ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Objective To investigate the effects and mechanisms of lncRNA OIP5-AS1 on cell proliferation and apoptosis in esophageal squamous cell carcinoma(ESCC).Methods TE-1 cells were randomly divided into control(normal culture),si-NC(transfected with si-NC),si-OIP5-AS1(transfected with si-OIP5-AS1),si-OIP5-AS1+NC inhibitor(transfected with si-OIP5-AS1,NC inhibitor),si-OIP5-AS1+miR-129 inhibitor(transfected with si-OIP5-ASS1,miR-129 inhibitor),NC mimic(transfected with NC mimic),miR-129 mimic(transfected with miR-129 mimic),miR-129 mimic+Vector(transfected with miR-129 mimic,Vector),miR-129 mimic+KRAS[transfected with miR-129 mimic,Kirsten rat sarcoma virus oncogene(KRAS)]groups.The expression of OIP5-AS1 and miR-129 in each group was detected by real-time fluorescence quantitative polymerase chain reaction assay.The expression levels of KRAS,N-cadherin,Vimentin and E-cadherin in cells were detected by Western blot assay.Cell proliferation was detected by cell counting kit-8(CCK-8),and apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)assay.Results The expression levels of OIP5-AS1 in cells of control,si-NC,si-OIP5-AS1,si-OIP5-AS1+NC inhibitor,si-OIP5-AS1+miR-129 inhibitor groups were 1.00±0.13,0.98±0.12,0.25±0.04,0.25±0.02 and 0.89±0.08;the expression levels of miR-129 were 1.00±0.15,0.97±0.07,2.06±0.17,2.04±0.11 and 1.22±0.15;72 h absorbance values(OD)were 1.16±0.12,1.11±0.09,0.58±0.03,0.58±0.05 and 0.94±0.10.The KRAS protein expression levels of NC mimic,miR-129 mimic,miR-129 mimic+Vector,and miR-129 mimic+KRAS groups were 1.08±0.07,0.41±0.06,0.40±0.06,1.03±0.10;the 72 h OD values were 1.17±0.10,0.59±0.03,0.60±0.04 and 0.90±0.05,respectively.si-NC group was compared with si-OIP5-AS1 group,si-OIP5-AS1+NC inhibitor group was compared with si-OIP5-AS1+miR-129 inhibitor group,NC mimic group was compared with miR-129 mimic group,miR-129 mimic+Vector group was compared with miR-129 mimic+KRAS group,the differences of the above indexes were statistically significant(all P＜0.05).Conclusion OIP5-AS1 can promote ESCC cell proliferation and epithelial mesenchymal transformation by regulating miR-129 targeting KRAS.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

Pogostemon cablin is a famous southern medicine.As the important raw material for modern medicine and industry,Pogostemon cablin becomes required with a large marketing demand.However,due to the serious continuous cropping obstacles in the growth process of Pogostemon cablin,the aggravation of diseases of Pogostemon cablin and the degradation of its quality arose.This paper outlined the ecological factors such as climate factors,soil factors and topographic factors suitable for the growth of Pogostemon cablin,analyzed the continuous cropping obstacles and diseases arising in the cultivation,reviewed the current ecological planting mode of Pogostemon cablin such as crop rotation,intercropping,relay-cropping and under-forest planting,and also made a comprehensive evaluation of the economic benefits,ecological benefits and social benefits of the ecological planting mode of Pogostemon cablin,aiming to provide a theoretical basis and a reference for the promotion of the ecological planting mode of Pogostemon cablin.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Aim To investigate the effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration(RAS-RH)on oxidative stress and inflammatory injury of human umbilical vein endothelial cells(HUVECs)induced by ionizing radiation.Methods The model of HUVECs damage induced by 6 Gy X-rays was estab-lished.HUVECs were treated with different concentra-tions of RAS-RH(100,200,400 μg·L-1).The proliferative activity of HUVECs was detected by CCK-8 method,the structural changes of mitochondria were observed by transmission electron microscope,the level of ROS was detected by DCFH-DA probe,the change of intracellular mitochondrial membrane potential was detected by JC-1 kit,and the apoptosis and cycle were detected by flow cytometry.The contents of IL-6 and TNF-α in cells were detected by ELISA.The activities of MDA,CAT,SOD and GSH-PX were detected by biochemical kit.The gene expression levels of Nrf2,HO-1,NF-κB,eNOS and IL-6 were detected by qRT-PCR,and the expression levels of Nrf2,HO-1,eNOS,NF-κB,p-NF-κB and IL-6 protein were detected by Western blot.Results Compared with the model group,RAS-RH could increase the activity of HUVECs induced by ionizing radiation,decrease the rate of ap-optosis,decrease the level of intracellular ROS,re-duce the injury of intracellular mitochondria,increase the level of mitochondrial membrane potential,promote the expression of Nrf2,HO-1 and eNOS,and inhibit the expression of NF-κB and IL-6.Conclusions RAS-RH has anti-radiation,antioxidant and anti-in-flammatory effects,which may reduce the oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation by activating the activity of Nrf2/HO-1 signal pathway,thus promoting the activity of cell proliferation.

Osteosarcoma, a highly malignant tumor originating from bone tissue, is characterized by a high mortality along with a poor prognosis. The heterogeneity of the tumor microenvironment plays a pivotal role in its development and prognosis. Single-cell sequencing technology emerges as a crucial tool in elucidating this heterogeneity by delineating the functional characteristics and gene expression patterns of tumor cells, immune cells, and stromal cells within osteosarcoma tissues. This technology enables the depiction of the intricate interaction network between these cells. Utilizing the high-resolution advantage of single-cell sequencing, novel cell subtypes such as SPP1 (+) macrophages, C1QC (+) macrophages, and CLEC11A (+) B cells have been identified in osteosarcoma tissues, contributing to tumor growth and invasion within the tumor microenvironment. Identification of osteosarcoma stem cell subpopulations suggests that SERPINA1_CSCL1, FUS_CSCL2, and SPP1_CSCL3 populations may serve as the origin of osteosarcoma cells. Moreover, single-cell sequencing has revealed that mregDCs promote immune escape and tumor progression by selectively expressing CCR7, CCL17, CCL19, and CCL22 factors, thereby recruiting Treg cells. Additionally, this technology aids in the development of personalized chemotherapy regimens by pinpointing potential drug resistance targets in osteosarcoma, leading to the establishment of a drug resistance risk score model. In terms of disease prognosis, single-cell sequencing has identified immune infiltration-associated genes in osteosarcoma (e.g., EPHX2, FDPS, GBP1, MMD, ZYX), facilitating the construction of a prognostic analysis model for osteosarcoma patients, thus aiding in prognostic prediction.

The concept of ethnic medicine is divided into a broad sense and a narrow sense. The broad concept refers to the traditional medicine of the Chinese nation, and the narrow concept refers to the traditional medicine of Chinese ethnic minorities. The external medicine is one of the main forms of ethnic medicine, and it is also the important content of ethnic medicine for external use, which is widely used in clinical practice. As the theory of ethnic medicine is unique, the application methods have certain characteristics, which are the key technical parts of clinical practice. However, the existing traditional Chinese medicine consensus formulation me-thods cannot meet the needs of the consensus formulation of the external ethnic medicine. Therefore, the methods suitable for expert consensus on external ethnic medicine are required. This article took Expert opinion on clinical application of Baimai Ointment as an exa-mple, and explorde a reasonable, effective, multi-dimensional, and multi-stage method to formulate expert consensus on the external ethnic medicine. In this research, three-dimensional sources of information, including ancient classics, clinical research evidence, and expert application experiences, were systematically and scientifically collected. After organization and analysis, the information was formed into comprehensive evidence. In a formal consensus meeting, part of the recommendations reached consensus. As to the issues that did not reach agreement, in-depth interviews were used to explore the reasons for the differences and resolve the disagreements. Finally, unanimous recommendations were reached. There are common problems during the formulation process of Expert opinion on clinical application of Baimai Ointment. This study is expected to provide references for the formulation of expert consensus on other external ethnic medicine.
Humans ; Biological Products ; Consensus ; Drugs, Chinese Herbal

OBJECTIVE: To retrospectively analyze the clinical efficacy of olecranon osteotomy approach in the treatment of Dubberley type Ⅲ coronal fractures of the distal humerus and summarize the treatment experience. METHODS: From January 2016 to June 2020, 17 patients (5 males and 12 females) with Dubberley type Ⅲ coronal fractures of the distal humerus were treated by olecranon osteotomy approach. The age ranged from 37 to78 years old with an average of (58.5±12.9) years old. According to Dubberley classification, there were 5 cases of type Ⅲ A and 12 cases of type Ⅲ B. The curative effect was evaluated using the Borberg-Morrey elbow function score. The flexion, extension and rotation range of motion of the elbow joint, complications and postoperative imaging evaluation were recorded. RESULTS: All the 17 patients got bony union. The follow-up time ranged from 12 to 33 months with an average of (15.6±5.6) months. There was 1 case of ischemic necrosis of capitulum humeri, 2 cases of traumatic arthritis and 1 case of heterotopic ossification, 1 case of malunion of fracture. The range of motion was (114.80±19.50) °. The Broberg-Morrey score was 85.3±8.2, excellent in 5 cases, good in 9 cases, fair in 3 cases and poor in 0 case. CONCLUSION Through olecranon osteotomy approach, the articular surface of distal humerus could be fully exposed, and the operation is convenient. Anatomical reduction and rigid fixation of the articular surface of distal humerus are the key factors for the succesful outcome.
Male ; Female ; Humans ; Adult ; Olecranon Process/surgery* ; Elbow Joint/surgery* ; Humeral Fractures/surgery* ; Retrospective Studies ; Fracture Fixation, Internal/methods* ; Humerus/surgery* ; Treatment Outcome ; Range of Motion, Articular