Thrombolytic therapy plays a vital role in reperfusion strategy for ST-segment elevation myocardial infarction(STEMI)patients.Previous Chinese expert consensus focused on pre-hospital thrombolysis therapy in STEMI patients was published in 2018 which tremendously promoted pre-hospital thrombolysis therapy.In recent years,plenty of research progress and results of clinical trials have been released in following areas such as STEMI reperfusion strategy,anti-platelet/anti-coagulants therapy,contemporary facilitated percutaneous coronary intervention,and so on.Meanwhile,the COVID-19 pandemic makes timely reperfusion for STEMI patients even more challenging.Therefore,this consensus has been proposed aiming to summarize recent progress in STEMI thrombolysis therapy and to provide practical & evidence-based instructions conforming to national conditions.We hope this consensus will contribute to the emergency management and long-term prognosis of STEMI patients.

Investigate the biofilm-forming ability and drug resistance of Hypervirulent Klebsiella pneumoniae (HvKP) to provide scientific basis for the treatment of HvKP-infection. A total of 96 Klebsiella pneumoniae strains isolated from clinical infection specimens in Changsha Central Hospital from January to December in 2021 were retrospectively collected, and the clinical data of patients were collected. The string test preliminarily distinguished between HvKP and classic Klebsiella pneumoniae (CKP). The biofilm-forming ability of clinical strains of Klebsiella pneumoniae (KP) was determined by microplate method. The Vitek 2 Compact automatic microbial identification/drug sensitivity analysis system was used for bacterial identification and drug sensitivity test. The clinical data of patients, biofilm forming ability and drug resistance in the HvKP group and those in the CKP group were compared and analyzed. The results showed that a total of 20 strains of HvKP were isolated from 96 non-repetitive KP, and the detection rate was 20.8%. HvKP mainly come from respiratory specimens, up to 75.0%.The prevalence of hepatobiliary diseases and the infection rate of multiple sites in patients with HvKP infection were higher than those in patients with CKP infection, and the difference was statistically significant(χ²=5.184,7.488;P=0.023,0.006).There was no significant difference between the two groups in terms of gender, age, ICU admission, hypertension, diabetes, coronary heart disease, lung disease, urinary system disease, central nervous system disease and laboratory test indexes (all P>0.05).17 (85.0%) strains of HvKP can form biofilm, including 2 strains with weak biofilm-forming ability (10.0%), 10 strains with moderate biofilm-forming ability (50.0%) and 5 strains with strong biofilm-forming ability (25.0%). Among the 76 CKP, 71 (93.4%) could form biofilm, including 13 (17.1%) with weak biofilm-forming ability, 30(39.5%) with moderate biofilm-forming ability and 28 (36.8%) with strong biofilm-forming ability. There was no significant difference in biofilm-forming ability between HvKP and CKP (χ²=1.470,P=0.225).The overall resistance rate of HvKP was not high, but a multi-resistant HvKP resistant to carbapenems was found. The detection rate of multi-resistant HvKP (5.0%) was lower than that of multi-resistant CKP (28.9%), and the difference was statistically significant (χ²=4.984, P=0.026).The resistance rate of HvKP to piperacillin/tazobactam, aztreonam, ciprofloxacin, levofloxacin, ceftazidime, cefepime, tobramycin, minocycline, doxycycline, and compound sulfamethoxazole was lower than that of CKP, and the difference was statistically significant (all P<0.05). In conclusion, most of hypervirulent Klebsiella pneumoniae can form biofilm in this study, but the difference of biofilm-forming ability is not obvious compared with classic Klebsiella pneumoniae. HvKP maintains high sensitivity to commonly used antibacterial drugs, but the drug resistance monitoring of the bacteria cannot be ignored.

Investigate the biofilm-forming ability and drug resistance of Hypervirulent Klebsiella pneumoniae (HvKP) to provide scientific basis for the treatment of HvKP-infection. A total of 96 Klebsiella pneumoniae strains isolated from clinical infection specimens in Changsha Central Hospital from January to December in 2021 were retrospectively collected, and the clinical data of patients were collected. The string test preliminarily distinguished between HvKP and classic Klebsiella pneumoniae (CKP). The biofilm-forming ability of clinical strains of Klebsiella pneumoniae (KP) was determined by microplate method. The Vitek 2 Compact automatic microbial identification/drug sensitivity analysis system was used for bacterial identification and drug sensitivity test. The clinical data of patients, biofilm forming ability and drug resistance in the HvKP group and those in the CKP group were compared and analyzed. The results showed that a total of 20 strains of HvKP were isolated from 96 non-repetitive KP, and the detection rate was 20.8%. HvKP mainly come from respiratory specimens, up to 75.0%.The prevalence of hepatobiliary diseases and the infection rate of multiple sites in patients with HvKP infection were higher than those in patients with CKP infection, and the difference was statistically significant(χ²=5.184,7.488;P=0.023,0.006).There was no significant difference between the two groups in terms of gender, age, ICU admission, hypertension, diabetes, coronary heart disease, lung disease, urinary system disease, central nervous system disease and laboratory test indexes (all P>0.05).17 (85.0%) strains of HvKP can form biofilm, including 2 strains with weak biofilm-forming ability (10.0%), 10 strains with moderate biofilm-forming ability (50.0%) and 5 strains with strong biofilm-forming ability (25.0%). Among the 76 CKP, 71 (93.4%) could form biofilm, including 13 (17.1%) with weak biofilm-forming ability, 30(39.5%) with moderate biofilm-forming ability and 28 (36.8%) with strong biofilm-forming ability. There was no significant difference in biofilm-forming ability between HvKP and CKP (χ²=1.470,P=0.225).The overall resistance rate of HvKP was not high, but a multi-resistant HvKP resistant to carbapenems was found. The detection rate of multi-resistant HvKP (5.0%) was lower than that of multi-resistant CKP (28.9%), and the difference was statistically significant (χ²=4.984, P=0.026).The resistance rate of HvKP to piperacillin/tazobactam, aztreonam, ciprofloxacin, levofloxacin, ceftazidime, cefepime, tobramycin, minocycline, doxycycline, and compound sulfamethoxazole was lower than that of CKP, and the difference was statistically significant (all P<0.05). In conclusion, most of hypervirulent Klebsiella pneumoniae can form biofilm in this study, but the difference of biofilm-forming ability is not obvious compared with classic Klebsiella pneumoniae. HvKP maintains high sensitivity to commonly used antibacterial drugs, but the drug resistance monitoring of the bacteria cannot be ignored.

ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology. MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information （NCBI）， and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed. Finally， AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them. ResultA total of 29 important chemical components in the prescription were screened out， including β-sitosterol， sesamin， and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved， such as protein kinase B1 （Akt1）， epidermal growth factor receptor （EGFR）， hypoxia inducible factor-1A （HIF-1A）， proto-oncogene tyrosine-protein kinase （SRC）， and matrix metalloproteinase-9 （MMP-9）. Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism， nucleic acid transcription， and metabolic enzyme pathway， and 28 key KEGG pathways， including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1. ConclusionKanglao granule improved the sterilization level and immune response through multi-component， multi-target， and multi-pathway interactions， thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

Objective:To optimize the decoction process of Digda-4 decoction(DGD-4D), and provide reference for the standardization study of decoction of Mongolian medicine decoction. Method:Taking DGD-4D as model drug, different decoction methods of Mongolian medicine were compared, HPLC was used to determine contents of aesculetin, geniposide, picroside Ⅰ and picroside Ⅱ.On the basis of single factor tests, central composite design-response surface methodology was adopted to optimize the decoction process of DGD-4D with transfer rates of 4 components and dry extract rate as indexes, regression model fitting was carried out by Design-Expert 8.0.6 software, prediction model of process parameters was established, and the optimal process was verified. Result:The optimal decoction condition of DGD-4D was determined to be adding 40 times the amount of water and decocting for 17 min, decocting once.Transfer rates of aesculetin, geniposide, picroside Ⅰ, picroside Ⅱ and dry extract rate were 70.01%, 94.11%, 61.23%, 92.32%, 32.89%, respectively. Conclusion:The optimum decoction process of DGD-4D is established, it has important reference significance for excavating, sorting, improving the level of Mongolian medicine preparations and ensuring the consistency of their clinical efficacy.

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by SLC7A7 gene mutation and often involves severe lesions in multiple systems. Lung involvement is frequently seen in children with LPI and such children tend to have a poor prognosis. This article summarizes the clinical manifestations and gene mutation characteristics of three children diagnosed with LPI by SLC7A7 gene analysis. All three children had the manifestations of aversion to protein-rich food after weaning, delayed development, anemia, hepatosplenomegaly, and osteoporosis, as well as an increase in orotic acid in urine. In addition, interstitial pneumonia and diffuse pulmonary interstitial lesions were observed in two children. SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A. After a definite diagnosis was made, all three children were given a low-protein diet and oral administration of citrulline [100 mg/(kg.d)], iron protein succinylate [4 mg/(kg.d)], calcium and zinc gluconates oral solution (10 mL/day) and vitamin D (400 IU/day). In addition, patient 3 was given prednisone acetate (5 mg/day). The children had varying degrees of improvement in symptoms and signs. It is hard to distinguish LPI from urea cycle disorder due to the features of amino acid and organic acid metabolism in LPI, and SLC7A7 gene analysis is the basis for a definite diagnosis of LPI.
Amino Acid Metabolism, Inborn Errors ; genetics ; Child ; Citrulline ; Fusion Regulatory Protein 1, Light Chains ; genetics ; Humans ; Lysine ; Mutation

BACKGROUND: The clinical experience of the treatment of the sternoclavicular joint dislocation and peripheral fracture is relatively lacking, but its incidence is increasing yearly. At present, there are few studies on the anatomy and biomechanics of the sternoclavicular joint in and outside China, and no systematic anatomical measurements of the sternoclavicular joint are reported. OBJECTIVE: To provide a biological reference for the clinical diagnosis and treatment of sternoclavicular joint dislocation or peripheral fractures by studying the anatomy and biomechanics of the sternoclavicular joint. METHODS: (1) A total of 16 specimens (32 sides) of adult antiseptic and moist cadaveric specimens were selected. The complete manubrium, bilateral clavicle and surrounding tissues of sternoclavicular joint were anatomically separated, and repair to bone-ligament-bone specimen models. (2) The areas of manubrium articular surface and the medial clavicular articular surface of all specimens were measured by the ink pattern combined with grid counting method. (3) The morphological features of the anterior and posterior sternoclavicular ligaments of the specimens in this group were observed, and the length, width and thickness were measured and analyzed statistically. (4) The left and right sternoclavicular joints of each specimen were randomly paired into A and B groups. Group A received simply cutting of anterior sternoclavicular ligament. Group B received simply cutting of posterior sternoclavicular ligament. Before and after cuting off the ligament, the anterior and posterior load experiments were performed on the anatomical sites with the same force arm length and perpendicular to the distal clavicle. The angles of joints and load-angle regression line slopes were compared between the two groups in the anterior and posterior directions load. RESULTS AND CONCLUSION: (1) The area of articular surface of manubrium (239.00±28.78 mm2) was smaller than the area of medial articular surface of the clavicle (482.56±44.89 mm2), and the difference was statistically significant (t=-40.105, P < 0.001). (2) The length, width and thickness of the anterior sternoclavicular ligament were (17.56±1.94 mm), (15.54±1.42 mm) and (1.93±0.32 mm), and the length, width and thickness of the posterior sternoclavicular ligament were (17.21±1.86 mm), (15.97±1.17 mm), and (2.07±0.29 mm) respectively;there was no significantly statistical difference in the length, width and thickness between them (P > 0.05). (3) Before cutting the ligaments, when the loads were 2, 4, 6, 8, and 10 N, the angle backwards of joint caused by loads in the forward direction was less than the angle of forwards of joints caused by loads in the backward direction, but only when the loads were 6, 8, and 10 N, the difference between them was statistically significant (P < 0.05). The slope of the regression line of load-angle for the loads in the forward direction was less than the slope of the regression line of load-angle for the loads in the backward direction, with statistical difference (F=31.413, P < 0.001). After the ligaments were cut, when the loads were 2, 4, 6, 8 and 10 N in the forward direction in group A and group B, the backward angulation of joint in group A was less than that in group B (P < 0.05). The slope of the load-angled regression line in group A was less than that in group B (F=52.224, P <0.001). When the loads in the backward direction in group A and group B were 2, 4, 6, 8 and 10 N, the forward angulation of joint in group A was greater than that in group B (P < 0.05), and the slope of the load-angled regression line in group A was greater than that in group B (F=12.503, P=0.008). (4) These results suggest that contact area between the articular surface of the medial clavicle and the articular surface of the manubrium is narrow, which determines the instability of the joint itself. The sternoclavicular ligament is extremely important for maintaining the joint stability. The forward angulation of joint restriction effect of sternoclavicular ligament was weaker than that of the backward angulation, also because of the joint in the anatomical position of the natural forward angulation, so the sternoclavicular joint was prone to anterior dislocation. It is necessary to pay attention to the repair and reconstruction of sternoclavicular ligament when sternoclavicular joint dislocation or peripheral fractures are treated by operations.

To establish the high performance liquid chromatography (HPLC) fingerprint for Digeda-4 decoction (DGD-4D), determine the contents of aesculetin, geniposide, picroside Ⅰ, picroside Ⅱ and ellagicacid in DGD-4D, and provide the scientific foundation for quality control of DGD-4D. The analysis was performed on Diamonsil(2) C₁₈ (4.6 mm×250 mm,5 μm) column, with methanol-0.1% phosphoric acid aqueous solution as mobile phase for gradient elution. The flow rate was 1.0 mL·min⁻¹; injection size was 10 μL; temperature was maintained at 30 °C, and the detection wavelength was set at 254 nm. The common mode of DGD-4D HPLC fingerprint was established, and the hidden information was analyzed by Chemometrics. Chromatographic peaks for DGD-4D were identified by HPLC and quantitative analysis was conducted for characteristic peaks. There were 17 common peaks in the fingerprints and the similarity of the fingerprints was over 0.9 in all 15 batches. The samples were broadly divided into four kinds by principal component analysis and clustering analysis. Four marker compounds were verified by partial least squares discriminant analysis, and No. 9, 12 and 14 peaks were identified as geniposide, picroside Ⅱ, and picroside Ⅰ respectively. The average recoveries were in the range of 95.91%-97.31%. The HPLC fingerprint method for content determination is reliable, accurate, rapid, simple, and reproducible, and can be used as one of the effective methods to control the quality of DGD-4D.
Chromatography, High Pressure Liquid ; Cinnamates ; Drugs, Chinese Herbal ; analysis ; standards ; Iridoid Glucosides ; Iridoids ; Methanol ; Principal Component Analysis ; Quality Control