Xianlian Jiedu Decoction alleviates colorectal cancer by regulating metabolic profiles, intestinal microbiota and metabolites.

BACKGROUND: Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. PURPOSE: The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. METHODS: The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. RESULTS: The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of ß-catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1, and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. CONCLUSION: The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.

External fixator combined with three different fixation methods of fibula for treatment of extra-articular open fractures of distal tibia and fibula: a retrospective study.

BACKGROUND: To compare the efficacy of three different fixation methods of fibula combined with external fixation of tibia for the treatment of extra-articular open fractures of distal tibia and fibula. METHODS: From January 2017 to July 2019, 91 cases of open fractures of distal tibia and fibula were treated with external fixator, and the fibula was fixed with non-fixation (group A, n = 35), plate-screw (group B, n = 30) and Kirschner wire (group C, n = 26). The operation time, intraoperative blood loss, surgical and implants costs, fracture healing time, postoperative complications, and American Orthopaedic Foot and Ankle surgery (AOFAS) scores were compared among the groups. RESULTS: Four patients were lost to follow-up, and 87 patients were followed up for 5-35 months (average, 14.2 months). The operation time of group C (114.92 ± 36.09 min) was shorter than that of group A (142.27 ± 47.05 min) and group B (184.00 ± 48.56 min) (P < 0.05). There was no difference in intraoperative blood loss among the three groups (P > 0.05). The surgical and implants costs in group C (5.24 ± 1.21, thousand dollars) is lower than that in group A (6.48 ± 1.11, thousand dollars) and group B (9.37 ± 2.16, thousand dollars) (P < 0.05). The fracture healing time of group C (5.67 ± 1.42 months) was significantly less than that of group A (6.90 ± 1.33 months) and group B (6.70 ± 1.12 months) (P < 0.05). The postoperative complications such as fractures delayed union and nonunion in group C (2 cases, 8.00%) is less than that in group A (13 cases, 39.39%) and group B (11cases, 37.93%) (P < 0.05). The wound infection and needle-tract infection did not differ among the three groups (P > 0.05). The excellent or good rate of ankle function was 69.70% in group A, 72.41% in group B and 84.00% in group C, with no statistical difference among the three groups (P > 0.05). CONCLUSION: Compared with simple external fixator fixation and external fixator combined with plate-screw osteosynthesis, external fixator combined with K-wire intramedullary fixation shortens the operative time and fracture healing time, reduced costs and complications of fracture healing, while the blood loss, infection complications and ankle function recovery showed no difference with the other two groups. External fixator combined with plate-screw osteosynthesis had no advantage in treating extra-articular open fractures of distal tibia and fibula when compared with simple external fixation.

Estimation and influence of blood loss under endoscope for percutaneous endoscopic lumbar discectomy (PELD): a clinical observational study combined with in vitro experiment.

PURPOSE: The purpose of this study is to come up with new methods to quantitate the blood loss under endoscope and explore the influence of blood loss on percutaneous endoscopic lumbar discectomy (PELD). METHODS: Clinical research and in vitro experiment are combined. In the in vitro experiment, 2.0-ml blood was diluted in different ratio to simulate the rinse solution of PELD, the hematocrit method (HCT-M) and red blood cell count method (RBC-M) were came up to estimate blood loss and the new methods were calibrated with the direct measurement method (Direct-M). In clinical research, 74 patients with L5/S1 disk herniation were treated with PELD, and HCT-M and the empirical method (EMP-M) were used to estimate the blood loss under endoscope. According to blood loss, all patients were divided into group A (≤ 10 ml) and group B (> 10 ml). The blood loss, operation time, fluoroscopy frequency, visual analog scale (VAS), and Oswestry Disability Index (ODI) scores were compared between the two groups. RESULTS: In the in vitro experiment, the hematocrit of the rinse solution was always stable over time. The estimated blood loss by HCT-M was stable and quite approximate to actual blood volume (2.0 ml) whatever the blood dilution ratio, while according to RBC-M, the estimated blood loss was close to the actual blood volume only when the dilution ratio was greater than 300 times. In clinical research, the blood loss estimated by HCT-M was higher than that by EMP-M in both groups (P < 0.05). There was a significant difference between group A and group B in blood loss (7.40 ± 1.61 vs 19.91 ± 10.94 ml), operation time (80.51 ± 34.70 vs 136.51 ± 41.88 min), and fluoroscopy frequency (6.92 ± 1.52 vs 11.11 ± 2.32 times) (P < 0.05). The VAS and ODI scores in group B were higher than that in group A 1 week after operation (P < 0.05); however, the scores were not different between the two groups at pre-operation (P > 0.05). CONCLUSION: HCT-M is a reliable method to estimate endoscopic blood loss in PELD. The amount of endoscopic blood loss affects the operative procedure in operation time and fluoroscopy frequency, as well as clinical effects in VAS and ODI scores after operation in short term.

Sub-anesthesia Dose of Isoflurane in 60% Oxygen Reduces Inflammatory Responses in Experimental Sepsis Models.

BACKGROUND: Sepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial in sepsis; however, their application in septic patients is limited because long-term hyperoxia may induce oxygen toxicity and anesthetic dose isoflurane has potential adverse consequences. This study was scheduled to find the optimal combination of isoflurane and oxygen in protecting experimental sepsis and its mechanisms. METHODS: The effects of combined therapy with isoflurane and oxygen on lung injury and sepsis were determined in animal models of sepsis induced by cecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysaccharide (LPS) or zymosan. Mouse RAW264.7 cells or human peripheral blood mononuclear cells (PBMCs) were treated by LPS to probe mechanisms. The nuclear factor kappa B (NF-κB) signaling molecules were examined by Western blot and cellular immunohistochemistry. RESULTS: The 0.5 minimum alveolar concentration (MAC) isoflurane in 60% oxygen was the best combination of oxygen and isoflurane for reducing mortality in experimental sepsis induced by CLP, intraperitoneal injection of LPS, or zymosan. The 0.5 MAC isoflurane in 60% oxygen inhibited proinflammatory cytokines in peritoneal lavage fluids (tumor necrosis factor-alpha [TNF-ß]: 149.3 vs. 229.7 pg/ml, interleukin [IL]-1ß: 12.5 vs. 20.6 pg/ml, IL-6: 86.1 vs. 116.1 pg/ml, and high-mobility group protein 1 [HMGB1]: 323.7 vs. 449.3 ng/ml; all P< 0.05) and serum (TNF-ß: 302.7 vs. 450.7 pg/ml, IL-1ß: 51.7 vs. 96.7 pg/ml, IL-6: 390.4 vs. 722.5 pg/ml, and HMGB1: 592.2 vs. 985.4 ng/ml; all P< 0.05) in septic animals. In vitro experiments showed that the 0.5 MAC isoflurane in 60% oxygen reduced inflammatory responses in mouse RAW264.7 cells, after LPS stimulation (all P< 0.05). Suppressed activation of NF-κB pathway was also observed in mouse RAW264.7 macrophages and human PBMCs after LPS stimulation or plasma from septic patients. The 0.5 MAC isoflurane in 60% oxygen also prevented the increases of phospho-IKKß/ß, phospho-IκBß, and phospho-p65 expressions in RAW264.7 macrophages after LPS stimulation (all P< 0.05). CONCLUSION: Combined administration of a sedative dose of isoflurane with 60% oxygen improves survival of septic animals through reducing inflammatory responses.

Structures and anti-cancer properties of two binuclear copper complexes.

The crystals of two binuclear copper-based complexes were obtained. One complex can remarkably induce apoptosis and inhibit angiogenesis to mediate tumour growth at a greater extent. Furthermore, this complex showed a strong energy-dependent and non-endocytotic uptake and exhibited multiple anti-cancer functions by inhibiting the expressions of p-Akt and p-Erk1/2 proteins and by decreasing the levels of reactive oxygen species.

Imidazo [4,5f][1,10] phenanthroline derivatives as inhibitor of c-myc gene expression in A549 cells via NF-κB pathway.

1,10-Phenanthroline has been shown to exhibit anticancer activity. Here, a series of imidazo [4,5f][1,10] phenanthroline derivatives 1-10 were synthesized and their biological activities were further elucidated. We found that 2-(4-Brominephenyl)-imidazo [4,5f][1,10] phenanthroline (compound 3) possessed potent antiproliferation activities again a variety of tumor cell lines using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometric analysis revealed that compound 3 induced both through apoptosis and necrosis in human lung adenocarcinoma cell line, A549. Moreover, compound 3 treatment led to up-regulation of IκBα and down-regulation of p65 and c-myc in A549 cells. Taken together, these results suggested that compound 3 inhibited cell proliferation by suppression of NF-κB activity and down-regulation of c-myc gene expression and may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially for lung cancer.

[Prevention of anterior glottic stenosis after CO2 laser cordectomy with chitosan].

OBJECTIVE: To observe the effect of immediate topical application of chitosan on preventing anterior glottic stenosis (AGS) after microsurgical resection of both vocal fold with CO2 laser, including the anterior commissure, in a canine model. METHODS: Sixteen canine larynges were injured by microresecting procedure of both vocal folds with CO2 laser. The dogs were randomly divided into two groups, chitosan group and control group. The chitosan and isotonic sodium chloride solution (control) were used for 5 minutes immediately after surgery. One week after the initial surgery, three dogs in each group were randomly selected , ultrastructure of fibroblast were examined with transmission electronic microscope and expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) were evaluated by enzyme-linked immunosorbent assay (ELISA). Three weeks after surgery, the rest dogs' glottic web were lysed and repeatedly treated with chitosan and isotonic sodium chloride solution respectively. The glottic wound healing and AGS formation were examined every week, and all larynges were harvested and examined histologically six weeks after the initial surgery. RESULTS: Transmission electronic microscope examination of the ultrastructure of fibroblast indicated that chitosan inhibited the proliferation of fibroblast. Chitosan increased the expression of bFGF and TGF-beta1, and bFGF and TGF-beta1 in chitosan group, which was significantly higher than that in control group (z=-2.887 and -2.005, P=0.002 and 0.041). Chitosan decreased the extent of AGS formation. Three weeks after the surgery, the AGS lesion in the control group affected mean 49% of the length of the vocal folds from the anterior commissure to the vocal process, while chitosan group affected mean 7%, which was significantly less than the extent of web formation in the control group, (z=-2.619, P=0.008). The grade of collagen content in chitosan group was significantly lower than that in control group (P=0.003). CONCLUSION: Chitosan is effective in preventing AGS after CO2 laser cordectomy.

Tanshinone IIA: a new activator of human cardiac KCNQ1/KCNE1 (I(Ks)) potassium channels.

Tanshinone IIA, one of the main active components from Chinese herb Danshen, is widely used to treat cardiovascular diseases including arrhythmia in Asian countries especially in China. However, the mechanisms underlying its anti-arrythmia effects are not clear. In this study we investigate the effects of tanshinone IIA on human KCNQ1/KCNE1 potassium channels (I(Ks)), human ether-a-go-go-related gene potassium channels (hERG), Kv1.5 potassium channels, inward rectifier potassium channels (I(K1)) expressed in HEK 293 cells using patch clamp technique. Tanshinone IIA potently and reversibly enhanced the amplitude of I(Ks) in a concentration dependent manner with an EC(50) of 64.5 microM, accelerated the activation rate of I(Ks) channels, decelerated their deactivation and shifted the voltage dependence of I(Ks) activation to negative direction. Isoproteronol, a stimulator of beta-adrenergic receptor, at 1 microM and sodium nitroprusside (SNP), a NO donor, at 1 mM, had no significant effects on the enhancement of I(Ks) by 30 microM tanshinone IIA. N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a selective protein kinase A inhibitor, at 0.1 microM and 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), a selective nitric oxide-sensitive guanylyl cyclase inhibitor, at 10 microM, also had no significant effects on the enhancement of I(Ks) by 30 microM tanshinone IIA. Tanshinone IIA did not affect expressed hERG channels, Kv1.5 channels and I(K1) channels. These results indicate that tanshinone IIA directly and specifically activate human cardiac KCNQ1/KCNE1 potassium channels (I(Ks)) in HEK 293 cell through affecting the channels' kinetics.

New sphingolipids from the root of Isatis indigotica and their cytotoxic activity.

Two new sphingolipids were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as (2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(1) and 1-O-beta-D-glucopyranosyl-(2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.