Objective:To investigate the effect of oral immunotherapy with donor human milk on feeding tolerance in premature infants with very low birth weight.Methods:A total of 94 extremely low birth weight preterm infants admitted to the neonatal Intensive Care Unit of Cangzhou People's Hospital from August 2022 to February 2024 were selected, These infants were randomized at 1:1 into 2 groups (47 cases each) using random number method. The control group were given oral 0.9% sodium chloride (oral drip), while the experimental group were given donor human milk (oral drip). General information were collected, including gender, delivery method, twins or not, small for gestational age or not, birth weight, gestational age, intestinal feeding of dairy products, and so on. Total intestinal feeding time, length of hospital stay and feeding intolerance were compared between groups.Results:The total intestinal feeding time and length of hospital stay were significantly shorter in the experimental group compared with the control group ( P<0.05). The incidence of feeding intolerance in the experimental group was also lower than that in the control group ( P<0.05). Conclusion:Oral immunotherapy with donor human milk can improve the feeding tolerance in premature infants with very low birth weight and shorten the hospital stay.

Objective To investigate the in vivo and in vitro antimicrobial activity of ceftazidime/avibactam(CZA)alone or in combination with aztreonam(ATM)against carbapenem-resistant Enterobacterales(CRE),and provide evidence for clinical anti-infective therapy.Methods The minimum inhibitory concentrations(MICs)of CZA and ATM against 52 clinically isolated non-repetitive CRE strains in a hospital from 2018 to 2022 were deter-mined with microbroth dilution method,and the combined antimicrobial susceptibility testing was performed with the chessboard dilution method.Time-killing curve and Galleria mellonella infection model were used to test the bac-tericidal effect of CZA alone or in combination with ATM.Results Among the 23 KPC-producing CRE strains,91.3％(n=21)had MIC ≤ 4 μg/mL for CZA,and 8.7％(n=2)had MIC ≥128 μg/mL for CZA.MIC of CZA to 29 CRE strains(strains producing NDM,IMP,KPC+IMP,and KPC+NDM)were all ≥128 μg/mL.Of the 31 CZA-resistant strains,93.5％(n=29)strains had fractional inhibitory concentration(FIC)＜0.5 for combination of CZA and ATM,while 6.5％(n=2)had FIC of 0-1.The time-killing curve showed that CZA had bactericidal effect on KPC-producing strains,and CZA combined with ATM had bactericidal effect on CZA-resistant strains.Compared with the monotherapy group,CZA combined with ATM treatment significantly improved the survival rate of CRE-infected Galleria mellonella(median survival time 120 hour,P=0.001).Conclusion CZA has good antimi-crobial activity against KPC-producing bacteria.The combination of CZA and ATM had synergistic bacteriostatic effect on CZA-resistant strains.

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.

italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To explore the material basis and potential mechanism of Sanhuang Yishen Capsules in the treatment of diabetes through network pharmacology, molecular docking and experimental verification.Methods:The active components and targets of Sanhuang Yishhen Capsules were screened using China Natural product chemical composition database and SymMap database, and the related targets of T2DM were screened by GeneCards database. The "Chinese materia medica-active component-target" network was constructed, and the intersection genes were enriched by GO and KEGG using R language. Key active components were selected for molecular docking verification with potential core targets. 60 rats were divided into normal group, model group, and Sanhuang Yishen Capsules group according to random number table method, with 15 rats in each group. In addition to the normal group, the diabetic rat model was prepared in the other groups, and the corresponding drugs were intragastric in each group for 8 weeks. The levels of fasting blood glucose (FBG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were measured by radioimmunoassay. Western blotting was used to detect protein expressions of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), Akt serine/threonine kinase 1 (AKT1), recombinant tumor protein p53 (TP53), and recombinant caspase 3 (CASP3).Results:A total of 160 active components and 298 targets of Sanhuang Yishen Capsules, 2194 targets related to T2DM, and 166 intersection targets were obtained. GO and KEGG analyzed a series of biological reaction processes mainly involved in signal transduction, oxidative stress, apoptosis, etc., and mainly involved in the regulation of P13K/Akt, P53, CASP3 and other targets. The results of molecular docking showed that the main active components obtained by screening had strong binding with the target. Compared with model group, FBG, FINS, HOMA-IR, TP53 and CASP3 in Sanhuang Yishen Capsules group decreased ( P<0.05), EGFR, EGF and Akt1 proteins increased ( P<0.05). Conclusion:The mechanism of Sanhuang Yishen Capsules for the treatment of may be related to the regulation of EGF/EGFR/P13K/Akt signaling pathway, TP53 signaling pathway, CASP3 signaling pathway, PPARG signaling pathway, ESR1 signaling pathway, PTGS2 signaling pathway, CAT signaling pathway and CTNNB1 signaling pathway.

Background and objective Tumor microenvironment(TME)is one of the important factors in tu-morigenesis and progression,in which tumor-associated macrophages(TAMs)play an important role in non-small cell lung cancer(NSCLC)progression.However,the mechanism of TAMs in NSCLC progression remains unclear,so this study aimed to investigate the role of TAMs in NSCLC progression and to find potential therapeutic targets.Methods Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the expression of prostaglandin E2 receptor 4(EP4)mRNA in NSCLC and normal lung tissues;the protein expression levels of cyclooxygenase-2(COX-2),EP4,cluster of differentiation 86(CD86),CD163 and CD31 were detected by immunohistochemistry(IHC)in 120 NSCLC tissues and 24 paracancerous tissues specimens.The nude mouse lung adenocarcinoma cell A549 and macrophage RAW264.7 co-transplanted tumor model was established.And the samples were collected by gavage with EP4 inhibitor E7046,and then stained with hematoxylin-eosin(HE),IHC,and immunofluorescence(IF),and then detected by Western blot for the epithelial mesenchymal transformation(EMT)of the tumor tissues of the nude mice in each group.Western blot was used to detect the expressions of EMT related protiens in each group of nude mice;full-length transcriptome sequencing was used to screen the key genes causing liver me-tastasis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results EP4 mRNA expression level in NSCLC tissues was generally lower than that in normal lung tissues(P<0.05);COX-2,EP4,CD163,CD31 proteins were differentially expressed in NSCLC tissues and adjacent tissues,and differences were observed in many clinico-pathological parameters of NSCLC patients;RAW264.7 shortened the latency period of tumorigenesis of A549 and promoted the proliferation of tumors and liver metastasis of tumors,and E7046 could reduce tumor cell proliferation activity,tumor tissue vascular density and M2-type macrophage infiltration in nude mice;IF staining showed that macrophages were mainly distributed around the metastatic foci of tumors;Western blot results showed that compared with A549 alone transplantation group,the relative expression of E-cadherin protein in tumor tissues of mice in A549 and RAW264.7 co-transplantation group was significantly decreased,and the difference was statistically significant(P<0.05),while the relative expression of N-cadherin protein was up-regulated,but the difference was not statistically significant(P>0.05);the main pathways enriched in the differ-ential genes of the full-length transcriptome were the PI3K-AKT and MAPK signaling pathways.Conclusion During NSCLC development,the COX-2/PGE2/EP4 axis may promote tumor progression by inducing macrophage functional activation,and EP4 may be a potential new target for tumor immunotherapy.This study provides new perspectives and ideas for in-depth exploration of the mechanisms of NSCLC development,as well as a theoretical basis for the development of new therapeutic strategies for NSCLC.

Aim To study the reversal effect of albiflorin(AL)on multidrug resistance of human ovarian cancer and the potential mechanism. Methods The drug resistance reversal effect of AL on SKOV3/DDP cells was detected by CCK-8 kit,and the effect of AL on P-glycoprotein(P-gp)function was detected by flow cytometry. The effects of AL on MYC,WWP1 and ABCB1 in SKOV3/DDP cells were detected by RT-qPCR and Western blot. The MYC-knockdown SKOV3/DDP cell line was constructed by RNA interference technology,and its drug resistance,P-gp function and related gene and protein expression changes were investigated. Results AL had a drug resistance reversal effect on SKOV3/DDP cells and a concentration-dependent inhibitory effect on P-gp function. The inhibitory effects of AL 25,50 and 100 μmol·L-1 on ABCB1/P-gp,MYC and WWP1 were gradually enhanced. The inhibitory effect of MYCi975,a MYC inhibitor,on ABCB1/P-gp,MYC and WWP1 was stronger than or equivalent to that of AL 100 μmol·L-1 group. After knockdown of MYC in SKOV3/DDP cells,cell drug resistance,P-gp function,and related gene and protein expression were inhibited. Conclusions The drug resistance reversal effect of AL on SKOV3/DDP cells may be related to the inhibition of P-gp function and the expression of ABCB1/P-gp,MYC and WWP1,which provides an experiment base for the development of AL as a drug resistance reversal agent for the clinical treatment of ovarian cancer.

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ² Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Antiviral Agents/therapeutic use* ; DNA, Viral/therapeutic use* ; Retrospective Studies ; Mutation ; Drug Resistance, Viral/genetics* ; Lamivudine/therapeutic use*