Quality markers of Dajianzhong decoction based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.

[Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway].

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.

Multiple stimulus-response berberine plus baicalin micelles with particle size-charge-release triple variable properties for breast cancer therapy.

OBJECTIVE: The aim was to develop a nanoscale drug delivery system with enzyme responsive and acid sensitive particle size and intelligent degradation aiming to research the inhibitory effect on breast cancer. SIGNIFICANCE: The delivery system addressed the problems of tissue targeting, cellular internalization, and slow drug release at the target site, which could improve the efficiency of drug delivery and provide a feasible therapeutic approach for breast cancer. METHODS: The acid sensitive functional material DSPE-PEG2000-dyn-PEG-R9 was synthesized by Michael addition reaction. Then, the berberine plus baicalin intelligent micelles were prepared by thin-film hydration. Subsequently, we characterized the physical and chemical properties of berberine plus baicalin intelligent micelles, evaluated its anti-tumor effects in vivo and in vitro. RESULTS: The target molecule was successfully synthesized, and the intelligent micelles showed excellent chemical and physical properties, delayed drug release and high encapsulation efficiency. In vitro and in vivo experiments also confirmed that the intelligent micelles could effectively target tumor sites, penetrate tumor tissues, enrich in tumor cells, inhibit tumor cell proliferation, inhibit tumor cell invasion and migration, and induce tumor cell apoptosis. CONCLUSION: Berberine plus baicalin intelligent micelles have excellent anti-tumor effects and no toxicity to normal tissues, which provides a new potential drug delivery strategy for the treatment of breast cancer.

Functional vinorelbine plus schisandrin B liposomes destroying tumor metastasis in treatment of gastric cancer.

Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy, accompanied by a high rate of metastasis and recurrence. In this paper, R8 (RRRRRRRR) modified vinorelbine plus schisandrin B liposomes had been successfully constructed for treating gastric cancer. In the liposomes, R8 was used to enhance the intracellular uptake, schisandrin B was incorporated into liposomes for inhibiting tumor cells metastasis, and vinorelbine was encapsulated into liposomes as antitumor drugs. Studies were performed on BGC-823 cells in vitro and were verified in the BGC-823 cell xenografts nude mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce BGC-823 cells apoptosis, inhibit the metastasis of tumor cells, and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate VEGF, VE-Cad, HIF-1a, PI3K, MMP-2, and FAK to inhibit tumor metastasis. In vivo results exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and induce tumor cell apoptosis. Hence, R8 modified vinorelbine plus schisandrin B liposomes might provide a safe and efficient therapy strategy for gastric cancer.

Assessment of the Clinical Usefulness of Preoperative Computed Tomography in Colorectal Cancer Patients Who Received Unplanned Reoperation.

BACKGROUND: In the unplanned reoperation of colorectal cancer patients, computed tomography (CT) is increasingly utilized to locate postoperative complications and previously unlocalized lesions. The purpose of this study is to explore the application of CT in the mortality and complications of the reoperation of colorectal cancer. Patients and Methods. We performed a retrospective review of collected data from the colorectal surgeries of 90 identified colorectal cancer patients who received an unplanned reoperation from 2010 to 2018. Patients were stratified according to those with preoperative CT imaging (CT group, n = 36) and those without preoperative CT imaging (NCT group, n = 54). Twenty-four statistical indicators of each patient were studied, including their preoperative risk, surgical characteristics, and postoperative outcomes, and satisfaction was evaluated. All data were statistically analysed for predicting postoperative complications by univariate and multivariate logistic regression analyses. RESULTS: Ninety patients received an unplanned reoperation in the study, and 40% (36/90) of these patients underwent preoperative CT examination. Patients' risk factors were similar between CT and NCT groups. Preoperative imaging was more commonly performed for reoperative new anastomosis + ileostomy but less common for reoperative Dixon's procedure. The operative duration of the NCT group was longer (139 vs. 104 min, respectively, P = 0.01). Preoperative NCT examination (OR 1.24; 95% CI = 1.09-1.42; P = 0.01) was an independent predictor of postoperative complications. Importantly, three patients died after an unplanned reoperation for colorectal cancer, which occurred only in the NCT group (5.6% vs. 0.0%, P = 0.01). CONCLUSION: The use of conventional preoperative CT optimizes the choice of the surgical site and the strategy of laparotomy, so as to reduce the length of operation. Preoperative imaging evaluation should be performed for patients undergoing repeat abdominal surgery.

CT of ovarian cancer: 3D cinematic rendering for preoperative evaluation.

BACKGROUND: Ovarian cancer is the second most common gynecologic malignancy. As the primary imaging modality, computed tomography (CT) can provide staging information for preoperative planning and determination of surgical resectability. As a new three-dimensional postprocessing tool for CT images, cinematic rendering (CR) has the potential to depict anatomic details accurately. CASE PRESENTATION: (Case 1) A 44-year-old married woman was diagnosed with recurrent ovarian cancer. CT images indicated the recurrent nodules and masses in the pelvic cavity and the upper middle abdominal peritoneum. The CR image showed that the multiple metastatic lesions and lymph nodes could not be completely removed by reoperation. The patient agreed to receive continued chemotherapy. (Case 2) A 51-year-old woman was admitted to our hospital due to abdominal distension and defecation that had increased for 6 months, with aggravation over the past 3 days. CT examination found cystic and solid masses in the bilateral ovarian area. The CR image demonstrated that the ovarian mass violated the posterior wall of the bladder and the anterior rectal wall. The preoperational imaging evaluation ensured the safety of the operation. CONCLUSION: CR could improve the visualization of ovarian cancer masses, metastatic lymph nodes, and peritoneal metastases. CR has a good clinical value and will be more helpful in the preoperational evaluation of ovarian cancer.

Recurrent Thymoma in the Retroperitoneal Space: A Rare Case Report.

Thymoma is an epithelial neoplasm of the thymus, which commonly lies in the anterior mediastinum and recurrences of thymoma generally are locally, and retroperitoneal recurrence is considered to be rare. A 46-year old Asian woman with invasive thymoma had undergone thymectomy 10 years ago. Computed tomography demonstrated a well-circumscribed mass in the left retroperitoneal space. The patient had not any symptom including myasthenia gravis. Because on the anterior mediastinum area shows no sign of tumor recurrence and the mass adjacent to the vertebral body, neurogenic tumor was suspected. Surgical resection was performed using a retroperitoneal approach, which revealed the tumor adhering neighboring diaphragm. The tumor was histologically diagnosed to be type B1 thymoma according to the World Health Organization classification. The retroperitoneal mass was an unusual local recurrence after thymectomy. The patients whose had under invasive thymectomy should be evaluated carefully when finding retroperitoneal mass during follow-up.