Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Objective: To explore the association between processed food consumption and anxiety symptoms among college students in Yunnan Province, so as to provide a reference for the prevention and treatment of anxiety symptoms in this population. Methods: A cluster random sample of 2 515 first year students from two universities in Yunnan Province was selected to carry out a longitudinal investigation which included a baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The food frequency questionnaire was administered to assess processed food consumption, and the Depression Anxiety Stress Scale-21 (DASS-21, Chinese version) was used to evaluate anxiety symptoms. A generalized estimation equation model was used to analyze the relationship between processed food consumption and anxiety symptoms. Results: The detection rates of T1-T4 anxiety symptoms among college students in Yunnan Province were 29.70%, 36.70%, 37.69% and 38.73 %, respectively, and the corresponding anxiety symptom scores were 4(0,8), 4(0,10), 4(0,12), 2(0,14). After controlling for demographic variables and confounding factors in the generalized estimation equation model, a statistically significant association was found between consumption of carbonated beverages ( β=0.06, 95%CI =0.03-0.08), and other processed snacks ( β= 0.04 , 95%CI =0.01-0.07) ( P <0.05). The stratified analysis by gender showed that the consumption of carbonated beverages ( β=0.08, 95%CI =0.05-0.12) and fast food ( β=0.03, 95%CI =0.00-0.06) was significantly associated with anxiety symptoms in female college students ( P <0.05). There was no significant association between processed food consumption and anxiety symptoms in male college students ( P >0.05). Conclusions Processed food consumption by college students in Yunnan Province may increase the risk of anxiety symptoms, particularly among female students. There is a need to strengthen guidance in respect to processed food consumption, so as to prevent and treat anxiety symptoms.

Brain organoids are self-organized 3D aggregates generated by human embryonic stem cells or human induced pluripotent stem cells. Their cell type and structure are similar to embryonic human brain, which are good in vitro models for the study of neurogenetic diseases and have been widely used in the study of neurogenetic diseases. This paper will discuss the advantages and challenges of brain organoids in the modeling of genetic diseases of the nervous system.

Objective To explore the effect and mechanism of sodium hydrosulfide(NaHS)on cerebral cortical injury in rats with cerebral ischemia-reperfusion.Methods A total of 80 male SD rats were divided into a sham operation group,an NaHS group,an ischemia-reperfusion group,and an ischemia-reperfusion+NaHS group using a random number table method,with 20 rats in each group.The rats in the ischemia-reperfusion group and ischemia-reperfusion+NaHS group were used to prepare ischemia-reperfusion models.The rats in the ischemia-reperfusion+NaHS group were given 50 μmol·kg-1 NaHS intraperitoneally after cerebral ischemia,while the rats in the ischemia-reperfusion group were given an equal volume of physiological saline intraperitoneally after cerebral ischemia.The rats in the sham operation group and NaHS group only had vessels isolated but not occluded with threads.The rats in the NaHS group were given 50 μmol·kg-1 NaHS intraperitoneally after vascular detachment,while the rats in the sham operation group were given an equal volume of physiological saline intraperitoneally after vascular detachment.Twenty-four hours after modeling,the neurological deficits of rats in the four groups were evaluated by using the modified neurological severity score(mNSS),the cerebral infarction of rats in the four groups was observed aftertriphenyltetrazolium chloride staining,the levels of pro-inflammatory cytokines interleukin-1β(IL-1β)and interleukin-18(IL-18)in theischemiccerebralcortical tissues of rats in the four groups were detected by using enzyme-linked immunosorbent assay,the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in the ischemic cerebral cortical tissues of rats in the four groups was detected by using Western blot,and the activity of microglia in the ischemic cerebral cortical tissues of rats in the four groups was detected by using immunofluorescence.Results The brain tissues of rats in the sham operation group and the NaHS group showed uniform orange red color,while the rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group had pale infarcted areas in the ischemic cerebral cortex and striatum.The cerebral infarction area of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly larger than that in the sham operation group and the NaHS group,while the cerebral infarction area of rats in the ischemia-reperfusion+NaHS group was significantly smaller than that in the ischemia-reperfusion group(P＜0.05).The mNSS scores of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly higher than those in the sham operation group and the NaHS group,while the mNSS score of rats in the ischemia-reperfusion+NaHS group was significantly lower than that in the ischemia-reperfusion group(P＜0.05).The relative expression levels of NLRP3 protein in the ischemic cerebral cortex of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly higher than those in the sham operation group and the NaHS group,while the relative expression level of NLRP3 protein in the ischemic cerebral cortex of rats in the ischemia-reperfusion+NaHS group was significantly lower than that in the ischemia-reperfusion group(P＜0.05).The levels of IL-1β and IL-18 in the ischemic cerebral cortex of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly higher than those in the sham operation group and the NaHS group,while the levels of IL-1β and IL-18 in the ischemic cerebral cortex of rats in the ischemia-reperfusion+NaHS group were significantly lower than those in the ischemia-reperfusion group(P＜0.05).The rats in both sham operation group and NaHS group showed normal morphology of microglia in the ischemic cerebral cortical area.Compared with the sham operation group and the NaHS group,the rats in the ischemia-reperfusion group showed a significant reduction in the protrusion of microglia in the ischemic cerebral cortical area and a significant increase in the brightness of microglial cell bodies,and the cells appeared as clumps,losing their normal morphology,with a higher proportion of activated microglia.Compared with the ischemia-reperfusion group,the rats in the ischemia-reperfusion+NaHS group showed an increase in the number of microglial processes in the ischemic cerebral cortex,with fewer activated microglia and significantly improved morphology.The total numbers of microglia in the ischemic cerebral cortex of rats in the ischemia-reperfusion group and theischemia-reperfusion+NaHS group were significantly lower than those in the sham operation group and the NaHS group,while the total number of microglia in the ischemic cerebral cortex of rats in the ischemia-reperfusion+NaHS group was significantly higher than that in the ischemia-reperfusion group(P＜0.05).Conclusion NaHS can significantly improve brain injury in ischemia-reperfusion rats by inhibiting the inflammatory response and microglial activation induced by NLRP3 and reducing the levels of pro-inflammatory cytokines IL-1β and IL-18.

Objective:To study the dosimetry effects of differently selected values of control point(CP)in Monaco radiotherapy planning system on dynamic intensity modulated radiation therapy(dIMRT)for esophageal cancer of middle and lower segment.Methods:Thirteen patients with esophageal cancer at middle and lower segment who received dIMRT in Shangluo Central Hospital from January to June 2023 were selected.In the Monaco radiotherapy planning system,nine groups of dIMRT plans were designed for each patient according to the 9 kinds of CP limit values(10,20,30,40,50,60,70,80 and 90).There were not changes in other optimized parameters except CP parameter.The differences of the dosimetry between target region and organs at risk(OAR)included lung,heart and spinal cord were analyzed.Results:With the increase of the CP limit value,the maximum dose of the target region which was radiation dose(D2%)of 2%volume of target region,the mean dose,which was radiation dose(D50%)of 50%volume of target region,and the homogeneity index(HI)appeared a trend of gradual stability after reduction,and the radiation dose(D98%)of 98%volume of target region which was the minimum dose of target region and the conformance index(CI)appeared a trend of gradual stability after increase.There was not significant in each dose indicator of OAR(P>0.05).The variation ranges of lung at 5,10,20,30 Gy dose(V5,V10,V20 and V30)were respectively 1.13%,0.75%,0.29%and 0.19%,and the maximum deviation of mean dose(Vmean)of lung was 18.7 cGy.The variation ranges of V10,V20,V30 and V40 in the heart were respectively 2.2%,1.23%,1.39%and 1.12%,and the maximum deviation of Vmean in the heart was 63.85 cGy,and the maximum deviation of Dmax in the spinal-cord was 70.78 cGy.There were statistically significant differences in the actual CP number(CPs),execution time(DT)of plan,and ratio value of machine unit(MU)of the complexity of plan to CPs(MU/CPs)among the plans of 9 groups(F=2.857,25.145,135.467,P<0.05),respectively.Conclusion:In the dIMRT plan of esophageal cancer of middle and lower segment,the maximum CP value is set at between 40-50,which can reduce the optimization time of the plan,the number of subfields and the treatment time of patients under the premise of meeting the dose of the target region and the OAR.

Purpose To analyze the expression and prog-nostic role of JMJD2D in lung adenocarcinoma.Methods In this study,the expression of JMJD2D mRNA in lung adenocarci-noma and prognosis were analyzed using TCGA and GEO data-bases.The protein expression and prognostic value of JMJD2D in lung adenocarcinoma were further validated by immunohisto-chemistry.GSEA analysis was performed to identify signaling pathways associated with JMJD2D,with review of the relevant literature.Results The expression of JMJD2D mRNA in lung adenocarcinoma in TCGA database(513 cases of lung adenocar-cinoma and 59 cases of paracancerous tissue)and GEO database(46 cases of lung adenocarcinoma and 45 cases of adjacent tis-sue)were significantly higher than those in the paracancerous tissues.Survival analysis showed that the overall survival of pa-tients with low expression of JMJD2D mRNA was significantly higher than that of patients with high expression,and high ex-pression of JMJD2D mRNA was associated with poor prognosis in patients with lung adenocarcinoma.The expression of JMJD2D in 208 cases of lung adenocarcinoma was higher(96.15％)than that in adjacent tissues(9.13％)(P＜0.001),and its high expression was related to the prognosis.The results of GSEA analysis showed that JMJD2D high expression was signifi-cantly enriched in DNA damage repair,DNA replication and cell cycle regulation.Conclusion This study identifies high expres-sion of JMJD2D as an adverse prognostic factor in lung adenocar-cinoma.Further research on JMJD2D may provide new thera-peutic targets for lung adenocarcinoma.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Objective:To investigate the prevalence of the decline of intrinsic capacity(IC)and to explore the effect of intrinsic capacity decline on falls and hospital readmission during 1 year follow-up.Methods:A total of 311 elderly patients treated in Geriatrics Department of Zhejiang Hospital were enrolled.General information and intrinsic ability data, including cognitive(simple mental state inventory), motor(Tinetti-Balance Scale and 4 m test), vitality(grip strength and mini-nutrition assessment table), perception(self-rated vision or hearing impairment), and psychosocial(Geriatric depression scale), were collected at admission.Falls and hospital readmission within 1 year after discharge were followed up.Multivariate Logistic regression analysis was used to investigate the relationship of baseline intrinsic ability at admission with falls and hospital readmission during 1-year follow-up.Results:Of 311 elderly hospitalized patients, 282(90.7%)had intrinsic capacity decline.During 1 year follow-up, 38 elderly patients(12.2%)had falls and 69 elderly patients(22.2%)were hospital readmitted.After adjusting for confounding factors such as age, gender, education level, comorbidities, multiple medications, fear of falling, and assistive tool use and so on, Logistic regression analysis showed that decreased balance ability was a risk factor for falls within 1 year in elderly patients( OR=3.515, 95% CI: 1.089-11.346, P=0.036), and slow walking speed was a risk factor for one-year hospital readmission( OR=2.426, 95% CI: 1.181-4.983, P=0.016). Conclusions:Decreased motor capacity is closely associated with falls and hospital readmission within 1 year in older patients.Great attention should be paid to the assessment and intervention of motor ability in elderly patients.

ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 （COVID-19）， and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system （FAERS） from January 1， 2015 to March 31， 2021. Information component （IC） and reporting odds ratio （ROR） methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis， and 45 positive drug adverse event signals were detected. Headache （IC₀₂₅=1.09， ROR₀₂₅=2.28）， pyrexia （IC₀₂₅=0.51， ROR₀₂₅=1.51） and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events with higher frequency. Autoimmune disorder （IC₀₂₅=4.42， ROR₀₂₅=24.03）， streptococcal infection （IC₀₂₅=4.12， ROR₀₂₅=19.82）， and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events. Acute lung injury， cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19， and some adverse events with high frequency and high death rate deserve further attention by medical staffs.

Objective:To investigate the expression of inositol 1, 4, 5-triphate receptor (IP 3R)-glucose-regulated protein 75 (Grp75)-voltage dependent anion channel 1 (VDAC1)-mitochondrial Calcium uniporter (MCU) Calcium axis molecules in proteinuria and to explore its upstream regulator. Methods:Sixteen Sprague Dawley rats were divided into control group (6 rats) and Adriamycin (ADR) group (10 rats). Nephropathy rat model was established by single injection of ADR through tail vein.The glomerular expression of IP 3R, Grp75, VDAC1, MCU and the activation marker of mammalian target of Rapamycin complex 1 (mTORC1) were analyzed by immunohistochemical staining.In cultured mouse podocyte, ADR was used to induce podocyte injury, and the Everolimus of different concentrations was applied for intervention.The expression of the Calcium axis molecules and apoptosis marker was analyzed. Results:Compared with control group, the glomerular expression of IP 3R (0.02±0 vs.0, P<0.001), Grp75 (0.04±0 vs.0, P<0.001), VDAC1 (0.04±0 vs.0.01±0, P<0.001), and MCU (0.05±0.01 vs.0.01±0, P<0.001) were significantly increased in ADR-induced nephropathy rats, and the activation marker of mTORC1 (0.57±0.01 vs.0.18±0, P<0.001) was increased as well.In cultured mouse podocytes, compared with control group, the expression of Grp75 (1.89±1.17 vs.0.16±0.08, P=0.001), VDAC1 (1.59±0.34 vs.0.20±0.07, P=0.006), and MCU (1.56±0.38 vs.0.46±0.35, P=0.014) were obviously increased in ADR induced podocytes, and the activation marker of mTORC1 (2.12±0.08 vs.0.39±0.09, P<0.001) was also increased.Compared with the ADR induced podocytes, the expression of Grp75 (0.26±0.20 vs.1.89±1.17, P=0.001), VDAC1 (0.40±0.26 vs.1.59±0.34, P=0.014) and MCU (0.60±0.32 vs.1.56±0.38, P=0.029) in podocytes treated with ADR and 1.0 nmol/L Everolimus were remarkably decreased, accompanied with the decrease of mitochondrial calcium [(2 664.00±140.57) U vs.(3 025.16±180.92) U, P=0.023] and apoptosis marker cleaved Caspase-3 (0.55±0.28 vs.1.48±0.45, P=0.011). Conclusions:The over-production of IP 3R-Grp75-VDAC1-MCU Calcium axis molecules accompanied with the hyper-activation of mTORC1 was involved in ADR induced nephropathy rats.mTORC1 inhibitor decreased the expression of Calcium axis molecules in mouse podocytes, which might involve in the mechanism of mTORC1 inhibitor′s effects on podocyte.