Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p-PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn.

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

Near-infrared AIE-active phosphorescent iridium(III) complex for mitochondria-targeted photodynamic therapy.

Mitochondria-targeted photodynamic therapy (PDT) has recently been recognized as a promising strategy for effective cancer treatment. In this work, a mitochondria-targeted near-infrared (NIR) aggregation-induced emission (AIE)-active phosphorescent Ir(III) complex (Ir1) is reported with highly favourable mitochondria-targeted bioimaging and cancer PDT properties. Complex Ir1 has strong absorption in the visible light region (∼500 nm) and can effectively produce singlet oxygen (1O2) under green light (525 nm) irradiation. It preferentially accumulates in the mitochondria of human breast cancer MDA-MB-231 cells as revealed by colocalization analysis. Complex Ir1 displays high phototoxicity toward human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. Complex Ir1 induces reactive oxygen species (ROS) production, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in MDA-MB-231 cells upon photoirradiation, leading to apoptotic cell death. The favorable PDT performance of Ir1in vivo has been further demonstrated in tumour-bearing mice. Together, the results suggest that Ir1 is a promising photosensitizer for mitochondria-targeted imaging and cancer phototherapy.

Synergy between Clinical Microenvironment Targeted Nanoplatform and Near-Infrared Light Irradiation for Managing Pseudomonas aeruginosa Infections.

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.

Antifungal Activities of cis-trans Citral Isomers against Trichophyton rubrum with ERG6 as a Potential Target.

Trichophyton rubrum causes ringworm worldwide. Citral (CIT), extracted from Pectis plants, is a monoterpene and naturally composed of geometric isomers neral (cis-citral) and geranial (trans-citral). CIT has promising antifungal activities and ergosterol biosynthesis inhibition effects against several pathogenic fungi. However, no study has focused on neral and geranial against T. rubrum, which hinders the clinical application of CIT. This study aimed to compare antifungal activities of neral and geranial and preliminarily elucidate their ergosterol biosynthesis inhibition mechanism against T. rubrum. Herein, the disc diffusion assays, cellular leakage measurement, flow cytometry, SEM/TEM observation, sterol quantification, and sterol pattern change analyses were employed. The results showed geranial exhibited larger inhibition zones (p < 0.01 or 0.05), higher cellular leakage rates (p < 0.01), increased conidia with damaged membranes (p < 0.01) within 24 h, more distinct shriveled mycelium in SEM, prominent cellular material leakage, membrane damage, and morphological changes in TEM. Furthermore, geranial possessed more promising ergosterol biosynthesis inhibition effects than neral, and both induced the synthesis of 7-Dehydrodesmosterol and Cholesta-5,7,22,24-tetraen-3ß-ol, which represented marker sterols when ERG6 was affected. These results suggest geranial is more potent than neral against T. rubrum, and both inhibit ergosterol biosynthesis by affecting ERG6.

Non-invasive physical therapy as salvage measure for ischemic skin flap: A literature review.

This review focuses on the available evidence regarding the molecular mechanisms and treatment potential of several non-surgical physical therapies for managing flap ischemia to propose a non-invasive, economical, and simple treatment to improve flap survival. A review of the literature was conducted on the topics of various non-invasive methods for the treatment of ischemic necrosis of the distal end of the flap between 1988 and 2019. A total of 52 published studies were reviewed on the applications of hyperbaric oxygen therapy, electrical stimulation therapy, heat stress pretreatment, phototherapy, and vibration therapy to manage skin flap necrosis. The underlying molecular mechanisms of these physical therapies on revitalizing the dying skin flaps were discussed and preliminary clinical uses of these therapies to salvage the necrotic skin flaps were pooled and summarized for clarifying the safety and feasibility of these methods. Various physical therapy regimens have been ushered to manage necrotic development in cutaneous flaps. With the refinement of these new technologies and enhancement of related basic science research on vascular revitalization, the prevention and treatment of flap ischemia will enter a new era.

Impact of Cinnamon Supplementation on cardiometabolic Biomarkers of Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND & OBJECTIVE: To date, cinnamon supplementation has been investigated due to its antioxidant and anti-inflammatory properties. Several studies have confirmed the effects of cinnamon supplementation on several markers of cardiometabolic health. However, the effects of cinnamon supplementation on inflammation and oxidative stress levels warrant further investigation. Hence, the current meta-analysis was conducted to elucidate the impact of cinnamon supplementation on biomarkers of inflammation and oxidative stress. METHODS: To perform this systematic review and meta-analysis, we employed the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic search of available clinical trials was performed using the following databases: PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, and Google Scholar, up to January 2020. RESULTS: After removing the duplicates, 1145 studies were eligible for analysis and 12 of them were included in the meta-analysis. The dose of cinnamon powder investigated in the included trials ranged from 1.5 to 4 g/day. Cinnamon supplementation resulted in a significant reduction of C-reactive protein (CRP) (weight mean difference (WMD): -2.22 mg/L, 95 % CI: -3.74, -0.69, P = 0.004) and malondialdehyde (MDA) (WMD: -0.79 mmol/L, 95 % CI: -1.28, -0.29, P = 0.002), and marginally statistical significant decrease in interleukin-6 (IL-6) (WMD: -1.48 pg/mL, 95 % CI: -2.96, -0.01, P = 0.049). Moreover, it was associated with an increase in the total antioxidant capacity (TAC) (WMD: 0.34 mmol/L, 95 % CI: 0.04, 0.64, P = 0.026). However, the levels of intercellular adhesion molecule-1 (ICAM-1) (WMD: 1.53 ng/mL, 95 % CI: -12.03, 15.10, P = 0.82) did not change significantly following cinnamon supplementation. CONCLUSIONS: Cinnamon supplementation may be an adjuvant for reducing inflammation and oxidative stress levels in humans.

Recoding the Cancer Epigenome by Intervening in Metabolism and Iron Homeostasis with Mitochondria-Targeted Rhenium(I) Complexes.

The development and malignancy of cancer cells are closely related to the changes of the epigenome. In this work, a mitochondria-targeted rhenium(I) complex (DFX-Re3), integrating the clinical iron chelating agent deferasirox (DFX), has been designed. By relocating iron to the mitochondria and changing the key metabolic species related to epigenetic modifications, DFX-Re3 can elevate the methylation levels of histone, DNA, and RNA. As a consequence, DFX-Re3 affects the events related to apoptosis, RNA polymerases, and T-cell receptor signaling pathways. Finally, it is shown that DFX-Re3 induces immunogenic apoptotic cell death and exhibits potent antitumor activity in vivo. This study provides a new approach for the design of novel epigenetic drugs that can recode the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.

Multifunctional low-temperature photothermal nanodrug with in vivo clearance, ROS-Scavenging and anti-inflammatory abilities.

Harsh photothermal temperatures, long-term body retention of nanoagents, elevated ROS and inflammation induction all threaten the normal tissues, thus hindering the translation of photothermal therapy (PTT) from bench to clinical practice. To resolve these problems, we have developed a disassembled theranostic nanodrug Qu-FeIIP based on the quercetin coordination. Herein, quercetin is not only the heat shock protein (Hsp 70) inhibitor but also the skeleton of Qu-FeIIP, realizing near-infrared light induced low-temperature PTT (45 °C) to ablate tumor completely without heat stress to normal tissues. Owing to the ROS scavenging ability of quercetin, Qu-FeIIP effectively reduces intracellular ROS and in vivo inflammatory factors (TNF-α, IL-6, IFN-γ) levels. Simultaneously, quercetin-Fe coordination is weakened when scavenging ROS, which triggers the Qu-FeIIP disassembling, resulting in effective clearance of nanoparticles from main organs 168 h post intravenous injection. Additionally, the photoacoustic and magnetic resonance dual-imaging capability of Qu-FeIIP offers excellent spatial resolution and imaging depth not only for precise tumor diagnosis but also for monitoring the nanodrug disassembling in vivo. Thus, Qu-FeIIP intrinsically integrates precise diagnosis, excellent low-temperature PTT efficacy, ROS elimination and anti-inflammatory action, dynamic disassembly and renal clearance ability into a single nanodrug, which is very promising for future clinical cancer treatment.

Calcium supplementation in CVVH using regional citrate anticoagulation.

INTRODUCTION: Calcium supplementation is one of the most important factors in maintaining the safety and efficacy of regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). The aims of this study were to assess the determinants of calcium requirements in RCA-CVVH and to simplify the calcium supplementation approach. METHODS: Our study consisted of two parts. The first part was a discovery phase to determine the key factors of calcium supplementation. Twenty critically ill patients who required RCA-CVVH were enrolled in this part. Systemic citrate, total calcium, protein-bound calcium, and ionized calcium concentrations were serially measured using the traditional RCA protocol. A two-phase calcium supplementation protocol was then proposed, and algorithms were developed for calcium supplementation. The second part of the study was the validation phase. Another 97 critically ill patients were enrolled and were treated with RCA-CVVH using the new version of the calcium supplementation protocol. FINDINGS: The loss of calcium flux in the extracorporeal circuit and the increase in citrate-calcium complexes in vivo were the main determinants of the required calcium supplementation. In the CVVH mode, the rate of calcium infusion had to be reduced after systemic citrate level reached a steady state. With the aid of mathematical models, systemic calcium levels could be stably maintained in the normal range, and the frequencies of calcium monitoring were reduced. DISCUSSION: Calcium supplementation during RCA-CVVH undergoes two phases. We propose mathematical models to quantify the need for calcium supplementation, which enable individualization of the RCA prescription and simplify the management of RCA in the CVVH mode.

Chinese herbal medicine, Jianpi Ligan decoction, improves prognosis of unresectable hepatocellular carcinoma after transarterial chemoembolization: a retrospective study.

OBJECTIVE: This study aimed to investigate the efficacy of Jianpi Ligan decoction (JLD) as an adjuvant therapy for patients with unresectable hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). METHODS: From March 2007 to March 2013, 103 patients with unresectable HCC who underwent TACE in our center were included in this retrospective study. Among the 103 patients, 53 patients accepted JLD along with TACE (JLD group) and 50 patients accepted TACE alone (control group). Indices including complication, toxicity, treatment success rate, and long-term survival were obtained for analysis and comparison. RESULTS: There was no significant difference in patient characteristics between the two groups. No procedure-related deaths or encephalopathy occurred. Fewer patients from the JLD group experienced constipation (7/53 vs 15/50, P=0.0377), abdominal bloating (5/53 vs 12/50, P=0.0466), and lack of appetite (35/53 vs 42/50, P=0.0360). The JLD group had lesser and lighter hepatic toxicity (P=0.0265) and gastrointestinal toxicity (P=0.0445) such as nausea and vomiting. The JLD group had a significantly higher treatment success rate than the control group (51/53 vs 40/50, P=0.0103). Three-year overall survival probability was significantly higher in the JLD group than in the control group (37.74% vs 26.00%; hazard ratio [HR] 0.6171; 95% confidence interval [CI], 0.3832-0.9938; P=0.0365 by log-rank test). No significant difference was found in 3-year overall survival probability (39.22% vs 32.50%; HR, 0.7449; 95% CI, 0.4398-1.2614; P=0.2491 by log-rank test) or 3-year intrahepatic recurrence-free survival probability in patients who achieved treatment success (37.25% vs 30.00%; HR, 0.7280; 95% CI, 0.4332-1.2233; P=0.2087 by log-rank test) between the two groups. CONCLUSION: Application of JLD was effective for reduction of side effects and improvement of long-term survival for patients with unresectable HCC treated by TACE.

[Effect of exogenous selenium on accumulation and chemical forms of cadmium in cucumber (Cucumis satiuus L.)].

Pot experiments were carried out to investigate the influence of different selenium (Se) levels (0, 0.5 and 1.0 mg x L(-1)) on the plant growth, concentration of malonaldehyde (MDA), activities of antioxidant enzymes, accumulation and chemical forms of cadmium (Cd) in cucumber when exposed to Cd (20 mg x kg(-1)). The results showed that dry weights of leaf, stem, root, fruit and plant, and concentrations and accumulation of Cd significantly differed between two varieties of cucumber Yanbai and Jinyou 1. With increasing levels of Se, the contents of MDA in the leaves of Yanbai increased, but the contents of MDA in the leaves of Jinyou 1 decreased. The contents of MDA in the roots of Yanbai first increased and then decreased, while the contents of MDA in Jinyou 1 first decreased and then increased. The variation trends of CAT, SOD and POD in the leaves and roots of both varieties were different with increasing levels of Se. The concentrations of different chemical forms of Cd in the fruit decreased after spraying of Se, compared with the control. Cadmium concentrations in the leaves, stem, roots and fruit of both varieties decreased by 3.2%-17.9%, 14.6%-28.2%, 5.1%-18.5% and 60.6%-75.8% in the presence of Se when exposed to Cd. Accumulation of Cd in the plant of both varieties was in order of Jinyou 1 > Yanbai in the presence or absence of Na2SeO3.

Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy. METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014). CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

Prophylactic adjuvant hepatic arterial infusion chemotherapy reduced hepatic metastases from Stage III colorectal cancer after curative resection.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of Stage III colorectal cancer patients after curative resection. METHODOLOGY: We randomly assigned 287 Stage III colorectal cancer patients after curative resection between 2002 and 2008 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (combined therapy) or 6 cycles of systemic chemotherapy alone (monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 2-hour infusion of Oxaliplatin (85mg/m2) on day 1 followed by folinic acid 200mg/m2 as a 2-hour infusion on days 2 and 3 and by 5-fluorouracil 2400mg/m2 as a 48-hour infusion on days 2 and 3. The treatment repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year disease-free survival (Combined therapy, 75.00%; Monotherapy, 63.27%; p=0.0035), overall survival (Combined therapy, 84.29%; Monotherapy, 65.31%; p=0.0006) and liver metastases-free survival (Combined therapy, 80.00%; Monotherapy, 69.39%; p=0.0451). CONCLUSIONS: HAIC effectively and safely prevents metachronous liver metastases and improves the prognosis of patients with Stage III colorectal cancer after curative resection.

Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen).

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.

[Preliminary studies on the nutrient characters of different kinds of Chinese goldthread soil].

OBJECTIVE: To study the changes of nutrient contents in Chinese goldthread soil before and after planting Coptis chinensis. METHOD: The soil in Shizhu, Chongqing, was analyzed for nutrient contents. RESULT AND CONCLUSION: The results indicated that the preplanted soil was strongly acidic and the levels of organic matter, total nitrogen and potassium were high. However, the content of total phosphorus was very low; so were the contents of other eleven nutrients. Variations of nutrients except zinc and molybdenum were large. After four years of planting C. chinensis, the soil pH was increased. Contents of organic matters, manganese, zinc and boron were increased, while the contents of iron and copper were decreased. In general, the variance coefficient of all nutrient elements and the difference of soil fertility were decreased.

Preliminary studies on the nutrient characters of different kinds of Chinese goldthread soil / 中国中药杂志

<p><b>OBJECTIVE</b>To study the changes of nutrient contents in Chinese goldthread soil before and after planting Coptis chinensis.</p><p><b>METHOD</b>The soil in Shizhu, Chongqing, was analyzed for nutrient contents.</p><p><b>RESULT AND CONCLUSION</b>The results indicated that the preplanted soil was strongly acidic and the levels of organic matter, total nitrogen and potassium were high. However, the content of total phosphorus was very low; so were the contents of other eleven nutrients. Variations of nutrients except zinc and molybdenum were large. After four years of planting C. chinensis, the soil pH was increased. Contents of organic matters, manganese, zinc and boron were increased, while the contents of iron and copper were decreased. In general, the variance coefficient of all nutrient elements and the difference of soil fertility were decreased.</p>