ObjectiveTo investigate the dynamic trajectories of prognostic scores and key clinical indicators in hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） patients without liver cirrhosis， to clarify their association with outcomes， and to provide new evidence for individualized prognostic assessment. MethodsA prospective study was conducted for the data of 154 non-cirrhotic HBV-ACLF patients who attended Beijing YouAn Hospital of Capital Medical University from January 2016 to December 2023， including prognostic scores and key biochemical indicators on Days 3， 7， 14， 21， and 28 of the disease course. According to the outcome of patients at 1 year， they were divided into death/liver transplantation group with 43 patients， liver cirrhosis group with 23 patients， and non-liver cirrhosis group with 88 patients， and the trajectory heterogeneity of different outcome subgroups was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data among the three groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data among the three groups； the Wilcoxon test was used between two groups. the chi-square test was used for comparison of categorical data between groups. The mean and its 95% confidence interval （CI） were calculated for each indicator at difference time points； the linear interpolation method was used to connect the means at adjacent time points and construct the group-specific longitudinal trend curve； the 95%CI was visualized using the semi-transparent ribbon area， with the transparency parameter （α=0.2） optimized to enhance the visual discrimination of overlapping intervals across multiple groups. A linear mixed-effects model was used to compare the longitudinal changing trend of each indicator between the patients with different outcomes； likelihood ratio was used to evaluate the significance of the interaction effect between time and group， and in case of the significant interaction effect， the slope based on the estimated marginal mean was used for comparison between two groups. ResultsThere were significant differences between the three groups in the incidence rates of ascites and grade Ⅲ — Ⅳ hepatic encephalopathy， MELD score， MELD-Na score， CLIF-C ACLF score， COSSH-ACLF Ⅱ score， total bilirubin （TBil）， international normalized ratio （INR）， alpha-fetoprotein， blood sodium， alanine aminotransferase， and procalcitonin at the baseline（all P0.05）. The analysis of dynamic trajectories showed that the death/liver transplantation group had high levels of prognostic scores and the biochemical parameters of TBil and INR （TBil400 μmol/L， INR2.5）， as well as a low level of platelet count （PLT） （100×10⁹/L）. The non-liver cirrhosis group had rapid improvements in indicators， with TBil200 μmol/L， INR1.5， and PLT100×10⁹/L by day 28， while the liver cirrhosis group showed a trend of recovery， with TBil200 μmol/L， INR2.0， and PLT 100×10⁹/L on day 28， with significant global heterogeneity in the temporal trends of the above indicators across the three groups （all P0.01）. ConclusionDynamic monitoring of prognostic scores and key clinical indicators can effectively stratify the 1-year outcomes of non-cirrhotic patients with HBV-ACLF. Patients with poor prognosis were typically characterized by INR 2.5 and TBil 400 μmol/L. Among those who survived beyond 1 year， individuals who subsequently progressed to cirrhosis were frequently identified by the presence of INR 1.5， TBil 200 μmol/L， and PLT 100×10⁹/L at day 28.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective To investigate the influence of metabolism-related factors(overweight and/or obesity,hyperglycemia,hypertension and dyslipidemia)on the 90-day prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),and to establish a predictive model.Methods A retrospective analysis was performed for the clinical data of 365 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The Affiliated Hospital of Southwest Medical University,from June 2018 to June 2022,and according to the 90-day follow-up results,they were divided into survival group with 273 patients and death group with 92 patients.General information and related laboratory markers were collected from all patients.The t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distribution continuous data between groups;the chi-square test was used for comparison of categorical data between groups.A Logistic regression analysis was used to determine whether metabolism-related factors were independent risk factors for the 90-day prognosis of HBV-ACLF patients,and the Kaplan-Meier analysis was used to investigate the correlation between metabolism-related factors and the 90-day survival rate of HBV-ALCF patients.The area under the ROC curve(AUC)was used to compare the value of different scoring models in predicting the 90-day prognosis of HBV-ACLF patients.Results The multivariate Logistic regression analysis showed that hypertension(odds ratio[OR]=4.698,95%confidence interval[CI]:1.904-11.593,P=0.001),alanine aminotransferase(OR=0.999,95%CI:0.999-1.000,P=0.010),triglyceride(TG)(OR=4.979,95%CI:2.433-10.189,P＜0.001),high-density lipoprotein cholesterol(OR=0.258,95%CI:0.087-0.762,P=0.012),apolipoprotein B(OR=0.118,95%CI:0.026-0.547,P=0.006),and CLIF-C OF score(OR=2.275,95%CI:1.150-4.502,P＜0.001)were independent influencing factors for the short-term prognosis of HBV-ACLF.The combined predictive model of metabolism-related factors had a larger AUC than the predictive model of a single factor,among which the predictive model of hypertension+TG+CLIF-C OF score had the largest AUC of 0.886.The patients with metabolism-related factors tended to have higher incidence rate of liver complications and 30-and 90-day mortality rates.Conclusion The presence of the metabolism-related factors such as hypertension and dyslipidemia can increase the severity of HBV-ACLF and the risk of short-term mortality,and the hypertension+TG+CLIF-C OF score predictive model has a good value in predicting the short-term prognosis of HBV-ACLF patients.

OBJECTIVE To investigate the value of magnetic resonance imaging(MRI)parameters in differentiation between olfactory neuroblastoma(ONB)and sinonasal diffusion large B cell lymphoma(DLBCL).METHODS Pathology-proven 34 ONB patients and 29 DLBCL patients with MRI examinations before treatment were included.The conventional MRI features and semi-quantitative parameters of two groups were documented and analysis.Statistical analysis between the two groups were performed.The independent sample t-test and was used for continuous variables in normal distribution,Mann-Whitney U test was used for non-normal distribution.The frequency of categorical variables were compared by Chi-square test.Logistic regression analysis was done to identify the most predictive MRI features for differentiation.RESULTS ONB often located in the nasal cavity olfactory recess and ethmoid sinus,characterized by intracranial extension through the cribriform plate,forming a'dumbbell'shape mass(P=0.004).DLBCL more often located in paranasal sinus,orbits(P<0.001,P=0.024).T2WI signal intensity of ONB were higher than DLBCL(P<0.001).ONB showed more signs of outward turbinate and lobulation(P=0.001,P=0.004).ADCave of ONB was obviously higher than DLBCL(P<0.001).On DCE-MRI,ONB showed higher CImax,WR(P<0.001,P=0.011),lower TTP than DLBCL(P=0.003).ONB presented more wash-out type TIC curve(P=0.022).Logistic regression analysis demonstrated that tumor location(olfactory cleft or maxillary sinus),T2WI intensity,ADCave with cutoff value of 0.82×10-3mm2/s and TTP with cut off value of 52 seconds were the most predictive MRI features for differentiation.CONCLUSION The multiple MRI conventional and functional parameters are helpful in differentiating ONB from DLBCL.

ObjectiveTo determine the death level and change trend of malignant tumors among residents in Yuyao， and to provide support for accurate prevention and control of malignant tumors. MethodsWe collected the death monitoring data of Yuyao registered residents from 2014 to 2021， and calculated the indicators， including crude mortality rate （CMR）， standardized mortality rate （SMR）， potential years of life lost （PYLL）， average years of life lost （AYLL）， and PYLL rate （PYLLR）. We also calculated the average annual change percentage （AAPC） using Joinpoint regression model. ResultsThere were 13 754 deaths from malignant tumors in Yuyao from 2014 to 2021， accounting for 26.54% of the total deaths in the same period. The average annual mortality rate was 205.63/10⁵， and the standardized mortality rate was 115.62/10⁵. The SMR showed a downward trend in 8 years （AAPC=-4.76%， t=-2.296， P=0.061）. The average annual mortality of malignant tumors was 274.15/10⁵， and the standardized mortality was 149.83/10⁵. The average annual mortality of female malignant tumors was 139.03/10⁵， the standardized mortality was 81.01/10⁵. Male mortality was higher than the female mortality （χ²=1 487.389， P<0.001）.The mortality rate of malignant tumors increased with age （AAPC=54.94%，t=27.678，P<0.001）. The mortality rate of malignant tumors in different age groups showed a downward trend in 8 years （AAPC=-5.74% for 0- years old group， -8.49% for 15- years old group， -6.02% for 45- years old group， and -3.49% for ≥65 years old group）. The top five causes of death from malignant tumors in residents were lung cancer， gastric cancer， liver cancer， esophageal cancer and colorectal cancer， accounting for 68.15% of all deaths from malignant tumors. Lung cancer ranked first among the causes of death from male and female malignant tumors. PYLL caused by malignant tumor death was 96 585.50 person years， AYLL was 7.02 years per person ， and PYLLR was 16.42‰. ConclusionThe mortality rate of malignant tumors among registered residents in Yuyao is on the decline， but it is still the primary death cause threatening the residents. Lung cancer is the malignant tumor that causes the greatest loss of life. It is urgent to build a comprehensive intervention system for malignant tumors that focuses on men， middle-aged and elderly people， advocate a healthy lifestyle， and combine early screening and reasonable treatment to block disease progress.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To understand the trend of Helicobacter pylori （Hp） resistance to clarithromycin and levofloxacin and to provide guidance for Hp eradication therapy. Methods:From January 2014 to December 2018， a total of 66 515 patients with gastrointestinal symptoms were enrolled in the First People's Hospital of Wenling. The patients were divided into the following groups： childhood （0 to 6 years old）； juvenile （7 to 17 years old）； youth （18 to 40 years old），middle age （41 to 65 years old），and old age （≥66 years old）. All patients received gastroscopy， gastric mucosal biopsy， Hp culture and drug sensitivity test of clarithromycin and levofloxacin. Results:The Hp positive rate showed a significant downward trend in 2016， 2017 and 2018 （χ²=14.317， 47.079， 88.054， all P<0.05）. The average resistance rate of Hp to clarithromycin from 2014 to 2018 was 22.72% （4 732/20 831） showing an increasing trend， but the increase was slower after 2017. The average resistance rate to levofloxacin was 30.55% （6 364/20 831）， and the overall trend showed a sharp rise from 2015 to 2017 （χ²=38.383， 49.569， both P<0.05）， and a significant decline was detected after 2017 （χ²=18.841， P<0.05）. The resistance rate of Hp to levofloxacin in patients increased with age. The clarithromycin resistance rate first decreased and then increased with age， and the resistance rate in old age （32.52%， 763/2 346） was higher than that in youth （22.09%， 1 086/4 916） and middle age patients （21.21%， 2 854/13 458）， and the differences were significant （χ²=991.071， 144.968， both P<0.05）. The resistance rate of Hp rose from 12.73% （14/110） in juvenile to 43.31% （1 016/2 346） in old age （χ²=228.867， P<0.05）. Conclusion:In recent years， the positive rate of Hp infection in Wenling area has a decreasing trend. Although the resistance rate of Hp to clarithromycin and levofloxacin has been rising slowly or decreasing， it is still at a high level. In the selection of Hp eradication program， the differences between patients in different age groups should be considered with particular attention on the minors.