OBJECTIVE To screen and quantitatively analyze the quality marker （Q-Marker） associated with anti-renal fibrosis in Shenqi shenshuai mixture （SQSS）， so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology， gene expression omnibus （GEO） and connectivity map （CMAP） databases， the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics，and 84 active ingredients with anti-renal fibrosis activity were further screened out， such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database， including berberine， quercetin， honokiol， nicotinamide， daidzein， coumarin， kaempferol， formononetin and amygdalin. The quantitative results showed that the average contents of the above components （excluding amygdalin） in 10 batches of SQSS were 2.523， 1.942， 26.848， 1.415， 0.692， 0.171， 0.374， 7.401 μg/mL， respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study， and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.

OBJECTIVE To screen and quantitatively analyze the quality marker （Q-Marker） associated with anti-renal fibrosis in Shenqi shenshuai mixture （SQSS）， so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology， gene expression omnibus （GEO） and connectivity map （CMAP） databases， the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics，and 84 active ingredients with anti-renal fibrosis activity were further screened out， such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database， including berberine， quercetin， honokiol， nicotinamide， daidzein， coumarin， kaempferol， formononetin and amygdalin. The quantitative results showed that the average contents of the above components （excluding amygdalin） in 10 batches of SQSS were 2.523， 1.942， 26.848， 1.415， 0.692， 0.171， 0.374， 7.401 μg/mL， respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study， and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.

Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms， they are often accompanied by a high risk of side effects. In recent years， the use of flavonoids from traditional Chinese medicine （TCM） in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors， regulating multiple cellular signaling pathways， alleviating oxidative stress， modulating immune system functions， inhibiting bone destruction， and suppressing angiogenesis. Due to their notable anti-inflammatory， antioxidant， and immunomodulatory activities， flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace， this paper explored research hotspots and frontiers in this field， systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids， provided a theoretical basis for their use in RA treatment and clinical applications， and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.

Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms， they are often accompanied by a high risk of side effects. In recent years， the use of flavonoids from traditional Chinese medicine （TCM） in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors， regulating multiple cellular signaling pathways， alleviating oxidative stress， modulating immune system functions， inhibiting bone destruction， and suppressing angiogenesis. Due to their notable anti-inflammatory， antioxidant， and immunomodulatory activities， flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace， this paper explored research hotspots and frontiers in this field， systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids， provided a theoretical basis for their use in RA treatment and clinical applications， and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

There are a variety of mechanical signals in the microenvironment of cells,which have temporal and spatial variability,which jointly regulate the histological processes such as cell proliferation,differentiation and migration.Piezo1 is a mechanically sensitive cationic channel.As a force sensor,it transmits signals to downstream pathways and participates in a variety of life activities in response to changes in the cell microenvironment.In this paper,the common signal pathways of Piezo1 were reviewed in order to identify the downstream signaling pathways regulated by Piezo1,thereby providing theoretical basis for inhibiting or delaying related diseases.

Toxoplasma gondii is an opportunistic pathogenic protozoan that causes zoonotic toxoplasmosis and is capable of infecting almost all warm-blooded animals,including humans.T.gondii infection is a globally prevalent zoonosis,posing a particularly high risk to immunocompromised populations.It presents a serious threat to public health and animal husbandry due to its complex life cycle and wide host range.Currently,the prevention and treatment of toxoplasmosis rely primarily on drugs,with a combination of sulfadiazine and pyrimethamine being the first choice in clinical practice.However,limitations in efficacy,side effects,and drug resistance restrict its widespread use.While some progress has been made in the development of anti-Toxoplasma drugs,no ideal treatment has yet been approved for market release or clinical trials.This paper reviews recent progress on the mechanisms of action and targets of novel anti-Toxoplasma drugs based on relevant studies.It aims to provide new ideas for future drug research and development while highlighting the opportunities and challenges in the field.

Decabromodiphenyl ether(BDE-209)and decabromodiphenyl ethane(DBDPE)are widely used brominated flame retardants,which have been detected in the atmosphere,water,soil,and various organisms.In this study,a method based on high-performance liquid chromatography-inductively coupled plasma-mass spectrometry(HPLC-ICP-MS)was developed for determination of BDE-209 and DBDPE in sediment.Firstly,the target compounds in the sediments were extracted by accelerated solvent extraction(ASE),and the extraction solvent was hexane/dichloromethane(1∶1,V/V).The extract was concentrated by rotary evaporation and purified by a composite silica gel column(6 g neutral silica gel,8 g acidic silica gel,and 4 g anhydrous sodium sulfate),concentrated by nitrogen blowing,and then re-dissolved with 1 mL of toluene for instrumental determination.The chromatographic separation was carried out on a TC-C18(2)column(250 mm×4.6 mm)with isocratic elution using methanol-isopropanol-water(89∶6∶5,V/V)as the mobile phase,and the samples were separated within 20 min.Further,the Br element was quantified by ICP-MS to realize the detection of the target.The results showed that the method established in this study exhibited good linearity(R2>0.999)in the range of 100-10000 ng/mL,and the limits of quantification(LOQs)of the method were 2.0 ng/g for BDE-209 and 10.0 ng/g for DBDPE,with the relative standard deviations(RSDs,n=3)lower than 10%,and the recoveries were in the acceptable range(80.9%-120.7%).The matrix effect was effectively controlled within 10%.In addition,by analyzing the actual sediment samples from Guangxi,a background point,and Taizhou,Zhejiang,a typical contaminated area,it was found that neither BDE-209 nor DBDPE was detected in the sediment from Guangxi,while the concentrations of BDE-209 and DBDPE in the sediment from Zhejiang ranged from 1591.8 to 3362.9 ng/g,which further demonstrated the applicability and reliability of the method for analyzing actual environmental samples.This study provided a strong technical support for the accurate detection of POPs in the environment.

Objective To develop an ICU patient care difficulty index based on psychosocial factors and to evaluate its reliability and validity,thereby providing a comprehensive tool for assessing the difficulties in ICU patient care.Methods Guided by Guarinoni theory,an index system was developed through systematic literature reviews,semi-structured interviews,two rounds of Delphi expert consultation and the analytic hierarchy process.Based on the drafted system,a questionnaire was formulated.The tests for validity and reliability were conducted on 290 patients selected by convenience sampling.Results The finalised ICU patient care difficulty index system was composed of 5 primary indices(the general condition of the patient,disease condition,nursing condition,social support,and organizational characteristics),13 secondary indices and 27 tertiary indices.The Kendall's coefficient of coordination W values were 0.380 and 0.498,respectively,indicating a statistically significant agreement(both P<0.001).The system demonstrated a robust reliability(Cronbach's α=0.896)and a good internal consistency.Validity was confirmed through a scale level-content validity index(S-CVI)of 0.94 and the item level-content validity indices(I-CVI)ranged from 0.87 to 1.00.Structural validity analysis,based on 8 extracted public factors,showed a cumulative variance contribution rate of 66.34%.Conclusion The ICU patient care difficulty index system shows a high reliability and validity,making it a valuable tool for accurately quantification of the difficulty in ICU patient care.This system provides a scientific basis for allocation of ICU nursing resource and performance distribution.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.