ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Objective To establish an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS)method for identifying the active ingredients of Zhizi Houpu decoction,and to predict its material basis and mechanism of anti-insomnia effects using network pharmacology.Methods The chemical components of Zhizi Houpu decoction were identified according to UHPLC-QTOF-MS ion fragmentation rule combined with compound library and literature review.Components with oral bioavailability(OB)≥30％and drug-like properties(DL)≥0.18 were selected to construct the Zhizi Houpu decoction-active ingredients-target network.The STRING database and the Database for Annotation,Visualization,and Integrated Discovery(DAVID)were used to screen key target proteins.Subsequently,enrichment analysis was performed for biological processes,molecular functions,cellular components,and signaling pathways.Results A total of 107 chemical components were identified,including 35 compounds related to insomnia and 11 anti-insomnia targets such as AKT serine/threonine kinase 1,tumor protein 53,and prostaglandin-endoperoxide synthase 2.Gene Ontology functional enrichment analysis indicated that Zhizi Houpo decoction may exert its effects through cellular components such as the presynaptic membrane,dendrite,and plasma membrane,by participating in biological processes like chemical synaptic transmission,G protein signaling pathway,and neuron apoptosis,and by regulating molecular functions such as G protein-coupled serotonin receptor activity.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that its anti-insomnia effects were mainly concentrated in pathways such as neuroactive ligand-receptor interaction,calcium signaling pathway,serotonergic synapse,and cyclic adenosine monophosphate signaling pathway.Conclusion The anti-insomnia effect of Zhizi Houpo decoction is the result of a synergistic action involving multiple components,multiple targets,and multiple pathways.Its material basis and mechanism of action are primarily related to regulating biological processes such as neurotransmitter metabolism,synaptic function,neuronal apoptosis,and inflammatory response.

BACKGROUND:Acupotomy is an effective method for the clinical treatment of osteoarthritis,with affirmed clinical outcomes,but the specific mechanisms remain unclear OBJECTIVE:To investigate the role of acupotomy in modulating chondrocyte autophagy to promote chondrocyte homeostasis in osteoarthritis. METHODS:Twenty-eight New Zealand rabbits were randomly divided into control group,osteoarthritis group,acupotomy group,and hyaluronic acid group,with seven rabbits in each group.The knee osteoarthritis rabbit model was prepared using the Videman method in the latter three groups.After modeling,the control group and osteoarthritis group received no interventions.The acupotomy group received acupotomy treatment 15 minutes per time,once a week,while the hyaluronic acid group received intra-articular injection of hyaluronic acid once a week,with a continuous treatment duration of 5 weeks.The day after the final intervention,knee joint macrostructure was observed using DR imaging,chondrocyte ultrastructure was examined through transmission electron microscopy,apoptosis of chondrocytes was assessed using Tunel staining,and western blot analysis was used to detect the expression of proteins related to the PI3K/Akt/mTOR pathway. RESULTS AND CONCLUSION:The DR imaging results revealed that the osteoarthritis group exhibited narrowed knee joint spaces and the formation of periarticular osteophytes,while the hyaluronic acid group and acupotomy group showed widened knee joint spaces with a reduction in periarticular osteophytes.Transmission electron microscopy results demonstrated a decreased number of autophagosomes in chondrocytes in the osteoarthritis group,along with nuclear shrinkage,nuclear membrane rupture,incomplete organelle morphology,and a clear tendency towards cell death.In contrast,both the hyaluronic acid group and acupotomy group exhibited a significant increase in autophagosomes,intact nuclear membranes,and a well-preserved cellular state.Tunel staining results indicated a considerable decrease in the number of apoptotic cells in the hyaluronic acid group and acupotomy group compared with the osteoarthritis group.Western blot results revealed that,compared with the control group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly decreased in the osteoarthritis group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly increased(P<0.05);compared with the osteoarthritis group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly increased in both the hyaluronic acid group and acupotomy group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly decreased(P<0.05).To conclude,acupotomy intervention can modulate the PI3K/Akt/mTOR signaling pathway to enhance the autophagic level in chondrocytes,thereby maintaining chondrocyte homeostasis.This ultimately leads to a slowdown in cartilage degeneration.

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

OBJECTIVE To evaluate the innovation and sustainable development ability of traditional Chinese medicine(TCM) preparation in medical institutions, and to provide reference for the decision-making of administrative departments and the sustainable development of TCM preparation in hospitals. METHODS Based on the information data of 133 medical institutions in Zhejiang Province, analytic hierarchy process was used to construct the evaluation system of innovation and sustainable development ability of TCM preparation of medical institutions, and the prediction model of evaluation system of TCM preparation room/center was built by back propagation neural network. RESULTS The evaluation index system for innovation and sustainable development of TCM preparations in medical institutions included 4 second-level indexes and 19 third-level indexes. Among them, the number of varieties developed, the number of over one million varieties, the number of registered varieties, the way of research and development, and the area of preparation room had higher weight values, which were 0.15758, 0.12928,0.09343, 0.07879 and 0.07458, respectively. The entropy weight method and analytic hierarchy process index weights were used to construct the back propagation neural network. The overall correlation coefficients of the training models of the Levenberg-Marquardt algorithm and the Scaled Conjugate Gradient algorithm were 0.98983 and 0.93480, respectively. CONCLUSION This study establishes a scientific and effective comprehensive evaluation system for the innovation and sustainable development ability of TCM preparations in medical institutions, which can realize the prediction and evaluation of the comprehensive ability of TCM preparations in medical institutions.

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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Objective To predict the target of Atractylodes-Panxia-Poria in the treatment of pancreatic cancer, and to explore its potential molecular mechanism by using network pharmacology and molecular docking. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, OMIM, GeneCards, STRING, DAVID and Cytoscape software were used to construct a series of network diagrams. The core targets and conduct GO analysis and KEGG pathway enrichment analyses of the target genes were selected. Finally, molecular docking verification of key active ingredients and potential targets were conducted by AutoDock software. Results A total of 35 active ingredients, 190 related targets, 1566 targets of pancreatic cancer and 76 intersection targets were screened for the treatment of pancreatic cancer with Atractylodes-Panxia-Poria. These intersection targets were mainly involved in several biological processes, including positive regulation of gene expression, cytokine-mediated signaling pathway and regulation of apoptotic process, etc, which were also related to pathways in cancer, hepatitis B, colorectal cancer, chemical carcinogenesis-receptor activation, pancreatic cancer, and MAPK signaling pathway, etc. Molecular docking results showed that the main active components of Atractylodes-Panxia-Poria had certain affinity with the potential targets of pancreatic cancer. Conclusion Atractylodes-Panxia-Poria mainly exerts a therapeutic effect on pancreatic cancer through multi-component, multi-target and multi-pathway, which provides a certain theoretical basis for the clinical application of Atractylodes -Panxia-Poria in the treatment of pancreatic cancer.