AIM To investigate the effects of iptakalim hydrochloride(Ipt) on the association and dissociation kinetic processes of [ 3H]glibenclamide(Gli) binding with sulfonylurea receptor(SUR 2B ) of ATP sensitive potassium channel (K ATP ) in vascular smooth muscles derived from Wistar rats,and to compare the properties of Ipt with those of nucleotides. The interactions between Ipt and nucleotides were also determined. METHODS The experiments of the association and dissociation kinetic processes of K ATP blocker[ 3H]Gli binding with endothelium denuded aorta smooth muscles were used. RESRLTS (1)The specific bindings of[ 3H]Gli with SUR 2B were not displaced by Ipt at the concentrations of 10 pmol?L -1 ～ 0 5 mmol?L 1 . Ipt 100 ?mol?L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of [ 3H]Gli binding with SUR 2B . (2)Opposite to Ipt, ATP 1 mmol?L -1 accelerated the association kinetic process and retarded the dissociation kinetic process of [ 3H]Gli binding with SUR 2B There was an interaction between ATP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B . (3) Similar with Ipt, ADP 1 mmol?L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of [ 3H]Gli binding with SUR 2B , there was an interaction between ADP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B . (4)Different from ATP and ADP, UDP had no effect on the association and dissociation kinetic process of [ 3H]Gli binding with SUR 2B . And there was not interaction between UDP and Ipt. CONCLUSION Ipt had no affinity with the binding sites of K ATP blocker in SUR 2B , but had negative allosterical modulation on it. The modulatory properties of Ipt were opposite to those of ATP, similar with those of ADP and different from those of UDP. There were interactions between ATP, ADP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B , but there was not interaction between UDP and Ipt.

ObjectiveTo investigate a cluster epidemic of coronavirus disease 2019 （COVID-19） infections in a school in Longchuan County， Yunnan Province， and further guide the prevention and control of COVID-19 in the border area. MethodsAccording to the Protocol on Prevention and Control of Novel Coronavirus Pneumonia （8th Edition）， an epidemiological investigation was performed on all COVID-19 cases to collect the information on demographics， onset， diagnosis and treatment， prognosis， and epidemiological history. Close contacts were also tracked to determine the transmission chains. ResultsIn this cluster epidemic， a total of 37 COVID-19 cases were identified， including 32 females and 5 males aged from 13 to 25 years， who were 35 students and 2 teachers. The student cases were found in four classes of two grades. Furthermore， gene sequencing showed that all cases had been infected with delta variants， belonging to the same transmission chain that was not related to the previous epidemics in Dehong Prefecture. In additionally， a total of 2 127 close contacts were found. After 21 days of centralized quarantine for medical observation， all close contacts tested negative for SARS-CoV-2. In the COVID-19 cases， only one case remained positive for SARS-CoV-2， while the other 36 cases were successfully treated and became negative. ConclusionThis school cluster is caused by the border villagers who contacted the water polluted with SARS-CoV-2. It warrants more strict management of students from border villages and their belongings to prevent similar epidemics in school settings.

BACKGROUNDAllergic asthma is a chronic airway inflammatory disease partly characterised by high concentration of T help 2 (Th2) cytokines in bronchoalveolar lavage fluid (BALF). There is no report on the relation of peripherally circulating blood lymphocytes and asthma. We explored the balance of Th2/Th1 cytokines in asthmatic mice. Exogenous recombinant interleukin (IL) 33 acted on murine peripheral circulating blood lymphocytes, IL-5 cytokine was selected for assessing Th2 cytokines and interferon-gamma (IFN-γ) for Th1 cytokines.

METHODSFemale specific pathogen free BABL/c mice were sensitised by intraperitoneal injection of 20 µg of ovalbumin emulsified in 1 mg of aluminium hydroxide gel in a total volume of 200 µl, and challenged for 30 minutes in 7 consecutive days with an aerosol of 2 g ovalbumin in 100 ml of PBS. Then we collected BALF and isolated lymphocytes from the peripheral blood. The lymphocytes were divided into two groups: asthmatic group and normal group. Th1/Th2 cytokines was detected by enzyme-linked immunosorbent assay (ELISA) kits.

RESULTSIn the asthma group, we found numerous eosinophils and lymphocytes on the glass slides. We then confirmed that the optimal concentration of IL-33 was 10 ng/ml and time of IL-33 stimulating lymphocytes was 24 hours. In the asthma group, the production of IL-5 was significantly increased over normal group after stimulation with IL-33 (P < 0.05) and the production of IFNγ was supressed from IL-33 stimulated lymphocytes (P < 0.05).

CONCLUSIONIL-33 acts on lymphocytes of peripheral blood increasing secretion of Th2 cytokines and inhibiting secretion of Th1 cytokines.

Animals ; Asthma ; chemically induced ; immunology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Interferon-gamma ; immunology ; metabolism ; Interleukin-33 ; Interleukin-5 ; immunology ; metabolism ; Interleukins ; immunology ; metabolism ; Lymphocytes ; immunology ; metabolism ; Mice ; Mice, Inbred BALB C

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNF (CHX/TNF)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.

To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

A fluorescein-labeled polyglutamic acid-based polyamino acid dexamethasone nanohydrogel was synthesized, and its gelation time was measured. The hydrogel was surgically injected into the round window niche of guinea pigs to determine its degradation time in the middle ear cavity in vivo. The safety, pharmacokinetics, and distribution patterns of dexamethasone in the inner ear were evaluated.

The hydrogel exhibited a gelation time of 80 seconds in a 37℃ water bath. In vivo, the hydrogel was almost completely degraded within 7 days in the middle ear cavity of guinea pigs. Transient hearing loss was observed one day after administration, but hearing gradually returned to normal over time. No significant cytotoxicity, vestibular stimulation signs, or pathological abnormalities in spiral ganglion cells were observed. Histopathological examination revealed no significant inflammatory reactions. Pharmacokinetic analysis demonstrated sustained drug release and prolonged dexamethasone activity. Immunofluorescence staining confirmed the distribution of dexamethasone in both the cochlea and vestibular organs.

The polyamino acid nanohydrogel exhibits excellent injectability and biodegradability, representing a safe and effective drug delivery system for the inner ear.