Objective To investigate the role of macrophages in the process of fine particulate matter (PM2.5)exposure induced damage to pulmonary blood-air barrier.Methods Eighteen male BALB/C mice (aged of 10 weeks,weighing 24～27 g)were randomly divided into control group and low-and high-dose PM2.5 exposure groups (receiving 1 .8 and 16.2 mg/kg,respectively),with 6 mice in each group.The control group received tracheal instillations of normal saline on days 1,4,and 7,whereas the exposure groups were administered corresponding dose of PM2.5 exposure at the same time points.In 24 h after last exposure,pathological changes in the lung tissues were observed,and the contents of total protein (TP ),lactate dehydrogenase (LDH ),and alkaline phosphatase (AKP ) in bronchoalveolar lavage fluid (BALF ),and F4/80 protein level in lung tissue were measured to evaluate the blood-air barrier damage and macrophage infiltration within the lung tissues.Additionally,an in vitro model of the blood-air barrier was established using A549 alveolar epithelial cells and EA.hy926 vascular endothelial cells.In combination with a THP-1 macrophage model,the supernatant PM2.5 supernatant,macrophage supernatant,and PM2.5-macrophage supernatant were incubated with the barrier model for 24 h,respectively.Transmembrane electrical resistance (TEER),sodium fluorescein permeability of the barrier model,and LDH release from the barrier cells were measured to ascertain the extent of macrophage-mediated enhancement in barrier damage induced by PM2.5 exposure.Furthermore,the expression of inflammatory cytokines,such as TNF-α,IL-1β,IL-6,and IL-8 in the macrophages after PM2.5 exposure was analyzed with quantitative real-time PCR (qPCR)and enzyme-linked immunosorbent assay (ELISA).Results PM2.5 exposure induced lung tissue damage in mice in a dose-dependent manner,significantly elevated the contents of TP,LDH and AKP in the BALF and caused marked infiltration of macrophages into the lung tissue,especially the high-dose exposure when compared with the mice from the control group (P<0.01 ).In vitro barrier model exposure experiments showed that in comparison with the treatment of 150 and 300 μg/mL PM2.5 and macrophage supernatant,the same doses of PM2.5-macrophage supernatant resulted in notably decreased TEER and significantly enhanced permeability in the barrier model (P<0.01 ),and markedly increased LDH release from epithelial and endothelial barrier cells (P<0.01 ).Additionally,the exposure of 150 and 300μg/mL PM2.5 led to a significant up-regulation of TNF-α,IL-1β,IL-6,and IL-8 in the macrophages (P<0.01 ).Conclusion Macrophages deteriorate PM2.5-induced functional impairment of the pulmonary blood-air barrier.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To describe the epidemiological distribution of hemorrhoids in a physical exami-nation population in China,which could provide evidence for precision prevention and early intervention of hemorrhoids.Methods:Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design,which collected information by a questionnaire and physical examination results from each subject.The epidemiological distribution of hemorrhoids was described using Logistic models.The gender-,age-,and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China(2010).Results:A total of 2 940 295 adult subjects were included in the study,of whom the average age was(41.7±14.0)years,and 52.6％were females.The standardized detection rate of hemorrhoids was higher for females(43.7％)than that for males(17.7％;P＜0.001)in this study.In the females,the age distribution of hemorrhoids was inverted U-shaped,with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years(63.5％).In the males,the standardized detection rate of hemorrhoids increased along with age,with the highest percentage of 17.2％in the age group of 50-59 years,and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly(P＜0.001 for trend test).The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females(P＜0.001).The standardized detection rate of hemorrhoids showed a positive corre-lation with body mass index(P＜0.001 for trend test in males).Conclusion:The detection rate of hemorrhoids varied to gender,age,obesity,and hypertension status,which could help to identify the risk factors and the high-risk sub-groups,and hence to strengthen health education and early detection accordingly,which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population.This study was conducted in a physical examination population,and the conclusions of this study should be extrapolated with caution.

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

In recent years， there have been both achievements and criticisms in using the methods of evidence-based medicine to evaluate the efficacy of traditional Chinese medicine （TCM）， which is mainly due to the differences between TCM and Western medicine. To facilitate the clinical evidence-based evaluation in TCM， this paper analyzes the challenges faced in TCM clinical evaluation， particularly in the diagnosis， clinical intervention， and efficacy assessment methods. Considering the current state of TCM clinical evaluation and our clinical research experience， we believe that establishing and refining the TCM disease-syndrome diagnostic system is a prerequisite for the practice of clinical evidence-based evaluation in TCM. Furthermore， this paper discusses the specific connotation， development， and challenges of the disease-syndrome diagnostic system， especially the choice of TCM disease name or modern medical disease name in this system. Then， the clinical application scenarios are expounded from ''TCM disease name + syndrome differentiation'' and ''Western medicine disease name + syndrome differentiation''. Moreover， this paper proposed solutions for practical issues such as the standardization of disease and syndrome diagnosis， selection of clinical evaluation methods， and application of evidence-based approaches in clinical evaluation. Establishing the criteria for the disease-syndrome diagnostic system is crucial for the determination of clinical intervention regimen， the selection of clinical research methods， and the establishment of evaluation indicators， which are essential for generating high-quality clinical evidence. To sum up， this paper reviews the development and current situation of the disease-syndrome diagnostic system and proposes an exploratory approach for the standardization and application of this system in clinical evidence-based evaluation. This approach aims to facilitate the integration of TCM with modern clinical practice， thereby achieving standardized evaluation of TCM efficacy and deepening the integration of TCM with evidence-based medicine.

Objective: To understand the impact of social media usage on the human papilloma virus(HPV) vaccination willingness among college students in Xinjiang, so as to provide a theoretical basis for early prevention of HPVrelated diseases and preventive education. Methods: From March to April 2022, a total of 834 college students were selected from three universities including Xinjiang Agricultural University, Xinjiang Normal University and Xinjiang Medical University by stratified cluster random sampling method for online and offline surveys. The demographic characteristics, social media usage, risk perception, HPV vaccination willingness were obtained through questionnaires, and the Logistic regression analysis method was used to explore the role of HPV vaccine risk perception between social media use and HPV vaccination willingness of college students. Results: Associations were found between social media use (contact intensity, satisfaction, trust), risk perception (risk perception disorder, risk perception benefit) and HPV vaccination willingness among college students (r=0.37, 0.34, 0.35; 0.25, 0.31, P<0.05). Risk perception benefit had an intermediary effect between social media contact intensity, social media satisfaction, social media trust and HPV vaccination willingness, and the intermediary effects were 0.03 (95%CI=0. 01-0.06), 0.04(95%CI=0.02-0.07), 0.04(95%CI=0.01-0.06),and the proportions of intermediary effect were 18.00%, 26.35%, 23.00%, respectively.Risk perception disorder had an intermediary effect between social media satisfaction and HPV vaccination willingness [0.02 (95%CI=0.00-0.04)], and the intermediary effect accounts for 11.36%. Conclusions Risk perception benefit is the most important related factors of HPV vaccine willingness, which plays an intermediary effect between social media usage and the willingness to HPV vaccination. HPV publicity and education should be strengthened on social media platforms to promote HPVrelated knowledge and awareness of active prevention of HPV infection among college students.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

Objective:To summarize long-term clinical follow-up results of segment instability between the upper instrumented vertebra (UIV) and the adjacent upper vertebra (UIV+1) and to establish the optimal timing for surgery for UIV+1.Methods:A retrospective analysis was conducted on 265 patients with lumbar degenerative diseases who underwent transforaminal lumbar interbody fusion (TLIF) surgery at the Department of Spinal Surgery, Zhongda Hospital, from January 2014 to December 2018. The cohort included 119 male and 146 female patients, with an average age of 64.93 years (range: 32-86 years). Preoperative dynamic imaging measured sagittal angulation (SA) and sagittal translation (ST) of the UIV+1/UIV segment. Patients with SA>10° or ST>2 mm were categorized into the unstable group, further divided into the unstable non-fusion group and the unstable fusion group based on whether UIV+1 expansion fusion was performed. The remaining patients were classified into the stable group. Imaging indicators, Visual Analogue Scale (VAS) scores, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores were compared among the groups, with JOA improvement rates calculated to assess clinical efficacy. Pearson correlation coefficient analysis was employed to examine correlations between preoperative imaging indicators and final follow-up JOA improvement rates. Receiver Operating Characteristic (ROC) curves and the maximum Youden index were utilized to determine thresholds for preoperative SA and ST.Results:The follow-up duration for all patients was 73.53±12.92 months (range: 61-108 months). The stable group (124 cases) included 61 males and 63 females, aged 64.31±9.83 years (range: 44-82 years). The unstable non-fusion group (59 cases) included 22 males and 37 females, aged 65.76±11.01 years (range: 32-86 years). The unstable fusion group (82 cases) included 36 males and 46 females, aged 65.26±8.68 years (range: 47-80 years). At the last follow-up, the unstable non-fusion group exhibited ΔSA 0.90°±1.97° and ΔST 0.77±1.27 mm, both significantly higher than the stable group's ΔSA 0.25°±1.57° and ΔST 0.34±0.34 mm ( t=3.564, P<0.001; t=2.311, P=0.022). Clinical improvements were lower in the unstable non-fusion group compared to the other two groups: VAS (2.28±0.83), ODI (5.91%±3.46%), JOA (24.11±1.78), with a JOA improvement rate of 60%. The stable group showed VAS (1.51±0.69), ODI (3.71%±1.75%), JOA (27.33±1.91), with a JOA improvement rate of 83%. The unstable fusion group had VAS (1.46±0.83), ODI (3.46%±1.81%), JOA (26.48±1.66), with a JOA improvement rate of 78%. These differences were statistically significant ( F=32.117, P<0.001; F=24.827, P<0.001; F=92.658, P<0.001; F=93.341, P<0.001). The JOA improvement rate was negatively correlated with preoperative SA ( r=-0.363, P<0.001) to a low extent, and with preoperative ST ( r=-0.596, P<0.001) to a moderate extent. ROC curve analysis determined the preoperative SA threshold as 11.5° and the preoperative ST threshold as 1.85 mm. Conclusion:Pre-existing instability of the responsible segment UIV and UIV+1 (SA>10° or ST>2 mm) may worsen during long-term follow-up after TLIF. When preoperative SA exceeds 11.5° and ST exceeds 1.85 mm between UIV and UIV+1, performing an extended fusion involving UIV+1 can ensure surgical efficacy over long-term follow-up.

Objective To analyze the correlation between cumulative fluid balance volume and increasing plasma volume and aggravated clinical congestion symptoms in patients with heart failure on admission for 1～7 d,and to explore the application value of cumulative fluid balance volume in predicting volume overload.Methods Using the convenience sampling method,235 heart failure patients hospitalized from October 2022 to February 2023 in a total of 3 tertiary hospitals in Nanjing,Lianyungang,Jiangsu Province,and Zhumadian,Henan Province,were selected and classified into an increasing/decreasing plasma volume group and an aggravated/alleviated clinical congestion symptoms group.General information,clinical characteristics,and 1～7 d cumulative fluid balance volume of the study subjects were collected to compare the differences in cumulative fluid balance volume between the 2 groups.Logistic regression was used to analyze the effect of cumulative fluid balance volume on plasma volume and clinical congestion symptoms.Receiver operating characteristic curves were used to analyze the optimal cutoff value of cumulative fluid balance volume for predicting increasing plasma volume and aggravated clinical congestion symptoms.Results Excluding 15 pat ients who were discharged early and 3 patients with inaccurate records of fluid intake and excretion,a total of 217 patients were included.The incidence of positive fluid balance was lowest on day 1,at 65.90%,with the smallest cumulative volume of(0.235±0.983)L;the highest incidence of positive balance occurred on day 6,at 75.58%,with the largest cumulative volume of(2.444±5.445)L.The cumulative fluid balance at 4～7 d in the increasing plasma volume group was higher than that in the decreasing plasma volume group,and the difference was statistically significant(P<0.05);the cumulative fluid balance at 4～7 d was an independent risk factor for plasma volume elevation,and a cumulative fluid balance of 2.308,3.361,3.518,and 3.702 L at 4～7 d was predictive of a plasma volume elevation,and areas under receiver operating characteristic curve were 0.686,0.721,0.647,and 0.766,respectively.The cumulative fluid balance for 4～7 d in the aggravated clinical congestion symptoms group was higher than that in the alleviated clinical congestion symptoms group,and the difference was statistically significant(P<0.05);the cumulative fluid balance for 4～7 d was an independent risk factor for the aggravated clinical congestion symptoms,and a cumulative fluid balance for 4～7 d of 2.574,3.383,4.995,and 4.235 L predicted aggravated clinical congestion symptoms,and area under receiver operating characteristic curve was 0.640,0.693,0.654,and 0.720,respectively.Conclusion The incidence of cumulative positive fluid balance in heart failure patients is high,and the amount of cumulative fluid balance can better predict the occurrence of volume overload,and the increase of plasma volume precedes the appearance of clinical congestion symptoms.It is suggested that heart failure patients with more than 3 d of cumulative positive balance should be closely monitored,and when the cumulative positive balance exceeds 2.308 L,measures should be taken in time to drain excessive fluid,so as to avoid the incidence of volume overload.

Objective:To summarize the clinical features and pregnancy outcomes of fetal micrognathia.Methods:This retrospective study enrolled 52 cases of fetal micrognathia diagnosed at Shandong Provincial Maternal and Child Health Hospital Affiliated to Qingdao University and Affiliated Maternity and Child Health Care Hospital of Nantong University from January 2014 to December 2022. Clinical features, genetic testing results, and pregnancy outcomes of the cases were summarized. These cases were divided into two groups based on whether they were complicated by other system anomalies: non-isolated micrognathia (49 cases) and isolated micrognathia (three cases). The non-isolated micrognathia cases were further divided into two subgroups: cleft palate group (21 cases) and non-cleft palate group (28 cases). Clinical features were compared between different groups. Statistical analysis was performed using two independent samples t-test, Chi-square test, or Fisher's exact test. Results:(1) The non-isolated micrognathia cases were complicated by one to six system anomalies, with the most common being facial anomalies (59.2%, 29/49), followed by circulatory system (51.0%, 25/49), musculoskeletal system (44.9%, 22/49), nervous system (34.7%, 17/49), digestive system (12.2%, 6/49), and urinary system anomalies (8.2%, 4/49). (2) Among 52 cases, nine non-isolated micrognathia cases received genetic testing, and the results indicated six with genetic abnormalities. (3) Forty-seven cases chose to terminate the pregnancies, while the other five cases continued the pregnancies (all fetuses were non-isolated micrognathia) and resulted in live births. Treatment was withdrawn in one live birth due to multiple anomalies, and the other four neonates required mechanical ventilation (two died after withdrawal of treatment; two underwent surgeries after birth and the prognosis of them was good during a one-year outpatient follow-up). (4) The proportion of women with polyhydramnios [28.6% (6/21) vs. 3.6% (1/28), Fisher's exact test, P=0.033] and the proportion of fetuses with confirmed Pierre Robin sequence [85.7% (18/21) vs. 7.1% (2/28), Fisher's exact test, P<0.001] were higher in the cleft palate group than those in the non-cleft palate group. Conclusions:Fetal micrognathia cases revealed by prenatal ultrasound should undergo a comprehensive screening for other system anomalies, especially cleft palate. Fetuses with micrognathia and multiple system anomalies often have a poor prognosis. Besides, it is recommended to take genetic testing. For fetuses with micrognathia, preparations for neonatal resuscitation at birth are essential to avoid adverse outcomes due to breathing difficulties.