Objective:To determine the median effective dose (ED 50) of remimazolam for preoperative sedation in pediatric patients of different ages. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification I or Ⅱ pediatric patients, aged 1-6 yr, scheduled for elective surgery in our hospital from July to December 2023, in whom the preoperative anxiety was still not relieved after non-drug intervention (preoperative separation anxiety score [PSAS]≥3), were selected. According to the age, the children were divided into 1-<2 yr group, 2-<3 yr group, 3-<4 yr group, 4-<5 yr group and 5-6 yr group. A child's PSAS score = 1 at the time of separation from parents was classified as satisfactory sedation, and a PSAS score ≥ 2 was classified as unsatisfactory sedation. The initial dose of remimazolam in each group was 0.3 mg/kg, dose ratio 1.15. If the child was satisfactorily sedated, the next patient received a lower dose of remimazolam, or conversely if the child was not satisfactorily sedated, a higher dose was given in the next patient. The test was ended when 7 alternating waveforms appeared. The Dixon-Massey method was used to calculate the ED 50 and 95% confidence interval. Results:In 1-<2 yr group, 2-<3 yr group, 3-<4 yr group, 4-<5 yr group and 5-6 yr group, a total of 120 children were included in this study, with 26, 23, 21, 27 and 23 cases, respectively, and the ED 50 (95% confidence interval) of remimazolam for preoperative sedation was 0.152 (0.126-0.178), 0.159 (0.135-0.183), 0.171 (0.147-0.196), 0.150 (0.126-0.174), and 0.146 (0.121-0.170) mg/kg, respectively. There was no significant difference between the groups ( P>0.05). Conclusions:The ED 50 of remimazolam for preoperative sedation is 0.152, 0.159, 0.171, 0.150 and 0.146 mg/kg for every 1 yr in children aged 1-6 yr, and the age factor does not affect the preoperative sedative effect of remimazolam in children of this age group.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

Abstract： Arsenic and arsenic compounds have been listed as one of the toxic and harmful environment pollutants, and drinking, seafood intake, use of skincare products and inhalation of tobacco smoke are main routes of exposure to human arsenic exposure. The adverse effects of arsenic on pregnant outcomes have been paid much attention. Prenatal exposure to high-level arsenic has been found to increase the risk of spontaneous abortion among pregnant women. Based on national and international epidemiological studies on the correlation between arsenic exposure and spontaneous abortion during the period between 1992 and 2020, we review the association between arsenic exposure and spontaneous abortion and describe the mechanisms underlying spontaneous abortion caused by arsenic exposure, so as to provide insights into early prevention of spontaneous abortion.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Objective To investigate the mRNA-based anticancer gene transfer in MSCs-mediated cytotox-icity of glioma cells. Methods TRAIL mRNA and PTEN mRNA were synthesized in vitro. Immunoblotting assay was used to detect the expression of TRAIL and PTEN in the transfected MSCs.Transwell co-culture was perform to detect the migration ability of MSCs after gene transfection. The bioluminescence,live/dead staining and real time cell analyzer were used to analyze the viability of DBTRG cells. Results Compared with non-transfected MSCs, an enhanced migration rate was observed in MSCs with two kind of mRNA transfection.TRAIL-and PTEN-mRNA-induced cytotoxicity in DBTRG glioma cell was correlated with the ratio of the conditioned medium of the transfect-ed MSCs. A synergistic action was observed in TRAIL and PTEN in the transwell co-culture model. Conclusion The present study reveals the effect of synthesized mRNA-based gene transfer on mesenchymal stem cell-mediated cytotoxicity of glioma cells(DBTRG).

Objective To explore a method to culture human aortic valvular interstitial cells and identify the phenotypes,to establish the cell model which would be used to study aortic valve diseases in vitro.Methods Normal aortic valves of the patient with acute Stanford A aortic dissection in Peking Union Medical College Hospital were preserved during the surgical operation.Human aortic valvular interstitial cells were isolated and amplified in vitro by modified collagenase digestion method.The cell phenotype was identified by the immunofluorescent staining.Results Human aortic valvular interstitial cells could be successfully isolated and amplified in vitro by modified collagenase digestion method,identified by positive staining of Vimention and α-SMA.Conclusions The cell model of human aortic valvular interstitial ceils could be successfully established in vitro by modified collagenase digestion method.The cell phenotype identification proved to meet the experimental requirements.So it could provide cellular foundations for the study of pathogenesis of degenerative aortic valve disease.

Objective To systemically assess impact on postoperative outcomes after red blood cell transfusion(RBCT) in coronary artery bypass graft surgey.Methods A meta-analysis was performed on the comparison and synthesis of findings from included studies published from January 1980 to January 2014.Pooled odds ratio(OR) and 95 ％ confidence interval(CI) were calculated using RevManS.3 software.Sensitivity analysis was conducted and possible publication bias was tested as well.Results Seven retrospective studies including 71 228 patients(33 872 RBCT cases,37 356 control cases) were eligible for inclusion.The pooled analysis revealed difference in the 30-day mortality OR =1.85 (95％ CI:1.35-2.54),1-year mortality OR =2.02 (95 ％ CI:1.44-2.84),shock OR =2.92 (95 ％ CI:1.96-4.35),renal dysfunction OR =7.67 (95 ％ CI:1.44-40.94),mediastinitis OR =2.26 (95 ％ CI:1.72-2.97),and myocardial infarction OR =3.53 (95 ％ CI:2.89-4.29).Conclusion Perioperative RBCT can incresase the risk of postoperative mortality and complications in coronary artery bypass graft surgey.High-quality randomized case cohort studies are still needed for the further proof of the risk.

With the development of molecular imaging technology, incorporate multiple modes of medical imaging imaging techniques of SPECT/CT and PET/CT technology with a certain degree of development. But compared to SPECT/CT and PET/CT technologies, SPECT/CT far earlier than PET/CT technology to clinical applications, due to a variety of factors influence SPECT/CT far PET/CT clinical applications to grow faster. This article highlights the progress and problems of SPECT/CT technology.
Diagnostic Imaging ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

Background Laser assisted in situ keratomileusis (LASIK) for myopia will change corneal asphericity and further affect the quality of vision.However,how operating parameters such as ablation depth and optic zone diameter affect corneal asphericity is still rarely reported.Objective Aim of this study was to investigate the influence of corneal ablation depth and optic zone diameter on corneal asphericity after LASIK for myopia.Methods This prospective study comprised 175 eyes of 89 patients with the spherical equivalent of (-5.93± 1.98)D and the best corrected visual acuity (BCVA) ≥ 1.0.The flap creation with the femtosecond laser combine iris recognize guided LASIK was performed on the patients who were available for the evaluation at postoperative 6 months.Corneal aspherical index (Q value) at the central corneal 6.0 mm were measured with Orbscan IIz-corneal topography before and 6 months after operation.Corneal ablation depth and optic zone diameter were recorded in operation.The changes of visual acuity and spherical equivalent before and after surgery were compared by self-control method,and the correlations between corneal ablation depth or optic zone diameter with alteration of Q value (AQ) after LASIK were assessed using multiple regression analysis.Results The mean spherical power,cylinder diopter and spherical equivalent were (-5.57 ± 1.89) D,(-0.71 ±0.55) D and (-5.93 ± 1.98) D before surgery,and those after surgery were (-0.25 ±0.30),(-0.14±0.22)D and (-0.32±0.37)D,showing significant differences between before and 6 months after LASIK (t=-32.39,-23.91,-35.18,all at P＜0.01).The Q values at the central corneal 6.0 mm were -0.13 ± 0.09 (-0.47-0.08) in preoperation and 1.09 ± 0.54 (0.22-2.51) in postoperation,with a significant increase in postoperation (t=29.37,P＜0.01).Corneal ablation depth was (95±28) μm and optic zone diameter was (6.32±0.26)mm.Ablation depth appeared to be positive correlation with AQ (β =0.803),and optic zone diameter showed a negative correlation with AQ (β =-0.149),with a multiple regression formula AQ =1.517+0.015×ablation depth-0.3 ×optic zone diameter.Conclusions LASIK for myopia increase corneal Q value.The increase of corneal ablation depth and decrease of optic zone diameter contribute to enlargement of corneal Q value.

Inferior vena caval (IVC) tumor thrombus with cardiac extension is a very rare phenomenon,which proliferates fast and could be very challenging to the surgery.This paper was designed to investigate the clinical value of transesophageal echocardiography (TEE) for the surgical resection of IVC tumor thrombus extending into right cardiac cavities.Six cases from our medical institute,preoperatively diagnosed as IVC tumor thrombus with cardiac extension and scheduled for the surgical resection,were retrospectively analyzed.In addition to real-time and dynamic monitoring,comprehensive TEE exams were performed for all the patients respectively after anesthesia induction,namely before tumor resection and after tumor resection.Cardiac extension was defined by the preoperative finding of cardiac mass originated from IVC tumor thrombus by transthoracic echocardiography,computerized tomography or CT angiography.In all the cases,intraoperative TEE provided an accurate and excellent view of the IVC tumor thrombus.For case three,the IVC tumor thrombus was found at the IVC entrance to right atrium without further cardiac extension; for case five,the IVC tumor thrombus proliferated into right atrium but the extended cardiac mass was very slim and flexible and the tricuspid valve was untouched; for case four,the IVC tumor thrombus extended into right atrium and even cross the tricuspid valve but the extended cardiac mass was also very slim and flexible.Based on the TEE-provided information,the originally scheduled surgical decision was modified and the surgical resection was performed without cardiopulmonary bypass (CPB).For the other three cases,the intraoperative TEE showed similar results to preoperative findings.The huge IVC tumor thrombus extended into the right heart,presented almost no flexibility and dramatically compromised the intracardiac blood flow.For the three cases,CPB support was indispensable for the tumor resection.The full TEE exam after tumor resection in all the six patients displayed clear surgical resection without tumor residuals,but in those three patients suffered with severely compromised cardiac extension,severe tricuspid regurgitation was noticed.All the six patients were closely monitored until discharged,and no TEE-related complications were observed.This paper reports about TEE' s utilization in a series of consecutive patients undergoing surgical resection of IVC tumor thrombus with cardiac extension.In addition to its safety and effectiveness,TEE can provide valuable information for surgical decision making,surgical intervention assessment and anesthesiamanagement strategies.