Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To explore the therapeutic effect of LuoFuShan Rheumatism Plaster(LFS)on neuropathic pain(NP)and its molecular mechanism.Methods Mouse models of sciatic nerve chronic constriction injury(CCI)were treated with low,medium,and high doses(2.2,4.4,and 8.8 cm2,respectively)of LFS by topical application for 14 consecutive days.The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold(MWT),paw withdrawal latency(PWL),plasma IL-6 and TNF-α levels,and histopathology of the sciatic nerve.Network pharmacology and molecular docking were used to identify the key targets and signaling pathways.The key targets were verified by RT-qPCR and immunohistochemistry.The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart,liver,and kidneys.Results Compared with the CCI group,LFS dose-dependently increased MWT and PWL,reduced plasma IL-6 and TNF-α levels,and alleviated sciatic nerve inflammation in the mouse models.Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling.Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF-α.In the mouse models of sciatic nerve CCI,LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve.LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart,liver and kidneys as compared with those in the CCI model group and sham-operated group.Conclusion LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.

INTRODUCTION: The primary objective of this guideline is to establish evidence-based recommendations for the clinical use of parenteral nutrition (PN) in adult patients within the acute hospital setting in Singapore. METHOD: An expert workgroup, consisting of healthcare practitioners actively involved in clinical nutrition support across all public health institutions, systematically evaluated existing evidence and addressed clinical questions relating to PN therapy. RESULTS: This clinical practice guideline developed 30 recommendations for PN therapy, which cover these key aspects related to PN use: indications, patient assess-ment, titration and formulation of PN bags, access routes and devices, and monitoring and management of PN-related complications. CONCLUSION This guideline provides recommendations to ensure appropriate and safe clinical practice of PN therapy in adult patients within the acute hospital setting.
Humans ; Singapore ; Parenteral Nutrition/adverse effects* ; Adult

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

Objective To explore the correlation between glycemic control and complexity of drug treatment regimens in elderly patients with type 2 diabetes mellitus.Methods A retrospective,cross-sectional study was conducted to collect the elderly patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology at the Geriatric Hospital of Nanjing Medical University from June 2022 to December 2024.The clinical characteristics and medication compliance of the patients were recorded through pharmaceutical consultations.The medication regimen complexity index(MRCI)and diabetes-specific medication regimen complexity index(D-MRCI)were calculated for each patient.Patients were divided into the target-achieving group and the non-target-achieving group based on whether their blood glucose met the criteria.Univariate analysis and multivariate Logistic regression analysis were used to identify the factors associated with adequate blood glucose control.Results A total of 152 patients were included,123(80.9%)had poorer glycemic control,31.6%exhibited good medication adherence,and 76.3%demonstrated good adherence to diabetes medications.The mean total MRCI score was(25.90±8.63),while the median D-MRCI score was 9.00(5.25,11.75),with 44.7%of patients classified as having high D-MRCI scores(D-MRCI>9).The results of Spearman correlation analysis indicated that the number of medications used by patients was highly correlated with the MRCI score(r=0.899,P<0.001),while the number of diabetes medications used was highly correlated with the D-MRCI score(r=0.705,P<0.001).Univariate analysis results revealed that high complexity diabetes medication regimen,duration of diabetes,the number of types of antidiabetic drugs,and the number of injectable antidiabetic medications were associated with glycemic control(P≤0.05).Multivariate analysis results showed that,high diabetes medication complexity was an independent risk factor for inadequate blood glucose control[OR=4.119,95%CI(1.121,15.139),P=0.033].Conclusion Higher D-MRCI(>9)was associated with poorer glycemic control.Simplifying medication regimens and optimizing medication management strategies may improve patient outcomes.

Objective To investigate the epidemiological characteristics of knee osteoarthritis(KOA)among military personnel in plateau regions and to explore its risk factors.Methods From July 2023 to July 2024,a multi-stage stratified cluster random sampling method was employed to survey the prevalence of KOA and related risk factors among military personnel in the northwest plateau regions of China,covering different altitudes(1500-4500 m)and geographical areas(Gansu,Qinghai,Tibet,and Xinjiang).All study subjects were divided into KOA and non-KOA groups based on the presence or absence of KOA.Variables including age,gender,body mass index(BMI),education level,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury were selected for univariate analyses between groups.Variables with P<0.05 in the univariate analyses were included in the binary multifactor logistic regression to identify risk factors for KOA.Results A total of 3000 questionnaires were distributed,and 2854 valid questionnaires were collected,with a response rate of 95.13%.The sample included 2584 males and 270 females,with 510 cases of KOA,resulting in a prevalence rate of 17.9%.Univariate analysis showed that there were statistically significant differences between KOA and non-KOA groups in terms of age,BMI,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury(P<0.05).However,no significant differences were found in gender and education level(P>0.05).Binary multivariate logistic regression analysis revealed that older age(OR=1.382,P=0.017),higher BMI(P<0.01),smoking(OR=1.929,P<0.01),higher military rank(OR=1.485,P=0.007),being a member of the Armed Police(P<0.01),longer service duration(P<0.01),higher regional altitude(OR=1.459,P<0.01),lower annual average temperature(OR=1.188,P=0.001),longer training duration(P<0.01),higher perceived training intensity(OR=2.450,P<0.01),and history of knee injury(OR=2.768,P=0.002)were independent risk factors for KOA.Conclusions Older age,overweight/obesity,smoking,higher military rank,being a member of the Armed Police,longer service duration,higher altitude,cold climate,longer training duration,higher training intensity,and history of knee injury are independent risk factors for KOA among military personnel in the northwest plateau regions of China.

Objective To investigate the expressions of annexin A2 and glycogen synthesis kinase-3β(GSK-3β)in cutaneous squamous cell carcinoma(CSCC)tissues,and to analyze their correlation with CSCC as well as their clinical pathological diagnostic value.Methods The pathological tissues of 68 patients with CSCC and 40 patients with keratoacanthoma(KA)who underwent surgical treatment in the Department of Dermatology of the Second Hospital of Nanning from October 2020 to May 2024 were collected,and the surrounding normal skin tissues of 32 patients with benign skin diseases were used as controls.The expressions of annexin A2,GSK-3β and β-catenin were detected by immunohistochemistry and Western blotting.Spearman was used to evaluate the correlation between the expressions of annexin A2 and GSK-3β and the pathological characteristics in CSCC.The receiver operating characteristic(ROC)curve was drawn to analyze the clinical diagnostic value of annexin A2 and GSK-3β in CSCC.Results Compared with the normal skin tissues,the expressions of annexin A2 and β-catenin in CSCC increased,and GSK-3β decreased(P＜0.05);Compared with the KA tissues,the expression of annexin A2 in CSCC tissues increased(P＜0.05).The expression of annexin A2 was negatively correlated with that of GSK-3β in CSCC(r=-0.3901,P＜0.01).GSK-3β expression was related to tissue differentiation,with lower expression in poorly differentiated patients'cancer tissues(P＜0.05).The sensitivity of annexin A2 and GSK-3β for diagnosis of CSCC was 85.3%and 41.2%,respectively,with specificities of 46.9%and 84.4%respectively.The sensitivity of annexin A2 for distinguishing between CSCC and KA was 85.3%,with a specificity of 40.0%.Conclusion Annexin A2 and GSK-3β may be used as potential biomarkers for the early diagnosis or differential diagnosis of CSCC,and play important roles in the development of CSCC.Their mechanism may be related to the activation of Wnt/β-catenin signaling pathway.

Objective:To evaluate the efficacy of angiogenesis inhibitors and poly ADP-ribose polymerase (PARP) inhibitors in the treatment of recurrent ovarian cancer using a mesh meta-system.Methods:Subject terms were used to search Pubmed, Embase, the Cochrane Library and web of science databases to collect randomized controlled trials related to angiogenesis inhibitors and PARP inhibitors in the treatment of recurrent ovarian cancer. The search time was established until January 1, 2024. Outcome measures included progression-free survival (PFS) and overall survival (OS). Bias risk assessment was performed using Revman 5.4 software and mesh meta-analysis was performed using gemtc package in R 4.3.1 software.Results:34 randomized controlled trials were included in the PFS and 26 in the OS. Olaparib ( HR=0.63, 95% CI: 0.40-0.99), rucaparib ( HR=0.48, 95% CI: 0.24-0.99), niraparib ( HR=0.49, 95% CI: 0.26-0.93), niraparib+ bevacizumab ( HR=0.17, 95% CI: 0.05-0.61), chemotherapy+ bevacizumab+ maintenance bevacizumab ( HR=0.54, 95% CI: 0.3-0.97) and chemotherapy+ bevacizumab ( HR=0.50, 95% CI: 0.31-0.81) had longer PFS than conventional platinum-based chemotherapy/chemotherapy+ placebo. Niraparib+ bevacizumab had the longest PFS of all pharmacological interventions. Chemotherapy plus bevacizumab ( HR=0.72, 95% CI: 0.57 -0.88) had a longer OS than conventional platinum-based chemotherapy/chemotherapy plus placebo. Conclusions:There is limited evidence that angiogenesis inhibitors alone (bevacizumab) or PARP inhibitors alone (niraparib, olaparib, and rucaparib) can improve PFS or OS in recurrent ovarian cancer, and that the combination of angiogenesis inhibitors and PARP inhibitors may be more beneficial in prolonging PFS or OS in recurrent ovarian cancer.