Objective:The Social Isolation Scale for people with type 2 diabetes mellitus (T2DM) was developed and tested for reliability and validity, which provided an effective tool for measuring the social isolation level of patients with T2DM.Methods:The initial scale was developed through literature review, qualitative interviews, and expert consultation. Convenience sampling method was used to select T2DM patients who met the inclusion and exclusion criteria for questionnaire survey. The item analysis method was used to select the items of the scale. Exploratory and confirmatory factor analyses were used to evaluate construct validity. The content validity of the scale was evaluated by the scale-level content validity index and the item-level content validity index. The criterion validity was verified by using the Lubben Social Network Scale-6 and the De Jong Gierveld Loneliness Scale. Reliability was tested through internal consistency and test-retest reliability.Results:Through literature review and qualitative interviews, 30 items of the scale were selected to form the first version scale. After two rounds of inquiries from 16 experts (expert authority coefficient = 0.897), the second version of the scale was formed. A total of 407 questionnaires were distributed in two stages using the second version scale. Among the 407 patients, there were 214 males and 193 females. Exploratory factor analysis extracted 4 common factors, with a cumulative variance contribution rate of 61.338%. The final scale was determined to include 4 dimensions and 16 items, with the dimensions being "social support network", "frequency of social participation", "satisfaction with interpersonal relationships", and "diabetes-related sense of isolation".The average content validity index at the scale level was 0.929, the content validity index at the item level was 0.830 - 1.000, and the criterion validity was - 0.647 and 0.681. The Cronbach′s α coefficient of the total scale was 0.822, and the test-retest reliability was 0.858.Conclusions:The Social Isolation Scale for people with T2DM has good reliability and validity. It is a reliable and valid tool for assessing social isolation in T2DM patients.

Objective Based on the theory of"stomach disharmony leads to restlessness",the causal relationship between gastroesophageal reflux disease and insomnia was discussed by Mendel randomization method with two samples.Methods The data were collected from genome-wide association studies,the exposure factor was gastroesophageal reflux disease,and the outcome variable was insomnia.Mendel randomization analysis is realized by inverse variance weighted method,MR-Egger method,simple model method,weighted model method and weighted median method.Sensitivity analysis includes pleiotropic test,heterogeneity test and one-by-one elimination test,and is calculated by MR-Egger method,Cochran Q test and one-out-of-one method in turn.Results A total of 75 single nucleotide polymorphisms(SNPs)were screened.The inverse variance weighted method showed that gastroesophageal reflux disease increased the risk of insomnia(OR=1.255,95%CI:1.071-1.470,P<0.05).The weighted median method also confirmed that there was a positive causal relationship between gastroesophageal reflux disease and insomnia(OR=1.403,95%CI:1.117-1.762,P<0.05).Multiple sensitivity analysis indicated that there was no pleiotropy and heterogeneity in the results of Mendelian randomized analysis,which verified the stability of the research results.Conclusion There is a positive causal relationship between gastroesophageal reflux disease and insomnia,which enriches the theoretical connotation of"stomach disharmony leads to restlessness"from the genetic point of view and lays a foundation for further study.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

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

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.

This report presents a rare case of viral encephalitis resulting from co-infection with human herpesvirus 7(HHV-7)and Epstein-Barr virus(EBV)in a 16-year-old patient with Crohn's disease following adalimumab therapy.The patient was treated with adalimumab,with an initial subcutaneous dose of 160 mg,followed by 80 mg at week 2,and maintenance doses of 40 mg every two weeks,three months after initiating treatment,the patient developed symptoms including headache,diplopia,and signs of intracranial hypertension.Metagenomic sequencing of the cerebrospinal fluid identified HHV-7 and EBV as the causative pathogens,with cranial magnetic resonance imaging supporting the diagnosis of viral encephalitis.Targeted antiviral therapy and supportive care led to significant resolution of neurological symptoms.Using the Naranjo's Assessment Scale,the association between adalimumab and viral encephalitis was evaluated,yielding a score of 5,indicating a"probable"causal link.This case underscores the importance of vigilant monitoring for rare central nervous system viral infections in patients with Crohn's disease receiving tumor necrosis factor inhibitors.

Purpose To analyze and compare the impact of incorporating molecular classification into the new FI-GO(2023)staging system for endometrial cancer(EC).Methods A retrospective analysis was conducted on 332 ca-ses of EC diagnosed and molecular subtyped by Department of Pathology Tianjin Central Hospital of Gynecology Obstet-rics in 2023.All cases were staged according to the FIGO(2023)staging criteria for EC.Results The median age of the 332 EC patients was 56 years(range:27-76 years).Molecular subtypes included 30 POLE mutation(POLE-mut),80 mismatch repair deficiency(MMRd),194 no specific molecular profile(NSMP),and 28 p53 abnormal(p53abn).Significant differences were observed among the four molecular subtypes regarding age,FIGO stage,patho-logical type,and lymph node metastasis rate(P＜0.05).However,no significant differences were found in the depth of myometrial invasion or lymphovascular space invasion.In the POLEmut group,19 cases(63.33％)were of non-ag-gressive histological types and 11(36.67％)were aggressive.After incorporating molecular subtyping,all 11 stage Ⅱ patients were downgraded to stage Ⅰ AmPOLEmut,increasing the proportion of stage Ⅰ patients from 62.07％to 100％.In the p53abn group,9 cases(32.14％)were non-aggressive and 19(67.86％)were aggressive.Molecular integra-tion led to the upstaging of 4 stage Ⅰ patients with myometrial invasion to stage Ⅱ Cmp53abn,increasing the proportion of stage Ⅱ patients from 34.61％to 50％.Conclusion Molecular subtypes p53abn and POLEmut are associated with distinct alterations in EC staging,specifically leading to tumor upstaging or downstaging.Our findings underscore the critical importance of comprehensive molecular subtyping in EC staging,as it refines prognostic risk stratification and provides valuable guidance for adjuvant treatment decisions.

OBJECTIVE To investigate the pharmacological efficacy and mechanism of action of Atractylenolide Ⅰ(Atr-Ⅰ)in inhibiting colorectal cancer.METHODS Among three active compounds of Atractylodes macrocephala,Atr-Ⅰ exhibited the highest anti-tumor potency by MTT assay.The optimal concentration of Atr-Ⅰ was determined.The effect of Atr-Ⅰ on LoVo cell prolifera-tion was assessed via a clonogenic assay,while its impact on apoptosis and cell cycle progression was evaluated using flow cytometry.The influence of Atr-Ⅰ on the migration and invasion of LoVo cell line was examined through wound healing and Transwell migration assays.Western blot analysis was performed to explore the effects and mechanisms of Atr-Ⅰ on proteins associated with mi-gration,proliferation,and epithelial-mesenchymal transition(EMT)in LoVo cells.The CT26 mouse subcutaneous tumor model was established,and histopathological analysis was conducted using hematoxylin-eosin(HE)staining.Western blot was also used to assess the effects of Atr-Ⅰ on EMT-related proteins in mouse tissues to elucidate underlying mechanisms.RESULTS Atr-Ⅰ significantly reduced colorectal cancer cell viability,with statistically significant differences between treatment and control groups(P<0.05,P<0.01).Atr-Ⅰ induced apoptosis in LoVo cells,with the treatment group showing significant differences compared to the control(P<0.05,P<0.01).Cell cycle analysis revealed that Atr-Ⅰ exerted anti-tumor effects by inducing G2/M phase arrest,with increased G2 phase cell numbers in the LoVo treatment group compared to the control(P<0.05).Wound healing and Transwell migration assays confirmed that Atr-Ⅰ significantly inhibited tumor cell migration and invasion(P<0.05,P<0.01).Western blot analysis demonstra-ted that Atr-Ⅰ specifically suppressed the expression of c-Myc and Bcl-2(P<0.05),as well as cell cycle-related proteins CDK1,Cyclin B1,and Cyclin D1(P<0.05),and angiogenesis-related proteins VEGF and MMP9(P<0.05).Additionally,Atr-Ⅰ down-regulated EMT-related protein N-cadherin and upregulated E-cadherin expression(P<0.05).It also reduced the expression of p-AKT and p-S6K1(P<0.05).CONCLUSION Atr-Ⅰ exhibits potent anti-tumor effects against colorectal cancer,potentially through modulation of the AKT/S6K1 signaling pathway.