Lipid Metabolism, Methylation Aberrant, and Osteoporosis: A Multi-omics Study Based on Mendelian Randomization.

BACKGROUND: Observational studies have shown a causal association between dyslipidemia and osteoporosis, but the genetic causation and complete mechanism of which are uncertain. The disadvantage of previous observational studies is that they are susceptible to confounding factors and bias, that makes it difficult to infer a causal link between those two diseases. Abnormal epigenetic modifications, represented by DNA methylation, are important causes of many diseases. However, there are no studies showing a bridging role for methylation modifications in blood lipid metabolism and osteoporosis. METHODS: SNPs for lipid profile (Blood VLDL cholesterol (VLDL-C), blood LDL cholesterol (LDL-C), blood HDL cholesterol (HDL-C), blood triglycerides (TG), diagnosed pure hypercholesterolaemia, blood apolipoprotein B (Apo B), blood apolipoprotein A1(Apo A1)), and bone mineral density (BMD) in different body parts (Heel BMD, lumbar BMD, whole-body BMD, femoral neck BMD) were obtained from large meta-analyses of genome-wide association studies as instrumental variables for two-sample Mendelian randomization. Assessment of the genetic effects of lipid profile-associated methylation sites and bone mineral density was carried out using the summary-data-based Mendelian randomization (SMR) method. RESULTS: Two-sample Mendelian randomization showed that there was a negative causal association between hypercholesterolaemia and heel BMD (p = 0.0103, OR = 0.4590), and total body BMD (p = 0.0002, OR = 0.2826). LDL-C had a negative causal association with heel BMD (p = 8.68E-05, OR = 0.9586). VLDL-C had a negative causal association with heel BMD (p = 0.035, OR = 0.9484), lumbar BMD (p = 0.0316, OR = 0.9356), and total body BMD (p = 0.0035, OR = 0.9484). HDL-C had a negative causal association with heel BMD (p = 1.25E-05, OR = 0.9548), lumbar BMD (p = 0.0129, OR = 0.9358), and total body BMD (p = 0.0399, OR = 0.9644). Apo B had a negative causal association with heel BMD (p = 0.0001, OR = 0.9647). Apo A1 had a negative causal association with heel BMD (p = 0.0132, OR = 0.9746) and lumbar BMD (p = 0.0058, OR = 0.9261). The p-values of all positive results corrected by the FDR method remained significant and sensitivity analysis showed that there was no horizontal pleiotropy in the results despite the heterogeneity in some results. SMR identified 3 methylation sites associated with lipid profiles in the presence of genetic effects on BMD: cg15707428(GREB1), cg16000331(SREBF2), cg14364472(NOTCH1). CONCLUSION: Our study provides insights into the potential causal links and co-pathogenesis between dyslipidemia and osteoporosis. The genetic effects of dyslipidaemia on osteoporosis may be related to certain aberrant methylation genetic modifications.

Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy.

BACKGROUND: Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study. RESULTS: Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8+ T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4+ CD28null T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2- SPP1+ foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses. CONCLUSIONS: We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies.

Incidence and risk factors of proximal junctional kyphosis in adolescent idiopathic scoliosis after correction surgery: a meta-analysis and systematic review.

AIM: To analyze the risk factors of proximal junctional kyphosis (PJK) after correction surgery in patients with adolescent idiopathic scoliosis (AIS). METHODS: PubMed, Medline, Embase, Cochrane Library, Web of Science, CNKI, and EMCC databases were searched for retrospective studies utilizing all AIS patients with PJK after corrective surgery to collect preoperative, postoperative, and follow-up imaging parameters, including thoracic kyphosis (TK), lumbar lordosis (LL), proximal junctional angle (PJA), the sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), pelvic incidence-lumbar lordosis (PI-LL), sacral slope (SS), rod contour angle (RCA) and upper instrumented vertebra (UIV). RESULTS: Nineteen retrospective studies were included in this meta-analysis, including 550 patients in the intervention group and 3456 patients in the control group. Overall, sex (OR 1.40, 95% CI (1.08, 1.83), P = 0.01), larger preoperative TK (WMD 6.82, 95% CI (5.48, 8.16), P < 0.00001), larger follow-up TK (WMD 8.96, 95% CI (5.62, 12.30), P < 0.00001), larger postoperative LL (WMD 2.31, 95% CI (0.91, 3.71), P = 0.001), larger follow-up LL (WMD 2.51, 95% CI (1.19, 3.84), P = 0.0002), great change in LL (WMD - 2.72, 95% CI (- 4.69, - 0.76), P = 0.006), larger postoperative PJA (WMD 4.94, 95% CI (3.62, 6.26), P < 0.00001), larger follow-up PJA (WMD 13.39, 95% CI (11.09, 15.69), P < 0.00001), larger postoperative PI-LL (WMD - 9.57, 95% CI (- 17.42, - 1.71), P = 0.02), larger follow-up PI-LL (WMD - 12.62, 95% CI (- 17.62, - 7.62), P < 0.00001), larger preoperative SVA (WMD 0.73, 95% CI (0.26, 1.19), P = 0.002), larger preoperative SS (WMD - 3.43, 95% CI (- 4.71, - 2.14), P < 0.00001), RCA (WMD 1.66, 95% CI (0.48, 2.84), P = 0.006) were identified as risk factors for PJK in patients with AIS. For patients with Lenke 5 AIS, larger preoperative TK (WMD 7.85, 95% CI (5.69, 10.00), P < 0.00001), larger postoperative TK (WMD 9.66, 95% CI (1.06, 18.26), P = 0.03, larger follow-up TK (WMD 11.92, 95% CI (6.99, 16.86), P < 0.00001, larger preoperative PJA (WMD 0.72, 95% CI (0.03, 1.41), P = 0.04, larger postoperative PJA (WMD 5.54, 95% CI (3.57, 7.52), P < 0.00001), larger follow-up PJA (WMD 12.42, 95% CI 9.24, 15.60), P < 0.00001, larger follow-up SVA (WMD 0.07, 95% CI (- 0.46, 0.60), P = 0.04), larger preoperative PT (WMD - 3.04, 95% CI (- 5.27, - 0.81), P = 0.008, larger follow-up PT (WMD - 3.69, 95% CI (- 6.66, - 0.72), P = 0.02) were identified as risk factors for PJK. CONCLUSION: Following corrective surgery, 19% of AIS patients experienced PJK, with Lenke 5 contributing to 25%. Prior and post-op measurements play significant roles in predicting PJK occurrence; thus, meticulous, personalized preoperative planning is crucial. This includes considering individualized treatments based on the Lenke classification as our future evaluation standard.

Comparison of Lumbar Interbody Fusion with 3D-Printed Porous Titanium Cage Versus Polyetheretherketone Cage in Treating Lumbar Degenerative Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the safety and radiological effectiveness of lumbar interbody fusion with a 3D-printed porous titanium (3D-PPT) cage versus a polyetheretherketone (PEEK) cage for the treatment of lumbar degenerative disease. METHODS: This study was registered at PROSPERO (CRD42023461511). We systematically searched the PubMed, Embase, and Web of Science databases for related studies from inception to September 3, 2023. Review Manager 5.3 was used to conduct this meta-analysis. The reoperation rate, complication rate, fusion rate, and subsidence rate were assessed using relative risk and 95% confidence intervals. RESULTS: Ten articles reporting 9 studies comparing lumbar interbody fusion with 3D-PPT cages versus PEEK cages for the treatment of lumbar degenerative disease were included. The subsidence rate at the 1-year follow-up in the 3D-PPT cage was significantly lower than that in the PEEK cage. The fusion rate in the 3D-PPT cage was significantly higher than that in the PEEK cage at the 6-month follow-up. No significant difference was identified between the 2 groups at the 12-month follow-up. No significant difference was identified between the 2 groups in terms of the complication rate and reoperation rate. There was a trend toward a lower complication rate and reoperation rate with the 3D-PPT cage. CONCLUSIONS: Compared with the PEEK cage, the 3D-PPT cage may be a safer implant. The 3D-PPT cage was associated with a higher fusion rate and lower subsidence rate. The 3D-PPT cage may accelerate the intervertebral fusion process, improve the quality of fusion and prevent the occurrence of subsidence.

The Relationship Between Modic Changes and Endplate Sclerosis in Patients with Lumbar Degenerative Disease: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To explore the relationship between modic changes (MCs) and endplate sclerosis in patients with lumbar degenerative disease. METHODS: This network meta-analysis was performed on the basis of Preffered Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement. This study was registered at the International Prospective Register of Systematic Reviews (CRD42024497370). We performed a systematic search of the PubMed, Web of Science, Embase, China national knowledge infrastructure, China Science and Technology Journal Database, and Wanfang databases from inception to December 22, 2023. STATA13.0 and RevMan 5.3 were applied to perform the meta-analysis. RESULTS: Seven studies with a total of 1510 endplates were divided into 6 groups according to the type of MCs. The endplate sclerosis rate in the single-type group was significantly lower than that in the mixed-type group. The endplate sclerosis rate in the type I MC (MC1) was significantly lower than that in the type II MC (MC2). The endplate sclerosis rate in the MC2 was significantly lower than that in the type III MC (MC3). The endplate sclerosis rate in the MC1/2 was significantly lower than that in the MC2/3. No significant difference was detected between MC1/2 and MC1/3 or between MC2/3 and MC1/3. For decreasing the endplate sclerosis rate, the order of the different types of MCs was MC1>MC2>MC1/2>MC2/3≈MC1/3>MC3. CONCLUSIONS: Endplate sclerosis occurs in all kinds of MCs. With increasing grade of MCs, the incidence of endplate sclerosis gradually increased. The endplate sclerosis rate in mixed-type MCs was significantly greater than that in MC2 and significantly lower than that in MC3. The endplate sclerosis rate in the mixed-type, including MC3 (MC1/3 and MC2/3), was significantly greater than that in the MC1/2.

Modic Changes Increase the Cage Subsidence Rate in Spinal Interbody Fusion Surgery: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To compare the effect of different Modic changes (MC) grades on the cage subsidence rate after spinal interbody fusion surgery. METHODS: We comprehensively searched the PubMed, Embase, and Web of Science databases from inception to August 13, 2023, for relevant randomized controlled trials and prospective and retrospective cohort studies. Review Manager 5.3 and STATA13.0 were used to conduct this meta-analysis. The subsidence rate was assessed using relative risk and 95% confidence intervals. RESULTS: Six studies with a total of 716 segments were allocated to four groups according to the type of MC. The subsidence rate in the non-Modic changes (NMC) was significantly lower than that in the MC. The subsidence rate in the NMC was significantly lower than that in the MC in the subgroup of cages with extra instrumentation. No significant difference was identified between the 2 groups in the oblique lumbar interbody fusion subgroup. The subsidence rate in the NMC was significantly lower than that in the MC in the transforaminal lumbar interbody fusion subgroup. The subsidence rate in the NMC was significantly lower than that in the MC1 and MC2. We found no significant difference between NMC and MC3, MC1 and MC2, MC1 and MC3, or MC2 and MC3. CONCLUSIONS: MC may be associated with a higher cage subsidence rate. With the increase in MC grades, the incidence of subsidence decreased gradually, but it was always higher than that in the NMC. Oblique lumbar interbody fusion may be a better choice for the treatment of lumbar degenerative disease with MC.

Posterior Pedicle Screw Fixation With Indirect Decompression Versus Direct Decompression in Treating Thoracolumbar Burst Fracture: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the safety and efficacy between posterior pedicle screw fixation with direct versus indirect decompression in treating patients with thoracolumbar burst fracture. METHODS: This study was conducted on the basis of PRISMA statement. We systematically searched the PubMed and Embase databases up to July 3, 2023. Relevant studies comparing indirect decompression and direct decompression were recruited. Weighted mean differences (WMDs), odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed for continuous and dichotomous data, respectively. P < 0.05 was considered statistically significant. RESULTS: The operation time (WMD: -37.14, 95% CI: [-42.64, 31.64], P < 0.00001, I2 = 0%) and intraoperative blood loss (WMD: -316.82, 95% CI: [-469.80, -163.85], P < 0.0001, I2 = 99%) of indirect decompression group were significantly lower. Percentage of anterior vertebral body height (WMD: 3.98, 95% CI: [2.36, 5.60], P < 0.00001, I2 = 32%) and encroachment rate of the spinal canal (WMD: 1.48, 95% CI: [0.56, 2.40], P = 0.002, I2 = 35%) of indirect decompression group were significantly higher. No statistical difference was identified in grades of neurologic recovery and Cobb angle. CONCLUSIONS: Posterior pedicle screw fixation with indirect decompression was safe and effective for thoracolumbar burst fracture with or without neurologic deficits when posterior longitudinal ligament was intact.

CPMI-ChatGLM: parameter-efficient fine-tuning ChatGLM with Chinese patent medicine instructions.

Chinese patent medicine (CPM) is a typical type of traditional Chinese medicine (TCM) preparation that uses Chinese herbs as raw materials and is an important means of treating diseases in TCM. Chinese patent medicine instructions (CPMI) serve as a guide for patients to use drugs safely and effectively. In this study, we apply a pre-trained language model to the domain of CPM. We have meticulously assembled, processed, and released the first CPMI dataset and fine-tuned the ChatGLM-6B base model, resulting in the development of CPMI-ChatGLM. We employed consumer-grade graphics cards for parameter-efficient fine-tuning and investigated the impact of LoRA and P-Tuning v2, as well as different data scales and instruction data settings on model performance. We evaluated CPMI-ChatGLM using BLEU, ROUGE, and BARTScore metrics. Our model achieved scores of 0.7641, 0.8188, 0.7738, 0.8107, and - 2.4786 on the BLEU-4, ROUGE-1, ROUGE-2, ROUGE-L and BARTScore metrics, respectively. In comparison experiments and human evaluation with four large language models of similar parameter scales, CPMI-ChatGLM demonstrated state-of-the-art performance. CPMI-ChatGLM demonstrates commendable proficiency in CPM recommendations, making it a promising tool for auxiliary diagnosis and treatment. Furthermore, the various attributes in the CPMI dataset can be used for data mining and analysis, providing practical application value and research significance.

Anterior, Posterior and Anterior-Posterior Approaches for the Treatment of Thoracolumbar Burst Fractures: A Network Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To compare the clinical and radiological results of the anterior approach versus the posterior approach versus the anterior-posterior approach for the treatment of thoracolumbar burst fractures. METHODS: The network meta-analysis was performed in accordance with the PRISMA Statement. Electronic searches of PubMed and Embase were conducted up to June 22, 2023, for relevant randomized controlled trials. STATA13.0 was used to perform network meta-analysis. p < .05 was considered significant. RESULTS: Nine RCTs with a total of 550 patients receiving surgical treatment in at least two of the three approaches, including anterior, posterior and anterior-posterior approaches, were included. The surgical duration and intraoperative bleeding volume in the posterior approach were significantly lower than those in the anterior (SMD, -1.72; 95% CI, -2.82, -0.62) and anterior-posterior approaches (SMD, 3.33; 95% CI, 1.65, 5.00). The surgical duration in the anterior approach was significantly lower than that in the anterior-posterior approach (SMD, 1.61; 95% CI, 0.12, 3.10). The Cobb angle in the anterior-posterior approach was significantly lower than that in the anterior approach (MD, -4.83; 95% CI, -9.60, -0.05). The VAS score in the posterior approach was significantly higher than that in the anterior approach (MD, 0.85; 95% CI, 0.55, 1.16) and anterior-posterior approach (MD, -0.84; 95% CI, -1.12, -0.55). No significant difference was identified among the three surgical approaches in implant failure rate and infection rate. CONCLUSION: All three approaches were safe approaches with advantages and disadvantages. The selection of surgical approaches for the treatment of thoracolumbar burst fractures may be individualized.

GastroBot: a Chinese gastrointestinal disease chatbot based on the retrieval-augmented generation.

Introduction: Large Language Models (LLMs) play a crucial role in clinical information processing, showcasing robust generalization across diverse language tasks. However, existing LLMs, despite their significance, lack optimization for clinical applications, presenting challenges in terms of illusions and interpretability. The Retrieval-Augmented Generation (RAG) model addresses these issues by providing sources for answer generation, thereby reducing errors. This study explores the application of RAG technology in clinical gastroenterology to enhance knowledge generation on gastrointestinal diseases. Methods: We fine-tuned the embedding model using a corpus consisting of 25 guidelines on gastrointestinal diseases. The fine-tuned model exhibited an 18% improvement in hit rate compared to its base model, gte-base-zh. Moreover, it outperformed OpenAI's Embedding model by 20%. Employing the RAG framework with the llama-index, we developed a Chinese gastroenterology chatbot named "GastroBot," which significantly improves answer accuracy and contextual relevance, minimizing errors and the risk of disseminating misleading information. Results: When evaluating GastroBot using the RAGAS framework, we observed a context recall rate of 95%. The faithfulness to the source, stands at 93.73%. The relevance of answers exhibits a strong correlation, reaching 92.28%. These findings highlight the effectiveness of GastroBot in providing accurate and contextually relevant information about gastrointestinal diseases. During manual assessment of GastroBot, in comparison with other models, our GastroBot model delivers a substantial amount of valuable knowledge while ensuring the completeness and consistency of the results. Discussion: Research findings suggest that incorporating the RAG method into clinical gastroenterology can enhance the accuracy and reliability of large language models. Serving as a practical implementation of this method, GastroBot has demonstrated significant enhancements in contextual comprehension and response quality. Continued exploration and refinement of the model are poised to drive forward clinical information processing and decision support in the gastroenterology field.

Tyrosine kinase inhibitors and atherosclerosis: A close but complicated relationship.

Targeted cancer therapies have revolutionized the treatment of the disease in the past decade. The tyrosine kinase inhibitor (TKI) class of drugs is a widely used option for treating various cancers. Despite numerous advances, clinical and experimental studies have demonstrated the atherosclerosis-inducing properties of these drugs that can cause adverse cardiovascular events. TKIs also have an atherosclerosis-preventing role in patients with cancer through different mechanisms under various conditions, suggesting that specific drugs play different roles in atherosclerosis regulation. Given these contradictory properties, this review summarizes the outcomes of previously performed clinical and basic experiments and shows how the targeted effects of novel TKIs affect atherosclerosis. Future collaborative efforts are warranted to enhance our understanding of the association between TKIs and atherosclerosis.

Carbon dots-functionalized extended gate organic field effect transistor-based biosensors for low abundance proteins.

Organic field effect transistors have emerged as promising platforms for biosensing applications. However, the challenge lies in optimizing functionalization strategies for the sensing interface, enabling the simultaneous detection of low abundance proteins while maintaining device performance. Here, we designed a carbon dots-functionalized extended gate organic field effect transistor. Leveraging the advantages of facile synthesis, tunable modification, small particle size, and cost-effectiveness of carbon dots, we implemented their integration onto the electrode surface. Through harnessing the covalent interactions of functional groups on the surface of carbon dots, we achieved effective immobilization of low abundance proteins without compromising device performance. Consequently, this biosensor exhibits a remarkably low limit of detection of 2.7 pg mL-1 and demonstrates high selectivity for the carcinoembryonic antigen. These findings highlight the superior capabilities of carbon dots in enhancing biosensor performance and emphasize their potential for early cancer detection.

Twisting Ovaries: Three Cases of Ovarian Torsion.

Ovarian torsion is a medical emergency that should be considered for every female presenting with abdominal pain. This series consists of three cases of females of varying ages presenting with abdominal pain who were all ultimately diagnosed with ovarian torsion. It highlights the variability in presentation, physical examination, and other factors related to the diagnosis.

Advanced imaging modalities provide new insights into coronary artery calcification.

Coronary calcification plays a major role as a key surrogate measure of plaque burden, providing powerful risk stratification and influencing preventive therapy. Depending on its location and density, microcalcifications may directly result in plaque rupture and adverse clinical events. Although macroscopic calcifications are frequently linked to advanced and stable plaques, the fact that a small number of thrombotic events are caused by plaques that possess a substantial amount of calcification should not be overlooked. Early and accurate assessment of calcium content in atherosclerotic plaques potentially enhances the identification of high-risk patients requiring preventive treatments. Non-invasive imaging allows for the visualization, detection, and quantification of calcific lesions, whereas intravascular imaging has the unique advantage of providing real-time and accurate information during calcium modification interventions. Simultaneously, emerging molecular imaging modalities aid in the investigation of calcification activity. This review summarizes advanced techniques for coronary artery calcification imaging, including their merits and limitations, in addition to their potential applications in both experimental and clinical settings.

A classification method of gastric cancer subtype based on residual graph convolution network.

Background: Clinical diagnosis and treatment of tumors are greatly complicated by their heterogeneity, and the subtype classification of cancer frequently plays a significant role in the subsequent treatment of tumors. Presently, the majority of studies rely far too heavily on gene expression data, omitting the enormous power of multi-omics fusion data and the potential for patient similarities. Method: In this study, we created a gastric cancer subtype classification model called RRGCN based on residual graph convolutional network (GCN) using multi-omics fusion data and patient similarity network. Given the multi-omics data's high dimensionality, we built an artificial neural network Autoencoder (AE) to reduce the dimensionality of the data and extract hidden layer features. The model is then built using the feature data. In addition, we computed the correlation between patients using the Pearson correlation coefficient, and this relationship between patients forms the edge of the graph structure. Four graph convolutional network layers and two residual networks with skip connections make up RRGCN, which reduces the amount of information lost during transmission between layers and prevents model degradation. Results: The results show that RRGCN significantly outperforms other classification methods with an accuracy as high as 0.87 when compared to four other traditional machine learning methods and deep learning models. Conclusion: In terms of subtype classification, RRGCN excels in all areas and has the potential to offer fresh perspectives on disease mechanisms and disease progression. It has the potential to be used for a broader range of disorders and to aid in clinical diagnosis.

Effectiveness of preoperative shaving and postoperative shampooing on the infection rate in neurosurgery patients: A meta-analysis.

OBJECTIVE: To evaluate the effectiveness of preoperative shaving and postoperative shampooing on the infection rate in neurosurgery. DESIGN: Meta-analysis. DATA SOURCE: We conducted a search of the Embase, CINAHL, Scopus and PubMed databases up until February 1, 2022. Comparative studies were included. No language restrictions were applied. REVIEW METHODS: Original articles that compared the infection rate of patients who had their hair shaved before neurosurgery to the infection rate of unshaven patients were included. Original articles comparing the infection rates of patients whose hair was early postoperative shampooing versus patients whose hair was not shampooed after neurosurgery were also included. The risk of bias was also evaluated using the Newcastle-Ottawa quality assessment scale by two authors independently. The meta-analyses were performed using Review Manager software (RevMan 5.3; Cochrane Collaboration). The odds ratios (ORs) and 95% confidence intervals (CIs) were assessed for dichotomous data (infection rate). The heterogeneity of the included studies was assessed using the I2 statistic (ranging from 0 to 100%). RESULTS: A total of 3451 studies were identified by searching the PubMed, Scopus, CINAHL and Embase databases. Fourteen studies met the inclusion criteria, however two studies did not provide data suitable for meta-analysis. Twelve studies were included in the review. Two historical control studies, four prospective studies, one clinical trial and five retrospective studies were identified. There were 4583 patients whose hair was not shaved and 4295 patients whose hair was shaved. Among them, there were 3874 patients whose hair was unshaved and was early postoperative shampooing. No significant difference in the infection rate was found between the unshaved group and shaved group (OR: 0.86, 95% CI [0.62, 1.19], P = 0.85, I2 = 0%). A significant difference in the infection rates in shunt surgery patients was found between the unshaved group and shaved group (OR: 0.43, 95% CI [0.19, 0.99], P = 0.89, I2 = 0%). No significant difference was found between the unshaved with early shampooing group and the shaved group (OR: 0.82, 95% CI [0.48, 1.41], P = 0.80, I2 = 0%). CONCLUSION: Hair preservation before neurosurgery and early shampooing after neurosurgery did not increase the infection rate.

GLUT1 participates in tamoxifen resistance in breast cancer cells through autophagy regulation.

Tamoxifen is an estrogen modulator widely used in the treatment of patients with ESR/ER-positive breast cancer; however, resistance limits its clinical application. Autophagy alterations have recently been suggested as a new mechanism for tamoxifen resistance. Glucose transporter 1 (GLUT1) has been reported to be associated with the development and metastasis of breast cancer, but the relationship among GLUT1, autophagy, and endocrine resistance remains unclear. Our present study found that GLUT1 expression and autophagy flux were upregulated in the tamoxifen-resistant breast cancer cell line MCF-7/TAMR-1 and that knockdown of GLUT1 promoted sensitization to tamoxifen. Moreover, knockdown of GLUT1 significantly decreased the enhancement of autophagy flux in tamoxifen-resistant cell lines. Furthermore, inhibiting autophagy in tamoxifen-resistant cells resulted in sensitization to tamoxifen. We conclude that GLUT1 contributes to tamoxifen resistance in breast cancer and that tamoxifen-resistant cells become resensitized to tamoxifen after GLUT1 silencing. These findings suggest GLUT1 as a new factor clinically associated with resistance to tamoxifen.

The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology.

Astragaloside IV (AS-IV) has been used to treat cardiovascular disease. However, whether AS-IV exerts a protective effect against hypertensive heart disease has not been investigated. This study aimed to investigate the antihypertensive and cardioprotective effects of AS-IV on L-NAME-induced hypertensive rats via network pharmacology and experimental pharmacology. The network pharmacology and bioinformatics analyses were performed to obtain the potential targets of AS-IV and hypertensive heart disease. The rat hypertension model was established by administrated 50 mg/kg/day of L-NAME for 5 weeks. Meanwhile, hypertension rats were intragastrically administrated with vehicle or AS-IV or fosinopril for 5 weeks. Cardiovascular parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rates, and body weight), cardiac function parameters (LVEDd, LVEDs, and fractional shortening), cardiac marker enzymes (creatine kinase, CK-MB, and lactate dehydrogenase), cardiac hypertrophy markers (atrial natriuretic peptide and brain natriuretic peptide), endothelial function biomarkers (nitric oxide and eNOS), inflammation biomarkers (IL-6 and TNF-α) and oxidative stress biomarkers (SOD, MDA, and GSH) were measured and cardiac tissue histology performed. Network pharmacological analysis screened the top 20 key genes in the treatment of hypertensive heart disease treated with AS-IV. Besides, AS-IV exerted a beneficial effect on cardiovascular and cardiac function parameters. Moreover, AS-IV alleviated cardiac hypertrophy via down-regulating the expression of ANP and BNP and improved histopathology changes of cardiac tissue. AS-IV improved endothelial function via the up-regulation of eNOS expression, alleviated oxidative stress via increasing antioxidant enzymes activities, and inhibited cardiac inflammation via down-regulating IL-6 and TNF-α expression. Our findings suggested that AS-IV is a potential therapeutic drug to improve L-NAME-induced hypertensive heart disease partly mediated via modulation of eNOS and oxidative stress.

An Emergency Department Clinical Algorithm to Increase Early Palliative Care Consultation: Pilot Project.

Introduction: The emergency department (ED) is a primary entry point of hospitals but does not have a system to identify and consult palliative care (PC) early in patients who meet criteria. Objectives: To determine the measurable effects of an ED PC consultation on patients who meet criteria, hypothesizing that ED PC consultation would lead to decreased average length of stay (ALOS), average direct cost per patient, decreased number of surgeries, and radiological tests performed per patient. Materials and Methods: A physician-led data-driven evidence-based algorithm was designed and piloted with implementation in two hospitals during January-March 2019 in Orlando, FL. A retrospective review of health record data was completed, comparing patients receiving PC consultation ordered in the ED versus those ordered after admission. Results: ED patients (n = 662) met PC criteria. PC consultation was ordered in ED for 80 (12.1%) cases. The following outcomes were lower for patients who received ED PC consultation than those who did not: ALOS by 6.4 days (6.74 vs. 13.14 days; p < 0.001), in-hospital mortality (12.5% vs. 19.1%; p = 0.11), surgery (11% vs. 37%; p < 0.01), radiological tests per patient (4.01 vs. 10.57; p < 0.001), and average direct cost per patient ($7,193 vs. $22,354). However, 30-day hospital revisit rates were relatively higher in those who did receive ED PC consultation than those who did not (20% vs. 13% p = 0.15). Conclusions: In this pilot project, PC patients can be identified in the ED with an algorithm that leads to earlier consultation and improved patient outcomes. Larger research trials are needed to replicate this strategy and results.

Lycium barbarum Polysaccharide Ameliorates Sjögren's Syndrome in a Murine Model.

SCOPE: This study aims to evaluate the therapeutic efficacy and mechanisms of Lycium barbarum polysaccharide (LBP) in primary Sjögren's syndrome (pSS). METHODS AND RESULTS: Non-obese diabetic mice (the pSS model) are randomly divided into four groups: Low dose LBP (LBP.L, 5 mg kg-1  d-1 ), high dose LBP (10 mg kg-1  d-1 ), low dose interleukin (IL)-2 (25 000 IU/d), and control (saline water). Drugs were treated for 12 weeks. LBP.L significantly reduces the salivary gland inflammation compared with the control group (histological score p LBP.L vs Control  = 0.019; foci number: p LBP.L vs Control  = 0.038). LBP.L also remarkably reduces the effector follicular helper T (Tfh) cells and the CD4+ IL-17A+ helper T (Th17) cells in both spleen and cervical lymph node (cLN) cells. Additionally, the ratios of regulatory T cell (Treg)/Tfh cells and Treg/Th17 cells are substantially increased in mice treated with LBP.L in both spleen and cLNs. LBP also inhibits Th17 and Tfh cells and markedly increases the Treg/Tfh ratio in human peripheral blood mononuclear cells. CONCLUSION: LBP.L inhibits the progression of pSS in mice, associated with modulation of T cell differentiation.