In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.

Abstract: Objective　This article summarizes the clinical characteristics and diagnosis and treatment experience of an elderly patient infected with Omicron variant BA.5.1.3 of COVID-19 in Hainan Province. Methods　The clinical data and treatment of an elderly patient infected with Omicron variant BA.5.1.3 of COVID-19 admitted to Haikou designated hospital on August 15, 2022 were retrospectively analyzed. Results　A 107-year-old female patient was admitted to the hospital with "fever and cough for 1 day". Two of her family members have infected with COVID-19. The patient initially developed fever, accompanied by cough, expectoration, a little white sticky sputum, accompanied by sore throat, muscle pain, fatigue. Nucleic acid test was positive in throat swab, indicating Omicron variant BA.5.1.3 infection. The patient was diagnosed as mild COVID-19 and treated with antiviral therapy, Chinese medicine conditioning, anticoagulation, electrolyte disorder regulation and symptomatic treatment for 9 days. The patient's clinical symptoms were relieved, and she was cured and discharged after two negative nucleic acid tests. One week later, the patient recovered well. Conclusions　Omicron variant BA.5.1.3 is highly infectious, and comprehensive treatment such as antiviral treatment and traditional Chinese medicine treatment has achieved good efficacy. For elderly patients, attention should be paid to maintaining the stability of organ function and internal environment, which is helpful to improve the prognosis of patients.

Objective To assess the association between NOD2 gene single nucleotide polymorphisms (SNPs) and leprosy in Chinese Yi population.Methods Whole blood samples were obtained from 300 patients with leprosy and 300 healthy human controls of Yi nationality in Sichuan province.Genomic DNA was extracted,and a SNaPshot assay was performed to determine the genotypes of four single nucleotide polymorphisms (SNPs) of the NOD2 gene,including rs9302752,rs7194886,rs8057341 and rs3135499.Chi-square test was conducted to compare allele frequency,and Hardy-Weinberg equilibrium was tested.Results The genotype distribution of all the four SNPs was consistent with Hardy-Weinberg equilibrium (all P ＞ 0.05).Significant differences were observed between the patients with leprosy and healthy controls in both genotype distribution and allele frequency of the SNP rs3135499 (both P ＜ 0.01),but not in those of the other three SNPs (all P ＞ 0.05).Conclusion The SNP rs3135499 of the NOD2 gene may be associated with the development of leprosy in Chinese Yi population.

In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.
Animals ; Antineoplastic Agents ; chemistry ; Biotin ; Drug Carriers ; chemistry ; Drug Screening Assays, Antitumor ; Humans ; Micelles ; Pancreatic Neoplasms ; drug therapy ; Photochemotherapy

BACKGROUNDThe goal of surgery in the treatment of intrinsic cerebral tumors is to resect the maximum tumor volume, and to spare the eloquent areas. However, it is difficult to discover the eloquent areas intraoperatively due to individual anatomo-functional variability both for sensori-motor and language functions. Consequently, the surgery of intrinsic cerebral tumors frequently results in poor extent of resection or permanent postoperative deficits, or both, and remains a difficult problem for neurosurgeons.

METHODSFrom January 2003 to January 2010, 112 patients with neuroepithelial tumors in/close to the eloquent areas were operated on under awake anesthesia with the intraoperative direct electrical stimulation for functional mapping of the eloquent areas. The extent of the tumors was verified by intraoperative ultrasonography. The maximal resection of the tumors and minimal damage of the eloquent areas were the surgical goal of all patients.

RESULTSTotally 356 cortical sites in 99 patients were detected for motor response by intraoperative direct electrical stimulation, 50 sites in 16 patients for sensory, 72 sites in 48 patients for language. Sixty-six patients (58.9%) achieved total resection, 34 (30.4%) subtotal and 12 (10.7%) partial. Fifty-eight patients (51.8%) had no postoperative deficit, while 37 patients (33.0%) had transitory postoperative paralysis, 26 patients (23.2%) with transitory postoperative language disturbance and 3 patients (2.7%) with permanent neurological deficits. No patient complained of pain recollection following operation.

CONCLUSIONSAwake anesthesia, intraoperative direct electrical stimulation and ultrasonography are three core techniques for the resection of intrinsic cerebral tumors near the eloquent areas. This new concept allows an improvement in the quality of surgery for neuroepithelial tumors in/adjacent to eloquent areas.

Adolescent ; Adult ; Aged ; Anesthesia ; methods ; Brain Mapping ; methods ; Brain Neoplasms ; diagnostic imaging ; surgery ; Deep Brain Stimulation ; methods ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Neuroepithelial ; diagnostic imaging ; surgery ; Ultrasonography

OBJECTIVE15-lipoxygenase (15-LO) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Gene expression profiling studies show the association between 15-LO and allergic asthma. This study was designed to observe the expression of 15-LO in lungs of asthmatic rats and examine the effects of dexamethasone on 15-lipoxygenase expression.

METHODSTwenty-seven male Sprague-Dawley (SD) rats were randomly divided into three groups: control, asthma and dexamethasone (DXM) intervention. An asthma model was prepared by sensitization and challenging with ovalbumin. The production of 15-LO in lung tissue homogenates was measured using ELISA.The expression of 15-LO mRNA in lungs was determined by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSThe levels of 15-LO mRNA and protein in the asthma group (0.51 ± 0.14 and 2080 ± 73 μg/mL, respectively) were lower than those in the control group (0.76 ± 0.15 and 2472 ± 106 μg/mL, respectively; P<0.01). DXM intervention increased significantly the levels of 15-LO mRNA and protein (1.02 ± 0.34 and 2562 ± 218 μg/mL) compared with the asthma group (P<0.01).

CONCLUSIONSThe production of 15-LO in lung tissues is reduced in asthmatic rats. DXM can increase the expression of 15-LO in lung tissues and thus might provide anti-inflammatory effects in asthmatic rats.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Arachidonate 15-Lipoxygenase ; analysis ; genetics ; Asthma ; drug therapy ; enzymology ; Dexamethasone ; pharmacology ; Lung ; enzymology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Directed evolution strategy (error-prone PCR) was conducted to improve the activity of lipase from Rhizopus chinensis CCTCC M201021. Through two rounds of ep-PCR and pNPP top agar screening, two optimum mutant strains 1-11 and 2-28 were obtained with 2 and 4 fold of enzyme activity higher than that of parent strain, respectively. DNA sequencing of mutant lipase 2-28 revealed four amino acid substitutions: A129S, K161R, A230T, K322R. According to the simulated protein structure of Rhizopus chinensis lipase, A129S, K161R, A230T were located on the surface of the protein. A230T substitution improved the stability of the alpha-helix loop. K322R, near the catalytic center of lipase, located at a loop, formed a salt-bridge with a nearby aspartic acid (negative charged). Electrostatic force pulled the loop to the opposite direction of the substrate channel and made it easier for substrate to enter the lipase catalytic domain. Purified lipase was characterized and the result showed that Km of 2-28 lipase decreased by 10% compared with Km of the parent lipase, and Kcat was 2.75 fold improved than that of the original lipase.
Directed Molecular Evolution ; Lipase ; chemistry ; genetics ; Point Mutation ; Protein Engineering ; Rhizopus ; enzymology ; genetics

OBJECTIVETo study the role of urotension-II in serum and bronchoalveolar lavage fluid (BALF) in the process of airway remodelling in asthmatic rats.

METHODSThirty-two male Sprague-Dawley (SD) rats were randomly divided into normal control and 2-week, 4-week and 8-week asthmatic groups (OVA inhalation of 2, 4 and 8 weeks respectively). Rats were sensitized and challenged by OVA to establish a model of asthma. The bronchial wall thickness and the airway smooth muscle thickness were measured by image analysis system. The urotension-II contents in serum and BALF were determined using ELISA.

RESULTSThe bronchial wall thickness and the airway smooth muscle thickness in the three asthmatic groups significantly increased compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the three asthmatic groups also increased significantly compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the 8-week asthmatic group were the highest, followed by the 4-week and the 2-week asthmatic groups (P<0.01). BALF urotension-II contents were positively correlated with the bronchial wall thickness and the airway smooth muscle thickness as well as serum U-II contents in the four groups.

CONCLUSIONSThe urotension-II contents in serum and BALF in the process of airway remodeling increase in asthmatic rats. The changes in serum and BALF urotension-II contents may be associated with airway remodeling in asthmatic rats.

Airway Remodeling ; Animals ; Asthma ; metabolism ; pathology ; Bronchi ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Male ; Muscle, Smooth ; pathology ; Rats ; Rats, Sprague-Dawley ; Urotensins ; analysis ; blood

OBJECTIVETo investigate the prevalence of rheumatic heart disease (RHD) among schoolchildren in Guangdong Province and Xinjiang Uygur Autonomous Region.

METHODSUsing a cluster sampling method, an epidemiological survey of RHD was conducted in 16 682 primary and high school students by auscultation in Guangdong Province and Xinjiang Uygur Autonomous Region from 2005 to 2006. Review of the clinical records, RHD survey in adults, and examination of the positivity rate of group A beta-hemolytic Streptococcus (GAS) by throat swab cultures in the students aged between 9 and 12 years in the sampled schools were also carried out.

RESULTSNo RHD patient was found in the sampled population. In Xinjiang, the prevalence of RHD was 12.9/1000 among adults, higher than that (2.2/1000) in Guangdong Province. The GAS-positive rate in the schoolchildren in Xinjiang ranged from 9.8% to 12.6%, higher than that in Guangdong (2.3%-3.9%).

CONCLUSIONThe GAS-positive rate among children and incidence of RHD in adults are higher in Xinjiang than in Guangdong. The prevalence of RHD among the schoolchildren shows a reduction compared with that in 1994.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cluster Analysis ; Female ; Heart Valve Diseases ; epidemiology ; Humans ; Male ; Mass Screening ; Prevalence ; Rheumatic Heart Disease ; epidemiology ; microbiology ; prevention & control ; Streptococcal Infections ; epidemiology ; Streptococcus agalactiae

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Membrane Transport Proteins ; genetics ; Middle Aged ; Mutation ; genetics ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Spastic Paraplegia, Hereditary ; genetics ; Young Adult