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.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

AIM:To evaluate the characteristics of ocular biometric parameters and the distribution of corneal astigmatism(CA)in patients with high myopia before cataract surgery.METHODS:A prospective cross-sectional study was conducted, and 695 cataract patients(695 eyes)with high myopia [defined as an axial length(AL)≥26.00 mm] scheduled to undergo cataract surgery at our hospital from January 2022 to December 2024 were consecutively enrolled, another 695 cataract patients(695 eyes)with normal ALs(22.00 mm ≤AL≤25.00 mm)who underwent cataract surgery at our hospital during the same period were included in the control group. For patients with both eyes eligible, the right eye was used for analysis. Before cataract surgery, IOL Master 700 was used to measure the ocular biometric parameters of both eyes for each patient in the two groups. The medical records and ocular biometric data in the two groups were recorded and collected.RESULTS:There were no statistically significant differences between the two groups in genger, age, corneal diameter, and central corneal thickness(all P>0.05). In the high myopia group, the mean AL was 29.20±2.61 mm, and 252 eyes(34.1%)had AL ≥30.00 mm(extremely high myopia). The mean anterior chamber depth(ACD), lens thickness, vitreous chamber depth(VCD), CA, AL/corneal radius of curvature and VCD/AL in the high myopia group were 3.45±0.40, 4.41±0.47, 21.34±2.60 mm, 1.18±0.78 D, 3.79±0.38, and 0.73±0.03, respectively, which were all greater than those in the control group(all P<0.01). In the high myopia group, 350 eyes(50.4%)had CA ≥1.00 D, 192 eyes(27.6%)had CA ≥1.50 D, and 94 eyes(13.5%)had CA ≥2.00 D, which were all higher than those in the control group(32.8%, 15.1%, and 6.6%, respectively; all P<0.001). In the high myopia group, 87 eyes(12.5%)had flat corneas, 424 eyes(61.0%)had moderate CA, and 40 eyes(5.8%)had high CA. These proportions were all higher than those in the control group(6.0%, 46.9%, and 2.9%, respectively; all P<0.001). In the high myopia group, ACD and ACD/AL were negatively correlated with AL(r=-0.162 and -0.661, respectively; all P<0.001), while both ACD and ACD/AL in the control group were positively correlated with AL(r=0.338 and 0.105, respectively; both P<0.01). In the high myopia group, CA increased with age when the patient's age was ≥50 years(r=0.197, P<0.001), which was consistent with the control group.CONCLUSION: The standardized ocular biometric data of cataract patients with high myopia before cataract surgery are helpful for ophthalmologists to accurately calculate the intraocular lens(IOLs)power and select the appropriate IOL type. The majority of high myopia patients need simultaneous correction of CA during cataract surgery.

Objective To investigate whether the application of automated software for computed tomography angiography(CTA)and computed tomography perfusion imaging(CTP)can improve in-hospital workflow for endovascular treatment(EVT)in acute ischemic stroke patients.Methods We included patients with acute ischemic stroke who received CTA and CTP evaluation followed by EVT through the stroke emergency pathway at the Affiliated Hospital of Southwest Medical University between January 1,2020 and December 30,2022.The patients were divided into two groups:control group and artificial intelligence(Al)group based on whether automated software was used for assessment.The control group consisted of patients who underwent manual post-processing of multimodal imaging before June 2021,while the AI group was composed of patients whose imaging was processed with automated software from July 2021 onwards.The primary outcome was door-to-puncture time(DPT),and the secondary outcome was the 90-day modified Rankin Scale(mRS)score.Results A total of 312 patients were included,with 145 in the control group and 167 in the AI group.The median age of all the patients was 68 years(range:58-74 years),and 55.4％(173 patients)were male.The median National Institutes of Health Stroke Scale(NIHSS)score at presentation was 16 scores(range:12-19 scores).The median DPT was reduced from 110 min(range:80-150 min)before the use of automated software to 95 min(range:65-125 min)after its implementation(P＜0.001).However,there was no significant difference in the proportion of patients achieving functional independence(mRS score of 0-2)between the two groups(39.3％vs.41.3％,P=0.719).Conclusion The application of multimodal CT automated software improves the in-hospital workflow for acute ischemic stroke patients by reducing the time to EVT.However,the software did not significantly impact neurological functional outcomes as measured by the mRS.

Objective To investigate whether the application of automated software for computed tomography angiography(CTA)and computed tomography perfusion imaging(CTP)can improve in-hospital workflow for endovascular treatment(EVT)in acute ischemic stroke patients.Methods We included patients with acute ischemic stroke who received CTA and CTP evaluation followed by EVT through the stroke emergency pathway at the Affiliated Hospital of Southwest Medical University between January 1,2020 and December 30,2022.The patients were divided into two groups:control group and artificial intelligence(Al)group based on whether automated software was used for assessment.The control group consisted of patients who underwent manual post-processing of multimodal imaging before June 2021,while the AI group was composed of patients whose imaging was processed with automated software from July 2021 onwards.The primary outcome was door-to-puncture time(DPT),and the secondary outcome was the 90-day modified Rankin Scale(mRS)score.Results A total of 312 patients were included,with 145 in the control group and 167 in the AI group.The median age of all the patients was 68 years(range:58-74 years),and 55.4％(173 patients)were male.The median National Institutes of Health Stroke Scale(NIHSS)score at presentation was 16 scores(range:12-19 scores).The median DPT was reduced from 110 min(range:80-150 min)before the use of automated software to 95 min(range:65-125 min)after its implementation(P＜0.001).However,there was no significant difference in the proportion of patients achieving functional independence(mRS score of 0-2)between the two groups(39.3％vs.41.3％,P=0.719).Conclusion The application of multimodal CT automated software improves the in-hospital workflow for acute ischemic stroke patients by reducing the time to EVT.However,the software did not significantly impact neurological functional outcomes as measured by the mRS.

A 75-year-old female patient with postoperative colon cancer received fruquintinib (5 mg once daily, 3 weeks on and 1 week off per 4-week cycle). The patient had normal blood pressure in the past, and approximately one week after medication, she developed hypertension with systolic blood pressure 180-190 mmHg and unknown diastolic pressure. The patient′s blood pressure was with adequate control after self-administration of nifedipine sustained-release tablets twice (20 mg/dose). After 3 weeks of fruquintinib treatment, bilateral lower limb edema occurred in the patient, leading to a 1-week drug discontinuation. Upon resuming the medication for 1 day, the patient suddenly developed dyspnea and loss of consciousness. Chest CT revealed signs of heart failure. Laboratory tests showed high-sensitivity cardiac troponin I (hs-cTnI) 0.27 μg/L, creatine kinase (CK)-MB 7.13 μg/L, myoglobin 132.88 μg/L, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4 039.8 ng/L. Fruquintinib was discontinued, and the patient received myocardial nutritional support, diuretics, anticoagulants, hepatoprotective agents, and potassium supplementation, etc. On day 2, the patient regained consciousness with hs-cTnI 0.28 μg/L, CK-MB 4.63 μg/L, myoglobin 34.25 μg/L, and NT-proBNP 10 181.3 ng/L. Antiplatelet therapy, diuretics, lipid-lowering agents, and antihypertensive treatment were initiated. On day 3, color doppler echocardiography confirmed myocardial infarction complicated by heart failure. Fruquintinib-induced acute non-ST-segment elevation myocardial infarction with acute heart failure was considered. On day 6 of fruquintinib discontinuation, NT-proBNP decreased to 295.8 ng/L, and all laboratory test parameters normalized on day 9. One month later, repeated tests showed no abnormalities in the myocardial enzyme.

A 75-year-old female patient with postoperative colon cancer received fruquintinib (5 mg once daily, 3 weeks on and 1 week off per 4-week cycle). The patient had normal blood pressure in the past, and approximately one week after medication, she developed hypertension with systolic blood pressure 180-190 mmHg and unknown diastolic pressure. The patient′s blood pressure was with adequate control after self-administration of nifedipine sustained-release tablets twice (20 mg/dose). After 3 weeks of fruquintinib treatment, bilateral lower limb edema occurred in the patient, leading to a 1-week drug discontinuation. Upon resuming the medication for 1 day, the patient suddenly developed dyspnea and loss of consciousness. Chest CT revealed signs of heart failure. Laboratory tests showed high-sensitivity cardiac troponin I (hs-cTnI) 0.27 μg/L, creatine kinase (CK)-MB 7.13 μg/L, myoglobin 132.88 μg/L, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4 039.8 ng/L. Fruquintinib was discontinued, and the patient received myocardial nutritional support, diuretics, anticoagulants, hepatoprotective agents, and potassium supplementation, etc. On day 2, the patient regained consciousness with hs-cTnI 0.28 μg/L, CK-MB 4.63 μg/L, myoglobin 34.25 μg/L, and NT-proBNP 10 181.3 ng/L. Antiplatelet therapy, diuretics, lipid-lowering agents, and antihypertensive treatment were initiated. On day 3, color doppler echocardiography confirmed myocardial infarction complicated by heart failure. Fruquintinib-induced acute non-ST-segment elevation myocardial infarction with acute heart failure was considered. On day 6 of fruquintinib discontinuation, NT-proBNP decreased to 295.8 ng/L, and all laboratory test parameters normalized on day 9. One month later, repeated tests showed no abnormalities in the myocardial enzyme.

Idiopathic pulmonary fibrosis (IPF) is a chronic debilitating lung disease with unknown etiology, complex syndromes and prolonged illness, which is difficult to cure. Based on the theory of "spleen is the envoy" in Huang Di Nei Jing, this article explained the TCM meaning of "spleen is the envoy" and the relationship between spleen and other four organs, especially the relationship between spleen and lung. It is believed that the onset of IPF is due to deficiency of lung and spleen qi, loss of solid defense and evil invasion of the nutritive and defensive levels; qi deficiency and depression lead to heat damage to yin, while long-term blood damage to collaterals involves yang. The pathological process shows the changes from qi entering blood and from meridian to collateral, which eventually leads to the imbalance of qi and blood, yin and yang, the stagnation of phlegm and blood stasis, the obstruction of lung collateral, the mixture of excess and deficiency, and the lingering is difficult to heal. In the treatment, the "spleen is the envoy" is the center, the lung and spleen are treated together, the qi of lung and spleen is strengthened, the yin of lung and stomach is nourished, and finally the root is protected. The treatment is based on syndrome differentiation, modified with syndromes, and the methods of promoting blood circulation, resolving phlegm, warming yang and dredging collaterals are supplemented in time, which provides a new idea for enriching the differentiation and treatment of IPF in TCM.

Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.