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.

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 .

Objective To analyze retrospectively the death pattern, risk factors, and death time of 253 patients at the Respiratory Care Unit of General Hospital of PLA in order to improve care quality and reduce mortality.Methods The information of patients was extracted from the hospital information system ( HIS) , and then classified and calculated accord-ing to different time points.Results Between November and next March,the mortality rate was higher than in other months (P<0.05), accounting for 19.5%.Mortality of those admitted between 8∶01 and 9∶00 or between 23∶01 and 24∶00 was higher than at other times(P<0.05), accounting for 41.7%and 50.0%, respectively.There was statistically significant difference(P<0.01) in mortality between days of the week,with the highest on Saturday, accounting for 43.1%.Mortality on non-work days was higher than on workday(P<0.01), accounting for 38.3% and 13.2%, respectively.Mortality at off-hour was higher than at office time(8∶00-11∶30 and 14∶30-18∶00 on workday) (P<0.01), accounting for 31.3%and 5.2%, respectively.Logistic regression analysis showed that age, month of admission, and the hour of discharge were associated with the outcome.Conclusion The high mortality between November and next March may be related to the higher incidence of respiratory diseases in winter, air pollution and cold weather.High mortality is also significantly associ-ated with the care quality of the medical staff.

Objective To investigate the epidemiological and clinical characteristics of measles in patients of different age groups in Northeast China in 2014.Methods The clinical data of patients with measles in ten hospitals of infectious diseases in Northeast China from January 2014 to June 2014 were collected.Patients were divided into <16 age group and ≥16 age group, and the epidemiology , clinical characteristics, treatment and prognosis of all patients were retrospectively reviewed .SPSS 17.0 was used for data analysis.Results There were 1 401 patients with measles, in which 402 were <16-year old, and 999 were ≥16-year old.Clinical manifestations were mainly maculopapule (100.0%), fever (84.58%), cough (85.80%), Koplik’ s spot (73.23%), pharyngeal hyperemia (71.23%), diarrhea (43.97%), expectoration (40.97%), tears (39.40%) and runny nose (30.55%).The incidences of Koplik’s spot, sputum, pharyngeal hyperemia and diarrhea in <16 age group were lower than those in ≥16 age group (χ2 =8.364, 29.768, 10.953 and 6.701, P<0.05 or <0.01); while the incidence of runny nose was higher than that in ≥16 age group (χ2 =6.703, P<0.05).Abnormalities were found in blood routine examination, C-reactive protein (CRP), liver and kidney function, serum electrolyte levels, myocardial enzymes, and so on.Increasing in WBC, PLT and creatine kinase isoenzyme (CKMB), and decreasing in WBC were observed in 38(9.45%), 122(30.35%), 279(69.40%) and 105(26.12%), patients in <16 age group, which were higher than those in ≥16 age group [45(4.5%), 14(1.40%), 347(34.73%) and 202(20.22%)], and the differences were of statistical significance (χ2 =12.593, 274.033, 139.385 and 5.830, P<0.05 or P<0.01).Increasing in alanine aminotransferase (ALT), CRP, total bilirubin level (TBil), creatine kinase (CK), and decreasing in albumin (Alb), K+, Na+, Cl-were observed in 70(17.41%), 7(1.74%), 38(9.45%), 7(1.74%), and 214(53.23%), 59(14.68%), 45(11.19%), 94(23.38%) patients in <16 age group, which were lower than those in ≥16 age group [668(66.87%), 89(8.91%), 277(27.73%), 714(71.47), and 268(26.83%), 339(33.93%), 642(64.26%), 450 (45.05%)], and the differences were of statistical significance (χ2 =281.230, 23.073, 50.687, 159.740, and 14.674,114.286, 44.268, 271.546, P<0.01).Laryngitis and pneumonia were the most common complications.The incidence of laryngitis in <16 age group was 12.69% (51/402), which was higher than that in ≥16 years group (93/999, 9.31%,χ2 =3.545, P<0.05);while the incidence of spot shadows demonstrated by X-ray in <16 years group ( 72.89%, 121/166 ) was higher than that in ≥16 years group (265/445, 59.55%,χ2 =9.249, P<0.01).Conclusions There are differences in clinical features of measles in patients between <16 age group and ≥16 age group.Basic immunization in children and revaccination in adults should be enhanced to control the epidemics of measles .

Objective To investigate the effect of luxS inactivation on the oxidative stress of Streptococcus mutans and perform preliminary analysis of potential mechanism.Methods Strains were grown to mid-logarithmic phase and divided into three groups,one was used as control and inoculated into normal TPY medium,and the other two groups were experimental groups,and there were separately inoculated into TPY containing 58.8 mmol/L hydrogen peroxideor TPY containing 58.8 mmol/L hydrogen peroxide and 0.1 mmol/L 2,2'-dipyridyl.The survival rate of strain was calculated at 0.5,1,and 2 h.All the data were statistically analyzed.Results Compared with the control group,the survival rate of luxS mutation was always higher than standard strain at all pre-determined time inexperimental groups (P＜0.05),and compared with experimental group without iron chelator,the survival rate of strains was not raised with the added of iron chelator (P＞0.05).Conclusion luxS gene is involved in oxidative stress tolerance of Streptococcus mutans,and the oxidative stress tolerance is not achieved by avoiding the toxic effects of the Fenton reaction

Objective To construct markless gene deletion mutant at the clpP loci on the chromosome of Streptococcus mutans(S.mutans).Methods ASp resistance gene was amplified by PCR,to construct the Sp resistance cassette where the Sp resistance gene was flanked with two loxP site.After the clpP gene was cloned into the pGEM-T-Easy TA cloning vector,it was digested and linked with the Sp resistance cassette,yielding homologous recombination vector pIB △ clpP-Sp.The vector was linearized and used for the transformation of S.mutans UA159,with transformants selected on TPY plates containing Sp.The selected strain was transformed with the thermosensitive plasmid pCrePA to excise the Sp resistance gene.The pCre-PA was then easily eliminated at nonpermissive temperature,resulting in a markless mutant strain carrying a deletion at the clpP loci,which was verified by PCR and DNA sequencing.Results The result of the PCR analysis and DNA sequencing indicated that a part of the clpP gene was deleted.There was a loxP at this loci without the Sp resistance gene.Conclusion The markless clpP-deletion mutant of S.mutans was constructed successfully,which laid a foundation for further study of its biological function and its influence on the cariogenicity of S.mutans.