscopic forceps, the implantation of stent and other occlusive devices and the closure of fistulas with autologous fat transplantation. In this article, we reviewed the progress of interventional diagnosis and treatment of TB by the search of published literatures from October 2022 to September 2023.

Objective: Osteoarthritis (OA) is often accompanied by debilitating pain that is refractory to available analgesics due in part to the complexity of signaling molecules that drive OA pain and our inability to target these in parallel. Fatty acid binding protein 5 (FABP5) is a lipid chaperone that regulates inflammatory pain; however, its contribution to OA pain has not been characterized., Design: This combined clinical and pre-clinical study utilized synovial tissues obtained from subjects with end-stage OA and rats with monoiodoacetate-induced OA. Cytokine and chemokine release from human synovia incubated with a selective FABP5 inhibitor was profiled with cytokine arrays and ELISA. Immunohistochemical analyses were conducted for FABP5 in human and rat synovium. The efficacy of FABP5 inhibitors on pain was assessed in OA rats using incapacitance as an outcome. RNA-seq was then performed to characterize the transcriptomic landscape of synovial gene expression in OA rats treated with FABP5 inhibitor or vehicle., Results: FABP5 was expressed in human synovium and FABP5 inhibition reduced the secretion of pronociceptive cytokines (interleukin-6 [IL6], IL8) and chemokines (CCL2, CXCL1). In rats, FABP5 was upregulated in the OA synovium and its inhibition alleviated incapacitance. The transcriptome of the rat OA synovium exhibited >6000 differentially expressed genes, including the upregulation of numerous pronociceptive cytokines and chemokines. FABP5 inhibition blunted the upregulation of the majority of these pronociceptive mediators., Conclusions: FABP5 is expressed in the OA synovium and its inhibition suppresses pronociceptive signaling and pain, indicating that FABP5 inhibitors may constitute a novel class of analgesics to treat OA., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: In recent years, the association between oral health and the risk of gastric cancer (GC) has gradually attracted increased interest. However, in terms of GC incidence, the association between oral health and GC incidence remains controversial. Periodontitis is reported to increase the risk of GC. However, some studies have shown that periodontitis has no effect on the risk of GC. Therefore, the present study aimed to assess whether there is a relationship between oral health and the risk of GC., Aim: To assess whether there was a relationship between oral health and the risk of GC., Methods: Five databases were searched to find eligible studies from inception to April 10, 2023. Newcastle-Ottawa Scale score was used to assess the quality of included studies. The quality of cohort studies and case-control studies were evaluated separately in this study. Incidence of GC were described by odds ratio (OR) and 95% confidence interval (CI). Funnel plot was used to represent the publication bias of included studies. We performed the data analysis by StataSE 16., Results: A total of 1431677 patients from twelve included studies were enrolled for data analysis in this study. According to our analysis, we found that the poor oral health was associated with higher risk of GC (OR = 1.15, 95%CI: 1.02-1.29; I 2 = 59.47%, P = 0.00 < 0.01). Moreover, after subgroup analysis, the outcomes showed that whether tooth loss (OR = 1.12, 95%CI: 0.94-1.29; I 2 = 6.01%, P > 0.01), gingivitis (OR = 1.19, 95%CI: 0.71-1.67; I 2 = 0.00%, P > 0.01), dentures (OR = 1.27, 95%CI: 0.63-1.19; I 2 = 68.79%, P > 0.01), or tooth brushing (OR = 1.25, 95%CI: 0.78-1.71; I 2 = 88.87%, P > 0.01) had no influence on the risk of GC. However, patients with periodontitis (OR = 1.13, 95%CI: 1.04-1.23; I 2 = 0.00%, P < 0.01) had a higher risk of GC., Conclusion: Patients with poor oral health, especially periodontitis, had a higher risk of GC. Patients should be concerned about their oral health. Improving oral health might reduce the risk of GC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pathological pain emerges from nociceptive system dysfunction, resulting in heightened pain circuit activity. Various forms of circuitry plasticity, such as central sensitization, synaptic plasticity, homeostatic plasticity, and excitation/inhibition balance, contribute to the malfunction of neural circuits during pain pathogenesis. Recently, a new form of plasticity in the spinal dorsal horn (SDH), named neural circuit polarization (NCP), was discovered in pain models induced by HIV-1 gp120 and chronic morphine administration. NCP manifests as an increase in excitatory postsynaptic currents (EPSCs) in excitatory neurons and a decrease in EPSCs in inhibitory neurons, presumably facilitating hyperactivation of pain circuits. The expression of NCP is associated with astrogliosis. Ablation of reactive astrocytes or suppression of astrogliosis blocks NCP and, concomitantly, the development of gp120- or morphine-induced pain. In this review, we aim to compare and integrate NCP with other forms of plasticity in pain circuits to improve the understanding of the pathogenic contribution of NCP and its cooperation with other forms of circuitry plasticity during the development of pathological pain.

The study aimed to investigate the dynamic characteristics of the cervical spine and determine the effect of the material properties of the cervical spinal components on it. A finite element model of the head-cervical spine was developed based on CT scan data, and the first six orders of modes (e.g. flexion-extension, lateral bending, and vertical, etc.) were verified by experimental and simulation studies. The material sensitivity study was conducted by varying elasticity modulus of cervical hard tissues (cortical bone, cancellous bone, endplates, and posterior elements) and soft tissues (intervertebral disc and ligaments). The results showed that increasing the elastic modulus of ligaments by 4 times increased the natural frequency by 77%, while increasing that of cancellous bone by 4 times only increased the natural frequency by 6%. In the axial mode, the cervical spine had not only axial deformation but also anterior-posterior deformation, with the largest deformation located at the intervertebral disc C6-C7. Decreasing the elastic modulus of a component in soft tissues by 80% increased modal displacement by up to 62%. The material properties of the intervertebral discs and ligaments had opposite effects on the modal displacement and deformation of the cervical spine. Low cervical discs were more susceptible to injury in a vertical vibration environment. Cervical spine dynamics were more sensitive to soft tissue material properties than to hard tissue material properties. Disc degeneration could reduce the range of vibratory motion of the cervical spine, thereby reducing the ability of the cervical spine to cushion head impacts.

Introduction: To understand the risk factors of asthma, we combined genome-wide association study (GWAS) risk loci and clinical data in predicting asthma using machine-learning approaches., Methods: A case-control study with 123 asthmatics and 100 controls was conducted in the Zhuang population in Guangxi. GWAS risk loci were detected using polymerase chain reaction, and clinical data were collected. Machine-learning approaches were used to identify the major factors that contribute to asthma., Results: A total of 14 GWAS risk loci with clinical data were analyzed on the basis of 10 times the 10-fold cross-validation for all machine-learning models. Using GWAS risk loci or clinical data, the best performances exhibited area under the curve (AUC) values of 64.3% and 71.4%, respectively. Combining GWAS risk loci and clinical data, the XGBoost established the best model with an AUC of 79.7%, indicating that the combination of genetics and clinical data can enable improved performance. We then sorted the importance of features and found the top six risk factors for predicting asthma to be rs3117098, rs7775228, family history, rs2305480, rs4833095, and body mass index., Conclusion: Asthma-prediction models based on GWAS risk loci and clinical data can accurately predict asthma, and thus provide insights into the disease pathogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Cancer stem cells (CSCs) shape the tumor microenvironment via neuroendocrine signaling and orchestrate drug resistance and metastasis. Cytokine antibody array demonstrated the upregulation of neurotrophin-3 (NT-3) in lung CSCs. This study aims to dissect the role of NT-3 in lung CSCs during tumor innervation., Methods: Western blotting, quantitative reverse transcription-PCR, and flow cytometry were used to determine the expression of the NT-3 axis in lung CSCs. NT-3-knockdown and NT-3-overexpressed cells were derived lung CSCs, followed by examining the stemness gene expression, tumorsphere formation, transwell migration and invasion, drug resistance, soft agar colony formation, and in vivo tumorigenicity. Human lung cancer tissue microarray and bioinformatic databases were used to investigate the clinical relevance of NT-3 in lung cancer., Results: NT-3 and its receptor tropomyosin receptor kinase C (TrkC) were augmented in lung tumorspheres. NT-3 silencing (shNT-3) suppressed the migration and anchorage-independent growth of lung cancer cells. Further, shNT-3 abolished the sphere-forming capability, chemo-drug resistance, invasion, and in vivo tumorigenicity of lung tumorspheres with a decreased expression of CSC markers. Conversely, NT-3 overexpression promoted migration and anchorage-independent growth and fueled tumorsphere formation by upregulating the expression of CSC markers. Lung cancer tissue microarray analysis revealed that NT-3 increased in patients with advanced-stage, lymphatic metastasis and positively correlated with Sox2 expression. Bioinformatic databases confirmed a co-expression of NT-3/TrkC-axis and demonstrated that NT-3, NT-3/TrkC, NT-3/Sox2, and NT-3/CD133 worsen the survival of lung cancer patients., Conclusion: NT-3 conferred the stemness features in lung cancer during tumor innervation, which suggests that NT-3-targeting is feasible in eradicating lung CSCs., (© 2024 S. Karger AG, Basel.)

Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson's disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity., (© 2023. The Author(s).)

Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60-88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.

Background: Children with Autism spectrum disorder (ASD) was frequently experienced dental anxiety and uncooperative behaviors during dental treatment. Oral health care was necessary because of the poor oral hygiene and prevalent dental diseases in this population., Aim: In this systematic review, we evaluated the effectiveness and feasibility for pediatric dentist to manage the dental anxiety in children with ASD., Design: PubMed, Embase, and Cochrane Library were systematically performed on the literature search. The date of eligible publications was from inception to January 2023. After that, the quality of eligible studies was assessed by the Newcastle Ottawa Scale (NOS). Review findings were summarized using the PRISMA Statement for reporting., Results: A total of six studies were systematically evaluated according to the inclusion and exclusion criteria. Five studies were conducted to evaluate ASD Children's anxiety and uncooperative performance in the progressive oral examination, oral disease prophylaxis and fluoride application. The other one study evaluated the success rate of treatment in decayed permanent tooth treatment. In the included studies, four studies indicated that it was extremely necessary to reduce dental anxiety of ASD children to increase the cooperation in sensory-adapted dental environment (SADE)., Conclusion: It is not always effective and feasible for pediatric dentist to manage the dental anxiety in children with autism during routine oral examination. Meanwhile, it is necessary for ASD children to conduct preoperative psychological assessment, to investigate parents' expectations and cooperation, and to determine whether to start corresponding dental treatment., (© 2023. The Author(s).)

Background: This study aimed to evaluate the value of non-invasive prenatal testing (NIPT) in the prenatal screening of foetal aneuploidy-associated diseases at different gestational ages., Methods: Briefly, cell-free foetal DNAs were extracted from plasma first, followed by DNA sequencing and bioinformatics analyses for chromosome aneuploidy (T21, T18, and T13), sex chromosome aneuploidy (SCA), and microdeletion/microduplication. Subsequently, the positive results were subject to karyotype analyses., Results: The pregnant women included in this study were divided into six groups, and the results, such as chromosome diagnoses, and clinical phenotypes, were collected for data analyses. According to the results of the data analysis, the positivity rates of foetal chromosomal abnormalities in pregnant women under 20, 20-24, 25-29, 30-34, 35-39, and >40 years old were 0%, 0.17%, 0.25%, 0.27%, 0.60%, and 1.66%, respectively. The positive predictive value (PPV) in the 20-24 years group was 41.67%, that in the 25-29 years group was 62.5%, that in the 30-34 years group was 66.67%, that in the 35-39 years group was 90.74%, and that in the >40 years group was 90.32%., Conclusion: Overall, NIPT detection in elderly pregnant women has excellent clinical application value in reducing the incidence of either birth defects or abortion caused by invasive chromosome examination.