An experimental study for quantitative assessment of fatty infiltration and blood flow perfusion in quadriceps muscle of rats using IDEAL-IQ and BOLD-MRI for early diagnosis of sarcopenia.

BACKGROUND: Severe sarcopenia may result in severe disability. Early diagnosis is currently the key to enhancing the treatment of sarcopenia, and there is an urgent need for a highly sensitive and dependable tool to evaluate the course of early sarcopenia in clinical practice. This study aims to investigate longitudinally the early diagnosability of magnetic resonance imaging (MRI)-based fat infiltration and blood flow perfusion technology in sarcopenia progression. METHODS: 48 Sprague-Dawley rats were randomly assigned into six groups that were based on different periods of dexamethasone (DEX) injection (0, 2, 4, 6, 8, 10 days). Multimodal MRI was scanned to assess muscle mass. Grip strength and swimming exhaustion time of rats were measured to assess muscle strength and function. Immunofluorescence staining for CD31 was employed to assess skeletal muscle capillary formation, and western blot was used to detect vascular endothelial growth factor-A (VEGF-A) and muscle ring finger-1 (MuRF-1) protein expression. Subsequently, we analyzed the correlation between imaging and histopathologic parameters. A receiver operating characteristic (ROC) analysis was conducted to assess the effectiveness of quantitative MRI parameters for discriminating diagnosis in both pre- and post-modeling of DEX-induced sarcopenic rats. RESULTS: Significant differences were found in PDFF, R2* and T2 values on day 2 of DEX-induction compared to the control group, occurring prior to the MRI-CSA values and limb grip strength on day 6 of induction and swimming exhaustion time on day 8 of induction. There is a strong correlation between MRI-CSA with HE-CSA values (r = 0.67; p < 0.001), oil red O (ORO) area with PDFF (r = 0.67; p < 0.001), microvascular density (MVD) (r = -0.79; p < 0.001) and VEGF-A (r = -0.73; p < 0.001) with R2*, MuRF-1 with MRI-CSA (r = -0.82; p < 0.001). The AUC of PDFF, R2*, and T2 values used for modeling evaluation are 0.81, 0.93, and 0.98, respectively. CONCLUSION: Imaging parameters PDFF, R2*, and T2 can be used to sensitively evaluate early pathological changes in sarcopenia. The successful construction of a sarcopenia rat model can be assessed when PDFF exceeds 1.25, R2* exceeds 53.85, and T2 exceeds 33.88.

Individual socioeconomic status as a modifier of the association between high ambient temperature and hospital admissions: a time series study in Hong Kong, 2010-2019.

Few studies have examined individual socioeconomic status (SES) as a potential modifier of ambient temperature-health associations, especially for temperature-related hospitalizations. We fit penalized distributed lag non-linear models within generalized additive models to study the short-term associations (0-3 days) between temperature and hospital admissions stratified by common causes, age, and individual SES, as determined by whether patients received public assistance (PA) to cover their medical fee at the time of hospitalizations, during the hot season (May 15 to October 15) in Hong Kong for the years 2010-2019. We calculated the ratio of relative risk (RRR) and corresponding 95% confidence interval (CI) to statistically test the difference of the associations between PA groups. For 75 + patients, the PA group had significantly increased risks of hospitalizations at higher temperature for most causes, with relative risks (RR, 99th %ile vs. 25%ile) and 95% CIs of 1.138 (1.099, 1.179), 1.057 (1.008, 1.109), and 1.163 (1.094, 1.236) estimated for all non-cancer non-external, circulatory, and respiratory admissions, respectively. There were slight decreases of RRs with higher temperature for 75 + patients without PA. The strengths of temperature-hospitalization associations were strongly and significantly different between PA groups for all examined causes for 75 + patients, with the most considerable discrepancy found for ischemic heart disease (RRR = 1.266; 95% CI, 1.137, 1.410). Hospitalizations for patients aged 15-74 were less affected by heat, and the difference of the associations between groups was small. Individual SES is a significant modifier of high temperature-hospitalization associations in Hong Kong among the elderly. Public health interventions are needed to better protect this subpopulation from adverse health impacts of high temperature.

Myrtenal and ß-caryophyllene oxide screened from Liquidambaris Fructus suppress NLRP3 inflammasome components in rheumatoid arthritis.

BACKGROUND: Liquidambaris Fructus (LF) is the infructescence of Liquidambar formosana. In Traditional Chinese Medicine, LF has been used to treat joint pain, a common symptom of arthritis and rheumatism; however, a lack of pharmacological evidence has limited its applications in modern clinics. Therefore, this study aims to explore the protective effect of LF on rheumatoid arthritis (RA) and to identify its active ingredients. METHODS: Rats with adjuvant-induced arthritis (AIA) were divided into 4 groups and administered petroleum ether extract of LF (PEL), ethyl acetate extract of LF (EEL), water extract of LF (WEL), or piroxicam (PIR) respectively for 3 weeks. Two additional groups were used as normal control (NC) and model control (MC) and administered distilled water as a placebo. The clinical scores for arthritis, bone surface, synovial inflammation and cartilage erosion were used to evaluate the therapeutic efficacy of each treatment. The serum IL-1ß and TNF-α level and the expression of NLRP3, IL-1ß and caspase-1 p20 in the synovial tissue of AIA rats were evaluated by ELISA and Western blot. The active ingredients of LF were investigated using network pharmacology and molecular docking methods, and their inhibition of NLRP3 inflammasome activation was verified in the human rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) model. RESULTS: PEL could alleviate paw swelling, bone and joint destruction, synovial inflammation and cartilage erosion in the AIA rats, with significantly superior efficacy to that of EEL and WEL. PEL reduced IL-1ß and TNF-α serum levels, and attenuated the upregulation of NLRP3, IL-1ß and caspase-1 p20 expression in the synovial tissue of AIA rats. Network pharmacology and molecular docking results indicated that myrtenal and ß-caryophyllene oxide were the main two active ingredients of PEL, and these two compounds showed significant inhibition on TNF-α, NLRP3, IL-1ß and caspase-1 p20 expression in RA-FLS. CONCLUSIONS: Myrtenal and ß-caryophyllene oxide screened from PEL could suppress the activation of NLRP3 inflammasome, thereby alleviating RA symptoms.

Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor α.

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

Food Poisoning Caused by Deoxynivalenol at a School in Zhuhai, Guangdong, China, in 2019.

Deoxynivalenol (DON) or "vomitoxin" is a mycotoxin produced by Fusarium species. Few food poisoning cases caused by DON have been reported since the 1990s in China. However, on May 16, 2019, the Zhuhai Center for Disease Control and Prevention received a case report from primary school "S" that many students began vomiting after eating breakfast. To discern the cause and control the outbreak effectively, an epidemiological investigation was carried out. This retrospective cohort study defined both suspected and probable cases of food poisoning using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry to detect 16 mycotoxins simultaneously. A total of 101 cases (14 suspected and 87 probable) were identified, with an overall attack rate of 8.1%. All cases were in grades 1-3. The main symptoms of probable cases were vomiting (100%) and nausea (63%). The average incubation time was 25 min after eating. Comparison of students who ate breakfast provided by the school with those who did not revealed the relative risk was 6.0 (95% confidence intervals [CI] = 2.2-16) among students in grades 1-3. The concentration of DON in the leftover raw breakfast noodles ranged from 6856 to 11,982 µg/kg and 878.3 to 1074.2 µg/kg in leftover cooked noodles. DON exposure was 1.3-1.6 µg/kg body weight for grades 1-2 and 1.7-2.1 µg/kg body weight for grade 3. The attack rate of grade 3 was 4.3 times higher than that for grades 1-2 (95% CI = 3.0-6.3). The food poisoning outbreak on May 16, 2019 in primary school "S" in China, was determined to be caused by DON-contaminated commercial raw noodles.

A minimally invasive alternative for the treatment of nutcracker syndrome using individualized three-dimensional printed extravascular titanium stents.

BACKGROUND: This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications. METHOD: The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV's primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 µm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed. RESULTS: The mean duration of surgery was 75 ±â€Š9 min, and the mean blood loss was 20 ±â€Š5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7°â€Š±â€Š4.3° to 48.0°â€Š±â€Š8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ±â€Š0.5 to 1.3 ±â€Š0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ±â€Š3.3 to 18.5 ±â€Š3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery. CONCLUSION: The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.

High HER-2 protein levels correlate with clinicopathological features in colorectal cancer.

AIM: To obtain a correlation between HER-2 expression and the clinicopathological features incolorectal cancers. (CRCs) using a meta.analysis based approach. MATERIALS AND METHODS: Electronic databases and reference lists were searched for relevant published studies. After inclusion and exclusion criteria were applied, case and control studies related to research topic were included in present meta-analysis. Data analysis was performed using Comprehensive Meta Analysis. (CMA) 2.0 software. RESULT: A total of 30 studies comprising 4,942 CRC patients and 521 healthy controls met the inclusion criteria. Our major results implied that the expression level of HER-2 was significantly higher in CRC patients than healthy controls (odds ratio (OR) = 10.436, 95% confidence interval (CI) = 5.498-19.810, P < 0.001). Sample stratification based on Dukes stages suggested that increased expression level of HER-2 protein was found in CRC patients with Dukes C/D compared with CRC patients with Dukes A/B (OR = 0.335, 95% CI = 0.198-0.568, P < 0.001). The current meta-analysis also found that, in CRC patients with lymph node metastasis (LNM), the HER-2 expression was significantly higher than that in CRC patients without LNM (OR = 1.987, 95%CI = 1.209-3.265, P = 0.007). CONCLUSION: Our meta-analysis study strongly suggests that HER-2 expression levels are clearly correlated with the clinicopathological features in CRC; therefore, HER-2 may be a potential biomarker for diagnosis and prognosis of CRC.

Correlation of human epidermal growth factor receptor protein expression and colorectal cancer.

AIM: To investigate the correlation between human epidermal growth factor receptor (HER-2) protein expression and colorectal cancer (CRC) using a case-control study and meta-analysis. METHODS: Tumor tissue specimens from 162 CRC patients were selected for the case group. Fifty cases were randomly selected, and normal CRC tissue at least 10 cm away from the tumor margins of these cases was used to generate the control group. The expression of the HER-2 protein in the 162 CRC tissue samples and the 50 adjacent normal mucosa tissue samples was detected via immunohistochemistry. The experimental data were analyzed using SPSS 18.0 software, and R software version 3.1.0 was utilized for further verification. RESULTS: The expression of HER-2 protein in the 162 CRC tissue samples was significantly higher than in the normal tissue specimens. The data showed that the expression of HER-2 in CRC was related to the Dukes' stage, the depth of invasion and lymph node metastasis. The HER-2-positive patients had lower 3- and 5-year OS rates than the HER-2-negative patients, but there was no significant difference. However, there was a statistically significant difference in the 3- and 5-year disease-free survival (DFS) rates of HER-2-positive and HER-2-negative patients. The results of the meta-analysis showed that the expression of HER-2 in CRC patients was statistically significantly increased over that of healthy people. The 3-year DFS rate in HER-2-positive patients was markedly lower than that in HER-2-negative patients. CONCLUSION: Down-regulation of HER-2 expression might be a dependable strategy for CRC therapy.