Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

Objective:To aid in the detection of thyroid cancer by using deep learning to differentiate the unique bioimpedance parameter patterns of different thyroid tissues.Methods:An electrical impedance system was designed to measure 331 ex-vivo thyroid specimens from 321 patients during surgery. The impedance data was then analyzed with one dimensional convolution neural (1D-CNN) combining with long short-term memory (LSTM) network models of deep learning. In the process of analysis, we assigned 80% of the data to training set (1072/1340) and the remaining 20% data to the test set (268/1340). The performance of final model was assessed using receiver operating characteristic (ROC) curves. In addition, sensitivity, specificity, positive predictive value, negative predictive value, Youden index were applied to compare impedance model with ultrasound results.Results:The ROC curve of the two-classification (malignant /non-malignant tissue) model showed a good performance (area-under-the-curve AUC=0.94), with an overall accuracy of 91.4%. To better fit clinical practice, we further performed a three-classification (malignant/ benign/ normal tissue) model, of which the areas under ROC curve were 0.91, 0.85, 0.92 for normal, benign, and malignant group, respectively. The results indicated that the area under micro-average ROC curve and the macro-average ROC curve were 0.91 and 0.90, respectively. Moreover, compared with ultrasound, the impedance model exhibited higher specificity.Conclusions:A deep learning model (CNN-LSTM) trained by thyroid electrical impedance spectroscopy (EIS) parameters shows an excellent performance in distinguishing among different in-vitro thyroid tissues, which is promising for applications. In future clinical utility, our study does not replace existing tests, but rather complements others, thus contributing to therapeutic decision-making and management of thyroid disease.

Humans ; Norepinephrine ; Bacterial Infections/drug therapy* ; Immunity, Innate

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Objective To explore the clinical efficacy of Chaiqi Ningshen Anmian Decoction(CNAD)combined with wrist ankle acupuncture(WAA)in treating chronic insomnia(CI)patients with heart and spleen deficiency.Methods CI patients diagnosed and treated at the Beijing Huairou Hospital of Traditional Chinese Medicine from April 2022 to April 2023 were selected,and patients were randomly divided into the Eszolam(ET)group and the combination group(CNAD combined with WAA)according to the random number table method,with 50 cases in each group.The primary outcome was clinical efficacy[evaluated by the Traditional Chinese Medicine Syndrome Integral(TCMSI)].Secondary outcomes included changes in cognitive function[assessed by the Montreal Cognitive Assessment(MoCA)],anxiety level[assessed by the Hamilton Anxiety Scale(HAMA)],sleep quality[assessed by the Pittsburgh Sleep Quality Index(PSQI)],glycated serum albumin(GA),serotonin(5-HT),interleukin-1 β(IL-1β),and C-reactive protein(CRP)before and after treatment in both groups.Results Before treatment,there was no significant differences in total TCMSI between the two groups(P＞0.05).After treatment,the total TCMSI of the combination group was significantly lower than that of the ET group(P＜0.05),and the treatment effectiveness rate was significantly higher in the combination group(P＜0.05).Before treatment,there were no significant differences in MoCA score,HAMA score,PSQI score,serum GA level,serum 5-HT level,serum IL-1 level and serum CRP level between the groups(P＞0.05).After treatment,the MoCA score,serum GA level,and serum 5-HT level in the combination group were significantly higher than those in the ET group(P＜0.05),while the HAMA score,PSQI score,serum IL-1β level,and serum CRP level were significantly lower in the combination group(P＜0.05).Conclusion Compared with ET,CNAD combined with WAA significantly improves insomnia symptoms in CI patients with heart and spleen deficiency,enhances cognitive function and sleep quality,and reduces anxiety levels.This may be related to the upregulation of serum 5-HT,IL-1 β and the inhibition of the inflammatory response.

Objective:To investigate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation in the treatment of plasma cell mastitis.Methods:A retrospective analysis was performed for the clinical data of 10 patients with plasma cell mastitis treated with ultrasound-guided percutaneous radiofrequency ablation in the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022. The postoperative complications, symptoms and signs of the patients, ultrasound imaging manifestations, treatment efficacy at 3 months after surgery, the reduction rate of ablation lesions at 1 month, 3 months, 6 months, and 12 months after surgery, the recurrence status within 1 year after surgery, and the satisfaction with the treatment effect were observed.Results:The reduction rates of ablation lesions at 1 month, 3 months, 6 months, and 12 months were 32.31%-51.00%[(42.78±4.48)%], 70.66%-86.68%[(70.45±12.43)%], 72.31%-100%[(86.91±7.45)%], 89.13%-100%[(96.07±7.45)%], respecctively. The symptoms and signs of 10 patients improved significantly 3 months after surgery, and there was no recurrence of the disease during the follow-up period, and the treatment effect was significant and satisfactory.Conclusions:Ultrasound-guided percutaneous radiofrequency ablation for the treatment of plasma cell mastitis is a minimally invasive, effective and safe treatment.

Objective:To investigate the effects of fluoride exposure on kidney injury in rats and the sirtuin 3 (SIRT3)-fork head protein O3a (FOXO3a)-tensin homolog induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (PARKIN) pathway.Methods:Twenty-four 4-week-old SD rats (clean grade, body mass 100 - 150 g) were selected and divided into three groups according to the randomized numeric table: control group, low fluoride group, and high fluoride group, with eight rats in each group (half male and half female). The control group was given free access to tap water (fluoride ion concentration < 0.5 mg/L), while the low fluoride and high fluoride groups were given free access to tap water and sodium fluoride solutions with fluoride ion concentrations of 5.0 and 50.0 mg/L, respectively, for a period of 180 days. The formation of dental fluorosis in rats was observed and recorded, and the femur, urine and blood samples of rats were collected to measure bone fluoride, urinary fluoride, and blood fluoride levels, and to detect kidney function related indicators (serum uric acid, creatinine, and urea nitrogen contents). Morphological changes of renal tissues stained with hematoxylin-eosin (HE) were observed under a light microscope. Real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of renal SIRT3, FOXO3a, PINK1, PARKIN, microtubule associated protein 1 light chain 3 (LC3), autophagy receptor protein (P62), respectively.Results:Seven and one rats in the low and high fluoride groups were found to haveⅠdegree dental fluorosis, while zero and seven rats were found to haveⅡdegree dental fluorosis. Compared with the control group, rats in the low and high fluoride groups had higher levels of bone fluoride (μg/g: 1.18 ± 0.06, 2.16 ± 0.07 vs 0.52 ± 0.05), urinary fluoride (mg/L: 4.43 ± 0.11, 7.46 ± 0.09 vs 2.58 ± 0.14), blood fluoride (μg/ml: 0.77 ± 0.06, 1.68 ± 0.10 vs 0.52 ± 0.08), serum uric acid (μg/ml: 61.01 ± 4.17, 103.92 ± 5.43 vs 28.68 ± 2.91), creatinine (μg/ml: 74.82 ± 9.61, 132.05 ± 5.35 vs 22.38 ± 4.11), and urea nitrogen (μg/ml: 13.36 ± 1.27, 14.55 ± 0.34 vs 0.29 ± 0.07, P < 0.05). Under the light microscope, the kidneys of the control group showed tight and orderly arrangement of renal tubules and glomerular cells, with complete and clear cell contours. The low fluoride group was similar to the control group and no significant abnormalities were observed. The high fluoride group showed abnormal glomerular structure and atrophy, with some areas of renal tubules showing epithelial cell edema and unclear intercellular boundaries. The results of qRT-PCR assay showed that compared with the control group, the low and high fluoride groups had lower mRNA expression levels of SIRT3 (0.82 ± 0.03, 0.58 ± 0.02 vs 1.00 ± 0.08), P62 (0.75 ± 0.07, 0.28 ± 0.09 vs 1.00 ± 0.07, P < 0.05), and higher mRNA expression levels of FOXO3a (1.35 ± 0.04, 3.01 ± 0.23 vs 1.00 ± 0.08), PINK1 (1.58 ± 0.09, 3.28 ± 0.09 vs 1.00 ± 0.07), PARKIN (1.51 ± 0.04, 1.67 ± 0.10 vs 1.00 ± 0.05), LC3 (1.74 ± 0.07, 2.38 ± 0.18 vs 1.00 ± 0.08, P < 0.05). The results of Western blotting showed that compared with the control group, the low and high fluoride groups had lower protein expression levels of SIRT3 (0.91 ± 0.01, 0.55 ± 0.03 vs 1.00 ± 0.01), P62 (0.94 ± 0.27, 0.66 ± 0.38 vs 1.00 ± 0.19, P < 0.05), and higher protein expression levels of FOXO3a (1.14 ± 0.03, 1.22 ± 0.05 vs 1.00 ± 0.02), PINK1 (1.46 ± 0.03, 1.56 ± 0.03 vs 1.00 ± 0.05), PARKIN (1.98 ± 0.02, 2.33 ± 0.11 vs 1.00 ± 0.06), LC3 (4.10 ± 0.58, 4.93 ± 0.33 vs 1.00 ± 0.13, P < 0.05). Conclusion:Exposure to fluoride can cause renal tissue injury in rats, with downregulation of SIRT3 and P62 expression levels, and upregulation of FOXO3a, PINK1, PARKIN, and LC3 expression levels.

Objective To explore the value of combined detection of cerebrospinal fluid lactate (LA), interleukin-27 (IL-27) and interferon-γ (IFN-γ) in diagnosing bacterial meningitis after neurosurgical operation in Intensive Care Unit (ICU). Methods A total of 54 patients with bacterial meningitis after neurosurgical operation in ICU were collected as disease group, and 62 patients without bacterial meningitis after operation were collected as control group. Fully automated biochemical analyzer and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of LA, IL-27 and IFN-γ in cerebrospinal fluid; the Logistic regression model was used to analyze the related factors affecting bacterial meningitis after operation; the receiver operating characteristic (ROC) curve was used to analyze the diagnostic values of LA, IL-27 and IFN-γ in cerebrospinal fluid for bacterial meningitis after operation. Results The glucose level in the disease group was significantly lower than that in the control group, while the white blood cell count and protein level were significantly higher than those in the control group (P < 0.01). The expression levels of LA and IL-27 in the cerebrospinal fluid in the disease group were significantly higher than those in the control group, while IFN-γ level in the cerebrospinal fluid was significantly lower than that in the control group (P < 0.01). Logistic regression analysis showed that LA, IL-27 and IFN-γ in the cerebrospinal fluid were the influencing factors of bacterial meningitis after neurosurgical operation in ICU (P < 0.05). The area under the curve (AUC) of LA combined with IL-27 and IFN-γ in cerebrospinal fluid in the diagnosis of bacterial meningitis after neurosurgical operation in ICU was 0.955, which was better than that of single diagnosis based on LA (AUC=0.806, Z=4.029, P < 0.001), IL-27 (AUC=0.858, Z=2.513, P=0.012) and IFN-γ (AUC=0.815, Z=3.680, P < 0.001) in cerebrospinal fluid, and the sensitivity and specificity of the combined diagnosis were 87.04% and 93.55% respectively. Conclusion The expression levels of LA and IL-27 in the cerebrospinal fluid of patients with bacterial meningitis after neurosurgical operation in ICU increase significantly, while the expression level of IFN-γ in the cerebrospinal fluid is significantly lower. The combined detection of three indicators has higher diagnostic value for postoperative bacterial meningitis compared with single detection.

Objective:To investigate the safety and efficacy of ultrasound-guided sclerotherapy combined with radiofrequency ablation on the complex lymphatic malformations (LM) in children.Methods:The clinical data of 21 children with complex LM treated with ultrasound-guided sclerotherapy combined with radiofrequency ablation in the First Affiliated Hospital of Zhengzhou University from June 2018 to October 2021 were retrospectively analyzed.Intraoperative and postoperative complications were recorded.Imaging examinations were performed at 1, 3, 6, 9, 12, 18, 24 months postoperatively to observe the recurrence, the volume of the lesions and their reduction rate were calculated, and the efficacy was analyzed. Friedman test was used to compare the lesion volume at different time points before and after surgery, and the reduction rate of lesion volume at 1 month postoperatively and other time points after surgery. Results:A total of 21 children were included in this study, among them, there were 12 males and 9 females, age range from 1 month to 5 years and 6 months, with a median age of 23 months.A total of 26 LM in 21 children were successfully treated, and no serious complications like organ damage occurred during and after surgery.One patient with abdominal LM had a postoperative infection, which was controlled by 3 weeks of catheter drainage.Four LM in 3 children recurred at 3 or 6 months after surgery, while all lesions were significantly narrowed down than those before surgery and they were cured after 1-3 sessions of continued sclerotherapy.There were significant differences in the lesion volumes before surgery and 1, 3, 6, 9, 12, 18 and 24 months postoperatively [222.26(159.57, 316.40) cm 3vs.43.06(22.74, 62.53) cm 3, 31.56(15.49, 45.94) cm 3, 25.21(9.63, 36.22) cm 3, 19.80(6.79, 28.81) cm 3, 12.80(3.93, 20.38) cm 3, 7.13(0, 11.34) cm 3, and 2.79(0, 4.93) cm 3; all P<0.05]. There were significant differences between the volume reduction rates at 1 month postoperatively and 3, 6, 9, 12, 18, and 24 months postoperatively [79.36(73.30, 87.81)% vs.85.40(81.09, 91.61)%, 88.85(84.70, 93.61)%, 91.67(87.87, 95.05)%, 94.15(94.47, 97.35)%, 97.11(95.02, 100.00)%, and 99.04(97.93, 100.00)%; all P<0.05]. Patients were followed up for 24 months, and all of them were cured. Conclusions:Ultrasound-guided sclerotherapy combined with radiofrequency ablation is a minimally invasive, safe and effective therapeutic strategy for children with complex LM.

Objective:To study the genetic profiles and clinical characteristics of neonatal-onset genetic epilepsy.Methods:From July 2016 to May 2021, patients with neonatal-onset genetic epilepsy admitted to our hospital and received second-generation genetic sequencing were enrolled in this study. According to the types of genetic variations, the patients were assigned into ion channel group and non-ion channel group. Clinical characteristics, treatments and prognosis of the two groups were compared.Results:A total of 36 patients with identified genetic variations were enrolled, involving 15 epilepsy-related genes. KCNQ2, SCN2A and STXBP1 were the most common pathogenic genes. 20 cases (55.6%) were in the ion channel group and 16 cases (44.4%) in the non-ion channel group. No significant differences existed in their general status, seizure types, EEG characteristics, treatments and outcomes between the two groups ( P>0.05). Among all 36 cases, the age of onset ranged from 10 min to 24 d after birth and 28 cases (78.8%) developed epilepsy within 1 week after birth. Developmental and epileptic encephalopathies were diagnosed in 20 patients. 7 patients were diagnosed with self-limited neonatal epilepsy, 2 were pyridoxine dependence, 2 were Zellweger syndrome and 1 case of self-limited familial neonatal-infantile epilepsy, Turner type mental retardation with epilepsy, PURA syndrome, Rett syndrome and 22q11.2 deletion syndrome, each. The patients received antiepileptic drugs including phenobarbital, levetiracetam, oxcarbazepine, topiramate, valproic acid, benzodiazepines (nizepam/clonazepam /clobazam/midazolam), lacosamide and lamotrigine. 5 patients died after giving up treatment. 31 patients were followed up for 6 to 50 months. 22 cases (71.0%) were controlled at 1- to 35-month-old including 21 cases (56.7%) with developmental delay. 6 cases (19.4%) had ineffective seizure control and 3 cases (9.7%) showed reduced seizures, all with varying degrees of developmental delay. Conclusions:Neonatal-onset epilepsy is correlated with multiple genes. KCNQ2, SCN2A, STXBP1 are the common pathogenic genes with multiple variants of KCNQ2 gene. Most patients have seizures within 1 week after birth. More than half of patients have ion channel related gene variations. Sodium channel blockers have certain effects as treatment.