Objective To investigate the effect of hedysarum polysacchcaide(HPS)on nuclear transcription factor-κB(NF-κB)/IκB kinase β(IKKβ)signaling pathway in cardiac tissue of db/db mice with diabetic cardiomyopathy(DCM).Methods Altogether 60 7-week-old male db/db mice were randomly divided into model group,control group and experimental-H,-M,-L groups,with 12 mice in each group.In addition,12 db/m mice of the same week age were selected as the normal group.Normal group and model group were given 0.9％NaCl by intragastric administration.Experimental-L,-M,-H groups were given 50,100 and 200 mg·kg-1 HPS suspension by intragastriction,respectively.Control group was given 4 mg·kg-1 rosiglitazone suspension by intragastric administration.Six groups of rats were given the drug once a day for 8 weeks.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in myocardial tissue were detected by enzyme-linked immunosorbent assay.The mRNA expression levels of NF-κB and IKKβ in myocardial tissue were detected by real-time fluorescence quantitative polymerase chain reaction.The correlation between the expression of NF-κB protein and the content of TNF-α and IL-6 was analyzed.Results The contents of IL-6 in myocardial tissue of normal,model,control and experimental-H groups were(1.24±0.54),(7.72±0.24),(2.90±0.50)and(2.78±0.56)ng·L-1;the contents of TNF-α were(1.96±0.52),(5.25±0.72),(2.84±0.86)and(2.82±0.58)ng·L-1;the mRNA expression levels of NF-κB were I.00±0.00,3.35±0.81,2.05±0.44 and 1.67±0.22;the mRNA expression levels of IKKβ were 1.00±0.00,2.92±0.07,1.51±0.07 and 1.41±0.08,respectively.Compared with the model group,the above indexes of the control and experimental-H groups were statistically significant(P＜0.01,P＜0.05).The expression of NF-κB protein was positively correlated with the content of IL-6 and TNF-α,and the correlation coefficients were 0.866 and 0.740(all P＜0.01).Conclusion HPS can alleviate the damage of myocardial pathology in mice,reduce myocardial collagen deposition and fibrosis,its mechanism may be through regulating the expression of NF-κB/IKKβ signaling pathway to play a role in inhibiting the inflammatory reaction.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg^-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg^-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P<0.05), while the number of crossing platforms significantly increased (P<0.05); The result of HE staining, Nissl staining and TEM showed that compared with the model group, the neurons in hippocampal CA1 area of rats in the EA Zhisanzhen group and nimodipine group were arranged orderly, and the morphology and structure of cells and organelle were complete; Immunohistochemical method and Western blotting showed that the expression of EphB2 and BMK1 in the CA1 region of hippocampus in the model group was significantly lower than that in the sham surgery group (P<0.05); Compared with the model group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05), while the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the non acupoint electroacupuncture group was not statistically significant (P>0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

OBJECTIVE: To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats. METHODS: Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve. RESULTS: In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment. CONCLUSION Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.
Animals ; Disease Models, Animal ; Epothilones ; Evoked Potentials, Visual ; Nerve Regeneration/physiology* ; Optic Nerve Injuries/metabolism* ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/physiology*

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective:To explore the effect of home-based rehabilitation training on a patient with posterior shoulder dislocation with reverse Hill-Sacks lesion. Methods:According to the preoperative and postoperative evaluation and the operation way, a four-phase home-based rehabilitation training plan was developed for the patient, which included the training of muscle strength and range of motion, and proprioceptive sensation training and so on. The patient was followed up in rehabilitation department regularly. The range of motion was measured, and were also evaluated with Manual Muscle Test, Visual Analogue Score (VAS) and modified Rowe Score. Results:Six months after operation, the active range of motion of flexion, extension, adduction, abduction and external rotation of his shoulder reached to the normal range, the active internal rotation reached to level L₃, the muscle strength recovered to the normal level, the VAS decreased from six preoperative to 0 postoperative, and the modified Rowe Score improved from 16 preoperative to 91. Ten months after operation, his active internal rotation reached to level L₁, and the modified Rowe Score was 93. Conclusion:Individualized remote guidance and reasonable home-based rehabilitation training might be effective on posterior shoulder dislocation with reverse Hill-Sacks lesion.