[Toxicity mechanism of Rhododendri Mollis Flos: based on serum metabolomics and network toxicology].

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor ß(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.

[Effects of different transfusion on intraoperative blood loss and postoperative drainage volume in posterior lumbar spinal surgery].

OBJECTIVE: To explore the effects of autotransfusion on intraoperative blood loss and postoperative drainage volume in posterior lumbar spinal surgery. METHODS: From June 2010 to January 2012, a total of 183 patients with lumbar disease were enrolled. There were 74 males and 109 females with an average age of 56.6 (31-81) years. There were lumbar disc herniation (n = 80), lumbar stenosis (n = 69), lumbar spondylolisthesis (n = 32) and discogenic pain (n = 2). And one-level (n = 83) and two-level (n = 100) operations were performed. The treatments were non-transfusion (n = 34), auto-blood (n = 109) and allogeneic blood (n = 20) and both (n = 20).Operative duration, operative level, intraoperative autologous blood transfusion, intraoperative allogeneic blood transfusion, intraoperative blood loss, immediate drainage volume, duration of drainage tube and final drainage volume were recorded. RESULTS: The mean intraoperative blood loss was (369.4 ± 284.0) ml and (568.8 ± 398.7) ml for two-level operation, there were significant differences between them(t = 3.94, P < 0.001). The final drainage volume was (186.3 ± 135.6) ml for one-level patients and (301.4 ± 286.8) ml for two-level patients, there were significant differences between them (t = 3.56, P < 0.05). The total intraoperative blood loss was (478.3 ± 364.3) ml and total final drainage volume was (249.2 ± 237.4) ml, there were significant differences between them(P < 0.001). There were significant differences in blood loss between autologous blood transfusion for non-transfusion groups (P < 0.001) .However, there was no difference for immediate drainage and final drainage comparing with other blood transfusion methods (P > 0.05) . CONCLUSION: Using autologous blood transfusion alone during operation has significant difference for inoperative blood loss compared with non-transfusion. Yet there is no effect on immediate or final drainage volume.

Kinesitherapy for Knee Osteoarthritis Patients Physical and Psychological Health Based on "Traditional Chinese Exercise" Management Modalities: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Traditional Chinese exercise ("TCE" management modalities), including but not limited to Tai Chi, Baduanjin, and Yijinjing, has a good effect on improving the physical function of patients with knee osteoarthritis, but less attention has been paid to the impact on the psychological health of patients, and currently there is insufficient evidence to support it. We conducted this study to provide a systematic synthesis of best evidence regarding the physical and mental health of patients with knee osteoarthritis treated by traditional Chinese exercise. Literature on the effectiveness of traditional Chinese exercise (Tai Chi, Baduanjin, Yijinjing, Qigong, etc.) versus conventional therapy (muscle-strength training of the lower extremity and aerobic training, wellness education, quadriceps strengthening exercises, etc.) on Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), Short Form-36 (SF-36), Timed Up and Go Test (TUG), and Berg Balance Scale (BBS) in knee osteoarthritis (KOA) from Pubmed, Web of Science, Ovid Technologies, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database, and SinoMed were collected from their inception to April 2022. Thirty-three studies with 2621 cases were included in this study. The study's results indicated that compared with conventional therapy, traditional Chinese exercise had more advantages on patients' WOMAC score, significantly reducing patients' overall WOMAC score (SMD = -0.99; 95% CI: -1.38, -0.60; p < 0.00001) and relieving pain (SMD = -0.76; 95% CI: -1.11, -0.40; p < 0.0001) in patients with KOA. It also has advantages over conventional therapy in improving mental component score (MCS) (SMD = 0.32; 95% CI: -0.00, 0.65; p = 0.05) and physical component score (PCS) (SMD = 0.34; 95% CI: 0.05, 0.62; p = 0.02). Compared with conventional therapy, traditional Chinese exercise can significantly reduce the effect on timed up and go test (TUG) score (SMD = -0.30; 95% CI: -0.50, -0.11; p = 0.002), beck depression inventory (DBI) score (SMD = -0.62; 95% CI: -1.03, -0.22; p = 0.002), and increase the impact on Berg Balance Scale (BBS) score (SMD = 0.60; 95% CI: 0.37, 0.83; p < 0.00001). The findings of this study indicated that traditional Chinese exercise improved body function and mental health in patients with knee osteoarthritis significantly. More high-quality clinical evidence-based data was needed to confirm the therapeutic effect of traditional Chinese exercise on the physical and mental health in KOA patients.

Tislelizumab with gemcitabine and cisplatin as a neoadjuvant regimen for muscle-invasive bladder cancer: case series.

Introduction and importance: The feasibility of combined tislelizumab with gemcitabine and cisplatin as a neoadjuvant regimen for muscle-invasive bladder cancer (MIBC) remains to be investigated. Case presentation: The neoadjuvant treatment not only shrunk tumours significantly but also lowered their stages from T4bN1M0, T3N0M0, and T3bN0M0 to pT1, pT0 and pTis, respectively. The treatment suppressed tumour cell proliferation and promoted luminal-to-basal transition. Clinical discussion: MIBC is an aggressive bladder cancer with poor prognosis. All three patients with MIBC benefited greatly from the neoadjuvant regimen (tislelizumab + gemcitabine + cisplatin). It appears that the effect of the treatment is independent of the levels of programmed death-ligand 1 nor the subtype of urothelial bladder cancer. Conclusion: Combination of tislelizumab with gemcitabine and cisplatin appeared to be a safe and efficacious neoadjuvant therapy for MIBC.

Exploring the pharmacological mechanisms of the flower of Rhododendron molle in rheumatoid arthritis rats based on metabolomics integrated network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, the flower of Rhododendron molle G. Don (RMF) is record in the Chinese pharmacopoeia, and is commonly utilized for treating rheumatoid arthritis (RA) in clinical practice. However, its precise mechanisms necessitate further exploration. AIM OF THE STUDY: To expound the effective components, targets, metabolites, and pathways participated in RMF's anti-RA effects by metabolomics integrated network pharmacology. MATERIALS AND METHODS: CIA rats were intragastric administered RMF for 2 weeks, following which the therapeutic effects were comprehensively evaluated. Serum metabolomics was adopted to investigate the differential metabolites (DEMs). UHPLC-Q-Exactive-MS method was applied to identify the components of RMF, and then network pharmacology was utilize to select the component-RA-targets. Molecular docking and Western blotting were utilized to validate the key targets. RESULTS: RA symptoms were alleviated by RMF through the inhibition secretion of pro-inflammatory factors IL-1ß, IL-6 and TNF-α, along with relief in bone destruction observed in CIA rats. Four targets, namely AKR1B1, TPH1, CYP1A1, and CYP1A2, were identified, along with their corresponding metabolites, namely D-glucose, D-mannose, L-tryptophan, 11-deoxycorticosterone, and 17α-hydroxyprogesterone. These were found to be involved in three key metabolic pathways: steroid hormone biosynthesis, tryptophan metabolism, and galactose metabolism. Additionally, five significant anti-RA active components were identified from RMF, including Rhodojaponin (Rj)-Ⅱ, Rj-Ⅲ, Rj-Ⅴ, Rj-Ⅵ, and quercetin. CONCLUSIONS: The anti-RA mechanisms of RMF were investigated in this study, focusing on active components, upstream targets, and downstream metabolites. These findings lay a foundation for the clinical practice and drug development of RMF.

Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model.

Bone microstructure refers to the arrangement and quality of bone tissue at the microscopic level. Understanding the bone microstructure of the skeleton is crucial for gaining insight into the pathophysiology of osteoporosis and improving its treatment. However, handling bone samples can be complex due to their hard and dense properties. Secondly, specialized software makes image processing and analysis difficult. In this protocol, we present a cost-effective and easy-to-use solution for trabecular bone microstructure analysis. Detailed steps and precautions are provided. Micro-CT is a non-destructive three-dimensional (3D) imaging technique that provides high-resolution images of trabecular bone structure. It allows for the objective and quantitative evaluation of bone quality, which is why it is widely regarded as the gold standard method for bone quality assessment. However, histomorphometry remains indispensable as it offers crucial cellular-level parameters, bridging the gap between two-dimensional (2D) and 3D assessments of bone specimens. As for the histologic techniques, we chose to decalcify the bone tissue and then perform traditional paraffin embedding. In summary, combining these two methods can provide more comprehensive and accurate information on bone microstructure.

The fibrinogen-albumin ratio as a novel prognostic factor for elderly patients with osteosarcoma.

To analyze the prognostic value of fibrinogen-albumin ratio (FAR) in predicting the overall survival in elderly osteosarcoma patients. One hundred nineteen elderly osteosarcoma patients (> 40 years old) from 2 centers were retrospectively reviewed and analyzed. The cutoff values of the biomarker were calculated via receiver operating characteristic curves, and the cohort was divided into high FAR group and low FAR group. The association between the FAR and clinical-pathological parameters was analyzed. And the prognosis of elderly osteosarcoma patients and the potential risk factors were analyzed using Kaplan-Meier method and Cox proportional hazards model. Finally, a clinical nomogram was constructed, and its predictive capacity was verified. According to receiver operating characteristic results, the cutoff value for FAR was 0.098, and the enrolled patients were divided into the low FAR group and high FAR group. The FAR was significantly correlated with several clinical-pathological characteristics, including age, tumor size, tumor stage, recurrence, and metastasis. Moreover, the multivariate Cox analyses results showed that the FAR, pathological fracture, and metastasis were independent risk factors for overall survival in elderly osteosarcoma patients. The predictive nomogram was subsequently constructed, representing satisfactory predictive performance for prognosis in elderly patients with osteosarcoma. The FAR value is a promising indicator for elderly osteosarcoma patients, which is correlated with the various clinical characteristics and prognosis. A clinical nomogram integrating FAR and other clinical indicators is a convenient and available tool to assess the prognosis and manage the individualized and precise treatment of elderly patients with osteosarcoma.

Percutaneous transforaminal endoscopic decompression combined with percutaneous vertebroplasty in treatment of lumbar vertebral body metastases: A case report.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PTED) is a procedure that is commonly used to treat lumbar disc herniation and spinal stenosis. Despite its less invasiveness, this surgery is rarely used to treat spinal metastases. Percutaneous vertebroplasty (PVP) has been utilized to treat lumbar vertebral body metastases but it has not proven useful in treating sciatic patients. CASE SUMMARY: A 68-year-old woman presented with low back pain and radicular symptoms. She couldn't straighten her legs because of severe pain. Computed tomography (CT) showed a mass lesion in the lung and bone destruction in the L4 vertebrae. The biopsy of the lung lesion revealed adenocarcinoma and the biopsy for L4 vertebrae revealed metastatic adenocarcinoma. PTED paired with PVP was performed on the patient due to the patient's poor overall physical state and short survival time. Transcatheter arterial embolization of vertebral tumors was performed before surgical resection to reduce excessive blood loss during the operation. The incision was scaled up with the TESSY technology. The pain was obviously relieved following the operation and no serious complications occurred. Postoperative CT showed that the decompression around the nerve root was successful, polymethyl methacrylate filling was satisfactory and the tumor tissue around the nerve root was obviously removed. During the 1-year follow-up period, the patient was in a stable condition. CONCLUSION: PTED in combination with PVP is an effective and safe treatment for Lumbar single-level Spinal Column metastases with radicular symptoms. Because of the small sample size and short follow-up time, the long-term clinical efficacy of this method needs to be further confirmed.

Epidural steroids following percutaneous endoscopic interlaminar discectomy: A protocol for systematic review and meta-analysis.

BACKGROUND: Percutaneous endoscopic interlaminar discectomy (PEID) has been widely used in the treatment of lumbar disc herniation and spinal stenosis, epidural steroids following PEID in an effort to reduce the incidence and duration of postoperative pain. Although steroids are widely thought to reduce the effect of surgical trauma, the observation index is not uniform, so the issue is still controversial. Therefore, the purpose of this paper is to systematically evaluate the efficacy and safety of local epidural steroids application following PEID. METHODS: We will search the following databases from their inception to August 2020, PubMed, Embase, Medline, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Web of Science, Wan Fang Database, Cochrane Library. The search strategy includes the MeSH terms. Meta-analysis will be performed using Rev Man V.5.3.5 statistical software. RESULTS: This study will provide a high-quality synthesis to evaluate the efficacy and safety of local epidural steroids following PEID. CONCLUSION: This systematic review will provide evidence to judge whether local epidural steroids application following PEID is an effective and safe intervention for patients. It will provide reliable evidence for its extensive application. REGISTRATION NUMBER: INPLASY2020100085.

Hyperbaric oxygen therapy for spinal cord injury: A protocol for systematic review and meta-analysis.

BACKGROUND: Hyperbaric oxygen (HBO) therapy can prevent further spinal cord injury (SCI) caused by spinal cord ischemia-reperfusion injury to the maximum extent, which has been reported increasingly in recent years. However its security and effectiveness still lack of high-quality medical evidence. In this study, we will perform a systematic review of previously published randomized controlled trials (RCTs) to evaluate the efficacy and safety of HBO therapy for SCI. METHODS: All potential RCTs on HBO therapy for SCI will be searched from the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang database and Chinese Biomedical Literature Database. We will search all electronic databases from their initiation to the September 30, 2020 in spite of language and publication date. Two contributors will independently select studies from all searched literatures, extract data from included trials, and evaluate study quality for all eligible RCTs using Cochrane risk of bias tool, respectively. Any confusion will be resolved by consulting contributor and a consensus will be reached. We will utilize RevMan 5.3 software to pool the data and to conduct the data analysis. RESULTS: The quality of the assessments will be assessed through Grading of Recommendations Assessment, Development, and Evaluation. Data will be disseminated through publications in peer-reviewed journals. CONCLUSION: This study will provide evidence to evaluate the efficacy and safety of HBO therapy for SCI at evidence-based medicine level. TRIAL REGISTRATION NUMBER: INPLASY 2020100084.

Influence of Ketorolac Supplementation on Pain Control for Knee Arthroscopy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy of ketorolac supplementation on pain control for knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the impact of ketorolac supplementation on pain intensity after knee arthroscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2018 for randomized controlled trials (RCTs) assessing the effect of ketorolac supplementation vs placebo on pain management after knee arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS: Ten RCTs involving 402 patients are included in the meta-analysis. Overall, compared with control group for knee arthroscopy, ketorolac supplementation is associated with notably reduced pain scores at 1 h (MD = -0.66; 95% CI = -1.12 to -0.21; P = 0.004) and 2 h (MD = -0.90; 95% CI = -1.74 to -0.07; P = 0.03), prolonged time for first analgesic requirement (MD = 1.94; 95% CI = 0.33 to 3.55; P = 0.02) and decreased number of analgesic requirement (RR = 0.41; 95% CI = 0.23 to 0.75; P = 0.003), but has no obvious impact on analgesic consumption (MD = -0.56; 95% CI = -1.14 to 0.02; P = 0.06), as well as nausea and vomiting (RR = 0.44; 95% CI = 0.12 to 0.21; P = 0.21). CONCLUSIONS: Ketorolac supplementation is effective to produce pain relief for knee arthroscopy.

Evaluation of the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid composite screws for intraarticular fractures in rabbits.

OBJECTIVE: To evaluate the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) composite screws in the intraarticular fracture model. MATERIALS AND METHODS: A total of 35 New Zealand White rabbits were used in a bilateral femoral intercondylar fracture model and randomly divided into two groups. n-CDHA/PAA screws were used in the experimental group, and medical metal screws were used in the control group. The fracture condition, range of motion, and the screw push-out strength were assessed, and an arthroscopic examination of knee joint was performed at 4, 8, and 12 weeks after surgery. The biodegradation of the n-CDHA/PAA screws in vivo was tested through weighing, and changes in screw structure were assessed by X-ray diffraction at 12 weeks after surgery. RESULTS: The general situation of all animals was good and showed no incision infection and dehiscence after surgery. X-ray scanning showed that significant callus growth was present in both groups at 4 weeks after surgery, and there was no significant difference (P>0.05) in the Lane-Sandhu score between the experimental and control groups at all time points after surgery. There were no statistically significant differences (P>0.05) in the range of motion and Oswestry Arthroscopy Score of arthroscopic examination of the knee joints between the two groups. The screw push-out strength of the control group was stronger than that of the experimental group at 4 weeks after surgery (P<0.05), but after that, there was no significant difference between the groups (P>0.05). The degradation tests showed that the n-CDHA/PAA screws degraded gradually after implantation, and the weight loss rate was approximately 16% at 12 weeks after surgery. The X-ray diffraction results showed that the crystal structure of the outer surface of the n-CDHA/PAA screw has changed at 12 weeks after surgery. CONCLUSION: The n-CDHA/PAA screw is an effective and safe implant as a potential internal fixation device for an intercondylar fracture of the femur, and its internal fixation effect was similar to that of medical metal screw.

Electroacupuncture preconditioning attenuates ischemic brain injury by activation of the adenosine monophosphate-activated protein kinase signaling pathway.

Electroacupuncture has therapeutic effects on ischemic brain injury, but its mechanism is still poorly understood. In this study, mice were stimulated by electroacupuncture at the Baihui (GV20) acupoint for 30 minutes at 1 mA and 2/15 Hz for 5 consecutive days. A cerebral ischemia model was established by ligating the bilateral common carotid artery for 15 minutes. At 72 hours after injury, neuronal injury in the mouse hippocampus had lessened, and the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive cells reduced after electroacupuncture treatment. Moreover, expression of adenosine monophosphate-activated protein kinase α (AMPKα) and phosphorylated AMPKα was up-regulated. Intraperitoneal injection of the AMPK antagonist, compound C, suppressed this phenomenon. Our findings suggest that electroacupuncture preconditioning alleviates ischemic brain injury via AMPK activation.

Generation and preliminary application of polyclonal antibodies against human Argonaute2 / 中国免疫学杂志

Objective:To generate rabbit polyclonal antibody against human Argonaute2 (Ago2) protein and to identify its functional characterization for determination of differential expression and cellular localization of Ago2 protein in various cell lines.Methods:DNAstar software was applied for searching the high antigenicity region of Ago2 gene sequence termed k-Ago2.Prokaryotic expressing plasmid was constructed and transformed to E.coli BL21 (DE3) to induce expression by IPTG.The fusion protein was injected into rabbits subcutaneously to produce polyclonal antibodies after purification by gel regaining.ELISA was operated to detect antibody titer.Western blot was used to identify the specificity and sensitivity of the antibodies and detect the differential expression of Ago2 protein in various cell lines.Meanwhile,immunofluorescence experiments were arranged to show cellular localization of Ago2 protein.Results:The prokaryotic expressing plasmid was constructed correctly.K-Ago2 protein was expressed and purified,and then rabbit polyclonal antibodies against Ago2 were generated after immunization with k-Ago2 protein.The titer detected by ELISA was 1∶19 000.Western blot results demonstrated the high specificity of the antibodies.Finally,we successfully observed the differential expression and cellular localization of Ago2 protein in various cell lines.Conclusion:The polyclonal antibody against Ago2 protein has been achieved successfully.It will be propitious for the intensive study of the RNAi mechanism and even profound clinical application.