OBJECTIVE To investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective:To determine the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition). Methods:A preliminary list of clinical issues for the guidelines was developed through literature review, clinical surveys, and expert interviews. This was followed by two rounds of Delphi questionnaire surveys, with quality control and statistical analysis conducted using expert positive coefficient, mean item scores, full score ratio, coefficient of variation, Cronbach′s α coefficient, and expert authority level to finalize the list of clinical issues.Results:The experts participating in the Delphi questionnaire surveys had multidisciplinary collaborative backgrounds and regional representativeness, with a high level of authority. The overall positive coefficient of expert participation in the surveys was 78.9%. Through two rounds of the Delphi method and based on the screening criteria of a mean score ≥3.5, coefficient of variation ≤30%, and full score ratio ≥30%, 17 clinical issues were ultimately included following an expert consensus meeting.Conclusions:Through the Delphi method and rigorous quality control, the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition) are determined, laying a foundation for the subsequent development of the guidelines.

Objective To investigate the efficacy of cannabidiol(CBD)in improving renal function and protecting the kidney in mice with unilateral ureteral obstruction(UUO).Methods A total of 24 healthy,8-week-old,WTC57BL/6 male mice were divided into the Sham group,UUO group and UUO+CBD group,with 8 rats in each group.The UUO models were established by ligating one side of the ureter and removing the contralateral kidney to ensure unilateral kidney hydronephrosis.In the UUO+CBD group,5 mg/kg CBD was intraperitoneally injected immediately after the operation,once a day for 10 days.The Sham and UUO groups were given the same amount of normal saline.Blood sample was collected through the inner canthus venous plexus of the orbit 24 hours after the last administration.The levels of serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),superoxide dismutase(SOD),and malondialdehyde(MDA)were detected with an automatic biochemistry analyzer.The histopathological sections were prepared,the pathological changes of renal tissues were observed under a light microscope,and the pathological injuries were scored.Mitochondrial quantity and morphological structure changes were observed with a transmission electron microscopy.Results Compared with the Sham group,the UUO group exhibited significantly higher levels of Scr[(22.55±3.29)μmol/L vs.(12.11±3.32)μmol/L],BUN[(18.62±2.15)mmol/L vs.(10.05±1.19)mmol/L],TNF-α[(21.04±2.56)pg/mL vs.(9.26±0.47)pg/mL],IL-1β[(10.25±1.25)pg/mL vs.(5.44±0.99)pg/mL],and MDA[(31.26±1.17)nmol/mL vs.(17.12±1.39)nmol/mL],but significantly lower level of SOD[(90.26±2.11)U/mL vs.(136.54±3.05)U/mL],all P＜0.000 1.Compared with the UUO group,the UUO+CBD group showed a significant decrease in the levels of Scr[(16.82±0.89)μmol/L vs.(22.55±3.29)μmol/L],BUN[(14.35±0.99)mmol/L vs.(18.62±2.15)mmol/L],TNF-α[(16.29±0.88)pg/mL vs.(21.04±2.56)pg/mL],IL-1β[(6.23±0.95)pg/mL vs.(10.25±1.25)pg/mL],MDA[(20.36±1.23)nmol/mL vs.(31.26±1.17)nmol/mL],and renal pathological damage score[(1.88±0.64)vs.(2.50±0.76)],but a significant increase in SOD level[(117.84±1.57)U/mL vs.(90.26±2.11)U/mL],all P＜0.000 1.Under electron microscopy,mitochondrial swelling,loss of inner membrane structure,and membrane rupture were observed in the UUO group,while the UUO+CBD group showed milder morphological changes.Conclusion CBD improves renal function in UUO model mice through anti-inflammatory,antioxidant and mitochondrial protection,and is a potential therapeutic drug for renal protection in clinic.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Central line associated bloodstream infection (CLABSI) is the most severe complication of indwelling intravascular catheters and one of the most common causes of intensive care unit (ICU)- or hospital-acquired infections. Once CLABSI occurs, it significantly increases the risk of mortality, long of hospital stay, and healthcare economic burden. In recent years, multiple large-scale clinical studies on the diagnosis, treatment, and prevention of CLABSI have been completed, providing evidence-based medical support for related practices. Additionally, evolving global trends in antibiotic resistance epidemiology and the development of novel antimicrobial agents necessitate adjustments in clinical management strategies. Based on these developments, the Chinese Society of Critical Care Medicine has updated and revised the Guideline on the Prevention and Treatment of Intravascular Catheter-Related Infections (2007). This guideline was developed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for evidence quality assessment. Guided by clinical questions, the working group initiated the process by defining key clinical issues, conducting literature searches, screening studies, performing meta-analyses, and synthesizing evidence-based findings to draft preliminary recommendations. These recommendations underwent iterative revisions through expert panel reviews, remote and in-person meetings, and two rounds of voting by the Standing Committee of the Chinese Society of Critical Care Medicine before finalization. The guideline comprises 52 recommendations, focusing on adult patients with central venous catheters in ICU. Key areas addressed include: selection of catheter insertion sites and techniques, catheter type and design, catheter management, prevention, diagnosis, and treatment of CLABSI. The guideline aims to provide ICU healthcare professionals with best practices for central line management, ensuring standardized clinical protocols for adult CLABSI.
Humans ; Catheter-Related Infections/therapy* ; Catheterization, Central Venous/adverse effects* ; Bacteremia/therapy* ; Intensive Care Units ; Cross Infection/prevention & control*

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Nucleic acid aptamers are short oligonucleotide sequences that can specifically bind to target substances with affinity comparable to or even better than protein antibodies.Due to their advantages of low cost,ease of modification,and low immunogenicity,aptamers have shown great potential in early cancer screening,diagnosis and targeted therapy.This paper systematically re-views the latest research progress on nucleic acid aptamers in immunotherapy,gene therapy,and drug delivery,discusses the current status and technical challenges of aptamers in cancer therapy and outlines future research directions.

Objective To investigate the efficacy of cannabidiol(CBD)in improving renal function and protecting the kidney in mice with unilateral ureteral obstruction(UUO).Methods A total of 24 healthy,8-week-old,WTC57BL/6 male mice were divided into the Sham group,UUO group and UUO+CBD group,with 8 rats in each group.The UUO models were established by ligating one side of the ureter and removing the contralateral kidney to ensure unilateral kidney hydronephrosis.In the UUO+CBD group,5 mg/kg CBD was intraperitoneally injected immediately after the operation,once a day for 10 days.The Sham and UUO groups were given the same amount of normal saline.Blood sample was collected through the inner canthus venous plexus of the orbit 24 hours after the last administration.The levels of serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),superoxide dismutase(SOD),and malondialdehyde(MDA)were detected with an automatic biochemistry analyzer.The histopathological sections were prepared,the pathological changes of renal tissues were observed under a light microscope,and the pathological injuries were scored.Mitochondrial quantity and morphological structure changes were observed with a transmission electron microscopy.Results Compared with the Sham group,the UUO group exhibited significantly higher levels of Scr[(22.55±3.29)μmol/L vs.(12.11±3.32)μmol/L],BUN[(18.62±2.15)mmol/L vs.(10.05±1.19)mmol/L],TNF-α[(21.04±2.56)pg/mL vs.(9.26±0.47)pg/mL],IL-1β[(10.25±1.25)pg/mL vs.(5.44±0.99)pg/mL],and MDA[(31.26±1.17)nmol/mL vs.(17.12±1.39)nmol/mL],but significantly lower level of SOD[(90.26±2.11)U/mL vs.(136.54±3.05)U/mL],all P＜0.000 1.Compared with the UUO group,the UUO+CBD group showed a significant decrease in the levels of Scr[(16.82±0.89)μmol/L vs.(22.55±3.29)μmol/L],BUN[(14.35±0.99)mmol/L vs.(18.62±2.15)mmol/L],TNF-α[(16.29±0.88)pg/mL vs.(21.04±2.56)pg/mL],IL-1β[(6.23±0.95)pg/mL vs.(10.25±1.25)pg/mL],MDA[(20.36±1.23)nmol/mL vs.(31.26±1.17)nmol/mL],and renal pathological damage score[(1.88±0.64)vs.(2.50±0.76)],but a significant increase in SOD level[(117.84±1.57)U/mL vs.(90.26±2.11)U/mL],all P＜0.000 1.Under electron microscopy,mitochondrial swelling,loss of inner membrane structure,and membrane rupture were observed in the UUO group,while the UUO+CBD group showed milder morphological changes.Conclusion CBD improves renal function in UUO model mice through anti-inflammatory,antioxidant and mitochondrial protection,and is a potential therapeutic drug for renal protection in clinic.