With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

ObjectiveCandidate genes related to the regulation of litter size traits in English Springer Spaniel breeding bitches are explored, and the genetic mechanism underlying fertility in this breed is investigated, in order to provide reference molecular markers for genomic selection of high fecundity. MethodsWhole genome resequencing was performed on English Springer Spaniel breeding bitches that had given birth to at least 3 litters, and the bitches were divided into a high-litter-size group and a low-litter-size group according to the average litter size. Selection signal analysis was used to obtain the intersection of fixation index (F_st) and nucleotide diversity (Pi) signals as highly selected regions, and candidate genes were screened based on gene annotation and functional enrichment analysis. ResultsThe average litter size in the high-litter-size group (7.41±1.27) was significantly higher than that in the low-litter-size group (3.82±1.20) (P＜0.05), and the total number of live offspring in the high-litter-size group (7.06±1.10) was extremely significantly higher than that in the low-litter-size group (3.67±1.11) (P＜0.01). A total of 3 155 706 SNPs were detected in the two groups, 63.09% of which were located in intergenic regions, 33.96% in intronic regions, and 0.38％, 0.57％, and 0.09％ in exonic regions, 3' untranslated regions (UTRs), and 5'UTRs, respectively. Among the SNPs in exonic regions, 5 256 were nonsynonymous variants, accounting for 43.55%. A total of 1 752 differential genes were identified after annotation screening. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG) enrichment analyses identified 13 candidate genes that may affect reproductive performance and litter size traits, including WDR35, SMAD7, RPGR, RERGL, PGRMC2, LOC482182, GIMD1, COX7B2, COX16, BMPR2, BMP6, BICD1, and SLC9C1. Their functions mainly involve reproductive hormone regulation, embryonic development, GTPase activation, and oocyte apoptosis. ConclusionEnglish Springer Spaniel breeding bitches have undergone significant artificial selection for litter size traits. These 13 candidate genes play key roles in oocyte maturation and regulation during early pregnancy, providing a new molecular basis for elucidating the genetic mechanism of canine reproductive traits.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Endoscopic full-thickness resection (EFTR) is a minimally invasive technique that is increasingly used for gastrointestinal stromal tumors (GISTs) originating from the muscularis propria. Despite its advantages over conventional surgery, such as complete tumor resection and faster recovery, EFTR faces challenges related to its efficacy, safety, and feasibility, particularly in gastric GISTs. By summarizing the literature published over the past decade, this review provides a comprehensive overview of the clinical outcomes of EFTR and the evolution of defect closure devices.

The shaoyang meridian is an important pivot between the internal organs and meridians system， with the functions of regulating qi and blood， balancing yin and yang， and coordinating the ascending and descending movement of qi. Dysfunction of the shaoyang pivot can lead to spleen and kidney deficiency， impaired liver and gallbladder qi regulation， and stagnation of qi and blood. It is believed that the onset and progression of Crohn's disease are closely related to shaoyang pivot dysfunction， with the core pathogenesis characterized by shaoyang disharmony， spleen deficiency， dampness retention， and blood stasis. Based on this understanding， the treatment principle centers on harmonizing the shaoyang pivot， supplemented by methods such as warming and nourishing the spleen and stomach， tonifying shaoyang， and soothing the liver and benefiting the gallbladder. Acupuncture is employed to target key acupoints along the shaoyang meridian to restore its regulatory functions， improve spleen and stomach transformation and transportation， facilitate liver and gallbladder qi flow， and promote the circulation of qi and blood. This provides a practical therapeutic approach for acupuncture-based treatment of Crohn's disease.

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with budesonide versus the intubation-surfactant-extubation (INSURE) technique in preterm infants (26–32 weeks’ gestation) with respiratory distress syndrome (RDS).Methods:This randomized controlled trial enrolled 136 premature infants with RDS admitted to our NICU between January 2021 and December 2023. Participants were allocated to either the LISA+budesonide group ( n = 70) or the INSURE group ( n = 66). The LISA+budesonide group received surfactant mixed with budesonide via a laryngoscope-guided catheter during noninvasive continuous positive airway pressure (NCPAP) ventilation, while the INSURE group underwent endotracheal intubation for surfactant delivery followed by extubation to NCPAP. Outcomes included adverse events during administration, blood gas parameters (PaO 2/FiO 2 [P/F ratio] and PaCO 2 at 1 h and 6 h post-administration), respiratory support duration, oxygen dependency, intubation rates within 72 h, apnea episodes, budesonide-related complications, and incidence of bronchopulmonary dysplasia (BPD). Results:The LISA+budesonide group exhibited significantly lower rates of adverse events during administration compared to the INSURE group: regurgitation (10.0% vs. 24.2%; P < 0.05), bradycardia (8.6% vs. 24.2%; P < 0.05), and oxygen desaturation (15.7% vs. 30.3%; P < 0.05). Intubation time did not differ between groups ( P > 0.05).At 1 h and 6 h post-administration, the LISA+budesonide group demonstrated higher P/F ratios ( P < 0.05), with no significant differences in PaCO 2 ( P > 0.05).The LISA+budesonide group required shorter durations of noninvasive respiratory support [(10.4 ± 4.4) d vs. (13.9 ± 5.2) d; P < 0.05] and total oxygen therapy [(15.7 ± 6.2) d vs. (19.2 ± 8.2) d; P < 0.05]. Rates of intubation within 72 h, PS re-administration, apnea episodes, weaning failure, and hospitalization length were comparable ( P > 0.05).BPD incidence was significantly lower in the LISA+budesonide group (10.0% vs. 22.7%; P < 0.05), with no increase in glucocorticoid-related complications ( P > 0.05). Conclusions:In preterm infants (26–32 weeks) with RDS, LISA with budesonide reduces adverse events during surfactant delivery, improves oxygenation, shortens respiratory support duration, and lowers BPD incidence without additional complications compared to INSURE.

The introduction of non-vitamin K antagonist oral anticoagulant (NOAC) into clinical use heralds a new age for anticoagulation therapy in patients with atrial fibrillation (AF).However,anticoagulation-related bleeding is currently a major challenge in the anticoagulation process.Assessing the risk of anticoagulation-related bleeding is an important part for the management of patients with AF.Clinical risk factor scores have moderate ability to predict the risk of anticoagulation-related bleeding.To improve the anticoagulation safety of NOACs,additional clinical and biological markers and genetic polymorphisms should be considered to enhance the predictive capability for anticoagulation-related bleeding.This review summarizes the challenges in the management of anticoagulation therapy,with emphases on the bleeding risk scores,biomarkers,clinical indicators,and genetic loci currently used to guide the risk assessment of anticoagulation-related bleeding in AF patients.This review is expected to provide research insights and reference frameworks for predicting and evaluating the bleeding risk associated with NOACs.
Humans ; Atrial Fibrillation/drug therapy* ; Anticoagulants/therapeutic use* ; Hemorrhage/chemically induced* ; Risk Assessment ; Administration, Oral ; Risk Factors

Objective To explore the relationships of cognitive impairment with cardiovascular death and all-cause death in menopausal women with hypertension.Methods A total of 4 595 natural-menopausal women with hypertension screened in Wuyuan County of Jiangxi Province from July to August 2018 were selected as the research subjects,and a follow-up investigation of death information was completed from June to August 2022.According to the baseline mini-mental state examination(MMSE)score,all subjects were allocated into a normal cognitive function group and a cognitive impairment group.The basic characteristics and the cumulative risk of death evaluated by the Kaplan-Meier curve were compared between two groups.The multivariate Cox regression model was adopted to analyze the effect of cognitive function on death,and the relationship between MMSE score and death was fitted by the restricted cubic spline.Results A total of 4 595 subjects with the mean age of(65.1±8.4)years were included in this study,in which and 1 859(40.5%)patients with cognitive impairment were detected.During a mean follow-up period of(3.9±0.4)years,199 all-cause deaths were collected,including 102 cardiovascular deaths.The normal cognitive function group and the cognitive impairment group had the cumulative all-cause death rates of 2.6%and 6.9%and the cumulative cardiovascular death rates of 1.0%and 4.0%,respectively.The Kaplan-Meier curve showed that the cumulative risks of all-cause death(χ²=47.287,P<0.001)and cardiovascular death(χ²=45.169,P<0.001)in the cognitive impairment group were higher than those in the normal cognitive function group.The results of multivariate Cox regression analysis indicated that compared with the normal cognitive function group,the cognitive impairment group had increased risks of all-cause death(HR=1.75,95%CI=1.28-2.39,P<0.001)and cardiovascular death(HR=2.56,95%CI=1.61-4.09,P<0.001).The results of the restricted cubic spline curve fitting showed that the MMSE score had linearly negative correlations with the risk of all-cause death(P_all<0.001, P n o n - l i n e a r i t y=0.519)and cardiovascular death(P_all<0.001, P n o n - l i n e a r i t y=0.195).Conclusion Cognitive impairment is an independent risk factor for all-cause death and cardiovascular death in menopausal women with hypertension,and early identification of cognitive impairment in this population is essential for timely intervention.
Humans ; Female ; Cognitive Dysfunction ; Hypertension/complications* ; Aged ; Middle Aged ; Menopause ; Proportional Hazards Models ; Risk Factors ; Cardiovascular Diseases/mortality* ; Cause of Death ; Kaplan-Meier Estimate

Objective:To investigate the factors influencing the efficacy of etanercept in the treatment of toxic epidermal necrolysis (TEN) across different countries and regions.Methods:A total of 17 articles (case analyses or case reports) were selected through a comprehensive search in 4 Chinese databases (CNKI, Wanfang, VIP, and SinoMed) and 4 English databases (PubMed, Cochrane Library, Embase, and Elsevier SD). Clinical data from 52 patients originating from 7 countries were collected. Independent variables included age, sex, race, culprit drugs, disease severity, presence or absence of complications, initial dose, timing of administration, number of administrations of etanercept, and combination therapy; and the duration of hospitalization served as the dependent variable. Univariate and multiple linear regression analyses were conducted sequentially.Results:Among the 52 patients, 26 were male and 26 were female, with a median age M ( Q1, Q3) of 57.0 (36.0, 71.5) years. The median hospitalization duration was 12.0 (8.0, 17.5) d, and the median severity-of-illness score for TEN (SCORTEN) was 2 (2, 4). A total of 33 patients (63.5%) had at least one comorbidity. The initial etanercept dose was 50 mg in 37 patients (71.2%). The median timing of etanercept administration was 3 (3, 6) days after disease onset. Etanercept was used as monotherapy in 26 patients (50.0%) and as combination therapy in 26 patients (50.0%). Multiple linear regression analysis showed that age (partial regression coefficient β [95% CI]: -0.106 [-0.194, -0.018]), disease severity (2.216 [0.452, 3.980]), timing of administration (1.343 [0.827, 1.858]), and combination therapy (11.993 [4.149, 19.838]) significantly influenced the hospitalization duration of TEN patients (all P < 0.05). However, sex, race, presence of comorbidities, initial dose, and number of administrations did not affect hospitalization duration (all P > 0.05). Based on the standardized regression coefficients, the factors influencing hospitalization duration in TEN patients were ranked from strongest to weakest as follows: timing of administration (0.632), combination therapy (0.595), disease severity (0.337), and age (-0.233) . Conclusions:Early administration of etanercept is the key to achieving clinical benefit in the treatment of TEN. In cases where the response is inadequate or the condition is severe, combination therapy may be considered.

Objective:To evaluate the efficacy and safety of spesolimab in the treatment of generalized pustular psoriasis (GPP) .Methods:Six patients with GPP were retrospectively collected from Nanjing Drum Tower Hospital from February 2024 to April 2024, including 2 males and 4 females, aged 16 - 50 years. Four patients had a history of plaque psoriasis. Before treatment, the GPP Area and Severity Index (GPPASI) scores of the patients ranged from 24.6 to 60.8 points, and their GPP Physician Global Assessment (GPPGA) scores ranged from 2 to 4 points. All the 6 patients were intravenously injected with a single dose of 900 mg of spesolimab. Their GPPASI and GPPGA scores were recorded at weeks 1, 4, and 12, and adverse reactions were monitored during the treatment and follow-up.Results:Twenty-four hours after treatment, pustules were markedly reduced in the 6 patients with GPP; at week 1, pustules completely subsided, but erythema persisted; at week 4, both GPPASI and GPPGA scores decreased to 0 points; at week 12, no recurrence was observed. The patients with comorbid hypertension (4 cases), diabetes (1 case), or kidney disease (2 cases) maintained stable pressure or blood glucose levels, or showed improved renal function during the treatment and follow-up. Two patients experienced a transient fever after the treatment with spesolimab, resolving spontaneously after 2 days; two other patients exhibited exacerbation of plaque psoriasis. During the 12-week follow-up, none of the 6 patients experienced serious adverse reactions such as infections.Conclusion:In this study, spesolimab demonstrated rapid-onset efficacy and favorable safety in the treatment of GPP; conventional-dose spesolimab seemed safe for GPP patients with kidney disease.