Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

The Effectiveness of the Educational Model Based on "Moral and Medical Integration" in the Nursing Students' Education in the Operating Theatre.

Objective: As the reform of China's medical and healthcare system progresses and the demand for medical and healthcare services increases, the humanistic quality of medical personnel has received more attention and concern. The humanistic quality of medicine for medical staff is specifically translated into the ethics of nursing for nursing staff. In this study, we explored the effectiveness of the education model based on "moral and medical integration" in the nursing students' education in the operating room. Methods: The "moral and medical integration" education model was implemented in The Affiliated Changzhou No. 2 People's Hospital since September 1, 2021, and 50 nursing students who received the traditional education model before the implementation from May 1, 2021, to August 31, 2021, were selected as the control group. The study group was composed of 50 nursing trainees who received the traditional education model from 1 September 2021 to 30 November 2021 and 50 nursing trainees who received the education model based on the "integration of moral and medical science". The nursing theory and nursing skills scores, professional nursing practice scores, moral courage scores, and satisfaction with teaching were compared between the two groups. Results: The nursing theory scores (t = 14.36, P < .001), nursing skills scores (t = 11.27, P < .001), and teaching satisfaction of the study group (t = 4.76, P < .029) were all higher than those of the control group . After the education, all the professional nursing practice ability scores(t=9.16, P < .001; t = 12.24, P < .001; t = 10.42, P < .001; t = 10.95, P < .001) and moral courage scores(t=7.81, P < .001; t = 11.76, P < 0.001; t = 15.11, P < .001; t = 12.24, P < .001) of the study group were higher than those of the control group (P < .05). Conclusion: The education model based on "moral and medical integration" can help improve the professional nursing level of nursing students in the operating theatre.

Screening and identification of antibacterial components in Artemisia argyi essential oil by TLC-direct bioautography combined with comprehensive 2D GC × GC-TOFMS.

One of the primary components that contribute to Artemisia argyi 's effectiveness is essential oil, which has an exceptional antibacterial effect that has been well documented. The actual cause of its antibacterial activity and associated mechanism, however, are still not completely understood. For the first time, comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (2D GC × GC-TOFMS) and thin-layer chromatography-direct bioautography (TLC-DB) were employed to investigate its antibacterial components. The antibacterial properties of A. argyi essential oil were investigated, and the antibacterial activity of six compounds was evaluated, using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil) as test microorganisms. TLC-direct bioautography was used to screen two bioactive clusters. Following 2D GC × GC-TOFMS identification of bioactive clusters, six compounds were evaluated for in vitro antibacterial activity verification. All the components tested displayed antibacterial action. Results showed that α-terpineol and eugenol had high potent antibacterial activity (MIC＜0.62 mg/mL, IC50＜2.00 mg/mL). For complex essential oils from traditional Chinese medicine, this method is efficient for quick screening and identifying antibacterial compounds.

Prevalence and risk factors of occupational neck pain in Chinese male fighter pilots: a cross-sectional study based on questionnaire and cervical sagittal alignment.

Background: Neck pain (NP) is a common musculoskeletal disorder among fighter pilots and has become a rising concern due to its detrimental impact on military combat effectiveness. The occurrence of NP is influenced by a variety of factors, but less attention has been paid to the association of NP with demographic, occupational, and cervical sagittal characteristics in this group. This study aimed to investigate the prevalence and risk factors of NP in Chinese male fighter pilots using a questionnaire and cervical sagittal measurements. Methods: Demographic and flight-related data, as well as musculoskeletal pain information, were gathered from Chinese male fighter pilots via a self-report questionnaire. Cervical sagittal parameters were measured and subtypes were classified using standardized lateral cervical radiographs. Differences in various factors between the case and control groups were analyzed using t-tests or chi-square tests. Binary logistic regressions were conducted to explore potential risk factors contributing to NP. Predictors were presented as crude odds ratios (CORs) and adjusted odds ratios (AORs), along with their respective 95% confidence intervals (CIs). Results: A total of 185 male fighter pilots were included in this cross-sectional study. Among them, 96 (51.9%) reported experiencing NP within the previous 12 months. The multivariate regression analysis revealed that continuous flight training (AOR: 4.695, 95% CI: 2.226-9.901, p < 0.001), shoulder pain (AOR: 11.891, 95% CI: 4.671-30.268, p < 0.001), and low back pain (AOR: 3.452, 95% CI: 1.600-7.446, p = 0.002) were significantly associated with NP. Conclusion: The high 12-month prevalence of NP among Chinese male fighter pilots confirms the existence of this growing problem. Continuous flight training, shoulder pain, and low back pain have significant negative effects on pilots' neck health. Effective strategies are necessary to establish appropriate training schedules to reduce NP, and a more holistic perspective on musculoskeletal protection is needed. Given that spinal integrated balance and compensatory mechanisms may maintain individuals in a subclinical state, predicting the incidence of NP in fighter pilots based solely on sagittal characteristics in the cervical region may be inadequate.

Metagenomics, metatranscriptomics, and proteomics reveal the metabolic mechanism of biofilm sequencing batch reactor with higher phosphate enrichment capacity under low phosphorus load.

The biofilm sequencing batch reactor (BSBR) process has higher phosphate recovery efficiency and enrichment multiple when the phosphorus load is lower, but the mechanism of phosphate enrichment at low phosphorus load remains unclear. In this study, we operated two BSBR operating under low and high phosphorus load (0.012 and 0.032 kg/(m3·d)) respectively, and used metagenomic, metatranscriptomic, and proteomics methods to analyze the community structure of the phosphorus accumulating organisms (PAOs) in the biofilm, the transcription and protein expression of key functional genes and enzymes, and the metabolism of intracellular polymers. Compared with at high phosphorus load, the BSBR at low phosphorus load have different PAOs and fewer types of PAOs, but in both cases the PAOs must have the PHA, PPX, Pst, and acs genes to become dominant. Some key differences in the metabolism of PAOs from the BSBR with different phosphorus load can be identified as follows. When the phosphorus load is low, the adenosine triphosphoric acid (ATP) and NAD(P)H in the anaerobic stage come from the TCA cycle and the second half of the EMP pathway. The key genes that are upregulated include GAPDH, PGK, ENO, ppdk in the EMP pathway, actP in acetate metabolism, phnB in polyhydroxybutyrate (PHB) synthesis, and aceA, mdh, sdhA, and IDH1 in the TCA cycle. In the meantime, the ccr gene in the PHV pathway is inhibited. As a result, the metabolism of the PAOs features low glycogen with high PHB, Pupt, Prel, and low PHV. That is, more ATP and NAD(P)H flow to phosphorus enrichment metabolism, thus allowing the highly efficient enrichment of phosphorus from low concentration phosphate thanks to the higher abundance of PAOs. The current results provide theoretical support and a new technical option for the enrichment and recovery of low concentrations of phosphate from wastewater by the BSBR process.

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.

Icariin inhibits prostate cancer bone metastasis and destruction via suppressing TAM/CCL5-mediated osteoclastogenesis.

BACKGROUND: Bone metastasis occurs in nearly 70% of patients with metastatic prostate cancer (PCa), and represents the leading cause of death in patients with PCa. Emerging evidence has demonstrated the potential activities of icariin in modulating bone metabolism and remodelling the tumor microenvironment (TME). However, whether icariin could inhibit PCa bone metastasis and destruction by modulating the TME as well as the underlying mechanisms remains unclear. PURPOSE: This study investigated whether icariin could inhibit PCa bone metastasis and destruction by modulating the bone TME as well as the underlying mechanisms. METHODS: Osteoclasts were induced from mouse bone marrow-derived macrophages (BMMs) or Raw264.7 cells. PCa cells were cultured in the conditional medium (CM) of macrophages in vitro or co-injected with macrophages in vivo to simulate their coexistence in the TME. Multiple molecular biology experiments and the mouse RM1-Luc PCa bone metastasis model were used to explore the inhibitory activity and mechanism of icariin on PCa metastasis and bone destruction. RESULTS: Icariin treatment significantly suppressed PCa growth, bone metastasis and destruction as well as osteoclastogenesis in vivo. Furthermore, icariin remarkably inhibited osteoclast differentiation, even in the presence of the CM of tumor-associated macrophages (TAMs), while exhibiting no obvious effect on osteoblasts. Moreover, icariin suppressed the M2 phenotype polarization of Raw264.7-derived TAMs and transcriptionally attenuated their CC motif chemokine ligand 5 (CCL5) expression and secretion via inhibiting SPI1. Additionally, CCL5 induced the differentiation and chemotaxis of osteoclast precursor cells by binding with its receptor CCR5. The clinicopathological analysis further verified the positive correlation between the TAM/CCL5/CCR5 axis and osteoclastogenesis within the TME of PCa patients. More importantly, icariin remarkably suppressed PCa metastasis-induced bone destruction in vivo by inhibiting osteoclastogenesis via downregulating the TAM/CCL5 pathway. CONCLUSION: Altogether, these results not only implicate icariin as a promising candidate immunomodulator for PCa bone metastasis and destruction but also shed novel insight into targeting TAM/CCL5-mediated osteoclastogenesis as a potential treatment strategy for osteolytic bone metastasis. This study helps to advance the understanding of the crosstalk between bone TME and bone homeostasis.

Coupled pyrite and sulfur autotrophic denitrification for simultaneous removal of nitrogen and phosphorus from secondary effluent: feasibility, performance and mechanisms.

The discharge standards of nitrogen (N) and phosphorus (P) in wastewater treatment plants (WWTPs) have become increasingly strict to reduce water eutrophication. Further reducing N and P in effluent from municipal WWTPs need to be achieved effectively and eco-friendly. In this study, a carbon independent pyrite and sulfur autotrophic denitrification (PSAD) system using pyrite and sulfur as electron donor was developed and compared with pyrite autotrophic denitrification (PAD) and sulfur autotrophic denitrification (SAD) systems through batch and continuous flow biofilter experiments. Compare to PAD and SAD, PSAD was more effective in simultaneous removal in N and P. At hydraulic retention time (HRT) 3 h, average effluent concentrations of total nitrogen (TN) and total phosphate (TP) of 1.40 ± 0.03 and 0.19 ± 0.02 mg/L were achieved when treating real secondary effluent with 20.65 ± 0.24 mg/L TN and 1.00 ± 0.24 mg/L TP. The improvement in simultaneous removal of N and P was attributed to the coupling of PAD and SAD in enhancing the transformation of sulfur and iron and enlarging the reaction zone in the pyrite and sulfur autotrophic denitrification biofilter (PSADB) system. Therefore, more biomass was accumulated and the microbial denitrification functional stability, including electrons transfer and consumption was enhanced on the surface of pyrite and sulfur particles in the PSADB system. Moreover, autotrophic denitrifiers (Thiobacillus and Ferritrophicum), sulfate-reducing bacteria (Desulfocapsa) and iron reducing bacteria (Geothrix), acting as contributors to microbial nitrogen, sulfur and iron cycle, were specially enriched. In addition, the leaching of iron ions was promoted, which facilitated the removal of phosphate in the form of Fe3(PO4)2·8H2O and Fe3PO4. PSADB has proven to be an efficient technology for simultaneous removal of N and P, which could meet increasingly stringent discharge standards effectively and eco-friendly.

Blood selenium level can alleviate the nephrotoxicity of lead and cadmium in the general population of the United States: a retrospective cross section analysis of population-based nationally representative data.

The current understanding of the interplay between blood selenium, cadmium and lead levels, and chronic kidney disease (CKD) is limited. Our objective was to investigate whether elevated blood selenium levels can mitigate the nephrotoxic effects of lead and cadmium. The exposure variables examined in this study include blood selenium, cadmium, and lead levels measured by ICP-MS. The outcome of interest was CKD, defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. In total, 10630 participants (mean (SD) age:48.9 ± 18.4; 48.3% male) were included in this analysis. The median (IQR) of blood selenium, cadmium, and lead levels was 191 (177-207) µg/L, 0.300 (0.180-0.540) µg/L, and 0.940 (0.570-1.510) µg/dL, respectively. We observed a significant positive association between cadmium and lead levels and CKD (OR; 1.86; 95%CI: 1.31- 2.64; OR:2.23; 95%CI:1.54-3.24). However, selenium had a negative association with CKD (OR:0.096; 95%CI:0.020-0.457). Based on a reference group with a selenium concentration of ≤ 191 µg/L and cadmium level of > 0.300 µg/L, a significant protective factor in the CKD was seen in subjects with high plasma selenium and lower cadmium concentrations (OR:0.685; 95%CI:0.515-0.912). Then selenium concentration of ≤ 191 µg/L and lead level of > 0.940 µg/dL were set as a reference group, and the OR for CKD decreased among the other group (OR:0.564; 95%CI;0.417- 0.762). The subgroup analysis indicated that there were no effect modifiers. Blood selenium has the potential to mitigate the nephrotoxic effects of lead and cadmium in the general population of the United States.

Integrated genotoxicity of secondary and tertiary treatment effluents in North China.

Genotoxic effects on aquatic organisms caused by wastewater discharging have raised extensive concerns. However, the efficiency of various wastewater treatment processes to reduce effluent genotoxicity was not well known. Genotoxic effects of effluents from four secondary wastewater treatment plants (SWTPs) and a tertiary wastewater treatment plant (TTP) in north China on Chinese rare minnows (Gobiocypris rarus) were evaluated and the toxicity reduction efficiency of various treatment techniques was compared. SWTPs and TTP final effluents disturbed the antioxidant system and lipid peroxidation, with malondialdehyde (MDA) contents in the fish livers and gills increasing to 1.4-2.4 folds and 1.6-3.1 folds of control, respectively. Significant increases in erythrocytes micronucleus (MN) frequency were induced by effluent, and liver DNA damage caused by final SWTPs effluent was 29-54 % lower than TTP effluent. Further, DNA repair gene atm and growth arrest gene gadd45a were remarkably upregulated by SWTP and TTP final effluents to 1.8-12 folds and 4.1-15 folds, respectively, being consistent with the chromosomal aberration and DNA damage in liver tissue. Integrated biomarker response (IBR) of the tertiary effluent was 49 %-69 % lower than the secondary effluents. However, the final ozone disinfection at TTP caused an increase in the DNA damage, suggesting the generation of genotoxic by-products. UV disinfection at secondary treatment removed part of genotoxicity, with a reduction in IBR of 0 %-47 %. The total semi-volatile organic compounds (SVOCs) detected in the final effluent contained 5 %-56 % potential genotoxic substances, removal of which was 9 %-51 % lower than non-genotoxic compounds. Microfiltration and reverse osmosis process exhibited good performance in removing both the integrated genotoxicity and the potential genotoxic SVOCs. Our finding shows that TTP is superior than SWTP for wastewater treatment due to higher genotoxicity removal, but ozone disinfection needs improvement by optimizing performance parameters or adding post-treatment processes, to achieve better protection for aquatic organisms against genotoxic contaminants.

Metagenomics reveals the metabolism of polyphosphate-accumulating organisms in biofilm sequencing batch reactor: A new model.

This study assessed the impact of the operating conditions of the biofilm sequencing batch reactor (BSBR) on the community structure and the growth/metabolic pathways of its polyphosphate-accumulating organisms (PAOs). There are significant difference with reference to the enhanced biological phosphorus removal (EBPR) process. The leading PAOs in BSBR generally are capable of high affinity acetate metabolism, gluconeogenesis, and low affinity phosphate transport, and have various carbon source supplementation pathways to ensure the efficient circulation of energy and reducing power. A new model of the metabolic mechanism of PAOs in the BSBR was formulated, which features low glycogen metabolism with simultaneous gluconeogenesis and glycogenolysis and differs significantly from the classic mechanism based on Candidatus_Accumulibacter and Tetrasphaera. The findings will assist the efficient recovery of low concentration phosphate in municipal wastewater.

Integrated estrogenic effects and semi-volatile organic pollutants profile in secondary and tertiary wastewater treatment effluents in North China.

Endocrine-disrupting effects on aquatic organisms caused by wastewater discharging have raised extensive concerns. However, the efficiency of various wastewater treatment processes to remove estrogenic activity in effluents and the association with organic micropollutants was not well known. We evaluated the estrogenic activity using a well-characterized in vivo bioassay featuring the Chinese rare minnows (Gobiocypris rarus) and analyzed 886 semi-volatile organic compounds (SVOCs) in effluents from four secondary wastewater treatment plants (SWTP A-D) and a tertiary wastewater treatment plant (TTP E) that utilized various common treatment processes in northern China. The final effluents from SWTPs and TTP E all exhibited estrogenic effects, increasing male fish plasma vitellogenin (VTG) contents and estradiol/testosterone (E2/T) ratios. Key regulating genes in the male fish liver including vtg1, vtg3, era, erß, and cyp19a were upregulated. TTP E demonstrated high performance in reducing estrogenic activity in the effluents, with a reduction of 64% in integrative biomarkers of estrogenic response (IBR). UV disinfection at SWTPs removed IBR by 14%- 33%, while ozone disinfection at TTP E did not reduce IBR. Several SVOCs including alkanes, chlorobenzenes, and phthalates, detected at ng/L to µg/L level, significantly correlated with effluent estrogenic activity. Our findings suggest the necessity and the potential means to improve the efficiency of current wastewater treatment approaches to achieve better protection for aquatic organisms against the joint effects of mixtures of various categories of micropollutants in effluents.

Investigating the Mechanism of Scutellariae barbata Herba in the Treatment of Colorectal Cancer by Network Pharmacology and Molecular Docking.

BACKGROUND: Colorectal cancer (CRC) is one of the most common gastrointestinal tumors, which accounts for approximately 10% of all diagnosed cancers and cancer deaths worldwide per year. Scutellariae barbatae Herba (SBH) is one of the most frequently used traditional Chinese medicine (TCM) in the treatment of CRC. Although many experiments have been carried out to explain the mechanisms of SBH, the mechanisms of SBH have not been illuminated fully. Thus, we constructed a network pharmacology and molecular docking to investigate the mechanisms of SBH. METHODS: We adopted active constituent prescreening, target predicting, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, differentially expressed gene analysis, and molecular docking to establish a system pharmacology database of SBH against CRC. RESULTS: A total of 64 active constituents of SBH were obtained and 377 targets were predicted, and the result indicated that quercetin, luteolin, wogonin, and apigenin were the main active constituents of SBH. Glucocorticoid receptor (NR3C1), pPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), cellular tumor antigen p53 (TP53), transcription factor AP-1 (JUN), mitogen-activated protein kinase 1 (MAPK1), Myc protooncogene protein (MYC), cyclin-dependent kinase 1 (CDK1), and broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) were the major targets of SBH in the treatment of CRC. GO analysis illustrated that the core biological process regulated by SBH was the regulation of the cell cycle. Thirty pathways were presented and 8 pathways related to CRC were involved. Molecular docking presented the binding details of 3 key targets with 6 active constituents. CONCLUSIONS: The mechanisms of SBH against CRC depend on the synergistic effect of multiple active constituents, multiple targets, and multiple pathways.

Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats.

Diabetic nephropathy (DN), a severe microvascular complication of diabetes, is one of the leading causes of end-stage renal disease. Huayu Tongluo Recipe (HTR) has been widely used in the clinical treatment of DN in China, and its efficacy is reliable. This study aimed to explore the renoprotective effect of HTR and the underlying mechanism. Male Sprague-Dawley rats were fed with high sugar and fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. Rats in each group were respectively given drinking water, HTR, and irbesartan by gavage for 16 weeks. 24-hour urine samples were collected every 4 weeks to detect the content of total protein and 8-OHdG. Blood samples were taken to detect biochemical indicators and inflammatory markers at the end of 16th week. Renal tissue was collected to investigate pathological changes and to detect oxidative stress and inflammatory markers. AMPK/Nrf2 signaling pathway and fibrosis-related proteins were detected by immunohistochemistry, immunofluorescence, real-time PCR, and western blot. 24h urine total protein (24h UTP), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), and triglyceride (TG) were decreased in the rats treated with HTR, while there was no noticeable change of blood glucose. HTR administration decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in kidneys, complying with reduced 8-OHdG in the urine. The levels of TNF-α, IL-1ß, and MCP1 and the expression of nuclear NFκB were also lower after HTR treatment. Furthermore, HTR alleviated pathological renal injury and reduced the accumulation of extracellular matrix (ECM). Besides, HTR enhanced the AMPK/Nrf2 signaling and increased the expression of HO-1 while it inhibited the Nox4/TGF-ß1 signaling in the kidneys of STZ-induced diabetic rats. HTR can inhibit renal oxidative stress and inflammation to reduce ECM accumulation and protect the kidney through activating the AMPK/Nrf2 signaling pathway in DN.

Comprehensive TCM treatments combined with chemotherapy for advanced non-small cell lung cancer: A randomized, controlled trial.

OBJECTIVE: We conducted this study to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in advanced non-small cell lung cancer (NSCLC) patients who underwent chemotherapy. DESIGN: This was a prospective, open-label, randomized controlled trial. NSCLC patients at stage IIIA, IIIB, or IV were randomly assigned to either TCM plus chemotherapy or chemotherapy alone. The comprehensive TCM treatment consisted of Kang Ai injection, herbal decoction, and Zhenqifuzheng capsules. The primary endpoint was quality of life (QOL) measured by the Functional Assessment of Cancer Therapy-Lung version 4.0. The secondary endpoints were chemotherapy completion rate, tumor response, and adverse events. All assessments were done at baseline, the third week, and the sixth week. RESULTS: Thirty-nine participants were randomly assigned to the treatment group and 36 to the control group. The QOL scores were significantly improved in the treatment group compared with those of the control group in social well-being (cycle 1, P = .048; cycle 2, P = .015), emotional well-being (cycle 1, P = .047; cycle 2, P = 4.29E-05), and functional well-being (cycle 1, P = .030; cycle 2, P = .003), while the QOL scores in the above 3 domains declined in the control group (P < .05). Both groups had a decline in the physical well-being score (cycle 1, P = .042; cycle 2, P = .017) and lung cancer symptom score (cycle 1, P = .001; cycle 2, P = .001) after 2 courses of intervention. The deterioration in physical well-being and lung cancer symptoms was noticeably smaller in the treatment group (P < .05). There were significant differences between the 2 groups in social well-being, emotional well-being, functional well-being, lung cancer symptom domain, and the total score (P < .05). Patients in the treatment group had a significantly lower incidence of platelet reduction than the control group (P = .028) after 2 cycles of treatment. No significant difference in nonhematological adverse events (AEs) was observed. CONCLUSION: This study illustrated that comprehensive TCM treatment could promote the QOL of NSCLC patients, alleviate symptoms, and reduce the AEs caused by chemotherapy, verifying the synergistic and attenuating effects of TCM in NSCLC patients undergoing chemotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR-TRC-13003637.

Kaempferol alleviates calcium oxalate crystal-induced renal injury and crystal deposition via regulation of the AR/NOX2 signaling pathway.

BACKGROUND: Calcium oxalate (CaOx) crystal deposition and crystal-induced renal tubular epithelial cell injury have been found to fundamentally contribute to the formation of CaOx nephrolithiasis. PURPOSE: In the current work, we aim to study the role and mechanism of kaempferol in CaOx crystal kidney deposition and crystal-induced renal injury. STUDY DESIGN: Mice models and HK-2 cells were used to investigate the effect of kaempferol in CaOx crystal-induced renal injury and crystal deposition in the kidney and its underlying mechanism by a series of experiments. METHODS: CaOx crystal deposition in mice renal tubulars and tubular damage were evaluated. And crystal adhesion to HK-2 cells, as well as cellular injury were identified. Furthermore, the effect of kaempferol on the expression of androgen receptor (AR) in renal tubular epithelial cells was assessed. The interaction between AR and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and the intrinsic molecular mechanism of how AR regulated NOX2 in HK-2 cells were dissected. Additionally, several different assays were applied to analyze the expression levels of various related genes in this study. RESULTS: It was revealed that kaempferol reduced CaOx crystal deposition in renal tubulars and crystal adhesion to HK-2 cells. Meanwhile, the results of in vivo and in vitro experiments corroborated that crystal-associated cellular injury, oxidative stress, inflammation and over-expression of OPN and CD44 in the kidney were ameliorated by kaempferol. Moreover, kaempferol functioned on inhibiting the expression of AR in renal tubular epithelial cells, and AR was able to up-regulate the expression of NOX2 at the transcriptional level by directly binding to the promoter of NOX2. Kaempferol decreased crystal deposition and crystal-induced renal oxidative and inflammatory injury by the down-regulation of AR/NOX2 signaling pathway. CONCLUSION: Taken together, our study findings suggest that kaempferol has a suppressive effect on renal AR expression, which can attenuate CaOx crystal deposition and crystal-induced kidney injury through repressing oxidative stress and inflammation in the kidney by modulating the AR/NOX2 signaling pathway. It demonstrates that kaempferol may have preventive and therapeutic potential for CaOx nephrolithiasis.

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1.

Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress in vitro. Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.

Hirudo Lyophilized Powder Ameliorates Renal Injury in Diabetic Rats by Suppressing Oxidative Stress and Inflammation.

As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.

Identification and candidate gene screening of qCIR9.1, a novel QTL associated with anther culturability in rice (Oryza sativa L.).

KEY MESSAGE: A novel QTL, qCIR9.1, that controls callus induction rate in anther culture was identified on chromosome 9 in rice, and based on RNA-seq data, Os09g0551600 was the most promising candidate gene. Anther culture, a doubled haploid (DH) technique, has become an important technology in many plant-breeding programmes. Although anther culturability is the key factor in this technique, its genetic mechanisms in rice remain poorly understood. In this study, we mapped quantitative trait loci (QTLs) responsible for anther culturability by using 192 recombinant inbred lines (RILs) derived from YZX (Oryza sativa ssp. indica) × 02428 (Oryza sativa ssp. japonica) and a high-density bin map. A total of eight QTLs for anther culturability were detected in three environments. Among these QTLs, a novel major QTL for callus induction rate (CIR) named qCIR9.1 was repeatedly mapped to a ~ 100 kb genomic interval on chromosome 9 and explained 8.39-14.14% of the phenotypic variation. Additionally, RNA sequencing (RNA-seq) was performed for the parents (YZX and 02428), low- (L-Pool) and high-CIR RILs (H-Pool) after 16 and 26 days of culture. By using the RNA of the bulked RILs for background normalization, the number of differentially expressed genes (DEGs) both between the parents and between the bulked RILs after 26 days of culture was drastically reduced to only 78. Among these DEGs, only one gene, Os09g0551600, encoding a high-mobility group (HMG) protein, was located in the candidate region of qCIR9.1. qRT-PCR analysis of Os09g0551600 showed the same results as RNA-seq, and the expression of this gene was decreased in the low-callus-induction parent (YZX) and L-Pool. Our results provide a foundational step for further cloning of qCIR9.1 and will be very useful for improving anther culturability in rice.

Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. METHODS: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. RESULTS: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. CONCLUSIONS: As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.