Traditional Chinese Medicine JingYinGuBiao Formula Therapy Improves the Negative Conversion Rate of SARS-CoV2 in Patients with Mild COVID-19.

Background: Traditional Chinese Medicine (TCM) JingYinGuBiao formula (JYGB) was recommended by the Expert consensus on Traditional Chinese Medicine diagnosis and treatment of COVID-19 infection in Shanghai. We evaluated the safety and efficacy of JYGB in treating mild COVID-19 patients. Methods: A prospective, double-blind, randomized, controlled trial was conducted (ClinicalTrial.gov registration number: ChiCTR2200058695). A total of 885 patients were randomized into the treatment group (administration of JYGB,n=508) or the control group (administration of TCM placebo, n=377) with 7-day treatment. The primary outcomes were the negative conversion rate and negative conversion time of SARS-CoV2 RNA. Secondary outcomes included the hospitalized days and symptom improvement. Results: A total of 490 and 368 patients in the treatment and control groups completed the study. The cumulative negative conversion rates at 2 days, 3 days, 4 days, and 6 days post randomization in the treatment group were all markedly higher than those in the control group (13.88% vs. 9.24%, P=0.04; 32.24% vs. 16.58%, P<0.001; 51.43% vs. 36.14%, P <0.001; 77.76% vs. 69.84%, P=0.008). Compared with the control group, after JYGB treatment, the median negative conversion time (4.0 [3.0-6.0] vs. 5.0 [4.0-7.0] days, P<0.001) and hospitalized days (6.0 [4.0-8.0] vs. 7.0 [5.0-9.0] days, P<0.001) were reduced. While the symptoms were improved, there were no significant differences in symptom disappearance rates between both groups. In addition, further sub-group analysis showed that for patients with interval time ≤4 days or patients≤ 60 years, the clinical effects of JYGB were more remarkable with an increase in cumulative negative conversion rates, a decrease in negative conversion time and hospitalized days. JYGB was well tolerated without any severe side effects. Conclusion: JYGB, a TCM prescription, improves the negative conversion rate of SARS-CoV2 in mild COVID-19 patients.

Effect of Xiaoyutang Combined with Intraperitoneal Heat Perfusion Chemotherapy on Immune Function, Circulating mir, Prognosis, and Survival of Postoperative Patients with Colorectal Cancer.

OBJECTIVE: To explore the effects of Xiaoyutang combined with intraperitoneal heat perfusion chemotherapy on immune function, circulating Mir, and prognosis and survival of postoperative patients with colorectal cancer. METHODS: A total of 96 patients with colorectal cancer who were treated in our hospital from May 2018 to August 2019 and followed up to August 2021 were selected as the study subjects. The patients were randomly divided into a control group and study group by a 1 : 1 random number table method, 48 cases in each group. Patients in the control group were given intraperitoneal thermal perfusion chemotherapy after surgery, and patients in the research group were treated with Xiaoyutang on this basis. The treatment cycle was 21 days, and all patients were treated for 3 consecutive cycles. The therapeutic efficacy, immune function (CD3+, CD4+, and CD4+/CD8+), circulating mir (mir-29a, mir-145, and mir-92a), prognosis, and survival of the two groups were compared. RESULTS: After 3 cycles of treatment, ORR and DCR in the study group were higher than those in the control group (60.42% vs. 37.50%) and 85.42% vs. 66.67%, respectively, with statistical significance (P < 0.05). There were statistically significant differences in CD3+, CD4+, CD4+/CD8+, mir-29a, mir-145, and mir-92a time points and intergroup and intergroup interactions between the two groups (P < 0.05); the levels of CD3+, CD4+, and CD4+/CD8+ in the study group were higher than those in the control group after 1, 2, and 3 cycles of treatment (P < 0.05); the expressions of mir-29a, mir-145, and mir-92a were significantly lower than those in the control group (P < 0.05). By the end of follow-up, 3 cases were lost to follow-up in the study group and 5 cases in the control group. The recurrence rate and mortality of the study group were lower than those of the control group at 1- and 2-year follow-up (P > 0.05), and the mean survival time of patients in the study group was higher than that in the control group; the differences were statistically significant (χ 2 = 5.151, P = 0.023). CONCLUSION: Xiaoyutang combined with peritoneal heat perfusion chemotherapy has a good postoperative effect on patients with colorectal cancer, which can effectively improve the immune function and circulating Mir of patients with colorectal cancer, reduce tumor recurrence, and improve the prognosis of patients.

Structural dependence of antidiabetic effect of steviol glycosides and their metabolites on streptozotocin-induced diabetic mice.

BACKGROUND: Stevia has been proposed as a potential antidiabetic sweetener, mainly based on inconsistent results from stevioside or the plant extract, yet lacking relative experimental evidence from individual steviol glycosides (SGs) and their metabolites. RESULTS: The results systematically revealed that the typical SGs and their final metabolite (steviol) presented an antidiabetic effect on streptozotocin (STZ) diabetic mice in all assayed antidiabetic aspects. In general, the performance strength of the samples followed the sequence steviol > steviol glucosyl ester > steviolbioside > rubusoside > stevioside > rebaudioside A, which is opposite to their sweetness strength order, and generally in accordance with the glucosyl group numbers in their molecules. This may imply that the antidiabetic effect of the SGs might be achieved through steviol, which presented antidiabetic performance similar to that of metformin with a dose of 1/20 that of metformin. Moreover, the 18 F-fluorodeoxyglucose traced micro-PET experiment revealed that stevioside and steviol could increase the uptake of glucose in the myocardium and brain of the diabetic mice within 60 min, and decrease the accumulation of glucose in the liver and kidney. CONCLUSIONS: The SGs and steviol presented an antidiabetic effect on STZ diabetic mice in all assayed aspects, with an induction time to start the effect of the SGs. Stevioside and steviol could increase uptake of glucose in the myocardium and brain of the diabetic mice, and decrease accumulation of glucose in the liver and kidney. The performance strength of the SGs is generally in accordance with glucosyl group numbers in their molecules.

Perioperative safety after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal origin: Experience on 254 patients from a single center.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a standard treatment for pseudomyxoma peritonei (PMP) recommended by Peritoneal Surface Oncology Group International (PSOGI). The study is to analyze the incidence of perioperative serious adverse events (SAEs) of CRS + HIPEC to treat PMP patients, and identify the risk factors, for guiding the prevention of SAEs. METHODS: This is a retrospective study on the PMP database established at our center. The clinicopathological features, treatment details and SAEs information on the PMP patients are systematically established in this database. The incidence, organ system distribution and severity of perioperative SAEs are analyzed. Univariate and multivariate analyses are performed to identify the independent risk factors. RESULTS: Among the 272 CRS + HIPEC procedures for 254 PMP patients, there are 93 (34.2%) SAEs. Six systems are involved in the SAEs, including infections (9.6%), digestive system (8.1%), respiratory system (6.3%), cardiovascular system (5.5%), hematological system (2.9%), and urinary system (1.5%), in terms of frequency. In terms of severity, the majority is grade III SAEs (27.9%), followed by grade IV SAEs (4.8%) and grade V SAEs (1.5%). Univariate analysis reveals 4 risk factors for perioperative SAEs: HIPEC regimens (P = 0.020), PCI (P = 0.025), intraoperative red blood cell transfusion volume (P = 0.004), and intraoperative blood loss volume (P = 0.002). Multivariate and logistic regression model analysis identifies only one independent risk factor for perioperative SAEs: intraoperative blood loss volume (P = 0.001, OR = 0.344, 95%CI: 0.182-0.649). CONCLUSIONS: PMP patients treated by CRS + HIPEC at experienced centers could have acceptable safety. Improving the surgical techniques and developing the integrated hemostasis techniques are essential to reduce intraoperative blood loss and decrease SAEs rate.

An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer.

Gefitinib is one of commonly used first-line treatment options for patients with positive EGFR mutation in non-small cell lung cancer (NSCLC). However, most patients with gefitinib treatment relapse over time due to the loss of drug sensitivity. Compound Kushen injection (CKI) has been used to treat lung cancer, including EGFR-mutated NSCLC. In this report, we examined the anti-cancer and drug sensitivity increased activities of CKI in gefitinib less sensitive NSCLC cell lines H1650 and H1975. Bioinformatics analysis was applied to uncover gene regulation and molecular mechanisms of CKI. Our results indicated that when associating with gefitinib in a dose-dependent fashion, CKI demonstrated the ability to inhibit the proliferation and to increase the sensitivity to gefitinib treatment in gefitinib less sensitive cell lines. This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect.

Pilot in vitro and in vivo study on a mouse model to evaluate the safety of transcutaneous low-frequency electrical nerve stimulation on cervical cancer patients.

INTRODUCTION AND HYPOTHESIS: To clarify whether the pulse electrical field (PEF) caused by transcutaneous low-frequency nerve electrical stimulation (TENS) enhances the proliferation of cervical cancer cells, leading to recurrence and metastasis, and the effect of such a PEF on a cervical cancer mouse model. METHODS: 1. In vitro experiment: SiHa cervical cancer cells treated with one session of microsecond PEFs for 30 min were divided into four groups: three experimental groups and the control group. Cell proliferation and migration were determined by CCK-8 proliferation and Transwell chamber Matrigel migration assay. 2. In vivo experiment: A mouse cancer model was established by subcutaneous implantation of SiHa cells that were then were randomly divided into the TENS group and control group. The former group received one session of TENS treatment and the control group received a sham pulse. The growth trend and tumor volume of each group were compared 28 days after PEF treatment. The proliferation and apoptosis of the tumor were determined by an immunohistochemical method. RESULTS: (1) The CCK-8 proliferation assay and cell migration ability showed no difference after PEF stimulation treatment (F = 2.478, P = 0.136 > 0.05 and F = 0.364, P = 0.779). (2) Tumor growth, size and weight showed no significant difference between the two groups. (3) Expression of VEGF, CD34, caspase-3 and Ki-67 in the tumor tissue showed no significant difference between the two groups. CONCLUSIONS: In vitro and in vivo experiments (mice) showed that the PEF created by TENS had no effect on the proliferation and migration of SiHa cervical cancer cells and also had no effect on the tumor growth, tumor cell apoptosis and proliferation.

A novel drug-free strategy of nano-pulse stimulation sequence (NPSS) in oral cancer therapy: In vitro and in vivo study.

Nano-pulse stimulation (NPS) is a novel technology to induce cancer apoptosis. In this study, based on the energy-dose effect of NPS, we designed a special NPS sequence (NPSS) with low field intensity. The effectiveness and mechanisms of NPSS on oral cancer therapy were evaluated by cell proliferation assays, microscopic investigation, JC-1 mitochondrial membrane potential assay, tumor inhibition assays, immunohistochemistry (IHC) assay, Ca2+, NOS and ROS detection assays, respectively. The results demonstrated that NPSS treatment significantly inhibited oral cancer growth in vitro and in vivo. Furthermore, we found that NPSS treatment induced an obviously apoptosis and mitochondrial membrane potential (ΔΨm) reduction in Cal-27 cells. Notably, further experiments revealed that the mechanisms of crosstalk signaling between NO, ROS and Ca2+ involvement in NPSS treatment. In conclusion, this is a proof-of-concept study that provides a potential alternative strategy for developing and applying NPSS in oral cancer therapy.

Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma.

The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the pro-apoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma.

Radiosensitization of oral tongue squamous cell carcinoma by nanosecond pulsed electric fields (nsPEFs).

Nanosecond pulsed electric fields (nsPEFs) are a non-thermal and non-toxic technology that induce a myriad of biological effects. They have been proven to be effective in tumor shrinkage, but few studies focus on its radiosensitization in oral tongue squamous cell carcinoma. The purpose of this research was to study the radiosensitization effect of nsPEFs on a human oral tongue cancer cell line Tca8113 and to investigate the potential antitumor mechanism. A Tca8113 cell line was tested respectively by MTT assay, clonogenic assay, flow cytometry assay, annexin V-FITC/PI assay, mitochondrial potential assay and total nitric oxide assay. Our results showed that nsPEFs had a time and field strength dependent inhibition effect on Tca8113 cells. The sensitization enhancement ratio (SER) of nsPEFs was 1.453±0.038. Furthermore, radiation induced G2/M arrest was augmented by treatment with nsPEFs. We observed many more Tca8113 cells showing early apoptosis after nsPEFs combined with radiotherapy. Additionally, the NO concentration was significantly increased after nsPEFs treatment. These findings indicate that combination of nsPEFs with radiotherapy can enhance the radiosensitivity of Tca8113 cells and nsPEFs could be a potential radiosensitizer for oral tongue squamous cell carcinoma.

Rational Evolution of Antimicrobial Peptides Containing Unnatural Amino Acids to Combat Burn Wound Infections.

Antimicrobial peptides have long been raised as a promising strategy to combat bacterial infection in burn wounds. Here, we attempted to rationally design small antimicrobial peptides containing unnatural amino acids by integrating in silico analysis and in vitro assay. Predictive quantitative sequence-activity models were established and validated rigorously based on a large panel of nonamer antimicrobial peptides with known antibacterial activity. The best quantitative sequence-activity model predictor was employed to guide genetic evolution of a peptide population. In the evolution procedure, a number of unnatural amino acids with desired physicochemical properties were introduced, resulting in a genetic evolution-improved population, from which seven peptide candidates with top scores, containing 1-3 unnatural amino acids, and having diverse structures were successfully identified, and their antibacterial potencies against two antibiotic-resistant bacterial strains isolated from infected burn wounds were measured using in vitro susceptibility test. Consequently, four (WL-Orn-LARKIV-NH2 , ARKRWF-Dab-FL-NH2 , KFI-Hag-IWR-Orn-R-NH2 and YW-Hag-R-Cit-RF-Orn-N-NH2 ) of the seven tested peptides were found to be more potent than reference Bac2A, the smallest naturally occurring broad spectrum antimicrobial peptide. Molecular dynamics simulations revealed that the designed peptides can fold into amphipathic helical structure that allows them to interact directly with microbial membranes.

Inhibitor or promoter? The performance of polysaccharides from Ganoderma lucidum on human tumor cells with different p53 statuses.

Polysaccharides from Ganoderma lucidum (GLPs) have been taken as effective supplements by both healthy people and cancer patients for many years. However, this short survey indicates that instead of inhibiting cancer cell growth, both submerge-cultured intracellular GLP and fruiting body GLP can stimulate the growth of human carcinoma cell lines lacking functional p53, such as HCT-116 p53(-/-), Saos-2, H1299, HL-60, MDA-MB-157. Conversely, the two GLPs inhibit all other assayed cells with functional p53. These results could be an alert since mutational inactivation of the tumor suppressor protein p53 is the most frequent genetic alteration found in human tumors.

Rhizoma Paridis Saponins Induces Cell Cycle Arrest and Apoptosis in Non-Small Cell Lung Carcinoma A549 Cells.

BACKGROUND: As a traditional Chinese medicine herb, Chonglou (Paris polyphylla var. chensiins) has been used as anticancer medicine in China in recent decades, as it can induce cell cycle arrest and apoptosis in numerous cancer cells. The saponins extract from the rhizoma of Chonglou [Rhizoma Paridis saponins (RPS)] is known as the main active component for anticancer treatment. However, the molecular mechanism of the anticancer effect of RPS is unknown. MATERIAL AND METHODS: The present study evaluated the effect of RPS in non-small-cell lung cancer (NSCLC) A549 cells using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Subsequently, the expression of several genes associated with cell cycle and apoptosis were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: RPS was revealed to inhibit cell growth, causing a number of cells to accumulate in the G 1 phase of the cell cycle, leading to apoptosis. In addition, the effect was dose-dependent. Moreover, the results of qRT-PCR and Western blotting showed that p53 and cyclin-dependent kinase 2 (CDK2) were significantly downregulated, and that BCL2, BAX, and p21 were upregulated, by RPS treatment. CONCLUSIONS: We speculated that the RPS could act on a pathway, including p53, p21, BCL2, BAX, and CDK2, and results in G1 cell cycle arrest and apoptosis in NSCLC cells.

[Electroacupuncture intervention combined with general anesthesia for craniocerebral operations].

OBJECTIVE: To determine the safety and effectiveness of electroacupuncture (EA) intervention combined with general anesthesia (GA) for craniocerebral tumor-removal surgery involving cerebral eloquent areas. METHODS: A total of 20 patients with cerebral tumors (durosarcoma, neurogliocytoma, metastatic tumor) involving the cerebral eloquent areas were recruited in the present summary. They were equally divided into general anesthesia (GA) group and EA + GA group. Patients of the EA + GA group were treated with EA stimulation (2 Hz/100 Hz) of the bilateral Fengchi (GB 20), Shuaigu (GB 8) and acupuncture stimulation of Quanliao (SI 18), Zulinqi (GB 41) and Taichong (LR 3), and not given intubation during surgery. Patients of the GA group were treated with intravenous administration of Propofol, Fentanyl, Midazolam, Isopropanol, etc. In addition, all the patients were given with controlled hypotension by intravenous injection of Propofol and Fentanyl. Dosages of Propofol and Sulfentanyl used were recorded. Karnofsky performance status scale was used to assess the patient's general well-being and activities of daily life. RESULTS: The craniocerebral tumor-removal surgery was successful in all the 20 patients. Compared with the GA group, the dosages of Sulfentanyl and Propofol of the EA+ GA group were significantly lower (P < 0.05). No significant difference was found between the GA and EA+ GA groups in Karnofsky performance scores (P > 0.05). Patients of the EA+GA group experienced successful tumour-removal surgery without trachea cannula, were awake and could make a good cooperation with the operator during surgery. They had no aggravation of neurofunctional disturbance following the operation. CONCLUSION: EA combined with general anesthesia is safe and effective for patients with craniocerebral tumor-removal operations involving cerebral eloquent areas.

Flavonoids identified from Korean Scutellaria baicalensis induce apoptosis by ROS generation and caspase activation on human fibrosarcoma cells.

The effects of flavonoids from Korean Scutellaria baicalensis on fibrosarcoma HT1080 cells and their underlying molecular mechanism were investigated in this study. Flavonoids affected HT1080 cell proliferation by interrupting cell cycle progress, obviously augmenting the proportion of sub-G1 and diminishing that of G1 phase, and undergoing apoptosis at the tested dosage (100-400 µg/mL). In addition, the mediated apoptosis was mainly caused by total reactive oxygen species (ROS) generation and by up-regulating the ratio of Bax/Bcl-xL, triggering caspase cascades (caspase-3, -9 and -8), and inactivating PARP, dose-dependently. The proteomics results showed that AP-4, ARID 5B, HNRNP K, PLOG, Prdx6, and myosin-1, associated with cell growth, differentiation and development, and overexpressed in gastric cancer, colorectal cancer, pancreatic cancer, etc., were statistically down-regulated after the flavonoids treatment. Taken together, our data demonstrated that flavonoids from Korean S. baicalensis induced apoptosis in HT1080 cells, which involved a hierarchy of cellular pathways and multiple signal proteins, and might be a potential anticancer therapeutic agent.

Effect of iodinated contrast media on renal function evaluated with dynamic three-dimensional MR renography.

PURPOSE: To assess the hemodynamic effect of iodinated contrast media (CM) on glomerular filtration rate (GFR) by using dynamic three-dimensional magnetic resonance (MR) renography in a rabbit model. MATERIALS AND METHODS: This study was approved by the university animal care and use committee. Twelve healthy male New Zealand rabbits (body mass range, 2.5-3.0 kg) were included. Two of them were sacrificed before MR examination to obtain renal histologic samples as controls. The other ten rabbits completed 4-minute dynamic contrast material-enhanced MR imaging 24 hours before and 20 minutes after intravenous injection of iopamidol (370 mg of iodine per milliliter) at a dose of 6 mL per kilogram of body weight. Blood volume (V(B)), GFR, and tubule volume (V(E)) of the renal cortex were determined with a two-compartment kinetic model. Maximum upslope (K(m)), peak concentration (P(c)), and initial 60-second area under the curve (IAUC) of the whole kidney renogram curve were measured with semiquantitative analysis. The self-control data were compared by using the Student paired t test. RESULTS: Iopamidol significantly decreased cortical V(B) (mean, 42.53% ± 10.16 [standard deviation] before CM administration vs 27.23% ± 16.13 after CM administration; P < .01), V(E) (mean, 22.40% ± 11.69 before CM administration vs 11.51% ± 6.58 after CM administration; P < .01), and GFR (mean, 31.92 mL/100 g per minute ± 12.52 before CM administration vs 21.48 mL/100 g per minute ± 10.02 after CM administration; P < .01). Results of whole-kidney renogram analysis showed a decrease in K(m), P(c), and IAUC caused by iopamidol administration. CONCLUSION: High-dose iopamidol resulted in a marked decrease in renal function, which could be detected at dynamic three-dimensional MR renography.

Targeting therapy of hepatocellular carcinoma with doxorubicin prodrug PDOX increases anti-metastatic effect and reduces toxicity: a preclinical study.

BACKGROUND: This study was to investigate the effects and safety of cathepsin B-cleavable doxorubicin (DOX)-prodrug (PDOX) for targeting therapy of metastatic human hepatocellular carcinoma (HCC) using DOX as a positive control drug. METHODS: The orthotopic nude mice model of highly metastatic HCC was established and the animals were randomized and treated with PDOX, DOX and saline, respectively. Hematology, biochemistry and tumor markers were studied. At autopsy, liver tumor weight and size, ascites, abdominal lymph nodes metastases, experimental peritoneal carcinomatosis index (ePCI), and tumor-host body weight ratio were investigated. Immunohistochemical studies and western blotting were done to investigate key molecules involved in the mechanism of action. RESULTS: Compared with Control, both PDOX and DOX could similarly and significantly reduce liver tumor weight and tumor volume by over 40%, ePCI values, retroperitoneal lymph node metastases and lung metastases and serum AFP levels (P < 0.05). The PDOX group had significantly higher WBC than the DOX group (P < 0.05), and higher PLT than Control (P < 0.05). Serum BUN and Cr levels were lower in the PDOX group than DOX and Control groups (P < 0.05). Compared with Control, DOX increased CK and CK-MB; while PDOX decreased CK compared with DOX (P < 0.05). Multiple spotty degenerative changes of the myocardium were observed in DOX-treated mice, but not in the Control and PDOX groups. PDOX could significantly reduce the Ki-67 positive rate of tumor cells, compared with DOX and Control groups. PDOX produced the effects at least via the ERK pathway. CONCLUSION: Compared with DOX, PDOX may have better anti-metastatic efficacy and reduced side effects especially cardio-toxicities in this HCC model.

Proteome analysis of the anti-inflammatory response of flavonoids isolated from Korean Citrus aurantium L. in lipopolysaccharide-induced L6 rat skeletal muscle cells.

Skeletal muscle is an important organ in our body and a dynamic composite of proteins. Citrus aurantium L. has been widely used in oriental medicine in Eastern Asia for a long time. It contains over 100 bioactive compounds and flavonoids that regulate the inflammatory response and tumorigenesis, through various mechanisms. In the present study, we investigated changes in the protein pattern using two-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF/MS) to assess the anti-inflammatory effect of flavonoids isolated from Korean C. aurantium L. in lipopolysaccharide (LPS)-induced L6 cells. L6 skeletal muscle cells were pretreated with flavonoids for 1 h and stimulated with LPS for 24 h. Proteins from the L6 cells of the control, LPS treated and flavonoid treated groups were extracted and resolved by 2-DE using pH 4-7 IPG strips loaded with 150 µg of protein. Forty-one differentially expressed protein spots were identified (more than two-fold was considered significant, p < 0.05), and 18 were detected by MALDI-TOF/MS. These results suggest that proteomics can be used to identify changes in the expression of marker proteins and the anti-inflammatory effect of flavonoids isolated from Korean C. aurantium L.

Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks.

Acupuncture, which is recognized as an alternative and complementary treatment in Western medicine, has long shown efficiencies in chronic pain relief, drug addiction treatment, stroke rehabilitation and other clinical practices. The neural mechanism underlying acupuncture, however, is still unclear. Many studies have focused on the sustained effects of acupuncture on healthy subjects, yet there are very few on the topological organization of functional networks in the whole brain in response to long-duration acupuncture (longer than 20 min). This paper presents a novel study on the effects of long-duration transcutaneous electric acupoint stimulation (TEAS) on the small-world properties of brain functional networks. Functional magnetic resonance imaging was used to construct brain functional networks of 18 healthy subjects (9 males and 9 females) during the resting state. All subjects received both TEAS and minimal TEAS (MTEAS) and were scanned before and after each stimulation. An altered functional network was found with lower local efficiency and no significant change in global efficiency for healthy subjects after TEAS, while no significant difference was observed after MTEAS. The experiments also showed that the nodal efficiencies in several paralimbic/limbic regions were altered by TEAS, and those in middle frontal gyrus and other regions by MTEAS. To remove the psychological effects and the baseline, we compared the difference between diffTEAS (difference between after and before TEAS) and diffMTEAS (difference between after and before MTEAS). The results showed that the local efficiency was decreased and that the nodal efficiencies in frontal gyrus, orbitofrontal cortex, anterior cingulate gyrus and hippocampus gyrus were changed. Based on those observations, we conclude that long-duration TEAS may modulate the short-range connections of brain functional networks and also the limbic system.

Cold plasma therapy of a tooth root canal infected with enterococcus faecalis biofilms in vitro.

INTRODUCTION: Complete sterilization of an infected root canal is an important challenge in endodontic treatment. Traditional methods often cannot achieve high-efficiency sterilization because of the complexity of the root canal system. The objective of the study was to investigate in vitro the feasibility of using a cold plasma treatment of a root canal infected with Enterococcus faecalis biofilms. METHODS: Seventy single-root teeth infected with E. faecalis biofilms were divided into 7 groups. Group 1 served as the negative control group (no treatment), and group 7 was the positive control group with teeth treated with calcium hydroxide intracanal medication for 7 days. Groups 2 to 6 included teeth treated by cold plasma for 2, 4, 6, 8, and 10 minutes, respectively. The disinfection of the E. faecalis biofilm was evaluated by colony-forming unit (CFU) counting. Scanning electron microscopy was used to evaluate the structural changes of the E. faecalis biofilm before and after plasma treatment. Confocal scanning laser microscopy was used to investigate the vitality of the microorganisms in the biofilm before and after plasma treatment. RESULTS: A significant decrease in the number of CFUs was observed after prolonged cold plasma treatment (based on the statistical analysis of the teeth in groups 2-6). Compared with the positive control group, cold plasma treatment of 8 or 10 minutes (groups 5 and 6) had a significantly higher antimicrobial efficacy (P < .05). The scanning electron microscopic analysis showed that the bacteria membrane was ruptured, and the structure of the biofilm was fully destroyed by the plasma. Confocal scanning laser microscopic studies indicated that the plasma treatment induced E. faecalis death and destruction of the biofilm. CONCLUSIONS: The cold plasma had a high efficiency in disinfecting the E. faecalis biofilms in in vitro dental root canal treatment.

Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: a perfusion fMRI study.

This article investigates the effects of postherpetic neuralgia (PHN) on resting-state brain activity utilizing arterial spin labeling (ASL) techniques. Features of static and dynamic cerebral blood flow (CBF) were analyzed to reflect the specific brain response to PHN pain. Eleven consecutive patients suffering from PHN and 11 age- and gender-matched control subjects underwent perfusion functional magnetic resonance imaging brain scanning during the resting state. Group comparison was conducted to detect the regions with significant changes of CBF in PHN patients. Then we chose those regions that were highly correlated with the self-reported pain intensity as "seeds" to calculate the functional connectivity of both groups. Absolute CBF values of these regions were also compared across PHN patients and control subjects. Significant increases in CBF of the patient group were observed in left striatum, right thalamus, left primary somatosensory cortex (S1), left insula, left amygdala, left primary somatomotor cortex, and left inferior parietal lobule. Significant decreases in CBF were mainly located in the frontal cortex. Regional CBF in the left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and further comparison showed that the regional CBF in these regions is significantly higher in PHN groups. Functional connectivity results demonstrated that the reward circuitry involved in striatum, prefrontal cortex, amygdala, and parahippocampal gyrus and the circuitry among striatum, thalamus, and insula were highly correlated with each element in PHN patients. In addition, noninvasive brain perfusion imaging at rest may provide novel insights into the central mechanisms underlying PHN pain.