The effect of Huanglian Jiedu Decoction on the intestinal flora of type 2 diabetes mellitus(T2DM) was investigated using 16S rRNA sequencing technology. Sixty rats were randomly divided into a normal group(10 rats) and a modeling group(50 rats). After one week of adaptive feeding, a high-fat diet + streptozotocin was given for modeling, and fasting blood glucose >16.7 mmol·L~(-1) was considered a sign of successful modeling. The modeling group was randomly divided into the model group, high-, medium-, and low-dose groups of Huanglian Jiedu Decoction, and metformin group. After seven days of intragastric treatment, the feces, colon, and pancreatic tissue of each group of rats were collected, and the pathological changes of the colon and pancreatic tissue of each group were observed by hematoxylin-eosin staining. The changes in the intestinal flora structure of each group were observed by the 16S rRNA sequencing method. The results showed that compared with the model group, the high-, medium-, and low-dose of Huanglian Jiedu Decoction reduced fasting blood glucose levels to different degrees and showed no significant changes in body weight. The number of islet cells increased, and intestinal mucosal damage attenuated. Alpha diversity analysis revealed that Huanglian Jiedu Decoction reduced the abundance and diversity of intestinal flora in rats with T2DM; at the phylum level, low-and mediam-dose of Huanglian Jiedu Decoction reduced the abundance of Bacteroidota, Proteobacteria, and Desulfobacterota and increased the abundance of Firmicute and Bacteroidota/Firmicutes, while the high-dose of Huanglian Jiedu Decoction increased the relative abundance of Proteobacteria and Bacteroidota/Firmicutes ratio, and decreaseal the relative; abundance of Firmicute; at the genus level, Huanglian Jiedu Decoction increased the relative abundance of Allobaculum, Blautia, and Lactobacillus; LEfse analysis revealed that the biomarker of low-and medium-dose groups of Huanglian Jiedu Decoction was Lactobacillus, and the structure of the intestinal flora of the low-dose group of Huanglian Jiedu Decoction was highly similar to that of the metformin group. PICRUSt2 function prediction revealed that Huanglian Jiedu Decoction mainly affected carbohydrate and amino acid metabolic pathways. It suggested that Huanglian Jiedu Decoction could reduce fasting blood glucose and increase the number of islet cells in rats with T2DM, and its mechanism of action may be related to increasing the abundance of short-chain fatty acid-producing strains and Lactobacillus and affecting carbohydrate and amino acid metabolic pathways.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Bacteria/drug effects* ; Blood Glucose/metabolism*

OBJECTIVE To systematically review the background of bioequivalence assessment of nasal sprays and nasal aerosols and the guiding considerations for the bioequivalence assessment of these complex drug-device combination products by regulatory authorities in the United States, the European Union(EU) and China. METHODS This article provided detailed explanations on the innovative weight of evidence assessment approach adopted by the US Food and Drug Administration(FDA), and the statistical rationale, methods and considerations for the bioequivalence assessment of nasal sprays and nasal aerosols. Using the calculation methods described in the draft guidance for budesonide inhalation suspension and the draft guidance for fluticasone nasal spray propionate issued by FDA, the statistical parameters of two-sided and one-sided population bioequivalence calculation were realized through R language programming, and pseudo-code for the population bioequivalence (PBE) calculation programs was provided. This article also presented a comprehensive review of published guidelines and summaries review principles of the EU and China for nasal sprays and nasal aerosols equivalence assessment. RESULTS & CONCLUSION Nasal sprays/nasal aerosols is the focus of innovative and generic drug development in recent years. This paper provided valuable considerations references for the research and development, quality control and bioequivalence evaluation of generic preparations of nasal sprays/nasal aerosols.

Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo. Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3’-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo. Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.

Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo. Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3’-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo. Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.

Objective To investigate the the treatment of class Ⅲ malocclusion by orthognathic surgery combined with postoperative orthodontics.Methods Nine patients with skeletal class Ⅲ malocclusion were treated by surgery-first approach without pre-surgical orthodontic from January 2012 to August 2014.The studied sample consisted of 7 women and 2 men (aged 15-28 years old, mean age 19.7 years), who had obvious mandibular protrusion.2 to 3 days after surgery, intermaxillary traction was used to made the maxilla and mandible together by board;we replaced a rubber band every 2 to 3 days and lasted for four weeks.We would dismantle board and performed conventional orthodontic treatment after patient's facial swelling subsided, and the positional relationship between the jaw stabilized.Results The face type of 9 patients were greatly improved after orthodontic treatment for 6.5 to 19.5 months.Patients and their family members felt satisfied, and their occlusal function returned to normal.At 3 to 32 months follow-up, the postoperative appearance and occlusion were becoming good without obvious signs of recurrence.Conclusions The surgery-first approach is an effective method to treat skeletal class Ⅲ malocclusion.

OBJECTIVE:To establish a method for the content determination of sinomenine in Qihuang capsule. METHODS:HPLC was performed on the column of welch C18-AQ with mobile phase of methanol-phosphate buffer(gradient elution) at flow rate of 1.0 ml/min,detection wavelength was 264 nm,column temperature was 30 ℃ and volume injection was 10 μl. RESULTS:The linear range of sinomenine was 0.200 3-10.016 0 μg(r=0.999 8),RSDs of precision,stability and reproducibility tests were lower than 1.0%,recovery was 98.80%-100.94%(RSD=0.79%,n=6). CONCLUSIONS:The method is simple,accurate and re-producible,and can be used for the content determination of sinomenine in Qihuang capsule.

Objective To evaluate the effect of ulinastatin on Th1/Th2 cell balance in a rat model of stress-induced gastric ulcer (GU).Methods Twenty-four male SPF Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =8 each) using a random number table:control group (group C),stress-induced GU group (group GU) and ulinastatin group (group U).The rats were subjected to water-immersion and restraint stress for 3.5 h to establish GU model in S and U groups.At 10 min before water-immersion,normal saline 0.4 ml and ulinastatin 100 000 U/kg were injected via the tail vein in GU and U groups,respectively.After GU model was established,the abdomen was opened after anesthesia.The whole stomach was exposed,and the gastric mucosal damage was evaluated under microscope,ulcer index (UI) was recorded,and the pathological changes of the gastric mucous membrane were observed.Spleen samples were obtained to detect T-bet,Gata-3,interferon-γ (IFN-γ),and interleukin-4 (IL-4) mRNA expression by RT-PCR.The ratio of T-bet mRNA expression/Gata-3 mRNA expression (T-bet/Gata-3) was calculated.Results Compared with group C,T-bet mRNA expression was significantly down-regulated,Gata-3 mRNA expression was up-regulated,T-bet/Gata-3 ratio was decreased,UI was increased,and no significant changes were found in IFN-γ and IL-4 mRNA expression in GU group,and UI was increased,and no significant changes were found in the other parameters in group U.Compared with group GU,the ratio of T-bet/Gata-3 was significantly increased,and UI was decreased,and no significant changes were found in T-bet,Gata-3,IFN-γ,IL-4 mRNA expression in group U.The gastric mucosal damage was significantly mitigated in GU group as compared with group U.Conclusion The mechanism by which ulinastatin mitigates stress-induced GU may be related to correction of Th1/Th2 cell imbalance in rats.

OBJECTIVETo compare the effects of propofol and inhalation anesthesia on the incidence of early postoperative cognitive dysfunction (POCD) in elderly patients undergoing noncardiac surgeries.

METHODSPubMed, Cochrane Library, CBM, CNKI, Wanfang data and VIP Database (by October 2012) were searched for randomized controlled trials (RCTs) comparing propofol and inhalation anesthesia for their impact on the incidence of early POCD in elderly patients undergoing noncardiac surgeries. After data extraction and quality evaluation, Stata 12.0 software was used for statistical data analysis.

RESULTSThirteen RCTs, including 2 comparing propofol with xenon, 7 comparing propofol with sevoflurane, and 4 comparing propofol with isoflurane were obtained, involving a total of 753 patients. The odds ratio of early POCD incidence between patients with propofol anesthesia and those with xenon anesthesia, sevoflurane anesthesia, and isoflurane anesthesia were 1.62 (95% CI 0.81-3.23, P=0.533), 0.67 (95% CI 0.39-1.14, P=0.830), and 0.20 (95% CI 0.08-0.50, P=0.925), respectively. Overall, the odds ratio of early POCD incidence between propofol anesthesia and inhalation anesthesia was 0.68 (95% CI 0.47-0.98, P=0.189). Egger's test showed a publication bias of the RCTs retrieved (P=0.011).

CONCLUSIONCompared with inhalation anesthesia, propofol anesthesia is associated with a lower incidence of early POCD in elderly patients, but this conclusion needs to be further verified by more well-designed large-scale RCTs.

Aged ; Aged, 80 and over ; Anesthesia, Inhalation ; Anesthetics, Inhalation ; Cognition Disorders ; epidemiology ; Humans ; Middle Aged ; Postoperative Period ; Propofol

AIM: To explore the way and the feasible time of olfactory ensheathing cells (OECs) transplanting to experimental autoimmune encephalomyelitis (EAE) rats, and to investigate the migration of OECs after transplanted to EAE and the possible mechanism of inducing the protective effect. METHODS: The Lewis rats, which were divided into MOG group and GPSCH group according to the induction by MOG~Igd and GPSCH separately, were used to made EAE model. The animals in MOG group were divided into 3 subsets: OECs blank group (MOG0 group, 4 rats );OECs transplantation by vena caudalis (MOG1 group, 7 rats);OECs transplantation by lateral cerebral ventricle (MOG2 group, 4 rats). The animals in GPSCH group were also divided into 2 subsets: OECs blank group (GPSCH0 group, 4 rats);OECs transplanted by vena caudalis (GPSCH1 group, 4 rats). OECs transplanted through different ways in peak incidence, then the rats were measured to determine whether the symptom was ameliorated. Two weeks after transplantion, the rats were killed and the methods of histofluorescence and histopathology (HE staining and Luxol fast blue staining) were used to examine the distribution of the labeled OECs in EAE rats' bodies and to explore whether there was some amelioration in histology. RESULTS: After OECs transplantation by vena caudalis or lateral cerebral ventricle, the rats' symptom improved. Compared to OECs blank groups, there was significant difference in clinical scores (F=18.470, P<0.01;t=-7.147, P<0.01). No significant difference between MOG1 group and MOG2 group was observed (P>0.05). The labeled OECs entered into the brain through the broken blood-brain-barrier after transplantation by vena caud-alis, the labeled OECs near the subpial area and around the lesions were found. OECs transplantation by the way of lateral cerebral ventricle showed great migration potential, the cells moved towards to the lesions extensively. No significant difference between OECs transplantation group and OECs blank group in histopathology (HE staining and LFB staining) was observed (P>0.05), and the same thing also happened between MOG1 group and MOG2 group (P>0.05). CONCLUSION: The transplantation of adult rats' OECs improves the EAE rats' symptom at some degree by the ways of vena caudalis or lateral cerebral ventricle.

To observe the therapeutic effect of Nitazoxanide(NTZ) on dogs infected with Giardia canis trophozoites.Eight dogs were infected with Giardia canis trophozoites and divided into four groups rondomly,G1:2 dogs treated with Nitazoxanide at a single dose of 1 mg/kg body weight;G2:2 dogs treated with NTZ at a single dose of 2 mg/kg;G3:2 dogs treated with NTZ at a single dose of 41 mg/kg;G4:2 dogs treated without drugs as control.All groups were examined for Giardia canis cysts by Zinc Sulfate Flotation.Each group was subjected to collect stool per day and counted cysts.The results of G2 and G3 were negative after 1th day.G1 were negative after 4th days.The results indicated that NTZ at a dose of 2 mg/kg and 4 mg/kg in dogs had a faourable effect on the dogs infected with Giardia canis.