Potential value of serum prealbumin and serum albumin in the identification of postoperative delirium in patients undergoing knee/hip replacement: an observational study and internal validation study.

Background: Postoperative delirium (POD) is a common postoperative neurological complication that can lead to a variety of postoperative complications. At present, the pathogenesis of POD is unclear. This study aims to explore the relationship between serum prealbumin and serum albumin and POD and whether serum prealbumin and serum albumin influence POD through POD core pathology. Objective: We enrolled 500 Chinese Han patients between September 2020 to January 2023. We analyzed the risk and protective factors of POD using the multivariate logistic regression. We also assessed the predictive power of serum prealbumin, serum albumin, and both in combination with CSF POD biomarkers. We used Stata MP16.0. to examine whether the association between serum prealbumin and serum albumin and POD was mediated by CSF POD biomarkers, and conducted an internal validation study to verify the accuracy of the combination of serum prealbumin + serum albumin + CSF POD biomarkers for predicting POD. The model was visualized using ROC curve and decision curve analysis (DCA). DynNom and Shiny packages were used to create an online calculator. Ten patients who had POD occurring from February 2023 to October 2023 were selected for internal verification. Results: Finally, a total of 364 patients were included in our study. Levels of serum prealbumin, serum albumin in the POD group were lower than those in the NPOD group. The lever of serum prealbumin, serum albumin were protective factors for POD. The relationship between serum prealbumin, serum albumin and POD was partially mediated by T-tau (12.28%) and P-tau (20.61%). The model combining serum prealbumin and serum albumin and POD biomarkers exhibited a relatively better discriminatory ability to predict POD. DCA also showed that the combination of serum prealbumin and serum albumin and POD biomarkers brought high predictive benefits to patients. The dynamic online calculator can accurately predict the occurrence of POD in the internal validation study. Conclusion: Preoperative low serum prealbumin and serum albumin levels were the preoperative risk factors for POD, which is partly mediated by T-tau and P-tau. The model combining serum prealbumin and serum albumin and CSF POD biomarkers can accurately predict the occurrence of POD. Clinical trial registration: http://www.clinicaltrials.gov, identifier ChiCTR2000033439.

Physical activity may a probably protective factor for postoperative delirium: the PNDABLE study.

Objective: This study aims to explore the relationship between physical activity (PA) and postoperative delirium (POD). Methods: We selected 400 patients from the Perioperative Neurocognitive Disorder and Biomarkers Lifestyle (PNDABLE) database, and the patients in the PNDABLE database were sampled and tested Alzheimer's biomarkers. The diagnosis of POD was made using the Confusion Assessment Scale (CAM) and the severity was assessed using Memorial Delirium Assessment Scale (MDAS). Mini-Mental State Examination (MMSE) scale was used to detect the mental state of the patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of preoperative cerebrospinal fluid (CSF) biomarkers, such as amyloid ß plaque 42 (Aß42), total tau protein (T-tau), and phosphorylated tau protein (P-tau). Logistic regression, sensitivity analysis, and post hoc analysis were used to explore the relationship between risk and protective factors on POD. We used the mediating effect to explore whether PA mediates the occurrence of POD through CSF biomarkers. Results: The incidence of POD was 17.5%. According to our research, the consequence prompted that PA might be the protective factor for POD [odds ratio (OR): 0.336, 95% confidence interval (95 CI) 0.206-0.548, P < 0.001]. The result of logistic regression revealed that CSF biomarker Aß42 (OR: 0.997, 95 CI 0.996-0.999, P < 0.001) might be a protective factor against POD, and the T-tau (OR: 1.006, 95 CI 1.003-1.009, P = 0.001) and P-tau (OR: 1.039, 95 CI 1.018-1.059, P < 0.001) might risk factors for POD. Sensitivity analysis confirmed the correlation between PA and CSF biomarkers in the patients with POD. Mediation effect analysis showed that PA may reduce the occurrence of POD partly through CSF biomarkers, such as Aß42 (proportion: 11%, P < 0.05), T-tau (proportion: 13%, P < 0.05), and P-tau (proportion: 12%, P < 0.05). Conclusion: Physical activity is probably a protective factor for POD and may exert a mediating effect through CSF biomarkers.

Remimazolam benzenesulfonate anesthesia effectiveness in cardiac surgery patients under general anesthesia.

BACKGROUND: Sedation with propofol injections is associated with a risk of addiction, but remimazolam benzenesulfonate is a comparable anesthetic with a short elimination half-life and independence from cell P450 enzyme metabolism. Compared to remimazolam, remimazolam benzenesulfonate has a faster effect, is more quickly metabolized, produces inactive metabolites and has weak drug interactions. Thus, remimazolam benzenesulfonate has good effectiveness and safety for diagnostic and operational sedation. AIM: To investigate the clinical value of remimazolam benzenesulfonate in cardiac surgery patients under general anesthesia. METHODS: A total of 80 patients who underwent surgery in the Department of Cardiothoracic Surgery from August 2020 to April 2021 were included in the study. Using a random number table, patients were divided into two anesthesia induction groups of 40 patients each: remimazolam (0.3 mg/kg remimazolam benzenesulfonate) and propofol (1.5 mg/kg propofol). Hemodynamic parameters, inflammatory stress response indices, respiratory function indices, perioperative indices and adverse reactions in the two groups were monitored over time for comparison. RESULTS: At pre-anesthesia induction, the remimazolam and propofol groups did not differ regarding heart rate, mean arterial pressure, cardiac index or volume per wave index. After endotracheal intubation and when the sternum was cut off, mean arterial pressure and volume per wave index were significantly higher in the remimazolam group than in the propofol group (P < 0.05). After endotracheal intubation, the oxygenation index and the respiratory index did not differ between the groups. After endotracheal intubation and when the sternum was cut off, the oxygenation index values were significantly higher in the remimazolam group than in the propofol group (P < 0.05). Serum interleukin-6 and tumor necrosis factor-α levels 12 h after surgery were significantly higher than before surgery in both groups (P < 0.05). The observation indices were re-examined 2 h after surgery, and the epinephrine, cortisol and blood glucose levels were significantly higher in the remimazolam group than in the propofol group (P < 0.05). The recovery and extubation times were significantly lower in the remimazolam group than in the propofol group (P < 0.05); there were significantly fewer adverse reactions in the remimazolam group (10.00%) than in the propofol group (30.00%; P < 0.05). CONCLUSION: Compared with propofol, remimazolam benzenesulfonate benefited cardiac surgery patients under general anesthesia by reducing hemodynamic fluctuations. Remimazolam benzenesulfonate influenced the surgical stress response and respiratory function, thereby reducing anesthesia-related adverse reactions.

Nitidine chloride inhibits the appearance of cancer stem-like properties and regulates potential the mitochondrial membrane alterations of colon cancer cells.

BACKGROUND: Nitidine chloride (NC) is a natural alkaloid that can inhibit tumor growth and induce apoptosis in varieties of cancers. However, the effec12/268t of NC on colon cancer (CC) cells has not been extensively studied. METHODS: Conlon cancer SW480 cells was treated with different concentrations of NC (0.25, 0.5, 1, 2.5, 5, 10, 25, 50, 100, and 200 µM) in DMEM medium for 24 hours. Western blotting (WB) was used to detect the expression of related proteins, such as Ki67, PCNA, NANOG, SOX2, OCT4, Bcl-2, Bax, Caspase-3, Caspase-9, ERK1/2, p-ERK1/2, AKT, p-AKT, STAT3, p-STAT3, P65 and p-P65. The pellet formation experiment was used to detect the pellet formation of stem cells. The JC-1 experiment was used to detect the change of mitochondrial membrane potential. Kit was performed to detect the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA). In vivo experiments were used to verify the results of in vitro experiments. TUNEL assay was designed to detect the apoptosis in mice tissue. IHC was used to detect expression of Ki67 and OCT4 protein in tissue. RESULTS: NC significantly inhibited the expression levels of Ki-67 and a proliferating cell nuclear antigen (PCNA). NC can reduce the pellet colony and pellet size of tumor stem cells and block the stem cell characteristics of CC cells. The corresponding stem cell marker molecules NANOG, SOX2, and OCT4 were also downregulated. NC treatment induced the mitochondrial membrane potential depolarization of CC cells. The expression of pro-apoptotic proteins such as caspase-3, caspase-9, and Bax were upregulated, while the expression level of apoptotic Bcl-2 was significantly down-regulated. Moreover, NC reduced SOD activity and MDA content in CC cells. In addition, studies on pathway phosphorylation have shown that NC inhibits the expression of p-erk and p-akt proteins. Finally, the results were further confirmed by experiments in nude mice. NC inhibited tumor growth in mice. NC promoted apoptosis in tissues. NC inhibited the expression of Ki67 and OCT4 in tissues. NC inhibited the phosphorylation of pathway proteins ERK1/2 and AKT in tissues. CONCLUSIONS: NC treatment inhibited the proliferation and stemness of CC tissues, promoted the apoptosis of tumor tissues, downregulated the expression of p-ERK and p-AKT in tumor tissues, which suggests that NC may play an important role in regulating ERK and AKT pathways.

3D Rosa centifolia-like CeO2 encapsulated with N-doped carbon as an enhanced electrocatalyst for Zn-air batteries.

Reasonable design and synthesis of high-efficiency rare earth oxides-based materials as alternatives to noble-metal catalysts are of great significance for oxygen electrocatalysis. Herein, we report three-dimension (3D) Rosa centifolia-like CeO2 encapsulated with N-doped carbon (NC) composites (CeO2@NC) for enhancing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities. This synthetic method allows CeO2 to tune the oxygen vacancy concentration and electronic structure of a series of CeO2@NC catalysts due to its large oxygen-storage-capacity (OSC) property. Moreover, benefiting from the exposed active sites in NC as well as the synergy between CeO2 and NC, among as-prepared samples, the resultant CeO2@NC-900 delivers a half-wave potential (E1/2) of 0.854 V, which is more positive compared with counterpart of NC-900 (0.806 V) and even comparable to that of commercial Pt/C catalyst (0.855 V). This indicates that the ORR electrocatalytic activity of CeO2@NC-900 is significantly improved. Meanwhile, CeO2@NC-900 exhibits satisfactory performance toward OER. For practical application, the CeO2@NC-900 involved rechargeable Zn-air battery possesses excellent energy efficiency, superior stability, and large energy density (666.1 Wh kgZn-1 at 5 mA cm-2). This approach provides a valid way to develop advanced rare earth oxides-based materials for energy applications.

Upregulation of miR-215 attenuates propofol-induced apoptosis and oxidative stress in developing neurons by targeting LATS2.

BACKGROUND: Propofol is an intravenous anesthetic agent that commonly induces significant neuroapoptosis. MicroRNAs (miRNAs) have been reported to participate in the regulation of propofol exposure-mediated neurotoxicity. MiR-215, as one of miRNAs, was found to regulate nerve cell survival. However, the mechanism through which miRNAs regulate propofol exposure-mediated neurotoxicity is still unclear. METHODS: Real-time PCR was used to detect miR-215 expression level. Cell viability was measured using MTT assay. Cell apoptosis was examined via flow cytometry analysis. ROS, MDA, LDH and SOD levels were assayed through ELISA kits. Dual luciferase reporter assay identified the interaction between miR-215 and large tumor suppressor 2 (LATS2). Protein level was detected using western blot analysis. RESULTS: MiR-215 expression was downregulated in propofol-treated rat hippocampal neurons. MiR-215 mimics promoted cell viability and reduced apoptosis in propofol-treated neonatal rat hippocampal neuron. MiR-215 mimics also caused inhibition of oxidative stress as evidenced by suppression of ROS, MDA and LDH levels as well as increase of SOD level. In addition, we found that large tumor suppressor 2 (LATS2) is a target of miR-215 and miR-215 mimics decreased LATS2 level in propofol-treated neonatal rat hippocampal neuron. Further, LATS2 overexpression suppressed the effect of miR-215 on propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron. CONCLUSION: Taken together, we demonstrate that miR-215 attenuates propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron by targeting LATS2, suggesting that miR-215 may provide a new candidate for the treatment of propofol exposure-induced neurotoxicity.

Transvaginal three-dimensional ultrasound combined with HD flow model for uterus scar diverticulum.

To study the influencing factors of scar diverticulum formation and its monitoring methods, 141 people with a history of cesarean section and kidney deficiency and blood stasis were selected as subjects. The transvaginal ultrasound technique was used to divide the case into the scar diverticulum case group and the complete group, and the clinical situation was analyzed. Transvaginal three-dimensional ultrasound combined with HD flow pattern was used to analyze the morphology of uterus scar diverticulum and the parameters of peripheral muscle blood flow. The relationship between the size of scar diverticulum and its influencing factors, the location of the uterus and the number of cesarean sections were studied. Studies have found that retroposition of the uterus or the number of cross-cutting will increase the possibility of uterus scar diverticulum formation. Therefore, transvaginal three-dimensional ultrasound combined with HD flow mode can identify and diagnose scar diverticulum.

Role of Ultrasound in the Detection of Rotator-Cuff Syndrome: An Observational Study.

BACKGROUND Physical tests are usually preferred to assess rotator-cuff syndrome but are insufficient to predict the morphology and size of the rotator-cuff. The objective of the study was to rate the ultrasound findings for patients with sudden shoulder pain and to determine potential predictors of the same. MATERIAL AND METHODS A total of 112 patients with sudden shoulder pain with rotator-cuff syndrome, suspected by orthopedic doctors, were subjected to ultrasonography. Real-time ultrasonography was done for the acromioclavicular joint, biceps, infraspinatus, posterior labrum, subscapularis, supraspinatus, teres minor tendon, and the sub-acromial-subdeltoid bursa. Each tendon was assessed via scanning planes in orientation as per longer and shorter axis, and from their myotendinous junction shoulder to bony insertions. Linear and logistic regression analysis were performed to predict the associations of medical history with rotator-cuff injury. RESULTS Ultrasonography identified that 82% of the enrolled patients had at least one particular cause of the rotator-cuff disorder. Among the rotator-cuff disorders, calcific tendonitis (54%) was observed more frequently followed by tendinopathy (32%), subacromial-subdeltoid bursitis (22%), and partial thickness tear (21%). Also, 46 patients (41%) had multiple findings. Older age (older than 40 years) was a strong predicting factor of rotator-cuff disorder (r²=0.36, P=0.0004). CONCLUSIONS Ultrasonography is a vital diagnostic procedure used by orthopedic surgeons for diagnosis of the rotator-cuff disorder(s) in patients with sudden shoulder pain.

Tumor necrosis factor-related apoptosis-inducing ligand inhibits the growth and aggressiveness of colon carcinoma via the exogenous apoptosis signaling pathway.

Colon cancer is one of the most common types of gastrointestinal tumor. Previous studies have demonstrated that tumor necrosis factor-(TNF)-related apoptosis-inducing ligand (TRAIL) reduces the aggressiveness of colon cancer tumors and promotes the apoptosis of colon carcinoma cells. In the present study, the inhibitory effects of TRAIL were investigated and the potential mechanism of TRAIL-mediated apoptosis was explored in colon cancer cells. Reverse transcription-quantitative polymerase chain reaction, western blotting, immunofluorescence, immunohistochemistry, TUNEL and flow cytometry assays were used to analyze the effects of TRAIL on the growth, migration, invasion and apoptosis of colon tumor cells. In vivo experiments were performed in mice to analyze the therapeutic effects of TRAIL. The results demonstrated that TRAIL significantly suppressed the growth of colorectal tumor cells in a dose-dependent manner (0.5-2.5 mg/ml) and also promoted colon tumor cell death. The migration and invasion of colon tumor cells were inhibited by the downregulation of fibronectin, Vimentin and E-cadherin. The apoptotic rate revealed that TRAIL (2.0 mg/ml) significantly promoted the apoptosis of colon tumor cells by regulating apoptosis-related gene expression. TRAIL administration promoted the apoptosis of colon tumor cells via the exogenous apoptosis signaling pathway due to the upregulation of caspase-3, caspase-8 and nuclear factor-κB protein expression. In vivo assays revealed that TRAIL administration significantly inhibited tumor growth and promoted apoptotic body and lymphocyte infiltration, which led to increased survival in tumor-bearing mice compared with the control group. Immunohistochemistry revealed that P53 and B-cell lymphoma-2 were downregulated in TRAIL-treated tumors. In conclusion, TRAIL treatment significantly inhibited the growth and aggressiveness of colon tumors by inducing apoptosis via the exogenous apoptosis pathway, which suggests that TRAIL may be a potential anticancer agent for colon carcinoma therapy.

LMO3 promotes gastric cancer cell invasion and proliferation through Akt-mTOR and Akt-GSK3ß signaling.

The present study assessed the biological functions of LIM domain only 3 (LMO3) in gastric cancer (GC) investigated and the underlying molecular mechanisms. It was revealed that the expression of LMO3 was significantly upregulated in GC tissues. A GC tissue microarray (n=164) indicated that LMO3 expression was closely associated with clinicopathological factors, as well as overall survival and disease-free survival of patients. After knockdown of LMO3 in MGC-803 and SGC-7901 cells, the invasion and proliferation were obviously suppressed. Furthermore, LMO3 knockdown suppressed the phosphorylation of Akt, mammalian target of rapamycin (mTOR) and glycogen synthase kinase (GSK)3ß signaling. An inhibitor of mTOR, dactolisib, abrogated recombinant LMO3 protein-induced GC cell invasion and proliferation, while an inhibitor of GSK3ß, CHIR-98014, only abrogated rLMO3 protein-induced proliferation. These results suggested that LMO3 promotes GC cell invasion and proliferation mainly through Akt/mTOR and Akt/GSK3ß signaling. LMO3 may serve as a potential therapeutic target for GC in the future.

Type 2 diabetes mellitus is associated with increased risks of sarcopenia and pre-sarcopenia in Chinese elderly.

Sarcopenia is a condition characterized by progressive and generalized loss of skeletal muscle mass and function. In this study, we used a cross-sectional study with 1090 community-dwelling Chinese citizens aged 60 years and older to evaluate the association of type 2 diabetes mellitus (T2DM) with the risk of sarcopenia and pre-sarcopenia. Sarcopenia was defined using the Asian Working Group for Sarcopenia (AWGS) criteria that include both muscle mass and muscle function/physical activity. Pre-sarcopenia was defined as having low skeletal muscle index but with normal muscle/physical activity. The prevalence of sarcopenia and pre-sarcopenia was significantly higher in T2DM patients than in healthy controls (14.8% vs. 11.2%, p = 0.035 for sarcopenia, and 14.4% vs. 8.4%, p = 0.002 for pre-sarcopenia). In multivariate logistic regression analyses adjusting by age, gender, anti-diabetic medication, energy intake, protein intake, physical activity, and visceral fat area, we found that Chinese elderly with T2DM exhibited significantly increased risks of sarcopenia (OR = 1.37, 95% CI = 1.02-2.03) and pre-sarcopenia (OR = 1.73, 95% CI = 1.10-2.83) compared to non-diabetic individuals. This is the first study to evaluate the association of T2DM with the risks of sarcopenia and pre-sarcopenia in China. Among a group of community-dwelling Chinese elderly, T2DM was significantly associated with increased risks of sarcopenia and pre-sarcopenia.

Propofol protects hippocampal neurons from apoptosis in ischemic brain injury by increasing GLT-1 expression and inhibiting the activation of NMDAR via the JNK/Akt signaling pathway.

Ischemic brain injury (IBI) can cause nerve injury and is a leading cause of morbidity and mortality worldwide. The neuroprotective effects of propofol against IBI have been previously demonstrated. However, the neuroprotective effects of propofol on hippocampal neurons are not yet entirely clear. In the present study, models of IBI were established in hypoxia-exposed hippocampal neuronal cells. Cell viability assay and apoptosis assay were performed to examine the neuroprotective effects of propofol on hippocampal neurons in IBI. A significant decrease in cell viability and a significant increase in cell apoptosis were observed in the IBI group compared with the control group, accompanied by a decrease in glial glutamate transporter-1 (GLT­1) expression as determined by RT-qPCR and western blot analysis. The effects of IBI were reversed by propofol treatment. The siRNA-mediated knockdown of GLT­1 in the hypoxia-exposed hippocampal neuronal cells led to an increase in cell apoptosis, Jun N-terminal kinase (JNK) activation and N-methyl-D­aspartate (NMDA) receptor (NR1 and NR2B) activation, as well as to a decrease in cell viability and a decrease in Akt activation. The effects of RNA interference-mediated GLT­1 gene silencing on cell viability, JNK activation, NMDAR activation, cell apoptosis and Akt activation in the hippocampal neuronal cells were slightly reversed by propofol treatment. The JNK agonist, anisomycin, and the Akt inhibitor, LY294002, both significantly blocked the effects of propofol on hippocampal neuronal cell viability and apoptosis in IBI. The decrease in JNK activation and the increase in Akt activation caused by GLT­1 overexpression were reversed by NMDA. Collectively, our findings suggest that propofol treatment protects hippocampal neurons against IBI by enhancing GLT­1 expression and inhibiting the activation of NMDAR via the JNK/Akt signaling pathway.

Up-regulation of miR-335 predicts a favorable prognosis in esophageal squamous cell carcinoma.

INTRODUCTION: MicroRNAs (miRNAs) are noncoding RNAs that regulate multiple cellular processes during cancer progression. MiR-335 has recently been identified to be involved in tumorigenesis of several cancers such as ovarian cancer and gastric cancer. However, the regulation of miR-335 in esophageal squamous cell carcinoma (ESCC) has not been reported yet. METHODS: Expression of miR-335 in tumor and their normal matched tissues was determined by quantitative real-time PCR in 67 ESCC patients and its association with overall survival of patients was analyzed by statistical analysis. RESULTS: The expression level of miR-335 was reduced in malignant tissue samples in comparison to normal matched tissue (P < 0.05). It was also proved that miR-335 expression was associated with ESCC histological grade, lymph node metastasis, tumor stage and clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that low miR-335 expression was associated with poor prognosis in ESCC patients. Multivariate analysis showed that miR-335 expression was an independent prognostic marker of overall survival of ESCC patients. CONCLUSIONS: The study proves for the first time that miR-335 is down regulated in a majority of ESCC patients. Our results indicate that miR-335 expression is an independent prognostic factor for patients with esophageal cancer, which might be a potential valuable biomarker for ESCC.