High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.

Sphincter of Oddi dysfunction (SOD) refers to the abnormal physiological function of sphincter of Oddi, which causes a series of syndromes in biliary tract, pancreas and liver. At present, the related research of SOD is becoming a hot spot, but its pathogenesis is not clear. This article will review the domestic and international literatures on SOD, review the advantages and disadvantages of experimental animals such as rabbits, dogs and guinea pigs, and analyze the characteristics of drugs and surgical modeling, so as to provide references for future related model establishment.

Objective:To investigate the influencing factors for splenomegaly secondary to acute pancreatitis (AP) and construction of a nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 180 patients with AP who were admitted to Xuanwu Hospital of Capital Medical University from December 2017 to December 2021 were collected. There were 124 males and 56 females, aged (49±15) years. Among them, 60 AP patients who developed secondary splenomegaly were taken as the case group, including 48 males and 12 females, aged (47±13)years, and the rest of 120 cases of AP without secondary splenomegaly were taken as the control group, including 76 males and 44 females, aged (50±16)years. Observation indicators: (1) occurrence and clinical characteristics of splenomegaly secondary to AP; (2) influencing factors for splenomegaly secondary to AP; (3) construction and evaluation of a nomogram prediction model for splenomegaly secondary to AP. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The univariate analysis was performed using statistical methods appropriate to the data type. The optimal cut-off value was determined by the receiver operating characteristic curves. Multivariate analysis was conducted using the Logistic regression model with forward method. Based on the results of the multivariate analysis, a nomogram prediction model was constructed. The receiver operating characteristic curve was drawn, and the discrimination was evaluated using the area under curve. The consistency of the nomogram prediction model was evaluated using calibration curve, and its clinical benefit was evaluated using decision curve. Results:(1) Occurrence and clinical characteristics of splenomegaly secondary to AP. The first detection time of 60 patients with splenomegaly secondary to AP was 60(30,120)days after the onset of AP. Cases with persistent respiratory dysfunction, multiple organ failure, severity of illness as mild or moderately severe/severe, pancreatic and/or peripancreatic infection, surgery were 19, 17, 4, 56, 37, 32 for 60 patients with splenomegaly secondary to AP, versus 16, 19, 43, 77, 39, 29 for 120 patients without splenomegaly secondary to AP, respectively, showing significant differences in the above indicators between the two groups ( χ2=8.58, 3.91, 17.64, 13.95, 15.19, P<0.05). (2) Influencing factors for splenomegaly secondary to AP. Resuts of multivariate analysis showed that white blood cell count <5.775×10?/L within 24 hours of AP onset, revised computed tomography (CT) severity index >7 in 3-7 days after onset and the presence of local complications were independent risk factors influencing the splenomegaly secondary to AP ( odds ratio=3.85, 2.86, 6.40, 95% confidence interval as 1.68-8.85, 1.18-6.95, 1.56-26.35, P<0.05). (4) Construction and evaluation of a nomogram prediction model for splenomegaly secondary to AP. The nomogram prediction model was constructed based on white blood cell count within 24 hours of AP onset, revised CT severity index in 3-7 days after onset and local complications. The area under the receiver operating characteristic curve of the nomogram prediction model was 0.76 (95% confidence interval as 0.69-0.83, P<0.05), with a sensitivity of 0.87 and a specificity of 0.55. The calibration curve demonstrated consistency between the predicted rate from the nomogram prediction model and the actually observed rate. The decision curve analysis indicated that the nomogram prediction model had favorable clinical practicability. Conclusions:Patients with AP who develop secondary splenomegaly tend to have a higher severity of illness than those develop no secondary splenomegaly. White blood cell count <5.775×10?/L within 24 hours of AP onset, revised CT severity index >7 in 3-7 days after onset and presence of local complications are independent risk factors influencing splenomegaly secondary to AP, and its nomogram prediction model can predict incidence rate of splenomegaly secondary to AP.

OBJECTIVE: To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD). METHODS: With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer. RESULTS: Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c.515C>A (p.Pro172Gln) and c.5983G>A (p.Ala1995Thr) in fetus 1, and c.5920G>T (pGly1974) and c.9908T>C (p.He3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers. CONCLUSION The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
Humans ; Fetus ; Chloroform ; Computational Biology ; Ethnicity ; Ribs

Objective:To study the changes in the sphincter of Oddi pressure in rabbits after bilateral vagus nerve trunk severance and the therapeutic effect of Qingre Lidan Decoction, to provide a new way for the treatment of sphincter of Oddi dysfunction.Methods:Twenty-four 1.5~2.0 kg New Zealand Large White rabbits of either gender were randomly selected and divided into the control group, the model group, and the treatment group. In the control group, only pyloroplasty was performed; in the model group and the treatment group, pyloroplasty plus bilateral vagus nerve trunk dissection at the level of the diaphragm were performed, and in the treatment group, one month of gavage treatment with Qingre Lidan Decoction was carried out 7 days after the operation. Multi-channel bio-signal acquisition system was used to record the pressure changes of the sphincter of Oddi in rabbits of each group; ELISA was used to detect the changes of inflammatory factors IL-6 and tumor necrosis factor TNF-α in the serum of rabbits.Results:The pressure of the sphincter of Oddi in the model group was significantly higher than those in the control group [low-pressure area: (51.95±0.35) mmHg (1 mmHg=0.133 kPa) vs (21.60±1.13) mmHg ( P<0.05) ; High pressure area: (60.75±0.49) mmHg vs (20.70±0.85) mmHg ( P<0.05)], the pressure of sphincter of Oddi in the treatment group of Qingre Lidan Decoction was lower than that of the model group [low-pressure area: (22.70±1.13) mmHg vs (51.95±0.35) mmHg ( P<0.05); high-pressure area: (32.15±0.49) mmHg vs (60.75±0.49) mmHg ( P<0.05)]. Serum IL-6 and TNF-αwere significantly elevated in the model group compared to the control group; IL-6 and TNF-α levels were decreased in the treatment group compared to the model group, and the differences were statistically significant ( P<0.05). Conclusion:Bilateral vagus nerve trunk severance leads to Oddi sphincter dysfunction, and treatment with Qingre Lidan Decoction could improve Oddi sphincter dysfunction.

Objective To review the research of self-management intervention in patients with hematopoietic stem cell transplantation,clarify the intervention elements,so as to provide references for clinical practice and future related research.Methods According to the scoping review framework,a literature search was performed in the PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,Wan fang Database,VIP,CBMdisc for all the studies on self-management intervention of patients with hematopoietic stem cell transplantation.The retrieval time was from the establishment of the database to December,2022.There were 2 researchers who extracted and analyzed the data of the included literature.Results A total of 12 articles were included,including 3 randomized controlled trials,8 quasi-experimental studies,and 1 mixed study.6 studies were conducted with interventions based on the theoretical basis or nursing model such as self-management oriented 5A nursing model,continuous nursing model,problem-based learning theory.The intervention methods of 12 studies included nurse-led self-management guidance,mobile applications,multidisciplinary collaboration,and graphic cards.The intervention time was mostly 1～3 months.The outcome indicators included feasibility evaluation indicators such as operability,ease of use,and user satisfaction of the application,and effect evaluation indicators such as self-management ability,quality of life,and medication compliance of patients.The results showed that self-management interventions could improve patient self-management ability,quality of life,medication compliance,and improve their psychological and nutritional status.Conclusion The research on self-management intervention in patients with hematopoietic stem cell transplantation is still in the development stage,and its positive effect has been preliminarily verified.Medical staff should strengthen the self-management evaluation of patients with hematopoietic stem cell transplantation,play the role of multidisciplinary team,use electronic health intervention methods,and formulate multi-level,scientific and effective self-management intervention programs.

Acute and chronic wounds seriously threaten patients' life health and quality of life, therefore, wound repair has become a hot topic of research for scholars at home and abroad in recent years. With the development of material science and tissue engineering, more and more biomaterials prepared from natural ingredients were used in basic research and clinical treatment of wound repair. Such biomaterials can be used as templates for wound tissue regeneration to induce autologous cell adhesion and migration, and promote the deposition of extracellular matrix, which have broad clinical application prospects. This paper reviews the characteristics and application advance of natural biomaterials which are popular in the field of wound repair, aiming to provide ideas for the research and development of new wound dressing and tissue engineering skin.

Objective:To analyze the effects of infectious complications [infected pancreatic necrosis (IPN) and extra-pancreatic infection (EPI)] on the outcomes of patients with severe acute pancreatitis (SAP), and evaluate the differences in infection time, infection site and infecting species between SAP patients with infections complications.Methods:The clinical data of 66 SAP patients with combined infectious complications admitted to Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed, and SAP patients were divided into IPN group ( n=7), EPI group ( n=14) and co-infection (EPI+ IPN) group ( n=45) according to the type of infection. Whether the study data conformed to a normal distribution was assessed by the Shapiro-Wilk test, normally distributed measures were expressed as mean ± standard deviation ( ± s), and ANOVA was used for comparison between groups; skewed measures were expressed as median (interquartile range) [ M ( Q1, Q3)], and the rank-sum test was used for comparison between groups. Bonferroni correction was used for multiple group comparisons ( P value significance level reduced to 0.017). Quantitative data were compared between groups using the χ2 test or Fisher's exact probability method. Results:There were no statistical differences between the three groups in terms of baseline data at admission (gender, age, etiology, modified CTSI score, degree of pancreatic necrosis, and number of organ failure) ( P>0.05), patients in the EPI group were referred earlier than the other two groups ( P<0.05). In clinical treatment, patients in the IPN group and co-infection group required multiple minimally invasive interventions compared with those in the EPI group ( P<0.05), and the number of patients requiring combined nutritional support, length of intensive care unit stay, and total length of hospital stay were higher in the co-infection group than in the other two groups ( P<0.05). In addition, 360 strains of pathogenic bacteria were cultured in this study, with Gram-negative bacteria being the most common, and patients with SAP were more likely to have EPI in the early stage of disease onset, with bacteremia and respiratory tract infections in the early stage (≤14 d), and bacteremia, urinary tract infections, and catheter-associated infections in the late stage (>14 d). Conclusions:Among patients with SAP, patients in the co-infection group had higher surgical intervention, nutritional support and length of hospital stay than those in the single infection group. It is advisable to prioritize EPI in SAP patients with suspected infections, and the common infectious strains in SAP patients are still predominantly Gram-negative bacteria, and clinicians need to adjust the treatment plan in a timely manner according to the changes in patients′ conditions.

Exosomes are extracellular vesicles containing DNA, RNA and protein. They participate in intercellular communication and play an important role in tumor growth and metastasis. Exosomes exist in a variety of body fluids. Blood, urine and cerebrospinal fluid can be separated and extracted. Exosomes derived from tumor cells have the characteristics of tumor cells. Studies have shown that exosomes are involved in many processes of tumorigenesis and development, including information transmission between tumor cells, invasion and metastasis of tumor cells. Exosomes can also be used as carriers to deliver drugs to target cells, which has the potential of targeted therapy. In the process of tumor treatment, drugs can be designed based on the targeted recognition characteristics of exosomes, so as to improve the bioavailability of anti-tumor drugs, reduce adverse reactions and enhance the therapeutic effect. The research and application of exosomes are very challenging. There is a huge heterogeneity in the types, sizes and sources of exosomes, and the production mechanism is also very complex. This paper reviews the extraction and identification methods of exosomes, and reviews the clinical application of tumor derived exosomes.