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.

Objective To explore the effect of spinal 360°circumferential resection decompression combined with bone cement fill-separation and pedicle screw fixation instrumentationb for patients suffering from spinal metastases.Methods Retrospectively analyzed the clinical data of 42 patients suffering from spinal metastases and underwent spinal 360°circumferential resection decompression combine with bone cement fill-separation and pedicle screw fixation instrumentation in our hospital from April 2012 to October 2016.The pain level were assessed by visual analogue scale(VAS),the functional impairment was classified by Karnofsky score(KPS) and the neurologic deficit was evaluated by Frankel grade before preoperation,1 week after operation and 3 months after operation.Results Through the following-up of 3 months,there was no neural symptoms relapse in primary segment.The VAS score was (0.57 ±0.79) points,and the KPS was (72.61 ± 19.12) points 3 months after operation,which were significantly improved compared with the data before operation (P ＜ 0.05).The VAS score improvement rate was (91.09％ ±13.73％),and the Frankel grade improvement rate was 80％.Conclusion Circumferential resection decompression combined with bone cement fill-separation and pedicle screw fixation instrumentationb for patients suffering from spinal metastases can effectively improve the neural symptoms and life-quality of patients and prevent neural symptoms relapsing in primary segment after operation.

To study the protective effect of astragalus saponin extracts (AS) on kidneys of diabetic rats. Totally 32 diabetic rats induced by streptozotocin (STZ) were divided into AS high and low dose groups, the positive control group and the model group (DM group) and orally administered with 50 mg x- kg(-1) x d(-1) AS 200, 25 mg x kg(-1) x d(-1) valsartan, 10 mL x kg(-1) x d(1) physiological saline, respectively. Another 8 healthy rats were collected in the normal control group (NC group, physiological saline 10 mL x kg(-1). d(-1)). All rats were treated for consecutively 6 weeks. After the administration, the body weight was measured every week, the concentration of blood glucose was monitored on week 2, 4 and 6. The total urine and total urinary protein (U-TP) in 24 h were measured by the metabolic cage method on week 6; At the end of week 6, blood samples were collected from hearts to detect blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA) , total cholesterol (CH) triglyceride (TG) by biochemical methods. Kidneys were collect to calculate the kidney hypertrophy index and observe the pathological sections. The laboratory results show that in the DM group, the blood glucose, metabolic cost in 24 h, kidney hypertrophy index, U-TP, BUN, Scr, UA, TG were significantly higher than that in the NC group (P < 0.01, P < 0.05) , with significant pathological changes; After the intervention with AS, the metabolic value in 24 h, kidney hypertrophy index, U-TP, BUN, Scr, UA, TG were significantly lower in the high dose group (P < 0.01, P < 0.05), and the kidney hypertrophy index, BUN, Scr, UA, TG in the low dose group were also significantly lower (P < 0.05), with slight reduction in renal pathological changes in both groups. In conclusion, Astragalus saponin extracts have a certain protective effect on kidneys of diabetic rats.
Animals ; Astragalus Plant ; chemistry ; Blood Glucose ; metabolism ; Blood Urea Nitrogen ; Diabetic Nephropathies ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; Uric Acid ; metabolism

A reliable method for simultaneous determinition of eleven representative components (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, shanzhiside, geniposidic acid, genipin-1-β-D-gentiobioside, geniposide and secoxyloganin) in combination of chromatographic fingerpint analysis for Reduning injection was developed by ultra high-performance liquid chromatography (UPLC). The method was performed on an Agilent ZORBAX SB-C18 anlytical column (3. 0 mm x 100 mm, 1. 8 µm) with a guard column of Agilent UPLC Guard ZORBAX SB-C18 (3.0 mm x 5 mm) at the column temperature of 30 °C. The gradient mobile phase consisted of acetonitrile (A)-0. 1% phosphoric acid (B) with a flow rate of 0. 4 mL . min-1. The injection volumn was 2 µL. The detection wavelengths were set at 324 nm and 238 nm for quantit tive analysis and 225 nm for fingerpint chromatography. Neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, shanzhiside, geniposidic acid, genipin-1-β-D-gentiobioside, geniposide and secoxyloganin were baseline seperated with good linearity relationships (r >0. 999) between concentration and peak areas over the linear ranges. The average recoverys of the investigated compounds were 103.5%, 100. 2%, 103. 3%, 102. 8%, 101. 3%, 102. 8%, 97. 36%, 99. 62%, 98. 16%, 102. 8%, 99. 27%, respectively. Reduning injection of forty-five batches was analyzed by UPLC finge print chromatography. Thirty batches were selected to generate the reference fringerprint chromatography with fourteen common peaks. The similarity values between the reference fringerprint chromatography and the remaining fifteen batches were higher than 0. 99. The developed method was fast, accurate and sensitive. It could be used as a reference for the quality control of multiple components determination and fingerprint chromatography for Reduning injection in future.
Chlorogenic Acid ; chemistry ; isolation & purification ; standards ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; standards ; Glucosides ; chemistry ; isolation & purification ; standards ; Iridoids ; chemistry ; isolation & purification ; standards ; Quality Control ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Time Factors

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

OBJECTIVETo investigate the effect and safety of two types of early enteral nutrition, total protein(TP) and total protein with fibers(TPF-FOS), after laparoscopic colectomy.

METHODSPatients with colon cancer were divided into TP group and TPF-FOS group. Oral nutrition was given from the first postoperative day. Hemoglobin, albumin, prealbumin, white blood cell count, C-reactive protein, procalcitonin were tested before operation and on the first and seventh postoperative day. The time to first flatus, time to first bowel movement, fever, infection, and diarrhea were observed after operation.

RESULTSNo significant difference was observed in hemoglobin, albumin, prealbumin, white blood cell count, C-reactive protein, and procalcitonin between these two groups. Higher proportion of patients defecated formed stool during the observation in TPF-FOS group(76.7% vs. 27.3%, P<0.01). Less abdominal bloating was found from the fourth to the seventh postoperative day in TPF-FOS group (5.8% vs. 15.2%, P<0.05).

CONCLUSIONSBoth TP and TPF-FOS can be safely used for early oral enteral nutrition after laparoscopic colectomy. TPF-FOS may be more beneficial to the recovery of gastrointestinal function.

Objective To analyze the surveillance results and grasp the situation of Keshan disease in Wudalianchi city Heilongjiang province.Methods In 2009,Kaifa village was selected as the surveillance point in Wudalianchi city,total resident population were monitored by routine clinical examination and 12-lead electrocardiogram(ECG) tracing.Suspected cases with Keshan disease were taken chest X-ray,and Keshan disease was diagnosed based on Keshan Disease Diagnostic Criteria (WS/T 210-2011).Results A total of 795 people were investigated,including 397 males and 398 females.Eighteen people were found to be the patients with Keshan disease,of which 13 cases were latent Keshan patients,5 cases were chronic Keshan patients.The overall detection rate was 2.27％,aged 24 to 83 years old.There was no acute type and subacute type of Keshan disease in the surveillance point.Twenty nine cases of abnormal ECG were detected,the detection rate was 3.65％ (29/795),of which the 18 patients with Keshan disease were all had abnormal ECGs,mainly taken the form of ST-T changes and completely right bundle branch blocked.Six cases of male patients with Keshan disease were detected,the detection rate was 1.52％ (6/397); 12 cases of female patients with Keshan disease were detected,the detection rate was 3.01％ (12/398).Conclusions There is still potential and chronic Keshan disease cases in Wudalianchi city.We must keep on the monitoring on Keshan disease,master the dynamical changes of the disease conditions,and carry out the targeted prevention and control of Keshan disease.

AIM:To evaluate the effects of atorvastatin (ATO) on atrial electrical remodeling in a rabbit mo-del of chronic atrial fibrillation (AF) produced by 3 weeks of rapid atrial pacing (RAP). METHODS:The sternotomy was performed and the pacing and testing electrodes were fixed to the left atria of 24 New Zealand white rabbits. The ani-mals were randomly divided into 3 groups. The rabbits in model group and ATO group were subjected to RAP for 3 weeks, and then were treated with placebo and ATO(2.5 mg·kg-1·d-1),respectively. The rabbits in sham group did not re-ceive RAP and drugs. Electrophysiological examination was performed to test heart rate, P-wave duration, atrial effective refractory period (AERP) and AF inducibility. The protein expression levels of Cav1.2, Kv4.3 and myeloperoxidase (MPO) were detected by Western blot. RESULTS:Sustained AF was induced in 5 and 4 rabbilts in model group and atorvastatin group and no rabbits in sham group was found. After 3 weeks of RAP, compared with sham group, heart rate and P-wave duration were increased and AERP was shortened in model group and ATO group(P<0.05). Compared with model group,AERP was increased in ATO group(P<0.05),while heart rate and P-wave duration had no difference be-tween these 2 groups. Compared with sham group, the protein levels of Cav1.2 and Kv4.3 were decreased, and protein level of MPO was increased in model group and ATO group (P<0.05). Compared with model group, Cav1.2 was in-creased and MPO was decreased in ATO group(P<0.05),while Kv4.3 had no difference between these 2 groups. CON-CLUSION:Atorvastatin suppresses the down-regulation of atrial Cav1.2 protein level and the shortening of AERP, thus preventing atrial electrical remodeling in a rabbit model of chronic AF. The effect of atrovastatin on reducing atrial MPO level may be the potential mechanism.

Objective To explore the relationship among the prevertebral soft tissue swelling and dysphagia rate after anterior cervical diskectomy and fusion(ACDF),and to investigate the prevertebral soft tissue swelling and dysphagia rate after Zero-p or traditionaI cage and titanium plate for one-level lesion of cervical myelopathy.Methods The clinical data of 54 patients with one-level lesion (C5/6) of cervical myelopathy who undelwent anterior cenrical discectomy and fusion by Zero-p (n =25) or traditional cage and titanium plate (n =29) were analyzed.The postoperative prevertebral soft tissue swelling was measured by lateral radiographs.Patients were divided into the swelling group (n =24) and the non-swelling group(n =30) based on the degree of prevertebral soft tissue swelling and the incidences of dysphagia were analyzed.Patients were divided into the Zero-p group (n =25)and the Cage group (n =29) based on surgical treatment,the postoperative prevertebral soft tissue swelling and dysphagia rate were compared.Results The rate of dysphagia in swelling group was 45.8％,which was higher than 13.3％ in non-swelling group,the difference was significant(P ＜0.05).The postoperative prevertebral soft tissue swelling was 6.22 mm averagely after Zreo-p,which was less than that after traditional cage and titanium plate for anterior cervical discectomy with fusion(9.25 mm),the difference was significant (P ＜ 0.05).The incidence of dysphagia in Zero-p group was 12％,which was lower than 41.4％ in Cage group,and the difference was statistically significant (P ＜ 0.05).Conclusion It is a clinical significance to evaluate the degree of prevertebral soft tissue swelling by cervical lateral X-ray after ACDF,when the degree of prevertebral soft tissue swelling is greater,the incidence of complications such as dysphagia is higher.In addition,The Zero-p for the treatment of single one-level lesion of cervical myelopathy(C5/6) has a lower degree of prevertebral soft tissue swelling and dysphagia rate than the traditional Cage and titanium plate fusion.

OBJECTIVETo observe syndrome types of Chinese medicine (CM) and distribution features of acute infectious diarrhea patients.

METHODSA retrospective study was performed in 465 acute infectious diarrhea patients. The distribution of CM syndrome and syndrome types in different seasons and genders were analyzed.

RESULTSLack of appetite [381 (81.94%)], fatigue [350 (75.27%)], abdominal pain [338 (72.69%)], tenesmus [325 (69.89%)], anal scorching hot [276 (59.35%)], nausea [25 (55.48%)], diarrhea [249 (53.55%)], short yellow-urine [240 (51.61%)], thirsty [210 (45.16%)], and abdominal distention [206 (44.30%)] were most often seen. The syndrome distribution were sequenced as intestinal damp heat syndrome [268 (57.63%)], dyspeptic retention in intestine and stomach syndrome [106 (22.80%)], cold-damp invading exterior syndrome [47 (10.11%)], Pi-Wei qi deficiency syndrome [23 (4.95%)], cold-damp disturbing Pi syndrome [21 (4.52%)]. The incidence ratio of intestinal damp heat syndrome was the highest in autumn (P < 0.01), while that of cold-damp invading exterior syndrome was the highest in winter (P < 0.01). Cold-damp disturbing Pi syndrome was more often seen in females than in males (P < 0.01), and its incidence ratio was the highest in autumn (P < 0.05). The incidence ratio of dyspeptic retention in intestine and stomach syndrome was the highest in winter (P < 0.01).

CONCLUSIONSIntestinal damp heat syndrome was the most often seen in acute infectious diarrhea. Incidence ratios of in- testinal damp heat syndrome and cold-damp disturbing Pi syndrome were higher in autumn, while those of cold-damp invading exterior syndrome and dyspeptic retention in intestine and stomach syndrome were higher in winter. Cold-damp disturbing Pi syndrome was more often seen in females.