Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Traditional Chinese medicines (TCMs) possess a rich historical background, unique theoretical framework, remarkable therapeutic efficacy, and abundant resources. However, the modernization and internationalization of TCMs have faced significant obstacles due to their diverse ingredients and unknown mechanisms. To gain deeper insights into the phytochemicals and ensure the quality control of TCMs, there is an urgent need to enhance analytical techniques. Currently, two-dimensional (2D) chromatography, which incorporates two independent separation mechanisms, demonstrates superior separation capabilities compared to the traditional one-dimensional (1D) separation system when analyzing TCMs samples. Over the past decade, new techniques have been continuously developed to gain actionable insights from complex samples. This review presents the recent advancements in the application of multidimensional chromatography for the quality evaluation of TCMs, encompassing 2D-gas chromatography (GC), 2D-liquid chromatography (LC), as well as emerging three-dimensional (3D)-GC, 3D-LC, and their associated data-processing approaches. These studies highlight the promising potential of multidimensional chromatographic separation for future phytochemical analysis. Nevertheless, the increased separation capability has resulted in higher-order data sets and greater demands for data-processing tools. Considering that multidimensional chromatography is still a relatively nascent research field, further hardware enhancements and the implementation of chemometric methods are necessary to foster its robust development.

Objective:To discuss the effect of Boschnikia rossica polysaccharides rapa polysaccharides(BRPS)on lipopolysaccharide(LPS)-induced inflammatory responses in the THP-1 macrophages,and to clarify its mechanism.Methods:The THP-1 monocytes were differentiated into the macrophages,and the inflammation model was established using LPS to induce the THP-1 macrophages.CCK-8 method was used to detect the survial rates of the THP-1 macrophages after treated with different concentrations(0,100,200,500,1 000,and 2 000 μg·L-1)of LPS and different concentrations(0,12.5,25.0,50.0,100.0,and 200.0 mg·L-1)of BRPS to select the concentrations for the subsequent experiments.The THP-1 macrophages were divided into blank group,model group,low dose of BRPS group(25.0 mg·L-1 BRPS),medium dose of BRPS group(50.0 mg·L-1 BRPS),and high dose of BRPS group(100.0 mg·L-1 BRPS).P38 inhibitor SB203580,ERK inhibitor U0126,c-Jun N-terminal kinase(JNK)inhibitor SP600125,and nuclear factor of kappa B(NF-κB)inhibitor BAY11-7082 were used to verify the effects on THP-1 cells.The THP-1 cells were divided into control group,LPS group,inhibitor group,100.0 mg·L-1 BRPS group,and inhibitor+100.0 mg·L-1 BRPS group.ELISA method was used to detect the levels of tumor necrosis factor α(TNF-α),interleukin(IL)-6,and IL-1β in culture fluid of the THP-1 macrophages in various groups;DCFH-DA fluorescence probe method was used to detect the reactive oxygen species(ROS)levels in the THP-1 macrophages in various groups;Hoechst33342/PI fluorescence staining method was used to detect the membrane damage in the THP-1 macrophages in various groups;JC-1 fluorescence staining was used to observe mitochondrial membrane potential in the THP-1 macrophages in various groups;Western blotting method was used to detect the expression levels of cyclooxygenase-2(COX-2),high mobility group protein B1(HMGB1),NOD-like receptor thermal protein domain assciated protein 3(NLRP3),cysteinyl aspartate specific protease(Caspase)-1,gasdermin D(GSDMD)-N,IL-1β,mitogen-activated protein kinase(MAPK),and nuclear factor-kappa B(NF-κB)related proteins in the THP-1 macrophages in various groups.Results:The CCK-8 method results showed that when the LPS concentration was 100-2 000 μg·L-1,the survival rates of the THP-1 macrophages were over 90%.Compared with 0 μg·L-1 LPS group,the IL-6 levels in culture fluid of the THP-1 macrophages in 100,200,500,1 000,and 2 000 μg·L-1 LPS group were increased(P<0.05),indicating a significant enhancement of the inflammatory response in the macrophages,so 100 μg·L-1 LPS was used to construct the inflammation model.After treated with 12.5,25.0,50.0,100.0,and 200.0 mg·L-1 BRPS,the survival rates of the THP-1 macrophage were 91.2%,93.8%,91.4%,90.6%,and 91.8%,respectively,so 25.0,50.0,and 100.0 mg·L-1 BRPS were selected as the drug concentrations for low,medium,and high doses of BRPS groups in the subsequent experiments.The ELISA results showed that compared with blank group,the levels of IL-6,TNF-α,and IL-1β in culture fluid of the THP-1 macrophages in model group were increased(P<0.05);compared with model group,the levels of IL-6,TNF-α,and IL-1β in low,medium,and high doses of BRPS groups were decreased(P<0.05).The DCFH-DA fluorescence probe method results showed that compared with blank group,the ROS level in the THP-1 macrophages in model group was increased(P<0.05);compared with model group,the ROS levels in low,medium,and high doses of BRPS groups were decreased(P<0.05).The Hoechst33342/PI fluorescence staining results showed that compared with blank group,the degree of membrane damage in the THP-1 macrophages in model group was increased;compared with model group,the degrees of membrane damage in low,medium,and high doses of BRPS groups were decreased.The JC-1 fluorescence staining results showed that compared with blank group,the mitochondrial membrane potential in the THP-1 macrophages in model group was decreased significantly;compared with model group,the mitochondrial membrane potential in low,medium,and high doses of BRPS groups were increased gradually.The Western blotting results showed that compared with blank group,the expression levels of COX-2,HMGB1,NLRP3,Caspase 1,GSDMD-N,and IL-1β proteins and the ratios of p-P38/P38,p-ERK/ERK,p-JNK/JNK,and p-NF-κB/NF-κB in the THP-1 macrophages in model group were increased(P<0.05);compared with model group,the expression levels of HMGB1,NLRP3,Caspase-1,GSDMD-N,and IL-1β proteins and the ratios of p-P38/P38,p-ERK/ERK,p-JNK/JNK,and p-NF-κB/NF-κB in the THP-1 macrophages in medium and high doses of BRPS groups were decreased(P<0.05),the expression levels of NLRP3,Caspase-1,and IL-1β proteins in the cells in low dose of BRPS group were decreased(P<0.05),the expression level of COX-2 protein in the cells in high dose of BRPS group was decreased(P<0.05).Compared with control group,the ratios of p-P38/P38,p-ERK/ERK,p-JNK/JNK,and p-NF-κB/NF-κB,and the expression level of IL-1β protein in the THP-1 macrophages in LPS group were increased(P<0.05);compared with LPS group,the ratios of p-P38/P38,p-ERK/ERK,p-JNK/JNK,and p-NF-κB/NF-κB,and the expression level of IL-1β protein in the THP-1 macrophages in inhibitor group,100 mg·L-1 BRPS group,and inhibitor+100 mg·L-1 BRPS group were decreased(P<0.05);compared with inhibitor group,the ratios of p-P38/P38,p-ERK/ERK,p-JNK/JNK,and p-NF-κB/NF-κB in the THP-1 macrophages in inhibitor+100 mg·L-1 BRPS group were decreased(P<0.05).Conclusion:BRPS inhibits the inflammatory response of the THP-1 macrophages,which may be related to the MAPK and NF-κB signaling pathways regulated by BRPS.

Pancreatic cystic neoplasm(PCN)is a category of pancreatic tumors with significant heterogeneity.In recent years,the detection rate of PCN has been increasing,and it has gradually become a concern of clinicians.Endoscopic ultrasound(EUS)can be close to the pancreas for scanning and biopsy,and it has certain advantages in the diagnosis and treatment of PCN.This review mainly summarizes the latest progress of EUS in the diagnosis and treatment of PCN.Cyst fluid molecular markers,such as Kirsten rat sarcoma viral oncogene homolog,GNAS complex locus,Von Hippel-Lindau tumor suppressor gene,as well as emerging endoscopic technologies such as EUS-guided needle based confocal laser endomicroscopy and through-the-needle biopsy,have all showed the potential to significantly improve the diagnostic accuracy of PCN.EUS-guided ablation is an emerging minimally invasive treatment technique for PCN,with the efficacy and safety of chemical ablation being supported by a substantial amount of research.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, a growing prevalence of racial and ethnic discrimination occurred when many Americans struggled to maintain healthy lifestyles. This study investigated the associations of racial and ethnic discrimination with changes in exercise and screen time during the pandemic in the United States. METHODS: We included 2,613 adults who self-identified as non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, or Hispanic from the Health, Ethnicity, and Pandemic study, a cross-sectional survey conducted among a nationally representative sample of United States adults between October and November 2020. We assessed self-reported racial and ethnic discrimination by measuring COVID-19-related racial and ethnic bias and examined its associations with changes in exercise and screen time using multivariable logistic regression models. We analyzed data between September 2021 and March 2022. RESULTS: COVID-19-related racial and ethnic bias was associated with decreased exercise time among non-Hispanic Asian (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.13 to 1.89) and Hispanic people (OR, 1.91; 95% CI, 1.32 to 2.77), and with increased screen time among non-Hispanic Black people (OR, 1.94; 95% CI, 1.33 to 2.85), adjusting for age, sex, education, marital status, annual household income, insurance, and employment status. CONCLUSIONS Racial and ethnic discrimination may have adversely influenced exercise and screen time changes among racial and ethnic minorities during the COVID-19 pandemic in the United States. Further studies are needed to investigate the mechanisms through which racial and ethnic discrimination can impact lifestyles and to develop potential strategies to address racial and ethnic discrimination as a barrier to healthy lifestyles.

Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.

ObjectiveTo investigate the effect of speech imagery therapy combined with traditional dysarthria training on dysarthria in children with cerebral palsy. MethodsFrom August to December, 2022, 21 children with cerebral palsy combined with dysarthria in Wuhu Fifth People's Hospital were randomly divided into three groups A, B and C. Group A was given traditional dysarthria training for 30 minutes everytime, group B was given implantable speech imagery combined with traditional dysarthria training for 40 minutes everytime, and group C was given additional speech imagery combined with traditional dysarthria training for 40 minutes everytime, five days a week, for three weeks. Articulation and Phonology Assessment Scale, Mouth Sensory-Motor Assessment Scale, and mandibular distance, tongue distance and vowel space area (VSA) were evaluated before and after treatment. ResultsThere was no significant difference in all the indexes among three groups before treatment (F < 1.247, P > 0.05). After treatment, the scores of phonological function and sensory-motor assessment scale increased (|t| > 2.575, P < 0.05), and the mandibular distance and VSA increased in groups A and B (|t| > 2.632, P < 0.05). The d-value of phonological function before and after treatment was more in groups B and C than in group A (P < 0.05), and no difference was found in the d-value of other indexes before and after treatment among three groups (P > 0.05). ConclusionBoth speech imagery therapies are effective in improving diction clarity, oral range of motion, and motion control ability in children with cerebral palsy, and are more effective in improving articulatory clarity than traditional speech-language training.

After decades of development,protein and peptide drugs have now grown into a major drug class in the marketplace.Target identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target selection.However,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are lacking.Here,we systematically explore the target spaces in the human genome specifically for protein and peptide drugs.Compared with other proteins,both suc-cessful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many aspects.Based on these features,we develop separate effective genome-wide target prediction models for protein and peptide drugs.Finally,a user-friendly web server,Predictor Of Protein and Peptide drugs'therapeutic Targets(POPPIT)(http://poppit.ncpsb.org.cn/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.