The treatment of multidrug-resistant gram-negative bacterial infections has become a challenge in today's healthcare field,and time-to-event data analysis has shown significant value in clinical prognostic studies of critically ill patients.This study comprehensively reviewed the results of the application of time-to-event analysis in clinical studies of anti-multidrug-resistant gram-negative bacterial drugs,aiming to provide a scientific basis for the optimization of therapeutic strategies and prognostic assessment of multidrug-resistant gram-negative bacterial infections,and to promote the widespread application of time-to-event analysis methods in similar studies.

Heart failure(HF)has become a major global medical burden.Despite the existence of several drugs for the treatment of HF,the progno-sis is still not optimistic,which motivates us to seek new treatments for this disease.Vericiguat,a novel soluble guanylate cyclase(sGC)stimulator,has been approved for use in patients with heart fail-ure.Cardiac remodeling is the important patho-physiological basis of cardiovascular disease occur-rence and development,and closely related to the prognosis of patients.Accumulating evidence sug-gests that vericiguat inhibits cardiac remodeling,but the molecular mechanism remains unclear.Therefore,an in-depth understanding of the molec-ular mechanism of action of vericiguat will be im-portant for future studies of this drug as a poten-tial therapy for slowing the severity of heart fail-ure.This article reviews the mechanism and re-search status of the inhibitory effect of Vericiguat on cardiac remodeling.

OBJECTIVE To provide a reference for optimizing and promoting the quality standards of Shechuan naolitong granules. METHODS Fifteen batches of Shechuan naolitong granules were used as samples to establish HPLC fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. Similarity evaluation and common peak identification were performed， and orthogonal partial least squares discriminant analysis （OPLS-DA） was used to assess quality differences among different batches and to screen quality differential components. Using salvianolic acid B（SAB） as the internal reference， quantitative analysis of multi-components by single-marker （QAMS） was developed to simultaneously determine geniposidic acid （GA）， chlorogenic acid （CA）， vaccarin （VA）， ferulic acid （FA） and senkyunolide I （SI）. The results were compared with those obtained by the external standard method. RESULTS A total of 13 common peaks were identified in the HPLC fingerprints of 15 batches of samples， and the similarities of the spectra were all above 0.96. Seven chromatographic peaks were identified as GA （peak 3）， CA （peak 6）， VA （peak 8）， FA （peak 9）， SI （peak 11）， SAB（peak 12） and TA（peak 13）. OPLS-DA indicated that the differential quality markers among 15 batches were peaks 5， 11 （SI）， and 12 （SAB）.Using SAB as the internal reference， the relative correction factors for GA， CA， VA， FA and SI were calculated as 1.058 4， 0.594 3， 0.643 3， 0.342 7 and 0.262 8， respectively. The mean content of GA， CA， VA， FA， SI and SAB across the 15 batches of samples were 0.155 0， 0.085 4， 0.140 3， 0.071 8， 0.072 7， 1.276 3 mg/g， respectively， showing no significant difference compared with the ESM （P＞0.05）. CONCLUSIONS The established HPLC fingerprint and QAMS are simple， efficient and economical， providing a reference for the quality control and further development of Shechuan naolitong granules.

This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

Objective:To analyse the role of economic toxicity on anxiety symptoms in maintenance hemodialysis (MHD) patients, in order to provide reference for reducing anxiety symptoms and improving mental health literacy in MHD patients.Methods:This was a cross-sectional survey. A convenience sampling method was used to select MHD patients from Hangzhou Second People's Hospital Affiliated to Hangzhou Normal University and Deqing Hospital Affiliated to Hangzhou Normal University as the study subjects. The General Information Questionnaire, Economic Toxicity Composite Rating Scale, Family Resilience Questionnaire, Chronic Disease Management Self-Efficacy Scale, Social Support Rating Scale, and Self-rating Anxiety Scale were applied.The pathway of economic toxicity on anxiety symptoms in MHD patients was analyzed by AMOS26.0.Results:A total of 290 questionnaires were distributed, and 274 valid questionnaires were collected, with an effective response rate of 94% (274/290). Among the patients, there were 153 males and 121 females, aged (62.35 ± 12.57) years. The patients' economic toxicity score was (23.07 ± 5.36) points and anxiety symptom score (54.65 ± 17.31) points. The structural equation model was well fitted with χ2/ df=1.452, root mean square error of approximation was 0.041,goodness-of-fit index was 0.946,comparative fit index was 0.982, incremental fit index was 0.983, Tucker-Lewis index was 0.978. The results of the path analysis showed that economic toxicity in patients with MHD directly predicted anxiety symptoms, with an effect size of 36.4%; self-efficacy, family resilience, and social support played a significant role in the pathway between economic toxicity and anxiety symptoms pathways, with effect sizes of 23.4%, 27.4%, and 12.8%, respectively. Conclusions:Economic toxicity and anxiety symptoms in MHD patients are at risk values, and economic toxicity can directly affect anxiety symptoms, or indirectly through the mediating role of self-efficacy, family resilience, and social support.

The treatment of multidrug-resistant gram-negative bacterial infections has become a challenge in today's healthcare field,and time-to-event data analysis has shown significant value in clinical prognostic studies of critically ill patients.This study comprehensively reviewed the results of the application of time-to-event analysis in clinical studies of anti-multidrug-resistant gram-negative bacterial drugs,aiming to provide a scientific basis for the optimization of therapeutic strategies and prognostic assessment of multidrug-resistant gram-negative bacterial infections,and to promote the widespread application of time-to-event analysis methods in similar studies.

Heart failure(HF)has become a major global medical burden.Despite the existence of several drugs for the treatment of HF,the progno-sis is still not optimistic,which motivates us to seek new treatments for this disease.Vericiguat,a novel soluble guanylate cyclase(sGC)stimulator,has been approved for use in patients with heart fail-ure.Cardiac remodeling is the important patho-physiological basis of cardiovascular disease occur-rence and development,and closely related to the prognosis of patients.Accumulating evidence sug-gests that vericiguat inhibits cardiac remodeling,but the molecular mechanism remains unclear.Therefore,an in-depth understanding of the molec-ular mechanism of action of vericiguat will be im-portant for future studies of this drug as a poten-tial therapy for slowing the severity of heart fail-ure.This article reviews the mechanism and re-search status of the inhibitory effect of Vericiguat on cardiac remodeling.

Objective:To analyse the role of economic toxicity on anxiety symptoms in maintenance hemodialysis (MHD) patients, in order to provide reference for reducing anxiety symptoms and improving mental health literacy in MHD patients.Methods:This was a cross-sectional survey. A convenience sampling method was used to select MHD patients from Hangzhou Second People's Hospital Affiliated to Hangzhou Normal University and Deqing Hospital Affiliated to Hangzhou Normal University as the study subjects. The General Information Questionnaire, Economic Toxicity Composite Rating Scale, Family Resilience Questionnaire, Chronic Disease Management Self-Efficacy Scale, Social Support Rating Scale, and Self-rating Anxiety Scale were applied.The pathway of economic toxicity on anxiety symptoms in MHD patients was analyzed by AMOS26.0.Results:A total of 290 questionnaires were distributed, and 274 valid questionnaires were collected, with an effective response rate of 94% (274/290). Among the patients, there were 153 males and 121 females, aged (62.35 ± 12.57) years. The patients' economic toxicity score was (23.07 ± 5.36) points and anxiety symptom score (54.65 ± 17.31) points. The structural equation model was well fitted with χ2/ df=1.452, root mean square error of approximation was 0.041,goodness-of-fit index was 0.946,comparative fit index was 0.982, incremental fit index was 0.983, Tucker-Lewis index was 0.978. The results of the path analysis showed that economic toxicity in patients with MHD directly predicted anxiety symptoms, with an effect size of 36.4%; self-efficacy, family resilience, and social support played a significant role in the pathway between economic toxicity and anxiety symptoms pathways, with effect sizes of 23.4%, 27.4%, and 12.8%, respectively. Conclusions:Economic toxicity and anxiety symptoms in MHD patients are at risk values, and economic toxicity can directly affect anxiety symptoms, or indirectly through the mediating role of self-efficacy, family resilience, and social support.

Objective:To investigate the distribution of potential suitable habitats for Ixodes persulcatus in Heilongjiang Province during different climatic periods. Methods:The geographical location data of Ixodes persulcatus in Heilongjiang Province from 1980 to 2023 were collected through literature search and field ecological investigation. The environmental factor variables were downloaded from the WorldClim website and the Resource and Environmental Science and Data Platform. A combination of SDMtune, ENMTools packages, and the maximum entropy (MaxEnt) model were used to predict the potential habitats of Ixodes persulcatus in Heilongjiang Province during different climatic periods and determine its dominant environmental factors. Among them, the time range of historical climatic period data was 1970 - 2000. The future climatic period data (2021 - 2040, 2041 - 2060) were selected as the low forcing scenario (SSP126 scenario) of the shared socioeconomic pathways (SSP) in the Beijing Climate Center - Climate System Model version 2-Medium Resolution, to simulate the impact of global warming on the distribution of potential habitats for Ixodes persulcatus in Heilongjiang Province. Results:A total of 83 geographical distribution sites of Ixodes persulcatus in Heilongjiang Province were obtained. After screening, 10 environmental factors were included in the MaxEnt model. Among them, the cumulative contribution percentage of annual precipitation, average annual temperature, and vegetation type was 67.3%. Compared with historical climatic period, the total potential habitats of Ixodes persulcatus in Heilongjiang Province increased from 29.81 × 10 4 km 2 to 32.24 × 10 4 km 2 in 2041 - 2060. The center of potential habitats moved to 47.75° N, and 128.66° E, with a northwest offset of 126.07° and a migration distance of 45.83 km. Conclusion:With global climate warming, the total potential habitats of Ixodes persulcatus in Heilongjiang Province has increased, showing an overall trend of migration to the northwest.

Objective:To explore the effects of curcumin on the biological characteristics and expressions of NF-κB pathway-related proteins in glucocorticoid-resistant acute lymphoblastic leukemia (ALL) cell line Jurkat.Methods:The drug-resistant ALL cell line Jurkat was selected, and 1 μmol/L dexamethasone was used as the optimal concentration for drug resistance of Jurkat cells, and the cells were passaged and cultured. The cells were divided into 10, 25 and 50 μmol/L curcumin groups, as well as 50 μmol/L pyrrolidinedithiocarbamate (PDTC) group, and control group (equal volume of culture medium without drug was added). The cells in each group were cultured for 72 h, and the cell morphology was observed under an inverted microscope. The CCK-8 method was used to detect the proliferation ability of Jurkat cells, flow cytometry was used to detect the apoptosis ability and cell cycle of Jurkat cells, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expressions of NF-κB p65, NF-κB p50, IκBα, and A20 mRNA, and Western blotting was used to detect the expressions of NF-κB p65, NF-κB p50, IκBα, caspase-8, caspase-3, bcl-2, and A20 proteins.Results:Jurkat cells were treated with 10, 25, 50 μmol/L curcumin and 50 μmol/L PDTC for 72 h. In the control group, the cell membranes were basically intact, the size was uniform, the cell was round and transparent, and the cell nucleus had uniform fluorescence; a large number of deformed cells and cell fragments were observed in curcumin groups with different concentrations and 50 μmol/L PDTC group, with concentrated and fragmented nuclei and obvious apoptosis. After treating Jurkat cells with different concentrations of curcumin and 50 μmol/L PDTC for 24, 48 and 72 h, respectively, the cell proliferation inhibition rates in curcumin groups with different concentrations and PDTC group were higher than those in the control group (all P < 0.01). The apoptosis rates at 72 h in the control group, 10 μmol/L curcumin group, 25 μmol/L curcumin group, 50 μmol/L curcumin group, and 50 μmol/L PDTC group were (4.9±0.1)%, (99.2±0.1)%, (99.9±0)%, (100.0±0)%, and (100.0±0)%, respectively, and the difference was statistically significant ( F = 2 876 604.40, P < 0.001); compared with the control group, the apoptosis rates in curcumin groups with different concentrations and 50 μmol/L PDTC group were higher, and the differences were statistically significant (all P < 0.01). Compared with the control group, the proportions of S-phase and G 2-phase cells were lower and the proportion of G 1-phase cells was higher in curcumin groups with different concentrations and 50 μmol/L PDTC group at 72 h, and the differences were statistically significant (all P < 0.01). Compared with the control group, the protein and mRNA expressions of NF-κB p65 and NF-κB p50 in curcumin groups with different concentrations and 50 μmol/L PDTC group were lower (all P < 0.01), while the protein expressions of IκBα, caspase-8 and caspase-3 were higher (all P < 0.01), the protein expression of bcl-2 was lower ( P < 0.01), and the protein and mRNA expressions of A20 were higher (both P < 0.01). Conclusions:Curcumin can effectively reverse glucocorticoid resistance and promote apoptosis in Jurkat cells, which may be related to the influence of curcumin on NF-κB pathway-related proteins.