This study presents a case of a girl of three year and 4 month old with ataxia and severe sen-sorineural hearing loss for 2 years.In order to improve hearing,she was hospitalized in the PUMC Hospital.Ge-netic testing performed found compound heterozygous variants of c.1186C＞T(p.P396S)and c.1357C＞T(p.R453W)in TWNK gene.After a multidisciplinary discussion of the case,the team suspected mitochondrial DNA depletion syndrome type 7(hepatocerebral type).The patient has shown nervous system impairment in-volvement but no evidence of liver dysfunction.The efficacy of cochlear implantation is uncertain and general anesthesia if applied will accelerate the progress of encephalopathy and might lead to multiple organ failure.Unsure of the perioperative safety,the parents of the girl did not chose the option of hearing intervention tempo-rarily,but chose oral symptomatic supportive treatment with coenzyme Q10,folate,levocarnitine,and complex vitamins as recommended.

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.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To evaluate the accuracy and stability of Eye-Monitor, a smart wearable device, in quantifying environmental risks related to myopia.Methods:A diagnostic test study was conducted.Forty-two subjects aged 18-25 years old were recruited from Shandong University of Traditional Chinese Medicine in December 2021.Forty-two Eye-Monitors were selected from 80 devices using the simple random sampling method.Static and dynamic tests were carried out to compare environmental risks related to myopia.The static tests included measurements under different working distances, different head tilt angles when sitting, and different light intensities.The dynamic tests included measurements under different near-work time, different outdoor activity time, different time watching computers, and different phone viewing time.Eye-Monitor with the largest sum of absolute values of total relative error was selected, Spearman rank correlation analysis was used to analyze the correlation between the set values and Eye-Monitor measurements, and the accuracy of the objectively measured values was evaluated by Bland-Altman consistency analysis.The stability of the objectively measured values from Eye-Monitor was evaluated by the coefficient of variation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-KS-2021005KY). Written informed consent was obtained from each subject.Results:There were significant correlations between the measured values and setting values in the working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time viewing phones ( rs=0.999, 0.998, 0.999, 0.998, 0.976, 0.959, 0.992, 0.997; all at P<0.001), with the 95% limits of agreement (LoA) of-1.23-2.32 cm, -1.49-4.24°, -13.90-26.90 lx, -6.46-0.11 minutes, -4.50-1.20 minutes, -4.01-1.34 minutes, -2.54-1.94 minutes and-2.15-0.45 minutes, respectively.More than 95% of dots were within the clinically acceptable LoA.The coefficients of variation of the measured values ranged from 1.23%-2.99%, 2.39%-8.25%, 0.87%-8.03%, 1.49%-12.52%, 6.63%-13.59%, 0.00%-14.15%, 1.20%-8.33 and 1.49%-12.51%, respectively, showing good stability.Eye-Monitor had good accuracy in measuring outdoor light intensity (95% LoA: -336.50-130.00 lx). Conclusions:The smart wearable device Eye-Monitor can be used to objectively monitor working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time watching phones, which are with good accuracy and stability.

Background: Job performance is known as an essential reflection of nursing quality. Colleague solidarity, positive emotion, and turnover intention play effective roles in a clinical working environment, but their impacts on job performance are unclear. Investigating the association between nurses’ colleague solidarity and job performance may be valuable, both directly and through the mediating roles of positive emotion and turnover intention. Methods: In this cross-sectional study, a total of 324 Chinese nurses were recruited by convenience sampling method from July 2016 to January 2017. Descriptive analysis, Spearman’s correlation analysis, and the structural equation model were applied for analysis by SPSS 26.0 and AMOS 24.0. Results: A total of 49.69% of participants were under 30 years old, and 90.12% of participants were female. Colleague solidarity and positive emotion were positively connected with job performance. The results indicated the mediating effects of positive emotion and turnover intention in this relationship, respectively, as well as the chain mediating effect of positive emotion and turnover intention. Conclusions In conclusion, dynamic and multiple supportive strategies are needed for nurse managers to ameliorate nursing job performance by improving colleague solidarity and positive emotion and decreasing turnover intention based on the job demand-resource model.

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*

Objective:To investigate the pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery.Methods:One hundred and four pediatric patients of either sex, aged 3-36 months, of American Society of Anesthesiologists Physical Status classification Ⅱ, with body mass index of 18.5-28.0 kg/m 2, diagnosed with oblique inguinal hernia and/or hydrocele, scheduled for laparoscopic high ligation of hernia sac and/or high ligation of sphingoid surgery, were included in the study. Intraoperative neuromuscle relaxation was assessed by transdermal stimulation of the ulnar nerve in the wrist using a TOF Guard monitor. Rocuronium 0.9 mg/kg, propofol 3 mg/kg, and sufentanyl 0.5 μg/kg were intravenously injected for anesthesia induction, and propofol 6-8 mg·kg -1·h -1 was intravenously infused to maintain anesthesia. The pediatric patients were divided into Ⅰgroup and Ⅱ group according to the degree of postoperative neuromuscular block. In group Ⅰ, sugammadex 2 mg/kg was intravenously injected when TOF returned to T 2 recurrence. In group Ⅱ, sugammadex 4 mg/kg was intravenously injected when the single stimulation count was 1 or 2 after tetanic stimulation. At 2 and 10 min after rocuronium administration, at the end of operation, 2 and 10 min after sugammadex administration, and when the children met the standard of leaving the resuscitation room, venous blood samples were collected for determination of plasma concentrations of rocuronium and sugammadex using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined using the Pheonix WinNonlin software. The onset of rocuronium and time for recovery of TOF ratio to 90% were recorded. Results:The pharmacokinetics of sugammadex was fitted to the nonlinear mixed-effect satrioventricular model.There was no significant difference in the peak concentration, area under the drug concentration-time curve, elimination half-life, apparent clearance, apparent volume of distribution, mean retention time, and time for TOF ratio returning to 90% between the two groups ( P> 0.05). Conclusions:The pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual is fitted to a nonlinear mixed-effect satrioventricular model, and sugammadex 2 and 4 mg/kg have similar pharmacokinetics in infants and young children undergoing daytime surgery.

Thymic epithelial tumor is a rare anterior mediastinal tumor. Surgery is the most important treatment for thymic tumors. However, non-surgical treatment is still an inevitable choice for unresectable advanced thymic tumors. The traditional treatment methods include chemotherapy and radiotherapy, but the effect is limited. With the development of immunotherapy therapy, some studies have attempted the exploration of immunotherapy for thymic tumors. Because of the low incidence rate of thymic tumors, these studies are mostly small retrospective analyses. This article review the clinical and basic research progress of immunotherapy for thymic tumors

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.