Objective: In this paper the pharmacodynamical mechanism of Heat Asthma Formula(HAF)(Herba Ephedrae, Rhizoma pinelliae, Flos Lonicerae, etc) in the treatment of bronchial asthma was discussed. Methods: By means of the radio labelled aglycone, applying phlogistic medium TXB2, ? receptor on bronchus and cyclic nucleotide (cAMP/cGMP) in lung tissue used as observed targets. Results: The results showed HAF could inhibit the release of phlogistic medium TXB2, improve the conjugate rate of ? receptor, adjust the proportion between cAMP and cGMP. Conclusion: The treatment on bronchial asthma of “Heat Asthma Formula” was perhaps concerned with above mentioned contents.

Objective To prospectively evaluate the sensitivity and specificity of ankle brachial index (ABI) in the diagnosis of lower extremity arterial disease(LEAD)by using conventional digital subtraction angiography (DSA) as the reference standard, and to research the threshold value of ABI screening test for diagnosis. Methods A total of 383 consecutive patients (245 men and 138 women, mean age (64.1±11.7) years] underwent conventional DSA and ABI measurement. Receiver operator characteristics (ROC) analysis was performed to assess possible threshold values for predicting the LEAD in these patients. Results Conventional DSA was used as the gold standard in defining≥50% luminal stenosis for the diagnosis of LEAD. 0. 95 was the overall cutoff of ABI which was associatcd with 93.0% sensitivity, 85.0% specificity, 8.81 positive likelihood ratio(+LR) and 0. 23 negative likelihood ratio(-LR) for detection of hemodynamically significant stenosis (lesions>≥50%) in all 383 subjects (P<0.01). The area under the ROC curve was 0. 953(95%CI 0.920～0.985). Conclusions ABI measurement is an accurate and reliable non-invasive alternative to conventional DSA in the diagnosis of lower extremity arterial disease. And the cut-off 0.95 is the threshold ABI value for detecting LEAD in Chinese population.

Objective:To evaluate the epidemiology of bacterial bloodstream infections in patients submitted to hematologic wards in southern China.Methods:A total of 50 teaching hospitals were involved based on the China Antimicrobial Resistance Surveillance System. The data of clinical isolates from blood samples were collected from January 1, 2019, to December 31, 2019. Antimicrobial susceptibility testing was conducted by the Kirby-Bauer automated systems, and the results were interpreted using the CLSI criteria.Results:The data of 1,618 strains isolated from hematologic wards in 2019 were analyzed, of which gram-negative bacilli and gram-positive cocci accounted for 71.8% and 28.2%, respectively. Of those, the five major species were most often isolated, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, coagulase-negative staphylococcus, and Streptococcus viridans. The prevalence rates of methicillin-resistant strains in Staphylococcus aureus and coagulase-negative staphylococcus were 19.7% and 80.6%, respectively. No gram-positive cocci were resistant to vancomycin, linezolid, and teicoplanin, and none of the enterococci were resistant to linezolid. The resistance rate of S. viridans to penicillin G was 6.9%, and those to ceftriaxone and cefotaxime were more than 25%. The resistance rate of E. coli and K. pneumoniae in Enterobacteriaceae was higher in children than that in adults. The resistance rate of K. pneumoniae to meropenem was 14.1%. The resistant rate of Enterobacter cloacae to carbapenem was more than 25%. P. aeruginosa was more sensitive to more antibiotics than 80%, but the resistance rate to meropenem in children was higher than that in adults (11.8% vs. 6.5%). The proportion of gram-positive cocci in the ICU and respiratory departments was higher than that in the hematology department. The detection rates of carbapenem-resistant E. coli and K. pneumoniae in the respiratory department were the lowest with 0.3% and 3.7%, respectively, while those of CRPA and CRAB in the hematology department were the lowest with 8.3% and 25.8%, respectively. The detection rate of all carbapenem-resistant organisms in the ICU was the highest among the three departments.Conclusion:The etiology and drug resistance of bacteria from blood samples in the hematology department are different from those in the ICU and respiratory departments. The proportions of K. pneumoniae, P. aeruginosa, E. cloacae, and S. viridans dominating in the department of Hematology were significantly higher than those in the ICU and respiratory departments in Guangdong region.

OBJECTIVES: This study aimed to explore the functions and potential regulatory targets of local macrophages in nonalcoholic fatty liver combined with Porphyromonas gingivalis (P. gingivalis)infection. METHODS: Single-cell RNA sequencing was used to analyze the phenotypes and functional changes in various cells in the liver tissue of nonalcoholic steatohepatitis (NASH) mice fed with P. gingivalis. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and immunofluorescence staining were applied to observe the inflammation and expression levels of macrophage antigen presenting functional markers in the NASH liver. Oil red staining was performed to observe the accumulation of local adipose tissue in the NASH liver. Results were verified through RT-PCRand RNA sequencing using P. gingivalis-lipopolysaccharide treated mouse peritoneal macrophages. RESULTS: In comparison with healthy livers with Kupffer cells, the NASH liver combined with P. gingivalis infection-related macrophages showed significant heterogeneity. C1qb, C1qc, Mafb, Apoe, and Cd14 were highly expressed, but Cd209a, H2-Aa, H2-Ab1, and H2-DMb1, which are related to the antigen presentation function, were weakly expressed. Further in vivo and in vitro investigations indicated that the activation and infiltration of these macrophages may be due to local P. gingivalis-lipopolysaccharide accumulation. CONCLUSIONS P. gingivalis-lipopolysaccharide induces a local macrophage immunotolerance phenotype in nonalcoholic fatty liver, which may be the key mechanism of periodontitis pathogen infection that promotes NASH inflammation and pathogenesis. This study further clarifies the dysfunction and regulatory mechanisms of macrophages in the pathogenesis of P. gingivalis-infected NASH, thereby providing potential therapeutic targets for its clinical treatment.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/pathology* ; Kupffer Cells/pathology* ; Porphyromonas gingivalis ; Lipopolysaccharides/metabolism* ; Inflammation/pathology* ; Macrophages/metabolism* ; Mice, Inbred C57BL

OBJECTIVE To investigate the effect of Lycii Fructus-Chrysanthemi Flos herbal pair on the occurrence and progres-sion of light source-induced myopia in guinea pigs.METHODS The three-band fluorescent lamp was used to irradiate guinea pigs to establish a model of light source-induced myopia.Lycii Fructus-Chrysanthemi Flos herbal pair extract was added in the feed to raise guinea pigs.Ophthalmic A-type ultrasonic measuring instrument was used to detect the eye axis.HE staining was used to observe pathological damage to the retina of the guinea pigs.Enzyme-linked immunosorbent assay(ELISA)was used to detect dopamine(DA)and melatonin(MT)levels in guinea pig retinas,and transcriptomic analysis and other methods were used to explore the effects of Lycii Fructus-Chrysanthemi Flos on light-induced myopia in guinea pigs.RESULTS After 6 weeks,compared with the normal group,the eye axis of model group guinea pigs increased significantly(P<0.01),thus,the myopia model was successfully established.Lycii Fruc-tus-Chrysanthemi Flos herbal pair extract could effectively slow down the thickening of the lens and the deepening of the vitreous cavi-ty,thereby delaying the overgrowth of the eye axis in model guinea pigs.The retinal tissue of guinea pigs in the model group became thinner,the thickness and number of cells in the inner and outer nuclear layer of the retina were significantly reduced,the ganglion nu-clei were sparse,the vacuolization of the ganglion cell layer was obvious.Lycii Fructus-Chrysanthemi Flos extract could protect retinal cells.The thickness and cell number of the retinal inner nuclear layer and outer nuclear layer were increased,and ganglion cell nuclei were increased.ELISA assay showed that the concentrations of DA and MT in the retina of model group guinea pigs were significantly reduced(P<0.05),and the medium and high doses of Lycii Fructus-Chrysanthemi Flos herbal pair extract could effectively increase the concentration of dopamine in the retina and serum of guinea pigs in the model group(P<0.01,P<0.001).The differential genes screened by eye transcriptomics analysis were mainly enriched in PPAR signals pathway,collagen-containing extracellular matrix and other related pathways.ELISA results showed that the high dose of Lycii Fructus-Chrysanthemi Flos extract could significantly increase the content of PPARγ and COL1A1(P<0.01)and reduce the content of SMA(P<0.05).CONCLUSION The Lycii Fructus-Chry-santhemi Flos herbal pair extract has effects on delaying the occurrence and progression of light source-induced myopia in guinea pigs,protecting retinal cells,improving DA secretion disorders caused by artificial light environment,and regulating the level of PPAR,which has positive significance for the prevention and control of light source-induced myopia and provides a scientific basis for the ra-tional use of drugs in clinical practice and the creation of eye health products.

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.

Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V₁) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V₂ and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E₂), progesterone (P₄), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E₂, P₄, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P₄ levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E₂ and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E₂ levels may serve as indicators for detecting drug efficacy.