Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Clinical status and challenges of new drugs for metabolic dysfunction-associated fatty liver disease].

Metabolic dysfunction-associated fatty liver disease (MASLD) is a major public health problem that seriously affects human health. At present, some good progress has been made in the research and development of new drugs for MASLD, but there is still great space for exploration. This paper summarizes and analyzes the reasons in the current clinical status and challenges for the research and development of new drugs for MASLD.

[Interpretation of the Chinese guideline for diagnosis and management of drug-induced liver injury (2023 version)].

Drug can cause almost all known types of acute, subacute, and chronic liver injuries. Drug-induced liver injury (DILI) is an important cause of unexplained liver injury in clinical practice. Correct diagnosis of DILI is challenging due to lack of specific diagnostic biomarkers, especially in patients with pre-existing liver disease and multiple concomitant drugs. A comprehensive understanding of the risk factors, clinical features, and prognosis of liver injury caused by different drugs will help physicians to recognize, diagnose, and manage it timely. Although the guideline was developed based on evidence-based medicine provided by the latest studies, there is limited high-quality evidence in the field of DILI. Therefore, this guideline should be interpreted with caution, and physicians should adopt an optimal diagnostic and therapeutic strategy for individual patients within the framework of the guideline.

IL-36 Regulates Neutrophil Chemotaxis and Bone Loss at the Oral Barrier.

Tissue-specific mechanisms regulate neutrophil immunity at the oral barrier, which plays a key role in periodontitis. Although it has been proposed that fibroblasts emit a powerful neutrophil chemotactic signal, how this chemotactic signal is driven has not been clear. The objective of this study was to investigate the site-specific regulatory mechanisms by which fibroblasts drive powerful neutrophil chemotactic signals within the oral barrier, with particular emphasis on the role of the IL-36 family. The present study found that IL-36γ, agonist of IL-36R, could promote neutrophil chemotaxis via fibroblast. Single-cell RNA sequencing data disclosed that IL36G is primarily expressed in human and mouse gingival epithelial cells and mouse neutrophils. Notably, there was a substantial increase in IL-36γ levels during periodontitis. In vitro experiments demonstrated that IL-36γ specifically activates gingival fibroblasts, leading to chemotaxis of neutrophils. In vivo experiments revealed that IL-36Ra inhibited the infiltration of neutrophils and bone resorption, while IL-36γ promoted their progression in the ligature-induced periodontitis mouse model. In summary, these data elucidate the function of the site-enriched IL-36γ in regulating neutrophil immunity and bone resorption at the oral barrier. These findings provide new insights into the tissue-specific pathophysiology of periodontitis and offer a promising avenue for prevention and treatment through targeted intervention of the IL-36 family.

[Evaluation of anticoagulant effect and predicted dose of low molecular weight heparin in hemodialysis by anti-â ©a factor activity].

The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC (OR value 1.319, 95%CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.

Development of a real-time impedance matching system for ion cyclotron resonance heating in experimental advanced superconducting tokamak.

To achieve stable operation of an ion cyclotron resonance heating (ICRH) system in the Experimental Advanced Superconducting Tokamak (EAST), a real-time impedance matching system needs to be established to respond to antenna load variation during long pulse discharges. A new impedance matching method based on capacitors was proposed in this study. By considering the reflected voltage of the transmission line as the feedback parameter, the real-time impedance-matching system can quickly control the motors based on a programmable logic controller to determine the minimum reflection voltage. A real-time impedance matching system was successfully used on the test platform in the laboratory and on the ICRH system in EAST. A significant result is that we can match the variable impedance within 1 s by suitably adjusting the motor controller to ensure high-power and long-pulse operation of the ICRH system to satisfy the requirements of the EAST experiment.

[A family with developmental glaucoma and microcornea due to novel ADAMTS18 gene mutations].

This case report presents a family with developmental glaucoma accompanied by microcornea resulting from novel mutations in the ADAMTS18 gene. The index case involves a 5-year-old twin brother, who, during a routine examination, exhibited elevated intraocular pressure persisting for over a month. The peak intraocular pressure reached approximately 25 mmHg (1 mmHg=0.133 kPa) in both eyes, with a corneal diameter of less than 10 mm. Ocular examination revealed an enlarged cup-to-disc ratio, and optical coherence tomography (OCT) demonstrated thinning of the retinal nerve fiber layer and ganglion cell layer. Ultrasound biomicroscopy combined with gonioscopy indicated partial angle closure and abnormal anterior chamber angle development. The ocular manifestations in the twin brother were consistent with those observed in the twin sister. The clinical diagnosis was bilateral developmental glaucoma with microcornea. Genetic sequencing identified two novel compound heterozygous mutations in the ADAMTS18 gene in the twins: Mutation 1 (M1) involving the variant site 1 (c.3436C>T:p.R1146W) and Mutation 2 (M2) involving the variant site 2 (c.1454T>G:p.F485C). Ocular examinations of four additional family members were normal. Genetic testing revealed that the twins' father and sister carried M1, while the index case's mother and brother carried M2. This report underscores a unique association between ADAMTS18 gene mutations and developmental glaucoma with microcornea within a familial context, emphasizing the importance of genetic screening for early diagnosis and targeted management strategies.

Design and analysis of radio frequency window for the China Fusion Engineering Test Reactor ion cyclotron range of frequency heating system.

The Ion Cyclotron Range of Frequency (ICRF) heating system of the China Fusion Engineering Test Reactor (CFETR) is intended to provide plasma heating with a minimum power output of 20 MW, which demands the Radio Frequency (RF) window to possess a higher performance requirement. This paper presents the design of an RF window for the CFETR ICRF heating system and focuses primarily on the design and confirmation of its electromagnetic performance. The RF window can be effectively matched in the operating frequency range and has an S11 of under -59 dB. The geometry of the cone type ceramics was optimized to reduce the surface tangential electric field distribution. An analysis of the electric field distribution of the RF window at 50 kV indicates that the pressure side was below 2.3 kV/mm and the vacuum side was below 1.3 kV/mm. Furthermore, a transmission line test bench with an open-terminated setup was constructed to conduct withstand voltage tests on the mockup, and the results showed that the mockup could withstand 62 kV for 2 s and 47 kV for 120 s.

[Progress in correlation between lymph node metastasis and prognosis of esophageal cancer].

The status of lymph node metastasis is an important parameter affecting the survival of patients with esophageal carcinoma, which is primarily determined by histological type and the depth of invasion. However, affected by pathological features, heterogeneity and individual differences of tumors, the present staging system of lymph node in esophageal carcinoma has not been unified, the rule of lymph node metastasis remains unclear, and the extent of lymphadenectomy is still controversial. Current lymph node staging system for esophageal carcinoma may be not effective enough, which may lead to inaccurate assessment of the stage and affect the clinicians' choice of treatment modalities, or even affect the conclusions of clinical trials. Therefore, it is essential to optimize the current lymph node staging system for esophageal carcinoma to guide the surgery-based multidisciplinary treatment, and effectively to evaluate the therapeutic effects and predict patients' prognosis.

[New technology and research progress in neurosurgery diagnosis and treatment].

Neurosurgery is a vital branch of medicine that deals with the surgical management of brain disorders. The increasing demand for clinical solutions drives technological innovation, and the rapid progress in science and technology enables new discoveries, knowledge, techniques, and instruments in neurosurgery, expanding the scope and accuracy of diagnosis and treatment, and enhancing therapeutic outcomes. The author team combines domestic and international literature and previous clinical and scientific research experience, focusing on practical clinical problems in several subspecialties, including neuroimaging, neuronavigation and surgical robot assistance, central nervous system tumors, surgical treatment of cerebrovascular disease, functional neurosurgery, neuroinjury and neural repair, and digital neurosurgery. The paper summarizes in detail the research hotspots and puts forward the research direction prospects, including the innovative application of imaging technology, the development of fine surgery, the innovation of neuro-oncology diagnosis and treatment, the surgical standardization of cerebrovascular disease, the progress of neuromodulation, the individualized neurological alternative treatment and the digitalization of multi-dimensional information in neurosurgery.

[Research advances on the application of music therapy in pain management of children with burns].

Pain after burns is a very common problem in children. Severe pain will not only hinder treatment, but also damage children's mental health if not handled in time. Therefore, pain management is very important in treating children with burns. As a safe, effective, and convenient non-drug therapy, music therapy has great advantages in relieving pain and is widely used in a variety of clinical fields. This paper focused on music therapy and its mechanism of pain relief, the current status of research on pain management of pediatric burns, the application and prospect of music therapy in pain management of pediatric burns, etc., to provide reference for clinical application.

[Research advances on severe burn infection and cytokine storm].

Mortality due to severe burns has always been at a high level. A large number of studies have shown that the rapid onset of infectious symptoms and rapid progression of severely burned patients are closely related to the occurrence of cytokine storm. However, in clinical practice, cytokine storm monitoring, early warning, and symptomatic treatment are still in exploratory stage. This article reviews the cytokine storm and its related cytokines, the mechanism, early warning, and treatment of cytokine storm induced by burn infection, aiming to provide clinical references for reducing infection and mortality in severely burned patients.

[Genetic susceptibility to drug-induced liver injury].

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.

[Statin-related drug-induced liver injury].

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.

Development of a novel combined nomogram integrating deep-learning-assisted CT texture and clinical-radiological features to predict the invasiveness of clinical stage IA part-solid lung adenocarcinoma: a multicentre study.

AIM: To develop a novel combined nomogram based on deep-learning-assisted computed tomography (CT) texture (DL-TA) and clinical-radiological features for the preoperative prediction of invasiveness in patients with clinical stage IA lung adenocarcinoma manifesting as part-solid nodules (PSNs). MATERIALS AND METHODS: This study was conducted from January 2015 to October 2021 at three centres: 355 patients with 355 PSN lung adenocarcinomas who underwent surgical resection were included and classified into the training (n=222) and validation (n=133) cohorts. PSN segmentation on CT images was performed automatically with a commercial deep-learning algorithm, and CT texture features were extracted. The least absolute shrinkage and selection operator was used for feature selection and transformed into a DL-TA score. The combined nomogram that incorporated the DL-TA score and identified clinical-radiological features was developed for the prediction of pathological invasiveness of the PSNs and validated in terms of discrimination and calibration. RESULTS: The present study generated a combined nomogram for predicting the invasiveness of PSNs that included age, consolidation-to-tumour ratio, smoking status, and DL-TA score, with a C-index of 0.851 (95% confidence interval: 0.826-0.877) for the training cohort and 0.854 (95% confidence interval: 0.817-0.891) for the validation cohort, indicating good discrimination. Furthermore, the model had a Brier score of 0.153 for the training cohort and 0.135 for the validation cohort, indicating good calibration. CONCLUSION: The developed combined nomogram consisting of the DL-TA score and clinical-radiological features and has the potential to predict the individual risk for the invasiveness of stage IA PSN lung adenocarcinomas.

[A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review].

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

[Characteristics of lymph node metastasis of right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma].

Objective: To understand the characteristics and influencing factors of lymph node metastasis of the right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma (ESCC), and to explore the reasonable range of lymph node dissection and the value of right recurrent laryngeal nerve lymph node dissection. Methods: The clinicopathological data with thoracic ESCC were retrospectively analyzed, and the characteristics of lymph node metastasis along the right recurrent laryngeal nerve and its influencing factors were explored. Results: Eighty out of 516 patients had lymph node metastasis along the right recurrent laryngeal nerve, the metastasis rate was 15.5%. Among 80 patients with lymph node metastasis along the right recurrent laryngeal nerve, 25 cases had isolated metastasis to the right recurrent laryngeal nerve lymph node but no other lymph nodes. The incidence of isolated metastasis to the recurrent laryngeal nerve lymph node was 4.8% (25/516). A total of 1 127 lymph nodes along the right recurrent laryngeal nerve were dissected, 115 lymph nodes had metastasis, and the degree of lymph node metastasis was 10.2%. T stage, degree of tumor differentiation and tumor location were associated with right paraglottic nerve lymph node metastasis (all P<0.05). The lymph node metastasis rate along the right recurrent laryngeal in patients with upper thoracic squamous cell carcinoma (23.4%, 26/111) was higher than that of patients with middle (13.5%, 40/296) and lower (12.8%, 14/109) thoracic squamous cell carcinoma (P=0.033). In patients with poorly differentiated ESCC (20.6%, 37/180) the metastasis rate was higher than that of patients with moderately (14.6%, 39/267) and well-differentiated (5.8%, 4/69; P<0.05). The lymph node metastasis rate of patients with stage T4 (27.3%, 3/11) was higher than that of patients with stage T1 (9.6%, 19/198), T2 (19.0%, 16/84) and T3 (18.8%, 42/1 223; P<0.05). Multivariate regression analysis showed that tumor location (OR=0.61, 95% CI: 0.41-0.90, P=0.013), invasion depth (OR=1.46, 95% CI: 1.11-1.92, P=0.007), and differentiation degree (OR=1.67, 95% CI: 1.13-2.49, P=0.011) were independent risk factors for lymph node metastasis along right recurrent laryngeal nerve of ESCC. Conclusions: The lymph node along the right recurrent laryngeal nerve has a higher rate of metastasis and should be routinely dissected in patients with ESCC. Tumor location, tumor invasion depth, and differentiation degree are risk factors for lymph node metastasis along right recurrent laryngeal nerve in patients with ESCC.

[Standardize the diagnosis and treatment of drug-induced liver injury, and strengthen clinical and translational research].

As a liver disease with the most complex clinical phenotype, drug-induced liver injury (DILI) poses great challenges in diagnosis and management in clinical practice. Although guidelines based on the latest research advances can provide clinicians with guidance on the identification, diagnosis, and management of DILI, the overall level of evidence in this field is relatively low and high-level evidence is limited. Therefore, we should interpret guidelines with caution and look forward to more clinical and translational research to address the huge unmet clinical needs in DILI.