Objective To investigate the correlation between the expression level of absent in melanoma 2(AIM2)in serum and the severity of acute cerebral infarction(ACI),and to evaluate the value of AIM2 in predicting early neurological deterioration(END)after intravenous thrombolysis with alteplase in ACI patients.Methods A total of 150 ACI patients were enrolled in ACI group,and an-other 30 healthy individuals physical examination were selected as control group.ACI patients were further divided into mild,moderate and severe groups according to the National Institutes of Health Stroke Scale(NIHSS)score at admission,and they were also divided into END and non-END groups based on the occurrence of END after intravenous thrombolysis.Clinical materials of ACI patients were collected;the expression level of serum AIM2 was measured by enzyme-linked immunosorbent assay(ELISA);the Logistic regression analysis was performed to identify the factors influencing END after intravenous thrombolysis in ACI patients;the receiver operating characteristic(ROC)curve was plot-ted to analyze the clinical performance of serum AIM2 expression level in predicting END after intravenous thrombolysis in ACI patients.Results The serum AIM2 expression level in the ACI group and the control group was(58.29±5.97)and(36.81±3.03)ng/mL respectively,with a significant be-tween-group difference(t=43.23,P＜0.05).The serum AIM2 expression level gradually in-creased in the mild,moderate and severe groups,with significant differences between each pair of groups(P＜0.01).The serum AIM2 expression level in ACI patients was positively correlated with the NIHSS score(r=0.941,P＜0.01).The NIHSS score,time from admission to thrombolysis,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,and AIM2 level in the END group were significantly higher or longer than those in the non-END group(P＜0.05).The results of mul-tivariate Logistic regression analysis showed that NIHSS score(OR=3.871,P＜0.001),time from admission to thrombolysis(OR=2.885,P=0.002),LDL-C(OR=3.118,P＜0.001)and AIM2(OR=3.761,P＜0.001)were influencing factors for END after intravenous thrombolysis in ACI patients.ROC curve showed that the area under the curve(AUC)for predicting END after in-travenous thrombolysis based on the serum AIM2 expression level at admission in ACI patients was 0.911;when the cut-off value of AIM2 was 66.56 ng/mL,the diagnostic sensitivity and specificity were 91.23％and 90.15％,respectively.Conclusion The expression level of serum AIM2 is sig-nificantly increased in ACI patients,and AIM2 expression level has certain advantages in predicting END after intravenous thrombolysis in ACI patients.

Objective:To explore the protective effect of small ubiquitin-related moditier protein specific peptidase 2 (SENP2) on acute kidney injury in septic mice by regulating NLRP3 inflammasome activation.Methods:Forty C57BL/6 mice were divided into 4 groups: namely the wild-type sham group (WT-Sham), wild-type cecal ligation and perforation group (WT-CLP), SENP2 gene knockout sham group (KO-Sham), and SENP2 gene knockout cecal ligation and perforation group (KO-CLP), with 10 mice in each group. It was observed the pathological damage of kidney tissue in each group of mice, used ELISA method to detect blood creatinine (SCr), blood urea nitrogen (BUN), plasma neutrophil gelatinase related lipoprotein (pNGAL), and plasma kidney injury molecule 1 (pKIM-1) levels, and determined plasma TNF-α, IL-1β, IL-4 and IL-10 levels. It was used immunohistochemical method to detect the expression of SENP2 protein in renal tissue, while used western-blotting to detect NLRP3, IL-1β, Caspase-1 and ASC protein expression in renal tissue.Results:Compared with the WT-Sham and KO-Sham groups, in the WT-CLP and KO-CLP groups, the pathological damage scores of the kidney tissue and the levels of SCr, BUN, pNGAL, pKIM-1, TNF-α and IL-1β in plasma were all significantly increased (all P<0.001), while the levels of IL-4 and IL-10 were all significantly reduced (all P<0.001), and the levels of NLRP3, IL-1β, Caspase-1 and ASC proteins were all significantly increased (all P<0.001). Moreover, compared with the WT-CLP group, the KO-CLP group showed a significant decrease in renal tissue injury scores in mice ( P?0.01), the levels of SCr, BUN, pNGAL, pKIM-1, TNF-α and IL-1β were all significantly reduced (all P<0.05), and the levels of NLRP3 [(0.71 ± 0.04) vs. (0.89 ± 0.01), P=0.011], IL-1β [(0.41 ± 0.02) vs. (0.57 ± 0.01), P=0.004], Caspase-1 [(0.41 ± 0.02) vs. (0.56 ± 0.02), P=0.009], and ASC [(0.27 ± 0.01) vs. (0.41 ± 0.02), P=0.009] were all significantly reduced. Conclusion:SENP2 participates in the occurrence and development of septic AKI by regulating the activation of NLRP3 inflammasomes.

Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

Objective:To investigate the incidence of mild cognitive impairment(MCI)and malnutrition among centenarians, as well as to explore the relationship between cognitive impairment and nutritional status.Methods:A cross-sectional study was conducted between November and December 2023, involving 121 elderly individuals aged ≥ 100 years in the Baoshan District of Shanghai.The survey collected general information and included the Ascertain Dementia 8-item Questionnaire(AD8), the Mini Nutritional Assessment Short-Form(MNA-SF), and anthropometric nutritional measurements such as waist circumference(WC), hip circumference(HC), arm circumference(AC), calf circumference(CC), and grip strength.The prevalence of MCI and malnutrition among centenarians was calculated, and the correlation between MCI and MNA-SF scores, along with anthropometric nutritional measurement indicators, was analyzed.Results:The age range of centenarians was between 100 and 105 years, with an average age of 101.0±3.5 years.The majority of centenarians were female(76.9%), illiterate(58.7%), and lived with family members(73.6%).All participants had medical insurance(100%).Most had no history of long-term smoking 118(97.5%), long-term alcohol consumption 108(89.3%), long-term use of health supplements 109(90.1%), long-term tea or coffee habits 114(94.2%), chronic medical conditions 84(69.4%), or family history of dementia 102(84.3%).Additionally, 62(51.2%)reported their health status over the past year as general.According to the AD8 screening results, the negative and positive detection rates of MCI in centenarians were 79(65.3%)and 47(34.7%), respectively.Based on the MNA-SF scoring results, the detection rates of normal nutrition, malnutrition risk, and malnutrition among centenarians were 36(29.8%), 61(50.4%), and 24(19.8%), respectively.There was a statistically significant difference in AC between the non-MCI group and the MCI group among centenarians( t=0.01, P=0.03).The AD8 scores of centenarians were significantly negatively correlated with AC, CC, and MNA-SF scores( r=-0.20, r=-0.26, r=-0.29; all P<0.05). Conclusions:The cognitive function of centenarians is associated with their nutritional status, indicating that higher cognitive abilities correlate with better nutritional status.

Objective:To investigate effects of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSCs-Exo)on bisphenol AF(BPAF)-induced oxidative damage and inflammatory factor release from endometrial stromal cells(hESCs).Methods:hESCs were divided into Control group,BPAF group(25 μmol/L BPAF treatment),BPAF+Exo group(25 μmol/L BPAF+hUCMSCs-Exo treatment),BPAF+Exo+LY group(25 μmol/L BPAF+hUCMSCs-Exo+10 μmol/L LY294002 treatment).Cell prolifera-tion was detected by MTT assay;apoptosis,intracellular ROS level,and mitochondrial membrane potential level were detected by flow cytometry;protein expressions of Bcl-2,Bax,Cleaved-caspase-3 and PI3K/AKT signaling pathway were detected by Western blot;mRNA expressions of inflammatory factors TNF-α,IL-6 and IL-1β were detected by RT-qPCR.Results:Compared with Control group,hESCs survival rate was gradually decreased(P<0.01),apoptosis rate was gradually increased with the increased concentration of BPAF(≥25 μmol/L).Compared with Control group,BPAF group showed increased ROS level,decreased mitochondrial membrane potential level,increased Bax and Cleaved-caspase-3 protein expressions,and decreased Bcl-2,p-PI3K and p-AKT protein expressions.Compared with BPAF group,cell survival rate of BPAF+Exo group was increased(P<0.01),ROS level decreased,mitochondrial membrane potential level increased,expressions of Bax and Cleaved-caspase-3 proteins decreased,and expressions of Bcl-2,p-PI3K and p-AKT increased.Compared with BPAF+Exo group,expressions of Bax and Cleaved-caspase-3 protein in cells of BPAF+Exo+LY group were increased,while expressions of Bcl-2,p-PI3K and p-AKT protein were decreased.Expressions of inflammatory factors TNF-α,IL-6 and IL-1β mRNA were significantly up-regulated in BPAF group compared with Control group(P<0.01),and expressions of inflammatory factors mRNA were significantly down-regulated in BPAF+Exo group compared with BPAF group(P<0.05).Conclu-sion:BPAF(≥25 μmol/L)inhibits proliferation of hESCs and promoted apoptosis.hUCMSCs-Exo inhibits BPAF-induced oxidative dam-age and inflammatory factors expressions in hESCs through PI3K/AKT signaling pathway.

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.

Objective:To evaluate the efficacy of rhomboid inter-costal and sub-serratus (RISS) block with ropivacaine-dexmedetomidine-dexamethasone for analgesia after thoracoscopic lobectomy.Methods:This study was a prospective, randomized, double-blind, controlled trial. From January 2021 to November 2023, 46 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, undergoing elective video-assisted thoracoscopic lobectomy at the Second Affiliated Hospital of Nanjing Medical University, were selected and assigned into 2 groups ( n=23 each) using simple randomization: ropivacaine group (R group) and ropivacaine-dexmedetomidine-dexamethasone group (RDA group). RISS block was performed preoperatively, with 20 ml of the drug solution injected at the target points of the rhomboid-intercostal muscle and the serratus anterior-intercostal muscle. R group received 0.375% ropivacaine 40 ml, while RDA group received 40 ml of the mixture containing 0.375% ropivacaine, dexmedetomidine 1 μg/kg, and dexamethasone 8 mg. Postoperative analgesia was performed with oxycodone (When the patient′s numerical rating scale [NRS] score >4 in post-anesthesion care unit, oxycodone 2 mg was intravenously administered as needed until the NRS score <4, and then a patient-controlled analgesia pump was initiated). The time of the first postoperative analgesic requirement, NRS scores at rest and during coughing at 1, 3, 6, 12, 24 and 48 h postoperatively, cumulative consumption of oxycodone in the periods of 0-12 h, >12-24 h, and >24-48 h, time to first ambulation, and incidence of related adverse reactions within 48 h postoperatively were recorded. Results:Compared with R group, the time to the first analgesic requirement was significantly prolonged, the cumulative consumption of oxycodone in the first 0-12 h postoperatively was reduced ( P<0.001), and no statistically significant changes were found in the time to first ambulation, NRS scores at rest and during coughing, or the incidence of postoperative adverse reactions in RDA group ( P>0.05). Conclusions:RISS block using a combination of ropivacaine, dexmedetomidine and dexamethasone can significantly prolong block duration, reduce postoperative opioid analgesic consumption, and provide good safety for the patients undergoing thoracoscopic lobectomy.