From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

In response to the challenge posed by the significant shape and scale variations of tumors and organs in three-dimensional medical images,which often results in low segmentation accuracy,an end-to-end three-dimensional fully convolutional segmentation model is introduced.A dilated cubic integration module is designed to achieve multi-scale integration at different resolution stages,thereby enhancing the recognition capability on complex boundaries.Subsequently,a cross-stage context fusion module is incorporated to merge shallow and deep features,thereby facilitating convergence and more precise localization of the target objects.Finally,features from the encoder are concatenated by the decoder to realize segmentation.The average Dice similarity coefficients reach 85.37%on the brain tumor segmentation dataset and 83.99%on the abdominal organ segmentation dataset.Experimental results indicate that the proposed model exhibits high accuracy in three-dimensional tumor and organ segmentation.

ObjectiveTo understand the experience， knowledge and attitudes of e-cigarette users in Shanghai， and to provide evidence for the development of intervention programs for e-cigarette use. MethodsThe Respondent-Driven Sampling （RDS） method was used to recruit 40 e-cigarette users for qualitative interviews from November 2020 to February 2021. NVivo （11.0） software was used to code interview records， and the thematic pattern and relationship analysis were conducted. ResultsIn terms of the reasons and user experience of e-cigarette use， most respondents used e-cigarettes for the first time after recommendation of friends； The reasons for the current use of e-cigarettes focus on the subjective feelings generated by the use of e-cigarettes （easy to use， replacing traditional tobacco， and having many flavors）. Compared with traditional tobacco use， respondents said e-cigarettes tasted good and had no physical impact （they could be used all the time without making them uncomfortable）. In terms of the awareness of e-cigarette use related knowledge， the respondents' opinions on whether e-cigarettes caused health risks were mostly based on their own experience of using them， and they said it was difficult to identify real information online. As for whether they were interested in relevant knowledge， most respondents said they wanted to learn about the professional knowledge related to e-cigarettes. Regarding the attitude related to the use of e-cigarettes， most respondents believed that e-cigarettes are addictive， e-cigarettes are not a safe alternative to traditional tobacco， ande-cigarettes couldn't help them quit smoking. Three out of ten respondents said they supported including e-cigarettes in the Regulation on Smoking Control in Public. ConclusionThere are certain characteristics of e-cigarette users' feelings， related knowledge and attitude towards e-cigarette use that should be targeted to carry out publicity， education and intervention.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

OBJECTIVE: To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them. METHODS: Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury. RESULTS: Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups. CONCLUSION The regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.
Animals ; Rats ; Nerve Fibers ; Nerve Regeneration ; Rats, Sprague-Dawley ; Sciatic Nerve/injuries*

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg^-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

Objective:To establish Sprague-Dawley (SD) rat models of cognitive impairment through repeated stimulation of lipopolysaccharide (LPS) in the early brain development, and to inquire into the effect of " multi-hits" mediated by inflammatory response on the histology and behavior of SD rat models and related molecular mechanisms.Methods:This study adopted a group design for experiments.The " multi-hits" SD rat models were established by intraperitoneal injection of LPS.According to the random number table method, 24 pregnant rats were randomly divided into 4 groups: control group, LPS1 group, LPS2 group and LPS3 group, 6 rats in each group.In the control group, saline was intraperitoneally injected into rats with gestational age of 18 days and 20-day-old neonatal rats.Rats with gestational age of 18 days were intraperitoneally injected with saline in the LPS1 group, 0.05 mg/kg LPS in the LPS2 group, and 0.1 mg/kg LPS in the LPS3 group.The pups in LPS1-3 groups were all injected intraperitoneally with 1 mg/kg LPS at the postnatal age of 20 days.The motor and cognitive function of the pups were evaluated overall by behavioral experiments such as forelimb suspension tests, grid tests and water maze tests.The relative expression of glial fibrillary acidic protein (GFAP), Notch1 and Jagged1 in brain tissue of pups was mainly detected by Western blot (WB) and histological experiments.One-way ANOVA analysis of variance and independent samples t- test were used to compare data among groups and between groups, respectively. Results:(1) Behavioral experiments: compared with the control group, LPS1-3 groups showed progressive decrease in forelimb suspension time [(34.81±5.66) s, (22.47±4.35) s, and (13.20±4.25) s vs.(43.88 ± 4.85) s], and the number of missteps in the grid experiment increased progressively (16.13±2.90, 20.75±3.10, 25.13±4.45 vs.9.00±2.72). The differences were statistically significant ( F=69.77, 35.59, all P<0.001). Both the escape latency and total distance in Morri′s water maze test increased progressively ( P<0.05). (2) WB experiment: the relative expression levels of GFAP, Notch1 and Jagged1 proteins in LPS1-3 groups were significantly higher than that in the control group ( P<0.05). (3) Hematoxylin-eosin (HE) staining and electron microscope pathology: compared with the control group, LPS1-3 groups had more loosely arranged frontal cortices and more obvious cell pyknosis.Under the electron microscope, the cytoplasm was swelling to varying degrees, mitochondrial cristae were broken, and part of the nuclear membrane was damaged. Conclusions:In the " multi-hits" cognitive impairment model, the damage to the brain tissue structure and behavioral changes of pups may be related to the up-regulation of Notch1/Jagged1 pathway mediated by repeated exposure to LPS.

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO₂) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO₂, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO₂ and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO₂ showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO₂ showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO₂ higher than female(r=-0.229, P<0.001); PeakVO₂ of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO₂ (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO₂(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO₂(t=-5.43, -0.31, respectively, all P<0.05). PeakVO₂ of male was higher than female(t=-6.03, P<0.05), and peakVO₂ of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R²=0.29) could be constructed: peakVO₂=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO₂. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.
Chronic Disease ; Cross-Sectional Studies ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Oxygen Consumption/physiology* ; Prognosis ; Retrospective Studies ; Stroke Volume/physiology*