Stress is a non-specific adaptive response of organisms to internal and external stimuli,which helps maintain the homeostasis of the body's internal environment.However,when the stress response exceeds the body's adaptation threshold,a variety of diseases will be induced.The morbidity and mortality of breast cancer rank the highest among female malignant tumors.Professor LIN Yi,the first master of traditional Chinese medicine(TCM)in the field of breast diseases who founded the theory of'treating breast diseases from the perspective of six stagnations',believes that six stagnations are the core pathogenesis of breast cancer,and six stagnations are closely related to the body's stress response system.TCM has unique advantages in adjusting the balance of stress homeostasis.By reviewing the classical TCM theory,the theory of'treating breast diseases from the perspective of six depressions'and the modern stress theory,this paper put forward the theory of'stress-based breast cancer prevention & treatment',and expounded the pathogenesis features,pathogenic characteristics and molecular mechanism of stress factors in mediating the development and progression of breast cancer.Moreover,the core idea and treatment principle based on the regulation of stress homeostasis were proposed,and the prescription and medication guided by the theory of'stress-based breast cancer prevention & treatment'were summarized.The establishment of the theory of'stress-based breast cancer prevention & treatment'enriches the theoretical system of breast cancer in TCM,and is expected to provide a new approach for improving the clinical prognosis of breast cancer patients.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 μg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 μg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 μg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1β and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.
Animals ; Mice ; Interleukin-6/genetics* ; Cytokines/metabolism* ; Polysaccharides/chemistry* ; RAW 264.7 Cells ; Anti-Inflammatory Agents/chemistry* ; Spectrophotometry, Infrared

OBJECTIVE: To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT). METHODS: Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed. RESULTS: All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle(P>0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group(P<0.01), and the Harris score of the failure group was lower than that of normal group(P<0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826. CONCLUSION The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.
Humans ; Treatment Outcome ; Fracture Fixation, Intramedullary ; Bone Nails ; Retrospective Studies ; Hip Fractures/surgery* ; Fracture Fixation, Internal

Objective: To evaluate the prostate health index (PHI) as a tool for the diagnosis of PCa with a PSA level of 4－10 μg/L and determine the best cut-off value of PHI. METHODS: Fifty-eight patients with a PSA level of 4－10 μg/L underwent transrectal ultrasound-guided prostatic biopsy in our hospital between April 2017 and June 2019. We constructed receiver operating characteristic (ROC) curves for the relationship of the biopsy results with the level of PSA, the ratio of ［－2］ proPSA to fPSA and PHI, and calculated the area under the ROC curves (AUC). RESULTS: Prostatic biopsy revealed 18 cases of PCa in the 58 patients (31.0%). Statistically significant differences were observed between the PCa and non-PCa groups in ［－2］ proPSA, %［－2］ proPSA and PHI, but not in tPSA, % fPSA and PSA-density. The AUCs of PSA, % fPSA, PSA-density, ［－2］ proPSA, %［－2］ proPSA and PHI were 0.556, 0.407, 0.533, 0.746, 0.751 and 0.774, respectively. The specificity of PHI was 27.50% (95% CI: 14.6%－43.9%), the highest among the above predictors at 90% sensitivity. By applying PHI to this cohort, 13 cases (22.4%) of unnecessary biopsy could be avoided. CONCLUSIONS The application of PHI can increase the accuracy of PCa prediction and reduce unnecessary prostatic biopsy.、.
Asians ; Humans ; Macau ; Male ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms/diagnosis*

The research on the pharmacodynamic substance basis of traditional Chinese medicine(TCM) is a key scientific issue for the inheritance and development of TCM. At present, a large number of remarkable achievements have been made in the field of chemical components in Chinese medicine, however, another important aspect, namely the physical structure and mode of action of the multi-component assembly of TCM, has not been clearly understood and deeply studied. From the bottleneck of restricting material ba-sic research, we objectively analyzed the common cause of the existing problems. Based on the new discoveries and advances of active substances from TCM emerging in recent years, we extracted and summarized the concept of structural Chinese medicine, elaborated the basic ideas, main features and research modes, hoping to provide theoretical and practical references for the study on the pharmacodynamic substance basis and other research fields of TCM.
Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.

Objective To understand the distribution characteristics of body fat content and basal metabolic rate among Xibo adults in Xinjiang and to explore the correlation between them. Methods The people aged between 35 and 70 were randomly selected to be the research object, and a total of 536 people (263 males and 273 females) were selected for the study. Subcutaneous fat, visceral fat, weight, stature, defat weight, body fat rate and basal metabolic rate were measured using the body composition analyzer. The correlation between body fat content and basal metabolic rate was studied by regression analysis, and regression equation coefficient was calculated. Results There were statistically significant in total fat, defate body weight and body fat percentage (P<0. 05) of different aged Xibo adults in Xinjiang, except for male visceral fat and female subcutaneous fat. There were statistically significant subcutaneous fat, total fat and body fat percentage(P<0. 05) between the sexes, except for visceral fat. The visceral fat content among Xibo adults in Xinjiang was negatively correlated with basal metabolic rate (P<0. 05). Conclusion Body lipid distribution is differences in different aged and gender among Xibo adults in Xinjiang. There is a negative correlation between visceral fat and basal metabolic rate.