ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

ObjectiveTo investigate the effects of 7-dehydrocholesterol reductase （DHCR7） in promoting proliferation， migration， and invasion of lung adenocarcinoma cells and the underlying signaling mechanisms. MethodsThe expression level of DHCR7 in lung adenocarcinoma and its prognosis were analyzed by using public databases. DHCR7 protein expression levels in the lung adenocarcinoma cell lines H1299 and A549 were assessed by Western blot， using the normal lung epithelial cell line BEAS-2B as a control. Small interfering RNA （siRNA） was used to knock down DHCR7 expression in H1299 and A549 cells. Assays including colony formation， CCK-8， wound healing， and Transwell experiments were conducted to assess the proliferation， migration， and invasion of the knockdown cells. Next， Western blot was employed to assess the phosphorylation levels of key signaling molecules in the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT）， janus kinase/signal transducer and activator of transcription 3 （JAK/STAT3），mitogen-activated protein kinase/extracellular signal-regulated kinase pathway （MAPK/ERK） （p-AKT， p-STAT3， p-ERK）. ResultsBioinformatics results indicated that both DHCR7 mRNA and protein were highly expressed in lung adenocarcinoma compared with normal tissues adjacent to cancer. Furthermore， higher DHCR7 mRNA level was associated with poor prognosis （P<0.001）. The expression levels of DHCR7 were significantly higher in both H1299 and A549 cells than that in BEAS-2B cells （P<0.05， P<0.01）. Compared with si-control， the proliferation， migration， and invasion abilities of si-DHCR7 H1299 and A549 cells significantly decreased. Among the phosphorylated signaling molecules detected， p-ERK was significantly downregulated （P<0.000 1， P<0.01） whereas p-AKT and p-STAT3 levels were not significantly changed. ConclusionDHCR7 has prominent effects in promoting the proliferation， migration， and invasion of lung adenocarcinoma cells， and the underlying mechanisms are related to the MAPK/ERK signaling pathway.

Objective:To investigate causal relationship between intestinal flora and risk of developing ankylosing spondylitis(AS)by a two-sample Mendelian randomization(MR)analysis.Methods:Genome-wide association study(GWAS)data on 211 types of intestinal flora and AS were obtained,and single nucleotide polymorphism(SNP)was used as an instrumental variable and sensi-tive SNPs were selected for analysis.Two-sample MR analyses were performed by inverse variance weighted(IVW)as well as MR-Eg-ger,Weighted median,to assess causal relationship between AS and intestinal flora by OR,and results were tested for heterogeneity and pleiotropy.Results:IVW analysis showed a significant causal relationship between 11 intestinal flora and AS risk.Among them,Verrucomicrobiae,Verrucomicrobiales,Verrucomicrobiaceae,Akkermansia,Erysipelatoclostridium,Holdermannia,Holdemania,Bacillales and Verrucomicrobia had positive causal effect on AS risk,while Dialister,Howardella and Oscillospira had negative causal effect.Causal effect estimates obtained by different methods(MR-Egger,Weighted median)were consistent,and sensitivity tests did not reveal significant horizontal pleiotropy and heterogeneity.Conclusion:Intestinal flora plays an important role in pathogenesis of AS,while specific mechanism remains to be further investigated.

Objective:To investigate causal relationship between intestinal flora and risk of developing ankylosing spondylitis(AS)by a two-sample Mendelian randomization(MR)analysis.Methods:Genome-wide association study(GWAS)data on 211 types of intestinal flora and AS were obtained,and single nucleotide polymorphism(SNP)was used as an instrumental variable and sensi-tive SNPs were selected for analysis.Two-sample MR analyses were performed by inverse variance weighted(IVW)as well as MR-Eg-ger,Weighted median,to assess causal relationship between AS and intestinal flora by OR,and results were tested for heterogeneity and pleiotropy.Results:IVW analysis showed a significant causal relationship between 11 intestinal flora and AS risk.Among them,Verrucomicrobiae,Verrucomicrobiales,Verrucomicrobiaceae,Akkermansia,Erysipelatoclostridium,Holdermannia,Holdemania,Bacillales and Verrucomicrobia had positive causal effect on AS risk,while Dialister,Howardella and Oscillospira had negative causal effect.Causal effect estimates obtained by different methods(MR-Egger,Weighted median)were consistent,and sensitivity tests did not reveal significant horizontal pleiotropy and heterogeneity.Conclusion:Intestinal flora plays an important role in pathogenesis of AS,while specific mechanism remains to be further investigated.

pAPN is a zinc-dependent metalloprotease,mediating the fusion between virus and host cell,and playing a role as the receptor of coronavirus.To explore the effect of pAPN on PEDV rep-lication,the full-length pAPN gene was amplified from the porcine small intestinal by PCR,and was cloned into the lentiviral vector via the homologous site digested with BamH Ⅰ and Not Ⅰ to obtain the recombinant lentiviral vector PLVX-pAPN-mCMV-ZsGreen1-puro.The recombinant lentiviral vector and helper plasmids pLP1,pLP2,pLP-VSVG were co-transfected into 293T cells for lentiviral packaging.Vero cells were infected with the packaged lentivirus and the pAPN gene overexpressing cells were screened by puromycin.The stable expression of Vero-pAPN monoclonal cell line was screened by a limited dilution method,and the effect of the cell line on the replication of PEDV was determined by qPCR for N mRNA transcription level,Western blot for N protein level,and TCID50.The results showed that the packaged lentivirus could infect Vero cells,and the monoclonal cell line Vero-pAPN(2C5)could stably expressed pAPN.The Vero-pAPN cell line can promote the replication of PEDV,the N gene mRNA transcription level was significantly different at 12-48 h(P＜0.05),the N protein expression level increased,and the TCID50 was significantly different at 24 and 48 h(P＜0.05).In conclusion,the Vero-pAPN cell line was constructed in this study and it can significantly promote the replication of PEDV,which provides a candidate cell line for PEDV vaccine production and isolation.

Objective:To analyze the epidemic characteristics of human brucellosis in Tangshan City, Hebei Province from 2016 to 2024, and to establish a prediction model for forecasting incidence of human brucellosis in Tangshan City from 2025 to 2028, so that to provide evidence for prevention and control strategies.Methods:The incidence data of human brucellosis in Tangshan City from 2016 to 2024 were collected. Brucella strains isolated from blood cultures of patients with acute brucellosis were identified.The onset time and demographic distributions of brucellosis were analyzed using descriptive epidemiological methods. Chi-square test was used for statistical analysis. Python software was used to establish a seasonal autoregressive integrated moving average model (SARIMA model) and predict the incidence of brucellosis in Tangshan City from 2025 to 2028. Results:From 2016 to 2024, a total of 2 446 cases of human brucellosis in Tangshan City were reported, with the highest incidence in 2016 (378 cases) and the lowest in 2022 (277 cases).Seasonal variation was observed, with 54.87%(1 342/2 446) occurring in spring and summer (March to July). The incidence rate of male was 5.28/100 000, which was significantly higher than that of female (1.94/100 000) ( χ2=554.96, P<0.001). The cases spanned all age groups, with the highest incidence among those aged 50 to 59 (30.25%(740/2 446)). Farmers engaged in cattle/sheep breeding accounting for 85.73% (2 097/2 446) of cases. A total of 236 blood samples were collected from patients with acute brucellosis, and 12 Brucella strains were isolated and identified as sheep type Ⅲ Brucella. The optimal model constructed was SARIMA (1, 0, 0) (1, 0, 1) 12, which was used to predict the incidence of human brucellosis in Tangshan City from 2025 to 2028. The results showed that the overall incidence was relatively stable, retaining the characteristic single annual peak. Conclusions:Human brucellosis in Tangshan City peaks in spring/summer and predominantly affects cattle/sheep farmers. The SARIMA (1, 0, 0) (1, 0, 1) 12 model effectively fits the epidemiological data of human brucellosis in Tangshan City well and enables reliable future trend predictions, supporting scientific and effective prevention and control work.

OBJECTIVE: To review the clinical characteristics of patients with traumatic spinopelvic dissociation (SPD) and explore the diagnostic and therapeutic methods. METHODS: A clinical data of 22 patients with SPD who underwent surgical treatment between March 2019 and August 2024 was retrospectively analyzed. There were 13 males and 9 females, with an average age of 35.5 years (range, 14-61 years). The causes of injury included falling from height in 16 cases, traffic accidents in 5 cases, and compression injury in 1 case. Sacral fractures were classified based on morphology into "U" type (9 cases), "H" type (7 cases), "T" type (4 cases), and "λ" type (2 cases). According to the Roy-Camille classification, there were 4 cases of type Ⅰ, 12 cases of type Ⅱ, 2 cases of type Ⅲ, and 4 cases of type Ⅳ. The Cobb angle was (35.7± 22.0)°. Sixteen patients were accompanied by lumbosacral trunk and cauda equina nerve injury, which was classified as grade Ⅱ in 5 cases, grade Ⅲ in 5 cases, and grade Ⅳ in 6 cases according to the Gibbons grading. The time from injury to operation was 2-17 days (mean, 5.7 days). Based on the type of sacral fracture and sacral nerve injury, 6 cases were treated with closed reduction and minimally invasive percutaneous sacroiliac screw fixation, 16 cases were treated with open reduction and lumbar iliac fixation (8 cases)/triangular fixation (8 cases). Among them, 11 patients with severe fracture displacement and kyphotic deformity leading to sacral canal stenosis or bony impingement within the sacral foramen underwent laminectomy and sacral nerve decompression. X-ray films and CT were reviewed during followed-up. The Matta score was used to evaluate the quality of fracture reduction. At last follow-up, the Majeed score was used to assess the functional recovery, and the Gibbons grading was used to evaluate the nerve function. RESULTS: All operations were successfully completed. All patients were followed up 8-64 months (mean, 20.4 months). Two patients developed deep vein thrombosis of the lower limbs, 2 had incision infections, and 1 developed a sacral pressure ulcer; no other complications occurred. Radiological examination showed that the Cobb angle was (12.0±6.8)°, which was significantly different from the preoperative one ( t=6.000, P<0.001). The Cobb angle in 16 patients who underwent open reduction was (14.9±5.5)°, which was significantly different from the preoperative one [(46.8±13.9)° ] ( t=8.684, P<0.001). According to the Matta scoring criteria, the quality of fracture reduction was rated as excellent in 8 cases, good in 7 cases, fair in 5 cases, and poor in 2 cases, with an excellent and good rate of 68.2%. Bone callus formation was observed at the fracture site in all patients at 12 weeks after operation, and bony union achieved in all cases at last follow-up, with a healing time ranging from 12 to 36 weeks (mean, 17.6 weeks). At last follow-up, the Majeed score was rated as excellent in 7 cases, good in 10 cases, fair in 4 cases, and poor in 1 case, with an excellent and good rate of 77.3%. One patient experienced a unilateral iliac screw breakage at 12 months after operation, but the fracture had already healed, and there was no loss of reduction. Among the 16 patients with preoperative sacral nerve injury, 11 cases showed improvement in nerve function (6 cases) or recovery (5 cases). CONCLUSION SPD with low incidence, multiple associated injuries, and high incidence of sacral nerve injury, requires timely decompression of the sacral canal for symptomatic sacral nerve compression, fractures reduction, deformities correction, and stable fixation.
Humans ; Adult ; Female ; Male ; Retrospective Studies ; Middle Aged ; Spinal Fractures/diagnostic imaging* ; Adolescent ; Sacrum/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Young Adult ; Pelvic Bones/surgery* ; Treatment Outcome ; Bone Screws

Objective To investigate the feasibility of estimating the real-ear-to-coupler difference(RECD)in children with head circumference,so as to further optimize the personalized and accurate matching scheme of hearing aid fitting for children.Methods A total of 106 children(197 ears)were enrolled in this study.Head circumference was measured using a soft ruler and RECD was measured using OmetroricsAuricalTM.SPSS software was used to analyze the correlation between the head circumference,month age and RECD values at each frequency of children.Results ① The head circumference of boys was slightly larger than that of girls,but there was no significant differ-ence between them(P＞0.05).② Unitary linear correlation analysis showed that RECD values at 750-6 000 Hz were negatively correlated with the head circumference,and a regression equation was established between RECD values at 1 000-6 000 Hz and the head circumference.③ RECD values calculated by regression formula based on the head circumference showed no significant difference between 1 000-3 000 Hz and 6 000 Hz and children's actu-al RECD values.Conclusion The individual RECD values of 0-6 years old children were correlated with the head circumference,and with the increase of the head circumference,RECD values at middle and high frequencies de-creased gradually.For children whose physical developments were not consistent with biological age,the RECD data at middle and high frequencies could be estimated based on the head circumference.

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*