Objective To explore the effect of neonatal exposure to different doses of Bisphenol A (BPA)on the hypothalamic -pituitary -testis axis in toddler and adolescent male rats.Methods Neonatal male Sprague -Daw-ley rats were randomly divided into 5 groups through random digital table method:control group,vehicle group,low -dose BPA [25 μg/(kg · d)]group,medium -dose BPA [50 μg/(kg · d)]group and high -dose BPA [250μg/(kg·d)]group.The rats were subcutaneously injected with respective agents on postnatal days 1 -7 (PND 1 -7).Pups were sacrificed on PND 22 and PND 50.The hypothalamus and testis were taken and weighed.The hypotha-lamic Kiss -1 mRNA and the testis androgen receptor (AR)mRNA were tested by using real -time fluorescence quan-titative and the levels of serum luteinizing hormone (LH),follicle stimulating hormone (FSH),testosterone (T)were tested by using radio immunity method,and inhibin B was measured by using enzyme linked immunosorbent assay. Results Compared with the controls,the level of serum FSH [(1 .610 0 ±0.693 2)IU /L,(1 .574 3 ±0.675 0)IU /L vs (2.362 9 ±0.580 3)IU /L](F =3.314,P =0.026),LH [(3.876 3 ±0.908 0)IU /L,(3.603 8 ±1 .350 2)IU /L vs (5.302 5 ±0.768 4)IU /L](F =3.1 39,P =0.027)and T [(0.383 8 ±0.1 77 8)μg/L,(0.442 5 ±0.21 4 1 )μg/L vs (0.782 5 ±0.282 1 )μg/L](F =5.1 06,P <0.01 )of medium and high -dose BPA groups,were decreased in PND 22,and the organ coefficient of testis [(0.952 90 ±0.049 1 5)%,(0.969 20 ±0.045 82)% vs (1 .022 80 ± 0.01 1 08)%](F =1 0.326,P <0.01 )and serum T [(1 .758 6 ±0.369 6)μg/L,(1 .71 8 8 ±0.395 7)μg/L vs (3.357 5 ±0.749 8)μg/L](F =1 3.799,P =0.01 2)were significantly decreased in PND 50.In high -dose BPA group of PND 22,the expression of hypothalamic Kiss -1 mRNA (0.068 80 ±0.01 1 79)was increased compared with the other groups (F =272.1 25,P <0.01 ),while in PND 50,compared with control group,the Kiss -1 mRNA (0.002 00 ±0.000 25,0.001 90 ±0.000 48 vs 0.001 40 ±0.000 1 7)of medium -and high -dose BPA groups was decreased(F =1 91 .826,P <0.01 ).Conclusions Neonatal exposure to the medium and high -dose BPA may impair the function of testis in toddler and adolescent male rats,and affect the hypothalamus -pituitary -testis axis.Neonatal exposure to the low -dose BPA does not have a significant influence on the hypothalamus -pituitary -testis axis.

At present, TCM treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) is based on the combination of disease differentiation and syndrome differentiation. Therefore, the establishment of IBS-D of liver stagnation and spleen deficiency syndrome combined with animal model as a combination of traditional Chinese and Western medicine innovation theory has become increasingly concerned about, and gradually become a new direction for the development of TCM experimental animal model. This article reviewed the research progress in IBS-D liver and spleen deficiency syndrome in recent years, discussed the establishment of IBS-D liver stagnation and spleen deficiency animal model and research ideas for the treatment of IBS-D, and provided references for mechanism research of TCM treatment for IBS-D and research and development of new medicine.

Background Idiopathic orbital inflammatory pseudotumor (IOIP) is a commom orbital disease,with serious eye symptoms and replase tendency,and its pathogenesis is still unclear.Nuclear factor-κB (NF-κB)-related proteins participate in many important pathophysiological process,however,whether NF-κB plays a role in the IOIP process is worthy of attention.Objective This study was to explore the roles of NF-κB pathway in IOIP pathogenesis.Methods Twenty-four IOIP specimens were collected during surgery in Beijing Tongren Hospital from September 2010 to May 2016.The histopathological characteristics of IOIP were examined by hematoxylin and eosin staining.The expression and location of NF-κB/p65,p-p65,p50 and inhibitor of κB (IκB-ot) were detected by immunohistochemistry and verified by immunocytochemistry and Western blot assay.Results The histopathological features of IOIP were numerous small lymphocyte infiltraion and fibrous tissue proliferation,and a lot of epithelioid cells were seen in lacrimal gland-involved specimens.NF-κB/p65 was positively expressed in the cytoplasm of all 24 specimens and the nucleus in 15 specimens with the expressing rate of 62.5％.p50 was expressed in the cytoplasm in 22 specimens with the expressing rate of 91.7％ and in the nucleus in 17 specimens with the expressing rate of 70.8％.The positive expression of p-p65 was found in 22 specimens with the expressing rate of 91.7％,and IκB-α was expressed in the cytoplasm of 11 specimens with the expressing rate of 45.8％.These results were confirmed by immunocytochemistry and Western blot assay.Conclusions NF-κB pathway is activiated during IOIP process,and NF-κB pathway may be involved in the pathogenesis of IOIP.

Objective To provide a reasonable processing scheme for physical cooling of one high fever neonate by evidence-based nursing. Methods According to PICO principle, we introduced a question and changed it to the form of retrieval conveniently, and retrieved Cochrane library, PubMed, and VIP information-in the form of Chinese science and technology periodical database. Results We totally retrieved physical cooling of 1 systematic literature and 1 clinical practice guideline. According to retrieval result and child′s disease′s conditions, shivering children, who stayed in thermal spike, would be stopped using physical cooling and be started to keep warm;when the temperature decreased, warm sponge bath did not utilize and colder water bag was enhanced its temperature between 30 ~36 ℃ to decrease temperature gradually. Children did not occur shivering and increased the comfort during the process of cooling. Conclusions Neonatal hyperpyrexia is not suitable to take warm sponge bath as physical cooling to decrease temperature and it should to reduce temperature gradually during the process of cooling.

Objective:To explore the clinical significance of the expression of nuclear factor of activated T cells 5 (NFAT5) in esophageal cancer tissues and the effect of the expression of knock-down esophageal cancer cells on their migration ability.Methods:The expression of NFAT5 in tissues of 26 patients with esophageal cancer and their adjacent tissues was detected by immunohistochemistry. Esophageal cancer cells ECA109 were divided into experimental group and control group. The experimental group ECA109 cells were transfected with NFAT5-siRNA plasmid, and the control group ECA109 cells were transfected with MOCK-siRNA plasmid. The mRNA content of NFAT5 was detected by fluorescence quantitative PCR. The expression of NFAT5, TLR4 and MyD88 proteins in the experimental group and control group were detected by Western blot. Transwell assay and cell scratch assay were used to detect the migration ability of the experimental group and the NC group.Results:Immunohistochemical test results showed that the positive rate of NFAT5 in esophageal cancer tissues was 80.77% (21 cases/26 cases) , and the expression rate was 15.38% (4 cases/26 cases) in corresponding adjacent tissues. The positive rate of NFAT5 protein in esophageal cancer tissues was significantly higher than that in adjacent tissues ( P<0.001) . The NFAT5 mRNA content of ECA109 cells in experimental group and control group decreased after transfection with corresponding siRNA. The protein expression levels of NFAT5, TLR4 and MyD88 in ECA109 cells in the experimental group were 0.28±0.08, 0.31±0.13 and 0.41±0.14, respectively. The protein expression levels of NFAT5, TLR4 and MyD88 in ECA109 cells in control group were 0.95±0.15, 0.84±0.22 and 1.04±0.26, respectively. The expression of TLR4 and MyD88 in esophageal cancer ECA109 cells decreased significantly ( P<0.05) . The scratch healing rate of esophageal cancer ECA109 cells was 52.67%±5.21% in the experimental group and 82.91%±7.26 % in the control group. Transwell experiment results showed that the number of successfully migrated cells in the experimental group was (35±5) , and the number of successfully migrated cells in the control group was (92±13) . The results showed that the migration ability of esophageal cancer ECA109 cells was significantly decreased after low expression of NFAT5 ( P<0.01) . Conclusions:The expression of NFAT5 is significantly increased in esophageal cancer tissues, and the expression of NFAT5 may be related to the malignant degree of esophageal cancer. Moreover, NFAT5 affects the migration ability of esophageal cancer cells by regulating TLR4/MyD88 signaling pathway.

AIM: To explore the protective effect of fluorofenidone (AKF-PD) on diethylnitrosamine-induced liver injury in rats and its inhibition of the TGF-β1/Smads pathway in hepatocytes. METHODS: Fifty-five male Sprague Dawley (SD) rats were randomly divided into three groups: model group (DEN group, n=20) were gavaged with DEN (10 mg/kg), 5 times for 14 weeks; control group (n=20) were gavaged with saline with the same volume of the model group; treatment group (DEN+AKF-PD Group, n=15), after 4 weeks of modeling, they were gavaged with AKF-PD (500 mg/kg) daily, and stopped at 14 weeks. At the end of experiment, the rats were killed by anesthesia and spinal dislocation. Masson staining was used to observe collagen deposition; primary hepatocytes were extracted and identified, and the levels of α-smooth muscle actin (α-SMA), TGF-β1, Smad3, and Smad7 mRNA, and the expression of Smad3 and Smad7 proteins in hepatocytes were detected. RESULTS: Compared with the control group, Masson staining showed that collagen deposition increased in the DEN group; AKF-PD treatment could significantly improve liver pathological damage and reduce collagen deposition. In addition, compared with the DEN group, the α-SMA, TGF-β1, and Smad3 mRNA levels of the AKF-PD group were significantly reduced, and the Smad7 mRNA level was increased. Moreover, AKF-PD treatment could dependably reduce the expression of Smad3 and increase Smad7. CONCLUSION: AKF-PD can significantly improve liver injury and fibrosis in rats caused by DEN. This effect may be related to the down-regulation of α-SMA, TGF-β1, and Smad3 mRNA levels in hepatocytes and the increase of Smad7 mRNA levels.

PPG(photoplethysmography)holds significant application value in wearable and intelligent health devices.However,during the acquisition process,PPG signals can generate motion artifacts due to inevitable coupling motion,which diminishes signal quality.In response to the challenge of real-time detection of motion artifacts in PPG signals,this study analyzed the generation and significant features of PPG signal interference.Seven features were extracted from the pulse interval data,and those exhibiting notable changes were filtered using the dual-sample Kolmogorov-Smirnov test.The real-time detection of motion artifacts in PPG signals was ultimately based on decision trees.In the experimental phase,PPG signal data from 20 college students were collected to formulate the experimental dataset.The experimental results demonstrate that the proposed method achieves an average accuracy of(94.07±1.14)%,outperforming commonly used motion artifact detection algorithms in terms of accuracy and real-time performance.

Objective:To explore the clinical characteristics and prognostic influencing factors of multiple primary lung cancer (MPLC), and to construct a prognostic prediction model.Methods:The clinical data and prognostic information of MPLC patients diagnosed by pathological examination included in the Surveillance, Epidemiology, and End Results (SEER) database from January 2010 to December 2020 were retrospectively analyzed. Patients were randomly divided into training and validation sets according to a 7:3 ratio using R software. Survival curves were plotted by using the Kaplan-Meier method and log-rank test was used for comparison between groups. The independent influencing factors of overall survival (OS) of MPLC patients in the training set were screened using univariate and multivariate Cox proportional hazards models, and accordingly, the nomogram predicting the survival rate of patients at 3, 5 and 8 years were plotted. In the training and validation sets, using the actual survival as the gold standard, the receiver operating characteristic (ROC) curves of the constructed models for predicting the patients' 3-, 5- and 8-year OS rates were plotted, the area under the curve (AUC) was obtained, and C-index of the model was analyzed by using R software. The calibration curves of 3-, 5- and 8-year OS rates predicted by the models and the actual OS rates were plotted.Results:A total of 5 495 MPLC patients were included, 3 846 in the training set and 1 649 in the validation set. The differences in the composition of patients of different ages and AJCC stages between the training and validation sets were statistically significant (both P < 0.05), and the differences in the comparison of other clinicopathological characteristics were not statistically significant (all P > 0.05). The results of multivariate Cox regression analysis showed that males (compared with females, HR = 1.256, 95% CI: 1.144-1.379, P < 0.001), age ≥ 70 years old (compared with 50-59 years old, HR = 1.201, 95% CI: 1.030-1.400, P = 0.019), FPLC with pathological types of squamous cell carcinoma or other types (compared with adenocarcinoma, HR = 1.275, 95% CI: 1.137-1.431, P < 0.001; HR = 1.208, 95% CI: 1.041-1.403, P = 0.013), and SPLC with pathological types of squamous cell carcinoma, small cell lung carcinoma, or other types (compared with adenocarcinoma, HR = 1.270, 95% CI: 1.121-1.440, P < 0.001; HR = 1.978, 95% CI: 1.642-2.384, P < 0.001; HR = 1.246, 95% CI: 1.090-1.424, P = 0.001), and AJCC stage Ⅲ and Ⅳ (compared with stage Ⅰ, HR = 1.645, 95% CI: 1.447-1.869, P < 0.001; HR = 2.078, 95% CI: 1.669-2.587, P < 0.001), FPLC without operation (compared with operation, HR = 1.263, 95% CI: 1.038-1.536, P = 0.020), SPLC without operation (operation vs. no operation, HR = 0.680, 95% CI: 0.579-0.799, P < 0.001), FPLC without lymph node dissection or with clearance of 1-3 regional lymph nodes (compared with clearance of ≥4, HR = 1.225, 95% CI: 1.016-1.477, P = 0.034; HR = 1.314, 95% CI: 1.103-1.566, P = 0.002), FPLC with maximum diameter 3-5 cm or >5 cm (compared with <3 cm, HR = 1.181, 95% CI: 1.053-1.324, P = 0.005; HR = 1.232, 95% CI: 1.069-1.420, P = 0.004), and SPLC with maximum diameter 3-5 cm or >5 cm (compared with <3 cm, HR = 1.560, 95% CI: 1.362-1.786, P < 0.001; HR = 1.727, 95% CI: 1.451-2.054, P < 0.001), and FPLC without chemotherapy (chemotherapy vs. no chemotherapy or unknown, HR = 0.744, 95% CI: 0.655-0.845, P < 0.001) were the independent risk factors of patients' poor OS (all P < 0.05). The results of Kaplan-Meier survival analysis showed that the OS of patients with different gender, race, age, two tumor locations, AJCC staging, pathological type of two lung tumors, maximum diameter of two tumors, and whether two tumors were treated surgically or not, and whether two tumors were treated with chemotherapy or not in the training set were compared, and the differences were all statistically significant (all P < 0.05). Based on the independent factors affecting the OS of MPLC patients screened by the results of multivariate Cox regression analysis, nomogram predicting the 3-, 5- and 8-year OS rates of MPLC were plotted. The results of ROC curve analysis showed that the C-index of the training set's nomogram was 0.679 (95% CI: 0.649-0.701), and the AUC values for predicting the 3-, 5- and 8-year OS rates were 0.601, 0.595 and 0.586, respectively; the C-index of the validation set was 0.678 (95% CI: 0.633-0.720), and the AUC values for predicting 3-, 5- and 8-year OS rates were 0.643, 0.631 and 0.626, respectively. The calibration curves showed that the 3-, 5- and 8-year OS rates of patients predicted by the nomogram models in both the training and validation sets were in good agreement with the actual results with a high goodness-of-fit. Conclusions:The established prognostic model has good predictive value and can effectively assess the prognosis of patients.

Type 1 diabetes mellitus (T1DM) is the main type of diabetes in children, which seriously endangers children′s health.With the development of technology, the emergence of artificial pancreas has brought new progress for the treatment of T1DM.Artificial pancreas can imitate the insulin physiological secretion of pancreas β cells to control glucose, and achieve close-loop management by accurately regulating insulin infusion through continuous glucose monitoring, insulin pump and control algorithms.Here the current clinical studies on the safety, effectiveness and limitations of artificial pancreas in the treatment of T1DM were reviewed.It is expected to provide another choice for children with T1DM.

Health insurance fund regulation (HIFR) is a vital issue in the modernization of healthcare security governance, with its importance as a primary task of the healthcare security department continually reinforced in policy practice. This study focused on the 22 specialized policies issued by the National Healthcare Security Administration from its establishment in 2018 to March 2024, deeply analyzed their issue characteristics, and summarized the evolutionary trends of policy changes, as well as the knowledge production patterns that existed in the series of policy formulation, implementation, and feedback processes. Our analysis revealed that the diverse issue characteristics had led to heterogeneous directions in HIFR policies. The policy development process presented distinct composite evolutionary trends, mainly manifested in four aspects: the integration of regulatory system and content, the convergence of professional and societal forces, the parallelism of special governance and regular supervision, and the complementarity of conventional and emerging methods. Additionally, the study demonstrated that the knowledge production embedded in policy evolution encompassed four different dimensions: problem rectification, norm setting, pilot experience, and technical absorption. Together with issue characteristics and policy evolution, they formed an integrated, dynamic, and open system of knowledge production, continuously promoting the renewal and iteration of regulation policies.