Peripheral neurotoxicity represents one of the most severe dose-limiting adverse reactions associated with oxaliplatin， with genetic polymorphisms playing a significant role in oxaliplatin-induced peripheral neuropathy （OIPN）. OIPN can be categorized as acute or chronic based on onset timing. The former presents clinically as sensory abnormalities or even motor disorders， while the latter presents clinically as limb sensory disorders that persist， numbness or pain in the hands and feet. The transporter genes OCT2， OCTN2， and NHE1 may be implicated in OIPN； drug-metabolizing enzyme gene GSTP1 Ile105Val， DPYD rs1801265， voltage-gated sodium channel （NaV） gene SCN4A rs2302237， SCN9A rs6746030， SCN10A rs12632942， and other associated genes such as HLA-G rs1610696， rs371194629 and CCNH rs2230641， rs3093816 are associated with severe OIPN. Conversely， DNA repair-related gene XRCC1 rs23885， NaV gene SCN9A rs3750904， rs12478318 and rs6754031 are associated with reduced OIPN risk. In the future， the genetic research findings on OIPN can be translated into clinical applications， ultimately achieving individualized precision medicine for patients.

Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

Obesity， a global chronic disease， is associated with adipose tissue dysfunction， which is one of the contributing factors to obesity. The cyclic adenosine monophosphate （cAMP） signaling pathway， a key regulator of lipid metabolism， plays a pivotal role in obesity development. Various of traditional Chinese medicine monomers， such as flavonoids， lignans， phenols， and terpenoids， as well as traditional Chinese medicine compound formulas like Xiaoyao powder， Shengmai powder， and Zexie decoction， can maintain energy homeostasis， balance adipose tissue function， regulate glucose metabolism， improve insulin resistance， and suppress inflammatory responses through cAMP signaling pathway regulation， thereby intervening in lipid metabolism for obesity treatment. Although a substantial amount of basic research has preliminarily elucidated the potential mechanisms by which traditional Chinese medicine intervenes in obesity through the cAMP signaling pathway， clinical translational research remains inadequate. There is an urgent need for large-sample， high-quality randomized controlled trials to validate these findings.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective To investigate serum β2-MG, sCHE, and PSGL-1 expression in patients with esophageal cancer and their relationship to lung infection after mediastinoscopy. Methods A total of 118 patients with esophageal cancer were selected and divided into infected and uninfected groups according to whether they developed lung infection after surgery. An automatic microbiological identification system was used to detect the pathogenic bacteria of lung infection. ELISA was used to detect the levels of β2-MG, sCHE, and PSGL-1. Multivariate logistic regression was used to analyze the influencing factors of postoperative lung infection in patients with esophageal cancer. ROC curves were plotted to analyze the assessment value of serum β2-MG, sCHE, and PSGL-1 on postoperative lung infection. Results Fifty-two strains of bacteria were isolated from the sputum of 38 patients with postoperative lung infections, and these included 35 (67.31%) Gram-negative, 14 (26.92%) Gram-positive, and 3 (5.77%) fungal strains. The difference in long-term smoking history between the infected and uninfected groups was statistically significant (P<0.05). Serum β2-MG and PSGL-1 levels were significantly higher and sCHE levels were significantly lower in the infected group than in the uninfected group (P<0.05). Serum β2-MG and PSGL-1 levels were sequentially higher (P<0.05) and sCHE levels were sequentially lower (P<0.05) in the mild, moderate, and severe lung infection groups. Long-term smoking history, β2-MG, and PSGL-1 were risk factors affecting postoperative lung infection in patients with esophageal cancer (P<0.05), and sCHE was a protective factor (P<0.05). The AUCs of serum β2-MG, sCHE, and PSGL-1 for assessing postoperative lung infections were 0.807, 0.845, and 0.800, respectively, and the AUC of the three combined factors for assessing postoperative lung infections was 0.954, which was superior to that assessed individually (Z_{combination vs. β2-MG}=2.576, Z_{combination vs. sCHE}=2.623, Z_{combination vs. PSGL-1}=2.574, all P<0.05). Conclusion The serum levels of β2-MG and PSGL-1 increase and the sCHE level decreases in patients with esophageal cancer and postoperative pulmonary infection, which are also related with lung infection. Combined testing can improve the evaluation value of postoperative pulmonary infection in patients.

Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

Objective: To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population. Methods: From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity. Results: The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05]. Conclusions Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.

BACKGROUND:Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality.How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays. OBJECTIVE:To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease. METHODS:CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy,and then single nucleated cell suspensions(bone marrow cells+splenocytes)from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease.These samples were randomly divided into the model group and the high-,moderate-,and low-dose Huangqintang groups.After modeling,the model,high-,moderate-,and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days.Clinical acute graft-versus-host disease grading,and survival time was recorded.Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring.The intestinal flora of mice in each group was detected using 16S rDNA sequencing.Autophagy-related markers were detected using immunofluorescence,immunohistochemistry,and PCR. RESULTS AND CONCLUSION:(1)Compared with the model group,the survival time of mice was significantly prolonged(P<0.01);the clinical acute graft-versus-host disease scores were significantly reduced(P<0.01);the pathological grading scores of the small intestinal mucosa were significantly diminished(P<0.01);the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α,interleukin-1β,and interleukin-6,were significantly decreased(P<0.01);the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang.(2)The study of intestinal flora found that compared with the model group,the pro-inflammatory strain Enterococcus was significantly reduced(P<0.05),while beneficial bacteria such as Clostridium_innocuum and Rhodococcus,a pro-autophagy bacterium,were significantly elevated(P<0.05)in the moderate-dose Huangqintang group.(3)Compared with the model group,the autophagy markers were significantly elevated in the moderate-dose Huangqintang group(P<0.05);under transmission electron microscopy,the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly.(4)The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues,and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa,which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.

BACKGROUND:The decreased postural control ability due to mild cognitive impairment in elderly people leads to the increased risk of falls.Dual-task is the primary research paradigm for evaluating the relationship between cognition and postural control in the scenes close to real life.The sample entropy of the plantar center of pressure(COP)displacement during standing can represent the complexity of postural control. OBJECTIVE:Based on the COP displacement sample entropy,to analyze the differences in postural stability characteristics and control strategies between older adults with mild cognitive impairment and cognitively normal older adults during the dual-task with postural control and spatial working memory,aiming to explore the impact of cognitive impairment on the postural control ability during standing. METHODS:Sixteen older adults with mild cognitive impairment and 17 cognitively normal older adults were eligible and selected for the study.They completed five test tasks,including spatial working memory,double-feet balance stance,Romberg stance,double-feet balance stance-spatial working memory dual-task,and Romberg stance-spatial working memory dual-task,with three valid completions of each task.The plantar COP data were collected by the Kistler 3D force platform.The indicators included cognitive behavior(cognitive score and reaction time)and kinematic indexes(COP displacement and sample entropy). RESULTS AND CONCLUSION:The older adults with mild cognitive impairment performed the spatial working memory task with the greatest cognitive score and the shortest reaction time,the double-feet balance stance-spatial working memory dual-task with moderate cognitive score and reaction time,and the Romberg stance-spatial working memory dual-task with the smallest cognitive score and the longest reaction time,where the differences were significant among the tasks(P<0.05).In the older adults with mild cognitive impairment,the anterior-posterior and medial-lateral COP displacements were significantly greater,and their sample entropy values were significantly smaller in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task than in the double-feet balance stance and Romberg stance tasks(P<0.05).In the spatial working memory task,there were no significant differences in cognitive score and reaction time between the both groups(P>0.05);however,in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,cognitive scores were significantly smaller and reaction times were longer in the older adults with mild cognitive impairment compared with the cognitively normal older adults(P<0.05).In the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,the older adults with mild cognitive impairment exhibited significantly greater anterior-posterior and medial-lateral COP displacements and significantly smaller sample entropy values compared with the cognitively normal older adults(P<0.05).All findings indicate that compared with cognitively normal older adults,older adults with mild cognitive impairment exhibit smaller complexity,poorer systematic adaption and decreased automatic regulation of the postural control during performing the dual-tasks,who are more susceptible to spatial working memory interference,leading to the increased risk of falls.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.