Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective:To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023.Methods:From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year.Results:The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [ OR (95% CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion:From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children′s age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective To explore the efficacy and safety of omalizumab in the treatment of allergic bronchopulmonary aspergillosis(ABPA).Methods The clinical data of 26 ABPA patients treated with omalizumab in Zhongshan Hospital,Fudan University from November 2018 to December 2023 and 24 ABPA patients treated with prednisone combined with itraconazole in the same period were analyzed retrospectively.The primary outcomes were exacerbation times and oral corticosteroid-sparing effect.The secondary outcomes were respiratory symptoms,circulating eosinophil count,total immunoglobin E(IgE)level,specific IgE for aspergillus,pulmonary function(the percentage value of forced expiratory volume in one second predicted[FEV1%pred]),fraction of exhaled nitric oxide(FeNO),thoracic computed tomography(CT)manifestation and adverse reactions.Results In omalizumab group,the exacerbation times of ABPA after 6 and 12 months of treatment were 0(0,0)times/6 months and 0(0,1)times/6 months,there was no significant difference(P=0.157),which were significantly lower than those of the baseline(1[1,2]times/6 months,P＜0.001).The oral dose of prednisone decreased from 10(5,15)mg/d(before treatment)to 3.125(0,5)mg/d(6 months after treatment,P＜0.001).After 12 months of treatment,the oral dose of prednisone was 0(0,3.125)mg/d,which was significantly lower than that of the baseline dose(P=0.003).After treatment with omalizumab for 12 months,the FeNO level decreased significantly(26[13,36]×10﹣9 vs 30[18,56]×10﹣9,P=0.049).There was no significant difference in blood eosinophil count,total IgE level,specific IgE for aspergillus and FEV1%pred before and after omalizumab treatment.After 6 months of treatment with omalizumab,respiratory symptoms were relieved in 23 patients(88.5%)and radiographic improvement was achieved in eight out of sixteen patients(50%)with mucus plugs.More patients successfully discontinued oral prednisone when treated with omalizumab for 12 months than those in control group(P=0.035).During the treatment of omalizumab,4(15.4%)patients had a slight increase in alanine aminotransferase(ALT),and 1 patient was complicated with hepatocellular carcinoma during follow-up.Conclusions Omazumab treatment can effectively reduce the number of acute episodes of ABPA,reduce the dosage of oral glucocorticoids,improve FeNO,facilitate the absorption of mucus plugs,and has high safety.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023.Methods:From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year.Results:The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [ OR (95% CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion:From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children′s age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Objective:To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia(CN-AML)patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients.Methods:151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively.34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology.The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared,and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed.Results:In 151 patients with CN-AML,55(36.42％)were positive for CEBPA mutation(including 36 cases of CEBPAdm and 19 cases of CEBPAsm),of which 41(74.55％)had co-mutations with other genes.The main mutated genes were GATA2(25.45％,14/55),TET2(21.82％,12/55),FLT3(20.00％,11/55),NRAS(12.73％,7/55)and WT1(9.09％,9/55),etc.Some cases had two or more concomitant gene mutations.Grouping the mutant genes according to their functions showed that CEBPA+group had lower mutation rates of histone methylation(P=0.002)and chromatin modification genes(P=0.002,P=0.033),and higher mutation rates of transcription factors(P=0.037)than CEBPA-group.In 55 patients with CEBPA+CN-AML,the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group(P=0.005),the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group(P=0.003),and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group,respectively(P=0.002,P=0.008).DFS of CEBPA+CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group(median DFS:12 months vs not reached)(P=0.034).Compared with DNA methylation gene mutation-negative group,CEBPA+CN-AML patients with DNA methylation gene mutation had lower CR rate(P=0.025)significantly shorter OS and DFS(median OS:20 months vs not reached,P=0.006;median DFS:15 months vs not reached,P=0.049).OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group(median OS:12 months vs 40 months)(P=0.008).Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts(P=0.046),concomitant DNA methylation gene mutation(P=0.006)and histone methylation gene mutation(P=0.036)were independent risk factors affecting the prognosis.Conclusion:CN-AML patients with CEBPA mutation have specific concomitant gene profile,and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

Objective:This study aims to develop a validated instrument for assessing the degree of integration perceived by patients in the services provided by general practitioner(GP)teams,and to evaluate the current state of integrated medical-prevention services.Methods:The survey tool was initially created through a review of existing literature and semi-structured interviews.It was subsequently refined and enhanced following consultations with experts.The utility of the instrument was confirmed through empirical research,which also facilitated an analysis of the status quo regarding the integration of medical and prevention services.Results:The devised instrument encompasses 18 items distributed across six dimensions:service comprehensiveness,service continuity,depth of service,continuity of relationship,patient-centricity,and service coordination.The cumulative score reflecting patients'perception of the integration level in GP teams'medical-prevention services was 54.30±12.45.Conclusion:The survey instrument developed in this research is characterized by its rationality,novelty,and practical relevance.It offers a patient-centered perspective for assessing the quality of integrated medical and prevention services for primary chronic diseases.While the overall perception of integration among patients is positive,there is a notable deficiency in the depth of services provided.There is a need for optimization of the service process,clarification of the service path,refinement of service management,and development of an integrated incentive mechanism for medical and preventive care,aiming for a deeper integration between medical services and preventive care.