Objective To explore a method for rapid and differential diagnosis of rejection after kidney transplantation through urine hyperspectral imaging technology. Methods Hyperspectral data information from urine samples of 118 recipients after kidney transplantation was collected, and a deep learning model was constructed to diagnose and classify the types of rejection. Results A deep learning diagnostic model based on the 34-layer residual network (ResNet-34) was constructed, and 118 patients were included and divided into the training set and the test set. Based on the pathological results of the transplanted kidney puncture, the urine samples of the patients were classified into five groups: the non-rejection group, the T-cell-mediated rejection group, the antibody-mediated rejection group, the mixed rejection group and the nephropathy recurrence group. The results showed that the diagnostic sensitivities of the model for the above five groups were 0.960, 0.980, 0.930, 0.940 and 0.943 respectively, and the diagnostic specificities were 0.983, 0.993, 0.997, 0.989 and 0.989 respectively. The overall diagnostic accuracy rate reached 95.7%. Conclusions The study provides a non-invasive, rapid and accurate auxiliary diagnostic method for the differential diagnosis of rejection after kidney transplantation.

Objective To evaluate the ambient dose equivalent rates of photons and neutrons inside and outside the door of a 10 MV accelerator room, and to report the shielding effect of boron-containing polyethylene as maze wall lining. Methods The ambient dose equivalent rates of photons and neutrons inside and outside the door of an accelerator room were taken as the research subject. The Kersey, Falcão, and modified Kersey methods were used to calculate the ambient dose equivalent rates of neutrons and neutron capture gamma rays inside and outside the door of the room before and after renovation. Measurements were made using an X-ray/γ-ray dose rate instrument and a neutron ambient dose equivalent rate meter. Calculated and measured results were compared. Results Before renovation, the measured neutron dose rate inside the door was 409 μSv/h, while the calculated values were 323 μSv/h (Kersey method), 428 μSv/h (Falcão method), and 219 μSv/h (modified Kersey method). The Falcão method yielded a value closest to the measured value, while the Kersey and the modified Kersey methods underestimated the value by 21% and 46%, respectively. After the installation of boron-containing polyethylene plates, the measured neutron dose rate inside the door was 190 μSv/h, with a 54% reduction. The neutron and photon ambient dose equivalent rates outside the door were 5.8 μSv/h and 6.0 μSv/h, respectively, before renovation, and 0.14 μSv/h and 1.6 μSv/h, respectively, after renovation. Conclusion For a 10 MV accelerator room, neutron shielding and protection measurements are necessary, especially for rooms with short mazes. The Falcão method provides the best estimate of neutron dose rates inside and outside the door. Using boron-containing polyethylene plates as maze wall lining is an economical and effective shielding method.

ObjectiveTo investigate the features of serum HBV RNA in different stages of the natural history of chronic hepatitis B virus （HBV） infection without antiviral treatment， as well as its correlation with serum HBV DNA and HBsAg. MethodsA total of 306 treatment-naïve patients with chronic HBV infection who attended Department of Infections Diseases and Hepatoloty， the Second Hospital of Shandong University from January 2023 to June 2024 were divided into six groups based on the different stages of natural history， i.e.， HBeAg-positive chronic HBV infection group with 29 patients， HBeAg-positive chronic hepatitis B （CHB） group with 107 patients， HBeAg-negative chronic HBV infection group with 18 patients， HBeAg-negative CHB group with 60 patients， HBeAg-positive indeterminate-phase chronic HBV infection group with 7 patients， and HBeAg-negative indeterminate-phase chronic HBV infection group with 85 patients. Real-time isothermal RNA amplification was used to measure serum high-sensitivity HBV RNA. The Kruskal-Wallis H test was used for comparison between multiple groups of continuous data， while the Mann-Whitney U test was used for comparison between two groups. The Spearman method was used to investigate the correlation of HBV RNA with HBV DNA and HBsAg. ResultsThe HBeAg-positive chronic HBV infection group showed the highest level of serum HBV RNA ［7.5 （7.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， followed by the HBeAg-positive CHB group ［7.4 （6.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， the HBeAg-negative CHB group ［4.5 （3.0‍ ‍—‍ ‍5.7） log₁₀ copies/mL］， and the HBeAg-negative chronic HBV infection group ［1.0 （1.0‍ ‍—‍ ‍2.0） log₁₀ copies/mL］； the HBeAg-positive indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 3.9 （3.7‍ ‍—‍ ‍5.7） log₁₀ copies/mL， and the HBeAg-negative indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 2.0 （1.0‍ ‍—‍ ‍3.0） log₁₀ copies/mL； there was a significant difference in serum HBV RNA level between the six groups （H=830.770， P<0.001）. There was a significant difference in HBV RNA level between the HBeAg-positive chronic HBV infection group and all the other groups except the HBeAg-positive CHB group （all P<0.001）. In the 306 patients with HBV infection， HBV RNA was strongly correlated with HBV DNA （r=0.92， P<0.001） and was moderately correlated with HBsAg （r=0.67， P<0.001）. The correlation between serum HBV RNA and HBsAg in HBeAg-positive patients （r=0.61， P<0.001） was stronger than that in HBeAg-negative patients （r=0.31， P<0.001）. For the patients with HBeAg-positive chronic HBV infection， the male patients with ALT>30 U/L and the female patients with ALT>19 U/L had a significantly lower serum HBV RNA level than the male patients with ALT≤30 U/L and the female patients with ALT≤19 U/L （P<0.001）， and there was no significant difference in serum HBV RNA level between the latter group of patients and the HBeAg-positive CHB group （P>0.05）. ConclusionIn patients with chronic HBV infection who do not receive antiviral therapy， there is a difference in serum HBV RNA level in different stages of natural history， and serum HBV RNA level has the strongest correlation with HBV DNA and a relatively weak correlation with HBsAg. In patients with HBeAg-positive chronic HBV infection， serum HBV RNA level in male patients with ALT>30 U/L and female patients with ALT>19 U/L are in the transition stage between HBeAg-positive chronic HBV infection and HBeAg-positive CHB.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

Objective:This study aims to investigate the differences in hemostatic efficacy and patient comfort between an innovative domestically produced biodegradable nasal packing sponge and a traditional absorbent sponge following endoscopic nasal surgery. Methods:A prospective, randomized controlled trial design was utilized, including 30 patients who were divided into two groups according to random allocation, each receiving one of the two types of nasal packing. The study assessed the hemostatic efficacy, comfort, and safety of the materials by comparing the rates of no bleeding within 24 hours after packing, re-bleeding rates after 48 hours, pain ratings in the head and nasal areas, scores on a visual analog scale for nasal ocular symptoms, and safety indicators between the two groups. Results:The rates of no bleeding within 24 hours post-packing were 73.33% for both the experimental and control groups, with a no-bleeding rate of 100% after 48 hours in both groups. The pain rating in the head and nasal areas at various times post-packing was Grade Ⅰ（100%） in both groups, with no statistically significant difference（P=1.000）. The experimental groups sneezing score on the day of packing was（0.73±1.03）, lower than the control groups（2.27±1.67）, （P=0.007）; after 48 hours, the experimental groups sneezing score was（0.67±0.98）, also lower than the control groups（1.67±1.18）, （P=0.019）. There was no significant difference between the two groups in the Lund-Kennedy scoring during endoscopic examinations at the screening period, 7 days, 1 month, and 3 months post-packing（P>0.05）. Laboratory tests for other examination indicators were normal in both groups. Conclusion:The innovative domestically produced biodegradable nasal packing sponge not only provides hemostatic efficacy comparable to imported materials but also significantly improves patient comfort after surgery. It represents an economical and effective choice for nasal packing materials.
Humans ; Prospective Studies ; Surgical Sponges ; Endoscopy/methods* ; Male ; Female ; Epistaxis/prevention & control* ; Middle Aged ; Nasal Surgical Procedures/methods* ; Adult

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

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OBJECTIVE: To explore the clinical features of the sepsis in immunocompromised hosts and establish an early warning equation. METHODS: A retrospective study was conducted on sepsis patients admitted to the intensive care unit (ICU) of Binzhou Medical University Hospital from October 2011 to October 2022. General information, infection site, etiology results and drug susceptibility, clinical symptoms, inflammatory indicators, acute physiology and chronic health status evaluation II (APACHE II), sequential organ failure assessment (SOFA), incidence of immune paralysis, and outcome during hospitalization were collected. Based on whether they met the diagnostic criteria for immunocompromised hosts, patients were divided into immunocompromised group and immune normal group. The clinical information of the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of patients with immunocompromised sepsis and the regression equation model was initially established. Omnibus test and Hosmer-Lemeshow test were used to evaluate the model. RESULTS: A total of 169 patients with sepsis were included, including 61 in the immunocompromised group and 108 in the normal immune group. The top 3 infection sites in the immunocompromised group were bloodstream infection, pulmonary infection and abdominal infection. The top 3 infection sites in the normal immune group were pulmonary infection, bloodstream infection and abdominal infection. The infection rate of Gram-negative bacteria in the immunocompromised group was significantly lower than that in the normal group [49.2% (30/61) vs. 64.8% (70/108), P < 0.05]. The infection rate of Gram-positive bacteria [27.9% (17/61) vs. 13.9% (15/108)] and multidrug-resistant bacteria [54.1% (33/61) vs. 29.6% (32/108)] were significantly higher than those in normal immune group (both P < 0.05). In terms of clinical symptoms, the proportion of fever in the immunocompromised group was significantly lower than that in the immune normal group [49.2% (30/61) vs. 66.7% (72/108), P < 0.05]. Neutrophil count (NEU) and neutrophil percentage (NEU%) in the immunocompromised group were significantly lower than those in the normal immune group. Lymphocyte percentage (LYM%), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), APACHE II score, combined shock rate, incidence of immune paralysis, and mortality during hospitalization in the immunocompromised group were significantly higher than those in the normal immune group. Logistic regression analysis showed that NLR, CRP and PCT were risk factors for patients with immunocompromised sepsis (all P < 0.05). The above indicators were used as covariables to construct a Logistic regression equation, that was, Logit (P) = 0.025X₁+0.010X₂+0.013X₃-2.945, where X₁, X₂ and X₃ represent NLR, CRP and PCT respectively. Omnibus test and Hosmer-Lemeshow test show that the model fits well and has certain early warning value. CONCLUSIONS Patients with immunocompromised sepsis have more intense inflammatory response, with Gram-negative bacteria being the predominant pathogen, and a higher incidence of Gram-positive bacterial infections and multi-drug resistant infections. The severity of the disease, in-hospital mortality, the incidence of shock and the incidence of immune paralysis after sepsis were significantly higher. NLR, CRP and PCT were independent risk factors for sepsis in immunocompromised hosts. The regression equation constructed based on this may have early warning significance for patients with immunocompromised sepsis.
Humans ; Sepsis/immunology* ; Immunocompromised Host ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Logistic Models ; Male ; APACHE ; Female ; Middle Aged ; Aged