Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2.

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

Effects of xenon anesthesia on postoperative neurocognitive disorders: a systematic review and meta-analysis.

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.

Prevalence and Predictors of Chronic Postsurgical Pain After Video-Assisted Thoracoscopic Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: Determining the prevalence of chronic postsurgical pain (CPSP) after video-assisted thoracoscopic surgery (VATS) and identifying CPSP predictors should improve the prognosis of patients undergoing VATS. Although several studies have investigated predictors of CPSP after VATS, there were significant dissimilarities in the findings due to the confounding of predictors. METHODS: PubMed, Cochrane, MEDLINE, Web of Science, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases were comprehensively searched using the Medical Subject Headings terms "pain, postoperative," "thoracic surgery, video-assisted," and all related free terms from inception until March 27, 2022. The Stata metaprop package was used to comprehensively analyze the incidence of CPSP following VATS. Furthermore, the pooled odds ratios (OR) or the standardized mean differences (SMD) and their corresponding 95% confidence intervals (95% CI) were calculated, and qualitative analyses were performed for predictors that could not be assessed quantitatively to evaluate the effects of the included risk factors on the occurrence of CPSP. Unadjusted odds ratios were utilized to consider the impact of non-significant estimates if the original study did not report them. RESULTS: Of the 4302 studies, 183 were considered eligible, and 17 were finally included in this study. The overall incidence of CPSP after VATS was 35.3% (95% CI 27.1-43.5%). The qualitative synthesis results revealed that female sex, age, and acute postoperative pain were definite predictors of CPSP after VATS. The number of ports, operation time, duration of drainage, and insufficient analgesia were also considered predictors. Consistent, quantitative synthesis results also showed that the aforementioned predictors were closely related to the occurrence of CPSP after VATS. Only by quantitative analysis, postoperative chemotherapy and an educational level less than junior school were also risk factors for CPSP. Other predictors displayed no evidence or unclear evidence of association with CPSP after VATS. CONCLUSION: This study preliminarily determined the incidence of CPSP after VATS based on the existing literature. Female sex, age, and acute pain were identified as risk factors for CPSP after VATS, and other potential risk factors were also identified and analyzed. However, as a result of the inclusion of retrospective studies and inevitable limitations in this systematic review and meta-analysis, the results of this study still need to be verified by large-scale prospective clinical studies. TRIAL REGISTRATION: CRD42022323179.

Nomogram prediction of chronic postsurgical pain in patients with lung adenocarcinoma after video-assisted thoracoscopic surgery: A prospective study.

Chronic postsurgery pain (CPSP) refers to persistent or repeated pain around the incision after surgery. Different from acute postoperative pain, the persistence of CPSP seriously affects the quality of life of patients. CPSP has a considerable global impact due to large surgical volumes. Although the development of video-assisted thoracoscopy (VATS) has reduced the risk of CPSP, it still seriously affects patients' quality of life. Clinical recognition of CPSP at an early stage is limited; therefore, we aimed to develop and validate a nomogram to identify the significant predictive factors associated with CPSP after VATS in patients with lung adenocarcinoma. We screened 137 patients with invasive adenocarcinoma of the lung from among 312 patients undergoing VATS. In this prospective study, patients were divided into the CPSP (n = 52) and non-CPSP (n = 85) groups according to the occurrence of CPSP. Relevant information was collected 1 day before surgery and 1-3 days after surgery, and the occurrence of CPSP was followed up by telephone at 3 months after surgery. Data on clinical characteristics and peripheral blood leukocyte miRNAs were used to establish a nomogram for predicting CPSP using least absolute shrinkage and selection operator (LASSO) regression methods. The area under curve (AUC) was used to determine the recognition ability of the nomograms. The model was subjected to correction and decision curve analyses. Four variables-body mass index (BMI), history of chronic pain, miR 550a-3p, and visual analog scale (VAS) score on postoperative day 2 (VAS2d)-were selected according to LASSO regression to build the nomogram. The nomogram demonstrated adequate calibration and discrimination in the prediction model, with an AUC of 0.767 (95% confidence interval: 0.679-0.856). The calibration plot showed the best fit between model predictions and practical observations, suggesting that the use of the proposed nomogram to predict CPSP is beneficial. A nomogram consisting of BMI, history of chronic pain, miR 550a-3p, and VAS2d predicted the risk of CPSP after VATS in patients with lung adenocarcinoma.

Photodynamic Therapy Initiated Ferrotherapy of Self-Delivery Nanomedicine to Amplify Lipid Peroxidation via GPX4 Inactivation.

Lipid peroxide (LPO) is the hallmark of ferroptosis, which is a promising antitumor modality for its unique advantages. However, a cellular defense system would weaken the antitumor efficacy of ferrotherapy. Herein, a GPX4 inhibitor of ML162 and a photosensitizer of chlorine e6 (Ce6) are used to prepare the self-delivery nanomedicine (C-ML162) through hydrophobic and electrostatic interactions to enhance ferroptosis by photodynamic therapy (PDT). Specifically, carrier-free C-ML162 improves the solubility, stability, and cellular uptake of antitumor agents. Upon light irradiation, the internalized C-ML162 generates large amounts of reactive oxygen species (ROS) to oxidize cellular unsaturated lipid into LPO. More importantly, C-ML162 can directly inactivate GPX4 to enhance the accumulation of toxic LPO, inducing ferroptotic cell death. Additionally, C-ML162 is capable of accumulating at a tumor site for effective treatment. This self-delivery system to amplify lipid peroxidation via GPX4 inactivation for PDT initiated ferrotherapy might provide an appealing strategy against malignancies.

Plasma Membrane-Targeted Photooxidant for Chemotherapy-Enhanced Lipid Peroxidation.

Although photodynamic therapy (PDT) is a promising antitumor strategy for tumor treatment, the short half-life and the limited diffusion distance of reactive oxygen species (ROS) greatly hamper its antitumor efficacy. Moreover, tumor cells develop antioxidative microenvironments to weaken the oxidative damage caused by PDT. Herein, a plasma membrane-targeted photooxidant (designated as SCPP) is prepared by the self-assembly of a chimeric peptide (Pal-K(PpIX)-R4) and sorafenib. Plasma membrane-targeted SCPP could enhance lipid peroxidation (LPO) through in situ PDT upon light irradiation. Moreover, sorafenib-mediated chemotherapy could block cystine/glutamate antiporter xCT (SLC7A11) to inhibit the syntheses of intracellular GSH and glutathione peroxidase 4 (GPX4), which would destroy the antioxidant defense system of tumors. As a consequence, SCPP achieves a highly efficient tumor inhibition through enhanced PDT and ferroptosis therapy. This study might provide guidance for multisynergistic tumor therapy with a sophisticated mechanism under unfavorable conditions.

Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.

Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O2 for enhanced PDT against hypoxic tumors. The carrier-free O2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.

Dexmedetomidine alleviates traumatic spinal cord injury in rats via inhibiting apoptosis induced by endoplasmic reticulum stress.

OBJECTIVE: To investigate the protective effect of dexmedetomidine (Dex) on traumatic spinal cord injury (TSCI) and to evaluate the involvement of inhibition of endoplasmic reticulum (ER) stress response in the potential mechanism. METHOD: Sprague-Dawley rats were randomly divided into five groups. The hind limb locomotor function of rats was evaluated at 1, 3 and 7 days after the operation. At 7 days after the operation, spinal cord specimens were obtained for hematoxylin and eosin (H&E), Nissl and TUNEL staining, as well as immunofluorescence and Western blot analyses to detect the level of apoptosis and the levels of proteins related to ER stress. RESULTS: 7 days after the operation, Dex treatment promoted the recovery and also inhibited apoptosis of neurons in the spinal cord. Additionally, Dexinhibited the expression of proteins related to ER stress response after spinal cord injury. CONCLUSIONS: Dex improves the neurological function of rats with TSCI and reduces apoptosis of spinal cord neurons. The potential mechanism is related to the inhibition of the ER stress response.

Carrier Free Photodynamic Synergists for Oxidative Damage Amplified Tumor Therapy.

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic.

Mitochondria Targeted O2 Economizer to Alleviate Tumor Hypoxia for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) often suffers from the exacerbated tumor hypoxia and the heterogeneous distribution of photosensitizers, leading to an inefficient ROS productivity and availability. In this work, a mitochondria targeted O2 economizer (designated as Mito-OxE) is developed to improve PDT efficiency by alleviating tumor hypoxia and enhancing the subcellular localization of photosensitizers. Specifically, the photosensitizer of protoporphyrin IX (PpIX) is modified with the hydrophilic polyethylene glycol and the lipophilic cation of triphenylphosphine (TPP) to fabricate the biocompatible mitochondria targeted photosensitizers (designated as Mito-PSs). And Mito-OxE is prepared by using Mito-PSs to load the mitochondrial oxidative phosphorylation inhibitors of atovaquone (ATO). Benefiting from the targeting capability of TPP, Mito-OxE can selectively accumulate in mitochondria after cellular uptake. Subsequently, the mitochondrial respiration would be suppressed to with the participation of ATO, resulting in a local hypoxia mitigation for enhanced PDT. Compared with Mito-PSs, Mito-OxE maximizes the therapeutic effect against hypoxic tumors under light irradiation. This design of mitochondria targeted O2 economizer would advance the development of targeted drug delivery system for effective PDT regardless of hypoxic microenvironment.

UGT1A1 rs4148323 A Allele is Associated With Increased 2-Hydroxy Atorvastatin Formation and Higher Death Risk in Chinese Patients With Coronary Artery Disease.

It is widely accepted that genetic polymorphisms impact atorvastatin (ATV) metabolism, clinical efficacy, and adverse events. The objectives of this study were to identify novel genetic variants influencing ATV metabolism and outcomes in Chinese patients with coronary artery disease (CAD). A total of 1079 CAD patients were enrolled and followed for 5 years. DNA from the blood and human liver tissue samples were genotyped using either Global Screening Array-24 v1.0 BeadChip or HumanOmniZhongHua-8 BeadChip. Concentrations of ATV and its metabolites in plasma and liver samples were determined using a verified ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method. The patients carrying A allele for the rs4148323 polymorphism (UGT1A1) showed an increase in 2-hydroxy ATV/ATV ratio (p = 1.69E-07, false discovery rate [FDR] = 8.66E-03) relative to the value in individuals without the variant allele. The result was further validated by an independent cohort comprising an additional 222 CAD patients (p = 1.08E-07). Moreover, the rs4148323 A allele was associated with an increased risk of death (hazard ratio [HR] 1.774; 95% confidence interval [CI], 1.031-3.052; p = 0.0198). In conclusion, our results suggested that the UGT1A1 rs4148323 A allele was associated with increased 2-hydroxy ATV formation and was a significant death risk factor in Chinese patients with CAD.

Self-Remedied Nanomedicine for Surmounting the Achilles' Heel of Photodynamic Tumor Therapy.

Oxygen-dependent photodynamic therapy (PDT) could exacerbate tumor hypoxia to induce the upregulation of hypoxia-inducible factor-1α (HIF-1α), which would promote tumor growth and metastasis. In this paper, a self-remedied nanomedicine is developed based on a photosensitizer and a HIF-1α inhibitor to surmount the Achilles' heel of PDT for enhanced antitumor efficacy. Specifically, the nanomedicine (designated as CYC-1) is prepared by the self-assembly of chlorine e6 (Ce6) and 3-(5'-hydroxy-methyl-2'-furyl)-1-benzylindazole (YC-1) through π-π stacking and hydrophobic interactions. Of special note, carrier-free CYC-1 holds an extremely high drug loading rate and avoids excipient-triggered adverse reactions. Intravenously administered CYC-1 prefers to accumulate in the tumor tissue for effective cellular uptake. More importantly, it is verified that CYC-1 is capable of inhibiting the HIF-1α activity, thereby improving its PDT efficacy on tumor suppression. Besides, CYC-1 has the overwhelming superiority in restraining tumor proliferation over the combined administration of Ce6 and YC-1, which highlights the advantage of this self-remedied strategy in drug delivery and tumor therapy. This study sheds light on the development of self-delivery nanomedicine for efficient PDT against malignancies.

Self-Delivery Photo-Immune Stimulators for Photodynamic Sensitized Tumor Immunotherapy.

Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy.

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect.

Neuropeptide Y (NPY), which is widely distributed in the nervous system, is involved in regulating a variety of biological processes, including food intake, energy metabolism, and emotional expression. However, emerging evidence points to NPY also as a critical transmitter between the nervous system and immune system, as well as a mediator produced and released by immune cells. In vivo and in vitro studies based on gene-editing techniques and specific NPY receptor agonists and antagonists have demonstrated that NPY is responsible for multifarious direct modulations on immune cells by acting on NPY receptors. Moreover, via the central or peripheral nervous system, NPY is closely connected to body temperature regulation, obesity development, glucose metabolism, and emotional expression, which are all immunomodulatory factors for the immune system. In this review, we focus on the direct role of NPY in immune cells and particularly discuss its indirect impact on the immune response.

MicroRNA-29a functions as a tumor suppressor through targeting STAT3 in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with high mortality in developing countries. A comprehensive understanding of the molecular mechanisms of tumor progression in laryngeal cancer is needed for new treatment strategies. MicroRNA-29a has been emerged as a critical miRNA in various cancers, and shown to regulate multiple oncogenic processes. In this study, we investigated the tumor suppressive role of miRNA-29a in laryngeal squamous cell carcinoma. We performed cell-based functional analysis after overexpression of miR-29a in AMC-HN-8 and HEP2 cells in vitro. It turned out that ectopic expression of miR-29a significantly inhibited cell proliferation, invasion, and migration in two LSCC cell lines (AMC-HN-8 and Hep2) in vitro. Further downstream target analysis by western blotting and luciferease reporter assay showed that overexpression of miR-29a significantly downregulated expression of STAT3, and STAT3 is a putative direct target of miR-29a in LSCC. In addition, the tumor suppressive function of miR-29a can be abrogated by forced expression of STAT3. Taken together, our data suggest that miR-29a functions as a tumor suppressor through targeting STAT3 in laryngeal squamous cell carcinoma.

Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease.

The selection of optimum statin intensity is inconclusive, and the association of plasma exposure of statins and metabolites with major adverse cardiovascular events (MACEs) is unclear. This study sought to compare the effect of low (quartile 1), intermediate (quartiles 2 and 3), and high (quartile 4) plasma exposure of statins and metabolites on MACE, re-ischemia events and death in patients with coronary artery disease (CAD) at 5 years. A total of 1,644 patients in atorvastatin (AT) cohort and 804 patients in rosuvastatin (RST) cohort were included, and their plasma concentration of statins and metabolites was categorized as low-, mid-, or high-group. The association between the plasma levels of statins and metabolites and the incidence of primary endpoint in patients was assessed by Cox proportional hazard models. Intensive AT exposure (Q4 > 5.32 ng/ml) was significantly associated with increased risk of death compared with low (hazard ratio [HR]: 1.522; 95% confidence interval [CI]: 1.035-1.061; P = 0.0022) or moderate exposure (HR: 2.054; 95% CI: 1.348-3.130; P = 0.0008). This association was also found in AT's five metabolites (all P < 0.01). In patients with RST treatment, moderate RST concentration (0.53-4.29 ng/ml) versus low concentration had a significantly lower risk of MACE and re-ischemia events. (HR: 0.532, 95% CI: 0.347-0.815, P = 0.0061 and HR: 0.505, 95% CI: 0.310-0.823, P = 0.0061, respectively). A higher plasma exposure of AT and metabolites has a significantly higher risk of death, and moderate RST exposure has a significantly lower risk of MACE and re-ischemia events in Chinese patients with CAD. The harms of high plasma exposure should be considered when prescribing statins to patients because it may be a risk factor for having poor prognosis in patients with CAD.

Effects of SLCO1B1 and GATM gene variants on rosuvastatin-induced myopathy are unrelated to high plasma exposure of rosuvastatin and its metabolites.

Myotoxicity is a significant factor contributing to the poor adherence and reduced effectiveness in the treatment of statins. Genetic variations and high drug plasma exposure are considered as critique causes for statin-induced myopathy (SIM). This study aims to explore the sequential influences of rosuvastatin (RST) pharmacokinetic and myopathy-related single-nucleotide polymorphisms (SNPs) on the plasma exposure to RST and its metabolites: rosuvastatin lactone (RSTL) and N-desmethyl rosuvastatin (DM-RST), and further on RST-induced myopathy. A total of 758 Chinese patients with coronary artery disease were enrolled and followed up SIM incidents for 2 years. The plasma concentrations of RST and its metabolites were determined through a validated ultra-performance liquid chromatography mass spectrometry method. Nine SNPs in six genes were genotyped by using the Sequenom MassArray iPlex platform. Results revealed that ABCG2 rs2231142 variations were highly associated with the plasma concentrations of RST, RSTL, and DM-RST (Padj < 0.01, FDR < 0.05). CYP2C9 rs1057910 significantly affected the DM-RST concentration (Padj < 0.01, FDR < 0.05). SLCO1B1 rs4149056 variant allele was significantly associated with high SIM risk (OR: 1.741, 95% CI: 1.180-2.568, P = 0.0052, FDR = 0.0468). Glycine amidinotransferase (GATM) rs9806699 was marginally associated with SIM incidents (OR: 0.617, 95% CI: 0.406-0.939, P = 0.0240, FDR = 0.0960). The plasma concentrations of RST and its metabolites were not significantly different between the SIM (n = 51) and control groups (n = 707) (all P > 0.05). In conclusion, SLCO1B1 and GATM genetic variants are potential biomarkers for predicting RST-induced myopathy, and their effects on SIM are unrelated to the high plasma exposure of RST and its metabolites.

[Clinical observation on treatment of active rheumatoid arthritis with Chinese herbal medicine].

OBJECTIVE: To study the efficacy and safety of Chinese drugs for expelling evil-wind, removing dampness, promoting blood circulation and invigorating yin in treating active rheumatoid arthritis (RA). METHODS: Sixty-seven patients with active RA were randomized into 3 groups, the Group A, B and C. They were made coequal in terms of age, sex and condition of disease and treated respectively with basic treatment (non-steroid anti-inflammation drug combined with immune inhibitor) only, basic treatment + small dose prednisone, and basic treatment + Chinese herbal medicine, all for 8 weeks. The efficacy and adverse effects of treatment were analyzed by scoring. RESULTS: The total effective rate was 20.0% (4/20) in Group A, 810% (17/21) in Group B and 85.7% (18/21) in Group C, the latter two were superior to the former one (P <0.01). Before treatment, comparison of disease activity score (DAS) among the three groups showed no significant difference (P > 0.05). After treatment, improvements of Ritchie arthritis index (RAI), number of swollen joint, erythrocyte sedimentation rate (ESR), general health (GH), and DAS were shown in Group B and C (P <0.05), while in Group A, improvement was only shown in GH (P <0.05). The difference of DAS between pre- and post-treatment was 0.25 +/- 0.77 in Group A, 0.87 +/- 0.60 in Group B and 0.92 +/- 0.59 in Group C, showing statistical significance between Group A vs B and A vs C (P = 0.0000). The total accumulative score of adverse reaction was 3.76 +/- 2.72 in Group C, 9.10 +/- 6.01 in Group A and 14.38 +/- 9.36 in Group B, also showing statistical significance among groups (P < 0.05). CONCLUSION: The combination of Chinese and Western medicine for active RA is effective and safe.