SS-31 inhibits mtDNA-cGAS-STING signaling to improve POCD by activating mitophagy in aged mice.

BACKGROUND: Neuroinflammation is crucial in the development of postoperative cognitive dysfunction (POCD), and microglial activation is an active participant in this process. SS-31, a mitochondrion-targeted antioxidant, is widely regarded as a potential drug for neurodegenerative diseases and inflammatory diseases. In this study, we sought to explore whether SS-31 plays a neuroprotective role and the underlying mechanism. METHODS: Internal fixation of tibial fracture was performed in 18-month-old mice to induce surgery-associated neurocognitive dysfunction. LPS was administrated to BV2 cells to induce neuroinflammation. Neurobehavioral deficits, hippocampal injury, protein expression, mitophagy level and cell state were evaluated after treatment with SS-31, PHB2 siRNA and an STING agonist. RESULTS: Our study revealed that SS-31 interacted with PHB2 to activate mitophagy and improve neural damage in surgically aged mice, which was attributed to the reduced cGAS-STING pathway and M1 microglial polarization by decreased release of mitochondrial DNA (mtDNA) but not nuclear DNA (nDNA). In vitro, knockdown of PHB2 and an STING agonist abolished the protective effect of SS-31. CONCLUSIONS: SS-31 conferred neuroprotection against POCD by promoting PHB2-mediated mitophagy activation to inhibit mtDNA release, which in turn suppressed the cGAS-STING pathway and M1 microglial polarization.

Association of cognitive impairment with the interaction between chronic kidney disease and depression: findings from NHANES 2011-2014.

BACKGROUND: Cognitive impairment (CoI), chronic kidney disease (CKD), and depression are prevalent among older adults and are interrelated, imposing a significant disease burden. This study evaluates the association of CKD and depression with CoI and explores their potential interactions. METHOD: Data for this study were sourced from the 2011-2014 National Health and Nutritional Examination Survey (NHANES). Multiple binary logistic regression models assessed the relationship between CKD, depression, and CoI while controlling for confounders. The interactions were measured using the relative excess risk of interaction (RERI), the attributable proportion of interaction (AP), and the synergy index (S). RESULTS: A total of 2,666 participants (weighted n = 49,251,515) were included in the study, of which 700 (16.00%) had CoI. After adjusting for confounding factors, the risk of CoI was higher in patients with CKD compared to non-CKD participants (odds ratio [OR] = 1.49, 95% confidence interval [CI]:1.12-1.99). The risk of CoI was significantly increased in patients with depression compared to those without (OR = 2.29, 95% CI: 1.73-3.03). Furthermore, there was a significant additive interaction between CKD and depression in terms of the increased risk of CoI (adjusted RERI = 2.01, [95% CI: 0.31-3.71], adjusted AP = 0.50 [95% CI: 0.25-0.75], adjusted S = 2.97 [95% CI: 1.27-6.92]). CONCLUSION: CKD and depression synergistically affect CoI, particularly when moderate-to-severe depression co-occurs with CKD. Clinicians should be mindful of the combined impact on patients with CoI. Further research is needed to elucidate the underlying mechanisms and assess the effects specific to different CKD stages.

Efficacy and safety of esketamine combined with propofol for curative endoscopic resection in colorectum: a prospective, randomized controlled trial.

BACKGROUND: Curative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection. METHODS: A total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded. RESULTS: Of the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction. CONCLUSION: Compared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I-III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2300069014 on 03/03/2023).

Cleidocranial dysplasia syndrome with epilepsy: a case report.

BACKGROUND: Cleidocranial dysplasia is a rare autosomal dominant disorder resulting in skeletal and dental abnormalities due to the disturbance in ossification of the bones. The prevalence of CCD is one in a million of live births, and epileptic seizures are rarer in this disease. CASE PRESENTATION: Herein, we present a case of a 10-year-old girl, who not only suffered with cleidocranial dysplasia, but experienced frequent seizures. We initiated an anti-epileptic treatment for this patient with dose adjustments to her weight of levetiracetam (10 mg/kg, bid) for 3 months. The epileptic seizures were controlled, but the intelligence level and control of epilepsy need to be followed up for a longer duration. CONCLUSIONS: In clinical practice, if a patient has unusual facies, typical clavicle defect, skull bone enlargement, and unclosed anterior fontanelle, we should consider the possibility of cleidocranial dysplasia, genetic detection are helpful to make a confirmed diagnosis. In such cases, early diagnosis and treatment is important to correct deformities and improve the quality of life of patients.

Indwelling catheter can increase postoperative urinary tract infection and may not be required in total joint arthroplasty: a meta-analysis of randomized controlled trial.

BACKGROUND: The purpose of this study was to investigate whether patients undergoing total joint arthroplasty (TJA) require catheterization. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure were systematically searched. All randomized controlled trials (RCTs) receiving either a urinary catheterization or no urinary catheterization were included. Meta-analysis results were assessed by RevMan 5.3 software. RESULTS: Seven independent RCTs were included, with a total sample size of 1533 patients, including 750 patients in the indwelling catheter group and 783 patients in the none-indwelling catheter group. Our pooled data analysis indicated that patients in the indwelling catheter group had a higher risk of urinary tract infection than patients in the none-indwelling catheter group (RR, 3.21; P = 0.0003). However, the meta-analysis indicated that there was no significant difference between the two groups in terms of urinary retention (RR, 0.67; P = 0.13), duration of the surgery (MD, - 0.37; P = 0.55), and length of hospital stay (MD, 0.15; P = 0.38). CONCLUSION: Based on the current evidence, this meta-analysis showed that urinary catheterization during TJA can increase the postoperative urinary tract infection, and it may not routinely be required for the patients undergoing TJA. LEVEL OF EVIDENCE: Level I, therapeutic study.

Perioperative multiple low-dose Dexamethasones improves postoperative clinical outcomes after Total knee arthroplasty.

BACKGROUND: The purpose of this study was to investigate the efficacy and safety of multiple low-dose dexamethasones in primary total knee arthroplasty (TKA). METHODS: One hundred fifty patients were equally randomized into 3 groups: Group A (n = 50) received 2 doses of normal saline only; Group B (n = 50) received with 1 dose of intravenous dexamethasone and 1 dose of normal saline; Group C (n = 50) received with 2 doses of intravenous dexamethasone. The clinical outcomes and complications were assessed. RESULTS: The CRP and IL-6 were significantly lower in Group C and B than Group A at 24, 48, and 72 h postoperatively (P < 0.001 for all). The intensity of postoperative nausea and vomiting (PONV) in Group C was lower than Group A at 24 (P < 0.001, P = 0.002), 48 (P = 0.005, P = 0.041) and 72 h (P = 0.017, P = 0.031) postoperatively and Group B at 24 h (P = 0.027, P = 0.019) postoperatively. Pain were significantly less in Group C than Group A at 24 (P < 0.001), 48 h (P = 0.037) postoperatively and Group B 24 h (P = 0.030) postoperatively. Patients in Group C had better range of motion (ROM) and satisfaction than Group A (P < 0.001, P = 0.002) and B (P = 0.001, P = 0.043). No differences were found in complications. CONCLUSIONS: The administration of 10 mg dexamethasone 1 h before the surgery, and repeated at 6 h postoperatively can significantly reduce the level of postoperative CRP and IL-6 and the incidence of PONV, relieve pain, achieve an additional analgesic effect, and improve the early ROM compared with the other two groups in TKA. LEVEL OF EVIDENCE: Therapeutic Level I. TRIAL REGISTRATION: The Chinese Clinical Trial Registry ( ChiCTR1800017036 ). Registered on July 9, 2018.

[Expression of ß-integrin family members in children with T-cell acute lymphoblastic leukemia].

OBJECTIVE: To study the expression of ß-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance. METHODS: Quantitative real-time PCR analyses were performed to assess the expression levels of ß-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively. RESULTS: The mRNA levels of integrins ß2, ß3, and ß5 were significantly lower in children with T-ALL than in controls (P<0.05). In T-ALL patients, high integrin ß3 expression was associated with lower white blood cell counts (<100×109/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P<0.05). In T-ALL patients, higher integrin ß5 expression was associated with relapse of T-ALL (P<0.05). Based on survival curve analysis, higher integrin ß3 expression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P<0.05). CONCLUSIONS: ß-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin ß5 is closely related to the risk of relapse of T-ALL. The expression of integrin ß3 is closely related the treatment response and prognosis of T-ALL.

The effect of different preventive strategies during total joint arthroplasty on periprosthetic joint infection: a network meta-analysis.

BACKGROUND: Periprosthetic joint infection after total joint arthroplasty has a large incidence, and it may often require two or more stages of revision, placing an additional burden on clinicians and patients. The purpose of this network meta-analysis is to evaluate the effect of four different preventive strategies during total joint arthroplasty on the prevention of periprosthetic joint infection. METHODS: The study protocol was registered at PROSPERO (CRD: 42,023,448,868), and the literature search databases included Web of Science, PubMed, OVID Cochrane Central Register of Controlled Trials, OVID EMBASE, and OVID MEDLINE (R) ALL that met the requirements. The network meta-analysis included randomized controlled trials, retrospective cohort studies and prospective cohort studies with the outcome of periprosthetic joint infection. The gemtc R package was applied to perform the network meta-analysis to evaluate the relative results of different preventive strategies. RESULTS: This network meta-analysis study included a total of 38 articles with 4 preventive strategies and negative controls. No improvement was observed in antibiotic-loaded bone cement compared with negative controls. Chlorhexidine showed the highest probability of delivering the best preventive effect, and povidone iodine had the second highest probability. Although vancomycin ranked after chlorhexidine and povidone iodine, it still showed a significant difference compared with negative controls. In addition, the incidence after applying chlorhexidine was significantly lower than that after applying negative controls and vancomycin. In the heterogeneity test between direct and indirect evidence, there was no apparent heterogeneity between them. CONCLUSION: The study indicated that chlorhexidine, povidone iodine and vancomycin showed significant efficacy in preventing periprosthetic joint infection after total joint arthroplasty, while antibiotic-loaded bone cement did not. Therefore, more high-quality randomized controlled trials are needed to verify the results above.

Rutin prevents pyroptosis and M1 microglia via Nrf2/Mac-1/caspase-1-mediated inflammasome axis to improve POCD.

BACKGROUND: Neuroinflammation following peripheral surgery plays a key role in postoperative cognitive dysfunction (POCD) development and there is no effective therapy to inflammation-mediated cognitive impairment. Recent studies showed that rutin, a natural flavonoid compound, conferred neuroprotection. However, the effects and mechanisms of rutin on cognition of surgical and aged mice and LPS-induced BV2 need deeper exploration. METHODS: The effect of rutin in vivo and vitro were evaluated by Morris water maze test, HE stainin, Golgi-Cox staining, IF, IHC, RT-PCR, Flow Cytometer and Western blotting. In vivo, aged mice were treated with rutin and surgery. In vitro, rutin, Nrf2 knockdown, MAC-1 overexpression and VX765, a caspase-1 inhibitor, were administration on BV2 microglial cells. RESULTS: Surgery led to compensatory increase in nuclear Nrf2 and rutin could further increase it. Neural damage was accompanied with high level in MAC-1, caspase-1-mediated pyroptosis and M1 microglia, while rutin recovered the process. Nrf2 inhibition abolished the effect of rutin with the increase of MAC-1, caspase-1-mediated pyroptosis and M1 microglia. Activation of MAC-1 abrogated protection of rutin by increase in pyroptosis and M1 microglia. Finally, we found that treatment with VX765 improved injury and increased M2 microglia against overexpression of MAC-1. CONCLUSIONS: Our study indicated that rutin may be a potential therapy in POCD and exerted neural protection via Nrf2/ Mac-1/ caspase-1-mediated inflammasome axis to regulate pyroptosis and microglial polarization.

Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux.

Brain metastases and lung metastases are major causes of treatment failure and related mortality in melanoma. Fluoxetine hydrochloride (FXT), a widely-used antidepressant, has emerged as a potential anticancer agent in preclinical studies. Previous research has shown its potential to inhibit melanoma. However, its efficacy and the underlying mechanisms in melanoma metastasis, especially concerning brain metastases and lung metastases, remain underexplored. This study investigates FXT's inhibitory effects on melanoma growth and metastasis to the lung and brain. Employing a combination of in vitro assays, we demonstrate FXT's potent suppression of melanoma growth through induction of intrinsic apoptosis, disruption of autophagic flux, and cell cycle arrest at the G0/G1 phase. In in vivo mouse models, we found that FXT exhibits strong inhibitory activity against melanoma brain metastases and lung metastases. Our findings provide a foundation for future clinical exploration of FXT as a novel treatment strategy for melanoma, underscoring its ability to target both primary and metastatic lesions.

An Amino Acids and Dipeptide Injection Inhibits the TNF-α/HMGB1 Inflammatory Signaling Pathway to Reduce Pyroptosis and M1 Microglial Polarization in POCD Mice: the Gut to the Brain.

Peripheral surgery-induced neural inflammation is a key pathogenic mechanism of postoperative cognitive dysfunction (POCD). However, the mechanism underlying neuroinflammation and associated neural injury remains elusive. Surgery itself can lead to gut damage, and the occurrence of POCD is accompanied by high levels of TNF-α in the serum and blood‒brain barrier (BBB) damage. Reductions in stress, inflammation and protein loss have been emphasized as strategies for enhanced recovery after surgery (ERAS). We designed an amino acids and dipeptide (AAD) formula for injection that could provide intestinal protection during surgery. Through the intraoperative infusion of AAD based on the ERAS concept, we aimed to explore the effect of AAD injection on POCD and its underlying mechanism from the gut to the brain. Here, we observed that AAD injection ameliorated neural injury in POCD, in addition to restoring the function of the intestinal barrier and BBB. We also found that TNF-α levels decreased in the ileum, blood and hippocampus. Intestinal barrier protectors and TNF-α inhibitors also alleviated neural damage. AAD injection treatment decreased HMGB1 production, pyroptosis, and M1 microglial polarization and increased M2 polarization. In vitro, AAD injection protected the impaired gut barrier and decreased TNF-α production, alleviating damage to the BBB by stimulating cytokine transport in the body. HMGB1 and Caspase-1 inhibitors decreased pyroptosis and M1 microglial polarization and increased M2 polarization to protect TNF-α-stimulated microglia in vitro. Collectively, these findings suggest that the gut barrier-TNF-α-BBB-HMGB1-Caspase-1 inflammasome-pyroptosis-M1 microglia pathway is a novel mechanism of POCD related to the gut-brain axis and that intraoperative AAD infusion is a potential treatment for POCD.

A nomogram to predict cognitive function impairment in patients with chronic kidney disease: A national cross-sectional survey.

Background: Cognitive function impairment (CFI) is common in patients with chronic kidney disease (CKD) and significantly impacts treatment adherence and quality of life. This study aims to create a simplified nomogram for early CFI risk detection. Methods: Data were obtained from the National Health and Nutrition Examination Survey cycles spanning from 1999 to 2002 and again from 2011 to 2014. Stepwise logistic regression was used to select variables and construct a CFI risk prediction model. Furthermore, C-statistic and Brier Score (BS) assessed model performance. Additionally, Kaplan-Meier survival curves were utilised to assess risk group-death prognosis relationships. Results: Of the 545 participants in the CKD model development cohort, a total of 146 (26.8 %) had CFI. The final model included the variables of age, race, education, annual family income, body mass index, estimated glomerular filtration rate, serum albumin and uric acid. The model had a C-statistic of 0.808 (95 % confidence interval (CI): 0.769-0.847) and a BS of 0.149. Furthermore, the 5-fold cross-validation internal C-statistic was 0.764 (interquartile range: 0.763-0.807) and BS was 0.154. Upon external validation, the model's C-statistic decreased to 0.752 (95 % CI: 0.654-0.850) and its BS increased to 0.182. The Kaplan-Meier survival curves demonstrated that intermediate-to-high-risk participants had shorter overall survival time than low-risk participants (log-rank test: p = 0.00042). Conclusions: This study established an effective nomogram for predicting CFI in patients with CKD, which can be used for the early detection of CFI and guide the treatment of patients with CKD.

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux.

The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.

The effects of vitamin B6 on the nutritional support of BCAAs-enriched amino acids formula in rats with partial gastrectomy.

BACKGROUND: Total parenteral nutrition with the formula of amino acids enriched branched-chain amino acids (BCAAs) could promote patients' recovery after gastrointestinal surgery. Previous studies reported that vitamin B6 could promote amino acid metabolism and enhance protein synthesis. The aim of this study was to determine if the addition of vitamin B6 to BCAAs-enriched formula can enhance postoperative nutritional status and intestinal function in rats undergoing partial gastrectomy, and the appropriate compatibility concentration of vitamin B6. METHODS: Fifty-six male rats were randomly divided into seven groups (n = 8 per group): (I) Control, (II) BCAAs-enriched formula group (BCAA), (III) BCAA plus vitamin B6 (50 mg/L), (IV) BCAA plus vitamin B6 (100 mg/L), (V) BCAA plus vitamin B6 (200 mg/L), (VI) BCAA plus vitamin B6 (500 mg/L), and (VII) BCAA plus vitamin B6 (1000 mg/L). All animals were performed partial gastrectomy and placed a jugular vein catheter. During enteral nutrition, blood and urine samples were repeatedly collected. Gastrocnemius muscle and small intestine were also collected at the end of experiment. RESULTS: The addition of vitamin B6 to BCAAs-enriched formula improved negative nitrogen balance after gastrectomy compared to the BCAAs-enriched formula group at POD1 (first postoperative day) and POD3 (third postoperative day), and 100 mg/L was an appropriate concentration of vitamin B6 to enhance the effects of BCAAs-enriched formula. The 3-methylhistidine/creatinine in BCAA plus vitamin B6 groups were significantly lower than that in the BCAA group at POD3. Moreover, BCAA plus vitamin B6 group significantly increased the cross-sectional area of the muscle fibers compared to the BCAA group. Transcriptome sequencing, GO and KEGG enhancement analysis also showed that BCAA plus vitamin B6 group showed muscle organ development and PI3K/AKT pathway enhancement compared to BCAA group. Moreover, AKT/mTOR/4EBP1 pathway was activated in BCAA plus vitamin B6 group. In addition, the results also showed that BCAA plus vitamin B6 decreased D-lactate, and exerted synergistic effects on intestinal morphology. CONCLUSION: The addition of vitamin B6 to BCAAs-enriched formula could improve nitrogen balance, promote muscle protein synthesis through AKT/mTOR/4EBP1 pathway, and alleviate intestinal mucosa damage after partial gastrectomy in rats. Overall, the results from this pre-clinical study support the use of vitamin B6 as an ingredient to BCAAs-enriched formula, and 100 mg/L may be an optimal concentration for rats.

Early identification of bloodstream infection in hemodialysis patients by machine learning.

Background: Bloodstream infection (BSI) is a prevalent cause of admission in hemodialysis (HD) patients and is associated with increased morbidity and mortality. This study aimed to establish a diagnostic, predictive model for the early identification of BSI in HD patients. Methods: HD patients who underwent blood culture testing between August 2018 and March 2022 were enrolled in this study. Machine learning algorithms, including stepwise logistic regression (SLR), Lasso logistic regression (LLR), support vector machine (SVM), decision tree, random forest (RF), and gradient boosting machine (XGboost), were used to predict the risk of developing BSI from the patient's clinical data. The accuracy (ACC) and area under the subject working curve (AUC) were used to evaluate the performance of such models. The Shapley Additive Explanation (SHAP) values were used to explain each feature's predictive value on the models' output. Finally, a simplified nomogram for predicting BSI was devised. Results: A total of 391 HD patients were enrolled in this study, of whom 74 (18.9%) were diagnosed with BSI. The XGboost model achieved the highest AUC (0.914, 95% confidence interval [CI]: 0.861-0.964) and ACC (86.3%) for BSI prediction. The four most significant co-variables in both the significance matrix plot of the XGboost model variables and the SHAP summary plot were body temperature, dialysis access via a non-arteriovenous fistula (non-AVF), the procalcitonin levels (PCT), and neutrophil-lymphocyte ratio (NLR). Conclusions: This study created an effective machine-learning model for predicting BSI in HD patients. The model could be used to detect BSI at an early stage and hence guide antibiotic treatment in HD patients.

Neutropenic Diet Cannot Reduce the Risk of Infection and Mortality in Oncology Patients With Neutropenia.

Background: The purpose of this systematic review and meta-analysis was to evaluate the effect of a neutropenic diet and a control diet on infection and mortality rates in oncology patients with neutropenia. Methods: We searched the following English electronic databases: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar Engine. Published studies involving neutropenic diets (study group) and control diets (control group) in oncology patients with neutropenia were searched. The focus of the meta-analysis was on the outcomes of infection and mortality rates. A subgroup analysis was also performed. Results: A total of 6 studies were included, with a total sample size of 1114 patients. The patients in the study group had a similar infection rate compared with the patients in the control group (P = 0.11). The patients in the study group had a similar mortality rate compared with the patients in the control group (P = 0.74). Another subgroup analysis showed that the incidence of infection was also similar for pediatric (P = 0.74) and adult (P = 0.11) oncology patients between the study and control groups. Conclusions: Based on the current evidence, this meta-analysis showed that the application of a neutropenic diet cannot reduce the risk of infection and mortality in oncology patients with neutropenia. However, more rigorous randomized controlled trials are needed to confirm this conclusion in the future.

Effectiveness of Impregnated Central Venous Catheters on Catheter-Related Bloodstream Infection in Pediatrics.

Background: The efficacy and safety of impregnated central venous catheters (CVCs) in pediatrics remain controversial. The purpose of this study was to evaluate the efficacy of impregnations for the prevention of catheter-related bloodstream infection (CRBSI). Methods: We searched the following five electronic databases: Medline, PubMed, Cochrane, Embase, and the Web of Science for randomized controlled trials (RCTs) up to March 2021. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a fixed-effects model. Assessment of publication biases was evaluated by Egger's test. Heterogeneity between studies was assessed based on the chi-square test and I 2 statistics, and sensitivity analysis and subgroup analysis were also performed. Results: A total of six RCTs with 3,091 patients were included. Impregnated CVCs provided significant benefits in reducing the risk of CRBSI (RR = 0.41, 95% CI: 0.26-0.66) in pediatric patients, especially in the pediatric group. No publication bias was observed in the Egger test for the risk of CRBSI. Drug type is a source of heterogeneity. Conclusion: Antimicrobial-impregnated CVCs are beneficial to prevent CVC-related complications in pediatrics.

Paediatric Erdheim-Chester Disease in the Lateral Ventricle: A Case Report and Review of the Literature.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis caused by the expression of CD68-positive and CD1a-negative foam tissue cells, which is polar in pediatric patients. The study reports a case of an 8-year-old Chinese boy who presented with polydipsia and polyuria for 4 years, followed by central nervous system symptoms. Magnetic resonance imaging (MRI) showed a large lesion in the lateral ventricle. The histiocytes stained positively for CD68, CD163 and negatively for CD1a, glial fibrillary acidic protein (GFAP) and langerin, and were partially positive for S100 by immunohistochemical assay. More importantly, BRAFV 600E staining was positive in tissue, and the BRAF V600E mutations was also detected by real-time quantitative PCR (RT-qPCR) in the intracranial lesion tissue. According to our review of the literature, this is a rare case of ECD in the ventricle, with a younger age.

Continuous Erector Spinae Plane Block Using Programmed Intermittent Bolus Regimen versus Intravenous Patient-Controlled Opioid Analgesia Within an Enhanced Recovery Program After Open Liver Resection in Patients with Coagulation Disorder: A Randomized, Controlled, Non-Inferiority Trial.

Purpose: Postoperative pain after open hepatectomy is significant. Preoperative coagulopathy limits the use of epidural analgesia, the gold standard for pain control in open abdominal surgery. Erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we compared the analgesic efficacy of patient-controlled continuous ESPB (CESPB) with hydromorphone patient-controlled intravenous analgesia (PCIA) after right subcostal incision hepatectomies in hepatocellular carcinoma patients with preoperative coagulopathy. Patients and Methods: In this randomized, controlled, unblinded, and noninferiority trial, 120 patients were randomized to receive either CESPB or PCIA as primary postoperative analgesia together with parecoxib (40mg Q12 h IV) for 3 days after surgery. The primary outcome was the average cough-elicited pain numeric rating scales (NRS) recorded at the seven follow-up time points of 20:00 on the day of surgery and 9:00 and 15:00 on the postoperative day 1 to day 3 (POD1 to POD3). Results: The average cough-elicited pain NRS score was 2.402 in the CESPB group and 2.676 in the PCIA group. The mean difference (95% CI) was -0.274 (-0.620 to 0.072), which demonstrated the noninferiority of CESPB to PCIA. Patients in the CESPB group had less intraoperative opioid consumption, a lower incidence of moderate-to-severe pain and PONV at POD3, and early resumption of oral intake. Conclusion: CESPB provides analgesic efficacy noninferior to opioid PCIA in the context of multimodal analgesia after right subcostal incision open hepatectomy.

Metabolomics study of the metabolic changes in hepatoblastoma cells in response to NTCP/SLC10A1 overexpression.

NTCP (SLC10A1) has been well recognized as a basolateral (sinusoidal) Na+-bile acid co-transporter that mediates the hepatic uptake of bile acids. However, little is known about the effects of NTCP (SLC10A1) on hepatoblastoma (HB) and its underlying metabolic mechanisms. In this study, we found that NTCP (SLC10A1) expression was downregulated in HB cells and tissues, and it was demonstrated that NTCP (SLC10A1) reduced cell viability, promoted cell cycle arrest and induced apoptosis of HB cells. The metabolic profiles of HB cells with NTCP (SLC10A1) overexpression were further examined to determine their biochemical alterations and deepen our understanding on the metabolic regulation of NTCP (SLC10A1) overexpression. The metabolomics study based on ultra performance liquid chromatography-mass spectrometry revealed alterations in the metabolites of HB cells following NTCP (SLC10A1) overexpression. Next, we stably overexpressed NTCP (SLC10A1) in HepG2 cells, and found that NTCP (SLC10A1)-overexpressing cells could inhibit the production of adenosine and decreased both mRNA and protein levels of HIF1α. Further overexpression of HIF1α in the NTCP (SLC10A1)-overexpression group restored the production of adenosine. Collectively, these findings provide strong evidence that NTCP (SLC10A1) overexpression significantly disrupts the metabolism of adenosine in HB cells and highlight that NTCP (SLC10A1) mediates adenosine production mainly through HIF1α.