OBJECTIVE To investigate the protective effects and potential mechanism of alisol B 23-acetate on acute alcoholic liver injury in mice. METHODS Fifty male Kunming mice were divided into the blank group， model group， and alisol B 23-acetate low-， medium- and high-dose groups （10， 20， 40 mg/kg）， with 10 mice in each group. Each group was given relevant drug solution or normal saline intragastrically， once a day， for 2 consecutive weeks. On the 15th day， mice in the blank group were given normal saline intragastrically， while the other four groups were given 12 mL/kg white wine intragastrically， twice at six-hour intervals， to establish an acute alcoholic liver injury model. On the 16th day of the experiment， the liver indexes of mice in each group were calculated； the serum levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglycerides （TG）， malondialdehyde （MDA） and glutathione （GSH） were also determined. The histopathological morphology of their liver tissues was observed and scored. The protein expressions of cytochrome P450 2E1 （CYP2E1）， Kelch-like ECH-associated protein 1 （Keap1）， nuclear factor erythroid 2-related factor 2 （Nrf2） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were measured in liver tissue. RESULTS Compared with model group， mice in each dosage group of alisol B 23-acetate showed varying degrees of recovery in body weight， along with improvements in pathological changes in liver tissues such as inflammatory cell infiltration and fatty vacu oles. Their liver indexes， histopathological scores of liver tissue， serum levels of ALT， AST， TC， TG and MDA， as well as the protein expressions of CYP2E1 and Keap1 in liver tissue， were all significantly decreased （ P ＜0.05 or P ＜0.01）. The serum GSH levels and the protein expressions of Nrf2 （except for the alisol B 23-acetate low-dose group） and NQO1 in liver tissue were significantly increased （ P ＜0.05 or P ＜0.01）， and the changes in the above quantitative indicators showed a dose-dependent pattern. CONCLUSIONS Alisol B 23-acetate can ameliorate acute alcoholic liver injury in mice， and its mechanism may be related to improving antioxidant capacity by regulating the Keap1/Nrf2/NQO1 signaling pathway while simultaneously improving liver lipid metabolism-related indexes.

Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

Objective:To explore the latent profile characteristics of fatigue in patients with non-small cell lung cancer (NSCLC) complicated by radiation-induced pulmonary fibrosis (RIPF), and to provide evidence for developing precision nursing strategies.Methods:A convenience sample of 120 patients with RIPF and NSCLC who received treatment at the First Affiliated Hospital of Zhengzhou University between January 2022 and December 2023 was recruited. Baseline demographic and clinical data and the Multidimensional Fatigue Inventory (MFI) were collected. Latent profile analysis (LPA) was performed to classify fatigue levels, and multinomial logistic regression was used to identify influencing factors. A total of 120 questionnaires were distributed, and 116 valid responses were obtained, with a valid response rate of 96.67% (116/120) .Results:LPA identified three latent classes of fatigue among the 116 patients: the physiological-cognitive compound fatigue group ( n=52), the emotional-sleep disturbance group ( n=38), and the mildly adaptive group ( n=26). Multinomial logistic regression revealed that age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Karnofsky Performance Status (KPS), sleep quality, and anxiety were significant factors associated with the physiological-cognitive compound fatigue group ( P<0.05). Sleep quality, anxiety, depression, pain, and KPS were significant factors associated with the emotional-sleep disturbance group ( P<0.05) . Conclusions:Patients with RIPF and NSCLC can be classified into three subtypes of fatigue. Differentiated nursing strategies should be developed accordingly to achieve precise and individualized interventions.

Objective The protective effect and molecular mechanism of electroacupuncture combined with massage on cartilage damage in knee Osteoarthritis rats were explored.Methods 50 SD rats were selected and divided into a control group,a model group,an electroacupuncture group,a massage group,and an electroacupuncture+massage group of 10 rats each using an odd even number method.The rats in the control group were not treated with modeling,and the rats in the other groups were injected with Papain into the articular cavity to build the right knee Osteoarthritis(KOA)model.The massage and electroacupuncture groups were intervened with electroacupuncture and massage for 2 weeks.The improved Le-quesne MG scale was used to evaluate the behavioral performance of rats.The pressure pain value and heat pain threshold of rats before and after intervention were calculated.After eight weeks,the rats were euthanized and abdominal aortic blood was collected.The serum levels of pain mediators(K+),5-hydroxytryptamine(5-HT),and dopamine(DA)were measured by ELISA in each group of rats.The right knee joint of rats was taken for HE staining Mankin score,TUNEL chondrocyte apoptosis analysis.Toluidine blue staining was used to observe the changes of cartilage matrix polysaccharide;Western blot was used to detect the concentration and expression of cartilage matrix factor type Ⅱ collagen(Collagen Ⅱ),C-terminal peptide(CTX Ⅱ),type Ⅱ collagen C-precursor peptide(CPⅡ),apoptosis related proteins Bax,Bcl-2,Cleared caspase-3,YAP,p-YAP in the knee joint tissues of rats in each group.Results After the establishment of the KOA model,the Lequesne MG score of rats increased significantly(P<0.05).Compared with the model group,the Lequesne MG scores of rats in the electroacupuncture group and massage group decreased significantly(P<0.05).The combination of the two can further reduce the Lequesne MG score significantly(P<0.05).Compared with the control group,the pain threshold(TWL,MWT)of the model group was downregulated significantly,and the levels of serum pain factors(K+,DA,5-HT)were upregulated significantly(P<0.05).Compared with the model group,the pain thresholds(TWL,MWT)of the electroacupuncture group and the massage group were upregulated significantly,while the levels of serum pain factors(K+,DA,5-HT)were downregulated significantly(P<0.05).The combination of the two reflected the highest pain threshold(TWL,MWT)and the lowest serum pain factor(K+,DA,5-HT)levels.The model group rats had significant joint cartilage fissures,cartilage matrix staining and staining area decreased,and Markin score and cell apoptosis ability were improved(P<0.05).Compared with the model group,the arrangement degree of the cartilage layer,staining degree of the cartilage matrix,and staining area of the electroacupuncture group and massage group were all improved,while the Markin score and cell apoptosis rate all decreased significantly(P<0.05).The combination can further reduce the Markin score and the degree of chondrocyte apoptosis(P<0.05).Compared with the control group,the expression of Collagen Ⅱ,CPⅡ,Bcl-2,and p-YAP proteins in the model group decreased significantly,while the expression of CTX Ⅱ,Bax,and Cleared caspase-3 proteins increased significantly(P<0.05).Conclusion The combination of electroacupuncture and massage intervention can significantly improve the pathological state of cartilage injury in rats with osteoarthritis,reduce knee joint pain,inhibit chondrocyte apoptosis,and play a protective role in cartilage injury.Its molecular mechanism may be related to the activation of Hippo YAP signaling pathway,which is worth further research in clinical practice.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective:To explore the latent profile characteristics of fatigue in patients with non-small cell lung cancer (NSCLC) complicated by radiation-induced pulmonary fibrosis (RIPF), and to provide evidence for developing precision nursing strategies.Methods:A convenience sample of 120 patients with RIPF and NSCLC who received treatment at the First Affiliated Hospital of Zhengzhou University between January 2022 and December 2023 was recruited. Baseline demographic and clinical data and the Multidimensional Fatigue Inventory (MFI) were collected. Latent profile analysis (LPA) was performed to classify fatigue levels, and multinomial logistic regression was used to identify influencing factors. A total of 120 questionnaires were distributed, and 116 valid responses were obtained, with a valid response rate of 96.67% (116/120) .Results:LPA identified three latent classes of fatigue among the 116 patients: the physiological-cognitive compound fatigue group ( n=52), the emotional-sleep disturbance group ( n=38), and the mildly adaptive group ( n=26). Multinomial logistic regression revealed that age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Karnofsky Performance Status (KPS), sleep quality, and anxiety were significant factors associated with the physiological-cognitive compound fatigue group ( P<0.05). Sleep quality, anxiety, depression, pain, and KPS were significant factors associated with the emotional-sleep disturbance group ( P<0.05) . Conclusions:Patients with RIPF and NSCLC can be classified into three subtypes of fatigue. Differentiated nursing strategies should be developed accordingly to achieve precise and individualized interventions.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

Objective:To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. Methods:A child (proband) diagnosed with DA5D and his family members (proband′s parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children′s Hospital in July 2022 due to " multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate′s pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants wer annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children′s Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands.Results:The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c. 1742_c.1743insT and maternal c. 2314T>G, for which the father and sister were carriers of the c. 1742_c.1743insT heterozygous variant and the mother was carrier of c. 2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c. 1742_c.1743insT variant was classified as likely pathogenic (PSV1+ PM2_Supporting), and c. 2314T>G was classified as uncertain (PM2_Supporting+ PM3+ PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c. 2314T>G(p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c. 2314T>G missense mutation resulted in the failure of forming 1 disulfide bond.Conclusion:The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.

Malignant hyperthermia(MH)is a rare perioperative disease with autosomal dominant inheritance,and its pathogenesis involves specific gene mutations.Its clinical feature is that conventional anesthetics can trigger abnormally high metabolic reactions in skeletal muscles.Although the incidence of this disease is low,the condition is dangerous,progresses rapidly,and has a high mortality rate;Its treatment relies on early diagnosis,timely application of the specific drug Dantrolene Sodium,and rapid and orderly comprehensive symptomatic supportive treatment.MH is a critical perioperative emergency that can occur during surgery.It presents with symptoms such as hyperpyrexia,metabolic acidosis,rhabdomyolysis,and dysfunction of multiple organ systems.If not treated promptly,it can quickly lead to life-threatening arrhythmias and cardiac arrest.This condition serves as an essential teaching example in anesthesia crisis resource management.As an effective teaching method,scenario simulation exercises can comprehensively enhance medical staff's personal technical,non-technical,and teamwork abilities through simulating emergency scenarios,teaching assessments,and retrospective discussions,especially suitable for comprehensive management training of fatal diseases.Many countries internationally have incorporated simulation exercises for MH into their routine teaching and training systems.The effectiveness of teaching and training for anesthesiologists in MH and their ability to handle anesthesia crisis events have been continuously improved through a periodic training model.This article systematically reviews the research progress and practical experience of scenario simulation exercises in emergency training for MH,with a focus on exploring how to establish a scenario simulation exercise plan for emergency application and comprehensive symptomatic support treatment of Dantrolene Sodium based on the actual situation in China,providing reference for improving the teaching and training quality of MH and other clinical crisis events.

Neuromyelitis optica spectrum disorders (NMOSD) refer to a group of autoimmune-mediated central nervous system inflammatory demyelinating diseases that primarily affect the optic nerve and spinal cord. Most patients have anti-aquaporin 4 (AQP4) autoantibodies. The activation of the complement system plays a crucial role in the pathogenesis of AQP4 IgG seropositive NMOSD. In recent years, complement inhibitors, such as eculizumab, have demonstrated promising efficacy and development prospects in AQP4 IgG seropositive NMOSD patients. This review article focuses on the advancements made in the utilization of complement inhibitors for the management of NMOSD.