Based on the theory of toxin in The Inner Canon of Yellow Emperor （《黄帝内经》）， this paper explores the concept and connotation of toxin from several aspects， including medicinal toxicity， pathogenic toxicity， pathoge-nesis and treatment of toxin pathogen. It explores the mechanism and significance of using toxin substances in curing and inducing diseases， sorts out the etiological and pathological evolution of toxic pathogens， clarifies the derivation and differentiation process from external toxins to internal toxins， and elucidates the interactions between toxin and other pathogenic factors such as phlegm， stasis， dampness， and fire. It further distinguishes the logical hierarchy of toxin caused by metabolic disorders such as sugar， fat， and drowning， clarifies that the essence of the etiology of "hidden toxin"， and determines the corresponding treatment principles and methods for toxic pathogens. It establishes a theoretical framework of traditional Chinese medicine toxic pathogen theory， providing theoretical basis for the clinical treatment of many diseases.

Objective To develop predictive models based on decision tree and logistic regression algo-rithms for pulmonary multidrug-resistant organism(MDRO)infection risk in intensive care unit(ICU)pa-tients,and compare their predictive performance to provide references for pulmonary MDRO infection preven-tion.Methods A total of 350 ICU patients admitted to the hospital from January 2021 to December 2023 were enrolled and divided into an infection group(n=52)and a non-infection group(n=298)based on the pres-ence of pulmonary MDRO infection.Clinical data from both groups were collected and analyzed to identify risk factors for pulmonary MDRO infection in ICU patients.Using the risk of pulmonary MDRO infection in ICU patients as the dependent variable and the indicators with statistically significant differences in univariate anal-ysis as the independent variables,predictive models for pulmonary MDRO infection risk were developed by u-sing decision tree algorithms and logistic regression analysis.The predictive performance of these two models was compared.Results There were statistically significant differences(P＜0.05)between the infection and non-infection groups in terms of age,history of diabetes,hospital stay≥2 weeks,indwelling urinary catheter,chlorine dioxide disinfection,prolonged bedridden status,and disturbance of consciousness.Logistic regression analysis with pulmonary MDRO infection risk in ICU patients as the dependent variable showed that age ≥60 years,indwelling catheter,hypoproteinemia,and disturbance of consciousness were risk factors for pulmonary MDRO infection in ICU patients,while chlorine dioxide disinfection was a protective factor.Based on these risk factors and regression coefficients,the original warning model was established as:logit(P 1)=0.856 × age+0.928 × indwelling catheter+0.916 × chlorine dioxide disinfection+0.866× hypoproteinemia+0.986 × disturbance of consciousness-4.371.The Hosmer-Lemeshow test indicated good model fit(coefficient of de-termination R2=0.579,P=0.531).The decision tree model for pulmonary MDRO infection risk in ICU pa-tients constructed using decision tree algorithm comprised 4 layers and 9 nodes,selecting four clinical features as nodes:presence of consciousness disturbance,indwelling catheter,hypoproteinemia,and age≥60 years,with consciousness disturbance being the most significant predictor.The decision tree model showed an area under the curve(AUC)of 0.892(95％CI:0.835-0.949)on receiver operating characteristic(ROC)analy-sis,compared to 0.862(95％CI:0.812-0.912)for the logistic regression model.Delong test revealed no sig-nificant difference in predictive performance between the two models(Z=1.148,P=0.095).Conclusion Both the decision tree model and logistic regression model established for predicting the risk of pulmonary MDRO infection in ICU patients demonstrate high predictive performance with comparable efficacy.

Objective·To analyze infertility couples,dyadic coping level by using latent profile analysis(LPA),and explore the heterogeneity and related factors of different profiles.Methods·From September to November 2023,257 newly diagnosed infertility couples in pre-infertility treatment with assisted reproductive technology(ART)were recruited from Reproductive Medicine Center,Renji Hospital,Shanghai Jiao Tong University School of Medicine.All couples were evaluated by using general information questionnaire,Fertility Problem Inventory(FPI),Dyadic Coping Inventory(DCI),and Fertility Quality of Life(FertiQoL)Tool.LPA was used to explore the dyadic coping profiles of the couples before ART treatment,and general information,FPI scores and FertiQoL scores were compared among the profiles.Multinomial Logistic regression analysis was used to explore the related factors of different profiles.Results·A total of 257 couples with infertility were included,with an average age of(30.15±3.07)years for females,(31.82±3.82)years for males,(3.75±2.16)years for marriage,and(2.90±1.92)years for infertility;there were 118 couples caused by male infertility,109 couples caused by female infertility,and 30 couples caused by both infertility;the average DCI score for males was(128.25±19.15)points,while for females it was(129.91±18.32)points.According to the dyadic coping levels,the infertile couples were divided into four profiles:common positive coping group(153 couples,59.5％),common negative coping group(85 couples,33.1％),male positive coping group(12 couples,4.7％),and male negative coping group(7 couples,2.7％).There were statistically significant differences in the infertile couples'age,FPI score,FertiQoL score,and remarriage rate among the four profiles(P＜0.05).Multinomial Logistic regression analysis results showed that,with the common positive coping group as the reference,the common negative coping group had older men(OR=1.122,95％CI 1.004-1.254,P=0.036),higher FPI scores for both males and females(male:OR=1.019,95％CI 1.003-1.035,P=0.018;female:OR=1.020,95％CI 1.004-1.036,P=0.015),and lower FertiQol scores for males(OR=0.966,95％CI 0.937-0.996,P=0.029).Conclusion·There are four types of dyadic coping profiles in infertile couples before ART treatment.Compared with the common positive coping couples,higher reproductive pressure,elder age,and lower perceived fertility quality of life of males,and higher reproductive pressure of females are all risk factors for common negative coping couples.

Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0～40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P＜0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P＜0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P＜0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.

Objective:To study the effects of Shengui Jiajian Pills on myocardial fibrosis and the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in elderly rats with hypothyroidism; To preliminarily explore the mechanism of Shengui Jiajian Pills in treating hypothyroid heart disease through the TGF-β1/Smads pathway.Methods:Totally 60 SD rats were randomly divided into normal group, model group, sodium levothyroxine group, and Shengui Jiajian Pills low-, medium-, and high-dosage groups, with 10 rats in each group. A model of elderly hypothyroid heart injury in rats was prepared by freely drinking 0.1% propylthiouracil (PTU) for 10 weeks. Each group of rats was gavaged with the corresponding drug once a day for 6 weeks. After the last gastric lavage, an electrocardiogram was performed, hematoxylin-eosin staining (HE) was used to observe pathological changes in the heart tissue; bitter acid-toluidine blue staining was used to detect fibrosis of the heart tissue; TUNEL staining was used to observe myocardial cell apoptosis; Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) in the serum, as well as brain natriuretic peptide (BNP), creatine kinase isoenzymes MB (CK-MB), and lactate dehydrogenase (LDH); Western blot was used to detect the relative expressions of TGF-β1, p-Smad2, p-Smad3, α-smooth muscle actin (α-SMA), matrix metalloproteinase-1 (MMP-1), TIMP1, Bax, and Caspase-3 in the heart tissue; and immunofluorescence was used to detect the positive expressions of TGF-β1, Smad3, α-SMA, and MMP-1 in the heart tissue.Results:Compared with the model group, the inflammatory cell infiltration and cell damage in the heart of rats in each dosage group of Shengui Jiajian Pills were improved, the myocardial fibrosis area ratio was significantly reduced ( P<0.05), and the myocardial cell apoptosis rate significantly decreased ( P<0.05), the levels of TSH, BNP, CLD, and HK-MB in serum significantly decreased ( P<0.05). The levels of FT3 and FT4 increased in the Shengui Jiajian Pills medium- and high-dosage groups ( P<0.05), while the positive expressions of TGF-β1, Smad3, α-SMA, and MMP-1 decreased ( P<0.05). The protein expression of TGF-β1, p-Smad3, MMP-1, Bax, and Caspase-3 decreased ( P<0.05), and the expression of TIMP-1 increased ( P<0.05). The expression of Smad7 increased in the Shengui Jiajian Pills medium-dosage group ( P<0.05). Conclusion:Shengui Jiajian Pills may reduce myocardial collagen fiber deposition by modulating the TGF-β1/Smad3 signaling pathway, thereby partially reversing the pathological features of hypothyroidism-induced myocardial injury, with more pronounced effects observed in the medium and high dosage groups.

Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.

Adrenal Glands ; Humans ; Hyperaldosteronism ; Retrospective Studies ; Singapore

Objective:To determine any effect of repeated thermal stimulation on the viability and functioning of inflamed human umbilical vein endothelial cells (HUVECs).Methods:Well-cultured HUVECs were divided into a normal group, a model group, a thermal stimulation 5 times group (group A), a thermal stimulation 9 times group (group B) and a thermal stimulation 13 times group (group C) and cultured under the same conditions. The normal group was not given any intervention. The model group was stimulated with 1μg/mL lipopolysaccharide for 1 hour. Groups A, B and C were first subjected to 5, 9 and 13 rounds of repeated thermal stimulation, each round lasting 4 minutes at 43℃ and 1 minute at room temperature. They were then incubated for one hour at 37℃ under a 5% CO 2 atmosphere with 1μg/mL lipopolysaccharide. Cell viability and the expression of NF-κB were evaluated using methyl thiazolyl tetrazolium and immunofluorescence assays. The levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined by enzyme-linked immunosorbent assay. Results:After the intervention, the average cell viability of the model group and of groups A and C was significantly lower than that of the normal group, while that of group B was significantly higher. After the intervention, the average NF-κB expression in the normal group was significantly different from that in the others, with group B′s level significantly different from that of the model group. After the treatment, the average expression of ICAM-1 and VCAM-1 in the model group had increased significantly, while that in groups A, B and C had decreased significantly compared with the normal group. The levels of groups A, B and C were then significantly different from that of the model group. The average ICAM-1 level of group B was significantly different from those of groups A and C.Conclusions:Repeated thermal stimulation can protect inflamed HUVECs and reduce the expression of HUVEC adhesion molecules.

OBJECTIVE: To investigate the pattern of shikonin-induced cell death in testicular cancer cell I-10 and seminoma TCAM-2 cells and explore the possible mechanism in light of mitochondrial function and glycolysis. METHODS: I-10 cells treated with 0, 1.2, 1.4 and 1.6 μmol/L shikonin and TCAM-2 cells treated with 0, 0.5, 1 and 1.5 μmol/L shikonin were examined for mitochondrial membrane potential and production of reactive oxygen species (ROS) using JC-1 kit and ROS kit, respectively. The levels of intracellular lactic acid in the cells were detected using a lactic acid kit. The inhibitory effect of shikonin on the proliferation of the cells was assessed with MTT assay. The death patterns of the cells were observed by transmission electron microscopy, and annexin V-FITC/PI double staining was used to detect cell apoptosis. Western blotting was used to detect the relative expression levels of the apoptotic proteins Bax, Bcl-2, and cleaved caspase-3, the autophagy- related protein LC3B and glycolysis- related proteins PKM2, GLUT1 and HK2. RESULTS: MTT assay showed that shikonin significantly inhibited the proliferation of I-10 and TCAM-2 cells in a time- and dose-dependent manner ( < 0.05). The IC values of shikonin in I-10 cells at 24, 48, and 72 h were 1.8, 1.36 and 1.16 μmol/L, as compared with 2.37, 0.8 and 0.41 μmol/L in TCAM-2 cells, respectively. Shikonin treatment significantly reduced mitochondrial membrane potential, increased ROS levels and lower the level of lactic acid in both I-10 and TCAM-2 cells ( < 0.05). Transmission electron microscopy and annexin V-FITC/PI double staining demonstrated that shikonin induced apoptosis and excessive autophagy in I-10 and TCAM-2 cells ( < 0.05). In both I-10 and TCAM cells, shikonin treatment significantly down- regulated the expressions of Bax, Bcl-2, cleaved caspase-3, PKM2, GLUT1 and HK2, and up-regulated the expression of autophagy-related protein LC3B ( < 0.05). CONCLUSIONS Shikonin can inhibit the proliferation, induce apoptosis and increase autophagy in both I-10 and TCAM-2 cells probably by affecting energy metabolism of the cells.

Objective:To explore the possible related factors of Beh?et's disease complicated with tendinitis, in order to better understand the etiology and development mechanism so to guide clinical diagnosis and treatment.Methods:The clinical data of patients with Beh?et's disease complicated with tendonitis treated at Department of Rheumatology and Immunology of Lanzhou University Second Hospital from October 2018 to September 2019 were retrospectively reviewed and related literature were reviewed.Results:Two patients were diagnosed as Beh?et's disease. Foot pain occurred during the treatment. Ultrasound showed tendonitis, and the corresponding treatment relieved the symptoms.Conclusion:Tendons may be involved and presents as a chronic change in patients with Beh?et's disease. In patients with rheumatic diseases, attention should be paid to the correlation between the disease and tendonitis. Aggressive treatment can prevent adverse consequences.