ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Objective:To summarize the clinicopathologic characteristics of malignant hypertension (MHT) patients with acute kidney injury (AKI) and application of renin-angiotensin-aldosterone system inhibitor (RAASi).Methods:It was a retrospective cohort study. The adult patients with MHT and AKI admitted to Peking University First Hospital from January 1, 2012 to July 14, 2022. The patients were categorized into RAASi group and non-RAASi group based on RAASi administration from AKI onset to discharge. The clinicopathological data between the two groups were compared, and application of RAASi was analyzed.Results:A total of 179 patients were enrolled with age of 31 (26, 37) years and 148 males (82.7%). Ninety-five patients (53.1%) received dialysis treatment. The common causes of MHT were essential hypertension (125 patients, 69.8%), renal hypertension (39 patients, 21.8%) and endocrine hypertension (7 patients, 3.9%). AKI severity distribution showed 41 patients (22.9%) in stage 1, 1 patient (0.5%) in stage 2 and 137 patients (76.5%) in stage 3. Among MHT patients, 94 patients (52.5%) had been treated with RAASi before AKI, and 13 patients (7.3%) discontinued RAASi after AKI. Among 85 patients (47.5%) without receiving RAASi treatment before AKI, 68 new patients (38.0%) received RAASi treatment after AKI, and 40 patients (22.3%) were treated with the support of dialysis. Compared with non-RAASI group ( n=30), proportions of chronic kidney disease ( χ2=6.324, P=0.012) and post-AKI hyperkalemia ( χ2=4.048, P=0.044) in RAASi group ( n=149) were lower, and the proportion of dialysis treatment ( χ2=5.638, P=0.018), admission diastolic blood pressure ( Z=-3.609, P<0.001) and maximum diastolic blood pressure during hospitalization ( Z=-1.978, P=0.048) were higher. There were no statistically significant differences in the rates of target blood pressure control and renal function recovery between the two groups during hospitalization (all P>0.05). During hospitalization, 64 patients received renal biopsies, of which 50 patients (78.1%) had typical MHT vascular lesions such as "onion skin" in renal arterioles. Twenty-seven patients (42.2%) were complicated with glomerular diseases, and IgA nephropathy was the most common type (85.2%, 23/27). The proportions of glomerular ischemia and sclerosis, endothelial cell proliferation and acute renal tubular injury in RAASi group ( n=54) were lower than those in non-RAASi group ( n=10), and proportions of thrombosis and "onion skin" change were higher than those in RAASi group ( n=10), but the differences were not statistically significant (all P>0.05). Renal function recovery occurred in 47 patients (26.3%) by discharge. Among 95 dialysis patients, 26 patients (27.4%) achieved dialysis independence at discharge. Conclusions:MHT patients with AKI exhibit severe renal pathology and short-term poor prognosis. RAASi is primarily prescribed to those with relatively better kidney function or those receiving dialysis support.

Objective:To investigate the serum sodium level and its fluctuation in patients with hospitalized acquired acute kidney injury (AKI) and explore their impacts on in-hospital mortality.Methods:It was a single-center retrospective study. The adult patients developing hospital-acquired AKI and receiving at least twice serum sodium tests admitted to Peking University First Hospital from January 1, 2018, to December 31, 2020 were included. Dysnatremia included hyponatremia (< 135 mmol/L) and hypernatremia (>145 mmol/L). The patients were divided into hyponatremia group, normal serum sodium group and hypernatremia group, and the differences of clinical data among the three groups were compared. The fluctuation of serum sodium level was evaluated by coefficient of variation. A restricted cubic spline was applied to investigate the association between serum sodium level at AKI onset and mortality. Poisson regression analysis was used to explore the mortality risk of dysnatremia at AKI onset, dysnatremia at admission, and coefficient of variation of serum sodium, respectively.Results:Among the enrolled 1 475 AKI patients, the age was 66.0 (55.0, 78.0) years, and 850 patients (57.6%) were males. The estimated glomerular filtration rate was 77.3 (50.4, 97.6) ml·min -1·(1.73 m 2) -1. The time from admission to AKI onset was 8 (4, 15) days. The incidence of hyponatremia and hypernatremia at admission were 19.6% (289/1 475) and 2.6% (39/1 475), respectively, while the incidence at AKI onset was 24.0% (354/1 475) and 12.7% (188/1 475), respectively. There was statistically significant difference in terms of age, the initial classification distribution of AKI, serum sodium at admission, serum sodium at the occurrence of AKI, the lowest serum sodium at hospitalization, the highest serum sodium at hospitalization, the coefficient of variation of serum sodium, and the proportions of heart failure, stroke, disseminated intravascular coagulation, sepsis, acute respiratory distress syndrome, shock, prerenal causes, circle diuretics and aldosterone antagonists among hyponatremia group, normal serum sodium group and hypernatremia group (all P<0.05). The restricted cubic spline analysis showed a "U"-shaped correlation between serum sodium level at AKI onset and in-hospital mortality. Poisson regression analysis showed that after adjusting for age, gender, number of chronic comorbidities, initial classification of AKI, basal estimated glomerular filtration rate and number of acute disease state, with normal serum sodium as the reference, hyponatremia ( RR=1.56, 95% CI 1.14-2.13) and hypernatremia ( RR=1.71, 95% CI 1.23-2.39) at AKI onset were correlated with an increased risk of in-hospital mortality. Hyponatremia at admission was correlated with an increased risk of in-hospital mortality ( RR=2.13, 95% CI 1.62-2.79), while there was no statistically significant association between hypernatremia and in-hospital mortality ( RR=1.22, 95% CI 0.62-2.44). After further adjusting serum sodium levels at admission and at the occurrence of AKI, the coefficient of variation of serum sodium level was still correlated with an increased risk of in-hospital mortality ( RR=1.23, 95% CI 1.14-1.33). Conclusions:Dysnatremia is common in patients with hospital-acquired AKI. The serum sodium level at AKI onset is correlated with in-hospital death in a "U" shape. Dysnatremia and serum sodium fluctuation are associated with an increased risk of in-hospital mortality.

Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

AIM:Hepatotoxicity of Brucea javani-ca picryl with broad-spectrum anticancer effect in nude mice based on hepatic drug metabolizing en-zyme CYP450 activity.METHODS:Fifty-six nude mice were randomly divided into blank group,Bru-cea javanica low-dose group(2 mg/kg),Brucea ja-vanica high-dose group(4 mg/kg),and cisplatin group(2 mg/kg),with 14 mice in each group.The blank group was injected with the same amount of normal saline every 3 days for 6 weeks.Calculate the mortality rate of nude mice in each group,ob-serve the general growth state of nude mice,re-cord the weight change of nude mice before and af-ter administration,weigh and record the liver weight after taking materials,and calculate the liv-er coefficient(liver weight/weight mass×100％),ob-serve and record the liver color and morphology.Hematoxylin-eosin(HE)staining was used to ob-serve the pathological changes of liver tissue.De-tection of alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(AKP)and albumin(ALB)levels in serum of nude mice by ELISA.Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6 and CYP2C9,which were key enzymes of drug metabolism in nude mice liver.RESULTS:Compared with the blank group,the mortality rate of nude mice in the low-dose Brucea javanica bitter alcohol group was 0,the growth state was good,the diet,movement,and mental state were normal,the weight change and liver coefficient ratio were consistent,the liver color was ruddy,the liver lobule morphology was complete under the microscope,the structure was clear,the liver cells were arranged regularly,and there was no inflammatory cell infiltration.There was no significant difference in the content of ALT,AST,LDH,AKP,and ALB.There was no significant difference in the mRNA and protein expression of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9(all P＞0.05).Compared with the blank group,the mortality rate of nude mice in the high-dose group of Brucea javanica bitter alcohol was 14.3％,the growth state was slightly poor,the diet,movement,and mental state were reduced,the weight growth was slow,the liver coefficient ratio was increased,the liver color was reddish brown,some liver lobule boundaries were unclear,a small number of liver cells were loosely arranged,the contents of ALT,AST,LDH,AKP,and ALB were signif-icantly increased,the mRNA levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced,and the protein expres-sions of CYP2E1,CYP3A11,CYP1A2,and CYP2D6 were significantly reduced(all P＜0.05 or P＜0.01),but there was no statistical difference in the mRNA and protein expression of CYP2C19,and the pro-tein expression of CYP2C9(P＞0.05).Compared with the blank group,the mortality rate of nude mice in the cisplatin group was 35.7％,the growth state was poor,the diet,action,and mental state were low,the weight gain was less,the liver coefficient ratio was significantly increased,the liver color was dark red,the liver sinusoids and central veins were congested,the hepatocytes were disordered,the nuclei were consolidated and contracted,and the arrangement was loose,the contents of ALT,AST,LDH,AKP,and ALB were significantly increased,and the mRNA and protein expressions of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced(all P＜0.05 or P＜0.01).CONCLUSION:The dose of Brucea javanica bitter alcohol is correlated with hepatotoxicity to nude mice.High doses of Brucea javanica bitter alcohol have hepatotoxicity to nude mice,which may be re-lated to reducing serum levels of ALT,AST,LDH,AKP,and ALB,inhibiting the expression of multiple subtypes of enzymes in the key enzyme CYP450 of liver drug metabolism,and then reducing the me-tabolism of toxic substances.

Objective:To explore the distant metastatic characteristics of metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) based on prostate-specific membrane antigen (PSMA) PET-CT.Methods:This is a retrospective cohort study. Ultimately, data from 227 patients with metastatic prostate cancer who underwent PSMA PET-CT examinations at Xiangya Hospital, Central South University between March 2016 and May 2025 were retrospectively reviewed, including 117 mHSPC patients with an age of (68.8±7.6) years (range:53 to 89 years) and 110 mCRPC patients with an age of (69.4±7.5) years (range: 49 to 88 years). Clinical and pathological data, along with metastatic characteristics identified via PSMA PET-CT, were collected and compared. Intergroup comparisons were performed using χ 2 tests. Results:The incidence rates of lymph node metastasis, bone metastasis, and visceral metastasis in the mHSPC group were 71.8% (84/117), 89.7% (105/117), and 11.1% (13/117), respectively, while those in the mCRPC group were 52.7% (58/110), 91.8% (101/110), and 15.5% (17/110), respectively. The incidence of lymph node metastasis in the mHSPC group was significantly higher than that in the mCRPC group ( χ2=8.800, P=0.003). Among patients with bone metastasis, the rates of osteoblastic metastasis, osteolytic metastasis, and mixed metastasis in the mHSPC group were 76.2% (80/105), 8.6% (9/105), and 15.2% (16/105), respectively, while the corresponding rates in the mCRPC group were 74.3% (75/101), 7.3% (8/101), and 16.4% (18/101), respectively, all indicating a relatively high probability of osteolytic and mixed bone metastases ( χ2=0.260, P=0.878). Among patients with mHSPC and mCRPC who tested positive for visceral metastasis, lung metastasis (9/13 and 8/17) and liver metastasis (4/13 and 9/17) were the most common sites of metastasis, but there was no significant difference in the composition of visceral metastasis between the two groups ( χ2=0.933, P=0.564). In this study, among 20 patients who progressed from mHSPC to mCRPC, 35.0% (7/20) had persistent or progressive activity at the original metastatic site, 35.0% (7/20) developed new metastatic lesions, and 30.0% (6/20) showed inhibitory changes in the original metastatic lesions. Among patients with imaging progression, 1/14 of patients with osteoblastic metastatic lesions at the mHSPC stage exhibited osteolytic changes upon progression to mCRPC. Conclusion:Compared with the mCRPC group, the mHSPC group has a higher lymph node metastasis rate,and both groups have common rates of osteolytic and mixed bone metastases and visceral metastasis.

OBJECTIVE To evaluate the economic burden of the intensive care unit(ICU)patients due to hospital-associated multidrug-resistant organisms(MDROs)infections based on propensity score matching(PSM)so as to provide evidence-based bases for prevention and control of hospital-associated MDROs infection and improvement of utilization efficiency of medical resources.METHODS A total of 2118 patients who were hospitalized in Zibo Central Hospital from Jan.1,2023 to Dec.31,2024 and conformed to the inclusion and exclusion criteria were re-cruited as the research subjects.The patients with hospital-associated MDROs infections were matched in a 1∶1 ratio by PSM(with the clamp value 0.02).Totally 309 pairs were successfully matched.The length of hospital stay and the costs were observed and compared between the MDROs group and the non-MDROs group.RESULTS The MDROs group was with the length of hospital stay 14.00 days longer than the non-MDROs group after the matching(Z=-5.750,P＜0.001),with the total cost of hospitalization increased by 91,420.84 yuan(Z=-8.271,P＜0.001).With the respect to the medical treatment expenses,the expenses of the MDROs group were higher than those of the non-MDROs group,covering the cost of medical service,therapeutic procedures,nursing,western medicine and TCM,and there were significant differences(P＜0.05).Among the differences in the costs between the two groups,the difference in the cost of western medicine was the most signif-icant(22,182.91 yuan),followed by the cost of clinical laboratory test for diagnosis(19,529.60 yuan)and the cost of therapeutic procedures(16,333.50 yuan).CONCLUSIONS The hospital-associated MDROs infections may lead to the extension of hospital stay length of the ICU patients,which then increases the economic burden.There-fore,it is necessary to strengthen the multidisciplinary collaboration and formulate corresponding measures so as to reduce the risk of such infections among the ICU patients.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.