The drug resistance of the carbapenem-resistant Enterobacteriaceae(CRE)strains was mainly induced by multiple approaches such as production of carbapenemases,increase of bacterial outer membrane permeability,activation of active efflux pump system,formation of biofilm and drug modifying mechanisms.Those mecha-nisms involve deletion,mutation,insertion and posttranscriptional modification of relevant encoding genes,which may affect the susceptibility of the CRE strains to antibiotics.At present,the conventional clinical thera-pies include the use of traditional antibiotics,either the one-drug use or combined use of drugs.The development of novel antibacterial therapy is under way.The epidemiological characteristics of CRE infections,drug resist-ance mechanisms,current and prospective treatment strategies for CRE infections(covering new application of the drugs in available,the novel drugs such as ceftazidime/avibactam,meropenem/vaborbactam and imipenem/rele-bactam)were deeply reviewed in this article,so as to provide reliable reference for clinical prevention,control and treatment of CRE infections.

This paper comprehensively discusses the impact of obesity on female fertility, oocyte quality, early embryonic development, and assisted reproductive technology (ART), and evaluates the relationship between obesity and pregnancy complications, proposing corresponding prevention and treatment strategies. Studies have shown that obesity adversely affects oocyte quality through chronic inflammation, oxidative stress, and disruption of metabolic pathways, including meiotic defects, mitochondrial dysfunction, and epigenetic alterations. Obesity also affects early embryonic development, potentially leading to placental dysfunction and restricted fetal growth. In the field of ART, obese women face more challenges, such as increased risk of gestational diabetes and decreased success rates of in vitro fertilization. Additionally, obesity is associated with an increased risk of various pregnancy complications, including hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and cesarean section. This paper emphasizes the importance of preconception and prenatal weight management and proposes strategies to improve the fertility of obese women through lifestyle changes, pharmacological treatment, and surgical intervention. Ultimately, this thesis provides personalized recommendations for the reproductive health of obese women to improve fertility and pregnancy outcomes, ensuring the health status of both mother and child.

Objective To investigate the mechanisms by which miR-23 regulates the PI3K/AKT/mTOR signaling pathway to influence myocardial remodeling,fibrosis,and angiogenesis in hypertensive heart failure(HF)rats.Methods Forty rats were randomly divided into four groups(n=10 per group):a control group,a model group,an antagomir-NC group,and an antagomir-23 group.The HF model was established using a high-salt diet,and intervention was performed via tail vein injection of antagomir-23.Cardiac function parameters,the degree of myocardial fibrosis,cell apoptosis levels,and the expression of angiogenesis-related proteins including CD31,VEGF,and bFGF were measured in each group.Concurrently,the activity of the PI3K/AKT/mTOR signaling pathway was assessed.A dual-luciferase reporter assay was conducted to confirm that miR-23 targets PI3K.Results Inhibition of miR-23 significantly improved cardiac function in hypertensive HF rats,reduced myocardial fibrosis and apoptosis,and enhanced the expression of CD31,VEGF,bFGF,and activated the PI3K/AKT/mTOR signaling pathway in hypertensive HF rats(all P<0.05).The dual-luciferase assay confirmed that miR-23 negatively regulates PI3K expression.Conclusion Inhibition of miR-23 can activate the PI3K/AKT/mTOR signaling pathway,promote angiogenesis,reduce myocardial damage,thereby delaying the progression of hypertensive heart failure.

This paper comprehensively discusses the impact of obesity on female fertility, oocyte quality, early embryonic development, and assisted reproductive technology (ART), and evaluates the relationship between obesity and pregnancy complications, proposing corresponding prevention and treatment strategies. Studies have shown that obesity adversely affects oocyte quality through chronic inflammation, oxidative stress, and disruption of metabolic pathways, including meiotic defects, mitochondrial dysfunction, and epigenetic alterations. Obesity also affects early embryonic development, potentially leading to placental dysfunction and restricted fetal growth. In the field of ART, obese women face more challenges, such as increased risk of gestational diabetes and decreased success rates of in vitro fertilization. Additionally, obesity is associated with an increased risk of various pregnancy complications, including hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and cesarean section. This paper emphasizes the importance of preconception and prenatal weight management and proposes strategies to improve the fertility of obese women through lifestyle changes, pharmacological treatment, and surgical intervention. Ultimately, this thesis provides personalized recommendations for the reproductive health of obese women to improve fertility and pregnancy outcomes, ensuring the health status of both mother and child.

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Improving the nitrogen use efficiency (NUE) of Brassica napus is of significant importance for achieving the national goal of zero growth in chemical fertilizer application and ensuring the green development of the rapeseed industry. This study aims to explore the effects of the nitrate transporter gene BnaNRT1.5s on the nitrogen transport and NUE of B. napus, providing excellent genetic resources for the development of nitrogen-efficient B. napus varieties. The spatiotemporal expression of BnaA05.NRT1.5 as a key nitrogen responsive gene was profiled by qRT-PCR at different growth stages and for different tissue samples of B. napus 'Westar'. Subcellular localization was employed to examine its expression pattern in the cells. Additionally, CRISPR/Cas9 was used to create BnaNRT1.5s knockout lines, which were subjected to hydroponic experiments under high nitrogen (12.0 mmol/L) and low nitrogen (0.3 mmol/L) conditions. After the seedlings were cultivated for 21 days, root and shoot samples were collected for weighing, nitrogen content determination, xylem sap nitrate content assessment, and calculation of total nitrogen and NUE. The B. napus nitrate transporter BnaA05.NRT1.5 was localized to the cell membrane. During the seedling and early bolting stages, BnaA05.NRT1.5 was predominantly expressed in roots, while it was highly expressed in old leaves and mature silique skin during the reproductive stage. Compared with the wild type, the mutant BnaNRT1.5s showed significant increases in the dry weight and total nitrogen of seedlings under both high and low nitrogen conditions. Under low nitrogen conditions, NUE in the roots of BnaNRT1.5s significantly improved. Notably, under both high and low nitrogen conditions, the nitrate content in the shoots of BnaNRT1.5s decreased significantly, while that in the roots increased significantly, resulting in a significantly decreased shoot-to-root nitrate content ratio. BnaNRT1.5s is involved in regulating the transport of nitrate from the roots to the shoots, and its mutation enhances nitrogen absorption and utilization in B. napus seedlings, promoting seedling growth. This study not only provides references for understanding the physiological and molecular mechanisms by which BnaNRT1.5s regulates NUE but also offers valuable genetic resources for improving NUE in B. napus.
Brassica napus/genetics* ; Anion Transport Proteins/metabolism* ; Nitrogen/metabolism* ; Nitrate Transporters ; Plant Proteins/metabolism* ; Nitrates/metabolism* ; Gene Expression Regulation, Plant ; Biological Transport

The drug resistance of the carbapenem-resistant Enterobacteriaceae(CRE)strains was mainly induced by multiple approaches such as production of carbapenemases,increase of bacterial outer membrane permeability,activation of active efflux pump system,formation of biofilm and drug modifying mechanisms.Those mecha-nisms involve deletion,mutation,insertion and posttranscriptional modification of relevant encoding genes,which may affect the susceptibility of the CRE strains to antibiotics.At present,the conventional clinical thera-pies include the use of traditional antibiotics,either the one-drug use or combined use of drugs.The development of novel antibacterial therapy is under way.The epidemiological characteristics of CRE infections,drug resist-ance mechanisms,current and prospective treatment strategies for CRE infections(covering new application of the drugs in available,the novel drugs such as ceftazidime/avibactam,meropenem/vaborbactam and imipenem/rele-bactam)were deeply reviewed in this article,so as to provide reliable reference for clinical prevention,control and treatment of CRE infections.

AIM: To explore the effect of lncRNA SNHG6 on injury of human retinal microvascular endothelial cells(hRMECs)induced by high glucose and its possible mechanism.METHODS: The D-glucose-induced hRMECs were used to establish normal glucose(NG)and high glucose(HG)cell injured model. In the HG group, the hRMECs were cultured in DMEM medium at a concentration of 25 mmol/L D-glucose for 24 h, while in the NC group, they were cultured in DMEM medium at a concentration of 5.5 mmol/L D-glucose; according to experimental design, si-NC, si-SNHG6, si-SNHG6 and anti-miR-NC and si-SNHG6 and anti-miR-186-5p were transfected into hRMECs, and then incubated at a concentration of 25 mmol/L D-glucose for 24 h, with HG+si-NC group, HG+si-SNHG6 group, HG+si-SNHG6+anti-miR-NC group and HG+si-SNHG6+anti-miR-186-5p group marked, respectively. The quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of lncRNA SNHG6 and miR-186-5p; dual-luciferase reporter assay was used to detect the targeting relationship; MTT assay and flow cytometry were used to detect the cell proliferation and apoptosis, respectively; enzyme linked immunosorbent assay(ELISA)was used to detect the levels of IL-1β, TNF-α, IL-8, IL-10; testing kits were used to detect activity of SOD and level of MDA; the Western blot was used to detect the protein expression of cleaved-caspase3, Bax and Bcl-2.RESULTS: The lncRNA SNHG6 expression increased in the HG group, while miR-186-5p expression decreased(both P<0.05). There was target binding of lncRNA SNHG6 with miR-186-5p. After the transfection of si-SNHG6, cell inhibition rate, apoptosis rate, cleaved-caspase3, Bax protein levels, IL-1β, TNF-α, IL-8 contents, and MDA activity were decreased(P<0.05), while Bcl-2 protein, IL-10 contents, and SOD activity were increased(P<0.05). Co-transfection of si-SNHG6 and anti-miR-186-5p increased cell proliferation inhibition rate, apoptosis rate, cleaved-caspase3, Bax, IL-1β, TNF-α, IL-8, and MDA(P<0.05), but decreased Bcl-2, IL-10 and SOD(P<0.05).CONCLUSION: Interfering with lncRNA SNHG6 could inhibit cell apoptosis, inflammation and oxidative stress of high-glucose- induced hRMECs by elevating the expression of miR-186-5p.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.