Elucidation of the anti-gastric cancer mechanism of Guiqi Baizhu Formula by integrative approach of chemical bioinformatics.

Gastric cancer (GC) has posed a great threat to the lives of people around the world. To date, safer and more cost-effective therapy for GC is lacking. Traditional Chinese medicine (TCM) may provide some new options for this. Guiqi Baizhu Formula (GQBZF), a classic TCM formula, has been extensively used to treat GC, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we evaluated the underlying mechanisms of GQBZF in treating GC by integrative approach of chemical bioinformatics. GQBZF lyophilized powder (0.0625 mg/mL, 0.125 mg/mL) significantly attenuated the expression of p-IGF1R, PI3K, p-PDK1, p-VEGFR2 to inhibit the proliferation, migration and induce apoptosis of gastric cancer cells, which was consistent with the network pharmacology. Additionally, atractylenolide Ⅰ, quercetin, glycyrol, physcione and aloe-emodin, emodin, kaempferol, licoflavone A were found to be the key compounds of GQBZF regulating IGF1R and VEGFR2, respectively. And among which, glycyrol and emodin were determined as key active compounds against GC by farther vitro experiments and LC/MS. Meanwhile, we also found that glycyrol inhibited MKN-45 cells proliferation and enhanced apoptosis, which might be related to the inhibition of IGF1R/PI3K/PDK1, and emodin could significantly attenuate the MKN-45 cells migration, which might be related to the inhibition of VEGFR2-related signaling pathway. These results were verified again by molecular dynamics simulation and binding interaction pattern. In summary, this study suggested that GQBZF and its key active components (glycyrol and emodin) can suppress IGF1R/PI3K/PDK1 and VEGFR2-related signaling pathway, thereby inhibiting tumor cell proliferation and migration and inducing apoptosis. These findings provided an important strategy for developing new agents and facilitated clinical use of GQBZF against GC.

Development and validation of a nomogram model for medication non-adherence in patients with chronic kidney disease.

OBJECTIVE: The high prevalence of medication non-adherence in patients with chronic kidney disease places a tremendous burden on healthcare resources. The study was designed to develop and validate a nomogram model of medication non-adherence in patients with chronic kidney disease in China. METHODS: A multicenter cross-sectional study was conducted. 1206 chronic kidney disease patients were consecutively enrolled from Be Resilient to Chronic Kidney Disease (registration number: ChiCTR2200062288) between September 2021 and October 2022 in four tertiary hospitals in China. The Chinese version of four-item Morisky Medication Adherence Scale was used to assess the medication adherence of the patients and associated factors consisted of socio-demographic information, self-designed medication knowledge questionnaire, the 10-item Connor-Davidson Resilience Scale, the Beliefs about Medicine questionnaire, the Acceptance Illness Scale, and the Family Adaptation Partnership Growth and Resolve Index. Least Absolute Shrinkage and Selection Operator regression was performed to select significant factors. Concordance index, Hosmer-Lemeshow test and decision curve analysis were estimated. RESULTS: The prevalence of medication non-adherence was 63.8%. Area under the curves ranged from 0.72 to 0.96 in internal and external validation sets. The predicted probabilities of the model were consistent with those of the actual observations by Hosmer-Lemeshow test (all P > .05). The final model included educational level, occupational status, duration of chronic kidney disease, medication beliefs (perceptions of the need to take medications and concerns about adverse effects), and illness acceptance (adaptation and acceptance of the disease). CONCLUSIONS: There is a high prevalence of medication non-adherence among Chinese patients with chronic kidney disease. A nomogram model based on five factors has been successfully developed and validated and could be incorporated into long-term medication management.

To study the protective effect of Huangqi Baihe Granules on Radiation brain injury based on network pharmacology and experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi baihe Granules (HQBHG), which is a key Chinese medical prescription, has a remarkable efficacy in oxidative stress and inflammation. Nevertheless, the therapeutic effect on Radiation brain injury (RBI) has rarely been studied. AIM OF THE STUDY: The study aimed to verify the effect of HQBHG against RBI and explore its potential mechanism. METHODS: The potential targets and mechanisms of HQBHG against RBI were predicted by network pharmacology and verified by established rat model of RBI Firstly, the therapeutic effect of HQBHG in RBI was confirmed by water maze test, HE staining and Enzyme-linked immunosorbent assay (ELISA). Secondly, the potential critical anti-RBI pathway of HQBHG was further explored by water maze, HE staining, immunofluorescence assays, ELISA and western blot. RESULTS: A total of 43 HQBHG anti-RBI targets were obtained. Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations showed that the treatment of HQBHG in RBI might be mainly related to oxidative stress, inflammation and PI3K/AKT pathway. Experimental studies have indicated that HQBHG can improve spatial learning and memory ability, alleviate pathological damage of brain tissue in RBI of rats. HQBHG also can down-regulate the levels of IL-1ß, TNF-α, ROS and MDA, meanwhile, GSH was significantly up-regulated. In addition, the HQBHG can increase the protein expression phosphorylations PI3K (p-PI3K), phosphorylations AKT(p-AKT) and Nrf2 in the brain tissue of RBI. CONCLUSION: HQBHG may alleviated RBI by regulated oxidative stress and inflammatory response through PI3K/AKT/Nrf2 pathway.

Deciphering the Active Compounds and Mechanisms of HSBDF for Treating ALI via Integrating Chemical Bioinformatics Analysis.

The Huashi Baidu Formula (HSBDF), a key Chinese medical drug, has a remarkable clinical efficacy in treating acute lung injury (ALI), and it has been officially approved by the National Medical Products Administration of China for drug clinical trials. Nevertheless, the regulated mechanisms of HSBDF and its active compounds in plasma against ALI were rarely studied. Based on these considerations, the key anti-inflammatory compounds of HSBDF were screened by molecular docking and binding free energy. The key compounds were further identified in plasma by LC/MS. Network pharmacology was employed to identify the potential regulatory mechanism of the key compounds in plasma. Next, the network pharmacological prediction was validated by a series of experimental assays, including CCK-8, EdU staining, test of TNF-α, IL-6, MDA, and T-SOD, and flow cytometry, to identify active compounds. Molecular dynamic simulation and binding interaction patterns were used to evaluate the stability and affinity between active compounds and target. Finally, the active compounds were subjected to predict pharmacokinetic properties. Molecular docking revealed that HSBDF had potential effects of inhibiting inflammation by acting on IL-6R and TNF-α. Piceatannol, emodin, aloe-emodin, rhein, physcion, luteolin, and quercetin were key compounds that may ameliorate ALI, and among which, there were five compounds (emodin, aloe-emodin, rhein, luteolin, and quercetin) in plasma. Network pharmacology results suggested that five key compounds in plasma likely inhibited ALI by regulating inflammation and oxidative damage. Test performed in vitro suggested that HSBDF (0.03125 mg/ml), quercetin (1.5625 µM), emodin (3.125 µM), and rhein (1.5625 µM) have anti-inflammatory function against oxidative damage and decrease apoptosis in an inflammatory environment by LPS-stimulation. In addition, active compounds (quercetin, emodin, and rhein) had good development prospects, fine affinity, and stable conformations with the target protein. In summary, this study suggested that HSBDF and its key active components in plasma (quercetin, emodin, and rhein) can decrease levels of pro-inflammatory factors (IL-6 and TNF-α), decrease expression of MDA, increase expression of T-SOD, and decrease cell apoptosis in an inflammatory environment. These data suggest that HSBDF has significant effect on anti-inflammation and anti-oxidative stress and also can decrease cell apoptosis in treating ALI. These findings provided an important strategy for developing new agents and facilitated clinical use of HSBDF against ALI.

Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment.

A tumor-related hypoxic microenvironment can promote the proliferation of gastric cancer cells, and hypoxic-induced autophagy is the main mechanism of protection against hypoxia in gastric cancer cells. Isorhamnetin (ISO) is a chemical substance derived from plants, mainly from the sea buckthorn. Previous studies have shown that ISO has antitumor effects, but the effects of ISO against gastric cancer in a hypoxic environment are still unknown. In this study, we investigated the effects of ISO against gastric cancer in a hypoxic environment and the mechanisms underlying ISO-induced gastric cancer cell death. The results show that ISO targeted PI3K and blocked the PI3K-AKT-mTOR signaling pathway, significantly inhibiting gastric cancer cell autophagy in a hypoxic environment, inhibiting cell proliferation, decreasing mitochondrial membrane potential, and promoting mitochondria-mediated apoptosis. ISO, a functional food component, is a promising candidate for the treatment of gastric cancer.

Incidence and risk factors for postoperative lingual neuropraxia following airway instrumentation: A retrospective matched case-control study.

BACKGROUND: Lingual nerve injury or neuropraxia is a rare but potentially serious perioperative complication following airway instrumentation during general anesthesia. This study explored the the incidence and perioperative risk factors for lingual nerve injury in patients receiving laryngeal mask (LMA) or endotracheal (ETGA) general anesthesia in a single center experience. METHODS AND RESULTS: All surgical patients in our hospital who received LMA or ETGA from 2009 to 2013 were included, and potential perioperative risk factors were compared. Matched controls were randomly selected (in 1:5 ratio) from the same database in non-case patients. A total of 36 patients in the records had reported experiencing tongue numbness after anesthesia in this study. Compared with the non-case surgical population (n = 54314), patients with tongue numbness were significantly younger (52.2±19.5 vs 42.0±14.5; P = 0.002) and reported lower ASA physical statuses (2.3±0.7 vs 1.6±0.6; P<0.001). Patient gender, anesthesia technique used, and airway device type (LMA or ETGA) did not differ significantly across the two groups. A significantly higher proportion of patients underwent operations of the head-and-neck region (38.9 vs 15.6%; P = 0.002) developed tongue numbness after anesthesia. Multivariate logistic regression analysis indicated that head-and-neck operations remained the most significant independent risk factor for postoperative lingual nerve injury (AOR 7.63; 95% CI 2.03-28.70). CONCLUSION: The overall incidence rate of postoperative lingual neuropraxy was 0.066% in patients receiving general anesthesia with airway device in place. Young and generally healthy patients receiving head-and-neck operation are at higher risk in developing postoperative lingual neuropraxy. Attention should be particularly exercised to reduce the pressure of endotracheal tube or laryngeal mask on the tongue during head-and-neck operation to avert the occurrence of postoperative lingual neuropraxy.

Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats.

BACKGROUND: Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. METHODS AND RESULTS: Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 µg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area. CONCLUSION: Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes.

Incidence and characteristic analysis of in-hospital falls after anesthesia.

BACKGROUND: In-hospital falls may result in serious clinical adverse consequences, but the effects of anesthesia in the occurrence of postoperative falls are still undetermined. Anesthesia may theoretically cause postoperative falls due to the residual pharmacologic and neuromuscular blocking effects of anesthetics. We retrospectively reviewed events of in-hospital falls occurred after anesthesia management to identify the incidence and risk factors of postanesthesia falls. METHODS: We reviewed the postanesthesia visit of patients received anesthesia in the Hualien Buddhist Tzu Chi General Hospital from January 2009 to December 2013. Falls happened within 24 h after anesthesia were recorded. The Poisson regression model was used for simultaneous analysis of the association between incidence proportion of postanesthesia falls and the potential risk factors. RESULTS: A total of 60,796 inpatients received anesthesia management over the past 5 years, and ten patients fell within 24 h after anesthesia. All cases happened in the general wards. Falls occurred more often at the bedside, presence of caregivers, and during the daytime. Patients underwent regional anesthesia, and old age significantly increased the risk of postanesthesia falls, while differences in gender and ASA physical status did not affect the occurrence of postanesthesia falls. CONCLUSIONS: The overall incidence proportion of postanesthesia falls is 1.6 cases per 10,000 patients (95 % CI 0.006 to 0.026 %) over a 24-h observation period. Falls are more commonly happened during the less expected periods after operation and are increased in the elderly and patients received regional anesthesia. This study highlights that more comprehensive clinical practice guidelines for postoperative care should be exercised to prevent the in-hospital falls.