OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

By systematically summarizing the basic situation of the Arctium lappa L.industry in our country,the strengths,weaknesses,opportunities,and threats(SWOT)analysis method,and the multi-expert review method were used to analyze,screen,and test the elements obtained.It is determined that the development of Arctium lappa L.industry should adopt the S-O strategy of relying on internal advantages to use external opportunities and judging from the orientation,the external opportunities are more pronounced,to take the opportunity of pioneering strategy.Based on utilizing external opportunities and exerting our advantages,we should adopt the strategy of product diversification,the strategy of expanding the international market,and the strategy of promoting science and technology to promote the efficient development of Arctium lappa L.industry.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition.OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques.METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes.RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition.OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques.METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes.RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.

By systematically summarizing the basic situation of the Arctium lappa L.industry in our country,the strengths,weaknesses,opportunities,and threats(SWOT)analysis method,and the multi-expert review method were used to analyze,screen,and test the elements obtained.It is determined that the development of Arctium lappa L.industry should adopt the S-O strategy of relying on internal advantages to use external opportunities and judging from the orientation,the external opportunities are more pronounced,to take the opportunity of pioneering strategy.Based on utilizing external opportunities and exerting our advantages,we should adopt the strategy of product diversification,the strategy of expanding the international market,and the strategy of promoting science and technology to promote the efficient development of Arctium lappa L.industry.

Objective To compare the value of the 2018 Chinese guideline prognostic score with that of the 2019 European Society of Cardiology(ESC)in the predicting efficiency for acute pulmonary embolism(APE)in 30-day all-cause mortality.Methods The data of the hospitalized patients with confirmed APE from January 2015 to December 2019 were retrospectively collected.According to death within 30 days,the patients were divided into a death group and a survival group.Subgroup analysis was performed according to gender,oxygen saturation and infection.The SPSS software was used to establish the receiver operating characteristic curve(ROC)for the two scores and calculated the area under the curve(AUC).The Delong's test was applied to compare the AUC differences.The net reclassification index(NRI)and integrated discrimination improvement(IDI)were calculated using the R software packages of survival,survIDINRI,and PredictABEL.Results 626 APE patients were enrolled,and 30-day death was predicted in those patients using two scores.In terms of overall discrimination,the 2018 Chinese guideline prognostic score was better than the 2019 ESC guideline prognostic score,with an AUC of 0.782 and 0.749,respectively;but there were no statistical differences between the two AUC(P＞0.05).In terms of prediction accuracy,the NRI of the 2019 ESC guideline prognostic score was 44.4%(95%CI:0.091～0.753),higher than that of the 2018 Chinese guidelines prognostic score,which increased by 58.6%(95%CI:0.161～0.917)in the correct reclassification to death group,while decreased by 14.2%(95%CI:-0.249～0.08)in the correct reclassification to survival group.IDI increased by 3.38%(P＜0.05).Subgroup analysis showed the prognostic scores of the 2018 Chinese guidelines and the 2019 ESC guidelines prognostic scores had predictive ability for patients with different gender and different oxygen saturation(P＜0.05),and the prognostic scores for co-infected population(AUC:0.749,0.772)(P＞0.05),non-coinfected population(AUC:0.652,0.833).Conclusions Both the 2018 Chinese guideline prognostic score and the 2019 ESC guideline prognostic score can predict 30-day mortality in APE patients,and have a better predictive ability for the co-infected population.However,the predictive accuracy of the former is higher than that of the latter in the survival group,and the score is more rapid and convenient for clinical application,while the latter has improved the prediction ability in the death group.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Objective To compare the characteristics of ulcer wound healing in current commonly used C57BL/6J-db/db mouse models of spontaneous gene mutation-induced type 2 diabetes and in C57BL/6J mice with diabetes induced by streptozotocin (STZ), and to provide a basis for related experimental studies on diabetic ulcer in animal models.Methods To establish the mouse models of diabetic ulcer wound, observe the healing time and calculate the wound healing rate at 0, 3, 5, 7, 10, 14 days.Tissue samples were collected at days 7 and 14.HE and Masson staining, and immunohistochemistry (CD31 and PCNA) were used to observe the pathological changes of the wound tissues.Gene expressions of collagen-IIIα, fibronectin and α-SMA were detected by fluorescent quantitative analysis.Results The wound healing time of db/db mice was significantly delayed compared with the STZ mice, which was extended from 16.6±0.8 d to 20.2±1.3 d (P< 0.001).Compared with the STZ group, the growth of granulation tissue in the db/db group was slow, the length of newly formed epithelium was insufficient, the collagen deposition was disordered, and the wound healing was poor.At 7 days, the expression of CD31 and PCNA was significantly lower in the db/db group (P< 0.01), and at 7 and 14 days, the increase of collagen-IIIα and α-SMA genes up-regulation was significantly lower in the db/db group than in the STZ group.Conclusions Both the two types of diabetic mice show delayed wound healing.However, compared with the STZ-induced diabetic mice, the gene mutation db/db mice are more suitable for studies of diabetic ulcer wound healing as regarding the extent of the delay and the degree of difficulty of wound healing.

Objective To investigate the survival , recurrence patterns and risk factors in patients with stage ⅢA-N2NSCLC treated with curative surgery and adjuvant chemotherapy and to explore the significance of postoperative radiation therapy .Mte hods The clinical data of 290 patients with pathologically diagnosed stage ⅢA-N2 NSCLC after curative resection and adjuvant chemotherapy from January 2010 to December 2014 at our department were retrospectively analyzed .The survival and recurrence patterns were observed , and the factors affecting locoregional recurrence were analyzed .Results The median survival time was 31.5 months.The 1-,3 -and 5-year survival rates were 88.3%, 46.0%and 33.2%, respectively.The median locoregional control time was 38.5 months.The 1-, 3-and 5-year locoregional control rates were 78.6%, 55.2%and 41.0%, respectively.The median distant metastasis-free survival was 26.8 months.The 1-, 3-and 5-year distant metastasis-free survival rates were 76.4%, 45.5%and 39.5%, respectively.The median progression-free survival was 19.1 months.The 1-,3-and 5-year progression-free survival rates were 64.1%, 32.5%and 23.8%, respectively .Univariate analysis showed that clinical N status, histological type, pathological T stage, operation mode, the number of positive N2 lymph nodes and the number of positive N 2 lymph node stations had a significant influence on overall survival; clinical N status, histological type, the number of positive N2 lymph nodes and the number of positive N 2 lymph node stations had a significant influence on locoregional control .Multivariate analysis demonstrated that the number of N2 positive lymph nodes( P=0.017) was an independent factor for overall survival of stage ⅢA-N2 patients;the number of N2 positive lymph nodes (P=0.009) and histological type (P=0.005) were independent factors for locoregional recurrence .For left-sided lung cancer , the lymph node station failure sites were mostly in 2R, 4R, 5, 6 and 7, and the contralateral mediastinum was frequently involved .For rights-ided lung cancer , the lymph node station failure sites were mostly in 2R, 4R,7 , 10R and surgical stump.Conclusions Clinical N2, squamous cell carcinoma , positive N2 nodes of more than 3 and multiple positive N2 stations are poor prognostic factors for locoregional recurrence .Locoregional recurrence of left lung cancer frequently involves the contralateral mediastinum , while that of the right lung cancer usually locates in the ipsilateral mediastinum .

Objective To investigate the survival , recurrence patterns and risk factors in patients with stage ⅢA-N2NSCLC treated with curative surgery and adjuvant chemotherapy and to explore the significance of postoperative radiation therapy .Mte hods The clinical data of 290 patients with pathologically diagnosed stage ⅢA-N2 NSCLC after curative resection and adjuvant chemotherapy from January 2010 to December 2014 at our department were retrospectively analyzed .The survival and recurrence patterns were observed , and the factors affecting locoregional recurrence were analyzed .Results The median survival time was 31.5 months.The 1-,3 -and 5-year survival rates were 88.3%, 46.0%and 33.2%, respectively.The median locoregional control time was 38.5 months.The 1-, 3-and 5-year locoregional control rates were 78.6%, 55.2%and 41.0%, respectively.The median distant metastasis-free survival was 26.8 months.The 1-, 3-and 5-year distant metastasis-free survival rates were 76.4%, 45.5%and 39.5%, respectively.The median progression-free survival was 19.1 months.The 1-,3-and 5-year progression-free survival rates were 64.1%, 32.5%and 23.8%, respectively .Univariate analysis showed that clinical N status, histological type, pathological T stage, operation mode, the number of positive N2 lymph nodes and the number of positive N 2 lymph node stations had a significant influence on overall survival; clinical N status, histological type, the number of positive N2 lymph nodes and the number of positive N 2 lymph node stations had a significant influence on locoregional control .Multivariate analysis demonstrated that the number of N2 positive lymph nodes( P=0.017) was an independent factor for overall survival of stage ⅢA-N2 patients;the number of N2 positive lymph nodes (P=0.009) and histological type (P=0.005) were independent factors for locoregional recurrence .For left-sided lung cancer , the lymph node station failure sites were mostly in 2R, 4R, 5, 6 and 7, and the contralateral mediastinum was frequently involved .For rights-ided lung cancer , the lymph node station failure sites were mostly in 2R, 4R,7 , 10R and surgical stump.Conclusions Clinical N2, squamous cell carcinoma , positive N2 nodes of more than 3 and multiple positive N2 stations are poor prognostic factors for locoregional recurrence .Locoregional recurrence of left lung cancer frequently involves the contralateral mediastinum , while that of the right lung cancer usually locates in the ipsilateral mediastinum .