Exploring the action targets (groups) of traditional Chinese medicine (TCM) is an important proposition to promote the innovation and development of TCM, but it has attracted a lot of attention as to whether it is related to the efficacy or the disease. Our team found that the metabolomic signature molecules in the development of diabetes mellitus (DM) were significantly associated with the clinical efficacy of Yuquan Pill through a large clinical sample study. Taking this as a clue, our team intends to expand the information on the omics features of DM development, and discover the key targets (groups) and their lead compounds for the hypoglycemic effect of Yuquan Pill. The project includes: ① Based on the retrospective clinical trials, using omics technology integrated with generative artificial intelligence, mining the characteristic information of proteome and microbiome, forming driving factors together with metabolome characteristic molecules, and characterizing the molecular trajectories of diabetes evolution and their interference by Yuquan Pill; ② Taking the evolving molecular trajectories as a link and pointer, using anthropomorphic modeling and molecular biology techniques such as chemical proteomics to discover the key targets (groups) of Yuquan Pill's hypoglycemic effect, with the prospective clinical samples for validation; ③ Evaluate the overall response of key targets (groups) using graph neural network technology, and search for drug-derived/endogenous lead compounds with proven clinical pathologies and clear mechanisms of action, so as to provide a new paradigm and technology for the discovery of complex active ingredient targets (groups) of TCM that are related to their clinical efficacy, as well as for the discovery of innovative medicines.

Objective:To determine the status of nutritional literacy and its influencing factors among the peritoneal dialysis (PD) patients. Methods:The patients who underwent PD and long-term follow-up in the Department of Nephrology,General Hospital of Eastern Theater Command between January and October,2023 were enrolled in this study. The status of nutritional literacy in the patients was assessed through collecting and analyzing the data on the patients' general information,the current nutritional status,and laboratory-and dialysis-related indicators. Results:The average score of nutritional literacy in the enrolled patients were (24.49±3.35). Significant differences in nutritional literacy scoring were observed in the different patient subgroups according to the patients' educational background,dialysis time or times of receiving multidisciplinary diet guidance (all P values<0.05). The nutritional literacy levels of PD patients were negatively correlated to the concentrations of serum calcium and prealbumin,and left ventricular posterior wall thickness,and postively correlated to prealbumin level(P<0.05). Basing on multiple linear regression analysis,the times of receiving multidisciplinary diet guidance,educational background and serum prealbumin level were identified as independent influencing factors for the nutritional literacy levels in PD patients,respectively (all P values<0.05). Conclusions:The present study showed that the nutritional literacy of PD patients was in the middle level. In clinical practice,to enhance multidisciplinary diet guidance and management at the early stage of PD could contribute to improve the nutritional status of PD patients. In addition,to increase the patients' nutritional knowledge and health management ability might be also helpful for the nutritional levels of PD patients.

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin⁺/CD31⁺ ratio, rather than the number of CD31⁺ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Humans ; Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; Mice, Nude ; Glycogen Synthase Kinase 3 beta/genetics* ; beta Catenin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Desmin/therapeutic use* ; Ki-67 Antigen ; Cell Line, Tumor ; Hypoxia ; RNA, Messenger/therapeutic use* ; Cell Proliferation

Objective To study the antifungal activity of phenazines derivatives. Methods The anti-fungal activity of phenazine compounds was evaluated initially with micro-liquid dilution. No significant antifungal activity against Candida albicans was found. Then, with the combination of phenazine compounds and fluconazole, the anti-fungal activity against fluconazole-resistant C. albicans was detected. Results The phenazine-17 had significant antifungal activity when combined with fluconazole through the inhibition of hyphae formation. Conclusion This study provides a new idea for the development of antifungal drugs and the solution of antifungal drug resistance.

A fast and sensitive UPLC-MS/MS method was established for the direct quantification of insulin aspart in human plasma. The plasma samples were extracted by solid phase extraction (SPE), an ESI ion source was used and operated in the positive ion mode with multiple reaction monitoring (MRM). Bovine insulin was chosen as internal standard and the chromatographic separation of insulin aspart was performed on Waters ACQUITY UPLC CSH C18 column (50 mm×2.1 mm, 1.7 μm). A mixture of acetic acid aqueous solution and acetonitrile with acetic acid at a flow rate of 0.6 mL·min^-1 in gradient elution mode was employed as mobile phase. We found that the method was validated over the range of 0.200-10.0 ng·mL^-1 for insulin aspart and showed excellent linearity. The intra-and inter-assay accuracy and precision were below 14.5% and the recovery was 36.7%-41.7% over the three concentration levels evaluated. The UPLC-MS/MS method was selective, accurate, sensitive and robust, and the method was successfully applied in supporting the pharmacokinetic research of two insulin aspart injections (Test Product and NovoRapid^®) in heathy male subjects. This clinical trial was approved according to the Ethics Committee of West China Hospital, Sichuan University (2017 Clinical Trial (Western Medicine) Approval (148)).

OBJECTIVE: Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis. METHODS: Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise. RESULTS: The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor. CONCLUSION Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.
Animals ; Apoptosis ; Carcinoma, Hepatocellular/therapy* ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Dynamins ; Liver Neoplasms/therapy* ; Mice ; Phosphatidylinositol 3-Kinase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction

Rhamnose synthase (RHM) is a key enzyme in the biosynthesis of uridine diphosphate rhamnose (UDP-Rha), reversibly converting uridine diphosphate-glucose (UDP-Glc) into UDP-Rha in the presence of NADH or NADPH. In this research, yeast extract (YE) was used to stimulate Sorbus aucuparia suspension cells. Based on a previous study of the transcriptome database of S. aucuparia suspension cells, two RHMs were cloned from S. aucuparia and named SaRHM1 (GenBank No.: MK213340) and SaRHM2 (GenBank No.: MK213341). The SaRHM1 gene contained a 2 007 bp open reading frame (ORF) encoding a polypeptide of 668 amino acids with a molecular weight of 75.25 kD, and a theoretical isoelectric point (pI) of 7.24. The SaRHM2 gene contained a 2 040 bp ORF encoding a polypeptide of 679 amino acids with a molecular weight of 76.26 kD and pI of 6.41. Bioinformatic analysis indicated that SaRHM1 and SaRHM2 contained two special sequences of GxxGxxG/A and YxxxK. Multiple sequence alignments and phylogenetic trees show that SaRHM1 and SaRHM2 have high sequence similarity with other plant species of RHMs. The results of enzyme activity assays in vitro revealed that both recombinant SaRHM1 and SaRHM2 are able to convert UDP-Glc into UDP-Rha. SaRHMs displayed maximum activity at 40 ℃ and a pH of 8 and 9, respectively. The K_m values of SaRHM1 and SaRHM2 for UDP-Glc were 212.4 ± 56.70 and 361.0 ± 63.74 μmol·L^-1, respectively, with V_max values of 235.5 ± 18.98 and 516.5 ± 22.30 nmol·min^-1·μg^-1, respectively. This study reports the cloning and sequencing of RHMs from S. aucuparia and verifies their function, which likely provide rhamnose donors for the subsequent biosynthesis of rhamnosides.

OBJECTIVE: To understand the true perception and attitude of the healthcare workers(HCWs) on the workplace violence(WPV) in a secondary Grade A hospital.METHODS: A total of 27 HCWs in a secondary Grade A hospital were selected as study subjects using a typical sampling method. Semi-structured interviews were conducted to collect the information of their perception and attitude on the types and effects of WPV, as well as on the coping measures and the work stress. The characteristics of WPV in the hospital were analyzed. RESULTS: The interviewees believed that verbal abuse was the most common type of WPV received by HCWs. Nurses and female workers were the main victims of WPV. Horizontal violence among colleagues and sexual harassment should not be ignored. Common causes of violent incidents for patients and their family members against HCWs included the fees for treatment, doctor-patient communication, patients alcohol abuse and treatment outcomes not meeting patients′ expectation. About half of the interviewees said that WPV had serious impact on their mental health. The follow-up coping measures to violent incidents were mostly to reassurance to patients with unconditional apology from the HCWs. More than half of the interviewees considered that they had acceptable workload, while some interviewees considered their work to be stressful. The interviewees suggested that improving doctor-patient communication, hospital systems, and the professional knowledge of HCWs were the recommended means to prevents and control the WPV. CONCLUSION: The perception and attitude of HCWs on WPV in this hospital are relatively scattered. Considering the complex causes, the serious consequences, and difficult coping measures, the hospitals, HCWs and all sectors of society need to take comprehensive measures to prevent WPV towards HCWs.

【Objective】 To conduct a retrospective study of the population characteristics, efficacy and influencing factors of rheumatoid arthritis (RA) patients who received iguratimod (IGU) treatment for at least 6 months from July 2015 to October 2020 and had more than 3 follow-up records. 【Methods】 In this study, 105 patients with RA were enrolled, and all the patients received IGU treatment for at least 6 months and were followed up three times. We observed their clinical manifestations before and after treatment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity index (DAS28), rheumatoid factor (RF), anticyclic citrullinated peptide (ACPA), immunoglobulins (IgG, IgA, and IgM), lymphocyte subsets, and observed and recorded adverse reactions. 【Results】 The course of disease and the positive rate of ACPA were significantly lower in IGU group than in the group of IGU combined with (MTX) treatment (P<0.05). The DAS28-ESR of the patients in IGU group was significantly lower than that in the IGU+MTX treatment group and IGU+leflunomide (LEF) treatment group (P<0.05). After 6 months of continuous treatment, visual analogue scale/score (VAS), CRP and DAS28 (ESR/CRP) in IGU group were significantly reduced. As the treatment time was extended to one year, the above indicators further improved, and the number of joint swelling (SW) and the number of joint tenderness (TEN) also significantly improved. After one year’s continuous treatment, the incidence of adverse reactions in IGU group was 32.3%(10/31). 【Conclusion】 For RA patients with early onset, short-course, and antibody-negative, IGU is an effective therapeutic drug and a treatment option for RA patients with interstitial lung disease. IGU is well tolerated and is also an effective and a safe combination therapy option.

【Objective】 To detect autoantibodies in Chinese systemic sclerosis (SSc) patients and analyze the relationship between clinical phenotype and autoantibodies in SSc. 【Methods】 We sequentially included 93 SSc patients. Their general information and clinical data were gathered. The differences in clinical characteristics among autoantibody negative and positive groups were analyzed statistically. 【Results】 Anti-nuclear antibodies were detected in 82 (88.2%) SSc patients. The positive rate of autoantibodies was detected in 26 cases (28.0%) of anti-Scl-70 antibody, 24 cases (25.8%) of anti-SSA/Ro-52 antibody, 19 cases (20.4%) of anti-U1-snRNP antibody, and 16 cases (17.2%) in anti-CENP-B antibody, respectively. The patients with positive anti-SSA/Ro-52 antibody had a significantly higher morbidity rate of pulmonary arterial hypertension (P=0.016). Patients with anti-Scl-70 antibody showed a higher incidence rate of digital tip ulcers or gangrene (P=0.004) and cardiac damage (P=0.014). The patients with anti-U1-snRNP antibody had a higher prevalence of pulmonary arterial hypertension (P=0.047) and Raynaud’s phenomenon (P=0.019), and showed an increased trend in the occurrence of interstitial lung disease (P=0.058). Those with anti-CENP-B antibody had a lower IgG level (P=0.049) and higher ALP (P=0.010) and γ-GT (P=0.003). The incidence of autoimmune liver disease was increased in anti-CENP-B positive patients (P=0.001). 【Conclusion】 Different autoantibodies in SSc are associated with clinical phenotype, and may contribute to the diagnosis, evaluation, and prognostic judgment of the disease.