Effects of neuraxial or general anaesthesia on postoperative adverse events in oldest-old patients (aged 90 years and older) with intertrochanteric fractures: a retrospective study.

BACKGROUND: To retrospectively analyse postoperative adverse events in oldest-old patients (aged 90 years and older) with intertrochanteric fractures treated under various anaesthetic techniques. METHODS: A total of 153 consecutive patients participated in this study, of which 127 patients who underwent surgery with neuraxial anaesthesia or general anaesthesia for intertrochanteric fractures between October 2019 and October 2022 were eligible and evaluated. They were divided into the neuraxial anaesthesia and general anaesthesia groups. The demographic characteristics and postoperative adverse events were compared between the two groups. RESULTS: A total of 13 patients (10.24%), including 6 in the neuraxial anaesthesia group (8.22%) and 7 in the general anaesthesia group (12.96%), died within 30 days after surgery. No significant differences between the two groups were observed. Postoperative delirium occurred in 40 patients (31.49%), including 17 (23.29%) in the neuraxial anaesthesia group and 23 (42.59%) in the general anaesthesia group; there was a significant difference between the two groups [P = 0.02, odds ratio (OR) = 0.41]. The other postoperative adverse events, including heart failure, acute stroke, acute myocardial infarction, pulmonary disease, anaemia, deep vein thrombosis, hypoproteinaemia, and electrolyte disorders, were not significantly different between the two groups. CONCLUSION: Our data suggest that different anaesthesia methods do not affect the incidence of adverse events, such as death within 30 days after surgery in oldest-old patients with intertrochanteric fractures. However, more patients developed delirium after surgery in the general anaesthesia group (23, 42.59%) than in the neuraxial anaesthesia group (17, 23.29%); this may indicate that spinal anaesthesia reduces the incidence of postoperative delirium (P = 0.02, OR = 0.41). TRIAL REGISTRATION: Retrospectively registered.

Risk Factors of Lower Extremity Deep Vein Thrombosis After Artificial Femoral Head Replacement for Elderly Femoral Neck Fractures and a Nomogram Model Construction.

Objective: To assess lower extremity deep vein thrombosis (DVT) risk factors after artificial femoral head replacement for elderly femoral neck fractures. A nomogram model was constructed to predict its risk. Methods: In analyzing 144 participants who underwent artificial femoral head replacement for elderly femoral neck fractures, researchers collected clinical data to identify factors associated with lower extremity DVT. The study collected numerous variables ranging from age and sex to history of lower extremity DVT and use of anticoagulant drugs after surgery. The patients were in two groups: those who developed DVT (n = 62) and those who did not (n = 82). Multivariate logistic regression analysis helped to identify factors influencing the occurrence of DVT after artificial femoral head replacement. The software packages used were R 4.1.0 and RMS. Results: Univariate and multivariate regression analysis identified age, ASA level, D-dimer of lower limb DVT, ALB, and PLT as predictive risk factors of lower extremity DVT after artificial femoral head replacement for elderly femoral neck fractures. Those risk factors were used to construct a clinical predictive nomogram. The calibration curves for hypertension in patients with OSAHS risk revealed excellent accuracy of the predictive nomogram model. The unadjusted concordance index (C-index) for the model was 0.877 [95% confidence interval (CI), 0.805-0.942]. The AUC was 0.8375002. Decision curve analysis showed that the predictive model could be applied clinically when the threshold probability was 20 to 80%. Conclusions: The researchers constructed and validated a clinical nomogram to predict the occurrence of lower extremity DVT after artificial femoral head replacement in elderly patients with femoral neck fractures. Age, ASA level, D-dimer, and history of lower limb DVT, ALB, and PLT were demonstrated to be predictive risk factors of lower extremity DVT in this circumstance. This practical prognostic nomogram may help improve clinical decision-making.

Perilla frutescens L. alleviates trimethylamine N-oxide-induced apoptosis in the renal tubule by regulating ASK1-JNK phosphorylation.

Trimethylamine N-oxide (TMAO) is associated with overall mortality in patients with chronic kidney disease (CKD). Previous findings suggest that P. frutescens (L.) can alleviate renal injury, but its effects and mechanisms underlying alleviation of TMAO-induced kidney damage remain unclear. In this study, a TMAO injury model, in vivo and in vitro, was established to clarify the effects and mechanisms of P. frutescens in alleviating TMAO-induced kidney injury. The results show that TMAO (60 mM/L) can induce the activation of apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK), thus aggravating downstream cell apoptosis in vitro. The study also found that P. frutescens aqueous extract (PFAE) (5 mg/mL) can inhibit TMAO-induced apoptosis by downregulating ASK1-JNK phosphorylation. In the in vivo experiments, it was demonstrated that TMAO can increase the levels of blood urea nitrogen and cystatin C, aggravating renal tubular epithelial apoptosis. The results also show that PFAE can reduce TMAO-induced renal damage by inhibiting ASK1-JNK phosphorylation in vivo. Our findings confirmed that P. frutescens can alleviate TMAO-induced renal tubule apoptosis by regulating ASK1-JNK phosphorylation, indicating that P. frutescens may be an effective treatment for alleviating TMAO damage in CKD.

[Effect of traditional Chinese medicine in attenuating chronic kidney disease and its complications by regulating gut microbiota-derived metabolite trimethylamine N-oxide: a review].

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.

Single-Segment Lumbar Intervertebral Disc Nucleus Excision on the Stability of Lumbar Segmental Sagittal Plane.

At present, lumbar disc herniation has become a problem that plagues people's health, life safety, and social and economic development. Among them, the research of lumbar disc nucleus pulposus tissue is the focus of the treatment of lumbar disc diseases. At present, the treatment methods of lumbar disc herniation are divided into conservative treatment and surgical treatment, among which surgical treatment can be divided into open surgery and minimally invasive surgery. Surgical treatment to remove the nucleus pulposus from the disc by fenestration includes conventional ablation of the nucleus pulposus and microscopic lumbar discs. This treatment is effective, but it has a great impact on the stabilization mechanism of the spine, with large soft tissue damage and large blood loss, which can easily cause nerve damage and postdural adhesions. At the same time, single-segment lumbar discectomy has also been gradually applied to the treatment of this disease. Under this, this paper studies single-segment lumbar disc nucleus pulposus resection. The lumbar nucleus resection is performed in a single segment in the physiological load area, which can greatly ensure the stability of the sagittal plane of the lumbar spine. In order to better understand the postoperative rehabilitation and clinical effects of single-segment lumbar discectomy, as well as the changes in the sagittal plane of the lumbar vertebrae before and after the operation, so as to provide a reference for further improving the quality of life of patients, this paper uses questionnaire survey and data analysis methods. According to the results of the questionnaire survey, compared with other operations, single-segment lumbar discectomy is more stable in the sagittal plane of the lumbar spine within the physiological load range, and there is less displacement. The displacement may be caused or influenced by different kinds of factors such as heavy loads or manual labor. In addition, most patients have less abnormal pain after surgery, indicating that the surgery has a certain effect on the treatment of the disease, and there are fewer abnormalities after surgery.

Aqueous Extract of Cimicifuga dahurica Reprogramming Macrophage Polarization by Activating TLR4-NF-κB Signaling Pathway.

PURPOSE: Cimicifuga dahurica (C. dahurica), which has been used in traditional oriental medicine for a long period, was reported to exert extensive antitumor activity, but the effect and molecular biological mechanism of C. dahurica on multiple myeloma (MM) has not been elaborated. Tumor-associated macrophages (TAMs) exhibit a sustained polarization between tumor killing M1 subtype and tumor supporting M2 subtype. And a lower ratio of M1/M2 is associated with tumor angiogenesis, proliferation and invasion. We explored the inhibitory effect of the aqueous extract of the root of C. dahurica (CRAE) on tumor growth by reprogramming macrophage polarization in the tumor microenvironment. METHODS: Mice bearing SP2/0 multiple myeloma were treated with CRAE. Western blotting (WB), immunohistochemistry (IHC) and immunofluorescence staining were utilized to assess tumor growth and TAM populations. Macrophages were depleted by injection of clodronate liposomes to determine and measure the role of CRAE as an anti-tumor agent by targeting macrophages. To simulate tumor microenvironment, MM cells H929 and TAMs were co-cultured using the transwell co-culture system. By using CRAE as an immunoregulator in M2-like macrophages, we analyzed CRAE-treated macrophage-associated surface markers and cytokines by flow cytometry and WB. RESULTS: The results indicated that CRAE treatment could reduce tumor burden of MM mice and a high degree of M1-like macrophages infiltration was detected in tumor tissues. In vitro co-culture system, CRAE significantly promoted the polarization of M2 to M1 phenotype, which led to the increase in apoptosis of myeloma cells. It was found that the M1 polarization induced by CRAE depended on the TLR4-MyD88-TAK1-NF-κB signal transduction. CONCLUSION: This study elucidated the anticancer mechanism of the aqueous extract of C. dahurica (CRAE) through reprogramming macrophage polarization and highlighted that CRAE could act as a potential novel option for cancer immunotherapy.

Artemisia capillaris Thunb. water extract attenuates adriamycin-induced renal injury by regulating apoptosis through the ROS/MAPK axis.

Artemisia capillaris Thunb. is widely used in the treatment of kidney diseases, but the underlying mechanism remain elusive. Therefore, this study aimed to elucidate the mechanism of Artemisia capillaris Thunb. in alleviating renal injury. And renoprotective effects of freeze-dried powder of Artemisia capillaris Thunb. water extract (WAC) were assessed using adriamycin (ADR)-induced renal injury to the NRK-52E cells and ADR-induced renal injury Sprague-Dawley rats (SD rats) models. The results show that WAC could alleviate ADR-induced renal injury in SD rats and the NRK-52E cell line, improved renal function (BUN 9.73 ± 0.35 vs 7.13 ± 0.15, SCR 80.60 ± 1.68 vs 60.50 ± 1.42, ACR 11.50 ± 0.50 vs 8.526 ± 0.15) or cell viability (IC50 = 1.08 µg/ml (ADR), cell viability increase 36.38% ± 6.74% (added 4 mg/ml WAC)), and reduced the apoptosis. Moreover, WAC inhibited the MAPK signal transduction, increased the expression of superoxide dismutase 1 (SOD1), and decreased the production of ROS. The treatment of N-acetylcysteine (NAC, antioxidant) in vitro showed that NAC inhibited apoptosis and alleviated renal injury by inhibiting oxidative stress and reducing the phosphorylation of proteins related to the MAPK signaling pathway. Therefore, these results suggested that WAC can alleviate ADR-induced renal injury and apoptosis by regulating the ROS/MAPK axis and has potential to be used as a renoprotective drug. PRACTICAL APPLICATIONS: Artemisia capillaris Thunb., which is a medicinal and edible plant, is widely used to treat kidney diseases in traditional Chinese medicine. The present research examined the renal protective effect of Artemisia capillaris Thunb. The results show that Artemisia capillaris Thunb. can effectively reduce renal tubular cell apoptosis through the ROS/MAPK axis in vivo and in vitro. In general, Artemisia capillaris Thunb. can be used as a potential herb to attenuate renal injury and further research can be conducted to explore its renoprotective mechanisms.

Chinese Herbal Medicine Suyin Detoxification Granule Inhibits Pyroptosis and Epithelial-Mesenchymal Transition by Downregulating MAVS/NLRP3 to Alleviate Renal Injury.

PURPOSE: Proteinuria is an independent risk factor of chronic kidney disease (CKD). Albumin-induced tubulointerstitial inflammation and epithelial-mesenchymal transition (EMT) via the activation of NLRP3 inflammasome is a potential therapeutic target for CKD. Suyin Detoxification Granule (SDG) improves proteinuria and postpones renal failure. However, the underlying mechanism is still unknown. METHODS: Firstly, the rat model of renal failure was established using intragastric administration of adenine. Renal function, proteinuria, inflammatory indicators in serum, and renal pathology were assessed, and renal immunohistochemical staining of NLRP3 inflammasomes was performed after intervention with low and high concentrations of SDG. Secondly, the model of renal tubular epithelial HK-2 cells was established using albumin in vitro, and the cell viability, EMT phenotype, and the expression of proteins in the NLRP3 inflammasome signaling pathway were measured after the freeze-dried powder of Suyin Detoxification Prescription (SDP) and CY-09, which is a selective and direct NLRP3 inhibitor, were co-incubated with albumin. ATP, SOD, mitochondrial membrane potential, and ROS were further measured in vitro, and changes in the mitochondrial function after SDP intervention were observed. The mitochondrial antiviral signaling protein (MAVS) was knocked down using siRNA, and the interaction between MAVS and NLRP3 was verified using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. RESULTS: SDG improved renal function and proteinuria, alleviated renal fibrosis, and reduced serum inflammation and the expression of the components of the NLRP3 inflammasome in the kidney. In vitro, SDP and CY-09 enhanced cell viability after injury with albumin and inhibited pyroptosis induced by the NLRP3 inflammatory signaling pathway and expression of proteins involved in EMT. It was further found that SDP alleviated the mitochondrial dysfunction caused by albumin. The knockdown of MAVS reduced the expression of NLRP3 pathway proteins and their mRNA levels and also weakened the co-localization of NLRP3, thus, reducing cell pyroptosis. CONCLUSION: SDP protected renal tubular epithelial cells from cell pyroptosis and EMT by regulating the albumin-induced mitochondrial dysfunction/ MAVS/ NLRP3-ASC-caspase-1 inflammasome signaling pathway.

Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology.

Chronic kidney disease (CKD) is a chronic progressive disease that seriously threatens human health. Some patients will continue to progress into the CKD stage 3-5 (also called chronic renal failure), which is mainly manifested by a decline in renal function and multi-system damage. Perilla frutescens (L.) Britton. (Lamiaceae) is one of the most widely used traditional Chinese medicine (TCM) herbs in CKD, especially in CKD stage 3-5. But its active components and mechanisms are still unclear. In this study, we used network pharmacology to analyze the active components of P. frutescens and the main therapeutic targets for intervention in CKD stage 3-5. Then, the key components were selected for enrichment analysis and identified by high performance liquid chromatograph (HPLC). Finally, we verified the critical components through molecular docking, and in vitro experiments. The results show that 19 main active components of P. frutescens were screened, and 108 targets were intersected with CKD stage 3-5. The PPI network was constructed and found that the core nodes AKT1, TP53, IL6, TNF, and MAPK1 may be key therapeutic targets. Enrichment analysis shows that related targets may be involved in regulating various biological functions, and play a therapeutic role in CKD stage 3-5 by regulating apoptosis, T cell receptor, and PI3K-AKT signaling pathways. Molecular docking indicates that the key active components were well docked with its corresponding targets. Five active components were identified and quantified by HPLC. According to the results, luteolin was selected as the critical component for further verification. In vitro experiments have shown that luteolin can effectively alleviate adriamycin (ADR)-induced renal tubular apoptosis and suppress AKT and p53 phosphorylation. The effects of luteolin to reduce apoptosis may be mediated by inhibiting oxidative stress and downregulating the mitogen-activated protein kinase (MAPK) and p53 pathways. In general, we screened and analyzed the possible active components, therapeutic targets and pathways of P. frutescens for treating CKD. Our findings revealed that luteolin can reduce renal tubular epithelial cell apoptosis and may be the critical component of P. frutescens in the treatment of CKD. It provides references and direction for further research.

Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation.

BACKGROUND AND OBJECTIVE: Doxorubicin (DOX) is an anthracycline antitumor antibiotic widely utilized in treating various tumors. Nevertheless, the toxicity of DOX toward normal cells limits its applicability, with nephrotoxicity considered a major dose-limiting adverse effect. Apigenin (APG), a flavonoid widely distributed in natural plants, has been reported to have antioxidant, anti-inflammatory, and mild tumor-suppressive properties. In this study, we investigated the role of APG in DOX-induced nephrotoxicity and chemotherapeutic efficacy. METHODS: Male BALB/c mice were administered DOX (11.5 mg/kg) via the tail vein to establish the DOX nephropathy model. After treatment with or without APG (125, 250, and 500 mg/kg) for two weeks, urine, serum, and tissue samples were collected to evaluate proteinuria, serum albumin, serum creatinine (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD) activity, malondialdehyde (MDA), glutathione (GSH), and pathological changes. Rat renal tubular epithelial cells (NRK52E), murine podocyte cells (MPC5), and murine breast cancer cells (4T1) were utilized to verify the effect of APG on DOX-induced cell injury. An MTT assay was employed to analyze cell viability. Apoptosis was evaluated using a colorimetric TUNEL staining and cleaved caspase-3 protein analysis by western blotting. A reactive oxygen species (ROS)/superoxide (O2-) fluorescence probe was employed to determine oxidative injury. Western blotting was used to analyze nephrin, α-smooth muscle actin (α-SMA), collagen I (Col1), fibronectin (FN), and SOD2 expression. The mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), IL-6, NACHT, LRR, PYD domain-containing protein 3 (NLRP3), caspase-1, and IL-1ß were tested by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: APG ameliorated DOX-elicited renal injuries in both the glomeruli and tubules. The DOX + APG groups had much lower tissue MDA, IL-6, TNF-α, NLRP3, caspase-1, and IL-1ß levels and generation of intracellular ROS, but significantly higher SOD activity and GSH levels compared to those of the DOX group. Additionally, APG attenuated DOX-induced morphological changes, loss of cellular viability, and apoptosis in NRK-52E and MPC-5 cells, but not in 4T1 cells. CONCLUSION: APG has a protective role against DOX-induced nephrotoxicity, without weakening DOX cytotoxicity in malignant tumors. Thus, APG may serve as a potential protective agent against renal injury and inflammatory diseases and may be a promising candidate to attenuate renal toxicity in cancer patients treated with DOX.

Localized Electrical Induction Heating for Highly Efficient Synthesis and Regeneration of Metal-Organic Frameworks.

Based on carbon fibers (CFs) delivered localized electrical induction heat, a novel electrical induction framework synthesis (EIFS) strategy has been developed to in-situ grow versatile metal-organic frameworks (MOFs) on CFs, resulting in the production of a set of MOF-coated CF (MOF@CF) fibers. Detailed studies on the production of UiO-66-NH2@CFs indicate that the use of EIFS leads to dramatically accelerated MOF growth at dozen times higher reaction rate than that of the conventional solvothermal reaction. By periodically switching anodes during EIFS reactions, uniform MOF@CF fibers with well-controlled MOF loadings have been achieved depending on the reaction conditions. Mediated by the embedded CFs in the resulting MOF@CFs, MOF@CFs exhibit well-regulated electrical induction heating capacities depending on MOF loadings and the applied voltages. Driven by such localized heat, up to 100% of the adsorbed CO2 in UiO-66-NH2@CF can be rapidly released, demonstrating an electrical induction framework regeneration (EIFR) process for highly efficient regeneration of MOFs. As CFs enable to rapidly deliver localized electrical induction with over 90% of electrothermal conversion efficiency and at rather low operation voltage, currently developed EIFS and EIFR process provide a highly efficient, low-energy, low operation cost, and safe way to highly efficient synthesis and regeneration of MOF materials.