Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.

BACKGROUNDA wealth of evidence has indicated that labor epidural analgesia is associated with an increased risk of hyperthermia and overt clinical fever. Recently, evidence is emerging that the epidural analgesia-induced fever is associated with the types of the epidural analgesia and the variations in the epidural analgesia will affect the incidence of fever. The aim of the present study was to investigate the effects of epidural analgesia with 0.075% or 0.1% ropivacaine on the maternal temperature during labor.

METHODSTwo hundred healthy term nulliparas were randomly assigned to receive epidural analgesia with either 0.1% ropivacaine or 0.075% ropivacaine. Epidural analgesia was initiated with 10 ml increment of the randomized solution and 0.5 µg/ml sufentanyl after a negative test dose of 5 ml of 1.5% lidocaine, and maintained with 7 ml bolus doses of the above mentioned mixed analgesics every 30 minutes by the patient-controlled epidural analgesia. The measurements included the maternal oral temperature, visual analog scale pain scores, labor events and neonatal outcomes.

RESULTSEpidural analgesia with 0.075% ropivacaine could significantly lower the mean maternal temperature at 4 hours after the initiation of analgesia and the oxytocin administration during labor compared with the one with 0.1% ropivacaine. Moreover, 0.075% ropivacaine treatment could provide satisfactory pain relief during labor and had no significant adverse effects on the labor events and neonatal outcomes.

CONCLUSIONEpidural analgesia with 0.075% ropivacaine may be a good choice for the epidural analgesia during labor.

Adult ; Amides ; administration & dosage ; therapeutic use ; Analgesia, Epidural ; adverse effects ; Analgesia, Obstetrical ; adverse effects ; Body Temperature ; drug effects ; Female ; Fever ; chemically induced ; Humans ; Labor, Obstetric ; Pregnancy ; Young Adult

OBJECTIVETo evaluate the efficacy and security of propranolol gel in treatment of Infantile hemangiomas.

METHODS51 consecutive infants with hemangiomas from October 2010 to September 2011 in Department of General Surgery Fuzhou General Hospital of Nanjing Military Command were treated with propranolol hydrochloride 3% gel. Changes in hemangioma size, texture, color, tumor blood flow peak were recorded.

RESULTSThe results were evaluated using Achauer system, responses of IHs to propranolol were considered scale I (poor) in 4 patient (17.24%), scale II (moderate) in 18 patients (24.14%), scale III (good) in 22 patients (44.83%) and scale IV (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P < 0.05), and no significant differences in response among different primary sites (P > 0.05).

CONCLUSIONSTopical use of propranolol hydrochloride 3% gel is an effective option for superficial hemangiomas.

Female ; Hemangioma, Capillary ; drug therapy ; Humans ; Hydrogels ; Infant ; Infant, Newborn ; Male ; Propranolol ; administration & dosage ; therapeutic use ; Skin Neoplasms ; drug therapy ; Treatment Outcome

OBJECTIVE To investigate toll-like receptor 4(TLR4)-related the regulation of Ornithog-alum caudatum extract(OCE)on inflammatory responses in lipopolysaccharide(LPS)activated macro-phages.METHODS Primary peritoneal macrophage,Raw 264.7,and THP-1 were incubated in 96-well plate for 24 h and treated with OCE of the concentration of 0-400 μg/ml for 4h.The viability of cells was measured by MTT assay.Specific concentrations of OCE were added into the medium of primary peri-toneal macrophage, Raw 264.7, and THP-1, respectively, then following with lipopolysaccharides (LPS). Cells were harvested and the total cellular protein and nuclear protein were extracted, and the protein content was determined using BCA protein assay Kit.The expressions of TLR4,inducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX-2),α-inhibitor of NF-κB(IκB-α)and nuclear factor-κB (NF-κB)were assayed by Western blot.The expressions of interleukin-1α(IL-1α),interleukin-1β(IL-1β), interleukin-18(IL-18),and tumor necrosis factor-α(TNF-α)were measured by RT-PCR.RESULTS The results of MTT showed that OCE has no cytotoxicity in Raw 264.7 cells between 1.56 μg/ml and 400 μg/ml. Compared with normal group,the expressions of TLR4,iNOS,COX-2,NF-κB and IL-1α,IL-1β,IL-18, TNF-α,the level of nitric oxide(NO)were significantly increased by LPS stimulation,while OCE pretreat-ment reduced these increase induced by LPS. However, OCE pretreatment reversed the reduction of IκB-α after LPS stimulation.CONCLUSION OCE might suppress TLR4 expression and block the inflamma-tion process of NF-κB and iNOS,further decrease the expression of COX-2 and inhibit the release of inflammatory factors.

OBJECTIVETo investigate the effects of caffeic acid ester fraction (Caf) from Erigeron breviscapus, mainly composed of dicaffeoylquinic acids (diCQAs), on microglial activation in vitro and focal cerebral ischemia in vivo.

METHODSThe production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) induced by lipopolysaccharide (LPS) treatment in rat primary cultured microglia were measured by Griess reaction or enzyme-linked immunosorbent assay. Cell viability of cortical neurons was measured using AlamarBlue reagent. The behavioral tests and the infarct area of brain were used to evaluate the damage to central nervous system in rat middle cerebral artery occlusion (MCAO) model of cerebral ischemia. Real time polymerase chain reaction was used to determine the expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β mRNA in ischemic cerebral tissues.

RESULTSCaf inhibited the production of NO, TNF-α and IL-1β induced by LPS treatment in primary microglia in a dose-dependent manner. Exposure of cortical neurons to conditioned medium from Caf-treated microglia increased neuronal cell viability (P<0.01) compared with conditioned medium from LPS-treated alone. In MCAO rat model of cerebral ischemia, Caf could significantly improve neurobehavioural performance and reduce percentage infarct volume compared with the vehicle group (P<0.05). Caf could also significantly inhibit the up-regulation of iNOS, TNF-α, and IL-1β gene expressions in ischemic cerebral tissues.

CONCLUSIONCaf could suppress microglial activation, which may be one mechanism of its neuroprotective effect against ischemia.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; drug therapy ; pathology ; prevention & control ; Caffeic Acids ; chemistry ; pharmacology ; Chemical Fractionation ; Chromatography, High Pressure Liquid ; Erigeron ; chemistry ; Gene Expression Regulation ; drug effects ; Infarction, Middle Cerebral Artery ; complications ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Microglia ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; chemistry ; pharmacology ; therapeutic use ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Plant Extracts ; pharmacology ; Quinic Acid ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Aim To study the changes in endogenous differential metabolites of cerebral cortex and hippocampus extracts from cognitive dysfunction rats induced by hyperuricemia using * H nuclear magnetic resonance (

Objective:To evaluate the value of susceptibility-weighted imaging(SWI) in diagnosis of Parkinson disease (PD) and assessment of disease severity.Methods:Totally 30 PD patients and 30 healthy volunteers underwent SWL The phase values of nuclei in extracorticospinal tract were measured and compared between PD patients and healthy subjects.Results:The phase values of sustantia nigra pars compacta,globus pallidus,putamen in PD group were all significantly lower than those in control group(P＜0.01).The phase values of sustantia nigra pars compacta,globus pallidus and putamen reduced at the early stage in PD group,and then further reduced along with the severity of disease(P＜0.05).Conclusions:SWI has important clinical value in diagnosing PD and evaluating the disease severity.

Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

OBJECTIVETo compare the clinical effects of isthmic spondylolisthesis by a single cage or double cages interbody fusion combined with pedicle screw fixation.

METHODSThe clinical data of 172 patients with isthmic spondylolisthesis underwent surgery from March 2000 to August 2008 were retrospectively analyzed. All cases underwent posterior pedicle screw fixation and interbody fusion, 89 cases with single cage fusion and 83 cases with double cages fusion. In single cage group, there were 56 males and 33 females, aged from 18 to 63 years old with an average of(41.60±8.20) years;25 cases were in L4 segment and 64 cases were in L5;according to the Meyerding standard, 32 cases were I degree, 46 cases were II degree and 11 cases were III degree. In double cage group, there were 49 males and 34 females, aged from 20 to 65 years old with an average of(43.30±6.39) years;21 cases were in L4 and 62 cases were in L5;according to the Meyerding standard, 25 cases were I degrees, 45 cases were II degree, and 13 cases were III degree. The operative time, intraoperative blood loss, postoperative drainage volum, bone fusion rate, intervertebral space height and the improvement of clinical symptoms were compared between two groups.

RESULTSAll the operations were successful and all patients were followed up for 18 to 83 months with an average of 4 years and 3 months. The operative time, intraoperative blood loss, postoperative drainage volume in single cage group were less than of double cage group(<0.05). Two weeks after operation, the intervertebral space height was significantly increased in two groups(<0.05), and there was no significant difference at the last follow-up between two groups. At 16 months after operation, all bone grafts of patients got bony fusion by X-rays. At the last follow-up, there were no statistically significant difference in JOA, ODI and VAS score between two groups, no pedicle screw loosening and breaking were found.

CONCLUSIONSSingle cage interbody fusion combined with pedicle screw fixation is as effective as with double cages interbody fusion in treatment of isthmic spondylolisthesis, it has the advantages of short operative time and less blood loss.

BACKGROUNDThe prevalence of chronic kidney disease (CKD) and prediabetes has increased in China, and at different rates in different locations. Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.

METHODSA total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method. An estimated glomerular filtration rate (eGFR), albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006. Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes, and association of insulin resistance (IR) with CKD and prediabetes was analyzed.

RESULTSThe age-standardized prevalence of CKD was 12.5%, eGFR < 60 ml×min(-1)×1.73 m(-2) was 2.7% and ACR (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes. Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.

CONCLUSIONCKD and prediabetes have become a major public health problem in Zhuhai, Southern China; insulin resistance may be an important risk factor.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State ; epidemiology ; Prevalence ; Renal Insufficiency, Chronic ; epidemiology ; Risk Factors ; Surveys and Questionnaires