OBJECTIVE: To develop and validate a predictive model for the risk of bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). METHODS: A literature search was conducted in PubMed, Cochrane Library, and Embase databases from inception to July 2022 to identify studies reporting statistically significant risk factors for CRKP-BSI. Relative risks (RR) were extracted and pooled. Based on factor weights, a risk-scoring model was established. For external validation, hospitalized CRKP-infected patients from January 2016 to January 2022 at Shanghai First People's Hospital were included. Clinical data were used to calculate individual risk scores. The predictive accuracy was assessed using receiver operator characteristic curve (ROC curve). Patients were stratified into low-to-intermediate-risk and high-risk groups based on the optimal cut-off, and CRKP BSI incidence was compared between groups. RESULTS: The literatures related to the risk factors of CRKP-BSI published from database inception to July 2022 was retrieved and screened from PubMed, Cochrane Library, and Embase. Fourteen risk factors were included in the scoring model: cardiovascular disease, severe neutropenia or immunosuppression, intensive care unit (ICU) stay history, prior hospitalization, carbapenem exposure, aminoglycoside exposure, antifungal exposure, endotracheal intubation or tracheostomy, mechanical ventilation, hemodialysis, central venous catheter, indwelling urinary catheter, CRKP colonization, and Klebsiella pneumoniae positivity at non infection sites. The total score ranged from 0 to 173.5 points. In the validation cohort of 230 CRKP-infected patients, 41 developed CRKP BSI. The model yielded an area under the curve (AUC) of 0.783 (95%CI was 0.689-0.876). The optimal cut off was 81.25 points, with sensitivity of 75.6% and specificity of 81.0%. Based on this cut off, 163 patients were categorized as low-to-intermediate risk and 67 patients as high risk. The incidence of CRKP BSI in the high-risk group was significantly higher than in the low-to-intermediate-risk group [64.2% (43/67) vs. 4.9% (8/163); RR = 13.175 (95%CI was 5.920-29.319), P < 0.001]. CONCLUSIONS The model, based on 14 routinely available clinical parameters, demonstrated good performance in predicting CRKP BSI risk and may assist clinicians in early identification of high risk patients.
Humans ; Klebsiella pneumoniae/drug effects* ; Klebsiella Infections/microbiology* ; Carbapenems/pharmacology* ; Risk Factors ; Bacteremia/microbiology* ; ROC Curve ; Carbapenem-Resistant Enterobacteriaceae

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Heart failure is a fatal stage of end-stage cardiovascular disease,which brings a huge medical burden to the society because of its high mortality and re-hospitalisation rates.Intestinal microecology is the largest and most com-plex microecosystem of human body.It is inhabited by tens of thousands of microorganisms in human gastrointestinal tract.In recent years,with the deepening of the study of intestinal flora,more and more studies have found that the im-balance of intestinal microecology can cause changes of metabolites in heart failure patients,which is one of the key triggers for the development of heart failure,therefore,using the intestinal microbial homeostasis as a new entry point for the treat-ment of heart failure will be a hotspot in medical research.However,the theory of Chinese medicine,"the spleen is the guardian",covers the physiological functions of the spleen,such as the spleen's main function of transporting,spleen's main function of ascending and clearing,and its main function of hiding camping,etc.,and the functions of intestinal flora and the"spleen is the guardian"are similar to a certain extent.Therefore,this paper starts from a holistic viewpoint and takes the theory of"spleen as the guardian"in Chinese medicine as an entry point to elaborate on the pathogenesis of intes-tinal microecological imbalance and heart failure,so as to provide a reference for Chinese medicine treatment or drug re-search.

Humans ; Asthma/drug therapy* ; Biological Therapy

COVID-19 ; Humans ; Inflammation/genetics* ; Lung ; Pneumonia ; SARS-CoV-2 ; Serologic Tests

Objective:To detect mutations in a pedigree containing two brothers with oculocutaneous albinism (OCA) by whole-exome sequencing and Sanger sequencing.Methods:Clinical data were collected from a pedigree with OCA, and DNA was extracted from peripheral blood samples obtained from the proband and other family members. The whole-exome coding region of the proband was directly sequenced by whole-exome sequencing technology to identify potential pathogenic mutations, and Sanger sequencing was conducted to verify the gene mutations.Results:Both the proband and his younger brother presented with generalized white skin, golden-yellow hair, bilateral nystagmus, photophobia, translucent iris, conjunctival congestion, and refractive errors of both eyes. The proband′s parents, grandparents, maternal grandparents, and children were all phenotypically normal, and his parents′ marriage was non-consanguineous. Three heterozygous mutations were identified in the OCA2 gene of both the proband and his younger brother, including a nonsense mutation c.1290T>A, and 2 missense mutations c.1363A>G and c.1204T>C. The mutation c.1204T>C has not been previously reported, and was a novel gene mutation in the OCA2 gene. In addition, 1 heterozygous mutation c.1204T>C was identified in the OCA2 gene in the proband′s father and daughter, 2 heterozygous mutations c.1290T>A and c.1363A>G were found in the OCA2 gene in the proband′s mother, and 1 heterozygous mutation c.1290T>A was identified in the OCA2 gene in the proband′s son and the daughter of the proband′s younger brother.Conclusions:Three gene mutations were identified in the OCA2 gene in the 2 patients with OCA, and the nonsense mutation c.1290T>A may be the pathogenic mutation causing the clinical phenotype of this family. These findings expand the pathogenic mutational spectrum of the OCA gene.

Objective: To evaluate the efficacy and safety of different positions external physical vibration lithecbole (EPVL) therapy for ureteral calculi related renal colic. Methods: This study was a prospective multicenter randomized controlled trial. The inclusion criteria was that patients volunteered to participate in the trial and signed informed consent, patients’age ranged from 18-65 years old, ureteral calculi related with renal colic, stone diameter was less than 7 mm, patients were not treated with analgesia, antispasmodic drugs. The exclusion criteria was that combination of severe urinary tract infection, severe hydronephrosis, urinary malformation, severe hypertension, history of cerebrovascular disease, vital organ dysfunction, obesity (BMI>35 kg/m²), history of ureteral calculi exceeded 2 months, abnormal blood coagulation. Patients were randomized into observation group and control group using random number table method. The observation group and the control group were placed on the physical vibration stone arranging machine with head low foot high position and head high foot low position respectively. The inclination angle was 24°. The secondary vibrator vibrated for 6 minutes, then the patient took the prone position and opened the main, the secondary vibrator. The treatment is completed after 6 minutes of vibration. The analgesic effect, stone removal, follow-up effects and adverse reactions in the two groups was compared. We defined the pain relief rate as(VAS score before treatment-VAS score after treatment)/VAS score before treatment×100%. Results: A total of 100 patients were included in the study, 50 in the observation group and 50 in the control group. There were no statistical difference in the age of the two groups [(41.8±11.7)years and (46.6±13.9 years)], gender distribution [37(male)/13(female) and 42(male)/ 8(female)], location of stones (in the observation group, 19 cases in upper ureter, 7 cases in the middle ureter and 24 cases in the lower ureter; in the control group, 12 cases in the upper ureter, 3 cases in the middle ureter, and 35 in the lower ureter), left and right distribution of stones [21(right)/ 29 (left) and 22 (right)/ 28(left)], long diameter of stones [(5.2±0.9)mm and(5.1±1.1)mm], VAS scores before treatment (7.5±1.4 and 7.6±1.5), and readmission rate [22%(11/50)With 18%(9/50)], 1 week stone removal rate [70%(35/50) and 64%(32/50)]. The incidence of adverse reactions was 8%(4/50) in the observation group including 3 cases of nausea, 1 case of vomiting. The incidence of adverse reactions was 4% in the control group (2/50), which 2 cases showed nausea. The number of patients who chose EPVL, ESWL or surgery for the subsequent treatment in observation group was 35 cases, 9 cases, and 6 cases respectively. The number of patients who chose EPVL, ESWL or surgery for the subsequent treatment in the control group was 35 cases, 10 cases and 5 cases respectively. There was no significant difference between the two groups (P>0.05). The VAS score after treatment of the observation group was lower than that of the control group (2.4±1.3 and 3.7±1.5, P<0.01). The total effective rate of the observation group was higher than that of the control group [94%(47/50) and 76%(38/50), P<0.01]. 46 patients underwent urinary ultrasonography to check the degree of hydronephrosis. The reduction rate of hydronephrosis was higher in the observation group than in the control group [54.5%(18/33) and 30.8%(4/13)], but there was no significant difference between the two groups (P=0.146). In the upper ureteral calculi, the VAS score of the observation group was lower than that of the control group (2.4±0.3 and 3.9±0.4, P<0.01). There was no significant difference in the total effective rate between the two groups. In the lower ureteral calculi, the observation group had low VAS score after treatment. In the control group (2.4±0.2 and 3.5±0.2, P<0.01), there was no significant difference in the total effective rate between the two groups; the middle segment stones were less included (10 in total) and were not discussed. Conclusions The external physical vibration lithecbole adopts " head high and low position" has better effect than "head low foot high position" in treatment of ureteral calculi with renal colic, and security is acceptable.

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on ( 6), and -19: , we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.
Adrenal Cortex Hormones ; adverse effects ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Betacoronavirus ; isolation & purification ; Coronavirus Infections ; drug therapy ; Critical Illness ; Drug Therapy ; Humans ; Nutritional Support ; Pandemics ; Pneumonia, Viral ; drug therapy ; Probiotics ; administration & dosage

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.