Sepsis is a heterogeneous syndrome.It is caused by infections,attributing to immune dysfunction pathologically.The disease is characterized by macrophage-mediated inflammation and immune response throughout its development.During septic development,macrophages metabolize crucially with glycolysis remarkably enhanced.The glycolystic enhancement facilitates septic development by promoting the inflammatory response of macrophages and altering their phenotype.Therefore,direct or indirect inhibition of macrophagic glycolysis can alleviate sepsis and neutralize damages to organs functionally,promoting the polarization of anti-inflammatory phenotype.In this review,we aim to investigate the relationship between macrophagic glycolysis and sepsis,focusing on researching into relevant molecular mechanisms by which glycolysis is regulated for treating sepsis.It is concluded that interfer-ing with macrophagic glycolysis may serve as a novel therapeutic strategy for treating sepsis.

Objective:To conduct a scoping review to analyse the types, performance, advantages and disadvantages of cognitive function assessment tools for ICU patients, to provide a reference for the evaluation of cognitive function in ICU patients in future.Methods:A scoping review study was conducted, literature on cognitive function assessment tools for ICU patients in 9 domestic and foreign databases including China National Knowledge Infrastructure, Wanfang Database, VIP Database, China Biology Medicine disc, PubMed, Web of Science, Cochrane Library, Embase and CINAHL were systematically searched. The search period was from the establishment of the database to May 20, 2024. Literature was independently screened by 2 researchers and relevant information was extracted and summarized.Results:Totally 17 studies were included, with 9 tools for assessing cognitive function in ICU patients, including 6 questionnaires, 1 test battery, 1 assessment software, and 1 telephone interview questionnaire. All of above were generalizable tools, except for the Chinese and English versions of the John-Hopkins Adapted Cognitive Exam as ICU-specific tools. The Mini-Mental State Examination was the most widely used assessment scale.Conclusions:Appropriate assessment tools should be selected according to the specific clinical setting, but there is still a lack of specialized and standardized assessment tools for cognitive dysfunction in ICU patients. In the future, standardized tools which fit our cultural context for evaluating cognitive function in ICU patients should be developed.

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Objective:To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.Methods:The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals [ROR method: ≥3 reports and the lower limit of the 95% confidence interval ( CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、 PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed. Results:A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1 888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort ( ROR=28.87, PRR=28.85), injection site discomfort ( ROR=24.48, PRR=24.40), sinus pain ( ROR=23.20, PRR=23.19), injection site vesicles ( ROR=17.63, PRR=17.61), and injection site rash ( ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity. Conclusion:The main AE of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

Objective:To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.Methods:The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals [ROR method: ≥3 reports and the lower limit of the 95% confidence interval ( CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、 PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed. Results:A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1 888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort ( ROR=28.87, PRR=28.85), injection site discomfort ( ROR=24.48, PRR=24.40), sinus pain ( ROR=23.20, PRR=23.19), injection site vesicles ( ROR=17.63, PRR=17.61), and injection site rash ( ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity. Conclusion:The main AE of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.

ObjectiveTo summarize the history and modern clinical application of Renshen Baidusan. MethodThe bibliometric method was used to retrieve the relevant publications of Renshen Baidusan from the ancient book database and China National Knowledge Infrastructure （CNKI）. The publications were screened according to the inclusion and exclusion criteria. The information of dynasty， book title， function， dosage and so on was extracted， on the basis of which the history， composition， dosage， decocting method， original medicinal plants， processing， and modern clinical application of this prescription were analyzed. ResultRenshen Baidusan was first recorded in the Formulary of the Bureau of Taiping People's Welfare Pharmacy， consisting of Bupleuri Radix， Glycyrrhizae Radix et Rhizoma， Platycodonis Radix， Ginseng Radix et Rhizoma， Chuanxiong Rhizoma， Poria， Aurantii Fructus， Peucedani Radix， Notopterygii Rhizoma et Radix， Angelicae Pubescentis Radix， Zingiberis Rhizoma Recens， and Menthae Haplocalycis Herba and with the effect of dispersing cold， removing dampness， reinforcing Qi， and relieving exterior. Later generations of physicians used this prescription on the basis of the record in Formulary of the Bureau of Taiping People's Welfare Pharmacy to treat cold （frequency of 112， 22.63%） and seasonal cold （frequency of 83， 16.77%）. Renshen Baidusan is widely used in modern clinical practice to treat respiratory diseases （frequency of 42， 17.65%）， skin diseases （frequency of 34， 14.29%）， and infectious diseases （frequency of 33， 13.87%）. This prescription is often modified to treat the syndrome of internal deficiency and external contraction， or external contraction of wind， cold and damp pathogens without deficiency of healthy Qi， which fully embodies the concept of treating different diseases with the same method in traditional Chinese medicine. ConclusionThe textual research reveals the key information of the classical prescription Renshen Baidusan， providing a basis for the subsequent development and application of compound preparations.

Objective To explore the changes of blood glucose level after glucocorticoid pulse therapy (GPT) and its influencing factors in patients with Graves ophthalmopathy (GO).Methods Medical records of GO patients hospitalized in Beijing Tongren Hospital from January 1,2013 to December 31,2018 and treated with GPT were collected and retrospectively analyzed.The incidence of glucocorticoid-induced diabetes mellitus (GIDM) during the GPT treatment (3 days) was counted.According to the monitoring data of fasting blood glucose (FBG) and postprandial blood glucose (PBG),the changes of FBG and PBG levels were calculated.Influencing factors for FBG and PBG levels were evaluated by multiple linear stepwise regression analysis.Results A total of 75 patients were enrolled in the study,including 44 males and 31 females,aged 22-69 years with the average age of (48 ±9) years;40 patients (53.3％) were with normal oral glucose tolerance test,27 (36.0％) with prediabetes,and 8 (10.7％) with diabetes mellitus;57 patients (76.0％) were with hyperthyroidism,11 (14.7％) with hypothyroidism,and 7(9.3％)with normal thyroid function.The peak values of FBG and PBG in 75 patients during GPT treatment were significantly higher than those before the treatment [FBG:(7.9 ± 1.3) vs.(5.3 ± 1.2)mmol/L,PBG:(13.5±2.8) vs.(8.1 ±2.8) mmol/L;both P＜0.001],and the differences were (2.7 ± 1.0) and (5.4 ± 2.6) mmol/L,respectively (P ＜ 0.001).Among the 67 patients without diabetes mellitus,54 (80.6％) developed GIDM during GPT treatment.The levels of FBG and PBG in the 8 patients with diabetes mellitus increased by (2.7 ± 1.4) and (3.7 ± 2.5) mmol/L during GPT treatment,respectively.Multiple linear stepwise regression analysis showed that the influencing factors of FBG level during GPT treatment were baseline FBG level (P ＜ 0.001) and history of hyperuricemia (P =0.002) and dyslipidemia (P =0.032);the influencing factors of PBG level were baseline glycosylated hemoglobin A1c (HbA1c,P =0.002) level,baseline PGB level (P =0.024),and serum free thyroxine level (FT4,P =0.021).Conclusions GPT had a significant effect on blood glucose level in patients with GO,which could lead to higher incidence of GIDM.The main influencing factors of blood glucose level were baseline levels of FBG,PBG,and HbAlc,FT4 levels,and history of hyperuricemia and dyslipidemia.

Objective To explore the changes of blood glucose level after glucocorticoid pulse therapy (GPT) and its influencing factors in patients with Graves ophthalmopathy (GO).Methods Medical records of GO patients hospitalized in Beijing Tongren Hospital from January 1,2013 to December 31,2018 and treated with GPT were collected and retrospectively analyzed.The incidence of glucocorticoid-induced diabetes mellitus (GIDM) during the GPT treatment (3 days) was counted.According to the monitoring data of fasting blood glucose (FBG) and postprandial blood glucose (PBG),the changes of FBG and PBG levels were calculated.Influencing factors for FBG and PBG levels were evaluated by multiple linear stepwise regression analysis.Results A total of 75 patients were enrolled in the study,including 44 males and 31 females,aged 22-69 years with the average age of (48 ±9) years;40 patients (53.3％) were with normal oral glucose tolerance test,27 (36.0％) with prediabetes,and 8 (10.7％) with diabetes mellitus;57 patients (76.0％) were with hyperthyroidism,11 (14.7％) with hypothyroidism,and 7(9.3％)with normal thyroid function.The peak values of FBG and PBG in 75 patients during GPT treatment were significantly higher than those before the treatment [FBG:(7.9 ± 1.3) vs.(5.3 ± 1.2)mmol/L,PBG:(13.5±2.8) vs.(8.1 ±2.8) mmol/L;both P＜0.001],and the differences were (2.7 ± 1.0) and (5.4 ± 2.6) mmol/L,respectively (P ＜ 0.001).Among the 67 patients without diabetes mellitus,54 (80.6％) developed GIDM during GPT treatment.The levels of FBG and PBG in the 8 patients with diabetes mellitus increased by (2.7 ± 1.4) and (3.7 ± 2.5) mmol/L during GPT treatment,respectively.Multiple linear stepwise regression analysis showed that the influencing factors of FBG level during GPT treatment were baseline FBG level (P ＜ 0.001) and history of hyperuricemia (P =0.002) and dyslipidemia (P =0.032);the influencing factors of PBG level were baseline glycosylated hemoglobin A1c (HbA1c,P =0.002) level,baseline PGB level (P =0.024),and serum free thyroxine level (FT4,P =0.021).Conclusions GPT had a significant effect on blood glucose level in patients with GO,which could lead to higher incidence of GIDM.The main influencing factors of blood glucose level were baseline levels of FBG,PBG,and HbAlc,FT4 levels,and history of hyperuricemia and dyslipidemia.

Objective: To discuss the therapeutic effect of using tibial island flap of second toe for the treatment of fibular hallux flap donor site defect. Methods: From March 2012 to April 2015, 18 tibial island flaps of second toe were transferred to repair donor site defect on fibular hallux that can not sutured directly, and the subsequent donor site wound on the second toe were sutured. Results: On an average of 13 months follow-up, all 18 flaps survived with primary healing. Texture and appearance of the tibial island flaps were satisfactory; The flaps had good sensory recovery, S3⁺ in 14 patients and S4 in 4 patients. Severe contracture of the first toe web were not observed. The donor site of second toe got good recovery with normal activity of interphalangeal joint. Conclusions The tibial island flap of second toe is a good option for treatment of the defect on fibular hallux flap donor site. Meanwhile, it also meets the requirement of " donor site care" .