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.

COVID-19 is a respiratory disease caused by SARS-CoV-2 infection,which has strong infectivity and seriously threatens human health all over the world. Vaccination is the most effective means to prevent SARS-CoV-2 infection. World Health Organization(WHO)has required the use of Global Standard 1(GS1)for the tracking and traceability of COVID-19vaccines and therapeutics. Traceability identification system is the basis and core of traceability system,as well as the premise of implementation of traceability,throughout the whole product traceability process. By carrying out unique global coding for all levels of packaging and logistics units of export vaccine products,and establishing vaccine traceability codes and logistics unit traceability codes,we can help export vaccine manufacturers establish traceability systems,realize the traceability of product information in production,circulation,use and other links,strengthen the quality and safety supervision of export vaccine products,strengthen the risk monitoring,early warning and effective disposal,as well as strengthen the recall of defective products and analysis of causes,so as to enhance the international market's trust and recognition of Chinese vaccine safety. This paper summarizes the importance of establishing traceability system for export vaccine products,the application of GS1 system in medical field at home and abroad,the traceability identification coding,barcode representation and quality requirements of export vaccine products,in order to provide a reference for establishing traceability identification system for export vaccine products in China and meeting the requirements of international standards and regulations.

BACKGROUND:Stable intertrochanteric fractures can be treated by closed reduction and internal fixation,but there is no absolute advantage for unstable intertrochanteric fractures with osteoporosis. OBJECTIVE:To investigate the efficacy of arthroplasty in the treatment of unstable intertrochanteric fractures in the elderly with osteoporosis by comparing the indexes related to closed reduction internal fixation and arthroplasty. METHODS:Clinical data of 102 elderly patients with unstable intertrochanteric fractures of the femur treated in Affiliated Hospital of Qingdao University from January 2017 to January 2020 were retrospectively analyzed.Patients were divided into two groups according to the surgical method.In the Gamma3 group,62 cases received Gamma3 internal fixation system.In the joint replacement group,40 cases received an artificial femoral head replacement or total hip replacement.Surgical information,hospitalization,hip function,and postoperative complications were compared between the two groups. RESULTS AND CONCLUSION:(1)There were statistical differences between the Gamma3 group and the joint replacement group in weight-bearing time(P＜0.001),hospital stay(P＜0.05),intraoperative bleeding(P＜0.001),and length of surgery(P＜0.001).The mean weight-bearing time and hospital stay were shorter in the joint replacement group than in the Gamma3 group.Intraoperative bleeding and duration of surgery were better in the Gamma3 group than in the joint replacement group.(2)There was no significant difference in Harris hip score,subitem centesimal hip score,and postoperative complications 12 months after surgery in both groups(P=0.526,0.788,0.228).(3)It is indicated that arthroplasty has achieved better outcomes in the treatment of elderly unstable intertrochanteric fractures combined with osteoporosis,enabling early weight bearing and functional exercise.Careful selection of the appropriate patient and prosthesis type for arthroplasty will result in greater patient benefit.

Objective:To carry out preimplantation genetic testing (PGT) for a Chinese pedigree affected with Rett syndrome (RTT).Methods:A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4, 2021 was selected as the study subject. Variant of the MECP2 gene was analyzed by next generation sequencing (NGS) and Sanger sequencing. Direct sequencing was also used to determine the carrier status for the c. 925C>T variant of the MECP2 gene in the blastocysts, and Sanger sequencing was used to validate the results. The MECP2 gene and 168 effective single nucleotide polymorphism (SNP) loci within 2 Mb ranges up- and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos, and embryos without the variant were subjected to the analysis for chromosomal aneuploidies. Results:PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant. The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid. Following genetic counselling, the couple had opted to transplant the optimal blastocyst. Following clinical pregnancy, prenatal diagnosis showed that the fetus has a normal chromosomal karyotype, and the c. 925C>T variant was not detected in the amniotic fluid sample. A healthy girl was born by Cesarean section at full term.Conclusion:NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.

Objective To analyze and discuss the medication rule of professor Ruan Yan in the treatment of children with allergic rhinitis by using data mining method,and to provide reference for the clinical research and patented drugs development for the treatment of children with allergic rhinitis.Methods The outpatient medical records of professor Ruan Yan for the treatment of children with allergic rhinitis were collected.Microsoft Excel 2010 software was used for frequency statistics.SPSS Clementine 12.0 software was used for association rule analysis,cluster analysis and factor analysis to obtain the data.The frequency of use of various drugs and the association rules between drugs were obtained.Then the medication rules in professor Ruan Yan's prescription were analyzed.Results A total of 308 Chinese medicine compounds were included,involving 80 kinds of Chinese medicines,among which relieving drugs and qi-invigorating herbs were high-frequently used.The distribution of traditional Chinese medicine syndrome types was mainly characterized by lung-qi deficiency-cold syndrome and lung-spleen qi deficiency syndrome.The medicinal properties were mainly spicy,warm and sweet,and most of them belonged to the lung,spleen and stomach meridians.Five core prescriptions were extracted by factor analysis.Four drug combinations were obtained by systematic cluster analysis.Conclusion Ventilating lung and opening the orifices,expelling wind and removing cold,strengthening the spleen and replenishing qi are basic therapeutic principles for professor Ruan Yan in the treatment of children with allergic rhinitis.The treatment mainly focused on dispelling evil,ventilating lung and opening the orifices,expelling wind and removing cold during the acute stage of allergic rhinitis.In the remission period,according to the principle of"treating disease must be based on its origin",the treatment should enhance children's physical fitness,tonify lung and strengthen spleen,thereby reducing recurrence.

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Objective To study the effect and potential mechanism of Chaihuang Yishen Granules on renal fibrosis in mice with chronic kidney disease.Methods Thirty-six C57BL/6 male mice were randomly divided into sham group,model group,low-,and high-dose Chaihuang Yishen Granules groups(3.835 g·kg-1 and 7.67 g·kg-1),positive control group and Mincle ligand trehalose-6,6-dibehenate(TDB 10 mg·kg-1)group.Unilateral ureteral obstruction(UUO)was used to establish the model of renal fibrosis in mice.One hour after operation,mice in each drug-treated group were given corresponding drugs by gavage,and sham operation group and model group were given saline by gavage,once a day for 7 consecutive days.The pathological changes and fibrosis in the kidneys of mice in all groups were observed by hematoxylin eosin staining and Sirius red staining.The expressions and secretions of inflammatory factor IL-1β,IL-6 and TNF-α in kidneys of all groups were detected by Real-time PCR and ELISA.Immunohistochemistry and Western Blot were used to detect fibrosis indicators,including α-SMA and Fn protein levels.Immunofluorescence and Western Blot were further used to determine protein levels of Mincle and its downstream signal Syk/NF-κB.The proportion of Mincle positive macrophages was analyzed by flow cytometry.Results Compared with the model group,low-and high-dose Chaihuang Yishen Granules can effectively improve UUO-induced renal injury and fibrosis,and inhibit α-SMA and Fn protein levels in the kidney(P＜0.01).Moreover,high-dose Chaihuang Yishen Granules can effectively reduce the expressions and secretions of inflammatory factor IL-1β,IL-6 and TNF-α of kidney in UUO model(P＜0.01),as well as inhibit phosphorylation of NF-κB(P＜0.01).The mechanism study showed that Chaihuang Yishen Granules could significantly reduce the protein level of Mincle and the activity of its downstream signal Syk in the kidney of UUO mice(P＜0.01).After TDB was used to activate Mincle,the effect of Chaihuang Yishen Granules on improving renal injury,inflammatory factor secretion and fibrosis was significantly reduced(P＜0.05,P＜0.01).Conclusion Chaihuang Yishen Granules can improve UUO-induced renal injury,inflammation and fibrosis,and its mechanism may be related to the down-regulation of Mincle/Syk/NF-κB signaling pathway.

AIM: To observe the effects and mechanisms of hederagenin (HDG) in improving psoriasis skin lesions and inflammation in mice. METHODS: A mouse model of psoriasis was established by depilation of the back and continuous application of imiquimod for 7 days in C57 mice. After modeling, HDG was administered orally (low dose: 25 mg · kg

Objective:To observe any effect of transcranial direct current stimulation (tDCS) on the cognition of stroke survivors and the integrity of their white matter fibers.Methods:Thirty persons with post-stroke cognitive impairment (PSCI) were randomly divided into an experimental group ( n=15) and a control group ( n=15). In addition to basic drug therapy and routine cognition training, the experimental group received 20 minutes of tDCS daily, 5 days per week for 3 weeks, while the control group received sham tDCS stimulation. Before and after the treatment, both groups′ cognitive functioning was evaluated using the mini-mental state examination (MMSE) and the Montreal cognitive assessment scale (MoCA). Their ability in the activities of daily living (ADL) was quantified using the modified Barthel index (MBI). Diffusion tensor imaging (DTI) was employed to observe any changes in the integrity of their white matter fibers. Results:The average MMSE, MOCA and MBI scores of both groups had improved significantly after the treatment, but the improvement in the experimental group was significantly greater than among the controls. The average fractional anisotroposy value of the affected inferior fronto-occipital fasciculus in both groups was positively correlated with the group′s average MMSE score and MoCA score.Conclusion:tDCS can effectively improve the cognition and functioning in the activities of daily living of stroke survivors. Its mechanism may be related to improving the integrity of the white matter fibers involved.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.