This study was aimed to confirm animal model and evaluating indicators of the chronic obstructive pulmonary disease combined with pulmonary interstitial fibrosis (PIF-COPD). PIF-COPD rats were induced by intratracheal administration of Bleomycin(BLM, 6 mg·kg-1) and cigarette smoke stimulation for 47 days. After that, the lung function and index were measured. Changes of pathomorphism of lung were observed with hematoxylin-eosin staining. Collagen protein I and III were determined by Sirius red staining. The protein antibody microarray chip was employed for serum cytokine expression pattern measurement. The results showed that in the lung function testing, the central airway resistance, tissue damping, dynamic elasticity of model rats increased significantly and the dynamic compliance reduced significantly. The lung index of model rats increased significantly (compared with the control group, P < 0.01). The pathological tests showed that lung tissues of model rats showed emphysema and fibration with inflammatory infiltration, and content of collagen type I and III increasing significantly. The contents of MMP-8, TIMP-1, IL-10, IL-13, PDGF-AA, Beta-NGF of model rats serum increased obviously compared with the control group and RAGE reduced compared with the normal control. It was concluded that rats which were induced by intratracheal administration of BLM (6 mg·kg-1) and cigarette smoke stimulation for 47 days can be used as animal model establishment of PIF-COPD. The respiratory function and serum levels of MMP-8, TIMP-1, IL-13, PDGF and NGF can be used as evaluating indicators of PIF-COPD model.

AIM: To research Fufang Jingshu Tablet's(Rhizoma Chuanxiong,Radix Angelicae Dahuricae,Rhizoma Gastrodiae,Rhizoma Cibotii,Flos Chrysanthemi) pharmacological effect. METHODS: We used carrageenan-induced rat foot edema model and cotton pellet-induced granuloma model to observe the tablet's effect on inflammation,used analgesymeter to assess normal rats' and sciatic-nerve-stem-ligation rats' mechanical withdrawal thresholds,used inclined plane methods to assess the tablet's effect on general extremity strength of sciatic-nerve-stem-ligation model. RESULTS: The tablet could obviously reduce carrageenan-induced foot edema and cotton pellet-induced granuloma,elevate normal rats' mechanical withdrawal thresholds and decrease percent change of mechanical threshold of ipsilateral hind paws,elevate sciatic-nerve-stem-ligation rats' staying angle on inclined plane. CONCLUSION: Fufang Jiangshu Tablet has significant anti-inflammatory and analgesic effects. Furthermore it can improve the movement disfunction stemed from nerve compression significantly.

This article was aimed to study effect of D-ribose on the high-energy phosphate metabolism of skeletal muscle tissues of tired mice. The model was made by burden swimming. And then, the mice were divided into four groups, which were the model group, D-ribose group, caffeine group, and D-ribose with caffeine group). Intragastric administrations of drugs were given to all mice in four groups, three times per day. And all mice continued to swim for three days. The time of swimming was recorded. Gastrocnemius of mice were removed after swimming or 3 days later to measure the concentration of ATP, ADP, AMP and IMP with the HPLC. The results showed that compared with the control group, the time of burden s wimming was significantly prolonged for mice in the D-ribose group and the D-ribose with caffeine group. After three-day recovery, the concentration of ATP, AMP and IMP of gastrocnemius in the D-ribose group and the D-ribose with caffeine group mice was significantly increased. There was no significant difference in the caffeine group mice. It was concluded that D-ribose is involved in the high-energy phosphate metabolism of skeletal muscle tissues of tired mice . D-ribose promotes the recovery of ATP concentration in the gastrocnemius of tired mice, and prolongs the time of burden swimming. Therefore, it has a certain anti-fatigue effect .

ObjectiveTo research the intestinal absorption characteristics in rats of multiple constituents,when Wuwei-Jiangya recipe was used in rats and showed reducing blood pressure effects.Methods ① After extracting Wuwei-Jiangya recipe,we fed it to rats once daily,until the blood pressure reduced; ②Establish Wuwei-Jiangya recipe and intestinal absorption of multiple constituents fingerprint by using reverted gut sac method and RP-HPLC fmgerprint.ResultsAfter one week's administration,there was the hypotensive effects and multiple constituents can be absorbed by intestine.ConclusionWhen the drug works,reverted gut sac method for studying intestinal absorption constituents can be used for locking the exposure constituents.

OBJECTIVETo evaluate the clinical value of multicolor melting curve analysis(MMCA) for detecting genetic mutations in G6PD deficiency.

METHODSA total of 402 peripheral blood samples(256 males and 146 females) were collected from suspected patients or their relatives at the Prenatal Diagnosis Center of Liuzhou Maternal and Child Health Hospital between March 2012 and May 2012. The samples were screened by G6PD/6PGD quantitative ratio testing. The reliability of the assay was evaluated by multiplex probe melting curve assay(which can detect 16 G6PD mutations) and DNA sequencing through a double blind study.

RESULTSOne hundred seventy cases with G6PD/6PGD ratio < 1.0 and 232 cases with G6PD/6PGD ratio ≥ 1.0 were detected by the enzymological method. DNA sequencing has identified 182 wild type samples, 151 hemizygous mutation samples, 5 female homozygous mutation samples, 54 female heterozygous mutation samples and 10 female double heterozygous mutation samples. Multicolor melting curve analysis has detected 185 wild type samples, 148 hemizygous mutation samples, 5 female homozygous mutation samples, 55 female heterozygous mutation samples and 9 female double heterozygous mutation samples. The specificity and sensitivity of G6PD gene mutation detection by multicolor melting curve analysis were 100%(182/182) and 98.6%(217/220), respectively. The positive predictive value and negative predictive value were 99.5%(216/217) and 98.4%(182/185), respectively, and the Youden's index was 0.986. The concordance rate of the sample detection between the melting curve assay and DNA sequencing was 99.0%(398/402). Twenty-one different genotypes were detected by the multicolor melting curve analysis and 24 different genotypes were detected by DNA sequencing. Four samples containing mutations(c.196T>A or c.406C>T) were not detected by multicolor melting curve analysis, which can be attributed to different technical settings of the two methods.

CONCLUSIONMulticolor melting curve analysis for G6PD gene mutation detection is a simple, rapid, sensitive and specific method, which can be used for clinical diagnosis of G6PD deficiency.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Glucosephosphate Dehydrogenase ; genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment