Remimazolam is a novel ultra-short-acting benzodiazepine characterized by rapid metabolism via hydrolysis by non-specific esterases.This mechanism enables fast onset and quick recovery,significantly shortening the duration of anesthesia and effectively reducing the risk of drug accumulation in the body.It ex-hibits high binding specificity for the γ-aminobutyric acid(GABA)receptor,leading directly to central nerv-ous system inhibition and producing a pronounced sedative effect.This profile offers a more precise and con-trollable approach to anesthesia in clinical practice.The safety and efficacy of remimazolam have been demon-strated across various clinical settings,including procedural sedation,induction and maintenance of general an-esthesia,and sedation in the intensive care unit(ICU).Its adverse effects are relatively infrequent and highly predictable,as substantiated by numerous clinical trials;however,the optimization of its dosing regimens re-quires further in-depth investigation.This review summarized the pharmacological properties of remimazolam and provides a detailed discussion on the impact of various factors on its pharmacodynamics.These factors in-clude basic patient characteristics(such as gender,age,obesity,hepatic and renal function,and circadian rhythms)and external influences(such as altitude and drug interactions).

ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials （RCT） of traditional Chinese medicine （TCM） for treating chronic atrophic gastritis （CAG）， so as to provide references for constructing the core outcome set （COS） of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated， and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included， with a sample size of 44-398 cases. 164 outcome indicators were reported， with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes， followed by physical and chemical examination （69.41%）， TCM syndrome （12.69%）， symptoms and signs （11.15%）， safety indicators （5.37%）， quality of life （0.65%）， long-term prognosis （0.65%）， and economic evaluation （0.08%）. According to the statistical analysis， there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG， including various indicators， non-standard name reports， unclear primary and secondary indicators， random combination of subjective and objective indicators， neglected patient report outcome indicators， missing long-term prognosis and economic indicators， insufficient reporting of safety indicators， and inconsistent measurement tools and measurement time points. ConclusionIn the past five years， there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.

Objective The study aimed to compare the diagnostic efficacy of QuantiFERON-TB Gold(QFT-TB)detection of specific cellular immune IGRAs in tuberculosis diagnostic laboratory for pulmonary tuberculosis,extrapulmonary tuberculosis and special population samples in vitro,which may provide evidence for clinical diagnosis and treatment.Methods A total of 546 patients with tuberculosis(AFB + 146 cases,AFB-247 cases),117 patients with molecular biology positive tuberculosis(Xpert 69 cases,TB-DNA 48 cases)and 36 patients with histopathological positive were collected from January to July 2023.There were 72 cases of extrapulmonary tuberculosis,276 cases of pleural effusion and 25 cases of ascites.QFT-TB method was used for detection,chi-square test was applied for com-parison between groups,and the methodological evaluation of positive rate and coincidence rate were all compared.Results The positive rates of QFT-TB in pulmonary tuberculosis,extrapulmonary tuberculosis and close contacts were 83.69%,69.44%,and 32.41%,respectively.The coincidence rates of QFT-TB in AFB +,GeneXpert,TB-DNA and pathological confirmed tuberculosis patients were 91.09%,88.40%,81.25%,and 72.22%,respectively.The positive rate of pleural effusion in patients with tuberculous pleurisy was 60.50%,and the uncertainty rate was 29.71%.The positive rate of ascites was 44.00%and the uncertainty was 36.00%.Conclusion QFT-TB test has good value in the auxiliary diagnosis of pulmonary tuberculosis,and has certain reference significance for the diagnosis of extrapulmonary tuberculosis based on the detection of pleural fluids and ascites.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Building a multi-source heterogeneous data fusion platform for clinical data centers has become a common consensus in the medical information industry. The data fusion platform built by a certain hospital consisted of five parts: data acquisition module, data processing module, data comparison and repair module, data subscription and application module, and data fusion management platform. Data quality check was conducted on data scattered across the hospital′s operational systems with different structures and types, diverse patterns and states, different sizes and versions. The platform could handle duplicate and redundant metadata, collect, transform, process, distribute, and load data as needed, and maintain data consistency through comparison and repair. This platform is capable of automatically capturing, analyzing, governing, and integrating different types of data across databases, operating systems, and hardware environments, meeting diverse medical data application needs, and supporting the high-quality development of intelligent hospitals

Objective To explore the relationship between hearing loss and cognitive function in the elderly population through propensity score matching method.Methods We analyzed the data of 7605 participants aged 60 and above who were included in the 2018 China Health and Retirement Longitudinal Study(CHARLS).The non-substitutable 1∶1 nearest neighbor matching method without caliper value was used for propensity score matching and G-computation was used to estimate the average treatment effect(ATE)of hearing loss on all dimensions of cognitive function.Results Before matching,there were 3626(47.68%)women,with 1409(18.53%)of whom suffering from hearing loss and 3031(39.86%)of whom suffering from cognitive impairment.After matching,1409 subjects were included in the hearing loss group and 1409,in the normal hearing group,with both groups sharing similar distribution of basic demographic characteristics.The results for the average treatment effect of the population indicated that the cognitive function scores of the hearing loss group were lower than those of the normal hearing group,with the overall cognitive function being 0.593 points lower(95%confidence intervel[CI]:-0.916--0.257,P<0.001),orientation being 0.183 points lower(95%CI:-0.302--0.055,P=0.004),immediate memory being 0.150 points lower(95%CI:-0.218--0.085,P<0.001),and language skills being 0.178 points lower(95%CI:-0.303--0.058,P=0.006).The prevalence of cognitive impairment of the hearing loss group was 4.2%higher than that of the normal hearing group(95%CI:0.007-0.077,P=0.020).Conclusion Hearing loss adversely affects the orientation,memory,and language skills of the elderly population and forms a potential risk factor for cognitive impairment in the elderly population.

Objective To investigate the prevalence and influencing factors of isolated diastolic hypertension(IDH)in the Tibetan population in Tibet and to provide some evidence for the prevention and control of hypertension and other related diseases in high-altitude areas.Methods A multistage stratified whole-group random sampling method was used to enroll participants from Ngari Prefecture,Nagqu City,Shannan City,and Lhasa City,Tibet.A total of 3 918 native Tibetans with complete data were enrolled in the survey between June 2020 and August 2023.The participants were aged from 18 to 80.The demographic data,life habits,and chronic disease prevalence of the participants were collected.Fasting venous blood samples were collected to perform the routine blood tests and blood biochemistry tests.The prevalence of IDH in subgroups with different characteristics was analyzed and the influencing factors were analyzed by multivariate logistic regression,accordingly.The predictive value of influencing factors on the prevalence of IDH was analyzed by the receiver operating characteristic(ROC)curve and the findings were compared with those of the previous prediction models for IDH.Results The prevalence of hypertension in the participants was 33.7%(n=1 321),among which,395 had IDH,accounting for 29.9%of the hypertensive patients.The results of multivariate regression showed that age,heart rate,body mass index,waist circumference,hemoglobin,and low-density lipoprotein cholesterol were associated with risks of developing IDH(P＜0.05).The area under the ROC curve(AUC)was 0.71,which indicated improved accuracy for predicting the risks for IDH in comparison with previous predictive models for IDH.Among the influencing factors,BMI showed the best predictive value for IDH risks.Conclusion The prevalence of IDH is high among Tibetans in Tibet,suggesting the necessity for rational allocation of health resources in accordance.Compared with the previous IDH prediction models,the model proposed in this study is more suited for the Tibetan population.Targeted interventions should be carried out for the high-risk populations,such as young and middle-aged adults and populations suffering from overweight/obesity,central obesity,high-altitude polycythemia,and dyslipidemia,so as to effectively control the occurrence and development of IDH.

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 ^-5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Neoplasm, Residual/pathology* ; Biomarkers, Tumor/genetics* ; Computational Biology

Objective:To investigate the effect of high glucose on scavenger receptor-A (SR-A) in human glomerular mesangial cells (HMC) and explore the mechanism of inflammatory injury mediated by SR-A in HMC cultured in high-glucose medium.Methods:According to the concentration of D-glucose in culture medium, HMC were divided into normal glucose group (5.5 mmol/L) and high glucose group (30 mmol/L), with mannitol group as hypertonic control. High glucose group was transfected with SR-A small interfering RNA (siSR-A) and the transfection control (siNC) group were set up. Western blotting technology was used to detect the levels of SR-A, NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-1β (IL-1β) protein. Immunofluorescent staining was applied to measure the SR-A in HMC. The mRNA of NLRP3, Caspase-1, IL-1β, FN, ColⅣ, α-SMA and GRP78 were detected by real-time quantitative PCR. The relative activity of Caspase-1 was detected by enzyme method and the concentration of IL-1β in culture medium was detected by enzyme linked immunosorbent assay. Flow cytometry was used to measure the cell cycles of HMC. One-way ANOVA and SNK-q test were used for statistical analysis.Results:The protein level of SR-A in high glucose group was higher than that in normal glucose group and mannitol group (1.23±0.21 vs. 0.68±0.10, 1.23±0.21 vs. 0.78±0.13, all P<0.05). In addition, mean fluorescence intensity of SR-A, protein levels of NLRP3 and IL-1β, mRNA of NLRP3, Caspase-1 and IL-1β, relative activity of Caspase-1 as well as the concentration of IL-1β in high glucose group were all significantly higher than those in normal glucose group and mannitol group (all P<0.05).After transfection induced silencing, SR-A protein in high glucose siNC group was higher than that in high glucose siSR-A group and normal glucose siNC group (1.23±0.10 vs. 0.20±0.01, 1.23±0.10 vs. 0.87±0.01, all P<0.01). In high glucose siNC group, the NLRP3, IL-1β proteins, the NLRP3, Caspase-1 and IL-1β mRNA, all of the mRNA levels of FN, ColⅣ, α-SMA, GRP78 and the proportion of DNA synthesis phase were all higher than those in high glucose siSR-A group and normal glucose siNC group (all P<0.05). Conclusion:High glucose can promote abnormal cell proliferation, increase mesangial matrix production and enhance oxidative stress response through upregulating SR-A expression, and ultimately aggravate cellular inflammatory damage in HMC, which may be associated with NLRP3-Caspase-1-IL-1β pathway regulated by SR-A expression.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.