As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

Objective:To analyze the causes of death of elderly inpatients,so as to provide direction for the precaution of geriatrics.Methods:The first page data of hospitalized medical records of elderly inpatients in medical department in the Second Hospital of Dalian Medical University from 2102 to 2019 were extracted, and the causes of death were analyzed. The statistical analysis was performed by Excel and SPSS 21.0 statistical software.Results:The number of deaths of elderly inpatients in medical department from 2012 to 2019 was 5 249. The proportion of deaths in ICU was 34.43%(1 807/5 249), in oncology department was19.03%(999/5 249), and in cardiovascular department was12.08%(634/5 249). The average age was (78.52 ± 7.82) years. Besides, the age of men was younger than women: (78.18 ± 8.00) years vs. (79.02 ± 7.52) years, and the differences was statistically significant ( P<0.01). Men(59.1%, 3 099/5 249) were more than women (40.96%, 2 150/5 249). The largest number of deaths was in the age of 75-84 years (42.56%, 2 234/5 249). The number of cases with combined above five diseases was 4 552(86.72%, 4 552/5 249). The top three causes of deaths of elderly inpatients in medical department from 2012 to 2019 were cardiocerebrovascular diseases (27.21%, 1 428/5 249), malignant tumor (25.74%, 1351/5 249) and respiratory system diseases (22.10%, 1160/5 249). From 2012 to 2015, the top three causes of deaths were malignant tumor, cardiocerebrovascular diseases and respiratorysystem diseases. From 2016 to 2019,the top three causes of deaths were cardiocerebrovascular diseases, malignant tumor, and respiratory system diseases. The most common cause in cardiocerebrovascular diseases of death was coronary heart disease (51.47%,735/1 428), cerebrovascular disease (43.70%,624/1 428),and hypertension(4.34%, 62/1 428). Among the patients with malignant tumor death, first cause of death waslung malignant tumor (37.53%, 507/1 351), the others in turn were gastric carcinoma (11.10%,150/1 351) and intestinal cancer (11.10%,150/1 351). Among the patients with respiratory system diseases, first cause of death was pulmonary infection (69.66%,808/1 160), the others in turn were chronic obstructive pulmonary disease (15.43%, 179/1 160) and interstitial lung disease (5.09%, 59/1 160). Conclusions:The average age of elderly inpatients in medical department is (78.52 ± 7.82) years. The death age of male is less than that of female, and the number is slightly more than that of female. The top three causes of deaths of elderly inpatients in medical department are cardiocerebrovascular diseases, malignant tumor, respiratorysystem diseases. From 2012 to 2015 the first cause of deaths is malignant tumor. From 2016 to 2019, the cardiocerebrovascular diseases rise to the first.

Three compounds were isolated from the extract of Taxus cuspidta Sibe et Zucc with the column chromatography on silica gel and preparative HPLC methods. Their structures were identified according to the physicochemical properties and spectral analysis, and they were identified as (E)-1-methoxy-2-O-(p-coumaroyl)-myo-inositol (1), 2-deacetoxy-7beta, 9a, 10beta-trideacetyltaxinine J (2) and (3aS, 4aR, 6S, 8S, 8aS, 9R, 10R, 10aS)-benz[f]azulene-6, 8, 9, 10 (3H)-terol, 3a, 4, 4a, 5, 6, 7, 8, 8a, 9, 10-decahydro-10a-(1-hydroxyl-1-methylethyl)-1, 8a-dimethyl-5-methylene (3). Among them, compound 1 was a new compound, and compounds 2, 3 were two novel natural products.
Azulenes ; chemistry ; isolation & purification ; Coumarins ; chemistry ; isolation & purification ; Inositol ; analogs & derivatives ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry ; Taxoids ; chemistry ; isolation & purification ; Taxus ; chemistry

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

OBJECTIVETo investigate the feasibility of peptide mass fingerprinting for non-invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA nephropathy (IgAN).?

METHODSAccording to the results of renal biopsy, 56 patients were divided into IgAN group (n=28) and non-IgAN group (n=28), and peptide mass fingerprints were acquired from these patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

RESULTSNine different peptides were identified between IgAN and non-IgAN. The two most distinctive differentially expressed peptides, with peptide peak values of 4476.46 and 1968.10, showed area under curve values of 86.18% and 79.77%. Principal component analysis demonstrated that the accumulated explained variance of the first 8 differential peptides reached 95%, suggesting the feasibility of differential diagnosis of IgAN from non-IgAN. Comparison with the Matrix protein database identified the peptide with a relative molecular mass of 5338.08 as a fragment of mucin 4 inform and the 2082.77 peptide as fragment of α1-II type collagen inform.

CONCLUSIONMALDI-TOF MS is feasible for differential diagnosis of IgAN and non-IgAN and also has great potentials in the classification of the subtypes of other systemic diseases.

Adult ; Diagnosis, Differential ; Feasibility Studies ; Female ; Glomerulonephritis, IGA ; diagnosis ; Humans ; Kidney Diseases ; diagnosis ; Male ; Middle Aged ; Peptide Mapping ; methods ; Peptides ; chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; Young Adult

OBJECTIVETo study expression of proto-oncogenes c-fos and its accompanying gene c-jun in osteoblasts activated by action of excessive fluoride in vivo and in vitro.

METHODSExperimental Wistar rats were exposed to sodium fluoride (NaF) added to their drinking water, and NaF was also added in cell culture supernatant for osteoblast-like cells in vitro. Expression of both mRNA and protein of c-fos and c-jun in bone-tissue of rats with chronic fluorosis and cultured osteoblast-like cells were determined by hybridization in situ, Western blot and immunohistochemistry at varied time periods after exposure.

RESULTSSodium fluoride could stimulate the proliferation of osteoblast in rats with chronic fluorosis and induce expression of both c-fos and c-jun in all envelops of the spine bone, as compared with its control group. Value of optical absorption in mRNA expression of c-fos and c-jun was 139.63 and 126.37, respectively, in rats with NaF plus high-calcium, significantly lower than that in control group with high-calcium only (107.74 and 117.48, respectively) (P < 0.001). Immunohistochemical analysis showed that protein level of c-fos and c-jun was significantly higher in rats with NaF plus high-calcium than that in control rats with high-calcium only, with values of optical absorption of 139.16, 131.15, 149.98 and 149.19 (P < 0.05), respectively, and protein level of c-fos and c-jun was significantly higher in rats with NaF plus low-calcium than that in control rats with low-calcium only, with values of optical absorption of 117.24, 111.46, 132.46 and 129.79 (P < 0.05), respectively. Western blotting showed that level of protein expression of c-fos and c-jun in periosteal osteoblasts was significantly higher in all rat groups with NaF than that in all control groups, with values of optical absorption of 123.32, 116.60, 115.97 and 108.30, respectively. mRNA expression of c-fos and c-jun in osteoblast-like cells treated with NaF for 12 h increased obviously, and remained at high level 48 h after exposure, with values of optical absorption of 114.80, 161.14, 118.20, and 150.41, respectively, as compared with that in control group (P < 0.001 and P < 0.05).

CONCLUSIONSExposure to excessive fluoride could stimulate activation and proliferation of both osteoblasts in rats and cultured osteoblast-like cells in vitro, and cause enhanced expression of mRNA and protein of both c-fos and c-jun. Over-expression of c-fos could play an important role in development and proliferation of skeletal lesions in rats with chronic fluorosis.

Animals ; Bone Diseases ; metabolism ; pathology ; Calcium ; pharmacology ; Cell Division ; drug effects ; Cells, Cultured ; Female ; Fluoride Poisoning ; metabolism ; pathology ; Gene Expression ; Male ; Osteoblasts ; cytology ; metabolism ; Proto-Oncogene Proteins c-fos ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-jun ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Sodium Fluoride ; pharmacology

Objective To understand the drug resistance of Mycobacterium tuberculosis(MTB)and susceptibility of multidrug-resistant MTB(MDR-MTB)to linezolid in Hebei Province, so as to guiding clinical treatment of MDR tuberculosis.Methods The isolated strains and clinical information of patients with tuberculosis in 6 hospitals of 5 cities in Hebei Province between January and December 2016 were collected, susceptibility of MTB to antituberculous drugs isoniazid(INH), rifampicin(RFP), streptomycin(SM), ethambutol(EMB), ofloxacin(OFX), and kanamycin(KM)were detected, 100 strains of MDR-MTB were selected by stratified random sampling method, susceptibility to linezolid was detected.Results Drug resistance rate and MDR rate of the initially treated cases were 26.6％(200/753)and 13.5％(102/753)respectively, drug resistance rate and MDR rate of the retreatment cases were 59.7％(132/221)and 53.4(118/221)respectively, drug resistance rate and MDR rate of the retreatment cases were both statistically higher than initially treated cases(χ2=83.7, P＜0.01;χ2=93.5, P＜0.01).Resistance rates of MTB to first-line antituberculous drugs INH, RFP, SM, and EMB were 25.8％, 23.7％, 16.7％, and 7.1％ respectively, to second-line antituberculous drugs OFX and KM were 4.7％(37/782)and 4.0％(31/782)respectively; susceptibility of MDR-MTB to linezolid was 80.8％ (59/73).Conclusion Drug resistance rate and MDR rate of the retreated tuberculosis patients are higher than initially treated patients, linezolid has good in vitro antimicrobial activity against MDR-MTB.

Objective To study the distribution of chronicles in formulae and set prescriptions and its reasons ac-cording to their source information.Methods After a standard table of formulae and set prescriptions sources was es-tablished according to the data of documented formulae and set prescriptions, their similarity was sequenced by measuring the edit distance using the string similarity algorithm. After it was checked, the chronicles of formulae and set prescriptions were calculated according to their documented first publication year.Results The emergence and development of formulae and set prescriptions were related with the laws of social stability and wars. The calcu-lated chronicles of formulae and set prescriptions were reliable.Conclusion Sequencing the similarity of formulae and set prescriptions can determine their emergence time, which is thus of great significance for calculating their dosages and may become supplementary method for abstracting information from the formulae and set prescriptions in the past dynasties.

BACKGROUNDAspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice.

METHODSThirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed.

RESULTSIn the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 ± 12.31 ng/g vs. 74.10 ± 11.45 ng/g, P = 0.027; sperm number: [14.94 ± 4.63] × 106 cells/ml vs. [8.79 ± 4.38] × 106 cells/ml, P = 0.002; sperm motility: 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 ± 11.01 ng/ml vs. 49.30 ± 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 ± 0.09 vs. 0.84 ± 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 ± 8.67, P = 0.005; sperm number: [4.34 ± 2.45] × 106 cells/ml, P = 0.018; sperm motility: 19.53 ± 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 ± 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 ± 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 ± 0.09, P < 0.001), and fertility was also suppressed (P < 0.05, respectively).

CONCLUSIONSKRBT had no adverse effect on fertility potential in aging male mice.

Aging ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Fertility ; drug effects ; Hypogonadism ; drug therapy ; Male ; Mice ; Nuclear Proteins ; analysis ; Sperm Count ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; Testis ; drug effects ; pathology ; Testosterone ; blood

To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.
Excipients ; chemistry ; Gels ; chemistry ; Polyethylene Glycols ; chemistry ; Polyvinyls ; chemistry ; Povidone ; chemistry ; Rheology ; Temperature ; Viscosity