Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

ObjectiveTo explore the regulatory effect and mechanism of Danggui Shaoyaosan combined with Yinchenhaotang on lipid metabolism in the mouse model of type 2 diabetes mellitus （T2DM） complicated with metabolic dysfunction-associated steatotic liver disease （MASLD） based on network pharmacology and animal experiments. MethodsTwenty-four MKR transgenic diabetic mice were randomly allocated into 4 groups： Model， low-dose （12.6 g·kg^-1） Chinese medicine （concentrated decoction of Danggui Shaoyaosan combined with Yinchenhaotang）， high-dose （25.2 g·kg^-1） Chinese medicine， and Western medicine （metformin， 0.065 g·kg^-1）. Six FVB mice were used as the normal group. All groups were treated for 6 consecutive weeks. The mice in the drug treatment groups were administrated with corresponding agents by gavage， and those in the normal group and model group received the same volume of distilled water. Fasting blood glucose， body weight， liver weight， glucose tolerance， liver function indicators， blood lipid levels， and pathological changes in the liver were evaluated for each group. Network pharmacology was employed to analyze the targets and pathways of Danggui Shaoyaosan combined with Yinchenhaotang in the treatment of T2DM complicated with MASLD. Molecular biological techniques were used to verify the enriched key targets. ResultsCompared with the model group， each treatment group showed reduced fasting blood glucose， body weight， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and liver weight （P<0.01）. The high-dose Chinese medicine group was superior to the low-dose group in reducing low-density lipoprotein （LDL）， increasing high-density lipoprotein （HDL）， and recovering glucose tolerance （AUC） and ALT （P<0.05）， with the effect similar to that of the Western medicine group. Morphologically， Chinese medicine groups showed reduced lipid accumulation and alleviated pathological damage in the liver tissue， with the high-dose group demonstrating more significant changes. Network pharmacology results showed that Danggui Shaoyaosan combined with Yinchenhaotang may exert therapeutic effects through multiple targets such as fatty acid synthase （FAS）， acetyl-CoA carboxylase （ACC）， B-cell lymphoma-2 （Bcl-2）， MYC oncogene （MYC）， and interleukin-1β （IL-1β）. Western blot showed that compared with the model group， the treatment groups demonstrated down-regulated protein levels of FAS and ACC （P<0.01） and up-regulated protein levels of peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and UCP1 （P<0.01）. Compared with the low-dose Chinese medicine group， the high-dose Chinese medicine group exhibited down-regulated protein levels of FAS and ACC and up-regulated protein levels of PGC-1α and UCP1 （P<0.05）. ConclusionDanggui Shaoyaosan combined with Yinchenhaotang has the effect of ameliorating T2DM complicated with MASLD and can improve the liver lipid metabolism by up-regulating the protein levels of Fas and ACC and down-regulating the protein levels of PGC-1α and UCP1.

BACKGROUND:The occurrence and development of various ophthalmic diseases are closely related to excessive oxidative stress,and the inhibition of oxidative stress response may produce preventive and therapeutic effects. OBJECTIVE:To explore the role of Pax6 gene expression on hydrogen peroxide-induced aging of mouse bone marrow mesenchymal stem cells(BM-MSCs). METHODS:Resuscitated BM-MSCs,Pax6/BM-MSCs,and shPax6/BM-MSCs were treated with hydrogen peroxide for 24 hours,and then β-galactosidase staining was performed.The proliferation index Ki67 expression and apoptosis were detected by flow cytometry.The expression of senescence-associated molecules(Wnt7a,p21,and p53)was detected by RT-PCR. RESULTS AND CONCLUSION:(1)After hydrogen peroxide treatment,the cells of the three groups showed senescence phenotype and β-galactosidase staining was positive.Compared with BM-MSCs group,the expression of positive cells in Pax6/BM-MSCs group was less and that in the shPax6/BM-MSCs group was more,and the difference was statistically significant(P<0.05).(2)The results of flow cytometry showed that compared with BM-MSCs group,the positive expression of Ki67 in the Pax6/BM-MSCs group increased and the level of apoptosis decreased,while the positive expression of Ki67 decreased and the level of apoptosis increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(3)RT-PCR showed that compared with the BM-MSCs group,the expression of Wnt7a,p53,and p21 decreased in the Pax6/BM-MSCs group,while the expression of Wnt7a,p53,and p21 increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(4)These findings indicate that overexpression of Pax6 can antagonize the aging progression of BM-MSCs induced by hydrogen peroxide,which may be related to Wnt signaling pathway.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To analyze the bed utilization efficiency of various clinical departments in a public hospital and provide reference for the rational allocation of departmental bed resources.Methods Based on the data from a tertiary specialized hospital in 2022,traditional bed efficiency indicators were used as the basis.The Case Mix Index(CMI)was introduced for ad-justment,and the reasonable range of beds for each department was calculated.Data Envelopment Analysis(DEA)was em-ployed to comprehensively evaluate the input-output efficiency of each clinical department and determine the direction for optimi-zing bed allocation.Results Among the 39 departments included in the study,10 departments had inappropriate bed settings.Among them,5 departments needed additional beds,while 5 departments needed to reduce the number of beds.Conclusion By adjusting the bed efficiency indicators using CMI and combining the DEA method,hospitals can obtain a scientific basis for dy-namically adjusting the number of beds in clinical departments.Hospitals should make rational use of bed resources and scientifi-cally plan departmental beds.

Objective To explore the effect of applying comprehensive interventions on promoting pathogen detec-tion before antimicrobial therapy in hospitalized patients.Methods Hospitalized patients who received therapeutic use of antimicrobial agents in a tertiary first-class hospital from January 2020 to December 2021 were selected as the research subjects.Comprehensive intervention measures were implemented from January 2021.The pathogen detec-tion rates,detection classification,and detection rates of key monitored departments before antimicrobial therapy were compared between the pre-intervention group(January-December 2020)and the post-intervention group(Janu-ary-December 2021).Results A total of 10 239 hospitalized patients who received therapeutic use of antimicrobial agents were included in analysis,4 526 cases were in the pre-intervention group and 5 713 cases in the post-interven-tion group.The pathogen detection rates before antimicrobial therapy,before restricted grade antimicrobial therapy,and before special grade antimicrobial therapy after intervention were 94.56％,94.72％,and 96.03％,respective-ly,which were higher than 83.74％,84.47％,and 84.95％before intervention,with statistical significance(all P＜0.05).The detection rate of targeted pathogens after intervention was 64.87％,higher than that before interven-tion(28.04％),with statistically significant difference(P＜0.05).The pathogen detection rates before therapeutic use of antimicrobial agents in departments of critical care medicine,pulmonary and critical care medicine,pediatrics,neurosurgery,and general surgery after intervention were 93.20％,91.17％,92.20％,94.12％,and 91.15％,re-spectively,higher than the rates before intervention,namely 85.00％,82.19％,83.20％,83.33％,and 83.03％,respectively,with statistical significance(all P＜0.05).Conclusion The application of comprehensive intervention measures can improve the pathogen detection rate before antimicrobial therapy of hospitalized patients.Close atten-tion should be paid to the pathogen detection indicators related to healthcare-associated infection diagnosis and for the detection of sterile body fluid.

Neonatal hyperbilirubinaemia, clinically presenting as jaundice, is a ubiquitous and commonly a benign metabolic condition in newborn infants.It is a leading cause of hospitalization of neonates in the first week of life.Serum bilirubin has been considered as the most potent superoxide with the peroxyl radical scavenger activity.However, uncontrolled hyperbilirubinaemia or rapidly rising bilirubin can reach a neurotoxic concentration, potentially leading to central nervous system sequelae.Thus, the health status of jaundiced newborn infants is dependent on striking an appropriate balance between the protective effects of serum bilirubin and the risk of bilirubin neurotoxicity.In order to standardize the management of neonatal hyperbilirubinemia (jaundice), many countries have developed clinical practice management guidelines.This review sorted out and briefly interpreted the main contents of clinical management guidelines for neonatal hyperbilirubinemia drafted by the American Academy of Pediatrics and other countries, aiming to provide references of clinical diagnosis and treatment practice to domestic pediatrician.

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Diabetes Mellitus, Type 2/metabolism* ; Occludin/pharmacology* ; Claudin-1/metabolism* ; Intestinal Mucosa ; Liver ; Triglycerides/metabolism* ; Diet, High-Fat ; Homeostasis ; Mice, Inbred C57BL

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.