OBJECTIVES: This study aimed to explore the biological functions and clinical value of mothers against decapentaplegic homolog (SMAD) 7 in head and neck squamous cell carcinoma (HNSCC) through bioinformatics analysis and basic experiments. METHODS: The expression of SMAD7 in HNSCC in public databases was studied. Western blot was used to detect the expression of SMAD7 in HNSCC cell lines and normal epithelial cells. The SMAD7 highly expressed HNSCC cell line HSC-4 was silenced, and CCK-8, Transwell assays, and cell scratch experiments were conducted to study the effect of SMAD7 on the biological functions of HSC-4 cells. HNSCC expression profile data were obtained from UCSC xena, and genes related to SMAD7 were selected for gene ontology and Kyoto encyclopedia of genes and genomes gene enrichment analysis, construction of a co-expression gene interaction network, and screening of related cell signaling pathways. Western blot was used to detect the expression changes of proteins in the related cell signaling pathways in HNSCC cells with silenced SMAD7. cBioPortal was utilized to analyze the mutation rate of the SMAD7 gene, and the MethSurv database was used to analyze the methylation level of the SMAD7 gene and its correlation with prognosis. The receiver operating characteristic curve was used to assess the diagnostic value of SMAD7 for HNSCC. TIMER2.0 was used to analyze the correlation between SMAD7 expression and immune cell infiltration. RESULTS: SMAD7 was highly expressed in HNSCC tumor tissues and some cell lines. Silencing the expression of SMAD7 can significantly inhibit the proliferation, migration, and invasion of cancer cells. Silencing SMAD7 can induce the downregulation of vascular cell adhesion molecule 1 (VCAM-1). The bioinformatics analysis showed that the mutation rate of the SMAD7 gene and the methylation level were significantly correlated with the prognosis of patients with HNSCC. The expression of SMAD7 was related to the level of immune cell infiltration in HNSCC. CONCLUSIONS SMAD7 promotes the proliferation, migration, and invasion of HNSCC cells by regulating the expression of VCAM-1. It may be a potential tumor biomarker and therapeutic target for HNSCC.
Humans ; Smad7 Protein/metabolism* ; Prognosis ; Squamous Cell Carcinoma of Head and Neck ; Head and Neck Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Signal Transduction ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Computational Biology

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate whether hsa_circ_0054595(circRTN4)is involved in glomerulosclerosis of lupus nephri-tis(LN)by regulating monocyte-derived TNF-α.Methods:RT-qPCR and immunofluorescence were used to detect the expression of TNF-α in monocytes of LN patients,and fluorescence in situ hybridization(FISH)was used to detect the expression of circRTN4.THP1 cells were transfected with circRTN4-siRNA and negative control NC-siRNA,respectively.RT-qPCR and Western blot were used to detect the expression of TNF-α in THP1cell,and ELISA was used to detect the expression of TNF-α in THP1 culture superna-tant.THP1 cells were transfected with mircoRNA mimics,and the expression of TNF-α was detected by Western blot.The direct bind-ing of miR-486-3p to TNF-α and circRTN4 were verified by reversion experiment and dual luciferase reporter gene experiment.MRL/lpr mice were injected with circRTN4 recombinant adeno-associated virus via tail vein,and the expression of circRTN4 in peripheral blood mononuclear cells of the mice was detected by RT-qPCR.ELISA was used to detect the expression of serum TNF-α.HE staining and PAS staining were used to observe the pathological changes,and immunofluorescence was used to detect the expression of FN.Results:The expressions of TNF-α and circRTN4 were increased in monocytes of LN patients(P<0.05).The expression of TNF-α in THP1 was significantly increased in the LN group(P<0.01).Knockdown of circRTN4 inhibited the expression and secretion of TNF-α(P<0.05),and this effect was achieved by binding to miR-486-3p(P<0.01).In vivo,knockdown of circRTN4 in peripheral blood monocytes of MRL/lpr mice reduced the expression of TNF-α in serum(P<0.05),and improved glomerular cell proliferation and FN deposition.Conclusion:Highly expressed circRTN4 in monocytes promotes the expression of TNF-α by binding to miR-486-3p,and participates in the occurrence and development of glomerulosclerosis in LN.

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.

Objective:To explore the perinatal management of patients with WD during pregnancy, and to determine its genetic etiology and the possibility of fetal morbidity using the genetic detection of amniotic fluid and umbilical cord blood.Method:In terms of fine management during the perinatal period, a case of K-F ring was found in the Ophthalmology Department of Beijing Friendship Hospital, Capital Medical University in March 2019 due to eye astringency and eye swelling, and the hepatology department further diagnosed WD for one artificial abortion. After the second pregnancy in October 2020, multidisciplinary consultation and standardized treatment during pregnancy including gynecology and obstetrics, liver disease center, anesthesiology department, gastroenterology department and nutrition department were carried out. The genomes of patients' venous blood, amniotic fluid and umbilical cord blood were extracted and analyzed for ATP7B gene variation by Sanger sequencing.Result:Through multi-disciplinary collaborative management, the patient gave birth successfully in the case of pregnancy complicated with liver cirrhosis, portal hypertension, splenomegaly with hyperfunction, thrombocytopenia, anemia, esophageal and gastric varices and other complications. The phenotype of the newborn was normal, and the Apgar score was 10-10-10. Sequencing results showed that the patient had ATP7B p.Arg778Leu and p.Val890Met, which were missense heterozygous variants reported in the mutation database, and ACMG was classified as pathogenic variants. The results of amniotic fluid and umbilical cord blood showed that the fetus had only p.Arg778Leu single heterozygous variation, and it was predicted that there would be no clinical phenotype of WD.Conclusion:Perinatal multidisciplinary collaborative management has important protective significance for the successful pregnancy of patients with WD. Genetic screening of amniotic fluid and umbilical cord blood is conducive to early detection of fetal WD.

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P < 0.001). There were significant differences in the number of patients with low or high expression of miR-486-5p between the patients with different TNM stages, presence or absence of lymphatic metastasis, and presence or absence of distant metastasis ( χ 2 =13.765, 5.157, and 6.638, all P < 0.05). Compared with CA19-9 alone, miR-486-5p+CA19-9 had a significantly better value in distinguishing the operable group from the benign pancreatic disease group (area under the ROC curve [AUC]=0.87, 95% confidence interval [ CI ]: 0.760-0.942; with a sensitivity of 81.3% and a specificity of 83.3%), distinguishing the operable group from the healthy control group (AUC=0.92, 95% CI : 0.836-0.970; with a sensitivity of 90.6% and a specificity of 86.4%), and distinguishing the operable group from the non-operable group (AUC=0.94, 95% CI : 0.884-0.998; with a sensitivity of 85.7% and a specificity of 93.7%) ( Z =2.841, 2.510, and 2.387, all P < 0.05), and the optimal cut-off values were 3.12, 3.21, and 6.63, respectively. Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.

Objective:To explore the risk factors that may affect the prognosis of sepsis in children.Methods:A retrospective study was conducted. Septic children who aged 28 days to 18 years old admitted to the department of critical care medicine of Xi'an Children's Hospital from January 2018 to May 2019 were enrolled. The general demographic data and clinical indicators within 8 hours after admission were collected, and the 28-day mortality was the end point. The differences of the indexes between the survival and the dead children were compared, and the risk factors of prognosis by binary Logistic regression analysis were analyzed. The predictive value of related risk factors on the prognosis was verified by receiver operating characteristic (ROC) curve.Results:A total of 165 children with sepsis were selected, 75 died in 28-days with a 28-day mortality of 45.45%. Compared with the survival group, the alanine aminotransferase (ALT), aspertate aminotransferase (AST), serum creatinine (SCr), creatine kinase isoenzyme (CK-MB), lactate (Lac) and procalcitonin (PCT) in the dead group significantly increased [ALT (U/L): 404.99±88.26 vs. 181.64±35.17, AST (U/L): 453.37±35.37 vs. 210.69±92.50, SCr (μmol/L): 156.46±105.65 vs. 54.32±25.46, CK-MB (U/L): 244.86±53.68 vs. 97.29±19.11, Lac (mmol/L): 5.55±1.66 vs. 2.49±1.29, PCT (ng/L): 35.55±15.87 vs. 18.66±4.91, all P < 0.01], while platelet count (PLT), serum ionized calcium concentration (iCa 2+) significantly decreased [PLT (×10 9/L): 81.49±29.53 vs. 165.43±97.81, iCa 2+ (mmol/L): 0.89±0.16 vs. 1.84±0.14, both P < 0.01]. There was no significant difference in gender, age, prothrombin time (PT), activated partial thromboplastin time (APTT), albumin (ALB) and blood urea nitrogen (BUN) between the two groups. Binary Logistic regression analysis showed that Lac, SCr and PCT were the risk factors for the prognosis of children with sepsis [odds ratio ( OR) and 95% confidence interval (95% CI) were 2.18 (1.22-3.09), 2.01 (1.00-2.07), 1.14 (1.07-1.21), respectively, all P < 0.01], while PLT and iCa 2+ were protective factors [ OR and 95% CI were 0.95 (0.93-0.98), 0.32 (0.12-0.42), respectively, both P < 0.01]. Further ROC curve analysis showed that Lac, PCT and SCr were all of predictive value for the prognosis of children with sepsis, and the area under ROC curve (AUC) was 0.881, 0.864, 0.711, respectively (all P < 0.01); the combined predicted AUC of Lac, SCr, PCT, PLT and iCa 2+ influencing factors was as high as 0.981, with the sensitivity of 97.6%, and the specificity of 98.7%. Conclusion:Lac, PCT and SCr are independent risk factors for the prognosis of children with sepsis.

Objective:To explore the expression of serum miR-224-5p in PDAC and its significance for early clinical diagnosis.Methods:From August 2018 to April 2020, 40 patients with PDAC (11 patients with early PDAC, 29 patients with advanced PDAC), 21 patients with chronic pancreatitis and 40 healthy volunteer controls admitted in Qingdao Municipal Hospital were enrolled. The level of serum miR-224-5p in each group was detected by qRT-PCR method, and the correlation with clinicopathological parameters was analyzed. The receiver-operating characteristic (ROC) curve of miR-224-5p, CA19-9 and miR-224-5p combined with CA19-9 were drawn, and the sensitivity and specificity of the diagnosis were calculated.Results:The serum miR-224-5p levels in early PDAC group, middle and late PDAC group, chronic pancreatitis group and healthy control group were 3.21(2.01, 4.60), 4.70(3.50, 8.26), 1.72(1.02, 2.78) and 1.38(0.89, 2.11), respectively; and the level of serum miR-224-5p in the middle and late PDAC group was significantly higher than that in the early PDAC group, and that in the early PDAC group was significantly higher than that in the chronic pancreatitis group and the healthy control group, and all the differences were statistically significant ( P<0.05). The sensitivity of serum miR-224-5p combined with CA19-9, miR-224-5p, and CA19-9 in the diagnosis of overall PDAC was 95.0%, 85.0% and 67.5%, respectively; and the specificity was 70.0%, 82.5% and 87.5%, respectively. The sensitivity for early PDAC was 90.9%, 72.7% and 63.6%, and the specificity was 85.0%, 72.5% and 87.5%, respectively. MiR-224-5p combined with CA19-9 has the highest specificity in the diagnosis of PDAC. The level of serum miR-224-5p in patients with PDAC was correlated with TNM stage, lymph node metastasis and distant metastasis (all P values <0.05). Conclusions:The expression of serum miR-224-5p was significantly up-regulated in patients with early PDAC, and The level of serum miR-224-5p in patients with PDAC was correlated with TNM stage, lymph node metastasis and distant metastasis. The sensitity of serum miR-224-5p and miR-224-5p combined with CA19-9 for early PDAC diagnosis were superior to CA19-9 alone, which can be used as a potential sensitive biological marker for early screening of PDAC.

Hepatolenticular degeneration (HLD) is an autosomal recessive inherited disorder of copper metabolism.The mutations in the ATP7B gene on chromosome 13 leads to the functional defect of ATP7B,which produces pathological deposits of copper in liver,brain,comea and kidney,with diverse clinical manifestations in various forms of liver disease,nervous system disease and corneal disease (Kayser-Fleischer rings).Early diagnosis and proper treatment can improve the prognosis of hepatolenticular degeneration.Conversely,it may progress to end-stage liver disease or severe motor dysfunction,which seriously affects patient quality of life.

Objective To investigate the consistency of fetal gallbladder volume (FGV) during middle-late pregnancy with three-dimensional ultrasonic virtual organ computer-aided analysis (VOCAL) technique at different rotation angles,and to analyze the correlation between FGV and gestation age.Methods A total of 157 healthy pregnant women underwent prenatal screening were included.The reference range of FGV was measured with three-dimensional ultrasonic VOCAL at 30°,18° and 12° rotation angle,respectively.The correlation between FGV and gestation age was observed,and the consistency of FGV values measured with VOCAL at different rotation step angles was compared.Results The correlations between FGV values measured with VOCAL at 30°,18°,12° rotation step angles and gestation age were all excellent (r=0.92,0.88,0.90;all P＜ 0.001).The consistency of FGV values measured with VOCAL at different rotation step angles was very good (30° and 18°,ICC=0.94;30° and 12°,ICC=0.97;18° and 12°,ICC=0.94).Conclusion Three-dimensional ultrasonic VOCAL can be used to establish the reference range of fetal gallbladder volume in middle-late pregnancy.The consistency of FGV values measured with VOCAL at different rotation step angles was very good,and the correlation between FGV and gestation age was excellent.