ObjectiveTo evaluate the efficacy and safety of Lianhua Qingke tablets in the treatment of acute bronchitis in children with the syndrome of phlegm-heat obstructing lung. MethodA randomized， open， parallel controlled， and multi-center clinical study was conduted. Children with acute bronchitis （syndrome of phlegm-heat obstructing lung） were randomly assigned to an observation group and a control group. The control group received routine basic treatment， and the observation group was treated with Lianhua Qingke Tablets on the basis of routine basic treatment. After 7 days of treatment， the clinical efficacy， TCM efficacy， time to symptom disappearance， time to cough disappearance， and clinical safety were compared between the two groups. ResultA total of 248 children were included （124 in the observation group and 124 in the control group）. After 7 days of treatment， the total response rate in terms of clinical efficacy in the observation group was 96.8% （120/124）， which was higher than that （90.3%， 112/124） in the control group （Z=-5.034， P<0.01）. The total response rate in terms of TCM syndrome in the observation group was 97.6% （121/124）， which was higher than that （93.5%， 116/124） in the control group （χ²=-5.326， P<0.01）. The scores of physical signs and TCM symptoms in the observation group were lower than those in the control group at the time of taking medicine for 3 days and 7 days （P<0.01）. The time to symptom disappearance and the time to cough disappearance in the observation group were shorter than those in the control group （P<0.01）. Drug-related adverse reactions occurred in neither group. ConclusionLianhua Qingke tablets demonstrate a definite effect on acute bronchitis in children with the syndrome of phlegm-heat blocking lung. The tablets can significantly shorten the course of disease and relieve cough and TCM symptoms， with high safety， which is worthy of clinical application and promotion.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease globally,with only one Food and Drug Administration(FDA)-approved drug for its treatment.Given MASLD's complex pathophysiology,ther-apies that simultaneously target multiple pathways are highly desirable.One promising approach is dual-modulation of the famesoid X receptor(FXR),which regulates lipid and bile acid metabolism.However,FXR agonists alone are insufficient due to their limited anti-inflammatory effects.This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD.Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger(2018)for molecular docking.Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance(SPR)binding assay,reporter gene ana-lysis,and reverse transcription-polymerase chain reaction(RT-PCR).The anti-inflammatory properties of these compounds were eval-uated in AML12 cells treated with tumor necrosis factor-alpha(TNF-α).Dual-function compounds with FXR agonism and inflamma-tion inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α.The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid.Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists,with 15 exhibiting a strong affinity for FXR recombinant protein.Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb.Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones.Three compounds(2,6,and 8)were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors,while one compound(12)acted as an FXR agonist to inhibit inflammation.These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and in-flammation.In conclusion,compounds 2,6,and 8(genistein,biochanin A,and 7-methoxyisoflavone,respectively)were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation,serving as potential candidates or lead compounds for MASLD therapy.

Objective To explore MRI findings of gouty arthritis(GA)of knee joint.Methods A retrospective study was conducted on 14 patients with GA of knee joint diagnosed with dual-energy CT,and their MRI findings were analyzed.Results In 14 patients with GA of knee joint,dual-energy CT showed that uric acid crystals were mainly deposited in tendons,ligaments,synovium and articular cartilage,including 6 cases in quadriceps tendon,4 cases in patellar ligament,2 cases in anterior and posterior cruciate ligaments,and the remaining 2 cases mainly involved the synovium around the knee joint.MRI showed that the signals of the tophi were similar to those of muscles on T1WI,while the signals on PDWI was diversified,mainly ranging from heterogeneous isointensity to heterogeneous hyperintensity.Conclusion The location and MRI signal characteristics of knee GA patients are specific,and MRI is conducive to display gout crystallization and early manifestations.

Objective:To analyze the morphology and molecular biology and clarify the taxonomic status of one Cupriavidus species strain SZY C1 isolated from clinical wound specimens. Methods:Strain SZY C1 was subjected to physiological and biochemical identification, 16S rRNA gene sequencing, and whole genome sequencing. Its genomic features and virulence genes were analyzed using bioinformatics software.Results:Strain SZY C1 was a gram-negative, non-fermenting bacterium wihout flagella and the ability to form spores. After culturing on Columbia blood agar plates for 24 h, it formed grayish-white colonies that were round, raised, opaque, and had neatly defined margins. Based on 16S rRNA gene sequence analysis, strain SZY C1 belonged to the genus Cupriavidus with the highest 98.52% similarity to Cupriavidus metallicuns. The genome size of strain SZY C1 was determined to be 5 515 517 bp, with a G+ C content of 67.87%. Whole genome sequencing showed that strain SZY C1 had the closest phylogenetic relationship with Cupriavidus agavae, with an average nucleotide identity value of 84.76% and a digital DNA-DNA hybridization value of 29.1%, which were lower than the identification threshold for prokaryotic species. The strain SZY C1 carried multiple virulence genes, drug resistance genes, and heavy metal resistance genes. Conclusions:Based on phenotypic and genomic analyses, the strain SZY C1 is a potential new species of the Cupriavidus genus.

OBJECTIVE To study the mechanism of interfering with long non-coding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 （LncRNA NNT-AS1） expressing to reduce paclitaxel （TAX） resistance in non-small cell lung cancer （NSCLC） cells. METHODS NSCLC TAX-resistant cell line （A549/TAX） was constructed， and the expressions of LncRNA NNT-AS1 in normal， parental， and drug-resistant cells were observed. The targeting relationship of microRNA-582-5p （miR-582- 5p） with LncRNA NNT-AS1 and high mobility group box2 （HMGB2） was verified. A549/TAX cells were cultured in vitro to observe the effects of interfering with LncRNA NNT-AS1 alone or interfering with LncRNA NNT-AS1 and miR-582-5p on the expressions of LncRNA NNT-AS1 and miR-582-5p， the mRNA and protein expressions of HMGB2， cell viability， clone formation and apoptosis. The effects of interfering with LncRNA NNT-AS1 on tumor growth and the expression of miR-582-5p and the mRNA and protein expressions of HMGB2 in tumor tissue were observed in nude mice. RESULTS Compared with normal cells， LncRNA NNT-AS1 was highly expressed in parental and drug-resistant cells （P＜0.05）， showing an increasing trend. It was validated that miR-582-5p had a targeting relationship with LncRNA NNT-AS1 and HMGB2. After interfering with the expression of LncRNA NNT-AS1， the expression of LncRNA NNT-AS1 and the mRNA and protein expressions of HMGB2， cell viability and the number of cloned cells in A549/TAX cell， decreased significantly， while the expression of miR-582-5p and the apoptotic rate increased significantly （P＜0.05）； simultaneously interfering with the expression of miR-582-5p could reverse above changes （P＜ 0.05）. Interfering with the expression of LncRNA NNT-AS1 in tumor cell could significantly reduce tumor volume and tumor weight of nude mice bearing tumors； at the same time， the expression of miR-582-5p was up-regulated significantly and the mRNA and protein expressions of HMGB2 were down-regulated significantly （P＜0.05）. CONCLUSIONS Interfering with the expression of LncRNA NNT-AS1 may alleviate TAX chemotherapy resistance in NSCLC through targeted up-regulation of miR-582-5p and down-regulation of HMGB2.

Objective:To evaluate the methodological quality and reporting quality of clinical practice guidelines or consensuses in the field of Chinese pancreatic diseases from 2016 to 2021, and provide reference for formulating clinical practice guidelines and consensuses in this field.Methods:VIP, Wanfang , CNKI and CBM databases were searched for articles published from January 2016 to March 2021. The main index terms were " pancreas" , " guideline" , " consensus" , and the supplementary index terms were " pancreatitis" , " pancreatic cancer" , " pancreatic head cancer" . Two researchers independently selected the literature. The appraisal of guidelines for research and evaluation (AGREE-China) was utilized to assess the methodological quality of the guidelines or consensuses, and the reporting items for practice guidelines in healthcare (RIGHT) tool was used to assess the reporting quality.Results:A total of 14 literature were included, including 7 literature on pancreatic cancer, 3 literature on acute pancreatitis, 1 literature on chronic pancreatitis and 3 literature on others. The results of the assessment by the AGREE-China tool showed that there were no document with a total score greater than or equal to 60.0 points, two with 40.0 to 59.9 points, eleven with 20.0 to 39.9 points, and one with less than 20.0 points. Among the results of RIGHT list, basic information was reported the highest(72.62%) and funding and declaration was the lowest(0).Conclusions:The methodological and reporting quality of the guidelines or consensuses on pancreatic disease in China from 2016 to 2021 are generally not high. In the process of developing domestic guidelines or consensuses on pancreatic diseases, the guideline developer should refer to AGREE-China and RIGHT to improve the quality of clinical practice guidelines or consensuses.

OBJECTIVE: To explore the genetic basis for a pedigree affected with Nance-Horan syndrome. METHODS: Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity. RESULTS: A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4). CONCLUSION The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.
Cataract/genetics* ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree ; State Medicine ; Tooth Abnormalities

OBJECTIVE: To explore the genetic basis for a pedigree affected with Alport syndrome. METHODS: Next generation sequencing and Sanger sequencing was carried out to detect potential variant of the COL4A5 gene among members from the pedigree and 100 unrelated healthy controls. RESULTS: A novel missense c.3293G>T (p.Gly1098Val) variant was found in the COL4A5 gene among 6 affected members but not the unaffected members of the pedigree or the 100 healthy controls. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.3293G>T variant was classified as pathogenic (PP1-strong+PM1+PM2+PP3+PP4). CONCLUSION By destructing the Gly-X-Y structure of its protein product, the c.3293G>T variant of the COL4A5 gene probably underlies the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COL4A5 variants.

OBJECTIVE: To analyze variant of IDS gene in a pedigree affected with mucopolysaccharidosis type II (MPS II). METHODS: The proband was subjected to next generation sequencing and Sanger sequencing to identify potential variants. Suspected variant was analyzed by its co-segregation with the disease in the pedigree. Its impact on mRNA splicing was analyzed by using reverse transcription PCR (RT-PCR). RESULTS: A hemizygous IVS1-3T>G variant was found in the IDS gene in the proband. RT-PCR results revealed two abnormal cDNA fragments of 600 bp and 300 bp. The 600 bp fragment had inserted 216 nucleotides at the 3' end of intron 1, while the 300 bp fragment had lost 109 nucleotides at the 5' end of exon 2, which resulted in two truncated proteins comprising 38 and 92 amino acids, respectively, instead of the normal product (550 amino acids). The proband and his mother were respectively hemizygous and heterozygous for the variant. The same variant was not found among 100 normal controls. CONCLUSION The IVS1-3T>G variant of the IDS gene probably underlies the MPS II in this pedigree by causing reduction or elimination of the IDS protein.