ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

When inflammation is continuously activated or dysregulated， it can induce chronic tissue injury and organ dysfunction， and participate in the occurrence and development of various inflammatory diseases such as atherosclerosis and inflammatory bowel disease. Owing to high targeting， long-acting efficacy and programmability， nucleic acid drugs provide a new direction for the treatment of inflammatory diseases. This article reviews the classification， mechanism of action and application progress of nucleic acid drugs in inflammatory diseases. It is found that small interfering RNA （siRNA） can specifically cut target mRNA through RNA interference to achieve inhibiting the expression of the target protein； antisense oligonucleotide （ASO） can inhibit target protein expression by inducing microRNA （miRNA） degradation or regulating splicing processes； miRNA can achieve network intervention by regulating multiple inflammatory target genes. At present， important breakthroughs have been made in the field of inflammatory diseases with siRNA drugs including Lumasiran， Nedosiran （for primary hyperoxaluria 1） and Inclisiran （for atherosclerosis）， ASO drugs including Donidalorsen （for hereditary angioedema）， Volanesorsen and Olezarsen （for familial chylomicronemia syndrome） and Lademirsen （for Alport syndrome）， as well as miRNA drugs including Obefazimod （for inflammatory bowel disease） and Remlarsen （for pathological fibrosis）. These drugs are expected to become a new generation of anti-inflammatory therapeutic strategies and bring more precise and efficient treatment options for patients with chronic inflammation and fibrotic diseases.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective This study compared organ doses and effective doses in typical adult patients during dental CBCT examinations using a head-and-neck anthropomorphic phantom and a whole-body phantom. It aimed to determine an appropriate method for evaluating effective dose in dental CBCT. Methods A domestically manufactured dental CBCT unit was used to scan an adult male anthropomorphic phantom under simulated clinical conditions. Thermoluminescent dosimeters were placed on organs and tissues of a whole-body anthropomorphic phantom. Organ equivalent doses were measured, and effective doses were calculated using two approaches: one based on all organ doses from the whole-body phantom, and the other based only on head-and-neck organ doses. Entrance surface air kerma (K_a,e) was also measured at the lens of the eye, thyroid, thymus, and gonads. Results The effective dose estimated with the whole-body phantom was 382.03 μSv. The effective dose estimated with the head-and-neck phantom was 354.03 μSv. The radiation dose to head-and-neck organs and tissues accounted for 92.7% of the total effective dose. The highest K_a,e values were found in the parotid glands, followed by the lens of the eye. Conclusion During dental CBCT scanning, the contribution of organ below the head and neck to the total effective dose is limited. To simplify dose assessment procedures, the effective dose for the patient can be evaluated using only a head-and-neck phantom.

ObjectiveTo investigate the association between neutrophil-to-lymphocyte and platelet ratio （NLPR） and recompensation in patients with hepatitis B cirrhotic ascites， and to establish an individualized risk prediction model. MethodsThe patients with hepatitis B cirrhotic ascites who were hospitalized in Department of Gastroenterology， The General Hospital of Western Theater Command of Chinese PLA， from January 2015 to December 2022 were enrolled. General information and laboratory markers were collected， and NLPR was calculated. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the chi-square test with correction was used for comparison of categorical data between two groups. The subjects were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set， univariate and multivariate binary Logistic regression analyses were used to investigate the independent influencing factors for recompensation in patients with hepatitis B cirrhotic ascites， and a nomogram was established； the receiver operating characteristic （ROC） curve was used to assess the value of the new model in predicting recompensation in patients with hepatitis B cirrhotic ascites， and the Delong test was used for comparison of the area under the ROC curve （AUC）. The calibration curve and the decision curve were plotted for the model， and the model was assessed in terms of degree of fitting and predictive benefits. ResultsA total of 360 patients were enrolled， among whom134 achieved recompensation. There were 252 patients in the training set and 108 patients in the validation set， and there were no significant differences in baseline characteristics between the two groups （all P>0.05）. The Logistic regression analysis showed that the onset of hepatic encephalopathy （odds ratio ［OR］=0.066， 95% confidence interval ［CI］： 0.008 — 0.545， P=0.012）， NLPR （OR=0.950， 95%CI： 0.912 — 0.989， P=0.012）， alpha-fetoprotein （OR=1.012， 95%CI： 1.005 — 1.020， P<0.001）， and albumin （OR=1.096， 95%CI： 1.031 — 1.166， P=0.003） were independent influencing factors for recompensation in patients with hepatitis B cirrhotic ascites. The above four factors were included in a nomogram predictive model， which had an AUC of 0.776， a sensitivity of 66.5%， and a specificity of 76.3% in the training set and an AUC of 0.746， a sensitivity of 63.4%， and a specificity of 75.7% in the validation set， while Model for End-Stage Liver Disease score， Child-Pugh score， and albumin-bilirubin score had an AUC of 0.574， 0.628， and 0.621， respectively. The nomogram model had a better performance than the other three scores in predicting recompensation in patients with hepatitis B cirrhotic ascites （Z=4.191， 3.369， and 3.527， P<0.001， P=0.001， and P<0.001）. The calibration curve and the decision curve showed that the model had a good degree of fitting， and the decision made using this model could bring net benefits. ConclusionNLPR has a good value in predicting recompensation in patients with hepatitis B cirrhotic ascites， and the nomogram model established can help to predict recompensation in such patients in clinical practice.

Objective:To assess the level of moral distress among pediatric nurses in China and explore its influencing factors, providing a reference for future interventions.Methods:A cross-sectional survey was conducted using a convenience sampling method from May 2022 to March 2023. Pediatric nurses meeting the inclusion and exclusion criteria were selected from children′s specialized hospitals, general hospitals, and maternal and child health hospitals across 16 provinces in China. Moral distress was assessed using the Chinese version of the Moral Distress Scale-Revised (MDS-R). Data analysis included descriptive statistics, non-parametric analysis, and multiple linear regression.Results:A total of 509 pediatric nurses participated in the survey, including 10 males and 499 females. Among them, 45 were aged ≤25 years, 268 were aged 26-35 years, 172 were aged 36-45 years, and 24 were aged >45 years.The median moral distress score was 58.00 (26.00, 77.50). Factors independently associated with higher levels of moral distress included having a master′s degree ( t = 2.33), working in a ward with more than 40 beds ( t = 3.38), working in a ward without parental accompaniment ( t = 2.60), being passively assigned to the nursing profession ( t = 2.63), and considering resignation but not leaving the job ( t = 3.85) (all P<0.05). Conclusions:Pediatric nurses in China experience a moderate level of moral distress. Further research is needed to understand its underlying causes and to develop preventive and intervention strategies.

Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.

Objective:To investigate the effect of KRAS,NRAS and BRAF gene mutations on the efficacy of pre-operative short-course radiotherapy combined with chemotherapy and postoperative liver metastasis in patients with stage Ⅱ～Ⅲ mid-low rectal cancer.Methods:The clinical data of 149 patients with stage Ⅱ～Ⅲ low rectal cancer admitted to Dongnan Hospital of Xiamen University from January 2017 to June 2020 were retrospectively analyzed.All patients received neoadjuvant therapy with preoperative short-course radiotherapy combined with chemotherapy and radical surgery,and were followed up until June 30,2023.The mutations of KRAS,NRAS and BRAF genes were de-tected by pathological tissue before surgery.The effect of neoadjuvant therapy was evaluated according to tumor re-gression grade(TRG).The risk factors of postoperative liver metastasis were analyzed by Logistic multivariate analysis.Results:There were 44 cases of KRAS,10 cases of NRAS and 12 cases of BRAF gene mutation in 149 patients with stage Ⅱ～Ⅲ low rectal cancer,and the mutation rates were 29.53%,6.71%and 8.05%.The incidence of positive vas-cular invasion in patients with KRAS gene mutation was higher than negative(P＜0.05).In NRAS mutation patients,the incidence of positive lymph node metastasis was higher than negative(P＜0.05),and the incidence of maximum tumor diameter≥5 cm was higher than that of maximum tumor diameter＜5 cm(P＜0.05).The clinical stage of BRAF muta-tion was higher in stage Ⅲ than in stage Ⅱ(P＜0.05),and the incidence of positive lymph node metastasis was higher than negative(P＜0.05).During the follow-up period,liver metastasis occurred in 42 patients,and the liver metastasis rate was 28.18%.The KRAS,NRAS and BRAF gene mutations in the effective group were 25.81%,2.15%and 3.23%,lower than those in the ineffective group(35.71%,14.29%and 17.07%,P＜0.05).Multiple factors found clinical stage Ⅲ(OR=10.620,95%CI:2.645～22.575),lymph node metastasis was positive(OR=8.774,95%CI:1.878～19.645),neoadju-vant therapy failed(OR=3.373,95%CI:1.014～11.218),KRAS gene mutation(OR=6.245,95%CI:1.876～20.789),BRAF gene mutation(OR=9.497,95%CI:1.754～19.335)were independent risk factors for postoperative liver metastasis of stage Ⅱ～Ⅲ mid-low rectal cancer.Conclusion:Mutations in the KRAS and BRAF genes of middle are associated with poorer efficacy of neoadjuvant therapy in patients with stage Ⅱ～Ⅲ mid-low rectal cancer and are also indepen-dent risk factors for postoperative liver metastasis.