CAR-T cell therapy in advanced thyroid cancer: from basic to clinical.

The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field.

Theory to practice: a success in breeding sugarcane variety YZ08-1609 known as the King of Sugar.

Sugarcane, a significant cash crop in tropical and subtropical regions, contributes to 80% of sugar production and 40% of bioethanol production in the world. It is a key sugar crop, accounting for 85% of sugar production in China. Developing new varieties with high yield, high sugar, and better stress resistance is crucial for the sustainable growth of sugar industry. Hybrid breeding is the most widely used and effective method, with over 98% of Chinese sugarcane varieties resulting from this approach. Over the past two decades, Chinese breeders have developed the theory of high-heterogeneous composite high-sugar breeding, leading to the successful breeding of the fifth-generation sugarcane varieties. Among them, YZ08-1609, a complex hybrid of Saccharum spp., was developed by Sugarcane Research Institute (YSRI) of Yunnan Academy of Agricultural Sciences. The average cane yield of YZ08-1609 was 14.4% higher than ROC22. It is highly resistant to mosaic disease, and highly tolerant to drought stress, but moderately susceptible to smut disease. Notably, YZ08-1609 stands out with a sucrose content of 20.3%, setting an international record, earning the reputation as "King of Sugar". To summarize experience and inspire breeding, we provided here the detailed insights into the selection of parents, breeding process, and characteristics of YZ08-1609. Besides, the biological mechanisms underlying its high yield and high sugar was excavated at both transcriptional and metabolic levels. The challenges and prospects in breeding sugarcane varieties especially with high sugar were also discussed, offering a foundation for the future development of high-sugar varieties.

Exploring the biological basis of CT imaging features in pancreatic neuroendocrine tumors: a two-center study.

Objective.Medical imaging offered a non-invasive window to visualize tumors, with radiomics transforming these images into quantitative data for tumor phenotyping. However, the intricate web linking imaging features, clinical endpoints, and tumor biology was mostly uncharted. This study aimed to unravel the connections between CT imaging features and clinical characteristics, including tumor histopathological grading, clinical stage, and endocrine symptoms, alongside immunohistochemical markers of tumor cell growth, such as the Ki-67 index and nuclear mitosis rate.Approach.We conducted a retrospective analysis of data from 137 patients with pancreatic neuroendocrine tumors who had undergone contrast-enhanced CT scans across two institutions. Our study focused on three clinical factors: pathological grade, clinical stage, and endocrine symptom status, in addition to two immunohistochemical markers: the Ki-67 index and the rate of nuclear mitosis. We computed both predefined (2D and 3D) and learning-based features (via sparse autoencoder, or SAE) from the scans. To unearth the relationships between imaging features, clinical factors, and immunohistochemical markers, we employed the Spearman rank correlation along with the Benjamini-Hochberg method. Furthermore, we developed and validated radiomics signatures to foresee these clinical factors.Main results.The 3D imaging features showed the strongest relationships with clinical factors and immunohistochemical markers. For the association with pathological grade, the mean absolute value of the correlation coefficient (CC) of 2D, SAE, and 3D features was 0.3318 ± 0.1196, 0.2149 ± 0.0361, and 0.4189 ± 0.0882, respectively. While for the association with Ki-67 index and rate of nuclear mitosis, the 3D features also showed higher correlations, with CC as 0.4053 ± 0.0786 and 0.4061 ± 0.0806. In addition, the 3D feature-based signatures showed optimal performance in clinical factor prediction.Significance.We found relationships between imaging features, clinical factors, and immunohistochemical markers. The 3D features showed higher relationships with clinical factors and immunohistochemical markers.

Multitask Deep Learning-Based Whole-Process System for Automatic Diagnosis of Breast Lesions and Axillary Lymph Node Metastasis Discrimination from Dynamic Contrast-Enhanced-MRI: A Multicenter Study.

BACKGROUND: Accurate diagnosis of breast lesions and discrimination of axillary lymph node (ALN) metastases largely depend on radiologist experience. PURPOSE: To develop a deep learning-based whole-process system (DLWPS) for segmentation and diagnosis of breast lesions and discrimination of ALN metastasis. STUDY TYPE: Retrospective. POPULATION: 1760 breast patients, who were divided into training and validation sets (1110 patients), internal (476 patients), and external (174 patients) test sets. FIELD STRENGTH/SEQUENCE: 3.0T/dynamic contrast-enhanced (DCE)-MRI sequence. ASSESSMENT: DLWPS was developed using segmentation and classification models. The DLWPS-based segmentation model was developed by the U-Net framework, which combined the attention module and the edge feature extraction module. The average score of the output scores of three networks was used as the result of the DLWPS-based classification model. Moreover, the radiologists' diagnosis without and with the DLWPS-assistance was explored. To reveal the underlying biological basis of DLWPS, genetic analysis was performed based on RNA-sequencing data. STATISTICAL TESTS: Dice similarity coefficient (DI), area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and kappa value. RESULTS: The segmentation model reached a DI of 0.828 and 0.813 in the internal and external test sets, respectively. Within the breast lesions diagnosis, the DLWPS achieved AUCs of 0.973 in internal test set and 0.936 in external test set. For ALN metastasis discrimination, the DLWPS achieved AUCs of 0.927 in internal test set and 0.917 in external test set. The agreement of radiologists improved with the DLWPS-assistance from 0.547 to 0.794, and from 0.848 to 0.892 in breast lesions diagnosis and ALN metastasis discrimination, respectively. Additionally, 10 breast cancers with ALN metastasis were associated with pathways of aerobic electron transport chain and cytoplasmic translation. DATA CONCLUSION: The performance of DLWPS indicates that it can promote radiologists in the judgment of breast lesions and ALN metastasis and nonmetastasis. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Biological Basis of Premature Ejaculation Based on Theory of "Brain-heart-kidney-semen Chamber" Axis / 中国实验方剂学杂志

The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine， the modern physiological characteristics of men's diseases， and clinical practice. According to this theory， dysfunctions of the brain， heart， kidney， and semen chamber are the core mechanisms for the occurrence of premature ejaculation， and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease， while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation， we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area， neuromodulation malfunction， central neurotransmitter imbalance， endocrine disorders， and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.

Research progress on the biological basis of Traditional Chinese Medicine syndromes of gastrointestinal cancers.

Gastrointestinal cancers account for 11.6 % of all cancers, and are the second most frequently diagnosed type of cancer worldwide. Traditional Chinese medicine (TCM), together with Western medicine or alone, has unique advantages for the prevention and treatment of cancers, including gastrointestinal cancers. Syndrome differentiation and treatment are basic characteristics of the theoretical system of TCM. TCM syndromes are the result of the differentiation of the syndrome and the basis of treatment. Genomics, transcriptomics, proteomics, metabolomics, intestinal microbiota, and serology, generated around the central law, are used to study the biological basis of TCM syndromes in gastrointestinal cancers. This review summarizes current research on the biological basis of TCM syndrome in gastrointestinal cancers and provides useful references for future research on TCM syndrome in gastrointestinal cancers.

[Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review].

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-ß/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

The Opaque Language of Sexuality: Medical Students' and Providers' Beliefs About Virginity.

Although virginity is not a medical term and is instead socially constructed, it remains unknown what medical providers believe about the biological basis of virginity. This study explored providers' and medical students' beliefs about virginity and the potential impact of such beliefs on healthcare. This was a concurrent mixed-method survey study of 124 medical students and 216 healthcare providers (Registered Nurse, Physician Assistant, Nurse Practitioner, and Doctor of Medicine) at Penn State Health and The Pennsylvania State University College of Medicine. Participants rated their level of agreement with common misconceptions about virginity on a six-point Likert scale. Open-ended questions gave respondents the opportunity to define virginity and to describe terms like virgin and virginal in the context of sexual experience and the medical lexicon. We identified common themes in the qualitative data using thematic analysis. Frequencies of misconceptions and statistically significant demographic associations were identified in the quantitative data. Definitions of virginity were varied and vague, most with negative connotations. A majority of respondents said that virginity has no biological basis. Many participants identified downsides to use of terms like virgin, virginity, and virginal in medicine. The most prevalent misconceptions about virginity were related to the hymen. Seventeen percent of students and 26% of providers at least somewhat agreed that it was possible to determine whether a person has engaged in vaginal intercourse through a gynecological exam. Misconceptions about virginity persist in medicine and bias, even if unintended, may impact the quality-of-care people with vaginas receive. Language around sexual health should be specific, inclusive, clinically relevant, and free from judgment. Medical education must continue to work to eliminate the concept of a biological basis to virginity.

Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

Study on biological basis of primary dysmenorrhea based in different progressive stages based on untargeted metabolomics / 中国药理学通报

Aim To explore its potential biological basis and the endogenous metabolic characteristics of urine during the formation of primary dysmenorrhea via untargeted urine metabolomics. Methods Twenty SD rats were randomly divided into control group and model group. The primary dysmenorrhea model was reproduced by estradiol benzoate combined with oxytocin, and the contrrol group took food and water freely. The differential metabolites and core metabolic pathways were found by multivariable pattern recognition method combined with ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. The receiver operating characteristic ( ROC ) curve was drawn by metaboanalyst 5.0 platform to evaluate the clinical diagnostic efficacy of core metabolites. Results A total of 46 metabolites with significant differences, such as hippuric acid, phenylacetaldehyde, prostaglandin G2, 6-hydroxy-5-methoxyindole glucuronide, were screened, mainly involving phenylalanine metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism. ROC curve showed that the area under the curve of four core biomarkers was greater than 0.7. Conclusions Different metabolic maps are presented in different progressive stages of primary dysmenorrhea, mainly involving the disorders of fatty acid metabolism, carbohydrate metabolism and amino acid metabolism. Meanwhile, the extracted characteristic bi¬omarkers have high diagnostic value for the evaluation of primary dysmenorrhea.

[Discussion on the biological basis of chronic prostatitis based on the "brain-centre-kidney-vessel" axis].

Chronic prostatitis is a common disease in male clinics. The theory of "brain-centre-kidney-vessel" axisis based on the basic theories of traditional Chinese medicine, the pathogenesis of modern men's diseases, and the theory of traditional Chinese medicine in men's medicine proposed by clinical practice. It takes the "brain-heart-kidney-vessel" axis as the entry point, the use of the vessel as the core pathogenesis, the meridians as the link, and the dysfunction of the brain, heart, and kidneys as the important conditions, and proposes that the biological basis between chronic prostatitis and the "brain-heart-kidney-vessel" axis is related to neurological, endocrine, and immunological disorders, as well as the biological basis of the "brain-heart-kidney-vessel" axis. It is also suggested that the biological basis between chronic prostatitis and the "brain-heart-kidney-sperm chamber" axis is related to the nerves, endocrine, immune and microenvironment. Through in-depth study of the biological basis of the "brain-cardiac-kidney-peritoneum" axis, we can better understand the pathogenesis of chronic prostatitis and provide reference for future clinical treatment.

Evaluation of Ingestive Behavior, Ruminal and Blood Parameters, Performance, and Thermography as a Phenotypic Divergence Markers of Residual Feed Intake in Rearing Dairy Heifers.

The objectives of this study were: (1) to identify and rank phenotypically divergent animals for residual feed intake (RFI) regarding their efficiency (high: HE or low: LE); (2) to evaluate their relationships with ingestive behavior, ruminal and blood parameters, performance, and infrared thermography; and (3) to determine if such measurements can be used as feed efficiency markers in rearing dairy heifers. Thirty-eight heifers, 143 d ± 4 (Mean ± SD) of age and 108.7 kg ± 17.9 of body weight were used. The animals were fed with a total mixed ration during the 91 d of the trial. A phenotypic divergence of DMI for RFI was observed between -0.358 and 0.337 kg/d for HE and LE, respectively. Dry matter intake (DMI) was lower in the HE (2.5 kg DMI/d vs. 3.1 kg DMI/d), as was the number of visits to the feed bin with consumption (59 vs. 71). Feed intake was the best predictor of said divergence. Water intake and number of visits to the feed bin were presented moderate correlations with RFI. The ruminal fermentation variables, blood metabolites, blood hormones (such as the other ingestive behavior variables), and infrared thermography were not able to accurately predict HE or LE animals.

[Biological basis of oligoasthenospermia based on the theory of "kidney governing reproduction"].

Guided by the theory of "kidney governing reproduction", ancient and present-day physicians treat male infertility mainly by tonifying the kidneys, with some innovation and development based on inheritance. Relating oligoasthenospermia (OAS), the author emphasizes "the kidney as the base and the essence chamber for use", and proposes "the deficiency of kidney essence and disability of the essence chamber" as the core pathogenesis of the disease. Kidney essence deficiency is the primary cause and essence chamber disability is the main factor for the development and progression of OAS. Disorders in the reproductive microenvironment are also important causes of OAS. Studies on the biological basis of the treatment of OAS from the kidney suggest that kidney tonification has a regulatory effect on the reproductive microenvironment. A systematic investigation into the molecular mechanism of "the deficiency of kidney essence and disability of the essence chamber" in the development and pathogenesis of OAS from the perspective of the reproductive microenvironment may provide some evidence for clinical intervention in the biological basis of OAS based on the theory of "kidney governing reproduction".

Biological Basis for ''Five-phase Evolution'' of Malignant Tumors / 中国实验方剂学杂志

China ranks the first in the morbidity and mortality of malignant tumors in the world. Traditional Chinese medicine （TCM） has played a crucial part in preventing recurrence of malignant tumors after surgery， enhancing efficacy and reducing toxicity of radiotherapy and chemotherapy， and promoting the survival of patients with advanced tumors. According to the whole process of tumor occurrence and development and via the long-term clinical practice， we proposed the "deficiency-cold-toxin-blocking-failure evolution theory" of malignant tumors， with depression in the whole process and cancer toxin as the core. The theory is a summary of pathophysiological status at different stages of tumor development based on the disease and syndrome. This paper analyzes the biological basis of the theory. To be specific， we believe that the ''deficiency'' is mainly caused by the tumor immunoediting abnormality and thus the escape of clearance. In addition， the ''cold'' is in line with the metabolic reprogramming of the tumor microenvironment. ''Toxin'' is manifested as the stemness of cancer cells induced by the tumor microenvironment. ''Blocking'' is closely related to the enhanced permeability and retention （EPR） effect of tumor neovasculature. ''Failure'' is exactly the cachexia caused by change of dominant metabolism. ''Depression'' is essentially stress-the accelerated progress of the neuroendocrine system. In combination with clinical practice， we conclude that method of reinforcing healthy Qi and adjusting the balance can help recover tumor immunoediting and restore the immunity to regulate the "deficiency". Moreover， replenishing Qi and warming Yang can correct the tumor metabolic programming to avoid "cold". Removing toxin and reinforcing healthy Qi can reverse tumor cell stemness and thus suppress the ''toxin''. Eliminating the ''blocking'' source can suppress tumor angiogenesis and help regulate the EPR. Regulating Yin and Yang will help relieve the change of dominant metabolism and futile cycle to avoid ''failure''. The method of relieving depression and regulating Qi can relieve neuroendocrine stress and prevent tumor progression， thus alleviating the "depression". Moreover， effect of these methods was tested with effective formulas. This study is expected to lay a foundation for the establishment of a new system for the clinical prevention and treatment of malignant tumors.

Biological Basis of Invigorating Qi and Activating Blood Cirulation in Regulating Neural Repair After Ischemic Stroke： A Review / 中国实验方剂学杂志

Stroke is the leading cause of death and disability. Therefore， it is critical to develop the approaches for improving recovery and neural repair after stroke. Recovery after stroke involves complex interrelated systems of neural repair. The whole process of neural repair requires a series of coordinated interactions， such as response of neuronal cell body to traumatic stimuli， neural stem cell proliferation and migration， axoplasmic transport of signaling molecules， construction of cytoskeleton， and formation of axonal growth cone， to achieve regeneration and growth. As a potential new target for the treatment of neurologic defects， neural remodeling has important research significance in both the specific mechanism of neural repair and the clinical treatment of neurologic defects. After brain injury， single therapy is often ineffective due to the complex mechanism of internal repair， and thus comprehensive therapy becomes the development direction to improve the brain repair. Invigorating qi and promoting blood can promote nerve function remodeling after injury through neural protection， angiogenesis， neurogenesis， loop reconstruction， and cytokine regulation， playing a key role in nerve repair after stroke. Its mechanism is associated with autophagy， immunomodulation， and microRNA regulation， which fully embodies the multi-pathway， multi-target， and overall regulation characteristics of invigorating Qi and activating blood. Therefore， it is of theoretical and guiding significance to study the brain function rehabilitation after stroke by invigorating qi and activating blood.

Regional radiomics similarity networks (R2SNs) in the human brain: Reproducibility, small-world properties and a biological basis.

A structural covariance network (SCN) has been used successfully in structural magnetic resonance imaging (sMRI) studies. However, most SCNs have been constructed by a unitary marker that is insensitive for discriminating different disease phases. The aim of this study was to devise a novel regional radiomics similarity network (R2SN) that could provide more comprehensive information in morphological network analysis. R2SNs were constructed by computing the Pearson correlations between the radiomics features extracted from any pair of regions for each subject (AAL atlas). We further assessed the small-world property of R2SNs, and we evaluated the reproducibility in different datasets and through test-retest analysis. The relationships between the R2SNs and general intelligence/interregional coexpression of genes were also explored. R2SNs could be replicated in different datasets, regardless of the use of different feature subsets. R2SNs showed high reproducibility in the test-retest analysis (intraclass correlation coefficient > 0.7). In addition, the small-word property (σ > 2) and the high correlation between gene expression (R = 0.29, p < 0.001) and general intelligence were determined for R2SNs. Furthermore, the results have also been repeated in the Brainnetome atlas. R2SNs provide a novel, reliable, and biologically plausible method to understand human morphological covariance based on sMRI.

Independent and reproducible hippocampal radiomic biomarkers for multisite Alzheimer's disease: diagnosis, longitudinal progress and biological basis.

Hippocampal morphological change is one of the main hallmarks of Alzheimer's disease (AD). However, whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment (MCI) to AD dementia and whether these features provide any neurobiological foundation remains unclear. The primary aim of this study was to verify whether hippocampal radiomic features can serve as robust magnetic resonance imaging (MRI) markers for AD. Multivariate classifier-based support vector machine (SVM) analysis provided individual-level predictions for distinguishing AD patients (n = 261) from normal controls (NCs; n = 231) with an accuracy of 88.21% and intersite cross-validation. Further analyses of a large, independent the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 1228) reinforced these findings. In MCI groups, a systemic analysis demonstrated that the identified features were significantly associated with clinical features (e.g., apolipoprotein E (APOE) genotype, polygenic risk scores, cerebrospinal fluid (CSF) Aß, CSF Tau), and longitudinal changes in cognition ability; more importantly, the radiomic features had a consistently altered pattern with changes in the MMSE scores over 5 years of follow-up. These comprehensive results suggest that hippocampal radiomic features can serve as robust biomarkers for clinical application in AD/MCI, and further provide evidence for predicting whether an MCI subject would convert to AD based on the radiomics of the hippocampus. The results of this study are expected to have a substantial impact on the early diagnosis of AD/MCI.

Exploration on Biological Basis Underling Different Syndromes of Nontraumatic Osteonecrosis of Femoral Head Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.

Researches on Diagnostic Criteria,Biological Basis,Evidence Based Medicine for Coronary Heart Disease with Blood Stasis Syndrome / 中国实验方剂学杂志

Coronary heart disease (CHD) has become a major disease that seriously endangers human health. It belongs to the category of " chest obstruction" and " genuine heart pain" in Chinese medicine, and blood stasis syndrome is its core pathogenesis of CHD, which runs through the disease all the time. On the basis of more than 30 years' clinical practice and taking " blood stasis syndrome of CHD" as the research object, the research group has carried out a comprehensive, in-depth and systematic studies on diagnostic criteria, biological basis, and evidence-based evaluation. The quantitative diagnostic criteria of blood stasis syndrome of CHD were established, and the research directions of quantification and objectivity of Chinese medicine syndromes were innovated. The biological basis of blood stasis syndrome of CHD was revealed from macroscopic characterization to organ cell molecular level. When the above research results are applied in the prevention and treatment, the accuracy of diagnosis and the clinical efficacy for CHD has been improved in Chinese medicine.

The Multidimensional Therapeutic Potential of Targeting the Brain Oxytocin System for the Treatment of Substance Use Disorders.

The neuropeptide oxytocin is released both into the blood and within the brain in response to reproductive stimuli, such as birth, suckling and sex, but also in response to social interaction and stressors. Substance use disorders, or addictions, are chronic, relapsing brain disorders and are one of the major causes of global burden of disease. Unfortunately, current treatment options for substance use disorders are extremely limited and a treatment breakthrough is sorely needed. There is mounting preclinical evidence that targeting the brain oxytocin system may provide that breakthrough. Substance use disorders are characterised by a viscous cycle of bingeing and intoxication, followed by withdrawal and negative affect, and finally preoccupation and anticipation that triggers relapse and further consumption. Administration of oxytocin has been shown to have a potential therapeutic benefit at each stage of this addiction cycle for numerous drugs of abuse. This multidimensional therapeutic utility is likely due to oxytocin's interactions with key biological systems that underlie the development and maintenance of addiction. Only a few human trials of oxytocin in addicted populations have been completed with the results thus far being mixed. There are numerous other trials underway, and the results are eagerly awaited. However, the ability to fully harness the potential therapeutic benefit of targeting the brain oxytocin system may depend on the development of molecules that selectively stimulate the oxytocin system, but that have superior pharmacokinetic properties to oxytocin itself.