Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Two pediatric heart failure patients were treated with pulmonary artery banding(PAB)at Fuwai Hospital,from December 2021 to January 2022.In the first case,an 8-month-old patient presented with left ventricular non-compaction cardiomyopathy(LVNC),left ventricular systolic dysfunction,ventricular septal defect,and atrial septal defect.The second case was a 4-month-old patient with LVNC,left ventricular systolic dysfunction,and coarctation of the aorta.After PAB,the left ventricular function and shape of both patients were significantly improved,without serious surgery-related complications.In these individual cases of pediatric heart failure,pulmonary artery banding exhibited a more satisfactory efficacy and safety compared to pharmacological treatment,especially for those with unsatisfactory medication results.Future clinical data are needed to promote the rational and broader application of this therapeutic option for indicated patients.

Objective To analyze the risk factors of intraoperative hypothermia in patients undergoing radical thyroidectomy under laparoscopy and to construct a nomogram prediction model. Methods A total of 336 patients who underwent laparoscopic radical thyroidectomy were selected as study subjects. According to intraoperative body temperature, they were divided into hypothermia group (195 cases) and normal temperature group (141 cases). The risk factors of intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy were analyzed using the Logistic regression model. The nomogram prediction model was constructed using R software. The prediction performance of the nomogram prediction model was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and Hosmer-Lemeshow goodness-of-fit test. Results There were significant differences in age, intraoperative blood loss, amount of fluid infusion, and operation time between the two groups (P < 0.05). Multivariate Logistic regression analysis showed that age>60 years, intraoperative blood loss >60 mL, amount of fluid infusion>1 000 mL, and operation time>2.5 h were risk factors for intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy (P < 0.05). A nomogram prediction model was constructed based on the four risk factors. The ROC curve showed that the area under the curve was 0.912 (95%CI, 0.884 to 0.941). The calibration curve and Hosmer-Lemeshow goodness-of-fit test showed that the slope of the calibration curve was close to 1 (χ²=9.140, P=0.243). Conclusion The nomogram prediction model based on age, intraoperative blood loss, amount of fluid infusion, and operation time has good predictive value for intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy.

Objective To investigate the effect of N6-methyladenosine (m⁶A) reading protein human antigen R (HuR) on the migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1 (PFK1). Methods The tissue samples of 33 patients who were first diagnosed as colorectal cancer in Zhengzhou Central Hospital Affiliated to Zhengzhou University from April to December 2022 were collected. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of HuR and PFK1 mRNA in colorectal cancer tissues and adjacent tissues. The expression of HuR mRNA in normal intestinal epithelial cells NCM460 and colorectal cancer cells HCT8, SW480, SW620, HCT116, LoVo, RKO and COLO205 was detected. Small interfering RNA (siRNA) was used to construct a HuR knockdown colorectal cancer cell model. The effects of HuR on the migration and invasion of colorectal cancer cells were detected by cell scratch assay and Transwell assay. The expression of PFK1 mRNA and protein was detected by qRT-PCR and Western blot. Glucose intake and pyruvate production were detected by glucose content kit and pyruvate content kit, respectively. The relationship between HuR and PFK1 was analyzed by bioinformatics analysis, and the effect of HuR on the stability of PFK1 mRNA was evaluated by actinomycin D assay. Results In colorectal cancer tissues, HuR and PFK1 were highly expressed at mRNA level; HuR was highly expressed at mRNA level in colorectal cancer cell lines. Down-regulation of HuR significantly inhibited the migration and invasion of colorectal cancer cells, as well as glucose consumption and pyruvate production. Knockdown of HuR could reduce the stability of PFK1 mRNA and its expression at mRNA and protein levels. There were m⁶A modification sites on PFK1. Conclusion The m⁶A reading protein HuR may regulate the migration, invasion and glycolysis of colorectal cancer cells by recognizing the m⁶A site on PFK1 and reducing the stability of PFK1 mRNA.

Objective To investigate the expression and mechanism of long non-coding RNA (lncRNA) GHRLOS2 in colorectal cancer tissues and cells. Methods Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of GHRLOS2 and microRNA-33b-5p (miR-33b-5p) in colorectal cancer tissues or cells. Overexpressing of GHRLOS2 in HCT116 and SW480 colorectal cancer cell lines were constructed, and the effects of overexpression of GHRLOS2 on the migration and invasion abilities in HCT116 and SW480 cell lines were detected by wound healing assay and Transwell assay. Glucose content in cells of overexpressing GHRLOS2 and control cells was detected using a glucose detection kit. Western blot was used to detect the expression level of PCK1 protein in cells. The targeted binding relationship between miR-33b-5p and PCK1 was predicted based on bioinformatics methods. Results The qRT-PCR results showed that the expression level of GHRLOS2 in colorectal cancer tissue samples was lower than that in adjacent non-cancerous tissues, and was lower in colorectal cancer cells than that in normal colon epithelial cells (P < 0.05). The expression of GHRLOS2 was correlated with grade classification, staging, and lymph node metastasis (P < 0.05). The expression level of miR-33b-5p in colorectal cancer tissues was higher than that in corresponding adjacent non-cancerous tissues (P < 0.001). The results of wound healing assay, Transwell assay, and glucose content detection showed that overexpression of GHRLOS2 significantly inhibited the invasion, migration, and glucose metabolism of colorectal cancer cells. Overexpression of GHRLOS2 inhibited the expression level of miR-33b-5p; GHRLOS2 functioned as a molecular sponge for miR-33b-5p, and PCK1 was a target of miR-33b-5p; overexpression of GHRLOS2 competitively bound to miR-33b-5p, thereby promoting increased expression of PCK1. Conclusion The expression of GHRLOS2 is downregulated in colorectal cancer tissues and cells, and it may regulate the invasion, migration, and glucose metabolism of colorectal cancer cells through the miR-33b-5p/PCK1 pathway, making it a potential biological target for targeted therapy of colorectal cancer.

Immunocytokines, employing targeted antibodies to concentrate cytokines at tumor sites, have shown potential advantages such as prolonged cytokine half-lives, mitigated adverse effects, and synergistic antitumor efficacy from both antibody and cytokine components. First, we present an in-depth analysis of the advancements of immunocytokines evaluated in preclinical and clinical applications. Notably, anti-PD-1-based immunocytokines can redirect cytokines to intratumoral CD8⁺ T cells and reinvigorate them to elicit robust antitumor immune responses. Then, we focus on their molecular structures and action mechanisms, striving to elucidate the correlations between diverse molecular structures and their antitumor efficacy. Moreover, our exploration extends to the realm of novel cytokines, including IL-10, IL-18, and IL-24, unraveling their potential in the construction of immunocytokines. However, safety concerns remain substantial barriers to immunocytokines' development. To address this challenge, we explore potential strategies, such as cytokine engineering and prodrug design, which can foster next-generation immunocytokines development. Overall, this review concentrates on the design of molecular structures in immunocytokines, underscoring the direction and focus of ongoing efforts to improve safety profiles while maximizing therapeutic efficacy.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

ObjectiveTo obtain the status of latent tuberculosis infection （LTBI） among tuberculosis （TB）-related health-care workers （HCWs） in Shanghai， and to explore the risk factors related to TB infection. MethodsA multi-center cross-sectional study was conducted by recruiting medical workers from multiple designated TB hospitals， centers for disease control and prevention， and community health service centers in Shanghai. Each subject was required to complete a questionnaire and to provide a blood sample for TB infection test. Univariate and multivariate analysis ware made in order to find risk factors relating to TB infection. ResultsA total of 165 medical workers were recruited， and the proportion of TB infection was 16.36% （95%CI： 11.49%‒22.76%）. Multivariate logistic analysis showed that clinical doctors and nurses （adjusted OR=9.756， 95%CI： 1.790‒53.188）， laboratory staffs （adjusted OR=78.975， 95%CI： 8.749‒712.918）， and nursing and cleaning workers （adjusted OR=89.920， 95%CI： 3.111‒2 598.930） had higher risk of TB infection. ConclusionThe overall LTBI prevalence among TB-related HCWs is low. However， working as doctors， nurses， laboratory staffs， nursing workers and cleaning workers are risk factors of TB infection. TB-related HCWs who work at hospitals are at risk of TB infection comparing to medical staffs who work outside hospitals.

Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC 50 ) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDL-RAD3 knockdown decreased the IC 50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.