Objective To study the mechanism of NS1619 on airway remodeling in asthmatic mice. Methods A total of 24 healthy female BALB/c mice were randomly divided into 3 groups:the control group, the oval albumin (OVA) group (the asthma group) and the NS1619 group (the intervention group), 8 mice in each group. Asthma group was induced with OVA, chal-lenged by continuous inhalation with 5%OVA from day 19 to 23, then changed to 3 times per week from day 24 to 55. Interven-tion group was inhaled with NS1619 (30μmol/L) before OVA. Control group was given with normal saline. The thickness of air-way smooth muscle and the area of collagen deposition in lung tissue slices were observed by HE and Masson staining, measured by a computer assisted image analysis system. The concentration ofα-smooth muscle actin (α-SMA) in cells was detected by immunohistochemistry. The expression of platelet derived grouth factor-BB, PDGF-BB (PDGF-BB) in serum was measured by immunosorbent assay. Results Compared with the asthma group, the pathologic changes of lung tissue, the thickness of airway smooth muscle and collagen deposition in the group treated with NS1619 were signiifcantly decreased (P<0.05). Compared with the asthma group, the levels ofα-SMA in cells and PDGF-BB in serum in NS1619 treated group were signiifcantly decreased (P<0.05). Conclusions NS1619 partly inhibited airway remodeling in asthmatic mice, partially by down-regulating the expres-sion level ofα-SMA and PDGF-BB.

Objective To investigate the distribution and sequence conservation of Hap adhensin encoding gene (hap) in clinical isolates of nontypeable Haemophilus influenzae (NTHi), to screen out and identify the predominant T-and B-cell (T-B) combined antigenic epitopes on Hap protein and to analyze their immunogenicity.Methods Sequence conservation of hap genes in NTHi strains and T-B combined antigenic epitopes were predicted using bioinformatic softwares.PCR was used to amplify the 156 bp segment at 5′-end and the 855 bp segment at 3′-end of hap gene (hap-5′-156 and hap-3′-855) and the amplified products were sequenced.Phage display systems of seven T-B combined antigenic epitopes located on the 55 aa segment at N-terminal and the 285 aa segment at C-terminal of Hap protein (Hap-N52 and Hap-C285) were constructed.Western blot assay and ELISA were performed to detect the antigenicity and immunoreactivity of different T-B combined epitopes displayed by recombinant phage PⅢ protein (rPⅢ).Results Hap protein encoded by the hap gene in NTHi was located on membrane surface.Sequences of the 156 bp segment at 5′-end and the 855 bp segment at 3′-end of hap genes extracted from different NTHi strains were relatively conservative, but many mutations were found in sequences at the middle regions of these hap genes.All of the 56 NTHi strains carried hap-5′-156 and hap-3′-855 segments and shared 92.3％-100％ identities in nucleotide and amino acid sequences of these segements.Hap-N5-24 in the Hap-N52 segment as well as Hap-C4-27, Hap-C28-47, Hap-C114-129, Hap-C150-173, Hap-C200-227 and Hap-C241-267 in the Hap-C285 segment was predicted as the T-B combined antigenic epitope with a higher score and less mutations.Results of Western blot assay and ELISA confirmed that the rPⅢ-displayed Hap-C4-27 and Hap-C150-173 epitopes presented clear hybridization bands with NTHi antisera, and 96.9％ (63/65) and 92.3％ (60/65) of serum samples from children with NTHi infection were positive for antibodies against Hap-C4-27 and Hap-C150-173 epitopes, respectively.Conclusion The gene of hap is widely distributed in clinical isolates of NTHi.Moreover, sequences of the 156 pb segment at 5′-end and the 855 bp segment at 3′-end of hap gene are conservative.Hap-C4-27 and Hap-C150-173 are the predominant T-B combined antigenic epitopes on Hap protein, suggesting that they can be used as epitope candidates for developing multiple antigenic peptide vaccines against NTHi.

Objective To observe the clinical efficacy and toxicity of intraperitoneal chemotherapy combined with intravenous chemotherapy in treatment of cervical cancer.Methods The experimental group of 40 patients received systemic chemotherapy of docetaxel and cisplatin combined abdominal intraperitoneal high-frequency hyperthermia in the control group,40 patients received docetaxel plus cisplatin chemotherapy,The efficacy and toxicity were observed.Results The complete remission rate of observotion group was 82.5％,significantly higher than 62.5％ in control group.Effective rate in observation group was 92.5％ and also significantly higher than 75.0％ in control gronp.After 6 cycles of chemotherapy,the improvement of the experimental group was 85.0％ higher than 57.5 ％ in control gronp.The differemles between the two groups was statistically significant(P ＜ 0.05); the main side effects during chemotherapy are gastrointestinal reactions,since the cells decreased,hair loss,the difference was not statistically significant(P ＞0.05).Conclusion The chemotherapy of docetaxel and cisplatin intraperitoneal chemotherapy can significantly improve the treatment of cervical cancer,without increasing side effects.

The organ-system-based curriculum (OSBC) medical teaching model with the organ system as the main line closely links the basic medical curriculum with the clinical practice,and breaks the boundaries between different subjects.As this novel teaching model is still in the early stage in China,Chongqing Medical University pioneered to reconstruct the teaching system for OSBC teaching reform,including the great efforts to integrate e the traditional 24 courses into 12,and to allocate talents from various basic and clinical teaching departments to form a new integrated teaching team.In 2011,this new mode was implemented in a pilot class of students.The results showed the 2011 five-year pilot class showed more satisfaction than did the traditional teaching class [(92.5 ± 4.6)％ vs.(72.5 ± 4.9)％,P＜0.05].Besides,the test scores of the pilot class and the traditional class were (80.0 ± 3.6) and (71.0 ± 5.9) respectively(P＜0.05),and the failing rate was (3.7％ in pilot class and 9.3％ in traditional class(P＜0.05).Since the pilot class perform better than the traditional one,the reform of OSBC was implemented for all five-year clinical medicine program in Chongqing Medical University in 2018.

Objective To compare the pharmacodynamics between different batches of recombinant decoy receptor innovative drug RC28-E1 and RC28-E2 in retinal angiogenesis and neovascularization,and analyze its mechanism.Methods Sixty postnatal Day 4 (P4) C57BL/6J mice were randomly divided into normal control group,vascular endothelial growth factor (VEGF)+fibroblast growth factor 2 (FGF2) group,VEGF+FGF2+RC28-E1 group,VEGF+FGF2+RC28-E2 group,VEGF+FGF2+conbercept group and VEGF+FGF2+FGF trap group by using a random number table,with 10 mice in each group.The mouse retinal explant culture system was established,and stimulated with the corresponding factors and drugs prepared in the starving culture media.The normal controls were treated with the starving media.Then the retinal explants were stained with Isolectin B4 and imaged.The number of filopodia per vascular length was quantified.In addition,ninety-six P7 C57BL/6J mice were randomly divided into normal control group,oxygen-induced retinopathy (OIR) model control group,OIR + RC28-E1 group,OIR + RC28-E2 group,OIR+conbercept group and OIR+FGF trap group by using a random number table,with 16 mice in each group.The normal controls were raised under normoxia for 10 days,and the rest of the groups were raised under hyperoxia for 5 days,then returned to normoxia for another 5 days.On P17,the retinas were isolated and stained with Isolectin B4.The stained retinas were mountedon the slides and photographed.The relative vessel obliteration and neovascularization in retina were analyzed with computer software.Then the protein levels of VEGF and FGF2 were examined by Western blot in the retinas of each group in the OIR experiment.Finally,in the RF/6A cells stimulated with VEGF and FGF2,the activities of the signaling pathways,including MEK-extracellular regulated protein kinases (Erk),protein kinase C (PKC) and protein kinase B (Akt) pathways,were examined by Western blot.All experimental procedures were evaluated and approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (SYXK 2009-0001),and were in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Results The results of retinal explant cultures showed that the numbers of filopodia per vascular length in VEGF + FGF2 + RC28-E1,VEGF + FGF2 + RC28-E2,VEGF + FGF2 + conbcrcept,and VEGF+FGF2+FGF trap groups were all significantly less than that in the VEGF+FGF2 group (all at P ＜ 0.001).The filopodia number in retinal vascular front in RC28-E1 group was similar to that in the RC28-E2 group (P =0.15),whereas the filopodia numbers in both groups were significantly decreased as compared to those in VEGF+ FGF2+conbercept group and VEGF+FGF2+FGF trap group (all at P＜0.001).The results from the OIR mouse model showed that the relative vessel obliteration area in OIR model control group was dramatically higher than those in the drug intervention groups (all at P＜0.05).There was no statistical significance in the relative vessel obliteration area between OIR+RC28-E1 group and OIR+RC28-E2 group (P =0.17),while the obliteration areas in both RC28-E-intervened groups were significantly lower than those in the OIR+conbercept group and OIR+FGF trap group (all at P＜0.05).The relative neovascular pixels in the intervention groups were significantly lower than those in the OIR model control group (all at P＜0.001).The neovascular pixels in OIR+RC28-E1 group were significantly lower than those in VEGF+FGF2+conbercept group and VEGF + FGF2 + FGF trap group (both at P ＜ 0.05),but comparable to those in OIR+RC28-E2 group (P =0.39).Western blot result showed that,the protein expression of VEGF and FGF2 in the OIR mouse retinas were significantly upregulated compared to those in the normal ones (both at P＜0.001).The upregulation of both genes were normalized by both RC28-E1 and RC28-E2.In addition,the stimulation of VEGF and FGF2 induced an enhanced activity in MEK-Erk pathway in RF/6A cells,whereas RC28-E1 inhibited the overactivation.Conclusions RC28-E1 and RC28-E2 both can inhibit angiogenesis in the retinal explants isolated from neonatal mice;they also reduce vessel obliteration and mitigate neovascularization in the OIR mouse model.Therefore,the pharmacology batch and pilot test batch of RC28-E have similar efficacies and reliable stability,and are superior in the anti-angiogenic and anti-neovascular efficacy to the currently clinically available drugs conbercept and FGF trap.RC28-E1 may suppress pathological neovascularization through inhibiting the overactivation of MEK-Erk pathway in retinal vascular endothelial cells.

【Objective】 To understand the structural characteristics of lapsed apheresis donors in our blood center and provide guidance for further improving recruitment and retention strategies by retrospectively analyzing the characteristics of lapsed apheresis donors in our center in recent years. 【Methods】 The apheresis donation and lapsed apheresis donors in Zhejiang Blood Center from 2016 to 2020 were statistically analyzed, and the general information of lapsed donors, including gender, blood type, age, education level and occupation composition, were compared and analyzed. The lapse of novel and long-term donors with different frequency were retrospectively analyzed. The SPSS 19.0 statistical software package was used for data analysis. 【Results】 In 2020, the total lapse of apheresis donors decreased by 16.6% as compared with 2016(P<0.05). The lapse rate of donors with blood groups A, B, O and AB was 1∶1∶1∶1, higher in female donors(59.0%) than males(50.0%), and dominated by age group of 18-35(66.3%). With the increase of age, the lapse rate decreased. Donors lapsed were mainly with college or above educational background(60.8%), with high proportion in students and the staff. In 2020, the lapse of novel apheresis donors decreased by 34.1% as compared with 2016, but the average lapse rate of novel apheresis donors was still as high as 70.5%. The average lapse rate of blood donors with different frequency was 52.5%, and the lapse rate decreased significantly with the increase of apheresis donation frequency. The average lapse rate of novel blood donors with whole blood donation experience was lower than those without (56.1% vs 82.9%). 【Conclusion】 Multiple measures for recruitment and retention have effectively reduced the lapse of apheresis donors. However, apheresis donors who are 18-35 years old, with college degree or above, students and staff were the main groups from lapsing. In addition, low-frequency and novel apheresis donors without whole blood donation experience were more likely to be lapsing. Targeted and personalized blood donation services should be further provided, and the management of " full cycle of blood donation" should be strengthened to reduce the lapsing, so as to retain more blood donors.