Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

Objective:Bibliometric analysis of SCI papers in Shanghai tertiary obstetrics and gynecology specialized hospitals from 2017 to 2021 was conducted to provide reference for further improving management measures and optimizing the quality of SCI papers in specialized hospitals.Methods:The Web of Science database was used to retrieve SCI papers published by tertiary obstetrics and gynecology specialized hospitals in Shanghai from 2017 to 2021. Based on bibliometric methods VOSviwer 1.6.17 and Scimago Graphica 1.0.23 was adopted to analyze the number, journals, domestic and international cooperation, and hot research areas.Results:2 721 papers were published by Shanghai Tertiary A obstetrics and Gynecology hospitals from 2017 to 2021. These papers published in 765 journals. The number of papers published and publication journals increased year by year. The number of papers and journals with an impact factor of 3~5 is the largest, accounting for 37.96% and 35.95% of the total number of papers and journals respectively. However, papers and journals with more than 10 points accounted for only 7.98% and 10.20% respectively. Scientific Reports, a comprehensive journal, published the largest number of papers. International cooperation is concentrated in the United States. Domestic cooperation is concentrated in universities and research institutions in Jiangsu, Zhejiang and Shanghai. The hot research areas focused on Oncology, Obstetrics & Gynecology, Genetics, Reproductive Biology and other basic medical fields.Conclusions:The number of papers published by Shanghai's tertiary obstetrics and gynecology specialized hospitals has increased year by year, but there are fewer highly influential journals. Domestic and international scientific research cooperation is limited to several institutions. The achievements in the field of basic research are far more than those in clinical research.

Objective To establish an animal model of neurogenic pulmonary edema (NPE),and to study the role of catecholamine and beta receptors in the occurrence of NPE. Methods The NPE model was established by injecting fibrinogen and thrombin into the cerebellum medullary pool of the rabbits. Twenty-four rabbits were divided into the control group,the saline group and the experimental group by random num-ber table. In the control group,only cerebellar medullary cistern puncture was carried out,and no drug was in-jected. Cerebrospinal fluid was drew out and the same amount of saline was injected into the cerebellum me-dullary pool in the saline group. Fibrinogen and thrombin were injected into the cerebellum medullary pool in the experimental group. The animals were intubated by tracheotomy,the femoral artery and the internal jugu-lar vein were dissected and connected with the PiCCO instrument to detect the blood pressure,heart rate,and respiratory rate before puncture and at 1 min,10 min,30 min after puncture. Serum samples were collected for the determination of epinephrine,norepinephrine,acetylcholine,endothelin-1,cardiac troponin I,brain natri-uretic peptide and neuropeptide Y levels before puncture and at 1 min,10 min after puncture. The rabbits weresacrificed at 3 hours after successful modeling,the pathological examination of lung was performed. Myocar-dial samples were taken to detect adrenergic beta receptors mRNA. Results (1)The heart rate,respiratory rate and mean arterial pressure at 1 min and 10 min after puncture in experimental group were significantly higher than those in control group and saline group. (2) The pathological examination of the rabbits′ lungs in experimental group found that the lung tissue was swollen and dark red in appearance with large areas of con-gestion. Under the microscope,the lung tissue was edema,bleeding,and inflammatory cells were infiltrated in the alveolar cavity,which was consistent with characteristics of NPE. (3)There was no difference in epineph-rine and norepinephrine concentration in all groups before the cerebellar medullary pool puncture. The concen-tration of epinephrine and norepinephrine at 1 min after puncture time were (200. 0 ± 251. 7)μg/ L,(448. 9 ± 356. 7)μg/ L in the experimental group,whcih were significantly higher than those of control group[(15. 4 ± 3. 4)μg/ L,(15. 9 ± 9. 7)μg/ L] and saline group[(17. 1 ± 3. 8) μg/ L,(29. 6 ± 18. 4) μg/ L] (P < 0. 05). The concentration of epinephrine and norepinephrine at 10 min after puncture were (397. 0 ± 797. 7)μg/ L, (221. 4 ± 173. 7)μg/ L in the experimental group,whcih were significantly higher than those of control group [(23. 3 ± 6. 4) μg/ L,(18. 8 ± 3. 9) μg/ L] and saline group[(16. 7 ± 9. 1) μg/ L,(20. 3 ± 6. 5) μg/ L] (P < 0. 05). (4)There was no significant difference in the levels of serum neuropeptide Y,acetylcholine and endothelin-1 among the three groups. (5)The mRNA of adrenergic beta-1 receptor in the experimental group was 0. 37 ± 0. 12,which was significantly lower than those in the control group (0. 54 ± 0. 13) and saline group (0. 56 ± 0. 14) (P < 0. 05). There was no significant difference in adrenergic beta-3 receptor mRNA among the three groups. Conclusion The NPE animal model was constructed by injecting fibrinogen and thrombin into the cerebellum medullary pool of the rabbits. Catecholamine and beta-1 receptor play a role in the occurrence of NPE rabbit model. There is no significant correlation between neuropeptide Y,acetylcholine,en-dothelin-1 and the occurrence of NPE in rabbits.

Objective: To analyze the relationship between inflammatory factors and relevant risk factors in patients of essential hypertension (EH) combining acute coronary syndrome (ACS) with its clinical significance. Methods: Our research included 3 groups: EH group, n=79 patients with standard criteria, EH+ACS group, n=85 and Control group, n=48 normal subjects. Blood levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), tryptase (TPS) and relevant clinical, biochemical parameters were measured; risk factors for cardiovascular disease were examined and the relationship between above parameters, risk factors and ACS occurrence in EH patients was studied by Logistic regression analysis. Results: The OR values were all greater than 1 in fibrinogen (Fbg), high-sensitivity C-reactive protein (hs-CRP), TPS, atherosclerotic plaque, Lp-PLA2 and EH grading. Fbg was the most significant independent risk factor (OR=22.242, 95% CI 6.458-76.609, P<0.0001), the standardized partial regression coefficient b'as absolute value (b') was 1.079 which was the highestone in above 6 variables with the strongest impact for ACS occurrence in EH patients. Conclusion: Fbg, hs-CRP, TPS, atherosclerotic plaque and EH grading were the independent risk factors for ACS occurrence in EH patients; Fbg was the highest risk factor for ACS occurrence with the strongest impact, which provided a new direction for ACS prevention and treatment.

Objective To investigate the changes of cellular immunity and humoral immunity in children with acute or critical illness. Methods Seventy-three critically ill children admitted to PICU of Chil-dren′s Hospital Affiliated to Fudan University during the period from April,2015 to September,2015 were the objects of study. Blood samples were collected within 48 hours after admition. The lymphocyte subpopulation was measured by flow cytometry,and the level of humoral immunity was measured by rate immune scatter turbidimetry,and the neutrophil function was measured by flow cytometry-DHR analysis. Twenty-three cases from 73 cases were detected the second time after admitted to hospital for seven days. Ten health children be-fore elective surgery were selected as control. Results (1) Compared with the control,the percentages of CD3 +T cells and CD8 +T cells were significantly decreased in critically ill children within 48 hours of admis-tion[(57. 43 ± 13. 46)%,(21. 26 ± 7. 87)% vs. (66. 24 ± 5. 27)%,(26. 82 ± 7. 63)%,P<0. 05]; At the same time,CD4 +T cells and NK cells had no significant change[(33. 42 ± 11. 29)%,(8. 83 ± 7. 77)% vs. (34. 89 ± 4. 94)% (11. 34 ± 5. 60)%,both P<0. 05]; While B cells were significantly increased[(31. 69 ±13. 83)% vs. (21. 08 ±7. 24)%,P<0. 05]. Neutrophil activation rate[(14. 32 ±14. 81)%] was signifi-cantly higher than the normal reference value ( 0 -10%) and the activation rate was more than 90% after stimulated by PMA. The plasma level of complement C3[(0. 88 ± 0. 31) g/L] was lower than that of the control group[(1. 19 ± 0. 18)g/L,P<0. 05]. (2) Compared with the first time,the percentages of CD3 +cells and CD4 + cells were increased after treated for one week in 23 patients[(61. 20 ± 13. 56)%,(36. 79 ± 9. 95)% vs. (56. 80 ± 13. 99)%,(32. 86 ± 10. 87)%,both P<0. 05]. No significant difference in neutrophil activation and activation rate after PMA stimulation was found compared with admition. IgA,IgM and comple-ment C3 were significantly increased[(0. 98 ± 0. 75) g/L,(1. 00 ± 0. 39) g/L,(1. 15 ± 0. 34) g/L vs. (0. 80 ± 0. 69) g/L,(0. 86 ± 0. 48) g/L,(0. 93 ± 0. 23) g/L,all P<0. 05]. Conclusion Immune disorders occur in critically ill children in the early stage of illness,the most obvious change is cellular immune response,and im-mune function starts to recover after one week.

OBJECTIVE Through researching the ABR threshold, the cochlear morphology and miR-96 expression in the cochlear of BALB/c mice at different month's age, to find out if the miR-96 can regulate the age related hearing loss of BALB/c mice.METHODS ABR testing, AO/PI staining and scanning electron microscope were used to observe the ABR threshold and cochlear morphology of the BALB/c mice at the ages of 3 months, 6 months, 12 months and 18 months. Real-time PCR was used to detect the expression of miR-96 in the cochlea of BALB/c mice at the ages of 3 months, 6 months, 12 months and 18 months.RESULTS The ABR thresholds of BALB/c mice were (18.5±8.3), (45.8±7.8), and (85.6±15.6) dB SPL separately at the age of 3, 6 and 12 months. At the age of 18 months, no response was observed in the ABR testing with 120 dB SPL acoustic stimulation. In the AO/PI staining, we found that the outer hair cells was apparently lost since the age of 6 months and the loss of hair cells aggravated as the month's age increased. At the age of 12 months, no outer hair cells was left, inner hair cells was lost apparently too. With the scanning electron microscope, we found the changes of deficiency, lodging, fusion, shortening and inversion in the hair cell cilia. And these changes were aggravated as the month's ages increased. At the age of 3 months, the relative expression of miR-96 (2-△CT) was 0.0225±0.0073. The relative expression of miR-96 (2-△CT) in the cochlea were 0.0162±0.0048, 0.0116±0.0048, and 0.0050±0.0014 at the age of 6 months, 12 months and 18 months separately, comparing with the relative expression of miR-96 at the age of 3 months, the differences were significant(P<0.05).CONCLUSION The hearing loss, hair cells loss, and cilia damage aggravated as the month's age increased, but the miR-96 expression in the cochlea decreased. Which suggest that miR-96 might play an important role in the age related hearing loss.

Objective To explore the effect of hypoxic preconditioning (HPC) on endoplasmic reticulum stress after traumatic brain injury in rats.Methods Forty-eight Sprague Dawley rats were randomly divided into HPC group (HPC modeling) and non-HPC group (without HPC modeling),with 24 rats in each group.And then,each of the group was further divided into four sub-groups (n=6):three sub-groups after traumatic brain injury (TBI) for one,3 and 7 days (TBI modeling,and drawing and observation after various TBI treatment times),and a control sub-group (without any treatment).HPC models were induced in the low-pressure oxygen chamber for 3 h daily continuing for 3 d.TBI models were established by modified Freeny's freely falling equipment.Modified neurological severity scale (mNSS) scores of the rats were recorded after brain injury.C/EBP homologous protein (CHOP) mRNA and protein expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blotting.TUNEL was used to evaluate the apoptotic rate and the correlation between CHOP levels and apoptotic rate was analyzed.Results The rnNSS scores,relative CHOP mRNA and protein expressions,and apoptotic rate in the one,3 and 7 days subgroups after TBI were significantly higher than those in the control group (P＜0.05);and these levels peaked at 3 d;the mNSS scores,relative CHOP mRNA and protein expressions,and apoptotic rate in HPC group were significantly lower than those in the non-HCP group (P＜0.05);and the correlation analysis showed the CHOP expressions were positively correlated with apoptotic rate in the in HPC group and non-HCP group (r=0.957,P=0.000;r=0.966,P=0.000).Conclusion HPC can down-regulate the expression of pro-apoptotic protein CHOP which participates in endoplasmic reticulum stress pathway,reduce neuronal apoptosis and improve neurological function.

OBJECTIVE To investigate a better surgical treatment for chronic otitis media.METHODS 106 patients with chronic otitis media were collected from hospital. We assessed effectss of ossicular chain reconstruction without incision of mastoid (method 1) and ossicular chain reconstruction with incision of mastoid (method 2).We compared therapeutic effect, complication, and surgical treatment between these two groups. Furthermore, we performed stratification analysis by normal or abnormal function of stapes, Eustachian and tendon of tensor tympani, using logistic regression model. RESULTS The improvement of hearing by method 1 and 2 were 85.71%, 68.00% (P=0.0296). The recovery rate of drying ear were 92.86%, 88.00% (P=0.3931). The proportion of continued tinnitus were 10.71%, 18.00% (P=2827). There were 85.71% and 36.00% samples with numeric pain score from 1 to 3 (P<0.0001). There were 89.29%, 24.00% samples with operation hour <2.0 hour (P<0.0001). For those patients with normal function of stapes, Eustachian and tendon of tensor tympani, the OR of method 1 were 2.91, 3.08 and 3.33 For those patients with abnormal function, the OR was 3.27, 2.89 and 1.33. CONCLUSION Ossicular chain reconstruction without incision of mastoid is a suitable surgical treatment for chronic chronic otitis media,it could improve hearing more effectively with entire debridement of the focus and shorter operation time.