BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

[Objective] To explore the influencing factors of quality monitoring index on the nucleic acid pooling detection mode and continuously improve the detection quality of nucleic acid laboratory. [Methods] The quality monitoring indicators (NAT reactive rate, NAT resolution reactive rate, NAT invalid batch rate, NAT invalid result rate, equipment failure rate) and causes of invalidity in our laboratory from January 1, 2020 to December 31, 2022 were retrospectively analyzed. The quality monitoring indicators of the laboratory during 2020 to 2022 were compared longitudinally. The quality monitoring indicators of the laboratory in 2022 were compared horizontally with the overall level in Shandong for the same period to find the differences. [Results] From 2020 to 2022, a total of 218 686 samples were detected, the NAT reactive rate was 0.15‰ (32 samples in total), the resolution reactive rate was 39.02%, the invalid batch rate was 1.06%, the invalid result rate was 1.18%, and the equipment failure rate was 3.58%. There were no differences in the NAT reactive rate, NAT resolution reactive rate and NAT invalid batch rate among different years (P>0.05), but there were differences in the invalid result rate (P<0.05). Equipment failure was the main cause of invalid results (56.53%). Compared with other laboratories in Shandong, there were differences in the NAT reactive rate and invalid result rate (P<0.05). There were differences in the reaction rate, resolution rate and invalid result rate among different reagents (P<0.05). Compared with other two laboratories using the same manufacturer's reagent, there were differences in the reactive rate and invalid result rate (P<0.05), but no difference in the resolution rate and invalid batch rate (P>0.05). [Conclusion] Establishing quality indexes for process control and regular analysis can timely detect potential risks in laboratory operation. The use of quality indicators to implement self-comparison and inter-laboratory comparison can help the laboratory systematically and scientifically evaluate its own operating status and formulate corresponding quality management strategies, thereby improving the laboratory's testing capacity and ensure the safety of blood use.

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

[This corrects the article DOI: 10.1016/j.apsb.2020.12.008.].

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

OBJECTIVE: To investigate the relationship between mean perfusion pressure (MPP) and the risk of sepsis-associated acute kidney injury (SA-AKI) and its prognosis, and to determine the optimal cut-off value of MPP for predicting SA-AKI. METHODS: A retrospective cohort study was conducted. The clinical data of adult patients with sepsis were collected from the Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2) database. The patients were divided into two groups based on the occurrence of SA-AKI. Baseline characteristics, vital signs, comorbidities, laboratory indicators within 24 hours of intensive care unit (ICU) admission, and clinical outcome indicators were collected. Mean MPP was calculated using the average values of mean arterial pressure (MAP) and central venous pressure (CVP), MPP = MAP-CVP. Cox regression models were constructed, relevant confounding factors were adjusted, and multivariate Logistic regression analysis was used to investigate the associations between MPP and the risk of SA-AKI as well as ICU death. The predictive value of MPP for SA-AKI was evaluated using receiver operator characteristic curve (ROC curve) analysis, and the optimal cut-off value was determined. RESULTS: A total of 6 009 patients were ultimately enrolled in the analysis. Among them, SA-AKI occurred in 4 755 patients (79.13%), while 1 254 patients (20.87%) did not develop SA-AKI. Compared with the non-SA-AKI group, the MPP in the SA-AKI group was significantly lowered [mmHg (1 mmHg≈0.133 kPa): 62.00 (57.00, 68.00) vs. 65.00 (60.00, 70.00), P < 0.01], and the ICU mortality was significantly increased [11.82% (562/4 755) vs. 1.59% (20/1 254), P < 0.01]. Three Cox regression models were constructed: model 1 was unadjusted; model 2 was adjusted for gender, age, height, weight and race; model 3 was adjusted for gender, age, height, weight, race, heart rate, respiratory rate, body temperature, hemoglobin, platelet count, white blood cell count, anion gap, HCO₃^-, blood urea nitrogen, serum creatinine, Cl^-, Na⁺, K⁺, fibrinogen, international normalized ratio, blood lactic acid, pH value, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, sequential organ failure assessment score, Charlson comorbidity index score, use of vasopressors, mechanical ventilation, and urine output. Multivariate Logistic regression analysis showed that when MPP was treated as a continuous variable, there was a negative correlation between MPP and the risk of SA-AKI in model 1 and model 2 [model 1: odds ratio (OR) = 0.967, 95% confidence interval (95%CI) was 0.961-0.974, P < 0.001; model 2: OR = 0.981, 95%CI was 0.974-0.988, P < 0.001], and also a negative correlation between MPP and the risk of ICU death (model 1: OR = 0.955, 95%CI was 0.945-0.965, P < 0.001; model 2: OR = 0.956, 95%CI was 0.946-0.966, P < 0.001). However, in model 3, there was no significant correlation between MPP and either SA-AKI risk or ICU death risk. when MPP was used as a multi-categorical variable, in model 1 and model 2, referring to MPP ≤ 58 mmHg, when 59 mmHg ≤ MPP ≤ 68 mmHg, as MPP increased, the risk of SA-AKI progressively decreased (OR value was 0.411-0.638, all P < 0.001), and the risk of ICU death also gradually decreased (OR value was 0.334-0.477, all P < 0.001). ROC curve showed that MPP had a certain predictive value for SA-AKI occurrence [area under the ROC curve (AUC) = 0.598, 95%CI was 0.404-0.746], and the optimal cut-off value was 60.5 mmHg. CONCLUSION MPP was significantly associated with the risk of SA-AKI, with an optimal cut-off value of 60.5 mmHg, and also demonstrated a significant correlation with the risk of ICU death.
Humans ; Acute Kidney Injury/physiopathology* ; Retrospective Studies ; Sepsis/physiopathology* ; Middle Aged ; Prognosis ; Male ; Female ; Aged ; Risk Factors ; Intensive Care Units ; Adult ; Logistic Models ; Proportional Hazards Models

Purpose: To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices. Materials and Methods: We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (△uHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis. Results: Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 ㎟ vs.877.23 ㎟ , p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher △uHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The △uHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003). Conclusions Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the △uHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.

Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.

Objective:To evaluate the incidence and case fatality rate of cardiovascular disease (CVD) among populations in urban and rural communities in eastern, central and western regions of China.Methods:The present study was based on the data of the Prospective Urban and Rural Epidemiology (PURE)-China cohort, which enrolled participants who had at least one follow-up visit and complete information on age and sex. Information on baseline demographics, cardiovascular risk factors, and prevention and treatment for CVD were collected. CVD and mortality events were documented using the standardized case report form of the PURE Global Study to assess the incidence and case fatality rate of CVD among populations in urban and rural communities in eastern, central and western China.Results:This study included a total of 47 262 community-dwelling participants (age: (51.1±9.6) years; female, n=27 529, 58.2%) from 115 urban and rural communities in 12 provinces across the eastern, central, and western regions of China. Over a follow-up period of 11.9 (9.5, 12.6) years, 2 686 deaths and 5 873 cardiovascular events were documented. The incidence of CVD was 11.90 (95%CI: 11.60-12.21)/1 000 person-years. A significant difference in CVD incidence was observed across regions ( Ptrend<0.001), which was highest in the western provinces (13.99 (95% CI: 13.33-14.65)/1 000 person-years), intermediate in the eastern provinces (11.92 (95% CI: 11.52-12.33)/1 000 person-years), and lowest in the central provinces (8.87 (95% CI: 8.25-9.50)/1 000 person-years). The 1-year case fatality rate of CVD demonstrated an increasing trend from eastern to western regions (eastern: 10.20% (95% CI: 6.95-14.73); central: 13.50% (95% CI: 9.90-18.14); western: 18.62% (95% CI: 14.95-22.94); Ptrend<0.001). Moreover, the incidence of major CVD was consistently higher in rural areas compared with urban areas across eastern ( P<0.001), central ( P=0.01) and western ( P<0.001)_regions, respectively. The 1-year case fatality rate in rural areas was also significantly higher compared with that in urban areas in both eastern ( P<0.001) and western regions ( P=0.02). Conclusions:The incidence and case fatality rate of CVD were high among middle-aged population in China, especially those in western regions with low socioeconomic levels and in rural areas.