Influence of Age Ranges on Relationship of Complex Aortic Plaque With Cervicocephalic Atherosclerosis in Ischemic Stroke.

BACKGROUND: Complex aortic plaque is a potential cause of acute ischemic cerebrovascular disease, which needs timely identification. Also as a marker for systemic atherosclerosis, complex aortic plaque may be indicated by significant (≥50%) cervicocephalic atherosclerotic stenosis. We aimed at examining whether age ranges would influence their association to more accurately estimate the risk of having complex aortic plaque in acute ischemic cerebrovascular disease. METHODS: Aortic arch and cervicocephalic arteries were simultaneously evaluated using computed tomography angiography. Middle-aged (45-64 years) and old-aged (65-85 years) acute ischemic cerebrovascular disease patients were divided into 2 groups according to whether there was an aortic arch plaque with thickness of greater than or equal to 4 mm or associated ulcerations or mural thrombus. RESULTS: Old-aged patients (n = 107) had a higher prevalence of complex aortic plaque (67.3% versus 30.9%, P < .001) than those middle aged (n = 178). Among middle-aged patients, the presence of extracranial significant atherosclerotic stenosis (adjusted odd ratio = 2.89, 95% confidence interval: 1.42-5.86) rather than intracranial ones independently predicted complex aortic plaque. Regarding the extent of significant cervicocephalic atherosclerotic stenosis, the presence of multi-segment, bilateral, simultaneous extracranial and intracranial, and simultaneous anterior and posterior circulation ones were independent indicators for complex aortic plaque in the middle-aged subgroup (adjusted odd ratio = 2.42, 2.05, 2.26, 2.14, respectively). By contrast, no statistical correlation of complex aortic plaque and significant cervicocephalic atherosclerotic stenosis was found among old-aged patients. CONCLUSION: Considering the ranges of age was important to more precisely predict complex aortic plaque with significant cervicocephalic atherosclerotic stenosis in acute ischemic cerebrovascular disease.

[Correlation between cognitive impairment and diabetic nephropathy in patients with Type 2 diabetes mellitus].

OBJECTIVE: To explore the correlation between diabetic nephropathy (DN) and cognitive impairment through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus patients at different stages of renal function.
 METHODS: Eighty six patients with Type 2 diabetes mellitus (T2DM) were enrolled for this study. According to the urinary albumin excretion rate (UAER), the patients were divided into a T2DM without DN group (DM group, n=33), an early DN group (DN-III group, n=26) and a clinical stage group (DN-IV group, n=27). Thirty healthy adults were selected as a control group (NC group). Biochemical indexes and UAER were measured, and glomerular filtration rate (GFR) was detected by single-photon emission computed tomography (SPECT). The cognitive function was measured by Montreal Cognitive Assessment (MoCA, Beijing version) and mini-mental state examination (MMSE). The peak areas of N-acetylasparte (NAA), creatine (Cr), choline-containing compounds (Cho) were detected by proton magnetic resonance spectroscopy (1H-MRS).
 RESULTS: 1) There was no statistical difference in MMSE scores between the DM group and the control group. The scores of MoCA in the DN-III group or in the DN-IV group were significant less than that in the NC group (F=3.66, P<0.05); 2) There was significant difference in left N-acetylaspartate (LNAA), left choline (LCho) among the diabetes groups. Compared with the DM group, the level of LNAA was decreased significantly (t=3.826, P<0.05) while the LCho was increased significantly (t=4.373, P<0.05) in the DN groups, with statistic difference between the 2 groups (t=3.693, P<0.05); 3) The MoCA scores of T2DM patients were negatively correlated with UAER (r=-0.285, P<0.05), while positively correlated with GFR (r=0.379, P<0.05); 4) Logistic regression analysis indicated that UAER and GFR were the major risky factors for diabetic cognitive impairment.
 CONCLUSION: Diabetic cognitive impairment is closely correlated with the nephropathy in patients with Type 2 diabetes. With the decline in glomerular filtration function, the cognitive disorder tends to be aggravated. The hippocampal brain metabolism may have some changes in left side of Cho/Cr in patients with diabetic nephropathy.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 Mpro and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

BACKGROUND: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. METHODS: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. FINDINGS: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. FUNDING: Funded by Sorrento Therapeutics.

[An observation and analysis of the features of depressive disorder in the incidence and progression of breast cancer].

OBJECTIVE: To explore the correlation between depressive disorder and breast cancer, and to study the features of depressive disorder in patients before and after suffering breast cancer. METHODS: Whether 40 breast cancer patients had depressive disorder and their degrees were assessed by filling in Hamilton Depression Rating Scale (HAM-D) at Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences. The correlation between depressive disorder and the occurrence and progression of breast cancer, as well as its features were studied. RESULTS: The occurrence of general depressive disorder in breast cancer patients before they suffered from breast cancer was 72.5% (29/40 cases). The occurrence of confirmed depression was 2.5% (1/40 cases). The total depressive disorder rate was 75.0% (30/40 cases).They were 60. 0% (24/40 cases), 7.5% (3/40 cases), and 67. 5% (27/40 cases) in breast cancer patients after they suffered from breast cancer. CONCLUSION: Breast cancer patients have depressive disorder to various levels before and after suffering from breast cancer, which should raise clinical attention and corresponding intervention.

Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report.

The present study reports a patient case with a 17α-hydroxylase deficiency accompanied by triple X syndrome. A 17α-hydroxylase deficiency leads to a very low 17α-hydroxylated steroid synthesis as well as a non-feedback increase in the adrenocorticotropic hormone level. Meanwhile, the progesterone level increases the 17α-hydroxyprogesterone level and decreases the dehydroepiandrosterone sulfate level. The patient is characterized by intractable hypokalemia, high urinary potassium, hyperaldosteronemia, hyporeninemia, hypocortisolemia, hypertension, gonadal and secondary sexual dysplasia, a decreased estrogen level, primary amenorrhea, and infertility. The imaging findings indicate a presence of multiple bilateral adrenal gland adenomas, and the sequencing indicates a missense CYP17A1-E7 gene pathogenic variant. The karyotype is a 47, XXX [3]/46, XX [47] low-level chimeric karyotype. The patient's parents are cousins. To our knowledge, this patient is the first case diagnosed with congenital adrenal hyperplasia caused by hydroxylase deficiency and triple X syndrome. The uniqueness of this case is that this patient has two very rare genetic diseases, probably due to the marriage of close relatives.

Relationship between thick or greasy tongue-coating microbiota and tongue diagnosis in patients with primary liver cancer.

Tongue diagnosis is a unique aspect of traditional Chinese medicine for diagnosing diseases before determining proper means of treatment, but it also has the disadvantage of relying on the subjective experience of medical practitioners and lack objective basis. The purpose of this article is to elucidate tongue-coating microbiota and metabolic differences in primary liver cancer (PLC) patients with thick or greasy tongue coatings. Tongue-coating samples were analyzed in 60 PLC patients (30 PLC with thick or greasy tongue-coating patients and 30 PLC with tongue-coating neither thick nor greasy) and 25 healthy controls (HC) using 16S rRNA gene sequencing technology. As compared to healthy individuals, tongue coatings of patients with PLC had elevated levels of Firmicutes and Actinobacteria. The abundance of Fusobacteria, SR1_Absconditabacteria_, and Spirochaete were higher in tongue coatings of healthy controls compared to samples in patients with PLC. In addition to site-specific differences, higher abundances of Fusobacteria and Actinobacteria were observed in thick or greasy tongue-coating patients as compared to non-thick and greasy tongue-coating patients. The inferred metagenomic pathways enriched in the PLC tongue-coating patients were mainly those involved in replication, recombination, and repair of protein. We also identify a tongue-coating microbiome signature to discriminate HC and PLC, including 15 variables on genus level. The prediction performance of the signature showed well in the training and validation cohorts. This research illustrates specific clinical features and bacterial structures in PLC patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

Analysis of the Impact of Medical Features and Risk Prediction of Acute Kidney Injury for Critical Patients Using Temporal Electronic Health Record Data With Attention-Based Neural Network.

Acute kidney injury (AKI) is one of the most severe consequences of kidney injury, and it will also cause or aggravate the complications by the fast decline of kidney excretory function. Accurate AKI prediction, including the AKI case, AKI stage, and AKI onset time interval, can provide adequate support for effective interventions. Besides, discovering how the medical features affect the AKI result may also provide supporting information for disease treatment. An attention-based temporal neural network approach was employed in this study for AKI prediction and for the analysis of the impact of medical features from temporal electronic health record (EHR) data of patients before AKI diagnosis. We used the publicly available dataset provided by the Medical Information Mart for Intensive Care (MIMIC) for model training, validation, and testing, and then the model was applied in clinical practice. The improvement of AKI case prediction is around 5% AUC (area under the receiver operating characteristic curve), and the AUC value of AKI stage prediction on AKI stage 3 is over 82%. We also analyzed the data by two steps: the associations between the medical features and the AKI case (positive or inverse) and the extent of the impact of medical features on AKI prediction result. It shows that features, such as lactate, glucose, creatinine, blood urea nitrogen (BUN), prothrombin time (PT), and partial thromboplastin time (PTT), are positively associated with the AKI case, while there are inverse associations between the AKI case and features such as platelet, hemoglobin, hematocrit, urine, and international normalized ratio (INR). The laboratory test features such as urine, glucose, creatinine, sodium, and blood urea nitrogen and the medication features such as nonsteroidal anti-inflammatory drugs, agents acting on the renin-angiotensin system, and lipid-lowering medication were detected to have higher weights than other features in the proposed model, which may imply that these features have a great impact on the AKI case.

[Effects of oxymatrine injection combined with low-dose paclitaxel on mRNA and protein expressions of vascular endothelial growth factor and CXC chemokine receptor 4 in human gastric carcinoma SGC-7901 cells].

OBJECTIVE: To investigate the effects of oxymatrine injection (OI) combined with low-dose paclitaxel on expressions of mRNAs and proteins of vascular endothelial growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4) in human gastric carcinoma SGC-7901 cells. METHODS: Methyl thiazolyl tetrazolium assay was used to examine the effects of OI combined with low-dose paclitaxel on proliferation of SGC-7901 cells. Real-time reverse transcription-polymerase chain reaction, immunofluorescence and enzyme-linked immunosorbent assay were employed to measure the expressions of VEGF and CXCR4 mRNAs and proteins in gastric carcinoma SGC-7901 cells respectively. RESULTS: Except that 20 µg/mL paclitaxel had no influence on expression of VEGF mRNA in SGC-7901 cells (P>0.05), 40 µg/mL OI or low-dose paclitaxel (20 µg/mL) inhibited the proliferation of SGC-7901 cells and reduced the expressions of VEGF and CXCR4 mRNAs and proteins in SGC-7901 cells (P<0.01). The expressions of VEGF and CXCR4 mRNAs and proteins in the OI plus low-dose paclitaxel group were markedly lower than those in the low-dose paclitaxel group (P<0.01). CONCLUSION: OI combined with low-dose paclitaxel can inhibit VEGF and CXCR4 of gastric carcinoma SGC-7901 cells markedly, which may be one of its mechanisms of anti-angiogenic ability.

Patients with Acute Ischemic Cerebrovascular Disease with Coronary Artery Stenosis Have More Diffused Cervicocephalic Atherosclerosis.

AIM: Coronary artery stenosis (CAS) ≥ 50% frequently coexists in patients with acute ischemic cerebrovascular disease (AICVD), which portends unfavorable outcomes. We sought to examine whether patients with AICVD with CAS had more severe and more diffused cervicocephalic atherosclerosis (CA). METHODS: Patients with AICVD were consecutively enrolled and underwent simultaneous computed tomography angiography (CTA) of the coronary and cervicocephalic arteries. A total of 140 patients were divided into "AICVD＋CAS" and "AICVD only" groups according to whether CTA showed stenosis of ≥ 50% in at least one coronary arterial segment. The relationship of the presence of CAS with the severity and extent of CA were examined. RESULTS: The CA severity characteristics, including the presence of stenosis ≥ 50% and the grade of the most severe stenotic segment, were not significantly different between the two groups. Regarding the extent of CA, the presence of stenosis ≥ 50% in both sides (adjusted odds ratio [OR]: 4.29, 95% confidence interval [CI]: 1.67-10.98), both extracranial and intracranial (adjusted OR: 5.26, 95% CI: 2.24-12.35), both anterior and posterior circulation (adjusted OR: 5.29, 95% CI: 2.22-12.64), and the number of stenotic segments ≥ 50% in cervicocephalic arteries (adjusted OR: 1.58, 95% CI: 1.28-1.96) were associated with CAS in patients with AICVD, independently of clinical demographics and CA severity characteristics. CONCLUSION: CA was similarly severe in patients with AICVD with and without CAS, but those with CAS had significantly more diffused CA. The extent of CA and CAS were mutual indicators in patients with AICVD, irrespective of CA severity.

Predicting asymptomatic coronary artery stenosis by aortic arch plaque in acute ischemic cerebrovascular disease: beyond the cervicocephalic atherosclerosis?

BACKGROUND: Asymptomatic coronary artery stenosis (ACAS) ≥50% is common in patients with acute ischemic cerebrovascular disease (AICVD), which portends a poor cardiovascular and cerebrovascular prognosis. Identifying ACAS ≥50% early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients. This study aimed to investigate whether aortic arch plaque (AAP), an early atherosclerotic manifestation of brain blood-supplying arteries, could be a predictor for ACAS ≥50% in AICVD. METHODS: In this cross-sectional study, atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography (CTA) in AICVD patients without coronary artery disease history. The patients were divided into ACAS ≥50% and non-ACAS ≥50% groups according to whether CTA showed stenosis ≥50% in at least one coronary arterial segment. The AAP characteristics of CTA were depicted from aspects of thickness, extent, and complexity. RESULTS: Among 118 analyzed patients with AICVD, 29/118 (24.6%) patients had ACAS ≥50%, while AAPs were observed in 86/118 (72.9%) patients. Increased AAP thickness per millimeter (adjusted odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.18-2.05), severe-extent AAP (adjusted OR: 13.66, 95% CI: 2.33-80.15), and presence of complex AAP (adjusted OR: 7.27, 95% CI: 2.30-23.03) were associated with ACAS ≥50% among patients with AICVD, independently of clinical demographics and cervicocephalic atherosclerotic stenosis. The combination of AAP thickness, extent, and complexity predicted ACAS ≥50% with an area under the receiver-operating characteristic curve of 0.78 (95% CI: 0.70-0.85, P < 0.001). All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS ≥50% in AICVD (all P < 0.05). CONCLUSIONS: Thicker, severe-extent, and complex AAP were significant markers of the concomitant ACAS ≥50% in AICVD, possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis. As an integral part of atherosclerosis of brain blood-supplying arteries, AAP should not be overlooked in predicting ACAS ≥50% for patients with AICVD.

Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis.

Complementary and integrative medicine (CIM) has been used for improving health-related quality of life (HRQOL) in patients with cancer. The objective of this review is to evaluate the effects of CIMs on the HRQOL of cancer patients. We identified randomized controlled trials (RCTs) involving patients with cancer at any stage by retrieving electronic databases from the inception to February 14, 2018 (Systematic Review Registration: PROSPERO CRD42018091609). The main outcomes were HRQOL scores and related domains such as physical well-being scores. The standardized mean difference was used for the analysis and heterogeneity was assessed with the I 2 statistic. A Bayesian framework was used to estimate the ranking order of efficacy in HRQOL change. Finally, 34 RCTs with 3,010 patients were included. As a whole, the results showed clearly superior efficacy of CIM in improving HRQOL. For different domains of HRQOL, different CIM interventions may play different roles. The ranking order of efficacy in change HRQOL was qigong plus mindfulness, Chinese herbal medicine, multimodal complementary medicine, qigong, nutritional supplement, mindfulness, acupuncture, yoga, and massage, and it was different among different domains. There was no evidence of publication bias. In conclusion, CIM may improve the HRQOL of cancer patients. More studies, especially focusing on male cancer patients, are needed to increase the confidence level of our findings.

Prognostic Role of Platelet-to-Lymphocyte Ratio in Hepatocellular Carcinoma with Different BCLC Stages: A Systematic Review and Meta-Analysis.

The role of platelet-to-lymphocyte ratio (PLR) in the prognosis of hepatocellular carcinoma (HCC) patients with different Barcelona Clinic Liver Cancer (BCLC) stages remains controversial. This systematic review and meta-analysis aimed to determine the efficacy of PLR on HCC prognosis. Five electronic databases were searched for clinical trials focusing on the role of PLR in the prognosis of HCC. A total of 297 potential studies were initially identified, and 9 studies comprising 2449 patients were finally enrolled to evaluate the association between the pretreatment PLR and clinical outcomes of overall survival (OS), disease-free survival (DFS), and event occurrence in patients with HCC in different BCLC stages. An elevated pretreatment PLR indicated unfavorable worse OS (HR = 1.73; 95% CI: (1.46, 2.04); P < 0.00001) and DFS (HR = 1.30; 95% CI: (1.06, 1.60); P = 0.01). Subgroup analysis indicated that high PLR indicated poor OS among BCLC-B/C patients without heterogeneity, while PLR in BCLC-A patients indicated high statistical heterogeneity with I2 value of 78%. As for the correlation between PLR and event occurrence, high PLR was related to poor clinical event occurrence only among BCLC-C patients, though obvious heterogeneity was observed in all different BCLC stages. In conclusion, PLR may be a significant biomarker in the prognosis of HCC in different BCLC stages.

Breast cancer stem-like cells can promote metastasis by activating platelets and down-regulating antitumor activity of natural killer cells.

OBJECTIVE: To investigate whether cancer stem cells (CSCs) more efficiently activating platelets and evading immune surveillance than non-CSCs thus promoting metastasis. METHODS: We enriched and identified sphere-forming cells (SFCs) and coincubated washed platelets with several platelet activators including collagen, 4T1 and SFCs. Platelet-coating tumor cells, platelet activation and TGF-ß1 release were analyzed. Then natural kell cells (NK) were incubated with supernatants of different activated platelet samples what we called sample release (SR). The degranulation assay and NKG2D expression on NK cells were conducted by flow cytometry. Finally tissue factor (TF) expression of SFCs or 4T1 were evaluated by western blot. RESULTS: Breast cancer cell line 4T1 could form spheres in serum-free medium at low adherence. Sphere-forming cells expressed high levels of the CD24-/lowCD44 + stem cell phenotype. Both sphere-forming cells or 4T1 were coated with abundant platelets while sphere-forming cells induced significantly higher expression of platelet activating receptor CD62p than 4T1 did (P < 0.01). And sphere-forming cells induced platelets to produce more TGF-ß1 than 4T1 did (P < 0.01). Furthermore, sample releases induced by sphere-forming cells caused more vigorous inhibition of NK cells antitumor reactivity (P < 0.05) and reduced NKG2D expression (P < 0.01). The final results showed that sphere-forming cells expressed higher levels of TF than 4T1 (P < 0.05). CONCLUSION: Our findings indicate that CSCs could efficiently activate platelets, induce platelets to secrete more TGF-ß1, decrease NKG2D expression and inhibit antitumor activity of NK cell, compared with 4T1. And higher levels of TF expression of CSCs may account for this correlation of CSCs and platelets.