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 delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.

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 review the incidence and treatment status of perioperative anemia in patients with gastric cancer.Methods:The clinicopathological data of gastric cancer patients who underwent surgery at Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Jan to Dec 2019 were collected. Univariate analysis and multivariate Logistic regression analysis were used to explore the risk factors of preoperative anemia in gastric cancer.Results:A total of 879 patients were included in this study. The incidence of preoperative anemia in patients with gastric cancer was 35.6%. The incidence of postoperative anemia was 63.5%. The proportion of patients with preoperative anemia receiving treatment was 17.3%, and the proportion of patients with postoperative anemia receiving treatment was 17.4%. Univariate analysis showed that age, nutritional risk screening 2002, T stage, M stage, tumor stage and lymph node metastasis were associated with preoperative anemia (all P<0.05). Multivariate Logistic regression analysis showed that age >60 years , nutritional risk screening 2002 ≥3, T 3-4 stage and M 1 stage were independent risk factors for preoperative anemia in patients with gastric cancer (all P<0.05). Conclusions:The incidence of perioperative anemia in patients with gastric cancer is high. At present, the proportion of patients with perioperative anemia receiving treatment is low. High nutritional risk, advanced age, late tumor T stage and distant metastasis are independent risk factors for preoperative anemia in patients with gastric cancer.

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.