Timing umbilical therapy in treatment of neurogenic bladder after spinal cord injury based on midnight-noon and ebb-flow doctrine: a randomized controlled trial. / åŸºäºŽå­åˆæµæ³¨ç†è®ºæ‹©æ—¶è„ç–—æ²»ç–—è„Šé«“æŸä¼¤åŽç¥žç»æºæ€§è†€èƒ±ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of timing umbilical therapy for neurogenic bladder after spinal cord injury based on the midnight-noon and ebb-flow doctrine. METHODS: Sixty patients with neurogenic bladder after spinal cord injury were randomly divided into a trial group and a control group, with 30 patients in each group. In the trial group, based on the midnight-noon and ebb-flow doctrine, umbilical therapy was given at the time zone, 15:00 to 17:00. In the control group, umbilical therapy was delivered at any time zones except the period 15:00 to 17:00. The herbal plaster was remained on the umbilicus for 4 h each time, once daily. One course of treatment was composed of 2 weeks and the treatment lasted 4 weeks. Before and after treatment, the urodynamic indexes (maximum urinary flow rate [Qmax], maximum detrusor pressure [Pdet-max], residual urine volume [RUV]), voiding diary (average daily number of voiding, average daily number of leakage, average daily voided volume), neurogenic bladder symptom score (NBSS), the score of urinary symptom distress scale (USDS) and the score of World Health Organization quality of life assessment-BREF (WHOQOL-BREF) were compared between the two groups; and the clinical efficacy of the two groups was assessed. RESULTS: After treatment, Qmax, Pdet-max, the average daily voided volume and the scores of WHOQOL-BREF were increased (P<0.05); and RUV, the average daily number of voiding, the average daily number of leakage, NBSS and the scores of USDS were all reduced (P<0.05) in comparison with those before treatment in the two groups. When compared with those in the control group, Qmax, Pdet-max, the average daily voided volume and the score of WHOQOL-BREF were all higher (P<0.05); and RUV, the average daily number of voiding, the average daily number of leakage, NBSS and the score of USDS were lower (P<0.05) in the trial group. The total effective rate was 96.7% (29/30) in the trial group, higher than that (76.7%, 23/30) in the control group (P<0.05). CONCLUSIONS: Timing umbilical therapy, based on the midnight-noon and ebb-flow doctrine, effectively relieves the symptoms of dysuria and improves the quality of life in patients with neurogenic bladder after spinal cord injury.

Research trends in complementary and alternative treatments for insomnia over the past decade: A bibliometrics analysis.

Insomnia is the most common sleep disorder, with persistent insomnia being associated with greater risk and leading to a range of functional consequences that place a heavy burden on patients and healthcare systems. A weight of evidence has shown that complementary and alternative medicine (CAM) seems to have a positive effect on improving sleep. However, the research trends of CAM intervention for insomnia have not been studied systematically through bibliometrics. We searched the relevant literature over the past decade in the Web of Science Core Collection database on September 20, 2022 and used CiteSpace and gCLUTO to visually analyze and cluster countries, institutions, authors, journals and keywords. Through screening, 1655 papers were included. In the past decade, the number of articles published in this field shown an annual trend of growth, with explosive growth in 2020. The USA has the largest number of publications, the University of Hong Kong is the leading institution in this field, and the most cited journal is Sleep. Mental condition and quality of life in patients with insomnia, insomnia related to cancer, effect of mindfulness meditation, yoga and aromatherapy on insomnia and the psychiatric symptoms resulting from the COVID-19 pandemic are at the forefront of this field. In this study, bibliometrics and visualization analysis were performed on related studies on CAM intervention for insomnia. This will be the focus and development direction of insomnia treatment in the future to formulate structured treatment plans for traditional Chinese medicine-related CAM, validate large-scale clinical trials, solve cancer comorbidity insomnia and related psychiatric symptoms and deal with mental health-related insomnia after public health outbreaks.

A chemometric study on the identification of 5-methylfurfural and 2-acetylfuran as particular volatile compounds of oxidized fish oil based on SHS-GC-IMS.

Fish oil develops particular off-odors, mainly fishy odor, from the oxidation of its characteristic fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA). Anchovy oil (AO) was taken as representative of fish oils. This was compared to three vegetable oils with different fatty acid compositions, i.e. camellia, sunflower and linseed oil, and differential volatile compounds were identified by static-headspace gas-chromatography ion-mobility-spectrometry (SHS-GC-IMS) and orthogonal partial-least-squares discriminant analysis (OPLS-DA) during oxidation at 60 °C. Three groups of differential volatile compounds detected at higher concentrations in the AO were screened out and two compounds, identified as 5-methylfurfural and 2-acetylfuran, were characteristic to the AO and not found in the vegetable oils. They were formed from both EPA and DHA, only present in the AO, and their formation mechanisms were proposed. The contents of 5-methylfurfural and 2-acetylfuran increased linearly with the oxidation time and consequently they could be used as oxidative markers of fish oils.

Treatment of Lung Cancer with Orally Administered Chinese Herbal Medicine: An Evidence Map between 1970-2020.

OBJECTIVE: Through showing the full picture of double-arm controlled clinical research and systematic review evidence in the field of orally administrated Chinese herbal medicine (CHM) for treatment of lung cancer, to provide a reference for future clinical research and to indicate a direction for future systematic reviews. METHODS: A comprehensive search of clinical controlled studies was performed regarding orally administered CHM treatment for lung cancer published from January 1970 to September 2020. The language was restricted to Chinese and English. Relevant data were extracted, the quality of systematic reviews was evaluated, and the research evidence was visually displayed. RESULTS: Randomized controlled trials were the most common type of research design. The research sample sizes were typically small. Oral CHM showed certain curative advantages in treating lung cancer. The key stages in oral CHM intervention for lung cancer are chemotherapy, radiotherapy, and late palliative treatment. The advantageous outcomes of oral CHM treatment of lung cancer are the short-term efficacy, quality of life, and adverse reactions. The perioperative stage, overall survival, pharmacoeconomic evaluation, and Chinese medicine decoctions are weak research areas. CONCLUSIONS: CHM has staged and therapeutic advantages in treating lung cancer. The overall methodological quality is poor, and the level of evidence requires improvement. It is necessary to carry out large-scale, standardized, and higher-quality research in the superior and weak areas of CHM treatment of lung cancer.

Pharmacological characterization of a novel metal-based proteasome inhibitor Na-AuPT for cancer treatment.

The ubiquitin-proteasome system (UPS) is essential for maintaining cell homeostasis by orchestrating the protein degradation, but is impaired in various diseases, including cancers. Several proteasome inhibitors, such as bortezomib, are currently used in cancer treatment, but associated toxicity limits their widespread application. Recently metal complex-based drugs have attracted great attention in tumor therapy; however, their application is hindered by low water-solubility and poor absorbency. Herein, we synthesized a new type of gold (I) complex named Na-AuPT, and further characterized its anticancer activity. Na-AuPT is highly water-soluble (6 mg/mL), and it was able to potently inhibit growth of a panel of 11 cancer cell lines (A549, SMMC7721, H460, HepG2, BEL7402, LNCap, PC3, MGC-803, SGC-7901, U266, and K562). In A549 and SMMC7721 cells, Na-AuPT (in a range of 2.5-20 µM) inhibited the UPS function in a dose-dependent fashion by targeting and inhibiting both 20 S proteasomal proteolytic peptidases and 19 S proteasomal deubiquitinases. Furthermore, Na-AuPT induced caspase-dependent apoptosis in A549 and SMMC7721 cells, which was prevented by the metal chelator EDTA. Administration of Na-AuPT (40 mg · kg-1 · d-1, ip) in nude mice bearing A549 or SMMC7721 xenografts significantly inhibited the tumor growth in vivo, accompanied by increased levels of total ubiquitinated proteins, cleaved caspase 3 and Bax protein in tumor tissue. Moreover, Na-AuPT induced cell death of primary mononuclear cells from 5 patients with acute myeloid leukemia ex vivo with an average IC50 value of 2.46 µM. We conclude that Na-AuPT is a novel metal-based proteasome inhibitor that may hold great potential for cancer therapy.

[Rapid quality evaluation of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle based on color digitization and multi-component determination].

To explore the color value changes after processing and further explore the correlations between color values and internal components, we established a rapid evaluation method for the quality of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. In this study, the color values of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle were digitized by a spectrophotometer, and the standard ranges of color values of the two herbal medicines were established. Further, a discriminant analysis model was established to quickly and accurately distinguish the two herbal medicines. The content of 9 flavonoids and 1 triterpene in Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle were determined by HPLC, and Pearson correlation analysis was adopted to analyze the correlations between the color values and the content of 10 components. The standard ranges of L~*, a~*, and b~* values were 65.539 6-68.305 8, 7.296 3-8.467 3, and 29.998 8-32.212 8 for Glycyrrhizae Radix et Rhizoma, and 43.654 3-47.166 4, 14.050 0-15.133 8, and 16.424 6-20.984 8 for Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, respectively. Glycyrrhizae Radix et Rhizoma had higher L~* and b~* values and lower a~* value than Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, which indicated that processing with honey decreased the white and yellow values and increased the red value. The original and cross validation of the established discriminant analysis model met the requirements, and the external validation of the model showed the prediction accuracy of 100%. Pearson correlation analysis showed that the a~* value was positively correlated with the content of liquiritin apioside and isoliquiritin apioside(P<0.05), while the L~* and b~* values were negatively correlated with the content of the above two components(P<0.05). After processing with honey, L~* and b~* decreased while a~* increased, and the content of liquiritin apioside and isoliquiritin apioside increased, which was consistent with the content determination results. This study reveals the regularity of the color values of Glycyrrhizae Radix et Rhizoma after processing with honey roasting, as well as the correlations between color values and component content, which provides a basis for the rapid quality evaluation of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle.

Acute and life-threatening complications in patients with anorexia nervosa: A case report and literature study.

Anorexia nervosa (AN) is characterized by a strong fear of weight gain and body image disorders and is classified as a mental illness that can cause direct damage to one's mental health and body. Many individuals with AN tend to commit suicide. Additionally, the disease can lead to chronic undernutrition and low body weight, adversely affecting each body system, exacerbating systemic medical complications, especially acute life-threatening complications. Therefore, AN has the highest mortality and disability rates among all mental diseases. There is a basic clinical need to identify and address the acute and critical complications of this disease as soon as possible. However, the current literature has a poor description of the acute and critical complications of AN and lacks a systematic review. We report a case of a patient with AN and severe hypokalemia, significant Q-T interval prolongation, stomach dilation, and intestinal obstruction who recovered after conservative treatment. The defecation method we used, to our knowledge, has not been previously reported in the literature. We also briefly review the various acute and life-threatening complications of AN.

Effects of the composite of buckwheat-oat-pea on blood glucose in diabetic rats / 北京大学学报(医学版)

OBJECTIVE@#To study the effects of buckwheat-oat-pea (BOP) composite flour [buckwheat ∶ oats ∶ peas=6 ∶ 1 ∶ 1 (quality ratio)] on blood glucose in diabetic rats.@*METHODS@#In this study, 64 male Sprague-Dawley rats were divided into 8 groups by fasting blood glucose (FBG) and body weight: normal control group, model control group, metformin group, buckwheat group, oats group, BOP low-dose group (BOP-L), medium-dose group (BOP-M), and high-dose group (BOP-H). The rats in the normal control group were fed with normal diet, the rats in the model control group and metformin group were fed with a high-fat diet (HFD), and the rats in the buckwheat group, oats group, and BOP-L, BOP-M, BOP-H groups were fed with HFD containing 10% buckwheat flour, 10% oat flour, 3.3% BOP, 10% BOP, 30% BOP, respectively. The HFD in all the groups had the same percentage of energy from fat (45%). After 30 days, the rats fed with HFD received intraperitoneal injection of streptozotocin (30 mg/kg, once a week for two weeks) to establish diabetes mellitus. After the model was successful established, the rats were fed for another 28 days. During the study, the body weight, food intake/body weight (FI/BW) and water intake/body weight (WI/BW), food utilization rate, 24 h urine volume, FBG, glucose area under curve (GAUC) of oral glucose tolerance test were measured regularly. At the end of the study, the fasting serum glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.@*RESULTS@#With the inducing of HFD and streptozotocin, compared with the normal control group, the rats in the model control group had higher FI/BW, WI/BW, 24 h urine volume, FBG, GAUC, HOMA-IR (P < 0.05), and lower body weight, food utilization rate (P < 0.05). Compared with the model control group, the rats in the three BOP groups all had higher body weight, food utilization rate (P < 0.05), and lower WI/BW, HOMA-IR (P < 0.05); the rats in the BOP-L and BOP-M groups had lower FI/BW, 24 h urine volume, FBG (P < 0.05), and the rats in the BOP-M group also had lower GAUC (P < 0.05). After the establishment of diabetes, there was no significant difference in blood glucose and the other indicators between the rats in the three BOP groups and the buckwheat group or the oats group (P>0.05).@*CONCLUSION@#The BOP had the effects of reducing blood glucose, insulin resistance and diabetic symptoms on diabetic rats, and had the value for further development and utilization.

Application Status of Chinese Medicine on Cancer Rehabilitation: A Preliminary Questionnaire Survey.

OBJECTIVE: To investigate the application status of Chinese medicine (CM) in cancer rehabilitation, so as to provide references for improving the level of CM cancer rehabilitation. METHODS: A survey questionnaire regarding "application status of CM rehabilitation in cancer patients" for oncologists (doctor version) and cancer patients (patient version) were developed, respectively. From September 2014 to November 2016, a total of 1,000 doctors from oncology department in 48 hospitals and 2,000 cancer patients from CM oncology department from 8 hospitals in China were recruited in this survey. The psychological, nutrition and exercise rehabilitation guidance for cancer patients provided by doctors, their mastery conditions regarding cancer staging treatment and CM syndrome differentiation, and recommendation from doctors on CM rehabilitation were investigated. Cancer patients' awareness on the importance of psychological, nutrition and exercise rehabilitation, as well as their knowledge and needs for rehabilitation were also analyzed. The impact of gender, age, professional title, hospitals grades of physicians on their knowledge of cancer staging treatment and CM syndrome differentiation, and the relationship between gender, age, education level and economic conditions and patient's knowledge along with the needs of CM rehabilitation were further analyzed. RESULTS: Totally 1,000 questionnaires were issued to doctors and 963 questionnaires returned, among which 948 were valid representing a response rate of 94.80%. A total of 2,000 questionnaires were issued to patients and 1,705 valid data finally returned with a response rate of 85.25%. The survey showed that cancer patients generally paid much attention to psychological, nutritional and sports rehabilitation, and had a strong demand for CM rehabilitation. Knowledge of CM rehabilitation was not well provided by oncologists, and the rehabilitation guidance as well as CM rehabilitation measures were obviously insufficient in cancer patients. Educational and economic levels were positively correlated with cognition level of CM rehabilitation knowledge among cancer patients (Kendall-tau_b correlation coefficients=0.130, 0.057, respectively; P<0.05). Gender and education level were positively correlated with the patients' willingness for taking CM measures (Kendall-tau_b correlation coefficient=0.057, 0.105, respectively; P<0.05). Age was negatively correlated with intention of applying CM measures (kendall-taub correlation coefficient=-0.105, P<0.05). CONCLUSIONS: Health education and professional training for both cancer patients and oncologists should be strengthened and CM rehabilitation knowledge among cancer patients and oncologists should be improved, so as to give full play to CM in cancer rehabilitation.

[Efficacy of medicinal penetration on acupoint as adjunctive therapy on histiocytic necrotizing lymphadenitis of heat-toxin syndrome: a randomized controlled trial].

OBJECTIVE: To evaluate the clinical efficacy of medicinal penetration on acupoint combined with medication for histiocytic necrotizing lymphadenitis (HNL) of heat-toxin syndrome, and to explore the methods of improving the clinical effect. METHODS: A total of 72 cases with HNL with heat-toxin syndrome were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with oral administration of prednisone tablets for 40 days (first 5 days: 10 mg, three times a day; since then, reduced by 5 mg every 7 days). In the observation group, on the basis of the medication in the control group, the patients were treated with acupoint application and ultrasonic drug penetration therapy, once a day for 14 days. The acupoints of Waiguan (TE 5), Fengchi (GB 20) of affected side and ashi points were selected. The changes of target lymph node swelling, visual analogue score (VAS), axillary temperature and total score of symptoms and signs were evaluated before treatment and 7, 14, 28 and 40 d into treatment; the changes of white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and lactic dehydrogenase (LDH) were evaluated on 14 d and 40 d into treatment; the patients were followed-up for half a year. RESULTS: ① Fourteen days into treatment, the clinical cured rate in the observation group was 38.9% (14/36), which was superior to 16.7% (6/36) in the control group (P<0.01); the clinical cured rates were both 100% in the two groups on 40 d into treatment. ② The VAS score, axillary temperature and the total score 7 d into treatment, as well as node swelling, VAS score, axillary temperature and the total score 14, 28 and 40 d into treatment in the two groups were significantly improved (P<0.01); the total score and VAS score of 7 d into treatment, target lymph node swelling, VAS score and total score of 14 d into treatment in the observation group were significantly improved than those in the control group (P<0.01). ③ Compared before treatment, WBC, CRP, ESR in the two groups were significantly improved 14 d and 40 d into treatment (P<0.01), and LDH in the two groups were decreased 40 d into treatment (P<0.01), but there was no significant difference between the two groups (P>0.05). ④ The recurrence rate in the observation group was 5.6% (2/36), which was similar to 16.7% (6/36) in the control group (P>0.05). CONCLUSION: The medicinal penetration on acupoint as adjunctive treatment could effectively relieve the discomfort symptoms of HNL patients with syndrome of heat and toxin, improve the clinical cured rate, and provide the research direction for shortening the course of medication.

Genome-wide analysis of the role of DNA methylation in inbreeding depression of reproduction in Langshan chicken.

Inbreeding depression of chicken reproduction is a major concern in the conservation of chicken genetic resources. To investigate the potential DNA methylation sites involved in the inbreeding depression of chicken reproduction, we carried out whole-genome bisulfite sequencing (WGBS) of hypothalamus and ovary tissues from the strongly and weakly inbred Langshan chickens, respectively. 5948 and 4593 differentially methylated regions (DMRs) were identified in the hypothalamus and ovary between the strongly and weakly inbred Langshan chickens, respectively. Large numbers of DMR-related genes (DMGs) were enriched in reproduction-related pathways. By combining the WGBS and transcriptome data, two DMRs in SRD5A1 and CDC27 genes were inferred as the most likely biomarkers of inbreeding depression of reproduction in Langshan chicken. Our study provides the first systematic investigation of the DNA methylation changes in strongly inbred chickens, and extends our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction.

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS: Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro.

Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid (HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit (NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 µg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1ß, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine (approval No. BUCM-3-2016040201-2003) in April 2016.

Heme oxygenase-1 attenuates seawater drowning-induced acute lung injury through a reduction in inflammation and oxidative stress.

OBJECTIVE: Heme oxygenase-1 (HO-1) plays a critical protective role in various insults-induced acute lung injury (ALI) through its strong anti-inflammatory, anti-oxidant, and anti-apoptotic properties, but its protective role and mechanism on seawater aspiration-induced acute lung injury remains unclear. This study aimed to explore the therapeutic potential and mechanism of HO-1 to attenuate seawater aspiration-induced ALI in vivo and in vitro. METHODS: The viability and invasion of A549 cell were analyzed through cell counting kit-8 and lactate dehydrogenase release assay; the transcriptional level of inflammatory cytokines (TNF-α, IL-6, IL-8 and MCP-1) and cell proliferation-related cytokines (FoxM1, Ccnb1 and Cdc25C) in seawater-treated A549 cell were tested by qPCR; apoptotic cells were analyzed by flow cytometryd; HO-1mRNA and protein were determined by qPCR and western blotting; the fluorescent indicators (DCFH-DA, dihydroethidium, MitoSox Red and Fluo-4) were used to monitor generation of ROS and mitochondrial function. The lung wet/dry weight radio and lactate dehydrogenase activity, Sirius red staining, TUNEL assay and immunohistochemical staining with anti-pan Cytokeratin antibody were analyzed in seawater-drowning mice. The role of HO-1 on seawater-drowning pulmonary injury was explored via HO-1 activity inhibitors (Zinc protoporphyrin) in vitro and in vivo. RESULTS: Seawater exposure decreased the cellular viability, increased the production of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α), induced cellular apoptosis and inhibited the expression of cell proliferation-related cytokines (FoxM1, Ccnb1 and Cdc25C). Moreover, seawater exposure led to mitochondrial dysfunction in A549 cells. Supplement of HO-1 sepcific inducer (heme) or its catalytic product (biliverdin) significantly attenuated seawater-induced A549 damage and promoted cell proliferation. However, Zinc protoporphyrin abolished the beneficial effects of HO-1 on seawater drowning-induced pulmonary tissue injury. CONCLUSION: HO-1 attenuates seawater drowning-induced lung injury by its anti-inflammatory, anti-oxidative, and anti-apoptosis function.

Low molecular weight heparin monotherapy for recurrent abortion with antiphospholipid system: A protocol of a systematic review.

BACKGROUND: Previous clinical studies reported low molecular weight heparin (LMWH) monotherpay has been utilized for the treatment of recurrent abortion (RCA) with antiphospholipid system (APS). However, its efficacy is still inconclusive. This systematic review aims to assess its efficacy and safety for patients with RCA and APS. METHODS: A systematic literature search for article up to February 2019 will be conducted in 9 databases: Cochrane Library, EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Inclusion criteria are randomized control trials of LMWH monotherpay for patients with RCA and APS. The Cochrane risk of bias tool will be used to evaluate the methodological quality for each qualified study. The summary results will be showed by using fixed-effects and random-effects models for pooling the data based on the heterogeneity of included studies. RESULTS: This systematic review will assess the clinical efficacy and safety of LMWH monotherpay in treating RCA with APS. The primary outcome is pregnancy loss. The secondary outcomes include frequency of preterm delivery, live birth rates, maternal and fetal complications, as well as adverse events. CONCLUSION: The findings of this study will summarize the present evidence to judge whether LMWH monotherpay is an effective therapy for patients with RCA and APS. DISSEMINATION AND ETHICS: The findings of this study will be published by through peer-reviewed journals. This study does not needs ethic documents, because it will not analyze individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121064.

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC).@*METHODS@#This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome.@*RESULTS@#Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients.@*CONCLUSIONS@#Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Effect of Cooling Blood Method in Inhibiting Macrophage Apoptosis Against Atherosclerosis / 中国实验方剂学杂志

Objective: To observe the effect of serum-containing Qingxin Tongmai decoction(QXTMD) on the apoptosis rate of mouse mononuclear macrophage cell line RAW264.7 induced by Acetylated low density lipoprotein (ac-LDL) and the expressions of type A scavenger receptor(SR-A), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), inositol-requiring enzyme 1α(IRE1α), exploring the possible mechanism of QXTMD in the treatment of atherosclerosis.Method: Eight New Zealand rabbits were randomly divided into the atorvastatin group (2.6 g·kg-1) low, medium and high-dose QXTMD groups (3.33, 6.66, 13.32 mg·kg-1). After 7 days of gavage, the carotid blood was collected to prepare drug-containing serum. The RAW264.7 cell line was stimulated with 2.5%, 5%, 10%, and 20% drug-containing serum culture for 6, 12, and 24 h, respectively. The cell proliferation rate was observed by cell counting kit-8 (CCK-8) method. The RAW264.7 cell line was cultured in vitro and divided into blank group, model group, atorvastatin group, and low, medium and high-dose QXTMY groups. The cells in blank group were cultured with bovine serum albumin(BSA). The model group was stimulated with BSA+50 mg·L-1 ac-LDL for 24 h. The other groups were stimulated with BSA+50 mg·L-1 ac-LDL+10% drug-containing serum for 24 h. The apoptosis rate and SR-A expression of RAW264.7 cells were detected by flow cytometry. The expressions of Bcl-2, Bax and IRE1α protein were detected by Western blot.Result: Compared with the blank group, the model group could increase the apoptosis rate of RAW264.7 cells (PPPPα (PPPPPConclusion: QXTMD can reduce the apoptosis rate of macrophages. The mechanism of atherosclerosis may be related to the expressions of Bax, IREα, SR-A and anti-apoptotic protein Bcl-2.

Effect of Puerarin on the Pharmacokinetics of Baicalin in Gegen Qinlian Decoction () in Mice.

OBJECTIVE: To study the pharmacokinetics of puerarin (PUE) in Gegen Qinlian Decoction (, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin (BAL) in mice. METHODS: GQD is composed of the concentrated granules of four Chinese herbs. Three dosages with different levels of PUE, including GQD, GQD co-administered with PUE, and GQD co-administration with two times the amount of PUE, were used to research the pharmacokinetics of PUE and BAL in mice. The indirect competitive enzyme-linked immunosorbent assay (icELISA) methods based on an anti PUE-monoclonal antibody (MAb)and BAL-MAb were employed to determine the concentration of PUE and BAL in mice blood. RESULTS: After the co-administration of GQD with PUE, the area under the curves (AUC0-14h) of PUE increased 2.8 times compared with GQD. At the dose of GQD co-administration at two times that of PUE, the (AUC0-14h) of PUE was almost equal to that of GQD co-administration of PUE, showing non-linear pharmacokinetics. The (AUC0-48h) of BAL showed a good dose-related increase of PUE (r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affects the absorption of BAL in mice. There was no significant difference in the other pharmacokinetic parameters, such as the first time of maximum concentration (Tmax), the second Tmax, or the mean residence time. CONCLUSIONS: The icELISA methods were successfully applied to pharmacokinetic studies of PUE and BAL in GQD in mice. The dosage variability of PUE of the main ingredient in GQD affects its own pharmacokinetic characteristics and the absorption characteristics of BAL.

Gambogic Acid Induces Cell Apoptosis and Inhibits MAPK Pathway in PTEN-/-/p53-/- Prostate Cancer Cells In Vitro and Ex Vivo.

OBJECTIVE: To investigate the effect of gambogic acid (GA) on the growth and cell death of castrate resistant prostate cancer (PC) with phosphate and tension homology (PTEN) and p53 genes deleted in vitro and ex vivo, and elucidate the underlying possible molecular mechanisms. METHODS: PTEN-/-/p53-/- PC cells and Los Angeles prostate cancer-4 (LAPC-4) cells were treated with GA for 24 h and 48 h, then cell viability was determined by cell proliferation assay. PTEN-/-/p53-/- PC cells organoids number was calculated under GA treatment for 1 week. In addition, cell titer glo assay was performed to analyze 3 dimensional cell viability of patients derived xenografts (PDX) 170.2 organoids. Flow cytometry was used to detect apoptotic cells treated with GA. And confocal image was performed to detect the apoptotic mitochondrial morphological changes. Apoptotic cell death related protein levels were measured through Western blot (WB) in GA treated cells and organoids. The expression levels of mitogen-activated protein kinases (MAPKs) pathway related ribonucleic acid (RNAs) and proteins were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and WB, respectively. RESULTS: The treatment of GA significantly reduced cell viability of PTEN-/-/p53-/- PC cells and LAPC-4 in a time- and concentration-dependent manner. In organoids, GA showed strong inhibition towards organoids' numbers and diameters and continuously led to a complete organoids inhibition with GA 150 nmol/L. Ex vivo results validated that GA 1 µmol/L inhibited 44.6% PDX170.2 organoids growth. As for mechanism, flow cytometry detected continuously increased apoptotic portion under GA treatment from 1.98% to 11.78% (6 h) and 29.94% (8 h, P<0.05). In addition, mitochondrial fragmentation emerged in GA treated cells indicated the mitochondrial apoptotic pathway might be involved. Furthermore, WB detected caspases-3, -9 activation and light chain (LC)-3 conversion with GA treatment. WB revealed decreased activity of MAPK pathway and down-regulation of downstream c-fos oncogene RNA level was detected by RT-PCR before undergoing apoptosis (P<0.05). CONCLUSION: GA was a potent anti-tumor compound as for PTEN-/-/p53-/- PC, which contributed to cell apoptosis via inhibition of the MAPK pathway and c-fos.

Effect of Puerarin on the Pharmacokinetics of Baicalin in Gegen Qinlian Decoction () in Mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the pharmacokinetics of puerarin (PUE) in Gegen Qinlian Decoction (, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin (BAL) in mice.</p><p><b>METHODS</b>GQD is composed of the concentrated granules of four Chinese herbs. Three dosages with different levels of PUE, including GQD, GQD co-administered with PUE, and GQD co-administration with two times the amount of PUE, were used to research the pharmacokinetics of PUE and BAL in mice. The indirect competitive enzyme-linked immunosorbent assay (icELISA) methods based on an anti PUE-monoclonal antibody (MAb)and BAL-MAb were employed to determine the concentration of PUE and BAL in mice blood.</p><p><b>RESULTS</b>After the co-administration of GQD with PUE, the area under the curves (AUC) of PUE increased 2.8 times compared with GQD. At the dose of GQD co-administration at two times that of PUE, the (AUC) of PUE was almost equal to that of GQD co-administration of PUE, showing non-linear pharmacokinetics. The (AUC) of BAL showed a good dose-related increase of PUE (r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affects the absorption of BAL in mice. There was no significant difference in the other pharmacokinetic parameters, such as the first time of maximum concentration (T), the second T, or the mean residence time.</p><p><b>CONCLUSIONS</b>The icELISA methods were successfully applied to pharmacokinetic studies of PUE and BAL in GQD in mice. The dosage variability of PUE of the main ingredient in GQD affects its own pharmacokinetic characteristics and the absorption characteristics of BAL.</p>