Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective To observe changes in voltage-dependent anion channel 3(VDAC3)in a mouse model of sepsis-induced myocardial injury and to explore its potential mechanism.Methods Twenty male C57BL/6J mice were divided randomly into a Sham group and Sepsis group,respectively(n=10 mice per group).Sepsis was induced by the cecal ligation and puncture(CLP).Serum levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,creatine kinase MB(CK-MB),and cardiac troponin T(cTnT)were detected by enzyme-linked immunosorbent assay.Pathological changes in heart tissue were observed by hematoxylin and eosin staining.Structural and functional changes in the heart were evaluated by echocardiography.Changes in total glutathione,reduced glutathione(GSH),oxidized glutathione,and malondialdehyde(MDA)in heart tissue were detected by spectrophotometry.The morphological structure of mitochondria in mouse cardiomyocytes was observed by transmission electron microscopy.Expression levels of IL-6,IL-1β,VDAC3,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),lipocalin-2(LCN2),and prostaglandin-endoperoxide synthase 2(PTGS2)mRNA were detected by real-time quantitative polymerase chain reaction and the localization and expression of VDAC3 and GPX4 proteins in mouse heart tissue were detected by immunofluorescence staining.The correlations between VDAC3 mRNA and GPX4,SLC7A11,PTGS2,LCN2,IL-6,and IL-1β mRNA were analyzed.Expression levels of VDAC3,GPX4,and SLC7A11 proteins were detected by Western blot.Results IL-6,TNF-α,CK-MB,and cTnT levels were significantly higher in the Sepsis group compared with the Sham group(P＜0.05).In the Sepsis group,myocardial fibers were torn,the ventricular wall was thickened and edematous,the mitochondrial membrane was ruptured,and mitochondrial cristae were broken or absent.GSH levels were significantly reduced in the Sepsis group(P＜0.05)and the lipid peroxide MDA was increased in the Sepsis group(P＜0.05)compared with the Sham group.VDAC3,GPX4 and SLC7A11 mRNA and protein levels were all lower in the Sepsis group compared with the Sham group(P＜0.05),while expression levels of IL-6,IL-1β,LCN2,and PTGS2 mRNA were increased(P＜0.05).VDAC3 mRNA was positively correlated with GPX4 and SLC7A11 mRNA levels,and negatively correlated with LCN2,PTGS2,IL-6,and IL-1β.Conclusions VDAC3 expression decreases in myocardial injury,and it may participate in the occurrence of sepsis-induced myocardial injury by regulating ferroptosis.

Objective To observe changes in voltage-dependent anion channel 3(VDAC3)in a mouse model of sepsis-induced myocardial injury and to explore its potential mechanism.Methods Twenty male C57BL/6J mice were divided randomly into a Sham group and Sepsis group,respectively(n=10 mice per group).Sepsis was induced by the cecal ligation and puncture(CLP).Serum levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,creatine kinase MB(CK-MB),and cardiac troponin T(cTnT)were detected by enzyme-linked immunosorbent assay.Pathological changes in heart tissue were observed by hematoxylin and eosin staining.Structural and functional changes in the heart were evaluated by echocardiography.Changes in total glutathione,reduced glutathione(GSH),oxidized glutathione,and malondialdehyde(MDA)in heart tissue were detected by spectrophotometry.The morphological structure of mitochondria in mouse cardiomyocytes was observed by transmission electron microscopy.Expression levels of IL-6,IL-1β,VDAC3,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),lipocalin-2(LCN2),and prostaglandin-endoperoxide synthase 2(PTGS2)mRNA were detected by real-time quantitative polymerase chain reaction and the localization and expression of VDAC3 and GPX4 proteins in mouse heart tissue were detected by immunofluorescence staining.The correlations between VDAC3 mRNA and GPX4,SLC7A11,PTGS2,LCN2,IL-6,and IL-1β mRNA were analyzed.Expression levels of VDAC3,GPX4,and SLC7A11 proteins were detected by Western blot.Results IL-6,TNF-α,CK-MB,and cTnT levels were significantly higher in the Sepsis group compared with the Sham group(P＜0.05).In the Sepsis group,myocardial fibers were torn,the ventricular wall was thickened and edematous,the mitochondrial membrane was ruptured,and mitochondrial cristae were broken or absent.GSH levels were significantly reduced in the Sepsis group(P＜0.05)and the lipid peroxide MDA was increased in the Sepsis group(P＜0.05)compared with the Sham group.VDAC3,GPX4 and SLC7A11 mRNA and protein levels were all lower in the Sepsis group compared with the Sham group(P＜0.05),while expression levels of IL-6,IL-1β,LCN2,and PTGS2 mRNA were increased(P＜0.05).VDAC3 mRNA was positively correlated with GPX4 and SLC7A11 mRNA levels,and negatively correlated with LCN2,PTGS2,IL-6,and IL-1β.Conclusions VDAC3 expression decreases in myocardial injury,and it may participate in the occurrence of sepsis-induced myocardial injury by regulating ferroptosis.

Objective:To analyze the effect of ultra-early enteral nutrition intervention on the prognosis of patients after severe craniocerebral injury surgery.Methods:A prospective study was conducted with 154 patients who underwent surgery for severe craniocerebral injury at the Neurosurgery Department of Qinhuangdao First Hospital.Patients were randomly divided into an experimental group and a control group using a random number table.Both groups received postoperative care in the Intensive Care Unit(ICU)with tracheal intubation retained within the postoperative 6 hours,and the head of the bed was elevated after 6 hours.The experimental group started ultra-early enteral nutritional support 6 hours after surgery,while the control group began early enteral nutritional support 24 hours after surgery.Total protein(TP),hemoglobin(Hb),albumin(ALB),prealbumin(PA),interleukin-6(IL-6),and C-reactive protein(CRP)were detected before intervention and on the 7th day post-intervention.The incidence of gastrointestinal complications,hospital-acquired infections,and prognostic indicators were recorded.Results:On the 7 days after intervention,TP,Hb,ALB and PA levels in the experimental group were significantly higher than those in the control group(P<0.05),and IL-6 and CRP levels were significantly lower than those in the control group(P<0.05).There was no significant difference in the incidence of abdominal distension,diarrhea,vomiting,and aspiration between the two groups(P>0.05).However,the incidence of hospital-acquired infections,ICU stay duration,total hospital stays,and mortality rate were all lower in the experimental group compared to the control group(P<0.05).Conclusion:Ultra-early enteral nutrition intervention can effectively improve the nutritional status and prognosis of patients after severe craniocerebral injury surgery.

Objective:To investigate the effect of individualized psychological nursing intervention on anxiety,de-pression and sleep quality of elderly patients with coronary heart disease(CHD)during the CO VID-19 epidemic.Methods:A total of 128 elderly CHD patients who were treated in our hospital during the CO VID-19 epidemic from Jan 2020 to Feb 2021 were selected,and randomly divided into control group(n=64,routine nursing)and in-tervention group(n=64,received individualized psychological nursing intervention),both groups were treated for one month.The scores of self-rating anxiety scale(SAS),self-rating depression scale(SDS)and Pittsburgh sleep quality index(PSQI)were compared between two groups before and after intervention.Results:Compared with before intervention,after intervention,there were significant reductions in scores of SAS,SDS,all dimensional scores and total score of PSQI in two groups,P＜0.01 all;compared with control group after intervention,there were significant reductions in scores of SAS[(53.31±1.87)points vs.(32.13±1.24)points],SDS[(44.14±1.38)points vs.(33.88±1.06)points]and total score of PSQI[(8.98±2.17)points vs.(7.33±1.26)points]in intervention group,P=0.001 all.Conclusion:The application of individualized psychological nursing intervention can significantly alleviate patient's anxiety and depression,improve quality of sleep in elderly CHD patients during the CO VID-19 epidemic,which helps to improve prognosis.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.