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.

OBJECTIVE To compare the clinical effects of different doses of meropenem in the treatment of septic shock. METHODS One hundred and six patients with septic shock were randomly divided into standard-dose group and high-dose group， with 53 cases in each group. Patients in the standard-dose group were given standard dose of meropenem （initial intravenous injection of 1 g meropenem more than 30 minutes， followed by 1 g meropenem intravenously every 8 hours， each time for more than 3 hours）； patients in the high-dose group were given high dose of meropenem （initial intravenous injection of 2 g meropenem more than 30 minutes， followed by 2 g meropenem intravenously every 8 hours， each time for more than 3 hours）； other treatment measures were determined based on the specific conditions of the patients. The main observation indicators were the increments of sequential organ failure assessment （SOFA） scores and simplified acute physiology score Ⅱ （SAPS Ⅱ） after 3， 5 and 7 days of treatment in both groups. Secondary observation indicators included in-hospital mortality， 90-day all-cause mortality， 7-day microbial cure rate， 7-day clinical cure rate， serum procalcitonin （PCT） and C-reactive protein （CRP） levels after 3， 5 and 7 days of treatment， hospitalization days in the intensive care unit， ventilator treatment days， the highest dose of norepinephrine. The occurrence of adverse drug reaction in the two groups was observed. RESULTS The increments of SOFA scores and SAPS Ⅱ after 7 days of treatment， the levels of PCT and CRP after 5 and 7 days of treatment as well as the 90-day all-cause mortality in the high- dose group were significantly lower than the standard-dose group （P＜0.05）. There were no statistically significant differences in other indicators between the two groups （P＞0.05）. CONCLUSIONS High-dose meropenem treatment for septic shock has better clinical effects and is safer than standard-dose meropenem.

OBJECTIVE To optimize the honey processing technology of Phellinus igniarius. METHODS The key factors of honey processing technology of P. igniarius （honey-water ratio， the mass ratio of honey-water to P. igniarius， the frying temperature and the frying time） were investigated by orthogonal test combined with analytic hierarchy process to determine the optimal technological parameters， using the internal quality （the contents of ergosterol， protocatechuic aldehyde and protocatechuic acid） and appearance traits as evaluation indexes. RESULTS The optimal process of honey-roasting P. igniarius was to take raw P. igniarius （1 cm3 square block）， add the appropriate amount of auxiliary materials （with 25 kg of refined honey and water for every 100 kg of P. igniarius）， mix well， moisten for 2 h until the auxiliary materials were completely absorbed； put it in a frying container， fry at the frying temperature of 130-140 ℃ for 5 min； take it out， put it in an oven at 50 ℃ for 2 h； take it out， and let it cool. The RSD of the results of three validation experiments was 0.68%. CONCLUSIONS The optimized honey processing technology of P. igniarius is stable and feasible.

OBJECTIVE To optimize the honey processing technology of Phellinus igniarius. METHODS The key factors of honey processing technology of P. igniarius （honey-water ratio， the mass ratio of honey-water to P. igniarius， the frying temperature and the frying time） were investigated by orthogonal test combined with analytic hierarchy process to determine the optimal technological parameters， using the internal quality （the contents of ergosterol， protocatechuic aldehyde and protocatechuic acid） and appearance traits as evaluation indexes. RESULTS The optimal process of honey-roasting P. igniarius was to take raw P. igniarius （1 cm3 square block）， add the appropriate amount of auxiliary materials （with 25 kg of refined honey and water for every 100 kg of P. igniarius）， mix well， moisten for 2 h until the auxiliary materials were completely absorbed； put it in a frying container， fry at the frying temperature of 130-140 ℃ for 5 min； take it out， put it in an oven at 50 ℃ for 2 h； take it out， and let it cool. The RSD of the results of three validation experiments was 0.68%. CONCLUSIONS The optimized honey processing technology of P. igniarius is stable and feasible.

Objective:To investigate the clinical characteristics and prognosis of duodenal neuroendocrine neoplasms.Methods:The clinical data of 35 patients with duodenal neuroendocrine neoplasms admitted to Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from Jan 2012 to Dec 2021 were retrospectively analyzed. The differences of clinical characteristics between periampullary and non-periampullary duodenal neuroendocrine neoplasms were analyzed. Kaplan-Meier curve was used for survival analysis, and the clinical factors affecting the prognosis were analyzed.Results:Of the 35 patients, 30 underwent tumor resection, 7 (23%) developed different degree of complications after operation and were improved and discharged after intervention. A total of 5 patients died during the follow-up period. Only 1 of 30 patients who underwent tumor resection died 30 months after operation due to disease progression, and the others had no recurrence or metastasis. Univariate analysis showed that tumor size, tumor grade, and tumor location were associated with the prognosis of patients (all P<0.05), and multivariate analysis showed that patients with tumors located.Away from the ampulla had a significantly better prognosis than those located around the duodenal ampulla ( P<0.01). Conclusions:Patients with duodenal neuroendocrine neoplasms have a good prognosis after complete resection; patients with duodenal neuroendocrine neoplasms located around the ampulla of Vater have a relatively poor prognosis compared with those away from the area of ampulla.

Objective:To explore the current situation and influencing factors of somatic and psychological symptoms among nursing undergraduate students.Methods:This study was a cross-sectional study. Through snowball sampling and convenience sampling, 806 nursing undergraduate students from East, South, Central, North, Northwest and Southwest China were selected as the research subjects from March to July 2021. A survey was conducted among nursing undergraduate students using the Patient Health Questionnaire-15 (PHQ-15), Patient Health Questionnaire-2 (PHQ-2), and Generalized Anxiety Disorder-2 (GAD-2) .Results:The positive detection rates of somatic symptoms, depression, and anxiety among 806 nursing undergraduate students were 66.5% (536/806), 14.3% (115/806), and 12.9% (104/806), respectively. The results of binomial Logistic regression analysis showed that chronic diseases, perceived health status, and water intake were the influencing factors for psychological and somatic symptoms of nursing undergraduate students ( P<0.05). Nursing undergraduate students' somatic symptoms, depression and anxiety were positively correlated ( P<0.05) . Conclusions:The detection rate of somatic symptoms among nursing undergraduate students is high. Families and universities should pay timely attention to the psychological and somatic health of nursing undergraduate students, and provide targeted psychological support for students with different characteristics.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective:To explore the clinical features, diagnosis, treatment and prognosis of rectal neuroendocrine tumor with lymphatic metastasis.Method:There were 153 case who were diagnosed with RNET, among them, there were 10 patients(6.5%) with lymphatic metastasis in Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from January 2012 to December 2020, including 4 males and 6 females, aged from 32 to 71 years old, and the median age was 56.5 years.Results:Of the 10 patients, 3 had tumors < 1 cm in diameter, 4 had 1 to 2 cm, and 3 had > 2 cm. Preoperative CT examination was performed in 10 patients, of which 9 suggested lymphatic metastasis; preoperative MRI examination was performed in 7 patients, of which 6 suggested lymphatic metastasis. All patients were received radical resection, in which Miles operation was performed in 2 cases, Dixon operation in 6 cases, and additional Dixon operation after endoscopic submucosal dissection in 2 cases.All patients were followed up for 51 months (ranged from 14 to 118 months). Nine patients had no recurrence or metastasis, and one patient had abdominal metastasis 40 months after surgery and died after 31 months of comprehensive treatment.Conclusions:Lymphatic metastasis is rare in rectal neuroendocrine tumor. Imaging examination has important reference value for judging the status of lymphatic metastasis. For rectal neuroendocrine tumor with lymphatic metastasis, radical resection is effective.

Objective:To explore the value of Caprini risk assessment scale and serum D-dimer in early prediction of postoperative lower extremities deep vein thrombosis (DVT) in patients with gastrointestinal malignant tumor.Methods:A total of 240 patients with gastrointestinal malignant tumors treated in Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from Jan to Oct 2020 were analyzed retrospectively.Results:Caprini score was 4 in 8 cases, 5-7 in 217 cases, and 8 in 15 cases. Sixty-seven patients developed lower extremity DVT after operation. No patients with Caprini score of 4 had DVT, 57 cases (26.3%) with a score of 5-7 had DVT; 10 cases whose score were ≥8 points (66.7%) developed DVT. There was a higher incidence of lower extremity DVT in patients ≥8 points than those of 5-7 points after surgery ( P<0.01). The postoperative Caprini score of the DVT group was higher than that of the non-DVT group (6.37±1.01 vs. 5.80±0.94, t=4.108, P<0.001). D-dimer on the first day after operation in DVT group (4.08±2.27 vs. 2.01±1.04, t=7.715, P<0.001) and the level of serum D-dimer (2.93±1.81 vs. 2.30±1.21, t=2.631, P<0.001) on day 3 was higher than that in the non-DVT group. According to the ROC curve, the best cut-off value for serum D-dimer to predict lower extremity DVT on the first postoperative day was 2.84 mg/L, the sensitivity was 70.1%, the specificity was 87.3%, and the area under the curve (AUC) was 0.815. The best cut-off value of D-dimer for predicting lower limb DVT on day 3 after surgery was 1.67 mg/L, sensitivity was 85.1%, specificity was 34.7%, and AUC was 0.611. Conclusions:Patients with gastrointestinal malignant tumors have a high incidence of postoperative lower extremity DVT. When the serum D-dimer exceeds 2.84 mg/L on the first postoperative day, the likelihood of postoperative lower extremity DVT is higher.

Objective:To identify the clinical factors associated with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced middle and low rectal cancer and establish a scoring system.Methods:In this retrospective analysis the clinical data of patients with locally advanced middle and low rectal cancer treated with nCRT combined with surgery at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from Jan 2016 to Jan 2020 were studied. Patients were divided into pCR group and non-pCR group. Single factor analysis and Logistic multivariate regression analysis were performed to explore pCR related factors after nCRT, and a pCR prediction scoring system was established.Results:The pCR was achieved in 33 patients (20.8%). Univariate analysis showed that the maximum thickness of the tumor≤25mm before nCRT ( P=0.046), concurrent oxaliplatin-combined intensive chemotherapy ( P=0.013), the NLR≤1.65 before nCRT ( P=0.004) and the serum CEA≤5 ng/ml before nCRT ( P=0.016) were significantly associated with pCR. In multivariate analysis, concurrent oxaliplatin-combined intensive chemotherapy, the NLR before nCRT and serum CEA before nCRT were independent related factors of pCR. The probability of pCR for patients with score of 0, 1, 2, and 3 was 42% (10/24), 30% (19/63), 5% (3/57) and 7% (1/15), respectively. The probability of pCR in patients with score≤1 point was 33% (29/87), and 6% (4/72) for score?1 point ( P?0.001). The area under the curve of the scoring system is 0.729 (95% CI: 0.638-0.820, P?0.001). Conclusions:Concurrent oxaliplatin-combined intensive chemotherapy, NLR≤1.65 before nCRT and serum CEA≤5 ng/ml before nCRT are independent predictors of pCR in locally advanced middle and low rectal cancer and the scoring system constructed in combination with above indicators can effectively predict pCR.