[Progress on economic evaluation of pneumococcal vaccine].

Review the literature on the economic evaluation of PCV-10, PCV-13 and PPSV-23 for providing references for decision-making and research in China. A total of 17 literatures were included, and the basic information to descriptive characteristics, methodology, modeling and the results were extracted. The 14 studies adopted Markov model, 2 studies adopted decision tree model and 1 study adopted probabilistic model. The cost including vaccine price and administration costs, direct medical expenses and indirect lost. All the 17 studies use QALY as the outcome, some studies also use LYG as the outcome. 9 of 13 studies (69.2%) involving people over the age of 50 concluded that pneumococcal vaccination was cost-effective. To provide effective references for decision-makers, China should collect the relevant epidemiological parameters, vaccine effect of pneumococcal disease in the Chinese population and carry out the economic evaluation of pneumococcal vaccination.

[Development of a hyperkalemia risk assessment model for patients with chronic kidney disease].

Objective: To investigate risk factors for hyperkalemia among chronic kidney disease (CKD) patients and establish a risk assessment model for predicting hyperkalemia events. Methods: Clinical data of CKD patients (stage 3 to 5) hospitalized between May 2017 and June 2020 from 14 hospitals were retrospectively collected and divided into training dataset and validation dataset through balanced random sampling. Multivariate logistic regression analysis was used to analyze risk factors for hyperkalemia in CKD patients and the factors were scored. Receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Meanwhile, the cut-off value with the best sensitivity and specificity were used to verify the accuracy of the model in validation dataset. Results: A total of 847 CKD patients were enrolled and further divided into training dataset (n=675) and validation dataset (n=172). There were 555 males and 292 females, with a mean age of (57.2±15.6) years. Multivariate logistic regression analysis showed that age, CKD stage, history of heart failure, history of serum potassium ≥5.0 mmol/L, diabetes, metabolic acidosis, and use of medications that increase serum potassium levels were risk factors for causing hyperkalemia in patients with CKD. Risk assessment model was established based on these risk factors. The AUC of the ROC curve was 0.809. Using 4 as the cut-off value, the sensitivity and specificity for predicting hyperkalemia events reached 87.1% and 57.0%, respectively. Conclusion: The model established in the current study can be used for predicting hyperkalemia events in clinical practices, which offers a new way to optimize serum potassium management in patients with CKD.

[Application of chromosomal analysis for 29 cases of fetuses with nasal bone absence or hypoplasia].

Objectives: To explore the chromosomal analysis for fetuses with nasal bone absence or hypoplasia. Methods: This was a retrospective study on 29 pregnancies nasal bone absence or hypoplasia which underwent prenatal diagnosis, including chorionic villi (CV), amniotic fluid or cordocentesis.The indication of the procedures and results were evaluated. Result: Fifteen (51.7%, 15/29) of chromosome abnormities were diagnosed with indication of fetal nasal bone absence or hypoplasia, including eight with trisomy 21, two with trisomy 13, two with X chromosome aneuploidy and three with pathogenic copy number variations (CNVs) respectively.The incidence of chromosomal abnormalities in fetus with nasal bone hypoplasia (2/5, 40%) was lower than that in fetus with nasal bone absence (13/29, 54.2%). The incidence of chromosomal abnormalities in fetus with non-syndromic nasal bone absence or hypoplasia (4/13) was lower than that in fetus with syndromic nasal bone absence or hypoplasia (11/16). Conclusion: The incidence of chromosomal abnormalities in fetus with nasal bone absence or hypoplasia was higher and prenatal diagnosis was recommended for all types of the disease.For the fetus with nasal bone absence or hypoplasia, it is recommended to give priority to CNVs for prenatal diagnosis.

Development and characterization of microsatellite markers for Solen grandis using Illumina sequencing approach.

Solen grandis is an important economic and overexploited bivalve species. In order to perform its fine-scale genetic analyses, 105 pairs of microsatellites with polymorphism were identified through Illumina Hiseq platform and bioinformatic assembly technology in this study. The estimated fragment size ranged from 100 to 268 bp and the number of alleles per locus varied between 2 and 23. Observed and expected heterozygosities varied from 0.0667 to 1.0000 and 0.0966 to 0.9492, respectively. Fourteen loci deviated significantly from Hardy-Weinberg equilibrium after Bonferroni correction. These microsatellite markers developed in this study would be helpful for future genetic studies on S. grandis and closely related species.

Significant prognostic values of nuclear genes encoding mitochondrial complex I subunits in tumor patients.

In cancer biology, it remains still open question concerning the oncogenic versus oncosuppressor behavior of metabolic genes, which includes those encoding mitochondrial complex I (CI) subunits. The prognostic value of nuclear genome mRNAs expression of CI subunits is to be evaluated in the tumor patients. We used the Kaplan Meier plotter database, the cBio Cancer Genomics Portal, and the Oncomine in which gene expression data and survival information were from thousands of tumor patients to assess the relevance of nuclear genome mRNAs level of CI subunits to patients' survival, as well as their alterations in gene and expression level in tumors. We presented that the relative expression level of overwhelming majority of the nuclear genes of CI subunits with survival significance (overall survival, relapse free survival, progression free survival, distant metastasis free survival, post progression survival, and first progression), had consistent effects for patients in each type of four tumors separately, including breast cancer, ovarian cancer, lung cancer, and gastric cancer. However, in gene level, frequent cumulative or individual alteration of these genes could not significantly affect patients' survival and the overexpression of the individual gene was not ubiquitous in tumors versus normal tissues. Given that reprogrammed energy metabolism was viewed as an emerging hallmark of tumor, thus tumor patients' survival might potentially to be evaluated by certain threshold for overall expression of CI subunits. Comprehensive understanding of the nuclear genome encoded CI subunits may have guiding significance for the diagnosis and prognosis in tumor patients.

Blood folic acid, vitamin B12, and homocysteine levels in pregnant women with fetal growth restriction.

Deficiencies in nutrients such as folic acid and vitamin B12 may play a role in fetal growth restriction (FGR). However, whether folic acid, vitamin B12, or homocysteine is associated with FGR in Chinese populations remains unclear. This study investigated the relationship between these nutrient deficiencies and FGR in pregnant Chinese women. We selected 116 mother and infant pairs, and categorized the neonates into the FGR, appropriate for gestational age, and large for gestational age groups. Birth weight, body length, head circumference, body mass index (BMI), and Rohrer's body index of the newborns were measured. Serum folic acid, vitamin B12, and homocysteine levels were measured in mothers during the first three days of their hospital stay. Results showed that the FGR group exhibited reduced folic acid and vitamin B12 levels and elevated homocysteine levels than those in the other two groups. Folic acid and vitamin B12 levels were positively correlated with birth weight, head circumference, and BMI, whereas homocysteine level was negatively correlated with these variables. The FGR ratio in the folic acid and vitamin B12 deficiency group was higher than that in the sufficiency group (χ2 = 4.717 and 4.437, P = 0.029 and 0.035, respectively). In addition, elevated homocysteine was associated with FGR (χ2 = 5.366, P = 0.021). In conclusion, we found that folic acid and vitamin B12 deficiency was associated with elevated homocysteine levels, which may increase susceptibility to FGR.

Observed impacts of insulin therapy on callus cell transforming growth factor-beta 1 expression in diabetic rats.

The expression of transforming growth factor-beta 1 (TGF-ß1) inside the callus cells of diabetic rats and the impact of insulin therapy on its expression and biomechanics was investigated. The rats were randomly divided as follows: an insulin therapy group (IT), a diabetic model group (DM), and a non-diabetic control group (NC). Bone specimens from each group were extracted at different times for immunohistochemical observation of the expression of TGF-ß1. Concurrently, the destruction torque and torsional stiffness were detected at different times. One to four weeks after fracture, TGF-ß1 was widely expressed in fractured callus cells and periosteal proliferating cells, while the expression inside diabetic cells was significantly reduced. The expression of TGF-ß1 decreased over the first 68 weeks, and the mature bone cells never expressed TGF-ß1. The destruction torque (Nm) detected in the 6th week revealed that there was a statistically significant difference between the DM, NC, and IT groups (P < 0.01). In conclusion, TGF-ß1 expression was significantly reduced inside the callus cells of diabetic rats. Insulin therapy increased TGF-ß1 expression inside the callus cells of diabetic rats and improved the biomechanical characteristics of the callus.

Anti-osteoporosis activity of red yeast rice extract on ovariectomy-induced bone loss in rats.

Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high costs. Monacolin K, an extract of red yeast rice (RYR, Hongqu), plays important roles in the management of dyslipidemia, coronary heart disease, and diabetes. Our study aimed to investigate the protective effect of monacolin K on ovariectomy-induced bone loss in rats. Fifty female Sprague-Dawley rats were randomly divided into a sham-operated and five ovariectomized (OVX) groups: OVX with vehicle, OVX with fluvastatin, and OVX with RYR extract of three graded doses. Bone mineral density (BMD), biochemical markers, and cell viability were analyzed by dual energy X-ray absorptiometry, enzyme-linked immunosorbent assay, and 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Gene expression was evaluated by real-time polymerase chain reaction amplification and western blot. Our results showed that administration of RYR extract markedly increased the bone mineral density in OVX rats. Moreover, RYR extract decreased the levels of bone turnover markers, including osteocalcin and tartrate resistant acid phosphatase activity. The MMT assay revealed that RYR extract treatment significantly improved the osteoblast viabilities in a dose-dependent manner (P < 0.05). At the molecular level, we further demonstrated that RYR extract enhanced the expression of Bmp2 and Bmp4 both at the mRNA and protein levels. Collectively, these data suggested RYR extract could protect against osteoporosis in ovariectomized rats, most likely through activation of BMP2/4 expression.

Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients.

Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a complex multifactorial disease. Patients with OPLL commonly present with symptoms in their 40s or 50s. The genetic basis of OPLL remains poorly understood. Exome capture combined with massively parallel DNA sequencing has been proposed as an efficient strategy to search for disease-causing genes of both monogenic and multigenic disorders. To identify candidate pathogenic genes associated with OPLL, we performed whole exome sequencing (WES) on two unrelated southern Chinese OPLL patients. The entire DNA coding region of the candidate genes was amplified by PCR and Sanger sequenced. The common single nucleotide polymorphisms were analyzed by association studies. WES revealed p.T265S/PTCH1, p.P1232L/PTCH1, and p.T902S/COL17A1 mutants in the two female cases with mixed OPLL. These were confirmed by Sanger sequencing. p.P1232L/PTCH1, p.N1374D/COL17A1 and p.T902S/COL17A1 were subsequently identified in three males with continuous OPLL and one female with mixed OPLL. The association studies indicated that the SNPs rs805698 and rs4918079 in COL17A1 were significantly associated with OPLL. This study suggests that WES may be a practical approach to revealing significant genetic involvement in OPLL. Variants of the PTCH1 and COL17A1 genes may contribute to the development of OPLL.

[Related factors of negative conversion time of nucleic acid in children with COVID-19].

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3rd to May 31st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.

[Analysis of withdrawal status and influencing factors in patients receiving methadone maintenance treatment in Hubei province].

Objective: To analyze the withdrawal in patients receiving methadone maintenance treatment (MMT) and its related influencing factors in Hubei province. Methods: The patients receiving MMT in clinics in Hubei province were selected from June 2006 to December 2021. The general demographic data, drug abuse history, and MMT information were collected. The survival data of patients with MMT were analyzed by the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. Results: A total of 26 716 patients receiving MMT were included in this study, and the gender ratio between men and women was 3.34∶1(20 557∶6 159). The duration of MMT was 0.01-15.72 years, and the median duration was 2.21 (95%CI: 2.16-2.26) years. At the end of the follow-up, the withdrawal proportion was 86.75% (23 175/26 716). MMT's 0-year, 2-year, 4-year, 9-year and 14-year cumulative probabilities appeared as 67.61%, 40.24%, 30.03%, 15.49% and 6.56%, respectively. Results from the Cox proportional hazards regression model showed that the factors of the withdrawal risk were higher in patients receiving MMT, including minority nationality (HR=1.66,95%CI:1.52-1.82), having jobs (HR=1.05, 95%CI:1.01-1.08), no history of compulsory isolation or detoxification (HR=1.04, 95%CI:1.01-1.09) and the enrollment in 2016-2021 (HR=1.46,95%CI:1.35-1.58). The factors of the withdrawal risk were lower in patients receiving MMT, including 60-year-olds or above (HR=0.56,95%CI:0.42-0.75), college degree or above education level (HR=0.83, 95%CI:0.75-0.91), outpatient services of other cities (HR=0.90, 95%CI:0.87-0.93), drug use for 20 years or more (HR=0.72, 95%CI:0.66-0.80), 90 mg or more per daily dosage (HR=0.73,95%CI:0.69-0.78) and the enrollment in 2011-2015 (HR=0.93,95%CI:0.89-0.97). Conclusions: The withdrawal proportions of patients receiving MMT were high in Hubei province. The withdrawal influencing factors were complex. The daily dose was an essential factor that can be intervened under the safe MMT condition, and a higher dose should be appropriately prescribed.

Expression of ICAM-1 in placental tissues and the association between its gene polymorphisms and pathogenesis of preeclampsia.

OBJECTIVE: The aim of this study was to explore the expression of intercellular adhesion molecule-1 (ICAM-1) in placental tissues of patients with preeclampsia, and to elucidate the association between its polymorphisms and pathogenesis of preeclampsia. PATIENTS AND METHODS: A total of 100 preeclampsia patients (Preeclampsia group) and 100 normal puerperae (Control group) were selected as research objects. The protein expression of ICAM-1 in placental tissues was detected via Western blotting and immunohistochemical staining. The single nucleotide polymorphisms (SNPs) rs134568, rs128343, and rs201931 in the promoter region of ICAM-1 were typed via conformation difference gel electrophoresis. Chi-square test was used to detect whether the distribution frequency of ICAM-1 genotype was in agreement with Hardy-Weinberg equilibrium. The associations of ICAM-1 alleles and polymorphic sites with pathogenesis of preeclampsia were analyzed as well. Finally, the correlation between GG genotype of ICAM-1 rs134568 and clinicopathological features of preeclampsia was analyzed. RESULTS: The protein expression of ICAM-1 in placental tissues was significantly higher in Preeclampsia group than that in Control group (p<0.05). ICAM-1 SNPs rs134568, rs128343 and rs201931 all met Hardy-Weinberg equilibrium (p>0.05). According to gene correlation analysis, ICAM-1 rs134568 polymorphism and alleles were associated with the pathogenesis of preeclampsia (p<0.05). However, ICAM-1 rs128343 and rs201931 polymorphisms and alleles had no associations with the pathogenesis of preeclampsia (p>0.05). Besides, systolic blood pressure, serum creatinine level and plasma albumin level showed no statistically significant differences between people with GG genotype of ICAM-1 rs134568 in Preeclampsia group and those in Control group (p>0.05). CONCLUSIONS: ICAM-1 expression increased significantly in placental tissues of patients with preeclampsia. In addition, rs134568 in the promoter region of ICAM-1 was associated with the pathogenesis of preeclampsia.

[Application of autologous cartilage in rhinoplasty for patients with traumatic nasal contraction and nasal dysfunction].

Objective: To explore the application and effect of autologous cartilage in rhinoplasty for patients with traumatic hernia and nasal dysfunction. Methods: From January 2017 to April 2019,30 patients with nasal trauma admitted to Department of Otorhinolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University were treated for 6 days to 14 years. All patients were accompanied by different degrees of nasal deformity and nasal ventilatory disorders. They were classified into three categories: light, medium and heavy. All of them were open at the same time. Rhinoplasty and nasal septum deviation correction. For mild to moderate nasal deformity and nasal ventilatory disorders, ear cartilage was used to modify the tip of the nose and strengthen the nasal septal cartilage support to modify the deformity of the nasal back. For severe nasal deformity and nasal ventilatory disorders, we engraved the costal cartilage into a "Y" shaped monolithic stent or flank costal cartilage to form a 2+1 or 4+1 stent, and the costal cartilage stent and the septal cartilage tail end were sutured. Reshape the nasal septum frame support and the nasal column to avoid collapse of the nose. Results: Three patients had a septal hematoma after operation and recovered normally after cleansing. All patients were followed up for 2 months to 2 years, and no complications such as nasal septum perforation and nasal bridge collapse occurred. The postoperative cure rate was 60.0% (18/30). All patients had a grade I nasal drop after surgery, and the effective rate was 100% (30/30). The patient's preoperative measurement deviation was (6.85±2.43) mm, the postoperative measurement deviation was (2.4±1.58) mm, the preoperative nasal appearance VAS score was (1.93±1.31), and the postoperative nasal appearance VAS score was (6.60±1.16), the difference in facial appearance deviation and VAS score before and after surgery was statistically significant (P<0.05). All patients had improved nasal ventilation after operation. The preoperative nasal ventilation VAS score was (1.97±1.07), the postoperative nasal ventilation VAS score was (6.53±1.04), and the difference between preoperative and postoperative nasal ventilation VAS scores was statistically significant (P<0.05). Conclusions: Autologous cartilage is effective in rhinoplasty in patients with traumatic nasal contraction and nasal dysfunction. One stage open rhinoplasty and nasal septum deviation surgery are performed to shorten the treatment time and improve the nasal appearance and nasal ventilation function. The patients got satisfaction.

Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons.

Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (IK) with an IC50 value of 146.0+/-5.8 microM in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of IK and its recovery from inactivation, suggesting that talatisamine had no allosteric action on IK channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific IK channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking IK channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.

Protective effects ROS up-regulation on premature ovarian failure by suppressing ROS-TERT signal pathway.

OBJECTIVE: Premature ovarian failure (POF) refers to the condition of pre-onset ovarian function failure, and is one commonly occurred disease in gynecology. Its pathogenic mechanism, however, is still unclear. Early study found decreased activity of telomerase reverse transcriptase (TERT). As an important factor to suppress TERT, oxidative stress has not been studied in POF. We, thus, investigated the role of reactive oxygen species (ROS)-TERT in POF. MATERIALS AND METHODS: Rat POF model was induced by a single intraperitoneal injection of cyclophosphamide plus 12 mg/kg busulfan. Level of follicle stimulating hormone (FSH) and inhibin B was measured by enzyme-linked immunosorbent assay (ELISA), along with hematoxylin and eosin (HE) staining to confirm successful generation of models. Western blot was applied to measure TERT expression, and N-acetyl-cysteine (NAC) or TERT small interfere RNA (siRNA) was injected to suppress ROS or TERT level, followed by HE staining to observe POF condition. RESULTS: In POF model, ovary tissues showed atrophy, less follicles, and more follicular atresia, plus mesenchymal hyperplasia. FSH and inhibin B level were significantly up-regulated and down-regulated, respectively (p<0.05). In POF rat, ROS level was elevated (p<0.05) whilst TERT level was decreased. NAC inhibited ROS level and enhanced TERT expression. In contrast, TERT siRNA further aggravated POF condition. CONCLUSIONS: ROS up-regulation inhibits TERT expression, suppresses TERT activity and facilitates POF. The ROS-TERT pathway may work as the target for treating POF.

Arachidonic acid attenuates brain damage in a rat model of ischemia/reperfusion by inhibiting inflammatory response and oxidative stress.

The aim of the present study was to study the effects of arachidonic acid (ARA) in a rat brain ischemia/reperfusion model induced by middle cerebral artery occlusion (MCAO). A total of 50 rats were randomly divided into five groups: control group, MCAO group, MCAO + ARA 0.3 g/kg group, MCAO + ARA 1 g/kg group, and MCAO + ARA 3 g/kg group. The MCAO + ARA groups received ARA by intraperitoneal injection daily for 14 consecutive days, while the rats in the control and MCAO groups were given equivalent volume of saline. We detected the Morris water maze test and pathological changes to investigate the ischemia/reperfusion injury. The protein levels of tumor necrosis factor-alpha and interleukin-6 in the hippocampus were detected by enzyme-linked immunosorbent assay kits. In addition, the activities of superoxide dismutase, glutathione peroxidase, and malondialdehyde were assayed in hippocampus homogenates to evaluate the oxidative stress after ischemia/reperfusion. The results indicated that ARA administration decreased biochemical parameters of inflammation and oxidative stress. Morris water maze test and histopathological examination further verified the protective effects of ARA on ischemia/reperfusion injury rats. These findings demonstrated that ARA could protect MCAO-induced brain injury rats by inhibition of inflammation and oxidative stress, suggesting that it may have potential as a therapy for cerebral ischemia/reperfusion injury.

Regulation of adipocyte differentiation by PEGylated all-trans retinoic acid: reduced cytotoxicity and attenuated lipid accumulation.

Obesity is major risk factor for many disorders, including diabetes, hypertension and heart disease. Unfortunately, there is a dearth of therapeutic agents available to clinicians for the treatment of obesity. The principal aim of this study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have favorable stability and biological activity in 3T3-L1 preadipocytes as an antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis, including survival of adipocytes and differentiation to mature adipocytes. The results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200 nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in addition, increased as the level of RA increased from 10 to 20 microM, whereas PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA-NP has potential as an antiobesity drug carrier due to its small particle size and PEGylated core-shell structure. In addition, our results suggest that PRA inhibits the process of adipogenesis and may be developed to treat obesity. Based on these results, PRA is suitable for adipocyte studies, and an enhanced effect of PRA with adipocyte differentiation offers a challenging approach for pharmaceutical applications.

[Scalp surface skin grafts in reconstruction of external auditory meatus in congenital aural atresia].

OBJECTIVE: To investigate the clinical application of scalp skin grafts in reconstruction of external auditory meatus in congenital aural atresia. METHODS: We conducted a retrospective study on 85 patients of congenital aural atresia, all of whom were unilateral, operated from March of 2008 to December of 2010 in ENT department of the Sun Yat-Sen Memorial Hospital. The patients enrolled in the study were between 6 to 37 years old (median age 12 years), 55 male and 30 female. Scalp surface graft in ipsilateral temporal region was harvested to cover the bony external auditory meatus. RESULTS: All of these scalp split-thickness skin grafts survived without necrosis, no restenosis was found in these external auditory meatus. Neither scar nor alopecia was found in the skin-harvesting region, and hairs grew well. Granulations occurred in 27 cases in the first to sixth month posteroperatively, 20 cases recovered after local treatment. In the first year, 30 cases obtained hearing improvement more than 15 dB, 36 cases gained more than 25 dB and 19 cases gained more than 35 dB. Totally 8 patients were lost in the 4 to 5 years of follow-up, 70 cases (70/77, 90.9%) developed new external auditory meatus, 7 cases (7/77, 9.1%) suffered from stenosis in different degrees, but no atresia was found in these patients. CONCLUSION: Scalp split-thickness skin grafts has significant clinical advantage in meatoplasty of congenital aural atresia.

Preparation, characterization and nasal delivery of alpha-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres.

In this study, alpha-cobrotoxin was incorporated into the microspheres composed of poly(lactide-co-glycolide) (PLGA) and poly[1,3-bis(p-carboxy-phenoxy) propane-co-p-(carboxyethylformamido) benzoic anhydride] (P(CPP:CEFB)) and intranasally delivered to model rats in order to improve its analgesic activity. The microspheres with high entrapment efficiency (>80%) and average diameter of about 25 microm could be prepared by a modified water-in-oil-in-oil (w/o/o) emulsion solvent evaporation method. Scanning electron micrograph (SEM) study indicated that P(CPP:CEFB) content played a considerable role on the morphology and degradation of the microspheres. The presence of P(CPP:CEFB) in the microspheres increased their residence time at the surface of the nasal rat mucosa. The toxicity of the composite microspheres to nasal mucosa was proved to be mild and reversible. A tail flick assay was used to evaluate the antinociceptive activity of the microspheres after nasal administration. Compared with the free alpha-cobrotoxin and PLGA microspheres, PLGA/P(CPP:CEFB) microspheres showed an apparent increase in the strength and duration of the antinociceptive effect at the same dose of alpha-cobrotoxin (80 microg/kg body weight).

In vitro and in vivo studies of cyclosporin A-loaded microspheres based on copolymers of lactide and epsilon-caprolactone: comparison with conventional PLGA microspheres.

A hydrophobic peptide, cyclosporin A (CyA), was incorporated in microspheres based on poly(lactide-b-epsilon-caprolactone) (P(LA-b-CL), LA/CL (in molar ratio): 78.7/21.3 and 48.1/51.9) and poly(lactide-co-glycolide) (PLGA, LA/GA: 80/20) using oil-in-water (O/W) emulsion solvent evaporation method. The microspheres were characterized by SEM, DSC and X-ray diffraction, and CyA release rate was determined by HPLC. It was revealed that CyA can be efficiently loaded into all the microspheres (exceed 96%). Compared to PLGA microspheres, P(LA-b-CL) microspheres liberated CyA more rapidly. Within the first day, about 75, 50 and 12% of CyA released from P(LA-b-CL) (48.1/51.9), P(LA-b-CL) (78.7/21.3) and PLGA microspheres, respectively, which can be attributed to the partial crystallization occurring in P(LA-b-CL) microspheres. CyA levels in whole blood were also tested. In comparison with PLGA microspheres, P(LA-b-CL) microspheres provided a higher blood level of CyA. The maximum CyA concentration in whole blood (approximately 520, 450 and 400 ng ml(-1) for P(LA-b-CL) (48.1/51.9) P(LA-b-CL) (78.7/21.3) and PLGA microspheres, respectively) was reached at the second day post administration. And then P(LA-b-CL) microspheres showed a constant CyA level (about 100-200 ng ml(-1)) for extended periods of time (several weeks). Such CyA-loaded P(LA-b-CL) microspheres displaying higher CyA concentration during the first few days and similar constant blood CyA level thereafter showed more advantages than those prepared with PLGA and could meet clinical needs more efficiently.