The efficacy of Xiangmei Pills on rats with ulcerative colitis(UC) was investigated by characterizing the spectrum of the active chemical components of Xiangmei Pills. Rapid identification and classification of the main chemical components were performed,and the therapeutic effects of Xiangmei Pills on the proteins and intestinal flora of UC rats were analyzed to explore the mechanism of its action in treating UC. Fifty SD rats were acclimatized to feeding for 3 d and randomly divided into blank group, model group,mesalazine group(0. 4 g·kg~(-1)), low-dose group of Xiangmei Pills(1. 89 g·kg~(-1)), and high-dose group of Xiangmei Pills(5. 67 g·kg~(-1)), with 10 rats in each group. 5% dextrose sodium sulfate(DSS) was given by gavage to induce the male SD rat model with UC,and the corresponding medicinal solution was given by gavage after 10 days, respectively. The therapeutic effect of Xiangmei Pills on rats with UC was evaluated according to body mass, disease activity index(DAI), and hematoxylin-eosin(HE) staining, and the histopathological changes in the colon were observed. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) technique was used to rapidly and accurately identify the main chemical constituents of Xiangmei Pills. Immunohistochemistry was used to detect the expression of aryl hydrocarbon receptor(AhR),interferon-γ(IFN-γ), mucin-2(MUC-2), and cytochrome P450 1A1(CYP1A1) in colon tissue. Interleukin-22(IL-22) expression in colon tissue was detected by immunofluorescence. The 16S r DNA high-throughput sequencing technique was used to study the modulatory effects of Xiangmei Pills on the intestinal flora structure of rats with UC. Pharmacodynamic results showed that compared with that of the blank group, the colon tissue of the model group was congested, and ulcers were visible in the mucosa; compared with that in the model group, the histopathology of the colon of the rats with UC in the groups of Xiangmei Pills were improved, with scattered ulcers and reduced inflammatory cell infiltration. Chemical analysis showed that a total of 45 components were identified by mass spectrometry information, including 15 phenolic acids, 8 coumarins, 15 organic acids, 3 amino acids, 2 flavonoids, and 2 other components. Compared with those in the blank group, the levels of Ah R, CYP1A1, MUC-2, and IL-22 proteins in the colon tissue of rats in the model group were significantly decreased, and the level of IFN-γ protein was significantly increased; the intestinal flora of rats in the model group was disorganized, with a decrease in the abundance of the flora; the relative abundance of Bacteroidetes,unclassified genera of Ascomycetes, Prevotella of the Prevotella family, and Prevotella decreased significantly, and that of Firmicutes decreased, but the difference was not statistically significant. The relative abundance of Bacteroidetes, Bifidobacterium, and Lactobacillus increased significantly. Compared with those of the model group, the levels of Ah R, CYP1A1, MUC-2, and IL-22proteins in the colonic tissue of the groups of Xiangmei Pills were significantly higher, and the levels of IFN-γ proteins were significantly lower. The recovery of the intestinal flora was accelerated, and the diversity of the intestinal flora was significantly increased. The relative abundance of Bacteroidetes was significantly increased, and that of unclassified genera of Ascomycetes,Lactobacillus, Prevotella of the Prevotella family, and Prevotella was significantly increased. The relative abundance of Bacteroidetes and Bifidobacterium was significantly decreased. This study demonstrated that Xiangmei Pills can effectively treat UC, mainly through the phenolic acid and organic acid components to stimulate the intestinal barrier, regulate protein expression and the relative abundance and diversity of intestinal flora, and play a role in the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Male ; Rats ; Gastrointestinal Microbiome/genetics* ; Chromatography, High Pressure Liquid ; Humans ; Mass Spectrometry ; RNA, Ribosomal, 16S/genetics* ; Bacteria/drug effects*

BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.

The expression level of NOD-like receptors(NLRP3)inflammasome is significantly elevated in breast cancer tissues,and a high level of NLRP3 inflammasomes is closely associated with breast cancer metastasis.Activation of NLRP3 inflammasome can induce the release of inflammatory factors into the tumor microenvironment(TME).These inflammatory factors,by signaling to cancer cells,reshape the TME to promote tumor growth and invasion,ultimately facilitating the process of epithelial-mesenchymal transition.This equips cancer cells with the ability to establish distant metastases and increase the formation of metastatic lesions.This review addresses the current research status and prospects of NLRP3 inflammasomes in the breast cancer TME and their role in breast cancer metastasis.The goal is to provide new insights for the study of breast cancer metastasis mechanisms and treatment strategies.

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated. The results showed that after oral administration of different doses of Zhachong Shisanwei Pills, the in vivo exposure of AG, VA, and GA was relatively high, with AUC_(0-∞) values ranging from 604.0-2 494.2, 1 305.4-4 634.5, and 2 177.5-4 045.7 h·ng·mL~(-1), respectively, while the exposure of CO, PI, and GL was relatively low, with AUC_(0-∞) values ranging from 37.8-238.2, 2.4-17.0, and 146.9-408.5 h·ng·mL~(-1), respectively. The C_(max) and AUC_(0-∞) of the six compounds were positively correlated with the administered dose. The T_(max) of PI and AG ranged from 0.3 to 2.0 h, their T_(1/2) ranged from 0.8 to 2.9 h, and their mean residence time(MRT) ranged from 1.0 to 3.7 h. The T_(max) of GL and VA was shorter(0.4-1.9 h), while their T_(1/2)(2.6-5.9 h) and MRT(2.5-8.5 h) were longer. Both CO and GA exhibited a bimodal phenomenon, with T_(max) ranging from 1.6 to 6.6 h, T_(1/2) ranging from 2.8 to 7.7 h, and MRT ranging from 4.1 to 12.9 h. Liver histopathology after 28 days of continuous multiple-dose administration of Zhachong Shisanwei Pills showed that the liver tissue remained normal at a low dose(crude drug 0.8 g·kg~(-1), approximately 5 times the clinical equivalent dose). However, as the dose increased(crude drug 1.1-3.0 g·kg~(-1), 6.9-18.8 times the clinical equivalent dose), varying degrees of liver damage were observed. Blood biochemical tests revealed no significant changes in the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid(TBA) in CCI rats from administration groups 1 to 3(crude drug 0.8, 1.1, 1.5 g·kg~(-1)). However, ALT, AST, ALP, and TBA levels in groups 4 and 5(crude drug 2.1, 3.0 g·kg~(-1)) showed significant increases. This study preliminarily elucidated the toxicokinetic characteristics of the six compounds in Zhachong Shisanwei Pills and their effects on liver tissue in CCI rats, providing data as a reference for clinical use.
Animals ; Tandem Mass Spectrometry/methods* ; Rats ; Drugs, Chinese Herbal/toxicity* ; Male ; Rats, Sprague-Dawley ; Brain Ischemia/blood* ; Chromatography, Liquid/methods* ; Polyunsaturated Alkamides/blood* ; Piperidines/toxicity* ; Benzodioxoles/toxicity* ; Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.
Humans ; Male ; Adolescent ; Adult ; Female ; Protein Kinase Inhibitors/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Treatment Outcome ; Retrospective Studies ; Dasatinib/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Thrombocytopenia

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.
Humans ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B/drug therapy* ; Hepatitis B virus ; Antiviral Agents/therapeutic use* ; Gastroenterology

【Objective】   As the main active ingredient of Tibetan medicine Hongjingtian (Rhodiolae Crenulatae Radix et Rhizoma), salidroside (Sal) has a good anti-apoptotic potential. Currently, there are some conflicting results on the anti-apoptotic mechanisms of Sal. Here we conducted a systematic review and meta-analysis to provide the preclinical evidence of its anti-apoptotic properties in preventing and treating hypoxic-ischemic cerebral damage(HICD). 【Methods】   The literature on the anti-apoptotic potential of Sal in the treatment of HICD from January 1, 1980 to November 9, 2021 was searched online using Chinese databases including Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database, and English databases including PubMed and Web of Science. The quality of the included articles was evaluated by the Cochrane Collaboration network bias risk assessment criteria, and meta-analysis was performed using RevMan 5.3 software. 【Results】  A total of 40 articles were finally included. Among the 40 articles, 30 were about in vivo animal experiments and 17 about in vitro cell experiments, and 7 of them included both animal and cell experiments. After analysis, it was found that Sal had significant effects on disease-related indicators of HICD (P < 0.05), such as cerebral infarctsize and brain water content. As to in vivo studies, Sal mainly affects the expressions of apoptotic factors through antiinflammation, anti-oxidation, activation of complement pathway, and regulation of signal transduction and autophagy, thus exerting anti-apoptotic potential in treating HICD. While for in vitro studies, Sal plays the anti-apoptotic role in HICD models mainly through anti-oxidation, anti-inflammation, reduction of Ca2+ overload, regulation of mitochondrial function, signal transduction, and C3 complement. 【Conclusion】  Sal can take anti-apoptotic effects to prevent and treat HICD through mechanisms such as anti-inflammation, anti-oxidation, enhanced autophagy, complement and signal transduction, regulation of mitochondrial membrane potential, and reduction of Ca2 + overload.

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe.We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.
Female ; Humans ; Cancer-Associated Fibroblasts/pathology* ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/pathology* ; Prognosis ; STAT3 Transcription Factor/metabolism* ; Drug Resistance, Neoplasm