Search

Abstract Colon adenocarcinoma (COAD) is a serious public health problem, the third most common cancer and the second most deadly cancer in the world. About 9.4% of cancer-related deaths in 2020 were due to COAD. Anoikis is a specialized form of programmed cell death that plays an important role in tumor invasion and metastasis. The presence of anti-anoikis factors is associated with tumor aggressiveness and drug resistance. Various bioinformatic methods, such as differential expression analysis, and functional annotation analysis, machine learning, were used in this study. RNA-sequencing and clinical data from COAD patients were obtained from the Gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Construction of a prognostic nomogram for predicting overall survival (OS) using multivariate analysis and Lasso-Cox regression. Immunohistochemistry (IHC) was our method of validating the expression of seven genes that are linked to anoikis in COAD. We identified seven anoikis-related genes as predictors of COAD survival and prognosis, and confirmed their accuracy in predicting colon adenocarcinoma prognosis by KM survival curves and ROC curves. A seven-gene risk score consisting of NAT1, CDC25C, ATP2A3, MMP3, EEF1A2, PBK, and TIMP1 showed strong prognostic value. Meanwhile, we made a nomogram to predict the survival rate of COAD patients. The immune infiltration assay showed T cells. CD4 memory. Rest and macrophages. M0 has a higher proportion in COAD, and 11 genes related to tumor immunity are important. GDSC2-based drug susceptibility analysis showed that 6 out of 198 drugs were significant in COAD. Anoikis-related genes have potential value in predicting the prognosis of COAD and provide clues for developing new therapeutic strategies for COAD. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings also suggest possible mechanisms that may affect prognosis. These results are the starting point for planning individualized treatment and managing patient outcomes.

Abstract Colon adenocarcinoma (COAD) is a type of cancer that arises from the glandular epithelial cells that produce mucus in the colon. COAD is influenced by various factors, including genetics, environment and lifestyle. The outcome of COAD is determined by the tumor stage, location, molecular characteristics and treatment. Disulfidptosis is a new mode of cell death that may affect cancer development. We discovered genes associated with disulfidptosis in colon adenocarcinoma and proposed them as novel biomarkers and therapeutic targets for COAD. We analyzed the mRNA expression data and clinical information of COAD patients from The Cancer Genome Atlas (TCGA) database and Xena databases, extracted disulfidptosis-related genes from the latest reports on disulfidptosis. We used machine learning to select key features and build a signature and validated the risk model using data from the Gene Expression Omnibus (GEO) database and Human Protein Atlas (HPA). We also explored the potential biological functions and therapeutic implications of the disulfidptosis-related genes using CIBERSORTx and GDSC2 databases. We identified four disulfidptosis-related genes: TRIP6, OXSM, MYH3 and MYH4. These genes predicted COAD patient survival and modulated the tumor microenvironment, drug sensitivity and immune microenvironment. Our study reveals the importance of disulfidptosis-related genes for COAD prognosis and therapy. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings may facilitate personalized cancer treatment.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.

Psoriasis is a chronic inflammatory disease that is considered by a network of immunocytes and cytokines. Among all, Th17 cells–derived IL-17 is a critical driving factor in the pathogenesis of psoriasis. Recently, disruption of the extracellular matrix was found to be related to psoriasis progression. In the present study, we aimed to investigate the role of heparanase (HPSE) in psoriasis and the crosstalk with the IL-17 signalling pathway. Skin tissues from non-affected areas and psoriatic lesion areas before and after 12 weeks of IL-17 monoclonal antibody treatment of 30 psoriasis patients were collected. HaCaT cells were treated with different concentrations of IL-17 antibody, and HPSE in cells and medium were measured with Western blotting assay as well as enzyme-linked immunosorbent assay (ELISA). In the imiquimod (IMQ)-induced psoriasis model, IL-17 protein and mRNA expression levels were measured, and changes in the proportion of Th17 cells were detected via flow cytometry. Our data showed that HPSE is upregulated in lesion tissues isolated from psoriasis patients, and was inhibited by anti-IL-17 treatment. In cutaneous cells and IMQ-induced psoriasis model, IL-17 promoted the synthesis of HPSE. Inversely, HPSE was also found to increase the percentage of Th17 cells derived from CD4+ T cells. Finally, we found that the combined treatments of HPSE inhibitor and IL-17 monoclonal antibody produced therapeutic effects on IMQ-induced psoriasis model. Our findings revealed the new role of HPSE in the pathogenesis of psoriasis and also provided a target for combined treatment of psoriasis.

Abstract Background Baihu-Guizhi decoction (BHGZD) is a well-documented traditional Chinese Medicine (TCM) prescription that has been extensively applied to treating rheumatoid arthritis. Despite of its beneficial outcomes, the chemical constituents of BHGZD have not been fully portrayed and the in vivo absorption, distribution, metabolism, and excretion (ADME) patterns of absorbed components have never been described. Methods Characterization of absorbed components and in vivo biotransformation profiling of these feature compounds were based on the ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Furthermore, the ultra-high-performance liquid chromatography tandem ion trap quadrupole mass spectrometry (UHPLC-Q-TRAP-MS/MS) system were performed to investigate the pharmacokinetics of active ingredients from BHGZD. Results In this study, we have identified and tentatively characterized 18 feature absorbed prototype and 15 metabolites of BHGZD in rat serum and the in vivo transformation pathways of these absorbed constituents were proposed. Besides, we have established novel quantitative methodology of five crucial components of BHGZD and have monitored the pharmacokinetic behaviors of these constituents spontaneously in rat serum after BHGZD gavage. After rats received two ways of BHGZD gavage, the pharmacokinetic behaviors of each compound exhibited relatively similar behaviors, as evidenced by similar curve track as well as relatively close time to reach maximum concentration (Tmax) and half washout time (T1/2). Whereas the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) values of five analytes with multiple dosage were a bit higher than single dosage. Conclusion This study added knowledge into the material basis and bio-transformation patterns of BHGZD in vivo, which would be of great value for exploring pharmacological effects and mechanism of BHGZD.

BackgroundLaparoscopic natural orifice specimen extraction surgery (NOSES) has been widely used in colorectal neoplasms. However, only a few studies have focused on robotic NOSES. This study compared the short-term clinical outcomes and long-term survival outcomes between robotic NOSES and conventional robotic resection (CRR) groups.MethodsFrom March 2016 to October 2018, a consecutive of 143 patients who underwent robotic sigmoid and rectal resection at the Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, were considered for inclusion in this study. Propensity-score matching (PSM) was conducted to account for differences in the baseline characteristics. After PSM, 39 patients were included in the robotic NOSES group, and 39 patients in the CRR group. The baseline characteristics between the two groups were all balanced and comparable.ResultsPatients in the NOSES group experienced less intraoperative blood loss (p=0.001), lower requirements for additional analgesia (p=0.020), shorter time to first flatus (p=0.010), and a shorter time to first liquid diet (p=0.003) than the CRR group. The 3-year overall survival rates (NOSES: 92.3% vs. CRR: 89.7% p=1.000) and 3-year disease-free survival rates (NOSES: 82.1% vs. CRR: 84.6% p=0.761) between the two groups were comparable.ConclusionRobotic natural orifice specimen extraction surgery is a safe and feasible surgery for patients with colorectal neoplasms. Robotic NOSES is associated with better short-term clinical outcomes and similar long-term survival outcomes to conventional robotic resection.

Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.

Duodenocolic fistula is a rare upper gastrointestinal fistula that can be benign or malignant. However, benign duodenocolic fistulas are particularly rare. Duodenocolic fistulas are often a complication of advanced colon cancer. The most common cause of benign fistulas is perforation of the duodenal ulcer. We report a case of a benign duodenocolic fistula in a patient who presented with abdominal pain, diarrhea, and weight loss. Gastroscopy and an upper gastrointestinal study confirmed the presence of the fistula. Surgery was performed, and the pathological examination demonstrated that the fistula originated from a duodenal ulcer.

Abstract To improve the utilization of okra seed, acidic and enzymatic hydrolyses of producing protein hydrolysates were respectively optimized by orthogonal experiment and response surface methodology using the degree of hydrolysis (DH) as evaluating index. Amino acid composition and antioxidant capacity in vitro of two kinds of hydrolysates were both analyzed. The degree of acidic hydrolysis was 58.53 ± 1.92% under the following optimized condition: hydrolyzing time 40 hr, temperature 95°C, ratio of acid solution to okra seed meal (OSM) powder was 5:1 (V:W/ml:g), and hydrochloric acid concentration was 18% (W/W). The degree of enzymatic hydrolysis was 16.26 ± 0.56% under the optimized condition: hydrolyzing time 8.20 hr, ratio of buffer to OSM powder was 10:1, and enzyme dosage was 3,100 International Units (IU) g−1. Enzymatic hydrolysates had a fuller range of amino acids and antioxidant capacity than acidic hydrolysates. The results provide technical support for the expansion of okra seed utilization.

Abstract Natural orifice specimen extraction surgery (NOSES) is especially suitable for colorectal surgery. Until now, most of the reports published were about laparoscopic NOSES, the reports about robotic NOSES are extremely rare. This study aims to explore the safety and feasibility of robotic NOSES for colorectal neoplasms. All patients underwent robotic NOSES from March 2016 to October 2019 in our hospital were enrolled for retrospective analysis. Clinicopathological data including patient characteristics, perioperative information and pathological information were collected and analyzed. According to the distance between tumor and anus or whether neoadjuvant chemoradiotherapy (nRCT) is performed, we grouped the cases and studied its influence on robotic NOSES. Also, we compared the previous reports on laparoscopic NOSES with our study and revealed advantages of robotic NOSES in terms of safety and feasibility. A total of 180 patients were enrolled. The average distance from the lower edge of the tumor to the anus was (8.64 ± 3.64) cm and maximum circumferential diameter (CDmax) of specimen was (3.5 ± 1.6) cm. In terms of safety, the average operation time, intraoperative blood loss, and postoperative hospital stay were (187.5 ± 78.3) min, (47.4 ± 34) mL, and (11.3 ± 7.5) days, respectively. In terms of feasibility, the average number of lymph node harvested was (14.8 ± 5). Robotic NOSES shows advantages in terms of safety and feasibility compared with laparoscopic NOSES. This procedure could not only be a safe procedure but also could achieve good oncological outcomes.

Abstract Although the survival rate of patients with cancer have increased due to the use of current chemotherapeutic agents, adverse effects of cancer therapy remain a concern. The reversal of drug resistance, reduction in harmful side effects and accelerated increase in efficiency have often been addressed in the development of combination therapeutics. Tazemetostat (EPZ-6438), a histone methyltransferase EZH2 selective inhibitor, was approved by the FDA for the treatment of advanced epithelioid sarcoma. However, the effect of tazemetostat on colorectal cancer (CRC) and 5-FU sensitivity remains unclear. In this study, the enhancement of tazemetostat on 5-FU sensitivity was examined in CRC cells. Our findings demonstrated that tazemetostat combined with 5-FU exhibits synergistic antitumor function in vitro and in vivo in CRC cells. In addition, tazemetostat promotes PUMA induction through the ROS/ER stress/CHOP axis. PUMA depletion attenuates the antitumor effect of the combination therapy. Therefore, tazemetostat may be a novel treatment to improve the sensitivity of tumors to 5-FU in CRC therapy. In conclusion, the combination of 5-FU and tazemetostat shows high therapeutic possibility with reduced unfavorable effects.

Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic‐pituitary‐thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.

Abstract Background Oral ulcer diseases are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. Kouyanqing Granule (KYQG) has been used to treat inflammatory diseases of the mouth and throat, including recurrent aphthous stomatitis (RAS), traumatic ulcers, oral leukoplakia and so on. However, the underlying molecular mechanisms of KYQG in treating these diseases are still unclear. We aimed to explore the possible mechanisms in KYQG for the treatment of oral ulcers. Methods An innovative network pharmacology method was established by incorporating targets searching and fishing, network analysis, and silico validation to discover the pharmacological mechanisms of action of KYQG for the treatment of oral ulcers. Then, we verified the reliability of this method by an animal experiment. Results Our data indicated that a total of 47 key targets were screened, which mainly involved in three function modules including the inhibition of inflammation, the regulation of immunological response, and the suppression of oxidative stress. The implementation of these functions relies on the complex multi-pathways network, especially TNF signaling pathway and HIF-1 signaling pathway. The results of the experimental verification indicated that KYQG significantly inhibited the serum levels of cyclooxygenase-2 (COX2), matrix metalloproteinase 9 (MMP9) and tumor necrosis factor-alpha (TNF-α) in rats with oral ulcer. Conclusion KYQG exhibited the therapeutic effects on oral ulcers probably by inhibiting inflammation, regulating immunological response, and suppressing oxidative stress through a complex multi-pathways network. Particularly, TNF signaling pathway and HIF-1 signaling pathway may play crucial roles in the protection of KYQG against oral ulcers. This work not only offers a method for understanding the functional mechanisms of KYQG for treating oral ulcer diseases from a multi-scale perspective but also may provide an efficient way for research and development of complex composition formula.

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124–mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.

Abstract GNA13 has been found overexpressed in various types of cancer, which is related to tumor metastasis and progression. However, the biological functions of GNA13 in colorectal cancer (CRC) progression remain unclear. This study aimed to explore the role of GNA13 in CRC and investigate the mechanism of how GNA13 promotes tumor growth. Interestingly, our findings showed that GNA13 is commonly upregulated in CRC, where these events are associated with a worse histologic grade and poor survival. Increased expression levels of GNA13 promoted cell growth, migration, invasion, and epithelial‐mesenchymal transition, whereas GNA13 silencing abrogated these malignant phenotypes. In addition, overexpressing GNA13 in cancer cells increased the levels of the chemokines CXCL1, CXCL2, and CXCL4, which contributed to CRC proliferation and colony formation. Moreover, our mechanistic investigations suggest that the NF‐κB/p65 signaling pathway was activated by the increase in GNA13 levels. Inhibiting the NF‐κB/p65 pathway with an inhibitor decreased GNA13‐induced migration, invasion and CXCL chemokine level increases, indicating the critical role of NF‐κB/p65 signaling in mediating the effects of GNA13 in CRC. Together, these results demonstrate a key role of GNA13 overexpression in CRC that contributes to malignant behavior in cancer cells, at least in part through stimulating angiogenesis and increasing the levels of the NF‐κB‐dependent chemokines CXCL1, CXCL2, and CXCL4.

Aim: To analyze the learning curve (LC) for robotic natural orifice specimen extraction surgery (NOSES) for colorectal neoplasms and evaluate safety and feasibility during the initial LC.Method: Patients who consecutively underwent robotic NOSES performed by two surgeons between March 2016 and October 2019 were analyzed retrospectively. The operation time was evaluated using the cumulative sum method to analyze the LC. The clinicopathological data before and after the completion of LC were extracted and compared to evaluate safety and feasibility.Results: In total, 99 and 66 cases were scheduled for robotic NOSES by Prof. Yao and Prof. Li, respectively. The peak points of LC were observed at the 42nd and 15th cases of Yao and Li, respectively, then operation time began to decrease. Only the operation time for Yao before the completion of LC (213.3 ± 67.0 min) was longer than that after the completion of LC (143.8 ± 33.3 min). For Yao nor for Li, other indices, such as postoperative hospital stay, intraoperative blood loss, conversion to laparotomy, incidence of anastomotic leakage, reoperation rate, and 90-day mortality rate lacked significant statistical differences(P > 0.05). In terms of feasibility, the number of lymph nodes harvested, positive resection margin rate, and total cost before and after the completion of LC had no significant statistical difference (P > 0.05).Conclusion: The cases before the completion of LC for robotic NOSES in colorectal neoplasms varied from 15 cases to 42 cases. Robotic NOSES is safe and feasible during the initial LC.

Oral ulcers are the most prevalent oral mucosal diseases globally, and no specific treatment schemes are currently available due to the complexity of oral ulcer diseases. Sleep deprivation increases the risk of a deterioration in oral health. Kouyanqing Granule (KYQG) has been used for decades in China to treat inflammatory diseases of the mouth and throat associated with the hyperactivity of fire due to yin deficiency syndrome. However, the mechanisms underlying the effects of KYQG in the treatment of oral ulcers are still unclear. The aims of this study were to investigate whether KYQG treatment could attenuate the symptoms of oral ulcers worsened by sleep deprivation and identify the involved metabolic pathways. First, we conducted chemical profiling of KYQG via UPLC–MS analysis. We then combined pharmacological and metabolomics approaches in a phenol-induced rat model of oral ulcers worsened by sleep deprivation. A total of 79 compounds were initially identified. Our observations showed that KYQG treatment induced a significantly higher healing rate in oral ulcers worsened by sleep deprivation. KYQG significantly reduced the levels of 5-HT and GABA in serum, and only decreased the 5-HT level in brain tissue after phenol injury followed by sleep deprivation. Moreover, KYQG administration significantly suppressed systemic inflammation by inhibiting TNF-α, IL-1β, IL-6, IL-18, and MCP-1. Immunohistochemical analysis further revealed that KYQG inhibited IL-6 expression in buccal mucosa tissues. KYQG treatment also significantly decreased the serum levels of ACTH, CORT, IgM, and 8-OHdG. Serum metabolomics analysis showed that a total of 30 metabolites showed significant differential abundances under KYQG intervention, while metabolic pathway analysis suggested that the altered metabolites were associated with the dysregulation of eight metabolic pathways. Taken together, our results indicated that KYQG attenuates the symptoms of oral ulcers worsened by sleep deprivation probably through the regulation of the neuroimmunoendocrine system, oxidative stress levels, and tryptophan metabolism. This study also provides a novel approach for addressing the increased health risks resulting from sleep deficiency using an herbal medicine formula.

Microctis Folium is the dried leaves of a plant (Microcos paniculata L.) used to improve the digestive system, alleviate diarrhoea, and relieve fever, but information regarding its chemical composition has rarely been reported. The traditional research approach of determining chemical composition has included isolating, purifying, and identifying compounds with high-cost and time-consuming processes. In this study, molecular networking (MN) and fingerprint analysis were integrated as a comprehensive approach to study the chemical composition of Microctis Folium by an ultra fast liquid chromatography-photo diode array detector-triple-time of flight-tandem mass spectrometry (UFLC-DAD-Triple TOF-MS/MS). Large numbers of mass spectrometric data were processed to identify constituents, and the identified compounds and their unknown analogues were comprehensively depicted as visualized figures comprising distinct families by MN. A validated fingerprint methodology was established to quantitatively determine compounds in Microctis Folium. Ultimately, 165 constituents were identified in Microctis Folium for the first time and the identified compounds and approximately five hundred unknown analogues were applied to create visualized figures by MN, indicating compound groups and their chemical structure analogues in Microctis Folium. The validated fingerprint methodology was indicated to be specific, repeatable, precise, and stable and was used to determine 15 batches of samples during three seasons in three districts. Furthermore, seasonal or geographic environmental influences on the chemical profile were estimated by principal coordinate analysis. The results can be used to control the quality of Microctis Folium, observe seasonal or geographic environmental influences on the chemical profiles, and provide a reference for further exploitation of potential active unknown analogues in the future.

Abstract Background Situs inversus totalis (SIT) refers to an unusual condition involving reversal of abdominal and thoracic viscera, with an incidence rate of 1/5000–20,000 adults. Minimally invasive surgeries for SIT patients are technically challenging, while the surgical experience for SIT patients is quite limited. Case presentation A 61-year-old man, previously diagnosed as SIT, came to our hospital for 6 months history of hematochezia and altered bowel habit. A diagnosis of rectal cancer was made in view of colonoscopic biopsy which confirmed an irregular circumferential lump of well differentiated adenocarcinoma at 10 cm from the anal verge. The computed tomography contrast-enhanced (thorax + abdomen + pelvis) scan revealed a total transposition of abdominal and thoracic organs and an enhanced eccentric mass of rectal but with no evidence of distant metastasis. Robotic low anterior resection (LAR) plus transanal natural orifice specimen extraction (NOSE) was performed after obtaining informed consent. The procedure was performed successfully and the patient convalesced nicely without any complications. The postoperative pathological diagnosis revealed a 4x4x0.6 cm3 moderately differentiated adenocarcinoma and circumferential clearance. Conclusions Robotic LAR plus transanal NOSE for rectal cancer patients with SIT can be performed safely and may be an effective approach in contrast to open or laparoscopic approach, despite the unconventional anatomy.

Aging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases. To date, the pharmacokinetic processes of naringin in aged individuals are still unknown. Thus, a rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS) method was established for the determination of naringin and its metabolite naringenin in rat plasma, urine, feces, and tissue homogenate. The pharmacokinetic parameters were calculated and a higher exposure of naringin and naringenin were observed in aged rats. Naringin and naringenin were mostly distributed in gastrointestinal tract, liver, kidney, lung, and trachea. Furthermore, a total of 39 flavonoid metabolites (mainly glucuronides and sulfates) and 46 microbial-derived phenolic catabolites were screened with ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Naringenin, hippuric acid, and 3-(4’-hydroxyphenyl)propionic acid were predominated metabolites. This study systemically investigated the pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats, revealing age- and gender-related changes in the in vivo behavior of naringin. These results would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in aged population.

The dynamic vibration absorbers have been applied to attenuate the critical or unbalanced vibration but may create the fluid-induced vibration instability in the rotor/seal system. The major purpose of this study is devoted to the effects of the dynamic vibration absorber on the nonlinear dynamic behavior and stability of the fluid-induced vibration in the rotor/seal system. The dynamic vibration absorber is attached on the shaft in the perpendicular directions. The model of the rotor/seal-dynamic vibration absorber system is established as the modified Jeffcott rotor system, and Muszynska nonlinear seal force is applied. The numerical method is used for the dynamic behavior analysis. The effects of the natural frequency and damping ratio of the dynamic vibration absorber on the dynamic behavior are discussed. The stability of the rotor/seal-dynamic vibration absorber system is judged by the eigenvalue theory. The variations of the instability threshold with the parameters of the dynamic vibration absorber are obtained. The results show that the instability threshold and instability vibration frequency are changed by the dynamic vibration absorber. The parameters of the dynamic vibration absorber must be selected carefully to avoid reducing the instability threshold and causing the instability vibration to occur in advance when the dynamic vibration absorber is applied to attenuate the critical or unbalanced vibration of the rotor/seal system.

A theoretical research on eliminating the instability vibration and improving the stability of the rotor/seal system using the inerter-based dynamic vibration absorber (IDVA) is presented in this paper. The modified Jeffcott rotor and Muszynska nonlinear seal force models are employed. The proposed IDVA is the damping element of the traditional dynamic vibration absorber (DVA) replaced by one of the six configurations of the inerter. The instability threshold speed of the system is obtained by applying the Routh–Hurwitz stability criterion. The quantum particle swarm optimization (QPSO) method is utilized to optimize the parameters of the IDVA. The numerical method is applied to investigate the nonlinear dynamic responses and stability. The results show that the IDVA can effectively improve the stability and reduce the instability vibration of the rotor/seal system. Furthermore, the performance of the IDVA is more effective than that of the traditional DVA.

Rotundic acid (RA) is a major triterpene constituent in the barks of Ilex rotunda Thunb, which have been widely used to make herbal tea for health care in southern China. RA has a variety of bioactivities such as anti-inflammation and lipid-lowering effect. However, little is known about the effects and mechanisms of RA on metabolic disturbance in type 2 diabetes (T2D) and its effect on gut microbiota. A T2D rat model induced by high fat diet (HFD) feeding and low-dose streptozotocin (STZ) injection was employed and RA showed multipronged effects on T2D and its complications, including improving glucolipid metabolism, lowering blood pressure, protecting against cardiovascular and hepatorenal injuries, and alleviating oxidative stress and inflammation. Furthermore, 16s rRNA gene sequencing was carried out on an Illumina HiSeq 2500 platform and RA treatment could restore the gut microbial dysbiosis in T2D rats to a certain extent. RA treatment significantly enhanced the richness and diversity of gut microbiota. At the genus level, beneficial or commensal bacteria Prevotella, Ruminococcus, Leuconostoc and Streptococcus were significantly increased by RA treatment, while RA-treated rats had a lower abundance of opportunistic pathogen Klebsiella and Proteus. Spearman’s correlation analysis showed that the abundances of these bacteria were strongly correlated with various biochemical parameters, suggesting that the improvement of gut microbiota might help to prevent or attenuate T2D and its complication. In conclusion, our findings support RA as a nutraceutical agent or plant foods rich in this compound might be helpful for the alleviation of T2D and its complications through improving gut microbiota.

The dynamic vibration absorbers have been applied to attenuate the rotor unbalance and torsional vibrations. The major purpose of this paper is to research the elimination of the fluid-induced vibration in the rotor/seal system using the absorber. The simplified rotor model with the absorber is established, and the Muszynska fluid force model is employed for the nonlinear seal force. The numerical method is used for the solutions of the nonlinear differential equations. The nonlinear responses of the rotor/seal system without and with the absorber are obtained, and then the rotating speed ranges by which the fluid-induced instability can be eliminated completely and partially are presented, respectively. The absorber parameters ranges by which the instability vibration can be eliminated completely and partially are obtained. The results show that the natural frequency vibration due to the fluid-induced instability in the rotor/seal system can be eliminated efficiently using the absorber. The appropriate natural frequency and damping ratio of the absorber can extend the complete elimination region of the instability vibration and postpone the occurrence of the instability vibration.

A novel nonlinear energy sink (NES) consisting of permanent magnetic springs and coil springs is proposed, and the vibration attenuation performance of the NES for unbalanced rotor system is investigated. Firstly, the nonlinearity of the magnet spring is analyzed and the structure of the NES is introduced. Then, the dynamic model of the rotor system with the NES is built, and the responses and stabilities of the system are studied by applying Complexification-averaging method. The strongly modulated responses (SMR) behavior, which is the most important performance characteristic of the NES, is analytically studied by combining Complexification-averaging method and multiscale method and numerically verified by Runge-Kutta method. The results show that the NES is effective in attenuating the vibration of unbalanced rotor, and the SMR occurrence range can be broadened by increasing the nonlinearity of the NES. And also, the NES has better performance over a wider frequency range than the linear absorber.

To suppress the vibration of a rotor system, a vibration absorber combining negative stiffness with positive stiffness together is proposed in this paper. Firstly, the negative stiffness producing mechanism using ring type permanent magnets is presented and the characteristics of the negative stiffness are analyzed. Then, the structure of the absorber is proposed; the principles and nonlinear dynamic characteristics of the absorber-rotor system are studied numerically. Finally, experiments are carried out to verify the numerical conclusions. The results show that the proposed vibration absorber is effective to suppress the vibration of the rotor system, the nonlinearity of the negatives stiffness affects the vibration suppression effect little, and the negative stiffness can broaden the effective vibration control frequency range of the absorber.

Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in human have not been well investigated. ECG was extracted using boiling water and then provided to volunteers for oral administration. Following the ingestion, urine samples were collected from volunteers over 48 h. The extract and urine samples were analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS) system to screen and identify flavonoids and derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were screened in urine samples collected post consumption. The overall excretion of naringenin metabolites corresponded to 5.45% of intake and occurred mainly within 4–12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were detected in urine. Obtained data revealed that flavonoids were abundant in the ECG extract, and these components underwent extensive phase II metabolism in humans. These results provided valuable information for further study of the pharmacology and mechanism of action of ECG.

Although Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are both the fruits of the same rutaceae plant at different stages of growth, they exert similar yet distinct clinical effects. The chemical composition is crucial for quality control as well as therapeutic application. To address this concern, it is significant to evaluate the similarities and differences of the constituents in both AF and AFI. The extract of AF and AFI were comprehensively analyzed by ultra fast liquid chromatography-photodiode array detector-triple-time of flight-tandem mass spectrometry (UFLC-DAD-Triple TOF-MS/MS). Among the 40 compounds detected, 19 metabolites were detected in both the AF and AFI; whereas 13 compounds were only detected in AF and five constituents were exclusively detected in AFI. In particular, even in AFI, three compounds were only identified in AFI (Citrus aurantium’ L. and its cultivar). Among the 18 compounds confirmed by standard database, 13 compounds were reported in AF and AFI for the first time. Furthermore, the distinction was also revealed by the content of naringin, hesperidin, neohesperidin, and synephrine. The study directly contributed to the similarities and differences of AF and AFI. Herein, similarities and the differences in chemical profiles of AF and AFI could explain the current clinical applications.

The efficiency and accuracy of common time and frequency domain methods that are used to simulate the response of a rotor system with malfunctions are compared and analyzed. The Newmark method and the incremental harmonic balance method are selected as typical representatives of time and frequency domain methods, respectively. To improve the simulation efficiency, the fixed interface component mode synthesis approach is combined with the Newmark method and the receptance approach is combined with the incremental harmonic balance method. Numerical simulations are performed for rotor systems with single and double frequency excitations. The inherent characteristic that determines the efficiency of the two methods is analyzed. The results of the analysis indicated that frequency domain methods are suitable single and double frequency excitation rotor systems, whereas time domain methods are more suitable for multifrequency excitation rotor systems.