[Objective] To perform genetic analysis on samples with weak agglutination and mixed agglutination of ABO blood group antigens in neonates, and to investigate the molecular biological characteristics of ABO subtypes in neonates. [Methods] Serological identification of ABO blood group was performed by tube method and microcolumn gel method. The ABO exons 2-7 were amplified by PCR, and the amplified products were sequenced by Sanger sequencing method to determine the genotype. [Results] Among the ABO blood group serological results of 14 neonates, 8 cases showed weakened A antigen, and 6 cases showed weakened B antigen. Seven samples were identified with ABO subtype alleles, with genotypes as A102/B101+c.538C>T, Aw26/B102, A205/O02, A205/B101(2 cases), Aw26/O02, B(A)06/O01, B101/O01(3 cases), A102/O01(2 cases), A102/B101 and B101/O02. Additionally, three other family members were also found to carry B(A)06 allele in a pedigree investigation. [Conclusion] For samples showing weakened antigens in ABO blood type identification of neonates, it is necessary to consider the possibility of ABO subtype in addition to age factors, and genetic testing can be used to prevent missed detection of ABO subtypes in neonates.

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Objective:To evaluate the relationship between hippocampal receptor-interacting protein kinase-1 (RIPK1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in postoperative neurocognitive dysfunction of aged rats with chronic knee arthritis pain.Methods:Sixty-four healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups ( n=16 each) using a random number table method: chronic knee arthritis pain group (group P), chronic knee arthritis pain+ operation group (group PS), RIPK1 inhibitor necrostatin-1+ chronic knee arthritis pain+ operation group (group NPS), and DMSO+ chronic knee arthritis pain+ operation group (group DPS). The knee arthritis model was prepared by intra-articular injection of monosodium iodoacetate (MIA) 1 mg into the left knee joint, and 12 weeks later exploratory laparotomy was performed under sevoflurane anesthesia. Necrostatin-1 6.25 mg/kg and the equal volume of DMSO were intraperitoneally injected at 1 h before operation in NPS group and DPS group, respectively. Thermal pain threshold was measured at 1 week before MIA injection and 6 and 12 weeks after MIA injection. Morris water maze test was used to evaluate the cognitive function at 7 days after surgery. Hippocampal tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the expression of RIPK1, phosphorylated RIPK1 (p-RIPK1), NLRP3, activated cysteine-aspartic protease caspase-1 (cl-caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot) and contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Thermal pain threshold was significantly decreased at 6 and 12 weeks after MIA injection as compared with that before injection ( P<0.05), and there was no significant difference in thermal pain threshold among the four groups ( P>0.05). Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was up-regulated, and the contents of IL-1β and IL-18 were increased ( P<0.05), and pathological changes of hippocampal neurons were marked in PS group, DPS group and NPS group. Compared with PS group and DPS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was down-regulated, the contents of IL-1β and IL-18 were decreased ( P<0.05), and pathological changes of hippocampal neurons were significantly attenuated in NPS group. Conclusions:Postoperative hippocampal RIPK1 function is enhanced in aged rats with chronic knee arthritis pain, which then activates NLRP3 inflammasomes, triggering neuroinflammation, and this process may be involved in the mechanism of postoperative neurocognitive dysfunction.

Tumor-associated macrophages （TAMs）， as the main immune cells in the human body， are key factors in maintaining the homeostasis of the tumor microenvironment. With high plasticity， they can polarize into the classically activated （M1） macrophages or alternatively activated （M2） macrophages under different conditions. M1 macrophages can inhibit tumor growth by phagocytosis， and M2 can inhibit the immune microenvironment to promote tumorigenesis and immune escape. Small molecules of traditional Chinese medicine have been widely studied in gastrointestinal tumors. These small molecules exert anti-tumor activity by enhancing TAM activity and promoting the polarization of macrophages. Targeted intervention in TAMs with these molecules has the potential to inhibit the development of gastrointestinal tumors. This article summarizes the research status and significance of small molecules of traditional Chinese medicine targeting TAMs against gastrointestinal tumors， aiming to provide reference for the future studies in this field.

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

Objective:To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value.Methods:A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ2 test. Results:Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients ( P ?

Objective:To explore the efficacy, safety, and feasibility of single port laparoscopic liver resection via umbilical cord, and summarize its surgical experience.Method:A retrospective analysis was conducted on 39 patients who underwent liver resection surgery at the Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University from February 2022 to September 2023. There were 19 patients in the transumbilical single-port laparoscopic group, including 5 males and 14 females, aged (49.6±2.5) years. There were 20 patients in the multi-port laparoscopic group, including 7 males and 13 females, aged (49.9±3.1) years. The intraoperative blood loss, operation time, intestinal recovery time, postoperative hospital stay and postoperative complications were compared between the single-port group and multi-port group.Results:All 39 patients successfully completed the surgery without any additional foramen or conversion to open surgery. The operation time of the single hole group (166.3±59.0) min was longer than that of the multi-port group (123.2±48.0) min, and the difference was statistically significant ( t=2.50, P=0.020). There were no statistically significant differences in intraoperative blood loss, intestinal recovery time, postoperative hospital stay, and postoperative complications between these two groups (all P>0.05). All patients had no postoperative complications such as bleeding, infection, or bile leakage. Follow up for 3~21 months showed no recurrence of primary diseases such as hepatic hemangioma, hepatic adenoma, and intrahepatic bile duct stones. The aesthetic effect of the umbilical incision in the single orifice group was significant, and patient satisfaction was 100%. Conclusion:Umbilical single-port laparoscopic liver resection surgery is safe and feasible, with significant minimally invasive and aesthetic effects.

Objective To investigate the effects of YAP on the occurrence and progression of acute liver failure by regulating the ferroptosis pathway and its underlying mechanism. Methods A total of 20 8-week-old C57BL/6 mice were randomly divided into four groups: a control group, an acute liver failure model group, a YAP agonist XMU-MP-1 treatment group and a YAP inhibitor verteporfin treatment group, five mice for each group. HE staining was used to observe the pathological changes of hepatic inflammation and necrosis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by liver biochemistry. Iron (Fe), malondialdehyde (MDA), glutathione (GSH) determination kits were used to measure their levels in liver tissues of each group. The changes of hepatocyte mitochondrial in each group were observed by electron microscopy. Real time PCR and Western blot analysis were used to detect the mRNA and protein expressions of YAP, glutathione peroxidase 4 (GPX4) and 5-lipoxygenase (5-LOX). Results Compared with the control group, mice in the acute liver failure model group and the YAP inhibitor verteporfin treatment group showed severe liver tissue congestion with inflammatory cell infiltration and structural damage to hepatic lobules. Liver injury was alleviated in the XMU-MP-1 treatment group. With the occurrence of liver failure, plasma ALT and AST levels significantly increased, and liver function was improved in XMU-MP-1 treatment group. Electron microscopy showed that mitochondria in hepatocytes of mice with liver failure became smaller and bilayer membrane density increased, while mitochondria changes in the XMU-MP-1 group were alleviated. In addition, the acute liver failure model group showed an increase in Fe and MDA contents, decreased protein expressions of GPX4, and enhanced expression of 5-LOX, suggesting that ferroptosis was involved in acute liver failure in C57BL/6 mice. Ferroptosis was inhibited by activation of YAP. Conclusion Activation of YAP may ameliorate liver injury by inhibiting ferroptosis.
Animals ; Mice ; Ferroptosis ; Glutathione ; Liver Failure ; Liver Failure, Acute/drug therapy* ; Mice, Inbred C57BL ; Verteporfin ; YAP-Signaling Proteins/metabolism*

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Objective:To investigate the diagnostic value of ultrasound elastography combined with enhancer of Zeste homolog 2 (EZH2) and breast cancer susceptibility gene 1 (BRCA1) proteins in triple-negative breast cancer.Methods:A total of 116 breast cancer patients selected for treatment in our hospital from 2019 to 2021 were analyzed, and ER and PR were analyzed according to the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Patients who were all HER2 negative were classified as TNBC group, with a total of 21 cases, and patients who were positive for ER, PR, and HER2 were classified as non-TNBC, a total of 95 cases. All enrolled patients underwent ultrasonic elastography examination. The positive expression of EZH2 and BRCA1 was detected by immunohistochemistry. Chi-square test was used to analyze the diagnostic value of ultrasound elastography combined with EZH2 and BRCA1 proteins in TNBC.Results:In the TNBC group, the proportion of smooth edges (35.09) and lobulation of lesions (9.52) was higher than that in the non-TNBC group (12.63, 5.26), while the proportion of burrs (28.57) and fuzziness (23.81) was lower than that in the non-TNBC group (50.53, 31.58). The proportion of calcifications (52.38) in the TNBC group was lower than that in the non-TNBC group (85.26). The non-attenuation ratio of rear echo (80.95) was higher than that of non-TNBC group (52.63). The proportion of blood flow grade enrichment (57.14) was lower than that in the non-TNBC group (63.16) (all P<0.05). The positive expression rate of EZH2 in the TNBC group (85.71) was higher than that of non-TNBC (63.16) ( P<0.001), and the positive expression rate of BRCA1 in the TNBC group (19.05) was lower than that of non-TNBC (55.79) ( P<0.05). The posterior echo non-attenuation ratio (88.89) and rich blood supply ratio (88.89) of EZH2 positive patients in the TNBC group were higher than those with negative (33.33, 0) (all P<0.05), and the rear echo non-attenuation ratio (25.00) and rich blood supply ratio (25.00) of BRCA1 positive in the TNBC group were lower than those with negative (52.94, 88.24) (all P<0.05) ; According to the pathological results, the sensitivity, specificity and accuracy of posterior echo for the diagnosis of TNBC were 25.37%, 91.84% and 53.44%, respectively. The sensitivity, specificity and accuracy of EZH2 were 23.08%, 92.11% and 45.69%, respectively. The sensitivity, specificity and accuracy of BRCA1 were 28.81%, 92.98% and 60.34%, respectively. The combined sensitivity, specificity and accuracy of the three were 53.13%, 95.24% and 83.62%, respectively. The sensitivity, specificity and accuracy of blood flow fraction for the diagnosis of TNBC were 25.81%, 90.74% and 56.03%, respectively. The sensitivity, specificity and accuracy of blood flow fraction, EZH2 and BRCA1 were 59.26%, 94.38% and 86.21%, respectively. Conclusion:The joint classification of the posterior echoes and blood flow in ultrasonic elastography combined with EZH2 and BRCA1 has important significance in the diagnosis of TNBC.