Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Production of alkaline pectinase: a case study investigating the use of tobacco stalk with the newly isolated strain Bacillus tequilensis CAS-MEI-2-33.

BACKGROUND: Tobacco stalk (TS), a major agricultural waste abundant in pectin, has resulted in concerns about the need for its reuse. The nicotine in TS is considered a chemical that is to\xic and hazardous to the environment. RESULTS: In this study, Bacillus tequilensis CAS-MEI-2-33 was isolated from cigar wrappers to produce alkaline pectinase using TS. Subsequently, the medium and fermentation conditions for the production of pectinase by B. tequilensis CAS-MEI-2-33 were optimized. The optimal fermentation period, pH of the initial fermentation medium, concentration of TS, and inoculum amount for B. tequilensis CAS-MEI-2-33 were 40 h, 40 g/L, 7.0, and 3%, respectively. Under optimal conditions, the pectinase activity was 1370 U/mL. Then, the enzymatic properties, such as the optimum pH, reaction temperature, temperature stability, and effects of metal ions, were studied. The optimal pH was determined to be 10.0, indicating that the enzyme was an alkaline pectinase. The optimal temperature was 40 °C, and pectinase activity was stable at 40 °C. The Ag+ metal ions were shown to remarkably promote enzyme activity. The pectinase was partly purified by ammonium sulfate precipitation, ion exchange chromatography, and Sephacryl S-100 chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and LC-MS/MS analyses were utilized to analyze the pectinase. CONCLUSIONS: This study provided a new alkaline pectinase candidate and a new strategy for the use of TS.

[Effects of light intensities on growth,physiological characteristic and chemical composition of Viola yedoensis].

The study is aimed to investigate the effects of light intensities on growth,photosynthetic physiology,antioxidant systems and chemical composition of Viola yedoensis and provide cultivation references for V.yedoensis.Five groups of V.yedoensis were planted under five light intensities conditions,namely 100%,80%,50%,35%,5%of full sunlight,and then morphological index,growth,chlorophyll fluorescence parameters,photosynthetic parameters and antioxidant enzyme system indexes were measured during harvest.The results showed that there was no significant difference in the biomass of V.yedoensis among 35% -100%full sunlight,but the biomass of those were significantly higher than that in the 5%full sunlight treatment(P<0.05).The net photosynthetic rate,transpiration rate,stomatal conductance,intercellular CO_2 concentration and water use efficiency increased firstly and then decreased with the decrease of light intensity;F_m,F_v/F_mand Yield in 5% full sunlight treatment were significantly lower than those in the other four groups(P<0.05).The structure of chloroplast was normal under light intensity ranged from 50%to 100% full sunlight.The lamellar concentration of chloroplast matrix decreased and the starch granules decreased in 35% full sunlight treatment,and the margin of lamellar layer of chloroplast and substrate were blurred,and the starch granules were small and the number of starch granules decreased significantly under 5% full sunlight.MDA content in 5%full sunlight treatment was significantly higher than those in the other four groups(P<0.05).The total coumarin content and total flavonoid content decreased with the decrease of light intensity.In summary,the light in-tensity range suitable for the growth of V.yedoensis is wide(ranging from 35% to 100% full sunlight).The content of flavonoids and coumarins is positively correlated with light intensity.

The Impact of Normal Range of Serum Phosphorus on the Incidence of End-Stage Renal Disease by A Propensity Score Analysis.

BACKGROUND: Although hyperphosphatemia is deemed a risk factor of the progression of chronic kidney disease (CKD), it remains unclear whether the normal range of serum phosphorus likewise deteriorates CKD. A propensity score analysis was applied to examine the causal effect of the normal range of serum phosphorus on the incidence of end-stage renal disease (ESRD). METHODS: A retrospective CKD cohort of 803 participants in a single institution was analyzed. Propensity score was estimated using 22 baseline covariates by multivariate binary logistic regression for the different thresholds of time-averaged phosphorus (TA-P) in the normal range of serum phosphorus incremented by 0.1 mg/dL from 3.3 to 4.5 mg/dL. RESULTS: The incidence rate of ESRD was 33.9 per 1,000 person-years over median follow-up of 4.3 years. Total patients showed the mean baseline phosphorus of 3.37 mg/dL and were divided to quartile. The higher quartile was associated with the parameters consistent with the advancement of CKD. A stratified Cox regression showed the highest hazard ratio (HR) at TA-P 3.4 mg/dL (HR 17.60, 95% CI 3.92-78.98) adjusted for baseline covariates such as sex, age, diabetic nephropathy, estimated GFR, serum albumin, Na-Cl, phosphorus, LDL-C and proteinuria. Adjusted HRs remained high up to TA-P 4.2 mg/dL (HR 2.22, 95% CI 1.33-3.71). After propensity score matching conducted at the thresholds of TA-P 3.4, 3.6, 3.8 and 4.0 mg/dL, the higher levels of TA-P showed the higher HRs by Kaplan-Meier analysis (p < 0.05 by stratified log-rank test). The numbers needed to treat were calculated as 3.9 to 5.3 over 5 years. CONCLUSIONS: The propensity score analysis shows that even the normal range of serum phosphorus clearly accelerates CKD progression to ESRD. Our results encourage clinicians to target serum phosphorus to inhibit CKD progression in the manner of 'the lower the better.'

[Effects of retained needling and non-retained needling on regulation of the cardiac autonomic nerve].

OBJECTIVE: To investigate the mechanism of retained needling and non-retained needling on the physiologic regulating effect of the cardiac autonomic nerve in healthy persons. METHODS: Sixty volunteers were randomly divided into a retained needling group and a non-retained needling group, 30 cases in each group. They were all received perpendicular needling at Neiguan (PC 6) and Jianshi (PC 5) retaining for 20 min in the retained nee dling group and without retaining in the non-retained needling group. The heart rate variability (HRV) indices, i.e., R-R interval, low frequency (LF), high frequency (HF) and LF/HF were observed. RESULTS: Compared with before acupuncture, the R-R interval were significant increased during the stimulation period and during the post-stimulation period in the retained needling group, especially during the stimulation period (all P < 0.01), and during the post-stimulation period of 5 min and 10 min in the non-retained needling group (P < 0.01, P < 0.05), then returned to pre-acupuncture level quickly, and the R-R interval in the retained needling group was significant ly higher than that in the non retained needling group at 10 min (P < 0.05). At 5 min, the HF were significantly higher, and the LF/HF were significantly lower than those before acupuncture (P < 0.01, P < 0.05), and there was no obvious change in LF in both groups. CONCLUSION: Retained needling and non-retained needling at Neiguan (PC 6) and Jianshi (PC 5) can both excite cardiac vagus nerve briefly and then the acupuncture effects reduce grad ually until disappearance, while no obvious changes can be found with cardiac sympathetic activity. Both of needling can reduce heart rate and the action time of heart rate decrease by retained needling is longer than non-retained needling.

Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study.

The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m(2) on day 1, leucovorin (calcium folinate, CF) 200 mg/m(2) on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m(2) as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57 months by combination chemotherapy. The 1- and 3-year survival rates were 89.7% and 79.3% with chemotherapy versus 69.0% and 62.1% without chemotherapy. The cumulative 1-year survival was significantly increased by chemotherapy (log-rank test, P = 0.043). The 6-month tumor-free survival rate was 24.1% higher with chemotherapy than without. The recurrence rate after LT was significantly different between the two groups at 6 months (P = 0.036), but not at 3 years (P = 0.102). The chemotherapy regimen was generally well tolerated. Post-LT adjuvant chemotherapy with oxaliplatin/5-FU/CF could not prevent tumor recurrence post-LT but may contribute to improve the survival of HCC patients who do not meet the Milan criteria. These results should be verified in a larger sample with a longer follow-up period.

[Prospective study of effect of recombinant human growth hormone on nutritional status and immune function in early postoperative stage of liver transplantation].

OBJECTIVE: To evaluate influence of recombinant human growth hormone (rhGH) on nutritional status and immune function in early postoperative stage of liver transplantation including hepatic function, acute rejection and infection rate, in order to assess its safety in clinical use. METHODS: Sixty patients with non-malignant diseases of the liver in terminal stages were randomly divided into two groups: treatment group (rhGH treatment n=30) and control group (n=30). All the patients received the same nutritional support and immunodepressant treatment regimes. The patients in treatment group received rhGH 10 U hypodermically daily for 10 days 24 hours after liver transplantation. The following parameters including siderophilin, prealbumin, albumin, urea nitrogen, CD4/CD8, immunoglobulin G (IgG), IgM, IgA, growth hormone (GH), insulin-like growth factor-1 (IGF-1), aspartate aminotransferase (AST), alanine aminotransferase (ALT), dosage of insulin to control blood sugar (8-10 mmol/L) were determined on 1st, 4th, 8th, 14th days after the operation, and acute rejection rate after 28 days of operation (confirmed by liver acupuncture biopsy), and infection rate were also assessed. RESULTS: Compared with control group, levels of siderophilin, prealbumin, CD4/CD8, GH, IGF-1 within 14 days in treatment group were increased significantly 14 days after the operation (all P<0.05), and level of urea nitrogen was decreased significantly (P<0.05). The level of albumin in treatment group was lower than that in control group 14 days after operation (P<0.05), while dosages of exogenous insulin were higher on 4th and 8th days after operation than that in control group (both P<0.05). There were no significant differences in levels of AST, ALT within 14 days, or acute rejection rate and infection rate within 28 days between two groups (all P>0.05). CONCLUSION: rhGH can accelerate recovery of nutritional status in the early liver transplantation period. It does not show superiority in improving immune function and influence on recovery of hepatic function, acute rejection or infection rate. The safety has been challenged by inducing high blood sugar as a side effect.

[Vascular effect of extract from mulberry leaves and underlying mechanism].

OBJECTIVE: To investigate the vascular activity of extract from mulberry leaves (EML) on rat thoracic aorta and the underlying mechanism. METHODS: Isolated thoracic rings of Sprague-Dawley rats were mounted on the organ bath and the tension of the vessel was recorded. RESULT: (1) EML produced a concentration-dependent vasorelaxation of aorta preconstricted by high K(+) (60 mmol/L) or 10(-6) mol/L phenylephrine (PE) in endothelium-intact and endothelium-denuded arteries. (2) EML at EC(50) concentration reduced the calcium dose-response curve. (3) After incubation of aorta with verapamil, EML induced vasocontraction of aorta preconstricted by PE, which was abolished by ruthenium red. CONCLUSION: The vascular effect of EML is biphasic, the vasorelaxation is greater than the vasocontraction. The vasorelaxation induced by EML may be mediated by inhibition of voltage-and receptor-dependent calcium channels in vascular smooth muscle cells, while the vasocontraction is via activation of ryanodine receptor in endoplasmic reticulum.

A novel alternative spliced variant of neutrophil gelatinase-associated lipocalin receptor in oesophageal carcinoma cells.

Recent studies suggest that NGAL (neutrophil gelatinase-associated lipocalin) is a novel iron transporter with functions distinct from that of transferrin and mediates a new iron-delivery pathway. To get a better understanding of NGAL function in oesophageal carcinoma, we analysed the expression of NGAL receptors in oesophageal carcinoma cells and identified a novel spliced variant designated NgalR-3. When expressed in a heterologous system, the protein produced from this novel spliced variant exhibits the biochemical characteristics of interaction and co-localization with NGAL protein in vivo. This new finding suggests that NgalR-3 may act as a potential NGAL receptor and play a role in NGAL-mediated iron transport in oesophageal carcinoma.

[A brief history of liver transplantation].

Since 1950s, the idea of liver transplantation (LT) was proposed, the technique of LT had been gradually and widely appliedin the field of clinical surgery, experiencing three stages of animal experiment, clinical probation and clinical application. It is generally acknowledged as the common and effective therapeutic method for terminal stage of liver diseases. Recently, the technique of LT has made rapid progress in Chinese mainland, Hong Kong and Taiwan. China is the second biggest LT country in the world, only next to USA.