Efficacy of the traditional Chinese medicine, Buyang Huanwu Decoction, at preventing taxane-induced peripheral neuropathy in breast cancer patients: A prospective, randomized, controlled study.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.

Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms.

The resistance and immune escape of methicillin-resistant Staphylococcus aureus (MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO- and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating icdA and icaA. It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO- penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.

Correlation between lactate dehydrogenase and QTc interval prolongation in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Corrected QT (QTc) interval prolongation is one of the common causes of sudden cardiac death in patients with maintenance hemodialysis (MHD) patients. However, there are few studies on QTc prolongation in MHD patients. The concentration of lactate dehydrogenase (LDH) in hemodialysis population increased, and LDH was associated with the mortality of MHD patients. This study aimed to investigate the relationship between QTc interval prolongation and LDH in MHD patients. METHODS: This is a cross-sectional observational study. Patients who underwent MHD for more than 3 months in the Second Affiliated Hospital of Nantong University from November 2012 to November 2019 with complete data were selected as the research subjects. The patients were divided into the normal QTc interval group and the QTc interval prolongation group. The general data of patients and clinical laboratory indicators were collected retrospectively from the electronic medical record system. Pearson correlation analysis and binary logistic regression were used to analyze the correlation between LDH and QTc interval prolongation; the cut-off value of LDH predicting QTc interval prolongation was calculated by receiver operating characteristic (ROC) curve. RESULTS: The LDH level in the prolonged QTc interval group was significantly higher than that in the normal group (301.96±110.91 vs. 215.39±67.65, t=-8.03, P<0.001). QTc interval and LDH (r=0.386) were positively correlated. Binary logistic regression analysis showed that LDH, serum potassium <4 mmol/L, serum phosphorus, and left ventricular end-diastolic diameter (LVDd) were independent related factors for QTc interval prolongation. The ROC curve results showed that LDH =220 U/L was the best cutoff point for predicting QTc interval prolongation in MHD patients, with a sensitivity of 81.45% and a specificity of 59.35%. Binary logistic regression analysis showed that the LDH >220 U/L group was 6.34 times more likely to have QTc interval prolongation than the LDH ≤220 U/L group (OR 6.34, 95% CI: 3.47-11.58, P<0.001). CONCLUSIONS: LDH in MHD patients is closely related to QTc interval prolongation. Serum LDH, ionic calcium, serum phosphorus and potassium may predict QTc interval prolongation. Monitoring related indicators can remind clinicians to intervene as soon as possible to reduce the potential risk of arrhythmia and sudden cardiac death (SCD).

Classification of Tea Leaves Based on Fluorescence Imaging and Convolutional Neural Networks.

The development of the smartphone and computer vision technique provides customers with a convenient approach to identify tea species, as well as qualities. However, the prediction model may not behave robustly due to changes in illumination conditions. Fluorescence imaging can induce the fluorescence signal from typical components, and thus may improve the prediction accuracy. In this paper, a tea classification method based on fluorescence imaging and convolutional neural networks (CNN) is proposed. Ultra-violet (UV) LEDs with a central wavelength of 370 nm were utilized to induce the fluorescence of tea samples so that the fluorescence images could be captured. Five kinds of tea were included and pre-processed. Two CNN-based classification models, e.g., the VGG16 and ResNet-34, were utilized for model training. Images captured under the conventional fluorescent lamp were also tested for comparison. The results show that the accuracy of the classification model based on fluorescence images is better than those based on the white-light illumination images, and the performance of the VGG16 model is better than the ResNet-34 model in our case. The classification accuracy of fluorescence images reached 97.5%, which proves that the LED-induced fluorescence imaging technique is promising to use in our daily life.

Liujunanwei decoction attenuates cisplatin-induced nausea and vomiting in a Rat-Pica model partially mediated by modulating the gut micsrobiome.

Studies show that traditional Chinese medicine (TCM), such as Liujunanwei (LJAW) decoction, can play important roles in alleviating side effects of chemotherapy. The purpose of this study was to understand how LJAW can counter chemotherapy-induced emesis via alteration of gut microbiota. We evaluated the effect of LJAW on cisplatin (DDP)-induced nausea and vomiting using a rat-pica model. Rats react to emetic-producing stimuli with increased kaolin consumption, a phenomenon called pica. The rats were injected with cisplatin and then randomly assigned to the control (DDP), Ondansetron or LJAW. The intake of kaolin and chow diet as well as body weights were recorded every 24 hours. Fecal samples were collected prior to, after three and seven days of treatment. The expression of proteins was measured by western blot. The concentration of cytokines and serotonin was evaluated using ELISA assay kits. Kaolin consumption in rats induced by cisplatin was reduced by 16.5%, 22.5%, and 30.1% in the LJAW group compared to the DDP group at 24 hours, 48 hours and 72 hours, respectively (p>0.05). LJAW significantly increased the food intake of the rats (13.94 ± 4.73 g) during the first 24 hours as opposed to the DDP (9.23 ± 3.77 g) (p<0.05). 16S rRNA gene sequencing showed the abundance of Bacteroidetes increased in cisplatin treated rats. In addition, cisplatin injection caused an enrichment of Escherichia-Shigella and Enterococcus at the genus level. While, enrichment of Blautia and Lactobacillus was presented in LJAW treated rats. Serotonin decreased in LJAW treated intestine and medulla oblongata tissues. Further, the protein expression of tryptophan hydroxylase 1 (TPH1) a rate limiting enzyme of serotonin was inhibited in LJAW treated rat's jejunum compared with cisplatin only treated rats. In addition, LJAW downregulated chemotherapy induced elevated inflammation. The results of this study indicated that LJAW is capable of decreasing cisplatin-induced kaolin intake in rat-nausea model (pica), which might be mediated through gut microbiome-induced anti-inflammation and anti-serotonin synthesis functions.

The interactions between traditional Chinese medicine and gut microbiota: Global research status and trends.

Background: There is a crosstalk between traditional Chinese medicine (TCM) and gut microbiota (GM), many articles have studied and discussed the relationship between the two. The purpose of this study is to use bibliometric analysis to explore the research status and development trends of the TCM/GM research, identify and analyze the highly cited papers relating to the TCM/GM. Methods: A literature search regarding TCM/GM publications from 2004 to 2021 was undertaken on August 13, 2022. The main information (full record and cited references) of publications was extracted from the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package, CiteSpace and VOSviewer were used for bibliometric analysis. Results: A total of 830 papers were included. The publication years of papers were from 2004 to 2021. The number of papers had increased rapidly since 2018. China had the most publications and made most contributions to this field. Nanjing University of Chinese Medicine and Beijing University of Chinese Medicine were in the leading productive position in TCM/GM research, Chinese Academy of Chinese Medical Sciences had the highest total citations (TC). Duan Jin-ao from Nanjing University of Chinese Medicine had the largest number of publications, and Tong Xiao-lin from China Academy of Chinese Medical Sciences had the most TC. The Journal of Ethnopharmacology had the most published papers and the most TC. The main themes in TCM/GM included the role of GM in TCM treatment of glucolipid metabolism diseases and lower gastrointestinal diseases; the mechanism of interactions between GM and TCM to treat diseases; the links between TCM/GM and metabolism; and the relationship between GM and oral bioavailability of TCM. Conclusion: This study gained insight into the research status, hotspots and trends of global TCM/GM research, identified the most cited articles in TCM/GM and analyzed their characteristics, which may inform clinical researchers and practitioners' future directions.

Targeting therapy effects of composite hyaluronic acid/chitosan nanosystems containing inclusion complexes.

In order to solve the difficulties in the treatment of Staphylococcus aureus infections, a novel enrofloxacin-cyclodextrin (ß-CD) inclusion complexes (IC) containing hyaluronic acid/chitosan (HA/CS) self-assemble composite nanosystems covered by poloxamer 188 was designed in our previous study. In this study, the sustained release peforemance, targeting delivery, and therapy effects of the enrofloxacin-composite nanosystems were evaluated in vivo. The enrofloxacin-composite nanosystems had uniform size and smooth surface with drug loading capacity (LC) of 9.92 ± 0.3%. Thermogravimetric analysis (TGA) showed that the material used for the preparation of the enrofloxacin-composite nanosystems did not affect the thermal stability of enrofloxacin. Compared with enrofloxacin injection and enrofloxacin polymeric nanoparticles, the enrofloxacin-composite nanosystems had excellent sustained-release performance in vivo. The enrofloxacin-composite nanosystems have specific targeting to the infection site of Staphylococcus aureus. The excellent sustained release and targeting delivery properties ensure that the anti-infective treatment effect of the enrofloxacin-composite nanosystems in vivo was higher than that of enrofloxacin injection and enrofloxacin polymeric nanoparticles. It can more effectively promote the wound healing. These results suggest that our previous designed enrofloxacin-composite nanosystems will be a promising formulation for effective targeting therapy of Staphylococcus aureus infections.

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokinetic-pharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection.

BACKGROUND: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. OBJECTIVES: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. METHODS: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC0-24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation. The dose was calculated based on the AUC0-24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. RESULTS: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 µg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 µg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC0-24h/MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. CONCLUSIONS: A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. Suis infections.

SIRT 3 was involved in Lycium barbarum seed oil protection testis from oxidative stress: in vitro and in vivo analyses.

CONTEXT: Lycium barbarum L. (Solanaceae) seed oil (LBSO) exerts LBSO exerts protective effects in the testis in vivo and in vitro via upregulating SIRT3. OBJECTIVE: This study evaluates the effects and mechanism of LBSO in the d-galactose (d-gal)-induced ageing testis. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats (n = 30, 8-week-old) were randomly divided into three groups: LBSO group (n = 10) where rats received subcutaneous injection of d-gal at 125 mg/kg/day for 8 weeks and intragastric administration of LBSO at 1000 mg/kg/day for 4 weeks, ageing model group (n = 10) received 8-week-sunbcutaneous injection of d-gal, and control group (n = 10) with same administration of normal saline. Lentivirus had established TM4 cells with SIRT3 overexpression or silencing before LBSO intervened in vitro. RESULTS: Treatment with LBSO, the levels of INHB and testosterone both increased, compared to ageing model. In vitro, we found the ED50 of LBSO was 86.72 ± 1.49 and when the concentration of LBSO at 100 µg/mL to intervene TM4 cells, the number of cells increased from 8120 ± 676.2 to 15251 ± 1119, and the expression of SIRT3, HO-1, and SOD upregulated. However, HO-1 and SOD were dysregulated by silencing SIRT3. On the other hand, the expression of AMPK and PGC-1α upregulated as an effect of SIRT3 overexpression by lentivirus, meanwhile the same increasing trend of that being found in cells treated with LBSO, compared to control group. DISCUSSION AND CONCLUSIONS: LBSO alleviated oxidative stress in d-gal-induced sub-acutely ageing testis and TM4 cells by suppressing the oxidative stress to mitochondria via SIRT3/AMPK/PGC-1α.

Effectiveness and safety of warm needle acupuncture on lumbar muscles strain: A protocol for systematic review and meta analysis.

BACKGROUND: Lumbar muscle strain (LMS) is the most common orthopedic syndrome, with high incidence globally and lingering disease, which seriously affects patients' work efficiency and quality of life. Warm needle acupuncture (WNA) is a treatment method combining acupuncture technology with warm and medicinal effect of moxibustion. It has outstanding curative effect and wide range of treatment, especially in the treatment of pain diseases. We aim to collect clinical evidence and demonstrate the efficacy and safety of WNA on LMS. METHODS/DESIGN: We will search the following database sources for the randomized controlled trials: PubMed, Cochrane Library, Excerpta Medica Database (EMBASE), Web of Science, WHO International Clinical Trials Registry Platform (TCTRP), Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Database (VIP), and the Wanfang Database.All randomized controlled trials of WNA for lumbar muscle strain (LMS) in the above database will be considered for inclusion, and high-quality articles will be screened for data extraction and analysis, to summarize the therapeutic effect of WNA on LMS patients. RESULT: This study will provide a rational synthesis of current evidences for warm needle acupuncture on lumbar muscle strain. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on LMS. TRIAL REGISTRATION: INPLASY2020120100 (DOI number: 10.37766/inplasy2020.12.0100).

Integration of lncRNA and mRNA profiles to reveal the protective effects of Codonopsis pilosula extract on the gastrointestinal tract of mice subjected to D­galactose­induced aging.

Codonopsis pilosula is a type of traditional Chinese medicine that exerts an anti­aging effect and can regulate the gastrointestinal (GI) system. The aim of the present study was to investigate the underlying molecular mechanisms responsible for the anti­aging effects of Codonopsis pilosula in the GI tract of mice with D­galactose­induced aging. First, a successful mouse model of aging was established, and Codonopsis pilosula water extract was then used for treatment. The anti­aging effects of Codonopsis pilosula on the GI tract were then detected from the perspectives of tissue structure, physiological function and cell ultrastructure. Finally, in order to explore the underlying molecular mechanisms, the expression profiles of lncRNAs and mRNAs in the stomach and intestine were examined using microarray technology. A total of 117 (41 lncRNAs and 76 mRNAs) and 168 (85 lncRNA sand 83 mRNAs) differentially expressed genes associated with the anti­aging effects of Codonopsis pilosula were identified in the stomach and intestine, respectively. Through integrated analysis of the stomach and intestine, 4 hub RNAs, including 1 lncRNA (LOC105243318) and 3 mRNAs (Fam132a, Rorc and 1200016E24Rik) were identified, which may be associated with the anti­aging effects of Codonopsis pilosula in the GI tract of aging mice. The Kyoto Encyclopedia of Genes and Genomes analysis revealed that the metabolic pathway was an important pathway underlying the anti­aging effects of Codonopsis pilosula in the GI tract. On the whole, in the present study, 4 hub RNAs associated with these effects and their regulatory networks were found in the GI tract of aging mice. In addition, the metabolic pathway was found to play an important role in these anti­aging effects in the GI tract.

Therapy of diarrhea in COVID-19 with external treatment of traditional Chinese medicine: A protocol for systematic review and meta-analysis.

BACKGROUND: Evaluating the effectiveness and safety of external treatment of traditional Chinese medicine therapy for COVID-19 with diarrhea is the primary purpose of this systematic evaluation program. METHODS: We will search the randomized controlled trials from inception to November 2020. The following database is our focus area: Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), VIP database for Chinese technical Periodicals, and Wanfang Database. We will choose articles published both in Chinese and English. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be carried out using Review Manager Software V.5.3. RESULTS: The results will provide high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: This studys decision will provide evidence of whether external treatment of traditional Chinese medicine is an effective and safe intervention for coronavirus disease 2019 with diarrhea. REGISTRATION NUMBER: INPLASY2020110095 (DOI number: 10.37766/inplasy2020.11.0095).

Mechanism of Mongolian Medicine Eerdun Wurile in Improving Postoperative Cognitive Dysfunction Through Activation of the PI3K Signaling Pathway.

OBJECTIVE: To study the effect of Eerdun Wurile (EW), a traditional Mongolian medicine, on the cognitive function of rats by activating the IRS-PI3K-AKT-GLUT4 pathway in an animal model of postoperative cognitive dysfunction (POCD). METHODS: Fifty clean-grade adults Sprague Dawley (SD) male rats were assigned to one of five groups: (1) a control group with no anesthesia (Group C), (2) a POCD model group with anesthesia only (Group P), (3) POCD group with low-dose EW treated (Group L), (4) a POCD group with high-dose EW treated (Group H), and (5) a POCD model group with dexmedetomidine treated (Group D) for positive control. The study started 7 days after all rats had acclimated to housing. Rats were trained in the Morris Water Maze navigation 5 days before surgery. All rats underwent the same maze for navigation and spatial exploration experiments on the preoperative day 1 and postoperative days 1, 3, 5, and their learning and memory abilities were assessed. At the end of the water maze experiment, rats were sacrificed to obtain hippocampal tissue. The mRNA levels of IRS-2, PI3K, AKT, and GLUT4 were measured in the hippocampus by real-time PCR, and the expression of IRS-2, PI3K, AKT, and GLUT4 protein in the hippocampus was determined by Western blotting to investigate the potential mechanisms at the molecular level. RESULTS: Compared to control Group C, Group P, L, H, and D showed prolonged escape latency (P < 0.05) and decreased number of times to cross the platform (P < 0.05) at 1, 3 and 5 days after surgery. Compared to Group P, Group L, H, and D showed a decrease in escape latency with an increased number of crossing the platform at all-time points after surgery (P < 0.05). Within individual P, L, H, and D groups, escape latencies decreased (P < 0.05) and the number of times that the platform was crossed increased (P < 0.05) between postoperative days 3 and 5 compared to postoperative 1 day. Compared to Group C, the mRNA expression of IRS-2, PI3K, AKT and GLUT4 in the hippocampus of P, L, H, and D groups were decreased (P < 0.05). Compared to Group P, IRS-2, PI3K, AKT, and GLUT4 in the hippocampus of L, H, and D groups were increased (P < 0.05). Compared with Group D, the expression levels of IRS-2 and AKT in both L and H groups were higher. The expression level of PI3K in Group L was also higher (P < 0.05) vs Group D. The expression of AKT mRNA in Group H was higher than in Group L (P < 0.05). Compared to Group C, the p-IRS-2/IRS-2 ratio in the hippocampus of Group P was higher than that of Group C (P < 0.05). Compared to Group P, the ratios of p-IRS-2/IRS-2 in Group L, Group H, and Group D were lower, and the ratios of the p-PI3K/PI3K, p-AKT/AKT, and p-GLUT4/GLUT4 were higher (P < 0.05). CONCLUSION: Administration of EW showed the effect on the signaling pathway in rats with POCD. The therapeutic effect was better in the low-dose group. This could be related to the insulin downstream signal molecule PI3K and the IRS-PI3K-AKT-GLUT4 signaling pathway.

Dosage Regimen Formulation and Therapeutic Effect Evaluation of Cyadox Nanosuspension Against Dairy Cow Mastitis Caused by Staphylococcus aureus.

AIMS: In this study, the dosage regimen establishment of cyadox nanosuspension against dairy cow mastitis caused by Staphylococcus aureus (S. aureus) was used as example to provide a general reference for the other novel nanocrystal preparations. METHODS: The effect of cyadox against S. aureus isolates from dairy cows were firstly estimated and then the dosing regimen of nanosuspension after intramammary administration was optimized according to the model of ex vivo pharmacokinetic (PK) and pharmacodynamic (PD). The therapeutic efficacy of the predicted dosage regimen was evaluated. RESULTS: The results demonstrated that cyadox has a concentration-dependent effect on S. aureus. The smallest and highest values of minimum inhibitory concentration (MIC) against 80 isolates was 8 and 64 µg/mL, respectively. The corresponding MIC 50 and MIC 90 was 16 and 32 µg/mL, respectively. The MIC against the pathogenic S. aureus SAHZ156001 in broth and milk were 16 and 32 µg/mL, respectively. The AUC 0-last and C max of cyadox in milk were 4442.877 µg*h/mL and 753.052 µg/mL, respectively. According to the inhibitory sigmoid E max modeling and dosage equation, the daily doses were predicted 1.6, 6.6, and 12.2 mL/gland to achieve bacteriostatic, bactericidal, and elimination effects. The dosage internal was daily administration for continuous three days. CONCLUSION: The clinical experiment showed that the efficient rates were 100, 100, and 90.9%, and the curative rates were 100, 81.8, and 63.6% in 12.2, 6.6 and 1.6 ml/gland groups, respectively. These results showed that cyadox nanosuspension had a good prospect as intramammary infusion to cure dairy cow mastitis infected by S. aureus. This study will be helpful for providing reference for nanocrystal preparation dosage regimen formulation.

Effects and mechanism of microRNA­218 against lung cancer.

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)­218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR­218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR­218 in XWLC­05 cells were markedly lower compared with those in immortalized lung epithelial BEAS­2B cells. The present study also demonstrated that overexpression of miR­218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC­05 and NSCLC cell line NCI­H157. Additionally, the results revealed that overexpression of miR­218 could induce XWLC­05 and NCI­H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR­218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B­cell lymphoma 2 (BCL­2) and BMI1 proto­oncogene, polycomb ring finger (BMI­1) at the mRNA and protein level in XWLC­05 and NCI­H157 cell lines. However, we did not observe any remarkable difference in the roles of miR­218 and miR­218­mediated regulation of BCL­2, BMI­1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR­218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL­2 and BMI­1 in Xuanwei lung cancer. The results demonstrated that miR­218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR­218 may be a novel approach for the treatment of Xuanwei lung cancer.

Newborn screening for primary carnitine deficiency in Quanzhou, China.

BACKGROUND AND AIMS: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by functional defects in the carnitine transporter OCTN2 due to mutations in SLC22A5. Here, we aimed to understand the incidence, clinical, biochemical, and molecular features of PCD in Quanzhou, China. MATERIALS AND METHODS: Newborn screening (NBS) was performed through tandem mass spectrometry (MS/MS) to detect genetic metabolic diseases. Next-generation sequencing was used to detect SLC22A5 mutations in patients with suspected PCD. RESULTS: From 364,545 newborns screened, 36 were diagnosed with PCD, in addition to five mothers. The incidence of PCD in children in the Quanzhou area was 1:10126. Eighteen SLC22A5 variants were found, with five novel ones. The most prevalent variant in neonatal and maternal patients was c.760C > T (p.R254*). Twenty-five neonatal patients received L-carnitine supplementation; however, one patient discontinued treatment and sudden death occurred. One sibling presented repeated fatigue, hypoglycemia, and coma, but the symptoms disappeared after treatment. Two mothers with PCD claimed to feel weak and easily fatigued. CONCLUSION: The incidence of PCD is relatively high in the Quanzhou area. Five novel variants were found, broadening the mutation spectrum of SLC22A5. NBS is effective in identifying PCD, and sudden death may be prevented with timely treatment.

Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial.

AIM: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. METHOD: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients' stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. RESULTS: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. -0.76, P = .002), Collinsella (coef.-0.61, P = .02), Ruminiclostridium_9 (coef. -0.64, P = .01). CONCLUSION: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.

Effect of family support on quality of postoperative life in patients with digestive cancer.

BACKGROUND: Digestive tumors are malignant tumors of epithelial origin with high rates of morbidity and mortality worldwide. At present, surgery is the main treatment for patients with digestive tumors. In this study, we conducted a survey of patients with digestive cancers to explore the influence of family support on postoperative quality of life, with the aim of providing a basis of reference for further improvement of the quality of life of such patients. METHODS: A total of 82 patients with digestive cancer who underwent surgery in Hospital of Chengdu University of Traditional Chinese Medicine between October, 2018 and April, 2019 were selected to take part. The self-made questionnaire, the European Cancer Research and Treatment Organization's Core Quality of Life Questionnaire for Cancer Patients, and the Family Support Scale were used to investigate the patients, and the collected data were statistically analyzed. RESULTS: The family support scores of the 82 enrolled patients ranged from 5 to 15 points, with an average score of (8.86±2.47) points; 60 cases (73.17%) scored ≥10 points and 12 cases (26.83%) scored <10 points. Patients who were married, aged under 30 years old, or employed as civil servants had higher family support scores than other patients (P<0.05). The scores for physical function, emotional function, and overall health status/quality of life in patients who had a high family support score were higher than those in patients who had a low family support score (P<0.05). According to the logistic regression model, Patients with higher age, getting married, with education level of bachelor degree or above, occupation as farmer and with other digestive tract tumor got higher family support score. (P<0.05). CONCLUSIONS: Good family support can effectively improve quality of postoperative life for patients with digestive cancer. Education, age, occupation and marriage are all independent factors that affect family support.

Liuweidihuang Pill Alleviates Inflammation of the Testis via AMPK/SIRT1/NF-κB Pathway in Aging Rats.

Liuweidihuang Pill (LP) is a traditional Chinese herbal formula that is often used in clinical practice to treat kidney deficiency syndrome. The present study investigated the antiaging effects of LP in a D-galactose- (D-Gal-) induced subacute aging rat model. The study also attempted to explore whether anti-inflammatory mechanisms that underpin the antiaging effects are mediated by the AMPK/SIRT1/NF-κB signaling pathway. Rats were subcutaneously injected with D-Gal at a dosage of 100 mg/kg/d for 8 weeks. Upon successful induction of aging in the rats, the animal was administered LP at 0.9 g/kg/d by gavage for 4 weeks. Proteins of the testis were subsequently examined by western blot analysis, and associated locations in the testicular tissue were determined by immunohistochemistry. We observed that LP exerted antiaging effects in aging rats following the activation of AMPK/SIRT1. It was also observed that LP inhibited the expression of NF-κB, thereby further attenuating inflammation of the testis. Therefore, LP can alleviate inflammation of the testis via the AMPK/SIRT1/NF-κB pathway in aging rats.

Integrative Analysis of Long Non-Coding RNAs (lncRNAs), miRNAs, and mRNA-Associated ceRNA Network in Lung Tissue of Aging Mice and Changes After Treatment with Codonopsis pilosula.

BACKGROUND Codonopsis pilosula is a traditional Chinese medicine that has an anti-aging effect. However, the anti-aging effect of Codonopsis pilosula on the lungs remains largely unknown, and the molecular mechanism also needs to be further studied. Thus, we investigated the protective effect of Codonopsis pilosula on the lungs of aging mice, and explored the underlying molecular mechanism. MATERIAL AND METHODS We established an aging mouse model and then treated the mice with Codonopsis pilosula. Microarray analysis and bioinformatics methods were used to comprehensively analyze the lncRNA-miRNA-mRNA (ceRNA) network. RESULTS Our results showed that we successfully established the aging mouse model. The microarray analysis showed that 138 lncRNAs, 128 mRNAs, and 7 miRNAs were significantly changed after aging, and 282 lncRNAs, 283 mRNAs, and 19 miRNAs were dysregulated after treatment with Codonopsis pilosula. To explore the signaling pathways involved, KEGG pathway analysis was performed. Compared with the ceRNA network in aging mice and after treatment with Codonopsis pilosula, we found that 3 mRNAs (Hif3a, Zbtb16, Plxna2) and 1 lncRNA (NONMMUT063872) were associated with the anti-aging effect of Codonopsis pilosula and they were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CONCLUSIONS Our results showed that Codonopsis pilosula has a protective effect on the aging lung, and the ceRNA network plays an important role in the anti-aging effect of Codonopsis pilosula.