[Effect of moxibustion on the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor in ankle synovial tissue of rats with adjuvant arthritis].

OBJECTIVE: To observe the effect of moxibustion on the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in ankle synovial tissue of rats with adjuvant arthritis(AA), so as to explore the mechanism of moxibustion in inhibiting synovial angiogenesis and improving joint symptoms of rheumatoid arthritis. METHODS: Sixty healthy male SD rats were randomly divided into normal group, model group, moxibustion group and medication group, with 15 rats in each group. AA rat model was established by subcutaneous injection of Freund's complete adjuvant into the right hind paw. Rats in the moxibustion group were treated with "Zusanli" (ST36), "Guanyuan" (CV4) and "Ashi" point moxibustion, 20 min each time, once a day, for consecutive 3 weeks. Rats in the medication group were given methotrexate (0.35 mg/kg) intragastric administration, twice a week, for consecutive 3 weeks. Foot plantar volume of rats was measured by toe volume mea-suring instrument. HE staining was used to observe the histopathology of ankle synovium. The protein expressions of HIF-1α and VEGF in ankle synovial tissue were detected by immunohistochemistry and Western blot. RESULTS: Compared with the normal group, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly increased (P<0.01) in the model group, the synovial tissue showed obvious hyperplasia and a large number of neovasculogenesis. Following the interventions, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly decreased (P<0.05, P<0.01) in both moxibustion and medication groups in contrast to the model group, and there was no obvious proliferation of synovial tissue, and only a few neovascularization was observed. Compared with the medication group, the foot plantar volume was decreased (P<0.05) in the moxibustion group. CONCLUSION: Moxibustion can improve joint swelling and inhibit synovial angiogenesis in AA rats, and its mechanism may be related to down-regulating of HIF-1α and VEGF protein expressions.

Cerebral blood flow regulates iron overload in the cerebral nuclei of hemodialysis patients with anemia.

Hemodialysis patients exhibit anemia-related cerebral hyperperfusion and iron deposition (ID). However, the mechanisms underlying the pathology of cerebral ID are not clear. We investigated the role of cerebral blood flow (CBF) in the pathophysiology of cerebral ID in hemodialysis patients with anemia. This study recruited 33 hemodialysis patients with anemia and thirty-three healthy controls (HCs). All the subjects underwent quantitative susceptibility mapping (QSM) and arterial spin labeling (ASL) to measure ID and CBF in the cerebral nuclei. Furthermore, we evaluated lacunar infarction (LI), cerebral microbleeds, and total white matter hyperintensity volume (TWMHV). Hemodialysis patients with anemia showed significantly higher ID and CBF in some nuclei compared to the HCs after adjusting for age, sex, and total intracranial volume (TIV) [P < 0.05, false discovery rate (FDR) corrected]. CBF showed a positive correlation with ID in both patients and HCs after adjustments for age, gender, and TIV (P < 0.05, FDR corrected). Serum phosphorus, calcium, TWMHV, hypertension, and dialysis duration were independently associated with ID (P < 0.05). Hemoglobin, serum phosphorus, and LI were independently associated with CBF (P < 0.05). Mediation analysis demonstrated that CBF mediated the effects between hemoglobin and ID. Our study demonstrated that CBF mediated aberrant cerebral ID in hemodialysis patients with anemia.

[Altitudinal variation pattern in Daphniphyllum macropodum leaf traits and influencing environmental factors in Mao'er Mountain, China]. / çŒ«å„¿å±±äº¤è®©æœ¨å¶æ€§çŠ¶æµ·æ‹”å˜å¼‚æ ¼å±€åŠå ¶çŽ¯å¢ƒå½±å“å› å­.

Analyzing the pattern of altitudinal variation in the leaf traits and their networks of a particular tree species of similar age and its influencing factors could contribute to understanding the impacts of environmental factors on leaf traits and excluding the interference of genetic factors. We investigated the stomatal, structural, chemical, and vein traits of Daphniphyllum macropodum leaves in middle-aged forests, following the altitudinal gradient (1100, 1500, and 1900 m) on Mao'er Mountain. The objectives of this study were to reveal patterns in leaf trait and leaf trait networks variation, the life strategy of the tree species, and the major environmental factors affecting the altitudinal variations. The results showed that leaf area, specific leaf area, leaf thickness, leaf dry matter content, chlorophyll content, nitrogen content, phosphorus content, C:N, C:P, vein density, and vein diameter varied significantly across altitudes. Mean annual temperature and total radiation explained 42.1% and 16.2% of leaf-trait variation, respectively. They served as key environmental factors driving the altitudinal variation in leaf traits. Mean annual temperature exhibited the greatest influence on leaf area (R2=0.73), and total radiation exerted the most prominent effect on leaf thickness (R2=0.72). Both relationships were significantly positive. D. macropodum exhibited low leaf nitrogen and phosphorus at the low altitude of 1100 m, and the overall and local trait networks were loose, adopting a conservative resource strategy. At the medium altitude of 1500 m, leaf nutrient contents were relatively high. The overall network of leaf traits was tightly connected and local network was loose. By enhancing the dependency among leaf traits, and improving phosphorus utilization efficiency, D. macropodum could cope with competition in deciduous forests and adopt resource acquisition strategies. Further, at the highest altitude of 1900 m, D. macropodum had relatively large leaf thickness, chlorophyll content, and leaf dry matter content, but relatively small leaf area. The local network connections were tight while the overall network looseness, indicating a resource conserving strategy. The trade-off relationship between C:P and leaf phosphorus content was closely related to phosphorus use efficiency, and its variation was an important indicator for identifying life strategies of D. macropodum in different altitudes.

ICG-loaded and 125I-labeled theranostic nanosystem for multimodality imaging-navigated phototherapy of breast cancer.

Multimodality imaging-navigated precise phototherapy has been well-established as a promising strategy for enhancing the diagnostic and therapeutic efficiency of cancer in preclinical trials. However, proper theranostic agents with adequate biosafety and biological efficacy as well as simple components and preparations are still in great demand to promote the clinical translation of this regimen. Here, we developed a multifunctional nanosystem based on the self-assembly of FDA-approved indocyanine green (ICG) and 125I-labeled glycopeptides, which were composed of FDA-approved natural polysaccharide sodium alginate and endogenous tyrosine, for fluorescence imaging/single photon emission computed tomography (FLI/SPECT)-guided synergistic photothermal/photodynamic therapy (PTT/PDT) of breast cancer. The as-prepared ICG@ADY(125I) NPs possessed a stable nanostructure and radiolabel, an ICG-equivalent ROS and hyperthermia generation property, and a preferable photo/photothermal stability and biocompatibility, favoring its tumor homing, multimodality imaging, and phototherapy with high biosafety. Consequently, ICG@ADY(125I) NPs smoothly accumulated in tumors by virtue of their long blood circulation (t1/2 = 15.76 ± 1.34 h) and the EPR effect, thereby presenting highly sensitive FLI/SPECT images to realize cancer diagnosis. Guided by multimodality imaging, accurate PTT/PDT was performed using NIR laser irradiation, achieving a high tumor inhibition rate (81.8%) against 4T1 breast cancer models without appreciable side effects. Altogether, this theranostic nanosystem may have huge potential for the clinical diagnosis and treatment of breast cancer.

Diffusion Tensor Imaging Evaluates Effects of Acupoint Injection at Zusanli (ST36) for Type 2 Diabetic Peripheral Neuropathy.

BACKGROUND Acupoint injection is a therapeutic method that combines acupuncture and Western medicine and shows good curative effects for neuropathies. This study aimed to explore the efficacy of acupoint injection for treating diabetic peripheral neuropathy (DPN) by magnetic resonance neuroimaging (MRN). MATERIAL AND METHODS Forty patients with DPN were randomly divided into an acupoint injection group (AI; n=20) and intramuscular injection group (MI; n=20). The AI group received an acupoint injection of mecobalamin at acupoint Zusanli (S36); the MI group received intramuscular injection of mecobalamin. The curative effect was evaluated by the Toronto Clinical Neuropathy Score and diffusion tensor imaging (DTI). RESULTS The neuropathy scores of both groups decreased from baseline (AI 9.31±2.36; MI 9.34±2.54) to after the 2-week treatment (AI 7.12±1.87; MI 7.86±2.11); the differences were not significant. The fractional anisotropy (FA) value showed significant differences on the common peroneal nerve (AI 0.36±0.04; MI 0.31±0.05; P<0.05) and tibial nerve (AI 0.38±0.07; MI 0.34±0.06; P<0.05) after treatment. Likewise, apparent diffusion coefficient (ADC) values between groups showed significant differences for the common peroneal nerve (AI 1.44±0.17×10⁻³ mm²/s; MI 1.61±0.20×10⁻³ mm²/s; P<0.05) and tibial nerve (AI 1.54±0.22×10-3 mm²/s; MI 1.60±0.17 10⁻³ mm²/s; P<0.05). CONCLUSIONS Patients with DPN showed lower nerve FA and higher ADC in DTI-MRN. The acupoint injection of mecobalamin could treat DPN and repair the damaged nerves, which was shown by elevated FA and lowered ADC. Our study provides clinical evidence for the application of acupoint injection therapy and the evaluation of DPN by MRN.

Anxiety During the COVID-19 Pandemic: A Web-Based Survey of Thyroid Cancer Survivors.

OBJECTIVE: Cancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors' health care interactions and quality of life. METHODS: An anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors' Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression. RESULTS: From May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04). CONCLUSION: During the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.

Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy.

OBJECTIVE: The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. MATERIALS AND METHODS: A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). RESULTS: We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. CONCLUSION: The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Polygonatum cyrtonema Hua polysaccharide exhibits anti-fatigue activity via regulating osteocalcin signaling.

In the present study, we explored the anti-fatigue activity and its potential mechanism of a purified Polygonatum cyrtonema polysaccharide (PCP) on mice using weight-loaded swimming test. Results showed that PCP remarkably prolonged the exhaustive swimming time of mice when compared with normal control group. Meanwhile, PCP decreased serum levels of lactic acid (LA), blood uric nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), and increased the contents of liver glycogen, muscle glycogen and muscle ATP. These results revealed that PCP had good anti-fatigue ability. The histomorphologic analysis showed that PCP increased the cross-section area of the muscle fibers. Furthermore, PCP significantly enhanced the protein levels of bone morphogenetic protein-2 (BMP-2), phosphor-Smad1, Runt-related transcription factor 2 (Runx2) and osteocalcin (OC) in skeleton. Similar variation was also observed in the expression of osteocalcin signaling mediators of phosphorylated cAMP-response element binding protein (p-CREB) and phosphorylated hormone-sensitive lipase (p-HSL) in skeletal muscle. These results suggested that PCP resisted fatigue possibly via regulating osteocalcin signaling.

Effects of non-supervised aerobic exercise on sleep quality and maternal-fetal attachment in pregnant women: A randomized controlled trial.

OBJECTIVES: This study was designed to evaluate the effect in pregnant women of a non-supervised aerobic exercise intervention on sleep quality and maternal-fetal attachment. DESIGN: Pretest-posttest randomized controlled trial. SETTING: Prenatal clinic of a medical center in southern Taiwan. PARTICIPANTS: One hundred and forty eligible, pregnant women were assigned systematically, at a random starting point, to either the experimental group (n = 70) or the control group (n = 70). INTERVENTION: Participants in the experimental group received a 20-minute, low-impact aerobic exercise video on DVD and were instructed to exercise at home at least three times per week for a period of three months. Participants in the control group received routine prenatal care only. MAIN OUTCOME MEASURES: The Pittsburgh Sleep Quality Index and Modified Maternal-Fetal Attachment Scale were used to assess outcome measures before the intervention and at four and 12-weeks post-intervention. RESULTS: The paired-sample t-tests revealed a significant improvement in sleep quality in the experimental group at 4-weeks posttest, which persisted through 12-weeks posttest. In addition, the experimental group reported a significantly higher mean score for maternal-fetal attachment at 4-weeks posttest than the control group. CONCLUSION: The results of this study indicate that performing aerobic exercise ameliorates the decline in sleep quality and improves maternal-fetal attachment in women who are pregnant. These findings may be used to encourage pregnant women to regularly perform low-impact aerobic exercise.

Taiwan nutritional consensus on the nutrition management for gastric cancer patients receiving gastrectomy.

Currently, consensus reports on the nutritional management for gastric cancer patients receiving gastric resection are lacking. The Gastroenterological Society of Taiwan therefore organized the Taiwan Gastric Cancer Nutritional Consensus Team to provide an overview of evidence and recommendations on nutritional support for gastric cancer patients undergoing gastrectomy. This consensus statement on the nutritional support for gastric cancer patients has two major sections:(1)perioperative nutritional support; and (2)long-term postoperative nutritional care. Thirty Taiwan medical experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. The key statements included that preoperative nutritional status affects the incidence of operative complications and disease-specific survival in gastric cancer patients undergoing gastrectomy. Following gastrectomy, both early oral and enteral tube feeding can result in a shorter stay than total parenteral nutrition. Compared to late oral feeding, early oral feeding can reduce hospital stay in gastric cancer patients receiving gastrectomy without an increase in complication rate. Routine supplementation with vitamin B12 is indicated for gastric cancer patients undergoing a total gastrectomy. Both high-dose oral vitamin B12 supplementation and intramuscular administration of vitamin B12 are equally effective in the treatment of vitamin B12 deficiency.

Application of Zizao Yangrong Granules for Treating Targeted Drugs-Related Skin Xerosis: A Randomized Double-Blinded Controlled Study.

Background: Dermatologic toxicities are the most common side effects associated with the targeted drugs epidermal growth factor receptor inhibitors (EGFRIs), in which xerosis commonly complicated by pruritus severely disturbs the quality of life. The study has observed the curative effect of Zizao Yangrong granules (ZYG) from Chishui Xuanzhu in the treatment of EGFRIs-related xerosis and pruritus, as well as evaluating the safety of the prescription. Methods: Patients (n = 68) who had xerosis after using EGFRIs were enrolled and then randomly divided into the treatment group and control group, respectively, receiving ZYG and placebo granules combined with vitamin E ointment. The intervention lasted 4 weeks. Changes in xerosis and pruritus were observed, and blood routine examination as well as liver and kidney function are observed as safety indexes. The water content of skin and qualify of life were observed. Results: A total of 66 out of 68 patients finished the study with 34 patients in each group. The effective rates of xerosis among the treatment group and control group were 84.8% and 69.7% after 2 weeks' treatment (P < .05), while they were 84.8% and 75.8% after 4 weeks' treatment (P < .05). The patients in the experimental group had better quality of life than that in the control group (P = .045). Conclusion: ZYG can effectively improve the skin dryness associated with EGFRIs, and significantly improve the quality of life of patients with good safety; however, larger randomized controlled trials are needed to verify these findings.

The influence of the Chuyou Yuyang granule on the Toll-like receptor/nuclear factor-κB signal pathway in Helicobacter pylori-positive peptic ulcer patients.

BACKGROUND: The cure rate of Helicobacter pylori (HP)-positive peptic ulcer has appeared to downward trend, and the resistance of the ulcer relapse has become a hot issue. METHODS: Hematoxylin and eosin staining was used to detect the repair of the damaged tissues in patients after treatment with the Chuyou Yuyang granule (CYYY). Elisa was used to analyze the expression of cytokine interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α) in the patients' serum. Western blot analysis was used to explore the mechanism of the CYYY. Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect the expression of microRNA-155a (miR-155a) and miR-146a in the blood of the patients and to confirm whether CYYY could cure peptic ulcer through regulation of miR-155a and miR-146a. RESULTS: The damaged gastric mucosal tissues of ulcer patients were significantly repaired by treating with CYYY. The pro-inflammatory cytokine IL18 and TNF-α were notably repressed after treating with CYYY. In addition, CYYY played a key role in regulation of the Toll-like receptor (TLR4)/nuclear factor-κB (NF-κB) signal pathway and the expression of miR-155a and miR-146a. CONCLUSION: CYYY was a highly effective therapeutic method for peptic ulcer patients by inhibiting the activation of the TLR4/NF-κB signal pathway and suppressing the expression of miR-155a and miR-146a.

Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer.

To investigate the clinical efficacy of autologous cytokine induced killer (CIK) cells transfusion combined with radiochemotherapy in the treatment of advanced cervical cancer. A total of 89 hospitalized patients with advanced cervical cancer were admitted and divided into the treatment group (44 cases, autologous CIK cells transfusion combined with radiochemotherapy) and the control group (45 cases, radiochemotherapy) by a randomized non-blind method. Comparisons of therapeutic efficacies, immune functions, life qualities and survival rates were analyzed between the two groups. The short-term therapeutic efficacy of the treatment group was significantly higher than that of the control group. There was no significant difference in 1, 2 and 3 year survival rates between the two groups. Compared with pre-treatment, levels of CD3+, CD4+/CD8+ in peripheral blood were increased in the CIK group, which were reduced in the control group. In the CIK group,only the feeling was depressed on the 25th day post-treatment (T25) compared with the day before treatment (B1). However in the control group, the function of body, role, social and holistic health was obvious disordered on day T25 compared with day B1. On day T25, there were significant differences in function of body, social and holistic health between two groups. Autologous CIK cells transfusion combined with radiochemotherapy shows better short-term efficacy than radiochemotherapy alone in the treatment of advanced cervical cancer, which obviously improves immune function and life quality of patients with low side effects.

Increased iron deposition of deep cerebral gray matter structures in hemodialysis patients: A longitudinal study using quantitative susceptibility mapping.

BACKGROUND: The cerebral iron overload in hemodialysis patients has been reported in a previous study, in which the evaluation of the changes in iron content could be affected by the cross-sectional analysis. PURPOSE: To investigate the longitudinal changes of iron deposition in hemodialysis patients using quantitative susceptibility mapping (QSM) and correlate these findings with the longitudinal changes of neurocognitive function and clinical factors. STUDY TYPE: Prospective; longitudinal. POPULATION: In all, 34 patients and 30 healthy controls (HCs); the mean follow-up interval was 22 ± 7 months. FIELD STRENGTH/SEQUENCE: 3.0T, susceptibility-weighted imaging (SWI). ASSESSMENT: QSM reconstructed from original phase data of SWI was used to measure the susceptibility of gray matter structures including bilateral caudate nucleus (CN), globus pallidus (GP), putmen (PUT), red nucleus (RN), substantia nigra (SN), dentate nucleus (DN), thalamus (THA), pulvinar of thalamus (PT). The Mini-Mental State Examination (MMSE) test and clinical factors were recorded. STATISTICAL TESTING: Analysis of covariance adjusting for age and gender as covariates or a paired t-test for the differences in susceptibility, MMSE scores, and clinical factors among baseline, follow-up patients, and HCs. Correlation and stepwise regression analysis for the relationship between susceptibility, MMSE scores, and clinical factors. RESULTS: The susceptibility of bilateral CN, GP, PUT, RN, SN, DN, THA, PT in follow-up patients was significantly higher than that in baseline between patients and HCs except for left THA (all P < 0.05; Bonferroni corrected). MMSE scores significantly negatively correlated with the susceptibility of bilateral CN, PUT, and RRN in the baseline examination and bilateral CN, PUT, RN, and DN in the follow-up examination (all P < 0.05; false discovery rate [FDR] corrected). The follow-up interval, creatinine, phosphorus, and calcium were independent factors for the increased susceptibility of some nuclei (all P < 0.05). DATA CONCLUSION: The iron deposition of gray matter nuclei in hemodialysis patients increased over roughly a 2-year period and may be a risk factor for neurocognitive impairment. Creatinine and abnormal calcium-phosphorus metabolism were independent risk factors for abnormal iron deposition. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:786-799.

Treatment of severe rash caused by crizotinib with both traditional Chinese medicine and Western medicine: Two case reports and literature review.

RATIONALE: Lung adenocarcinoma is the most common pathologic pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment. Crizotinib is generally well tolerated while its most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac and endocrine abnormalities. Rash caused by crizotinib is rarely seen, and there are few case reports of severe rash caused by crizotinib. PATIENT CONCERNS AND DIAGNOSES: Here we report cases of an 81-year-old man and a 66-year-old woman with ALK-rearranged advanced lung adenocarcinoma. When patients came to our department, they both had crizotinib-induced severe rash. INTERVENTIONS: Crizotinib was initiated as the 1st-line treatment without other therapies. We treated severe rash with traditional Chinese medicine (TCM) therapy called Zhiyang Pingfu liquid along with Western medicine. Zhiyang Pingfu liquid consists of Scutellaria baicalensis 20 g, Portulaca oleracea 30 g, Cortex Dictamni 30 g, Sophora flavescens 30 g, and other substances. Western medicine includes Minocycline hydrochloride tablets and Aprepitant capsules. OUTCOMES: Both patients achieved a partial response when treated with crizotinib, and suffered from severe rash. With Zhiyang Pingfu liquid and Western medicine, their rash gradually disappeared with no sign of cancer progression. Also the male patient did not relieve after taking only antibiotics (standard therapy) and anti-allergic medicine. LESSONS: Despite the dramatic benefit of crizotinib for patients with ALK rearrangement, crizotinib-induced severe rash needs to be dealt with caution. This is the 1st case in which TCM and Western medicine are used to successfully treat crizotinib-induced severe rash. The mechanism of crizotinib-induced rash deserves further attention in future research.

Feasibility of Formal Mindfulness-Based Stress-Resilience Training Among Surgery Interns: A Randomized Clinical Trial.

Importance: Among surgical trainees, burnout and distress are prevalent, but mindfulness has been shown to decrease the risk of depression, suicidal ideation, burnout, and overwhelming stress. In other high-stress populations, formal mindfulness training has been shown to improve mental health, yet this approach has not been tried in surgery. Objective: To test the feasibility and acceptability of modified Mindfulness-Based Stress Reduction (MBSR) training during surgical residency. Design, Setting, and Participants: A pilot randomized clinical trial of modified MBSR vs an active control was conducted with 21 surgical interns in a residency training program at a tertiary academic medical center, from April 30, 2016, to December 2017. Interventions: Weekly 2-hour, modified MBSR classes and 20 minutes of suggested daily home practice over an 8-week period. Main Outcomes and Measures: Feasibility was assessed along 6 domains (demand, implementation, practicality, acceptability, adaptation, and integration), using focus groups, interviews, surveys, attendance, daily practice time, and subjective self-report of experience. Results: Of the 21 residents included in the analysis, 13 were men (62%). Mean (SD [range]) age of the intervention group was 29.0 (2.4 [24-31]) years, and the mean (SD [range]) age of the control group was 27.4 (2.1 [27-33]) years. Formal stress-resilience training was feasible through cultivation of stakeholder support. Modified MBSR was acceptable as evidenced by no attrition; high attendance (12 of 96 absences [13%] in the intervention group and 11 of 72 absences [15%] in the control group); no significant difference in days per week practiced between groups; similar mean (SD) daily practice time between groups with significant differences only in week 1 (control, 28.15 [12.55] minutes; intervention, 15.47 [4.06] minutes; P = .02), week 2 (control, 23.89 [12.93] minutes; intervention, 12.61 [6.06] minutes; P = .03), and week 4 (control, 26.26 [13.12] minutes; intervention, 15.36 [6.13] minutes; P = .04); course satisfaction (based on interviews and focus group feedback); and posttraining-perceived credibility (control, 18.00 [4.24]; intervention, 20.00 [6.55]; P = .03). Mindfulness skills were integrated into personal and professional settings and the independent practice of mindfulness skills continued over 12 months of follow-up (mean days [SD] per week formal practice, 3 [1.0]). Conclusions and Relevance: Formal MBSR training is feasible and acceptable to surgical interns at a tertiary academic center. Interns found the concepts and skills useful both personally and professionally and participation had no detrimental effect on their surgical training or patient care. Trial Registration: ClinicalTrials.gov identifier: NCT03141190.

[Research development of ginkgo terpene lactones].

Ginkgo terpene lactones, as an important active ingredient from Ginkgo leaves, has high medicinal values and has been widely used in clinics. This article would review the researches both at home and abroad, including chemical composition, structure-activity relationship, analytical methods, pharmacological effects, pharmacokinetic characteristics, and so on, providing a reference for further development and utilization of ginkgo terpene lactones.

Quality of life and psychological distress are differentially associated with distinct symptom-functional states in terminally ill cancer patients' last year of life.

OBJECTIVE: Quality of life (QOL) and psychological distress at end of life (EOL) heavily depend on symptom distress and functional impairment, which may not deteriorate synchronously at EOL. METHODS: Using multivariate hierarchical linear modeling, we simultaneously evaluated the differential association of 5 previously identified, worsening conjoint symptom-functional states with QOL, anxiety symptoms, and depressive symptoms over 317 terminally ill cancer patients' last year of life. Quality of life, anxiety symptoms, and depressive symptoms were measured by the McGill Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale, respectively. RESULTS: Quality of life, anxiety symptoms, and depressive symptoms deteriorated significantly more for patients in the 4 worst symptom-functional states (states 2-5) than in the best state (state 1). Quality of life did not differ significantly among patients in states 2 to 5. However, patients in state 4 had significantly lower anxiety-symptom levels than patients in states 2, 3, and 5, whose anxiety-symptom levels did not differ significantly. In contrast, depressive-symptom levels differed significantly between participants in any 2 of the worst symptom-functional states, except between participants in states 3 and 5 as well as between those in states 2 and 4. CONCLUSION: The 5 distinct symptom-functional states contributed to worsening QOL, anxiety symptoms, and depressive symptoms, but each was negatively and uniquely associated with psychological well-being in terminally ill cancer patients' last year of life. CLINICAL IMPLICATIONS: The psychological well-being and QOL of high-risk patients in states 3 and 5 may be improved at EOL by targeting them with appropriate symptom management interventions and facilitating their functioning.

Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice.

To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and molecular changes in response to feeding a typical American fast food or Western diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS diet showed increased body, liver, and epididymal fat pad weight as well as increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (a measure of liver injury) and liver triglyceride content. Coadministration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver triglycerides. NDGA treatment also improved insulin sensitivity but not glucose intolerance in mice fed the ALIOS diet. In mice fed the NDGA+ALIOS diet, NDGA supplementation induced peroxisome proliferator-activated receptor α (PPARα; the master regulator of fatty acid oxidation) and mRNA levels of carnitine palmitoyltransferases Cpt1c and Cpt2, key genes involved in fatty acid oxidation, compared with the ALIOS diet. NDGA significantly reduced liver endoplasmic reticulum (ER) stress response C/EBP homologous protein, compared with chow or the ALIOS diet, and also ameliorated ALIOS diet-induced elevation of apoptosis signaling protein, caspase 3. Likewise, NDGA downregulated the ALIOS diet-induced mRNA levels of Pparg, fatty acid synthase Fasn, and diacylglycerol acyltransferase Dgat2 NDGA treatment of ALIOS-fed mice upregulated the hepatic expression of antioxidant enzymes, glutathione peroxidase 4, and peroxiredoxin 3 proteins. In conclusion, we provide evidence that NDGA improves metabolic dysregulation by simultaneously modulating the PPARα transcription factor and key genes involved in fatty acid oxidation, key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling pathways.

Biotransformation of ginsenosides F4 and Rg6 in zebrafish.

Ginsenosides F4 and Rg6 (GF4 and GRg6), two main active components of steamed notoginseng or red ginseng, are dehydrated disaccharide saponins. In this work, biotransformation of ginsenosides F4 and Rg6 in zebrafish was investigated by qualitatively identifying their metabolites and then proposing their possible metabolic pathways. The prediction of possible metabolism of ginsenosides F4 and Rg6 using zebrafish model which can effectively simulate existing mammals model was early and quickly performed. Metabolites of ginsenosides F4 and Rg6 after exposing to zebrafish for 24 h were identified by Ultraperformance Liquid Chromatography/Quadrupole-Time-of-Flight Mass Spectrometry. A total of 8 and 6 metabolites of ginsenosides F4 and Rg6 were identified in zebrafish, respectively. Of these, 7 and 5, including M1, M3-M5, M7-M9 and N1 (N5), N2, N4 (N9), N7-N8 were reported for the first time as far as we know. The mechanisms of their biotransformation involved were further deduced to be desugarization, glucuronidation, sulfation, dehydroxylation, loss of C-17 and/or C-23 residue pathways. It was concluded that loss of rhamnose at position C-6 and glucuronidation at position C-3 in zebrafish were considered as the main physiologic and metabolic processes of ginsenosides F4 and ginsenosides Rg6, respectively.