OBJECTIVE To develop a prediction model for durable clinical benefit （DCB） in patients with advanced esophageal squamous cell carcinoma （ESCC） receiving programmed death-1 （PD-1） inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator （Lasso） regression， and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method， and the model was evaluated by the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio （LMR） [odds ratio （OR）＝1.97， 95% confidence interval （CI）： 1.15-3.36， P＝0.013]， albumin （ALB） content （OR＝1.35， 95%CI： 1.13-1.60， P＜0.001）， body mass index （BMI） category 1 [normal vs. low： OR＝ 0.28， 95%CI （0.09-0.96）， P＝0.042]， BMI category 2 [overweight-obesity vs. low： OR＝0.08， 95%CI （0.01-0.59）， P＝0.013]， and treatment regimen [monotherapy vs. monotherapy combination therapy： OR＝0.07， 95%CI （0.01-0.50）， P＝0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 （95%CI： 0.746-0.904）， with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2＝ 9.930， P＝0.270， and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR， ALB content， BMI， and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

[Objective]Childhood trauma(CT)is considered one of the major risk factors for developing major depres-sive disorder(MDD)in adulthood.However,the neural basis of MDD patients with CT(CT-MDD)remains poorly under-stood.Therefore,the objective of our study is to explore the resting-state global brain functional connectivity(FC)in CT-MDD.[Methods]A total of 34 CT-MDD and 34 healthy controls performed resting-state fMRI.Whole-brain voxel-level degree centrality(DC)analysis was performed,and the brain regions with significant differences between the two groups were selected as region of interest(ROI)for further estimating the global brain FC.Subsequently,correlation analysis was performed between DC values,FC values in abnormal brain areas and clinical characteristics.[Results]The CT-MDD group showed increased DC value of the right middle frontal gyrus(MFG)compared with the healthy controls.Seed-based FC revealed that the CT-MDD group showed increased connections between the left precuneus and the right MFG or the right medial prefrontal cortex,relative to healthy controls(threshold at P<0.05).Additionally,the DC value of the right MFG was correlated with the severity of CT.[Conclusion]Our results show the increased FC between the left precuneus and the ROI(right MFG)as well as the right medial prefrontal cortex,which are two important brain regions within the de-fault mode network(DMN),and might suggest increased synchronism between the cognitive executive networks and DMN in CT-MDD.These findings may provide insights into the pathophysiological mechanisms underlying CT-MDD.

ObjectiveTo obtain high-quality chloroplast genome information on Stemona tuberosa and clarify its structure， sequence features， and phylogenetic status. MethodThe Illumina NovaSeq 6000 and PacBio RS Ⅱ platforms were used for library construction and sequencing of S. tuberosa， respectively. The data from both sequencing platforms were combined and subjected to bioinformatics analysis for genome assembly and base correction， resulting in a high-quality chloroplast genome. Subsequently， sequence features， repetitive sequences， gene diversity， and phylogeny were analyzed. ResultThe chloroplast genome size of S. tuberosa was determined to be 154 379 bp. The structure of the chloroplast genome followed the typical quadripartite circular form， consisting of a pair of inverted repeat regions （IRs） with a length of 27 074 bp， a small single-copy region （SSC） of 17 924 bp， and a large single-copy region （LSC） of 82 307 bp. The average GC content was 37.86%. A total of 121 genes were annotated， including 30 tRNA genes， four rRNA genes， and 87 protein-coding genes. Among them， six tRNA genes and 12 protein-coding genes contained introns. In the chloroplast genome of S. tuberosa， 49 long repetitive sequences and 59 single-nucleotide simple sequence repeats （SSRs） were identified. Comparative analysis of chloroplast genomes among four Stemona species revealed high diversity in the ycf1 and ndhF genes. The phylogenetic tree constructed based on the chloroplast genome showed consistent classification with the current taxonomic status of S. tuberosa. ConclusionThe high-quality chloroplast genome of S. tuberosa was successfully assembled， providing valuable information on the structure and sequence features of chloroplast genomes in four Stemona species， including S. tuberosa. These findings lay a foundation for the identification， evolution， and phylogenetic studies of medicinal plants in the genus Stemona.

Purpose/Significance Through the establishment of the pharmaceutical rebate prevention system,the capacity of preven-tion of pharmaceutical rebate can be improved,and the data security of patients can be protected more effectively.Method/Process With the help of information security equipments such as network access control,database audit,and resource monitoring platform,the algorithm of the original pharmaceutical rebate prevention system is optimized,and the comprehensive mobile terminal platform is com-bined to achieve a full range of pharmaceutical rebate prevention system and online audit and archiving.Result/Conclusion A more comprehensive defense system is built,and the system provides a more timely and efficient prevention and control means with clearer po-sitioning for data security management departments and discipline inspection departments.

Objective:To explore alterations of myocardial mechanics in mice models of physiological aging.Methods:Mice aged from 3 weeks to 24 months were chosen(n=50). Conventional echocardiography and layer speckle tracking echocardiography(LS-STE)were applied to evaluate alterations of myocardial mechanics in different ages(each for 10 mise). Pathological myocardial alterations in the aging process were detected using HE and Masson's trichrome staining.Results:Clear age-dependent changes in mice of different ages were observed when assessed using parameters of conventional echocardiography( P<0.05 for all). Values from parameters of LS-STE also showed that longitudinal, circumferential and radial strain in both the endocardium and the epicardium gradually decreased during physiological aging( P<0.05 for all). Compared with the 3-weeks old group, longitudinal strain in the endocardium was significantly reduced in the 14-months old group[(-23.49±2.32) vs.(-17.19±2.28), P<0.05]; Compared with the 3-weeks old group, radial strain, longitudinal strain in the endocardium, longitudinal strain in the epicardium, circumferential strain in the endocardium and circumferential strain in the epicardium were significantly reduced in the 24-months old group[(32.90±5.01) vs.(21.80±5.54), (-23.49±2.32) vs.(-15.44±2.27), (-13.23±3.19) vs.(-7.59±2.21), (-25.93±4.09) vs.(-20.31±4.08), (-9.30±1.92) vs.(-6.01±1.04), P<0.05)]; HE and Masson's trichrome staining of the myocardium indicated increases in the cross-sectional area of cardiomyocytes and fibrosis during the aging process. Conclusions:LS-STE can accurately detect early cardiac dysfunction and pathological myocardial alterations associated with aging in mice and may serve as an effective tool in evaluating anti-myocardial aging.

Objective:To study on the effects of gastrointestinal function and portal vein hemodynamics applicated with abdominal hot compressing with evodiae fructus and crude salt after hepatectomy.Methods:A total of 60 patients who underwent hepatectomy were randomly divided into 2 groups by random number table method, with 30 in each group. The control group was treated with conventional basic western medicine, while the treatment group was treated with medicinal evodiae fructus and crude salt hot compress on abdomen on the basis of the control group. The portal vein diameter (PVD), portal venous flow velocity (PVV), recovery time of main clinical indexes, clinical symptom scores and liver function indexes were dynamically monitored at different observation time points.Results:The scores of abdominal distension, nausea and vomiting in the treatment group were significantly lower than those in the control group 3 days after treatment ( t values were -3.489 and -2.740, respectively, all Ps<0.05). The recovery time of bowel sounds, first exhaust time and first defecation time in the treatment group were significantly earlier than those in the control group ( t values were -3.622, -4.297 and -4.151, respectively, all Ps<0.01). With the extension of treatment time, ALT in 2 groups showed a gradual downward trend ( P<0.05 or P<0.01), DBIL in control group was significantly higher at 3 days after treatment than before ( t=-2.157, P=0.039), and TBIL was significantly lower at 7 days after treatment than before ( t=2.175, P=0.038). The PVD ( t values were 3.528, 2.160) and PVV ( t values were 11.096, 4.264) of the treatment group were significantly higher than those of the control group 3 and 5 days after treatment ( P<0.01 or P<0.05). Conclusion:Early application of abdominal hot compressing with evodiae fructus and crude salt hot compress on abdomen after hepatectomy can improve the portal vein blood circulation and promote the rehabilitation of gastrointestinal function in patients with hepatectomy.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic expo-nential decay model.The potential effect of thimerosal on protein function,particularly for thiol-containing proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.

The adverse health effects of air pollution remains a daunting public health problem globally. The research of the health effects of air pollution provides important evidence for ambient air quality standard establishments and air pollution interventions. In recent years, causal inference has been gradually introduced into the observational study of environmental epidemiology, which provides more statistical method options for the study of causal relationships between air pollution and population health effects. Controlling confounders in observational studies is a major challenge for causal inference. This study introduces the causal inference methods for the identification and control of confounding factors currently used in the study of air pollution and population health effects, in order to provide methodological reference and basis for the causal inference study of air pollution and population health effects in China.

The adverse health effects of air pollution remains a daunting public health problem globally. The research of the health effects of air pollution provides important evidence for ambient air quality standard establishments and air pollution interventions. In recent years, causal inference has been gradually introduced into the observational study of environmental epidemiology, which provides more statistical method options for the study of causal relationships between air pollution and population health effects. Controlling confounders in observational studies is a major challenge for causal inference. This study introduces the causal inference methods for the identification and control of confounding factors currently used in the study of air pollution and population health effects, in order to provide methodological reference and basis for the causal inference study of air pollution and population health effects in China.