Postoperative cognitive dysfunction(POCD)is one of the common complications in the perioperative period,and it has a high incidence in elderly patients,and the large production of neuroinflammatory factors under surgical stimulation is the main cause of postoperative POCD.As an ultra-short-acting benzodiazepine of γ-aminobutyric acid receptor agonist,remimazolam can play a sedative-hypnotic and anxiolytic role in clinical practice,and can reduce inflammatory factors in the central nervous system and improve postoperative cognitive dysfunction by inhibiting neuroinflammatory response and oxidative stress.This article reviews the protective effect and mechanism of remimazolam on postoperative cognitive function,so as to provide a basis for the clinical use of remimazolam.

This data article describes the"Typical Regional Activity Patterns"(TRAP)dataset,which is based on the Tackling Key Problems in Air Pollution Control Program.In order to explore the interaction between air pollution and physical activity,we collected activity patterns of 9,221 residents with different occupations and lifestyles for three consecutive days in typical regions(Jinan and Baoding)where air pollutant concentrations were higher than those in neighboring areas.The TRAP dataset consists of two aspects of information:demographic indicators(personal information,occupation,personal habits,and living situation)and physical activity pattern data(activity location and intensity);additionally,the exposure measures of physical activity patterns are included,which data users can match to various endpoints for their specific purpose.This dataset provides evidence for exploring the attributes of activity patterns of residents in northern China and for interdisciplinary researchers to develop strategies and measures for health education and health promotion.

Remazolam is a γ-aminobutyric acid(GABA)receptor agonist.It is a short-acting benzodiazepine drug that has just been launched in China in recent years.Its mechanism of action is to enhance inhibitory neurotransmitters of GABA in the central nervous system.It has been widely used in clinical practice for sedation,hypnosis,anti anxiety,and the treatment of insomnia.Meanwhile,remazolam is mainly used for induction and maintenance of general anesthesia during the perioperative period,with a fast onset time and a brief duration of action.Recent studies have shown that remazolam can protect important organs and alleviate organ damage by reducing inflammatory responses and oxidative stress,regulating cell apoptosis,and other pathways.This article summarizes the protective effects and mechanisms of remazolam on the brain,heart,liver,and lung,providing a theoretical basis for the clinical application of remazolam.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Purpose: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). Methods: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients’ initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)–free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. Results: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). Conclusion For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

ObjectiveTo explore a new model for lens-induced myopia （LIM） in mice and describe the changes of diopter and ocular biological parameters. MethodsTwenty-seven 21-day-old C57BL/6 mice were divided into three groups （ratio， 5：1：3）： LIM group， plano lens （PL） group and normal control （N） group. The right eyes were intervened while the left eyes were left as control. The refraction was detected with retinoscopy after the pupils were dilated with compound topicamide and ocular axial length was measured by optical coherence tomography （OCT） in vivo at baseline and 1， 2， 3， and 4 weeks after the intervention. Paired t test was performed between left and right eyes within each group. Welch's ANOVA was used for comparison among the three groups. When the difference was statistically significant， the Dunnett's T3 was used to correct P value for pairwise comparison. ResultsAfter 2 weeks of defocus induction， the refraction of the intervened eye in LIM group shifted to myopia about （-2.55±1.54） D（t=6.430， P＜0.000 1）， and the ocular axial length （AL） increased about （0.051±0.024） mm（t=7.837， P＜0.000 1）. The difference of interocular change in refraction in LIM group compared with PL group and N group was -2.30 D （P=0.014） and -2.55 D （P＜0.000 1）， respectively. The difference of interocular change in AL in LIM group was 0.048 mm （P<0.000 1） and 0.047 mm （P<0.000 1） compared with that in PL group and N group， respectively. With the extension of intervention time， the degree of myopia drift increased. ConclusionIn this study， a clasp-based and detachable LIM model was described and validated. After 2 weeks of intervention， the refraction shifted significantly toward myopia and the AL increased significantly. The LIM model is simple to construct and can provide a reference for the model construction of animal experiments in myopia research.

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

Humans ; East Asian People ; Psoriasis/drug therapy* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Treatment Outcome ; Severity of Illness Index

ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.