ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

Objective To search,evaluate and integrate the best evidence of wound procedural pain management in patients with chronic wounds,and to provide evidence-based references for clinical practice.Methods Following the"6S"evidence model,we systematically searched relevant literature of wound procedural pain management in patients with chronic wounds,including clinical practice guidelines,clinical decisions,expert consensuses,evidence summaries,recommended practice and systematic reviews,with the search period from the datebase establishment to December 2022.The quality evaluation,extraction and integration for evidence were conducted independently by 2 researchers,respectively.Results A total of 17 articles were involved,including 2 guidelines,1 expert consensus,3 clinical decisions,6 evidence summaries,2 recommended practice,3 systematic reviews.34 pieces of best evidence were synthesized into 9 categories,including general principles,pain assessment and documentation,replacement and selection of the wound dressing,wound cleaning,wound debridement,negative pressure wound therapy,drug intervention strategies,non-drug intervention strategies,education and training.Conclusion The best evidence of wound procedural pain management in patients with chronic wounds in this study is scientific and practical.Medical staff can select and apply the best evidence based on clinical situation and patient willingness to reduce wound procedural pain.

Objective:To evaluate the effect of vagus nerve stimulation on the homologous phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/Parkin signaling pathway on myocardial injury induced by hepatic ischemia-reperfusion (I/R) in rats.Methods:Twenty-seven clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=9 each) using a random number table method: sham operation group (Sham group), hepatic I/R group (HI/R group) and vagus nerve stimulation group (VNS group). The liver I/R injury model was made by clamping the liver pedicle for 1 h followed by 6-h reperfusion. In VNS group, the left cervical vagus nerve was stimulated by a voltage with a frequency of 20 Hz and a wave width of 0.1 ms immediately after liver ischemia, lasting for 1 h. The stimulation voltage was adjusted with the rat heart rate, and the heart rate decreased by more than 10% of the basic value was considered as a successful stimulation. The rats were anesthetized at the end of reperfusion, and carotid blood samples were collected for determination of the serum cardiac troponin I (cTnI) concentration by enzyme-linked immunosorbent assay. Then rats were sacrificed, and left ventricular myocardial tissues were taken for determination of the apoptosis in cardiomyocytes (by TUNEL) and expression of PINK1, Parkin, p62, Bax and Bcl-2 (by Western blot). The apoptosis rate was calculated. Results:Compared with Sham group, the concentrations of serum cTnI and apoptotic rate of cardiomyocytes were significantly increased, the expression of PINK1, Parkin and Bcl-2 in myocardial tissues was down-regulated, and the expression of p62 and Bax was up-regulated in HI/R group and VNS group ( P<0.05). Compared with HI/R group, the concentrations of serum cTnI and apoptotic rate of cardiomyocytes were significantly decreased, the expression of PINK1, Parkin and Bcl-2 in myocardial tissues was up-regulated, and the expression of p62 and Bax was down-regulated in VNS group ( P<0.05). Conclusions:The mechanism by which vagus nerve stimulation alleviates myocardial injury induced by hepatic I/R is related to activation of the PINK1/Parkin signaling pathway in rats.

Objective:To investigate clinical characteristics of and genetic variants in the NF1 gene in children with neurofibromatosis type 1 (NF1) .Methods:Clinical data were collected from 22 children with NF1, who were admitted to the Department of Dermatology, Children's Hospital, Capital Institute of Pediatrics from January 2022 to September 2023, and were analyzed. Next-generation sequencing was performed to detect NF1 mutations in the probands, and the variants were verified in the family members by Sanger sequencing. A homology modeling software was used to predict the three-dimensional protein structure, and analyze the characteristics of gene mutations.Results:Among the 22 children with NF1, there were 14 males and 8 females, and they were aged from 3 months to 12 years at the clinic visit. All the 22 children presented with multiple café-au-lait spots, and their age at onset ranged from birth to 2 years. Nine patients were accompanied by freckles in the axillary or inguinal regions, 2 by cutaneous neurofibromas, 2 by juvenile xanthogranuloma, 2 by learning disabilities, and Lisch nodules of the iris, central precocious puberty and scoliosis occurred in 1 case each; 5 cases showed characteristic manifestations of neurofibroma on brain magnetic resonance imaging. A total of 5 types of NF1 gene variants were identified in the 22 patients, including complete heterozygous deletion of the NF1 gene (1 patient), missense variants (4 patients, one of whom carried 2 types of missense variants), frameshift variants (8 patients), nonsense variants (6 patients), and classical splicing variants (3 patients). Among the 22 variants, 7 were unreported variants, including c.758T>A (p.Val253Glu), c.2360dupC (p.Thr788Asnfs*5), c.5513T>G (p.Leu1838*), c.2774dupT (p.Leu925Phefs*11), c.6894dupT (p.Val2299Cysfs*7), c.6882_6883delCT (p.Phe2295Leufs*10), and c.6448A>T (p.Lys2150*). Of the unreported variants, 6 were frameshift or nonsense variants leading to different degrees of truncated protein expression, and severely affecting protein function; based on the three-dimensional protein structure prediction analysis, it was uncertain if the missense variant c.758T>A (p.Val253Glu) affected protein conformation. In 2 children, the NF1 variants were inherited from their mothers; 1 child carried 2 NF1 missense variants, 1 of which was a spontaneous mutation potentially causing the disease, while the other one with unknown pathogenicity was inherited from the phenotypically normal father; the remaining 19 children all carried spontaneous mutations.Conclusions:Children with NF1 mainly present with multiple café-au-lait spots at the early stage, and some characteristic manifestations such as cutaneous neurofibroma, juvenile xanthogranuloma, and Lisch nodules of the iris can also occur. NF1 gene pathogenic variants are complex and diverse, and 22 variants were identified in this study, enriching the spectrum of NF1 gene variants.

Objective:To explore the association between cardiovascular health behaviors and hyperuricemia (HUA) among community residents of different age groups.Methods:It was a cross-sectional study. A total of 2 138 community residents aged (47.1±11.6) years with 1 012 males (47.3%) were selected by cluster sampling method as study subjects in Taiyuan Nanzhai Community from March to November 2020. There were 104 cases aged 8-18 years (underage group), 868 cases aged 19-44 years (youth group), 625 cases aged 45-59 years (middle-aged group), 375 cases aged 60-74 years (young elderly group), and 166 cases aged≥75 years (elderly group). Blood uric acid was measured and>420 μmol/L was defined as HUA, there were 385 cases with high uric acid level (HUA group) and 1 753 cases with normal uric acid levels (control group). The general information was collected by questionnaires, and general ergonomic indicators were measured on-site by medical personnel. The cardiovascular health behaviors included smoking, exercise, diet, and sleep in study subjects were documented. Multivariate logistic regression model was used to analyze the related factors of HUA.Results:Among 2 138 participants, 1 161 (54.3%) had never smoked (up to standard), and the order of proportion of non-smokers from high to low was underage group, elderly group, young elderly group, young group and middle-aged group ( P<0.001); 486(22.7%) people met the dietary standards, and the order of proportion of meeting the dietary standards from high to low was underage group, elderly group, young elderly group, middle-aged group, and young group ( P<0.001); 554(25.9%) people achieved physical fitness standards, and the order of the proportion of achieving physical fitness standards from high to low was young elderly group, middle-aged group, elderly group, underage group, and young group ( P<0.001); 783 (36.6%) people met the sleep standards, and the order of proportion meeting the sleep standards from high to low was underage group, youth group, middle-aged group, young elderly group, and elderly group ( P<0.001). Among the participants, only 39 (1.8%) met the standards for all 4 types of behaviors; 485 (22.7%), 1 229 (57.5%), and 424 (19.8%) had low, medium, and high total scores for ideal cardiovascular health behaviors, respectively. The total score of ideal cardiovascular health behaviors ranked from high to low was elderly group, young elderly group, underage group, middle-aged group, and young group ( P<0.001). The multivariate logistic regression analysis showed that body mass index (BMI) ( OR=1.125, 95% CI: 1.086-1.165) was positively correlated with HUA, while female ( OR=0.241, 95% CI: 0.182-0.320), total score of cardiovascular health behaviors (compared to lower level, intermediate level: OR=0.186, 95% CI: 0.127-0.273, high level: OR=0.038, 95% CI: 0.020-0.072), and number of achieved healthy behavior items ( OR=0.757, 95% CI: 0.621-0.922) were negatively correlated with HUA. Conclusions:The underage group has the highest number of people who meet the smoking, dietary, and sleep standards, the young and elderly group has the highest number of people who meet the exercise standards, and the elderly group has the highest total score for ideal cardiovascular health behaviors. There is a positive correlation between BMI and HUA, while there is a negative correlation of HUA with female, the total score and number of achieved items of cardiovascular health behaviors.

Background and purpose:Rectal cancer is one of the malignant tumors that seriously harm human health in the world,ranking third in incidence and second in mortality.With the development of social and economic level,the incidence and mortality of colorectal cancer in China are increasing,and China becomes one of the countries with high incidence of colorectal cancer disease in the world.The recommended treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy combined with surgery,which greatly improves the prognosis of patients.However,intestinal adverse reactions such as diarrhea caused by neoadjuvant chemoradiotherapy are increased,and some patients are forced to delay or interrupt treatment due to serious side effects.Amifostine is a broad-spectrum normal cell protective agent,which has good protective effect against various radiochemotherapy toxicity.We conducted a retrospective analysis of patients with locally advanced rectal cancer who received neoadjuvant radiotherapy combined with irinotecan concurrent chemotherapy to investigate whether concurrent use of amifostine alleviated gastrointestinal and hematological toxicities.Methods:A retrospective cohort analysis was used in this study.Clinical data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy at the Affiliated Cancer Hospital of Fudan University during the period of discharge from January 1,2018 to December 31,2019 were retrospectively collected.The patients were divided into 2 groups by whether amifostine was used during the same period.The main purpose of the study was to analyze whether amifostine can reduce gastrointestinal and hematological toxicities,and secondary objectives included whether amifostine could alter tumor marker levels,mesorectal fascia invasion(MRF)positive rate,extramural vascular invasion,positive rate of EMVI and pathological complete response(pCR).Using SAS9.4 statistical software,the normality test was carried out for continuous variables.The rank sum test of Wilcoxon was performed when the diarrhea grade did not conform to normal distribution.Analysis of variance was performed for intra-group comparison,and Wilcoxon rank sum test was performed for inter-group comparison.Because of the imbalance between groups,the difference between the two groups was compared using a generalized linear model.This study strictly followed the STrengthening the Reporting of OBservational studies in Epidemiology(STROBE)guidelines to ensure the transparency of the research methodology and the reliability of the results.Results:Finally,154 eligible patients were included,of whom 78 were in the amifostine group and 76 were in the control group.The highest grade of diarrhea in amifostine group was 1.00(1.00,1.00),lower than that in control group(2.00,3.00),and the difference between groups was statistically significant(P＜0.01).After radiotherapy,white blood cell count(WBC),hemoglobin(HB)and absolute neutrophil count(ANC)from the two groups were obtained.ANC and platelet count(PLT)showed no statistically significant difference(P＞0.05),and the lowest values of WBC,RBC and PLT did not have statistically significant difference between the two groups during neoadjuvant period(P＞0.05).Amifostine may not alleviate hematological toxicity.Carbohydrate antigen 72-4(CA72-4)(Z=2.22,P=0.03),carbohydrate antigen 50(CA50)(Z=-2.49,P=0.01)and carbohydrate antigen 24-2(CA24-2)had statistically significant difference(Z=-2.29,P=0.02).There were no significant differences in MRF positive rate(P=0.11),EMVI positive rate(P=0.61)and pCR rate(P=0.94)between the two groups.Conclusion:Concurrent administration of amifostine in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy can reduce gastrointestinal toxicity and reduce the levels of tumor markers CA72-4,CA50 and CA24-2.However,it may have no significant effect on improving hematological toxicity,MRF and EMVI positive rate and pCR rate.

Cell-in-cell(CIC)is a phenomenon described as the active infiltration of one or more living cells into another living cell,forming intracellular structures and producing biological effects.This phenomenon was first ob-served and detailed in the early 20th century.However,it has only become an active area of research in cell biology in the past decade.As research advanced,scientists gradually recognized that the phenomenon of CIC exists in many biological systems and diseases,and has important physiological and pathological significance in evolution,development,homeosta-sis,and diseases,especially in tumors,which has important clinical research value.Currently,five forms of CIC struc-tures have been identified:cell cannibalism,phagoptosis,enclysis,entosis,and emperipolesis.Each form represents a distinct interaction between cells,characterized by unique cell types,biological characteristics,molecular mechanisms,and implications in pathophysiology.This article aims to review the cell types involved in each CIC structure,their biologi-cal characteristics and the molecular mechanisms driving these interactions,and to explore the potential clinical signifi-cance in the diagnosis,treatment and prognosis of human diseases.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Objective:To compare the therapeutic effects of intramedullary nail fixation, simple tibial plate fixation, and tibial plate + posterior-to-anterior screw fixation in the surgical treatment of lower 1/3 spiral fracture of the tibia combined with posterior malleolar fracture.Methods:A retrospective study was conducted to analyze the clinical data of 78 patients with lower 1/3 spiral fracture of the tibia combined with posterior malleolar fracture who had been treated at Department of Orthopedics, The Hospital Affiliated to Qingdao University from June 2015 to June 2022. There were 46 males and 32 females with an age of (48.9±14.6) years. The patients were divided into 3 groups according to their fixation methods. Group A (18 patients) underwent simple intramedullary nail fixation, group B (40 patients) simple tibial plate fixation, and group C (20 patients) tibial plate fixation for tibial fractures and posterior-to-anterior screw fixation for posterior malleolar fractures. The operation time, intraoperative blood loss, fracture union time, postoperative complications, as well as ankle-hindfoot scores of American Orthopaedic Foot and Ankle Society (AOFAS) and Baird-Jackson scores at pre- and post-operation were compared among the 3 groups.Results:The differences in the preoperative baseline data were not statistically significant among the 3 groups, indicating comparability ( P>0.05). All patients were followed up for (24.9±10.1) months. The fracture union time in Group A was 14.0(13.0, 14.0) weeks, significantly longer than that in groups B and C [13 (13, 14) weeks] ( P<0.05). The AOFAS ankle-hindfoot score and Baird-Jackson score at the last postoperative follow-up in all patients were better than those before surgery ( P<0.05). The AOFAS ankle-hindfoot scores at the last follow-up in groups B and C [95.5 (86.0, 96.0) points and 96.0 (89.5, 98.5) points] were significantly higher than that in group A [86.5 (78.0, 93.0) points] ( P<0.05), and the Baird-Jackson scores at the last follow-up in groups B and C [93.0 (88.8, 95.0) points and 95.0 (91.0, 98.0) points] were also significantly higher than that in group A [86.0 (78.0, 89.5) points] ( P<0.05). All the 7 cases of complications (3 ones of poor fracture union and 4 ones of anterior knee pain) were observed in group A. Conclusion:In the surgical treatment of lower 1/3 spiral fracture of the tibia combined with posterior malleolar fracture, tibial plate fixation and tibial plate + posterior-to-anterior screw fixation can achieved better therapeutic effects than intramedullary nail fixation.

Objective:To investigate the feasibility and clinical diagnostic value of rapid arterial spin labeling (ASL) imaging in brain glioma.Methods:Patients with glioma admitted to Beijing Tiantan Hospital, Capital Medical University from May 2021 to December 2022 were prospectively enrolled. All patients received MR rapid ASL (scan time: 1 min) and conventional ASL (scan time: 4 min 30 s), where the cerebral blood flow (CBF) perfusion maps were obtained. The qualitative analysis of CBF signal intensity and quantitative analysis of average CBF values from both tumor solid and edema regions were conducted by two radiologists independently. Kappa test and intraclass correlation coefficient ( ICC) were used to analyze the consistency of qualitative and quantitative results, respectively. Results:A total of 30 patients with brain glioma were included. The 2 physicians used rapid ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 1, 6, 23 cases and 0, 5, and 25 cases, respectively; and used conventional ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 0, 9, and 21 cases, respectively. The results of qualitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( Kappa was 0.830 and 0.850 respectively). The results of quantitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( ICC 0.940—0.994). Conclusion:Rapid ASL with shorter scanning time could be applied in assessing tissue perfusion in brain glioma and contribute to the clinical diagnosis of gliomas.