Evaluating the carbon footprint of sedation practices in intensive care.

BACKGROUND: Healthcare's carbon footprint contributes to 4.4% of global net emissions and intensive care units (ICUs) are very resource intensive. Existing studies on environmental sustainability in ICUs focused on carbon footprint generated from energy and electricity consumption, use of medical consumables and equipment, but few studies quantified carbon footprint generated from pharmaceuticals used in ICUs. AIM: To evaluate carbon footprint arising from sedation practices in the ICUs. STUDY DESIGN: A pilot, prospective observational study was conducted in two ICUs from 1 August to 22 September 2022 in Singapore General Hospital. Adult patients who were consecutively sedated, intubated and expected to be mechanically ventilated for at least 24 h were included. Total amount of analgesia and sedatives used and wasted in eligible patients were collected. Carbon emission from ICU sedation practices were then quantified using available life cycle assessment data. RESULTS: A total of 31 patients were recruited. Top analgesia and sedative used in both ICUs were fentanyl and propofol, respectively. Carbon footprint from sedative usage and wastage across 7 weeks in both ICUs were 2.206 kg CO2-e and 0.286 g CO2-e, respectively. In total, this equates to driving 15.8 km by car. Proportion of drug wasted ranged from 5.1% to 25.0%, with the top reason for wastage being the drug was no longer clinically indicated. Recommendations to reduce carbon footprint include choosing sedatives with lower carbon emissions where possible and having effective communication among doctors and nurses regarding management plans to minimize unnecessary wastage. CONCLUSION: Our study quantified carbon footprint arising from sedation practices, mainly drug usage and wastage in two ICUs in Singpore General Hospital. RELEVANCE TO CLINICAL PRACTICE: Adopting a holistic approach to environmental sustainability in the ICU, sedation practices also contribute to generating greenhouse gases, albeit small, and can be targeted to reduce unnecessary carbon footprint.

Predictability of buprenorphine-naloxone treatment retention: A multi-site analysis combining electronic health records and machine learning.

BACKGROUND AND AIMS: Opioid use disorder (OUD) and opioid dependence lead to significant morbidity and mortality, yet treatment retention, crucial for the effectiveness of medications like buprenorphine-naloxone, remains unpredictable. Our objective was to determine the predictability of 6-month retention in buprenorphine-naloxone treatment using electronic health record (EHR) data from diverse clinical settings and to identify key predictors. DESIGN: This retrospective observational study developed and validated machine learning-based clinical risk prediction models using EHR data. SETTING AND CASES: Data were sourced from Stanford University's healthcare system and Holmusk's NeuroBlu database, reflecting a wide range of healthcare settings. The study analyzed 1800 Stanford and 7957 NeuroBlu treatment encounters from 2008 to 2023 and from 2003 to 2023, respectively. MEASUREMENTS: Predict continuous prescription of buprenorphine-naloxone for at least 6 months, without a gap of more than 30 days. The performance of machine learning prediction models was assessed by area under receiver operating characteristic (ROC-AUC) analysis as well as precision, recall and calibration. To further validate our approach's clinical applicability, we conducted two secondary analyses: a time-to-event analysis on a single site to estimate the duration of buprenorphine-naloxone treatment continuity evaluated by the C-index and a comparative evaluation against predictions made by three human clinical experts. FINDINGS: Attrition rates at 6 months were 58% (NeuroBlu) and 61% (Stanford). Prediction models trained and internally validated on NeuroBlu data achieved ROC-AUCs up to 75.8 (95% confidence interval [CI] = 73.6-78.0). Addiction medicine specialists' predictions show a ROC-AUC of 67.8 (95% CI = 50.4-85.2). Time-to-event analysis on Stanford data indicated a median treatment retention time of 65 days, with random survival forest model achieving an average C-index of 65.9. The top predictor of treatment retention identified included the diagnosis of opioid dependence. CONCLUSIONS: US patients with opioid use disorder or opioid dependence treated with buprenorphine-naloxone prescriptions appear to have a high (∼60%) treatment attrition by 6 months. Machine learning models trained on diverse electronic health record datasets appear to be able to predict treatment continuity with accuracy comparable to that of clinical experts.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children.

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes.

High-dimensional, spatially resolved analysis of intact tissue samples promises to transform biomedical research and diagnostics, but existing spatial omics technologies are costly and labor-intensive. We present Fluorescence In Situ Hybridization of Cellular HeterogeneIty and gene expression Programs (FISHnCHIPs) for highly sensitive in situ profiling of cell types and gene expression programs. FISHnCHIPs achieves this by simultaneously imaging ~2-35 co-expressed genes (clustered into modules) that are spatially co-localized in tissues, resulting in similar spatial information as single-gene Fluorescence In Situ Hybridization (FISH), but with ~2-20-fold higher sensitivity. Using FISHnCHIPs, we image up to 53 modules from the mouse kidney and mouse brain, and demonstrate high-speed, large field-of-view profiling of a whole tissue section. FISHnCHIPs also reveals spatially restricted localizations of cancer-associated fibroblasts in a human colorectal cancer biopsy. Overall, FISHnCHIPs enables fast, robust, and scalable cell typing of tissues with normal physiology or undergoing pathogenesis.

Role and Mechanism of Epigenetic Regulation in the Aging of Germ Cells: Prospects for Targeted Interventions.

In modern times, a notable trend toward delayed childbearing has been observed in most developed countries. As a result, sperm aging and quality loss, as well as premature ovarian failure (POF), have emerged as major causes of infertility. The pathogenesis of sperm aging and POF is complex and has not been clearly elucidated. However, evidence from some studies has linked germ cell aging to epigenetic modifications. Epigenetics refers to the heritable changes in gene expression that occur in the absence of any alterations to the gene's nucleotide sequence. This paper systematically reviewed and analyzed the relevant literature to describe the relationship of DNA methylation, non-coding RNA regulation, histone modifications, chromatin remodeling, and RNA modifications with sperm aging and POF. In addition, we analyzed how sperm aging and POF can be mitigated via epigenetic interventions. This review could provide new therapeutic insights and guide strategies for improving sperm quality and ovarian function.

[Distribution Characteristics and Environmental Driving Factors of Cyanobacteria Community in Impounded Lakes and Reservoirs in Shandong on the East Route of South-to-North Water Diversion Project].

To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa, and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa, and M. wesenbergii. The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa, and M. wesenbergii had growth advantages when the water temperature was higher than 25℃. In addition, shallow water was more conducive to the growth of C. raciborskii. It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.

Pyroptosis and inflammasomes in cancer and inflammation.

Nonprogrammed cell death (NPCD) and programmed cell death (PCD) are two types of cell death. Cell death is significantly linked to tumor development, medication resistance, cancer recurrence, and metastatic dissemination. Therefore, a comprehensive understanding of cell death is essential for the treatment of cancer. Pyroptosis is a kind of PCD distinct from autophagy and apoptosis in terms of the structure and function of cells. The defining features of pyroptosis include the release of an inflammatory cascade reaction and the expulsion of lysosomes, inflammatory mediators, and other cellular substances from within the cell. Additionally, it displays variations in osmotic pressure both within and outside the cell. Pyroptosis, as evidenced by a growing body of research, is critical for controlling the development of inflammatory diseases and cancer. In this paper, we reviewed the current level of knowledge on the mechanism of pyroptosis and inflammasomes and their connection to cancer and inflammatory diseases. This article presents a theoretical framework for investigating the potential of therapeutic targets in cancer and inflammatory diseases, overcoming medication resistance, establishing nanomedicines associated with pyroptosis, and developing risk prediction models in refractory cancer. Given the link between pyroptosis and the emergence of cancer and inflammatory diseases, pyroptosis-targeted treatments may be a cutting-edge treatment strategy.

Biological roles of A-to-I editing: implications in innate immunity, cell death, and cancer immunotherapy.

Adenosine-to-inosine (A-to-I) editing, a key RNA modification widely found in eukaryotes, is catalyzed by adenosine deaminases acting on RNA (ADARs). Such RNA editing destabilizes endogenous dsRNAs, which are subsequently recognized by the sensors of innate immune and other proteins as autologous dsRNAs. This prevents the activation of innate immunity and type I interferon-mediated responses, thereby reducing the downstream cell death induced by the activation of the innate immune sensing system. ADARs-mediated editing can also occur in mRNAs and non-coding RNAs (ncRNAs) in different species. In mRNAs, A-to-I editing may lead to missense mutations and the selective splicing of coding regions. Meanwhile, in ncRNAs, A-to-I editing may affect targeting and disrupt ncRNAs maturation, leading to anomalous cell proliferation, invasion, and responses to immunotherapy. This review highlights the biological functions of A-to-I editing, its role in regulating innate immunity and cell death, and its potential molecular significance in tumorigenesis and cancer targeted therapy and immunotherapy.

Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse.

Identification of unique gene markers of normal and cancer stem cells is an effective strategy to study cells of origin and understand tumor behavior. Lineage tracing experiments using the Cre recombinase driven by a stem cell-specific promoter in the CreERT2 reporter mouse model enables identification of adult stem cells and delineation of stem cell activities in vivo. In our recent research on the mouse stomach, Iqgap3 was identified as a homeostatic stem cell marker located in the isthmus of the stomach epithelium. Lineage tracing with the Iqgap3-2A-CreERT2;Rosa26-LSL-tdTomato mouse model demonstrated stem cell activity in Iqgap3-expressing cells. Using the Iqgap3-2A-CreERT2 mouse model to target oncogenic KrasG12D expression to Iqgap3-expressing cells, we observed the rapid development of precancerous metaplasia in the stomach and proposed that aberrant Iqgap3-expressing cells may be critical determinants of early carcinogenesis. In this chapter, we detail a lineage tracing protocol to assess stem cell activity in the murine stomach. We also describe the procedure of inducing KrasG12D expression in Iqgap3-expressing homeostatic stem cells to explore their role as cells of origin and to trace the early cellular changes that precede neoplastic transformation.

Prevalence estimation of ATTRv in China based on genetic databases.

Introduction: Amyloid transthyretin (ATTR) is divided into either hereditary (ATTRv) or sporadic (ATTRwt) and ATTRv is a rare hereditary disease transmitted as an autosomal dominant manner. Its global prevalence is traditionally estimated as 5,000 to 10,000 persons. However, it may be underestimated and the exact prevalence of ATTRv in China mainland remains unknown. Methods: The Genome Aggregation database (gnomAD) database (containing 125,748 exomes) and two genomic sequencing databases--China Metabolic Analytics Project (ChinaMAP) (containing 10588 individuals) and Amcarelab gene database (containing 45392 exomes), were integrated to estimate the prevalence of ATTRv in the world and mainland Chinese populations. Pathogenic variants allele frequency and the prevalence of ATTRv was calculated. Results: Six variants, counting 470 alleles, were defined as pathogenic variants in gnomAD. The prevalence of ATTRv in the world population was 57.4/100,000. Two variants (2 allele counts) and 15 variants (34 individuals) were defined as pathogenic variants in the ChinaMAP database and the Amcarelab exome database, respectively. Thus, the estimated prevalence interval of ATTRv in mainland China was 18.9/100,000-74,9/100,000. Conclusion: The present study demonstrated that the previous prevalence was greatly underestimated using traditional methods. Therefore, raising awareness of the disease is essential for recognizing ATTRv in its early stage.

Cyclopropane-Containing Specialized Metabolites from the Marine Cyanobacterium cf. Lyngbya sp.

Marine cyanobacteria are known to produce structurally diverse bioactive specialized metabolites during bloom occurrence. These ecologically active allelochemicals confer chemical defense for the microalgae from competing microbes and herbivores. From a collection of a marine cyanobacterium, cf. Lyngbya sp., a small quantity of a new cyclopropane-containing molecule, benderadiene (2), and lyngbyoic acid (1) were purified and characterized using spectroscopic methods. Using live reporter quorum-sensing (QS) inhibitory assays, based on P. aeruginosa PAO1 lasB-gfp and rhlA-gfp strains, both compounds were found to inhibit QS-regulated gene expression in a dose-dependent manner. In addition to lyngbyoic acid being more active in the PAO1 lasB-gfp biosensor strain (IC50 of 20.4 µM), it displayed anti-biofilm activity when incubated with wild-type P. aeruginosa. The discovery of lyngbyoic acid in relatively high amounts provided insights into its ecological significance as a defensive allelochemical in targeting competing microbes through interference with their QS systems and starting material to produce other related analogs. Similar strategies could be adopted by other marine cyanobacterial strains where the high production of other lipid acids has been reported. Preliminary evidence is provided from the virtual molecular docking of these cyanobacterial free acids at the ligand-binding site of the P. aeruginosa LasR transcriptional protein.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

OBJECTIVE: The combination of stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitors (ICIs) is actively being explored in advanced non-small-cell lung cancer (NSCLC) patients. However, little is known about the optimal fractionation and radiotherapy target lesions in this scenario. This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs. METHODS: The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec. 2015 to Sep. 2021. Patients were grouped according to radiation sites. Progression-free survival (PFS) and overall survival (OS) were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank (Mantel-Cox) test. RESULTS: A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study. Radiation sites included lung lesions (lung group, n=43), bone metastases (bone group, n=24), and brain metastases (brain group, n=57). Compared with the brain group, the mean PFS (mPFS) in the lung group was significantly prolonged by 13.3 months (8.5 months vs. 21.8 months, HR=0.51, 95%CI: 0.28-0.92, P=0.0195), and that in the bone group prolonged by 9.5 months with a 43% reduction in the risk of disease progression (8.5 months vs. 18.0 months, HR=0.57, 95%CI: 0.29-1.13, P=0.1095). The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group. The mean OS (mOS) in the lung and bone groups was longer than that of the brain group, and the risk of death decreased by up to 60% in the lung and bone groups as compared with that of the brain group. When SBRT was concurrently given with ICIs, the mPFS in the lung and brain groups were significantly longer than that of the bone group (29.6 months vs. 16.5 months vs. 12.1 months). When SBRT with 8-12 Gy per fraction was combined with ICIs, the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups (25.4 months vs. 15.2 months vs. 12.0 months). Among patients receiving SBRT on lung lesions and brain metastases, the mPFS in the concurrent group was longer than that of the SBRT→ICIs group (29.6 months vs. 11.4 months, P=0.0003 and 12.1 months vs. 8.9 months, P=0.2559). Among patients receiving SBRT with <8 Gy and 8-12 Gy per fraction, the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group (20.1 months vs. 5.3 months, P=0.0033 and 24.0 months vs. 13.4 months, P=0.1311). The disease control rates of the lung, bone, and brain groups were 90.7%, 83.3%, and 70.1%, respectively. CONCLUSION: The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients. This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens. Dose fractionation regimens of 8-12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Images of giant cell tumor and chondroblastoma around the knee: retrospective analysis of 99 cases.

Background: It is difficult to differentiate giant cell tumors of the bone (GCTB) from chondroblastoma around the knee based on imaging findings. This study analyzed the imaging features of these 2 diseases for better differentiation. Methods: This retrospective cross-sectional cohort study reviewed data of patients with pathologically confirmed GCTB (n=81; age 15-75 years; median age 33 years) and chondroblastoma (n=18; age 12-34 years; median age 14 years). In all, 18 imaging signs were analyzed. Results: Patients with chondroblastoma were relatively younger than those with GCTB. On imaging, lesion length was significantly (P<0.00001) smaller in chondroblastoma [range, 15.80-78.30 mm; mean ± standard deviation (SD) 34.15±18.24 mm; 95% confidence interval (CI): 24.05-44.25 mm] than in GCTB [range, 30.10-117.50 mm; mean ± SD 59.73±15.28 mm; 95% CI: 56.24-63.22 mm]. Significantly more (P<0.05) chondroblastoma lesions had calcification (76.5% vs. 1.3%), lobulation (77.8% vs. 32.1%), and swelling range >15 mm (84.6% vs. 41.1%) than did GCTB lesions, whereas significantly more (P<0.05) GCTB lesions were greater than half the host bone diameter (74.1% vs. 16.7%) and had a lesion long axis that was consistent with that of the host bone (98.8% vs. 27.8%). There were no significant differences (P>0.05) between the 2 tumors in the remaining 11 imaging signs. Conclusions: A narrow zone of transition, intratumor calcification, lobulation, tumor transverse diameter greater than the bone diameter, maximum lesion length, consistency between the tumor and bone long axes, and edema range around the lesion >15 mm are parameters that can be used to differentiate GCTB from chondroblastoma around the knee.

A cost avoidance study of critical care pharmacists' interventions in a tertiary institution in Singapore.

PURPOSE: The economic impact of critical care pharmacists in the intensive care unit (ICU) setting has not been evaluated in Singapore despite ICUs being high-cost areas. This study was conducted to determine the costs avoided as a result of pharmacists' interventions within multidisciplinary ICU teams in a tertiary hospital in Singapore. METHODS: A single-center, retrospective observational study of accepted pharmacists' interventions was conducted over 6 months in 2020. We adopted a previously published systematic approach to estimate the costs avoided by the healthcare system through pharmacists' interventions. Interventions were independently reviewed by a critical care pharmacist, an intensivist, and an investigator. Cost avoidance was calculated in terms of the additional ICU length of stay that would have resulted had a pharmacist not intervened as well as the direct cost savings achieved. RESULTS: There were 632 medication-related problems (MRPs) associated with the 527 accepted interventions, as some interventions involved multiple MRPs. The most common interventions included correcting inappropriate drug regimens (n = 363; 57%), recommending drug monitoring (n = 65; 10%) and addressing omission of drugs (n = 50; 8%). Over 6 months, gross cost avoidance and net cost avoidance achieved were $186,852 and $140,004, respectively, resulting in a ratio of potential monetary cost avoidance to pharmacist salary of 3.99:1. The top 3 interventions that resulted in the greatest cost avoidance were those that corrected inappropriate drug regimens ($146,870; 79%), avoided adverse drug events (ADEs) ($10,048; 5%), and led to discontinuation of medications without any indication ($7,239; 4%). CONCLUSION: Pharmacists can reduce healthcare expenditure substantially through cost avoidance by performing various interventions in ICUs, particularly in the areas of correcting inappropriate drug regimens, avoiding ADEs, and discontinuing unnecessary medications.

Undiagnosed cardiovascular risk factors including elevated lipoprotein(a) in patients with ischaemic heart disease.

Objectives: This study aims to investigate the prevalence of undiagnosed cardiovascular risk factors in patients with ischaemic heart disease (IHD). Methods: We assessed the prevalence of previously undiagnosed cardiovascular risk factors, including elevated lipoprotein(a) [Lp(a)], among consenting patients with IHD who were admitted to hospital. Clinical information, including dietary history, from patients with newly diagnosed IHD and known IHD were compared. Results: Of the 555 patients, 82.3% were males and 48.5% of Chinese ethnicity. Overall, 13.3% were newly diagnosed with hypertension, 14.8% with hypercholesterolemia, and 5% with type 2 diabetes (T2DM). Patients with newly diagnosed IHD, compared to those with known IHD, had a higher prevalence of new diagnoses of hypercholesterolemia (29.1% vs. 2.0%, p < 0.001), hypertension (24.5% vs. 3.4%, p < 0.001) and T2DM (7.3% vs. 3.1%, p = 0.023). Active smoking was prevalent in 28.3% of patients, and higher in newly diagnosed IHD (34.1% vs. 23.2%, p = 0.005). Elevated Lp(a) of ≥120 nmol/L was detected in 15.6% of all patients, none of whom were previously diagnosed. Dietary habits of >50% of patients in both groups did not meet national recommendations for fruits, vegetables, wholegrain and oily fish intake. However, patients with known IHD had a more regular omega-3 supplement intake (23.4% vs. 10.3%, p = 0.024). Conclusion: Increased detection efforts is necessary to diagnose chronic metabolic diseases (hypertension, hypercholesterolemia, T2DM) especially among patients at high risk for IHD. Cardiovascular risk factors, in particular elevated Lp(a), smoking, and suboptimal dietary intake in patients with IHD deserve further attention.

Transthoracic Echocardiography Revealed Inferior Vena Cava and Right Atrial Occupation:Report of One Case / 中国医学科学院学报

One case with ascites and lower limb edema as the initial manifestations was reported.The echocardiography revealed inferior vena cava and right atrial occupation,which combined with increased alpha fetoprotein and imaging examination,suggested liver malignant tumor combined with tumor thrombus of inferior vena cava and right atrium.After targeted therapy combined with immunotherapy,the tumor shrank and alpha fetoprotein decreased significantly,suggesting that the treatment was effective.The median survival time of the patient was 3 months.This patient had a clear history of cirrhosis due to hepatitis B and was clinically diagnosed with advanced liver cancer,which suggested the importance of early liver cancer screening.

Evolutionary Law of Syndrome and Syndrome Elements during the Malignant Transformation of Chronic Hepatitis B / 中医杂志

ObjectiveTo clarify the evolutionary laws of syndromes and syndrome elements at different stages during the malignant transformation of chronic hepatitis B （CHB）. MethodsA total of 671 patients with hepatitis B virus infection， who were admitted to the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine and The Fifth Medical Center of Chinese PLA General Hospital from July 1st， 2020 to June 30th， 2021， were included， involving 120 cases of CHB， 340 cases of hepatitis B liver cirrhosis （HBLC）， 64 cases of precancerous lesions with hepatitis B liver cirrhosis （PLHC）， and 147 cases of hepatitis B liver cirrhosis with hepatocellular carcinoma （HCC）. A Survey form of traditional Chinese medicine syndrome during malignant transformation of chronic hepatitis B was designed， and the general information， auxiliary examination and the four examinations results were collected. Factor analysis and K-means clustering were used to determine and statistically analyze the syndrome and syndrome elements. ResultsFive traditional Chinese medicine （TCM） syndrome types were identified in CHB patients， while there were six TCM syndrome types in HBLC， PLHC and HCC stages. Among CHB patients， the main syndromes were liver constraint and spleen deficiency （53.33%） and liver-gallbladder damp-heat （21.67%）， and the dominant syndrome elements were qi stagnation （27.60%）， heat （17.71%） and qi deficiency （17.71%）. In the HBLC stage， the syndromes were mainly blood stasis obstructing the collaterals （23.83%） and liver constraint and spleen deficiency （22.35%）， with dominant syndrome elements being blood stasis （19.25%）， dampness （17.46%）， and qi deficiency （15.01%）. For the PLHC stage， the primary syndrome types were blood stasis obstructing the collaterals （29.68%） and liver-kidney yin deficiency （20.31%）， and the leading syndrome elements were blood stasis （22.12%）， yin deficiency （15.93%）， and qi deficiency （15.04%）. In the HCC stage， the syndrome was dominated by blood stasis obstructing the collaterals （33.34%） and liver-kidney yin deficiency （19.73%）， with the main syndrome elements being blood stasis （24.52%）， yin deficiency （16.09%）， and qi deficiency （15.33%）. During the progression of CHB to malignancy， there was a gradual decrease in excess syndromes including liver-gallbladder damp-heat and water-dampness internal obstruction from 21.67% to 19.04%. In contrast， deficiency syndromes including liver-kidney yin deficiency and spleen-kidney yang deficiency increased from 15.83% to 31.97%. Additionally， excess syndrome elements including qi stagnation， heat and dampness decreased from 59.89% to 34.48%， while deficiency syndrome elements including qi deficiency， yin deficiency and yang deficiency increased from 32.30% to 41.00%. ConclusionDuring the malignant transformation of CHB， there exists a progression of syndrome and syndrome elements， shifting from qi stagnation， heat and qi deficiency to blood stasis （predominantly excess）， dampness and qi deficiency， and then to blood stasis （predominantly deficiency）， yin deficiency and qi deficiency， characterized by “deficiency-excess complex， and shift from excess to deficiency”.

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.