AIM To improve the quality of Compound Yuxingcao Tablets.METHODS The HPLC fingerprints were established,after which the contents of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,forsythoside I,forsythoside A,quercitrin,3,5-O-dicaffeoylquinic acid,4,5-O-dicaffeoylquinic acid,baicalin,oroxyloside,wogonin and baicalein were determined.The analysis was performed on a 30 ℃ thermostatic Waters XBridge C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 327 nm.Subsequently,principal component analysis and orthogonal partial least squares discriminant analysis were adopted.RESULTS There were 21 common peaks in the fingerprints for 22 batches of samples with the similarities of more than 0.85.Twelve constituents showed good linear relationships within their own ranges(R20.999 8),whose average recoveries were 93.68％-101.16％with the RSDs of 0.95％-2.35％.Baicalin,wogonin and forsythoside A were taken as quality differential components.CONCLUSION This simple and accurate method can be used for the quality control of Compound Yuxingcao Tablets.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To improve the quality of Compound Yuxingcao Tablets.METHODS The HPLC fingerprints were established,after which the contents of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,forsythoside I,forsythoside A,quercitrin,3,5-O-dicaffeoylquinic acid,4,5-O-dicaffeoylquinic acid,baicalin,oroxyloside,wogonin and baicalein were determined.The analysis was performed on a 30 ℃ thermostatic Waters XBridge C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 327 nm.Subsequently,principal component analysis and orthogonal partial least squares discriminant analysis were adopted.RESULTS There were 21 common peaks in the fingerprints for 22 batches of samples with the similarities of more than 0.85.Twelve constituents showed good linear relationships within their own ranges(R20.999 8),whose average recoveries were 93.68％-101.16％with the RSDs of 0.95％-2.35％.Baicalin,wogonin and forsythoside A were taken as quality differential components.CONCLUSION This simple and accurate method can be used for the quality control of Compound Yuxingcao Tablets.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective In order to shorten the transparency time of clear,unobstructed brain imaging cocktails and computational analysis(CUBIC),improve the transparency efficiency,and explore the possibility of applying hydrophilic tissue transparency technique,this study was conducted to optimize the perfusion of CUBIC technique and compare it with four hydrophilic tissue clearing method in terms of tissue transparency effect,transparency time,area change,volume change and adeno-associated virus(AAV)fluorescence retention.Methods Brain,liver,spleen and kidney of 6 adult Institute of Cancer Research(ICR)mice were subjected to clearing treatment by SeeDB,FRUIT,ScaleS and CUBIC method,respectively.The area and gray value of the samples were measured by Image J 1.8.0,and the volume before and after transparency was measured by drainage method to compare the transparency effect,time and size deformation of each group.Perfusion optimization of the CUBIC was performed by improving the perfusion rate with the optimal perfusion dose,each group of the experimental sample size was 6.Fluorescence preservation by different techniques was evaluated by injecting AAV in the motor cortex of 16 adult mice and taking the cervical spinal segments for transparency treatment after four weeks,and the fluorescence photographs were measured by Image J 1.8.0 to measure the mean fluorescent intensity.Results The optimal perfusion rate and dose of CUBIC was 15 ml/min and 200 ml respectively.For transparency ability and speed,the perfusion CUBIC had the lowest mean gray value and took the shortest time,while CUBIC consumed the longest time,and SeeDB,FRUIT,and ScaleS did not show good transparency ability.In terms of area and volume changes,several techniques showed different degrees of expansion after transparency of tissues or organs.In terms of fluorescence retention,perfusion CUBIC showed the best retention of green fluorescent protein(GFP)fluorescence signal,followed by CUBIC,ScaleS,FRUIT,and SeeDB.Conclusion Perfusion CUBIC technique shows the best tissue transparency,the shortest transparency time,and the most AAV fluorescence retention compared with other techniques.

Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

Cerebroprotein hydrolysate oral liquid (COL) is a neuroprotective preparation composed of various amino acids and peptides, which has beneficial effects on diverse central system diseases. However, the therapeutic effect and potential mechanism of oral COL on ischemic stroke (IS) still need to be explored. This study aims to investigate the therapeutic effects and underlying mechanisms of COL on IS in vivo and in vitro. An IS rat model was established through middle cerebral artery occlusion (MCAO) surgery, and triphenyltetrazolium chloride (TTC) staining, behavioral scoring, Evans blue leakage, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining were performed to investigate the effects of COL on cerebral infarct size, neurological function, blood-brain barrier (BBB) and neuroinflammation in IS rats. An in vitro model of IS was established on hCMEC/D3 cells through oxygen-glucose deprivation/reperfusion (OGD/R), and cell counting kit-8 assay, reactive oxygen species (ROS) detection, scratch test and Transwell test were conducted to examine the influence of COL on cell viability, oxidative stress and migration ability. Lipidomics technology, real-time quantitative PCR and Western blot experiments were used to investigate the regulation and mechanism of COL on lipid metabolism in the brain of IS rats. All the animal experiments were approved by Ethical Committee of Animal Experiments of China Pharmaceutical University (No.2022-02-23). Our results showed that intragastric administration of COL could significantly reduce the area of cerebral infarction, improve neurological deficits, lower the levels of inflammatory factors, and protect against the blood-brain barrier damage of rats with IS. OGD/R modeling resulted in a significant decrease in the viability, an elevation in intracellular ROS levels, and a weakened cell migration ability of hCMEC/D3 cells. COL treatment could effectively protect hCMEC/D3 cells from damage caused by OGD/R. More importantly, cerebral ischemia led to significant lipid metabolism disorders in the brain of rats, and significant accumulation of intracerebral triglycerides (TAG) and ceramides (Cer) was observed in IS rats. COL was proved to significantly reverse lipid metabolism disorders in the brain of IS rats and reduce the content of cytotoxic lipid Cer by upregulating the intracerebral levels of an acid ceramidase called N-acylsphingosine amidehydrolase 1 (ASAH1). In summary, COL was proved to be a promising and effective candidate for IS treatment, which could alleviate cerebral ischemic injury by regulating abnormal lipid metabolism.

OBJECTIVE: To explore weight-bearing stability of Pilon fracture fixed by external fixator. METHODS: Six ankle bone models (right side) and 4 pairs (8 ankle cadaver specimens) were selected. Pilon fracture model was prepared by using the preset osteotomy line based on Ruedi Allgower Pilon fracture type. Pilon fracture model was built by using a minimally invasive osteotomy. After ankle bone model and cadaver specimen model were fixed with external fixator, axial load was carried out on mechanical loading machine. After ankle bone model and cadaver specimen model were fixed with external fixator, axial load was carried out on mechanical loading machine. Axial loads of 150, 300 and 450 N were applied to ankle bone model, and displacements of fibula fracture blocks, lateral tibia fracture blocks and medial tibia fracture blocks in three-dimensional space (X, Y and Z axes) were recorded by dynamic capture instrument. Axial loads of 300, 600 and 900 N were applied to ankle cadaver model fixed by external fixator. X-ray films of Pilon fracture cadaver model fixed by external fixator under different loading conditions were taken. The anterior tibial angle, tibial malleolar point angle, talus shift value, talus tilt angle, lateral malleolar shift value, lateral malleolar shift value, medial malleolar separation shift value and articular surface step displacement value were measured under different loads by digimizer software. RESULTS: After 150, 300 and 450 N axial loads were applied to Pilon fracture models fixed by external fixator, no loosening or fracture of external fixator was observed, and no loosening, fracture or irreversible plastic deformation of Kirschner needle were observed. The displacement values of fibular fracture pieces on X-axis(around) were 0.032 (-0.022, 0.269), 0.061 (-0.002, 0.427), 0.212(-0.016, 1.223) mm, and the displacement values on Y-axis(above and below) were 0.002(-0.031, 0.103), 0.051(-1.133, 0.376), 0.128 (-1.394, 0.516) mm, and displacement values on Z-axis (front and rear) were -0.003 (-0.130, 0.171), 0.137 (-0.076, 0.433), 0.030(-0.487, 0.478) mm;the displacement values of lateral tibial fractures on X-axis were 0.000(-0.108, 0.027), 0.083(-0.364, 0.050), -0.121(-0.289, 0.165) mm, and displacement values on Y-axis were -0.009(-0.200, 0.025), -0.179(-0.710, 0.084), -0.257(-0.799, 0.027) mm, and displacement values on Z-axis were 0.112(-0.024, 0.256), 0.157(-0.068, 0.293), -0.210(-0.035, 0.430) mm;the displacement values of medial tibial fracture block on X-axis were -0.010(-0.060, 0.013), -0.165(-0.289, 0.056), -0.181(-0.395, 0.013) mm, and the displacement values on Y-axis were -0.036(-0.156, 0.007), -0.104(-0.269, 0.178), -0.245(-0.380, -0.011) mm, and displacement values on Z-axis were -0.005(-0.372, 0.189), -0.012 (-1.774, 0.380), 0.200 (-1.963, -0.540) mm. After 300, 600 and 900 N axial loads were applied to Pilon fracture cadaverous models fixed with external fixators, there were no significant difference in anterior tibial angles, angles of malleolar points of tibia, oblique angles of talus, fracture steps, shift values of talus, lateral shift values of lateral malleolus, lateral shift values of medial malleolus, lateral shift values of medial malleolus between under different loading conditions and those without loading (P>0.05). No loosening or fracture of external fixator as a whole, loosening, fracture or irreversible deformation of Kirschner needle at the local fixed fracture end occurred. CONCLUSION The early weight-bearing external fixator could maintain stability of fracture end and ankle joint, and the maximum weight is not more than 300 N. In clinical practical application, material characteristics of the implant and type of fracture should be selected.
Humans ; Weight-Bearing ; Biomechanical Phenomena ; External Fixators ; Tibial Fractures/physiopathology* ; Fracture Fixation/instrumentation* ; Male

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis