Band 9, Heft 2

Hypervirulent Klebsiella pneumoniae (hvKp) is an evolving pathotype with higher virulence than classical K. pneumoniae (cKp) and is characterized by community-acquired, multiple sites of infections and young and healthy hosts. hvKP infections were primarily found in East Asia and have been increasingly reported worldwide over the past few decades. To better understand the clinical challenges faced by China with hvKP, this review will provide a summary and discussion focused on recognizing hvKP strains and prevalence of antibiotic-resistant hypervirulent strains in China and the mechanisms of acquiring antimicrobial resistance. Compared with cKP, hvKP is likely to cause serious disseminated infections, leading to a higher mortality. However, sensitive and specific clinical microbiology laboratory tests are still not available. Given the limited published data due to the clinical difficulty in differentiating hvKP from cKP, extrapolation of the previous data may not be applicable for the management of hvKP. A consensus definition of hvKP is needed. Furthermore, an increasing number of reports have described hvKp strains with antimicrobial resistance acquisition, increasing the challenges for management of hvKP. China, as an epidemic country, is also facing these challenges. Quite a number of studies from China have reported antibiotic-resistant hvKP strains, including extended-spectrum β-lactamase (ESBL), and carbapenem-, tigecycline-, and colistin-resistant strains. hvKP infections, especially those of antimicrobial-resistant strains, pose to be a great threat for public health in China. Therefore, an immediate response to recognize the hypervirulent strains and provide optimal treatments, especially those with resistance determinants, is an urgent priority for China.

Thyroid autoimmunity (TAI) is prevalent in women of live-birthing age and has independently been associated with complications of fertility and pregnancy, in the case of spontaneous conception or after assisted reproductive technology (ART) treatment. However, it remains challenging to identify causation between infertility and TAI, even interventional trials looking at the impact of levothyroxine (LT4) treatment on fertility and pregnancy outcomes due to differences among study results which related to small scales, impropriate study designs, enrollment criteria of infertility cause and titer/hormone concentration measurements. Furthermore, many questions remain unsettled in ART management in AITD infertile women attempt pregnancy. Therefore, further observational and interventional trials are needed more comprehensive multiple-center, double blinded, and randomized.

Background and Objectives Obesity is the accumulation of adipose tissue caused by excess energy in the body, accompanied by long-term chronic low-grade inflammation of adipose tissue. More than 50% of interstitial cells in adipose tissue are macrophages, which produce cytokines closely related to insulin resistance. Macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). This study aimed to investigate the effect of gastric hormone des-acyl ghrelin (DAG) on the polarization phenotype of macrophages and elucidate the role of macrophages in adipose tissue inflammation and insulin sensitivity and its molecular mechanism. Methods Mice were subcutaneously administrated with DAG in osmotic minipumps. The mice were fed a normal diet or a high-fat diet (HFD). Different macrophage markers were detected by real-time revere transcription polymerase chain reaction. Results Exogenous administration of DAG significantly inhibited the increase of adipocyte volume caused by HFD and reduced the number of rosette-like structures in adipose tissue. HFD in the control group significantly increased M1 macrophage markers, tumor necrosis factor α (TNFα), and inducible NO synthase (iNOS). However, these increases were reduced or even reversed after DAG administration in vitro . The M2 markers, macrophage galactose type C-type Lectin-1 (MGL1), arginase 1 (Arg1), and macrophage mannose receptor 1 (MRC1) were decreased by HFD, and the downward trend was inhibited or reversed after DAG administration. Although Arg1 was elevated after HFD, the fold increase after DAG administration in vitro was much greater than that in the control group. Conclusion DAG inhibits adipose tissue inflammation caused by HFD, reduces infiltration of macrophages in adipose tissue, and promotes polarization of macrophages to M2, thus alleviating obesity and improving insulin sensitivity.

Background and Objective HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS. Methods Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes. Results 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20β, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF . Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking. Conclusion HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

Background and Objectives Acute upper gastrointestinal bleeding (UGIB) is a common problem that can cause significant morbidity and mortality. We aimed to compare the performance of the ABC score (ABC), the AIMS65 score (AIMS65), the Glasgow-Blatchford score (GBS), and the pre-endoscopic Rockall score (pRS) in predicting 90-day mortality or rebleeding among patients with acute UGIB. Methods This was a prospective multicenter study conducted at 20 tertiary hospitals in China. Data were collected between June 30, 2020 and February 10, 2021. An area under the receiver operating characteristic curve (AUC) analysis was used to compare the performance of the four scores in predicting 90-day mortality or rebleeding. Results Among the 1072 patients included during the study period, the overall 90-day mortality rate was 10.91% (117/1072) and the rebleeding rate was 12.03% (129/1072). In predicting 90-day mortality, the ABC and pRS scores performed better with an AUC of 0.722 (95% CI 0.675–0.768; P <0.001) and 0.711 (95% CI 0.663–0.757; P <0.001), respectively, compared to the AIMS-65 (AUC, 0.672; 95% CI, 0.624–0.721; P <0.001) and GBS (AUC, 0.624; 95% CI, 0.569–0.679; P <0.001) scores. In predicting rebleeding in 90 days, the AUC of all scores did not exceed 0.70. Conclusion In patients with acute UGIB, ABC and pRS performed better than AIMS-65 and GBS in predicting 90-day mortality. The performance of each score is not satisfactory in predicting rebleeding, however. Newer predictive models are needed to predict rebleeding after UGIB.

Background and Objectives Lymphocyte-to-monocyte ratio (LMR) has emerged as a new indirect marker of inflammation, which is associated with adverse outcomes in cardiovascular diseases. The aim of this study was to evaluate whether admission LMR is associated with contrast-induced nephropathy (CIN) in patients who underwent percutaneous coronary intervention for acute coronary syndrome (ACS). Methods A total of 873 patients were assessed. LMR was calculated via dividing lymphocyte count by monocyte count. Results LMR was significantly lower in the with-CIN group. ROC analysis showed that the LMR ratios <2.52 predicted CIN development with sensitivity of 66.3% and specificity of 55.8%. Multivariate analysis showed that eGFR, admission glucose, and LMR were independent predictors of CIN in patients with ACS. Conclusion LMR is an easily accessible marker and could be used as a predictor of CIN in patients with ACS undergoing percutaneous coronary intervention.

Background and Objectives The majority of coronavirus disease 2019 (COVID-19) cases are nonsevere, but severe cases have high mortality and need early detection and treatment. We aimed to develop a nomogram to predict the disease progression of nonsevere COVID-19 based on simple data that can be easily obtained even in primary medical institutions. Methods In this retrospective, multicenter cohort study, we extracted data from initial simple medical evaluations of 495 COVID-19 patients randomized (2:1) into a development cohort and a validation cohort. The progression of nonsevere COVID-19 was recorded as the primary outcome. We built a nomogram with the development cohort and tested its performance in the validation cohort. Results The nomogram was developed with the nine factors included in the final model. The area under the curve (AUC) of the nomogram scoring system for predicting the progression of nonsevere COVID-19 into severe COVID-19 was 0.875 and 0.821 in the development cohort and validation cohort, respectively. The nomogram achieved a good concordance index for predicting the progression of nonsevere COVID-19 cases in the development and validation cohorts (concordance index of 0.875 in the development cohort and 0.821 in the validation cohort) and had well-fitted calibration curves showing good agreement between the estimates and the actual endpoint events. Conclusions The proposed nomogram built with a simplified index might help to predict the progression of nonsevere COVID-19; thus, COVID-19 with a high risk of disease progression could be identified in time, allowing an appropriate therapeutic choice according to the potential disease severity.