Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

OBJECTIVE: To explore the association between blood glucose trajectories within 7 days of intensive care unit (ICU) admission and mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: Based on the MIMIC-IV database, sepsis-associated ARDS patients with daily blood glucose monitoring data within 7 days of ICU admission were selected. Blood glucose trajectories were analyzed using group-based trajectory modeling (GBTM), and the optimal number of groups was determined based on the minimum Akaike information criterion (AIC), Bayesian information criterion (BIC), average posterior probability (AvePP), odds of correct classification (OCC), and proportion of group membership (Prop). Baseline characteristics including demographics, comorbidities, severity scores, vital signs, laboratory indicators within the first 24 hours of ICU admission, and treatments were collected. Kaplan-Meier survival curves were used to compare 28-day and 1-year survival across trajectory groups. Multivariate Logistic regression was performed to evaluate the associations between glucose trajectory groups and in-hospital mortality, ICU mortality. The incidence of hypoglycemia within 7 days in the ICU was analyzed among different groups. RESULTS: A total of 3 869 patients with sepsis-associated ARDS were included, with a median age of 63.52 (52.13, 73.54) years; 59.6% (2 304/3 869) were male. Based on glucose levels within 7 days, patients were categorized into three groups: persistent hyperglycemia group (glucose maintained at 10.6-13.1 mmol/L, n = 894), moderate glucose group (7.8-8.9 mmol/L, n = 1 452), and low-normal glucose group (6.1-7.0 mmol/L, n = 1 523). There were statistically significant differences in 28-day mortality and 1-year mortality among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [28-day mortality: 11.42% (174/1 523), 19.83% (288/1 452), 25.50% (228/894), χ ² = 82.545, P < 0.001; 1-year mortality: 23.31% (355/1 523), 33.75% (490/1 452), 39.49% (353/894), χ ² = 77.376, P < 0.001]. Kaplan-Meier analysis showed that higher glucose trajectories were associated with significantly lower 28-day and 1-year cumulative survival rates (Log-rank test: χ ² were 83.221 and 85.022, both P < 0.001). There were statistically significant differences in in-hospital mortality and ICU mortality among the low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [in-hospital mortality: 9.65% (147/1 523), 19.70% (286/1 452), 24.50% (219/894), χ ² = 102.020, P < 0.001; ICU mortality: 7.22% (110/1 523), 16.05% (233/1 452), 20.13% (180/894), χ ² = 93.050, P < 0.001]. Logistic regression confirmed that, using the persistent hyperglycemia group as the reference, the low-normal glucose group had significantly lower risks of in-hospital mortality and ICU mortality after multiple factor adjustment. Although the moderate glucose group showed a trend toward lower mortality, the differences were not statistically significant. Using the moderate glucose group as a reference, the low-normal glucose group had 43.1% lower in-hospital mortality [odds ratio (OR) = 0.569, 95% confidence interval (95%CI) was 0.445-0.726, P < 0.001] and 42.0% lower ICU mortality (OR = 0.580, 95%CI was 0.439-0.762, P < 0.001). There was no statistically significant difference in the incidence of hypoglycemia within 7 days of ICU admission among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [2.82% (43/1 523), 2.69% (39/1 452), 3.02% (27/894), χ ² = 0.226, P = 0.893]. CONCLUSIONS Blood glucose trajectories during ICU stay are closely associated with prognosis in patients with sepsis-associated ARDS. Persistent hyperglycemia (10.6-13.1 mmol/L) is linked to significantly higher short- and long-term mortality.
Humans ; Respiratory Distress Syndrome/etiology* ; Sepsis/blood* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Blood Glucose/metabolism* ; Hospital Mortality ; Aged

Retrieving keyframes most relevant to text from small intestine videos with given labels can efficiently and accurately locate pathological regions. However, training directly on raw video data is extremely slow, while learning visual representations from image-text datasets leads to computational inconsistency. To tackle this challenge, a small bowel video keyframe retrieval based on multi-modal contrastive learning (KRCL) is proposed. This framework fully utilizes textual information from video category labels to learn video features closely related to text, while modeling temporal information within a pretrained image-text model. It transfers knowledge learned from image-text multimodal models to the video domain, enabling interaction among medical videos, images, and text data. Experimental results on the hyper-spectral and Kvasir dataset for gastrointestinal disease detection (Hyper-Kvasir) and the Microsoft Research video-to-text (MSR-VTT) retrieval dataset demonstrate the effectiveness and robustness of KRCL, with the proposed method achieving state-of-the-art performance across nearly all evaluation metrics.
Humans ; Video Recording ; Intestine, Small/diagnostic imaging* ; Machine Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms

The orientation of the acetabular cup in hip joint anteroposterior radiograph is a key factor in evaluating the postoperative outcomes of total hip arthroplasty (THA). Currently, measurement of the acetabular cup anteversion angle primarily relies on manual drawing of auxiliary lines by orthopedic surgeons and calculations using scientific calculators. This study proposes an automated computer-aided measurement method for the acetabular cup anteversion angle based on hip joint anteroposterior radiograph. The proposed method segments hip prosthesis images using an improved Otsu algorithm, identifies feature points at the acetabular cup opening by combining circle-fitting theory and the cup's geometric characteristics, and fits an ellipse to the cup opening to calculate the anteversion angle. A total of 104 hip joint anteroposterior radiographs, including 71 right-sided and 81 left-sided prostheses, were analyzed. Two orthopedic surgeons independently measured the postoperative anteversion angles, and the results were compared with computer-generated measurements for correlation analysis. Spearman and Pearson correlation analyses demonstrated significant correlations between the proposed method and manual measurements for both the right group ( r = 0.795, P < 0.01) and the left group ( r = 0.859, P < 0.01). This method provides a reliable reference for orthopedic surgeons to assess postoperative prognosis.
Humans ; Acetabulum/anatomy & histology* ; Arthroplasty, Replacement, Hip/methods* ; Algorithms ; Hip Prosthesis ; Hip Joint/diagnostic imaging* ; Radiography ; Image Processing, Computer-Assisted/methods*

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

To analyze the transmission characteristics of newly reported HIV-infected students aged ≥18 years in Nanjing City from 2016 to 2022 and provide evidence for AIDS publicity and intervention among young students. The pol region sequences of newly reported HIV-infected students and non-student HIV-infected individuals in Nanjing City from 2016 to 2022 were collected, and the BLAST tool was used to search the published global non-Nanjing reported HIV infection sequences in the LANL HIV database. The basic molecular transmission network and regional molecular transmission network were constructed using the HIV-TRACE in a pairwise genetic distance threshold of 1.0%. 332 sequences of infected students aged≥18 years in Nanjing City, 1 904 sequences of non-student-infected individuals in Nanjing City and 1 698 non-Nanjing-infected individuals were obtained. Among the 332 infected students, the main route of infection was homosexual (96.39%), and the subtypes were CRF01_AE (37.95%), CRF07_BC (37.65%) and CRF105_0107 (10.24%). There were 890 sequences in the regional molecular transmission network, of which 21.80% were infected students in Nanjing City, 39.89% were non-student-infected individuals in Nanjing City, and 38.31% were non-Nanjing-infected individuals. In the CRF105_0107 transmission cluster, non-student-infected individuals from Nanjing accounted for 66.95% (81/121), while in the CRF07_BC transmission cluster, non-Nanjing-infected individuals accounted for 56.66% (200/353). There were 1 644 edges connected to infected students within the regional molecular transmission network, with local transmission accounting for 64.72% and regional transmission accounting for 35.28%. Regional transmission was mainly in Guangdong Province (19.83%) and other cities in Jiangsu Province (4.50%). The HIV-1 subtypes of newly reported HIV-infected students aged≥18 years in Nanjing City are mainly CRF01_AE, CRF07_BC and CRF105_0107, with local transmission as the main transmission characteristics. There is transmission between students and non-students.

Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.

Objective:To investigate the correlation between long-term statin use and Helicobacter pylori( Hp)infection in the elderly, and to compare the effects of rosuvastatin combined with bismuth-containing quadruple therapy for Hp eradication on lipid levels in elderly patients with mixed hyperlipidemia. Methods:A retrospective analysis was conducted on 1 181 elderly patients with hyperlipidemia, cardiovascular and cerebrovascular diseases, and peripheral arterial disease who were treated at the First Hospital of Lanzhou University between March 2019 and December 2023.According to the results of carbon 14 urea breath test(C 14-UBT), the subjects were divided into the Hp infection group and the non- Hp infection group.Multivariate logistic regression methods were used to analyze the correlation between Hp infection and statin use.A prospective case-control analysis was conducted on 109 patients with mixed hyperlipidemia and Hp infection treated during the same period, they were treated with rosuvastatin combined with bismuth-containing quadruple therapy for Hp eradication.The successful eradication people were selected as the eradication group (n=95). Patients with hyperlipidemia and Hp infection unwilling eradication was selected as the control group (n=109), and treated with rosuvastatin.Changes in lipid levels were compared over a consecutive 6-month period. Results:The overall Hp infection rate was 53.94%(637/1 181). Univariate analysis showed that the infection rate in women was higher than in men.Body mass index(BMI), low-density lipoprotein cholesterol(LDL-C), fasting blood glucose(FBG)levels in the Hp(+ )group were higher than in the Hp(-)group.Long-term low-dose aspirin users had a higher infection rate than non-users.The infection rate was lower in statin users than in non-users[42.65%(374/877) vs.55.59%(169/304), χ2=15.234, P<0.001]. Multivariate analysis showed that women had a higher infection risk than men ( OR=1.441, 95% CI: 1.102-1.729, P=0.011). Higher FBG and LDL-C levels increased the risk of Hp infection ( OR=1.406, 95% CI: 1.271-2.286, P<0.001, OR=1.118, 95% CI: 1.017-1.387, P=0.010). Aspirin use increased the risk of Hp infection( OR=1.162, 95% CI: 1.034-1.294, P=0.021), while statin use reduced the risk of Hp infection ( OR=0.177, 95% CI: 0.018-0.311, P<0.001). The Hp eradication rate was 87.16%(95/109). At 1-and 2-months post-eradication, statistically significant differences were observed between the eradication and control groups in LDL-C, total cholesterol(TC), changes from baseline, and target achievement rates(all P<0.05). At 1-month post-eradication, a statistically significant difference was observed in high-density lipoprotein cholesterol(HDL-C) levels between the two groups.Additionally, at both 1-and 2-months post-eradication, significant differences were found in the changes in HDL-C levels from baseline between the eradication group and the control group(all P<0.05). Conclusions:Long-term statin use in the elderly may reduce the risk of Hp infection.Rosuvastatin combined with a standard quadruple therapy does not improve the Hp eradication rates in elderly patients with mixed hyperlipidemia, but it facilitates short-term achievement of cholesterol targets.

Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.