Effect of Helicobacter Pylori Infection on Glucose Metabolism, Lipid Metabolism and Inflammatory Cytokines in Nonalcoholic Fatty Liver Disease Patients.

Objective: To probe into the influence of Helicobacter pylori (Hp) infection on glucose metabolism, lipid metabolism, and inflammatory cytokines in patients with nonalcoholic fatty liver disease (MASLD). Methods: A total of 140 MASLD patients admitted to our Hospital between June 2020 and May 2021 were selected as the research objects. Based on the presence or absence of Hp infection, they were divided into the study group (73 cases with infection) and control group (67 cases without infection). Glucose metabolism indicators [fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), fasting insulin (FINS), glycated hemoglobin (HbAlc)], lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory indicators [interleukin-37 (IL-37), interleukin-18 (IL-18)] were measured and compared between the two groups. Results: In terms of glucose metabolism indicators, the study group exhibited higher levels of FBG (5.84±0.49 vs 5.40±0.51, t=2.535, P=0.012), 2hPG (7.26±1.30 vs 6.50±1.53, t=3.321, P<0.001), and FINS (11.13±4.13 vs 9.12±3.72, t=3.224, P<0.001), and Insulin resistance index (HOMA-IR) (2.97±0.35 VS 2.13±0.54, t=3.761, P<0.001) and a lower level of HbAlc (5.25±0.56 vs 6.12±0.57, t=5.473, P<0.001) compared to the control group. Regarding lipid metabolism indicators, the study group exhibited higher levels of TC (5.64±1.49 vs 5.01±1.32, t=3.332, P<0.001), TG (1.89±0.34 vs 1.32±0.43, t=3.411, P<0.001), and LDL-C (3.31±0.43 vs 2.12±0.29, t=4.142, P<0.001), and a lower level of HDL-C (1.45±0.21 vs 1.78±0.42, t=4.347, P<0.001) compared to the control group. As for the inflammatory indicators, the study group exhibited higher levels of IL-37 (45.56±6.02 vs 34.02±3.28, t=9.332, P<0.001) and IL-18 (73.57±5.82 vs 60.34±4.84, t=10.141, P<0.001) compared to the control group. Conclusion: It is crucial to place appropriate emphasis on the impact of Hp infection on the glucose metabolism, lipid metabolism, and inflammatory response in MASLD patients, warranting careful consideration during the treatment of these patients.

Price for waiting: the adverse outcomes of boarding critically ill elderly medical patients in the emergency department.

PURPOSE: Boarding, the period in which a patient spends in the emergency department (ED) before admission, may be hazardous to critically ill patients, particularly the elderly. This study investigated the associations of boarding with hospital course, prognosis, and medical expenditure in older patients. METHODS: From January 2019 to December 2021, the medical records of older patients (age ≥ 65) visiting the ED of a tertiary referral hospital who were admitted to the medical intensive care unit (ICU) were retrospectively reviewed. Eligible patients were categorized into two groups according to boarding time with a cutoff set at 6 h. Primary outcomes were in-hospital mortality, ICU/hospital length of stay, and total/average hospitalization cost. Subgroup analyses considered age and disease type. RESULTS: Among 1318 ICU admissions from the ED, 36% were subjected to boarding for over 6 h. Prolonged boarding had a longer ICU (8.9 ± 8.8 vs. 11.2 ± 12.2 days, P < .001) and hospital (17.8 ± 20.1 vs. 22.8 ± 23.0 days, P < .001) stay, higher treatment cost (10.4 ± 13.9 vs. 13.2 ± 16.5 thousands of USD, P = .001), and hospital mortality (19% vs. 25% P = .020). Multivariate regression analysis showed a longer ICU stay in patients aged 65-79 (8.3 ± 8.4 vs. 11.8 ± 14.2 days, P < .001) and cardiology patients (6.9 ± 8.4 vs. 8.8 ± 9.7 days, P = .001). Besides, the treatment cost was also higher for both groups (10.4 ± 14.6 vs. 13.7 ± 17.7 thousands of USD, P = .004 and 8.4 ± 14.0 vs. 11.7 ± 16.6 thousands of USD, P < .001, respectively). CONCLUSION: Extended ED boarding for critically ill medical patients over 65 years old was associated with negative outcomes, including longer ICU/hospital stays, higher treatment costs, and hospital mortality.

The Synergistic Effects of Corbicula fluminea and Sarcodia montagneana on Alleviating Systemic Inflammation and Osteoarthritis Progression.

Osteoarthritis (OA) is a progressive disease that causes pain, stiffness, and inflammation in the affected joints. Currently, there are no effective treatments for preventing the worst outcomes, such as synovitis or cartilage degradation. Sarcodia montagneana and Corbicula fluminea are common species found in the ocean or in freshwater areas. Their extracts are demonstrated to possess both antioxidative and anti-inflammatory functions. This study aimed to investigate the synergistic effects of the extracts of Sarcodia montagneana (SME) and Corbicula fluminea (FCE) on reducing local and systemic inflammation, as well as their efficacy in OA symptom relief. An in vitro monocytic LPS-treated THP-1 cell model and in vivo MIA-induced mouse OA model were applied, and the results showed that the combinatory usage of SME and FCE effectively suppressed IFN-γ and TNF-α production when THP-1 cells were treated with LPS. SME and FCE also significantly decreased the systemic TNF-α level and joint swelling and prevented the loss of proteoglycan in the cartilage within the joints of OA mice. The data shown here provide a potential solution for the treatment of osteoarthritis.

[Pharmacokinetics, pharmacodynamics, and tissue distribution of oral co-loaded puerarin/daidzein mixed micelles in rats].

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.

Hysteresis effects of different levels of storm flooding on susceptible enteric infectious diseases in a central city of China.

BACKGROUND: Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time. METHODS: Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model. RESULTS: There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71-4.76) and 8.16 (95% CI: 2.93-22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40-2.35) and 3.31 (95% CI: 1.97-5.55) after 5 days of general flooding and heavy flooding, respectively. CONCLUSIONS: Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.

Transumbilical Silicone Implants Breast Augmentation (TUSBA).

Transumbilical breast augmentation with pre-filled silicone implants has been performed previously, but technical challenges remain to accommodate more implant options and dissection planes. We aimed to demonstrate the feasibility of transumbilical breast augmentation using various types of pre-filled silicone implants (TUSBA), and its applicability for subglandular, subfascial, dual-plane implantation. In the early stage, TUSBA was primarily performed using endoscope-assisted blunt dissection, and later converted to full endoscopy dissection to achieve better results. Endoscope was used to confirm the pocket and check bleeding for both groups. For endoscope-assisted group, surgical techniques were modified from conventional TUBA. In full endoscopy TUSBA, the entire dissection process was performed under endoscopic monitoring. Preliminary data of patients undergoing TUSBA from June 2016 to April 2021 were retrospectively reviewed. Breast implants with smooth, textured or nanotextured surface properties and round or anatomical shapes were used, with sizes up to 500 mL. Seventy-four patients with mean age 36.4 years (range: 21-55 years) were enrolled in this study. Follow-up ranged from 1 month to 4 years and 6 months (mean: 15.6 months). No excessive postoperative pain in breast or abdomen was reported. Surgery outcomes were aesthetically pleasing in both groups. In the endoscope-assisted group, 3 (4.6%) required major revisional procedures. No revision was required in the full endoscopy group. TUSBA with various types of silicone implants is feasible, and accommodable to all dissection planes. Full endoscopy technique is helpful in reducing the higher complication rate.

Hypocapnia is an independent predictor of in-hospital mortality in acute heart failure.

AIMS: Acute heart failure (AHF) poses a major threat to hospitalized patients for its high mortality rate and serious complications. The aim of this study is to determine whether hypocapnia [defined as the partial pressure of arterial carbon dioxide (PaCO2 ) below 35 mmHg] on admission could be associated with in-hospital all-cause mortality in AHF. METHODS AND RESULTS: A total of 676 patients treated in the coronary care unit for AHF were retrospectively analysed, and the study endpoint was in-hospital all-cause mortality. The 1:1 propensity score matching (PSM) analysis, Kaplan-Meier curve, and Cox regression model were used to explore the association between hypocapnia and in-hospital all-cause mortality in AHF. Receiver operating characteristic (ROC) curve and Delong's test were used to assess the performance of hypocapnia in predicting in-hospital all-cause mortality in AHF. The study cohort included 464 (68.6%) males and 212 (31.4%) females, and the median age was 66 years (interquartile range 56-74 years). Ninety-eight (14.5%) patients died during hospitalization and presented more hypocapnia than survivors (76.5% vs. 45.5%, P < 0.001). A 1:1 PSM was performed between hypocapnic and non-hypocapnic patients, with 264 individuals in each of the two groups after matching. Compared with non-hypocapnic patients, in-hospital mortality was significantly higher in hypocapnic patients both before (22.2% vs. 6.8%, P < 0.001) and after (20.8% vs. 8.7%, P < 0.001) PSM. Kaplan-Meier curve showed a significantly higher probability of in-hospital death in patients with hypocapnia before and after PSM (both P < 0.001 for the log-rank test). Multivariate Cox regression analysis showed that hypocapnia was an independent predictor of AHF mortality both before [hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.23-3.98; P = 0.008] and after (HR 2.19; 95% CI 1.18-4.07; P = 0.013) PSM. Delong's test showed that the area under the ROC curve was improved after adding hypocapnia into the model (0.872, 95% CI 0.839-0.901 vs. 0.855, 95% CI 0.820-0.886, P = 0.028). PaCO2 was correlated with the estimated glomerular filtration rate (r = 0.20, P = 0.001), left ventricular ejection fraction (r = 0.13, P < 0.001), B-type natriuretic peptide (r = -0.28, P < 0.001), and lactate (r = -0.15, P < 0.001). Kaplan-Meier curve of PaCO2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO2 tertile was associated with increased risk of in-hospital mortality in AHF (all P < 0.05). CONCLUSIONS: Hypocapnia is an independent predictor of in-hospital mortality for AHF.

Clinical summary of pediatric acute lymphoblastic leukemia patients complicated with asparaginase-associated pancreatitis in SCCLG-ALL-2016 protocol.

Asparaginase-associated pancreatitis (AAP) is a common and fatal complication after ASNase treatment in acute lymphoblastic leukemia(ALL). Here, a total of 1063 pediatric ALL patients treated with SCCLG-ALL-2016 regimen were collected since October 2016 to June 2020, including 35 patients with AAP. The clinical characteristics of AAP and non-AAP patients were compared. In AAP patients, the possible factors that affected the recurrence of AAP were analyzed, and the possible risk factors related to ALL-relapse were discussed. The results showed that age was a risk factor (P = .017) that affect the occurrence of AAP. In AAP patients, AAP tended to develop after the second use of PEG-ASNase (25.71%). In the follow-up chemotherapy, 17 patients re-exposed to ASNase and 7 cases developed AAP again with a percentage was 41.2%. There were no special factors that related with the recurrence of AAP. This study also found no association between the occurrence of AAP and prognosis of ALL, with the 4-year incidence of ALL relapse in AAP and non-AAP patients were 15.9% v.s.11.7% (HR: 1.009, 95% CI:0.370-2.752, P = .986), and there were no special factors that related with the ALL relapse among AAP patients. Based on the above results, the occurrence of AAP is related to age and should be vigilant after the second use of PEG-ASNase after use in pediatric ALL patients. Moreover, AAP is not associated with ALL relapse, but there is a high AAP recurrence rate when re-exposure to ASNase.

A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy.

BACKGROUND: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. METHODS: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. RESULTS: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment. CONCLUSIONS: Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity.

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

Anticancer peptide Q7 suppresses the growth and migration of human endometrial cancer by inhibiting DHCR24 expression and modulating the AKT-mediated pathway.

Endometrial cancer is one of the most common malignancy affecting women in developed countries. Resection uterus or lesion area is usually the first option for a simple and efficient therapy. Therefore, it is necessary to find a new therapeutic drug to reduce surgery areas to preserve fertility. Anticancer peptides (ACP) are bioactive amino acids with lower toxicity and higher specificity than chemical drugs. This study is to address an ACP, herein named Q7, which could downregulate 24-Dehydrocholesterol Reductase (DHCR24) to disrupt lipid rafts formation, and sequentially affect the AKT signal pathway of HEC-1-A cells to suppress their tumorigenicity such as proliferation and migration. Moreover, lipo-PEI-PEG-complex (LPPC) was used to enhance Q7 anticancer activity in vitro and efficiently show its effects on HEC-1-A cells. Furthermore, LPPC-Q7 exhibited a synergistic effect in combination with doxorubicin or paclitaxel. To summarize, Q7 was firstly proved to exhibit an anticancer effect on endometrial cancer cells and combined with LPPC efficiently improved the cytotoxicity of Q7.

High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer.

Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P = .001), vascular invasion (P = .042), perineural invasion (P = .012), and poor regression change after CRT (P = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT.

For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.

Using the Sankey diagram to visualize article features on the topics of whole-exome sequencing (WES) and whole-genome sequencing (WGS) since 2012: Bibliometric analysis.

BACKGROUND: Sequencing technologies, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), have been increasingly applied to medical research in recent years. Which countries, journals, and institutes (called entities) contributed most to the fields (WES/WGS) remains unknown. Temporal bar graphs (TBGs) are frequently used in trend analysis of publications. However, how to draw the TBG on the Sankey diagram is not well understood in bibliometrics. We thus aimed to investigate the evolution of article entities in the WES/WGS fields using publication-based TBGs and compare the individual research achievements (IRAs) among entities. METHODS: A total of 3599 abstracts downloaded from icite analysis were matched to entities, including article identity numbers, citations, publication years, journals, affiliated countries/regions of origin, and medical subject headings (MeSH terms) in PubMed on March 12, 2022. The relative citation ratio (RCR) was extracted from icite analysis to compute the hT index (denoting the IRA, taking both publications and citations into account) for each entity in the years between 2012 and 2021. Three types of visualizations were applied to display the trends of publications (e.g., choropleth maps and the enhanced TBGs) and IRAs (e.g., the flowchart on the Sankey diagram) for article entities in WES/WGS. RESULTS: We observed that the 3 countries (the US, China, and the UK) occupied most articles in the WES/WGS fields since 2012, the 3 entities (i.e., top 5 journals, research institutes, and MeSH terms) were demonstrated on the enhanced TBGs, the top 2 MeSH terms were genetics and methods in WES and WGS, and the IRAs of 6 article entities with their hT-indices were succinctly and simultaneously displayed on a single Sankey diagram that was never launched in bibliographical studies. CONCLUSION: The number of WES/WGS-related articles has dramatically increased since 2017. TBGs, particularly with hTs on the Sankey, are recommended for research on a topic (or in a discipline) to compare trends of publications and IRAs for entities in future bibliographical studies.

Multi-factor combined biomarker screening strategy to rapidly diagnose Alzheimer's disease and evaluate drug effect based on a rat model.

Alzheimer's disease (AD) represents the main form of dementia; however, valid diagnosis and treatment measures are lacking. The discovery of valuable biomarkers through omics technologies can help solve this problem. For this reason, metabolomic analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) was carried out on plasma, hippocampus, and cortex samples of an AD rat model. Based on the metabolomic data, we report a multi-factor combined biomarker screening strategy to rapidly and accurately identify potential biomarkers. Compared with the usual procedure, our strategy can identify fewer biomarkers with higher diagnostic specificity and sensitivity. In addition to diagnosis, the potential biomarkers identified using our strategy were also beneficial for drug evaluation. Multi-factor combined biomarker screening strategy was used to identify differential metabolites from a rat model of amyloid beta peptide 1-40 (Aß1-40) plus ibotenic acid-induced AD (compared with the controls) for the first time; lysophosphatidylcholine (LysoPC) and intermediates of sphingolipid metabolism were screened as potential biomarkers. Subsequently, the effects of donepezil and pine nut were successfully reflected by regulating the levels of the abovementioned biomarkers and metabolic profile distribution in partial least squares-discriminant analysis (PLS-DA). This novel biomarker screening strategy can be used to analyze other metabolomic data to simultaneously enable disease diagnosis and drug evaluation.

7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection.

BACKGROUND: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. METHODS: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. RESULTS: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. CONCLUSIONS: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.

Preventing Substance Abuse in Adolescents: A Review of High-Impact Strategies.

Substance abuse has been an intractable societal concern in the US for more than half a century. The recent opioid epidemic has only accentuated this problem. Adolescents are significant long-term contributors to the crisis due to their susceptibilities to drug abuse and impressionable age. This review examines the particular vulnerabilities of the adolescent brain to drug abuse and the risk and protective factors thereof, especially in light of the Rat Park studies. In addition, the article provides an overview of the evidence-based prevention program registries and offers detailed summaries of two: Blueprints for Healthy Youth Development (Blueprints) and the Washington State Institute for Public Policy (WSIPP). By combining inputs from Blueprints and WSIPP, five programs with the highest benefit-cost ratios (BCR) were identified: Functional Family Therapy, Positive Family Support, Lifeskills Training, Positive Action, and Good Behavior Game. In light of their outstanding characteristics, these programs are poised to be widely implemented and to make a measurable difference in the fight against substance and opioid abuse.

The relationship amid land finance and economic growth with the mediating role of housing prices in China.

Taking cities at prefecture-level and above in China as the research object, we theoretically analyze the effects of land finance on housing prices and economic growth as well as the effects of housing prices on economic growth, consider the mediating role of housing prices, and construct a random-effects model of land finance affecting economic growth. It is of great significance to make rational use of land finance to promote the economic development and formulate the "city specific policies" plan for the real estate market. The 278 resource-based cities with relatively well-developed land and real estate markets in China are selected to test the mediating effect of housing prices on land finance affecting economic growth in resource-based cities by type based on panel data from 2011-2019. The results show that (1) land finance significantly and positively affects economic growth and housing prices in cities at the prefecture-level and above nationwide, but there is some variability in the degree of influence. The central region has the smallest impact on economic growth but the largest impact on housing prices; the eastern region has the deepest impact on economic growth; and the western region has the smallest impact on housing prices. (2) In the national sample cities and cities in the northeast region, housing prices have a significant partial mediating effect at the 1% level on economic growth affected by land finance, accounting for 22.03 and 2.84%, respectively. The mediating effect of urban housing prices on land finance affects economic growth in the eastern, central, and western regions is not significant.