ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Objective To investigate the incidence trend of infectious diseases among kindergarten children in Yangpu District, Shanghai, and to provide scientific reference for prevention and control strategies of infectious diseases among key populations. Methods Descriptive epidemiology method and Joinpoint regression analysis model were used to analyze the surveillance data of infectious diseases among kindergarten children. Results The average annual reported incidence of infectious diseases among kindergarten children in Yangpu District was 3,344.08/100,000, showing a downward trend (AAPC=-5.51, 95%CI: -13.02~2.63). Intestinal (65.49%) and respiratory (34.48%) infectious diseases were the main cases. There were 7,378 cases of hand, foot and mouth disease (62.95%), 1,885 cases of influenza (16.08%), 1,378 cases of varicella (11.76%), and 392 cases of mumps (3.34%), accounting for 94.14% of all reported cases. Hand, foot and mouth disease (AAPC=-17.68%, 95%CI: -27.52~-6.51), mumps (AAPC=-9.33, 95%CI: -14.86~-3.45) and varicella (AAPC=-7.32, 95%CI: -17.35~3.93) showed an overall decreasing trend, while influenza (AAPC=32.19, 95%CI: 12.49-55.34) was on the rise. The incidence of the disease showed double peak distribution, and the high incidence months were from May to July and from September to December. The male to female ratio was 1.39:1. Conclusion The incidence of infectious diseases among kindergarten children in Yangpu District shows a downward trend. It is necessary to continue to increase the coverage rate of Enterovirus 71(EV71), influenza, chickenpox and MMR combined live attenuated vaccine, strengthen monitoring and early warning, actively carry out health guidance, and effectively control the occurrence of common infectious diseases in kindergarten children.

Objective To explore the clinical efficacy of robot-assisted coronary artery bypass grafting through a small incision in the left intercostal space in the treatment of multivessel coronary disease. Methods A retrospective analysis was conducted on the clinical data of patients who underwent coronary artery bypass grafting through a small incision in the left intercostal space at Central China Fuwai Hospital of Zhengzhou University from January 1, 2023 to October 15, 2024. Patients were divided into a robotic group and a minimally invasive group based on whether the surgery was assisted by the Da Vinci robot. Results A total of 81 patients were included, with 57 in the minimally invasive group, including 41 males and 16 females, with a median age of 65.0 (57.5, 69.5) years; and 24 in the robotic group, including 17 males and 7 females, with a median age of 61.0 (56.0, 69.0) years. There was no statistically significant difference in baseline data between the two groups (P>0.05). The robotic group had less intraoperative bleeding [300 (200, 438) mL vs. 500 (375, 600) mL, P=0.006], shorter postoperative mechanical ventilation time [15.0 (13.3, 23.5) h vs. 22.0 (15.5, 39.5) h, P=0.037], and lower incidence of postoperative pain [8 (33.3%) vs. 33 (57.9%), P=0.043]. The hospitalization cost in the robotic group was higher than that in the minimally invasive group [130491 (123298, 135691) yuan vs. 123892 (115543, 133449) yuan, P=0.023]. There was no statistical difference in postoperative laboratory indicators between the two groups (P>0.05). There was also no statistical difference in the duration of surgery, postoperative 24 h drainage volume, ICU stay time, postoperative hospital stay or incidences of perioperative compications including pleural effusion, transfusion, new-onset atrial fibrillation, acute kidney injury, non-union of incision, major cardiovascular and cerebrovascular adverse events, and reoperation between the two groups (P>0.05). Conclusion Compared with the minimally invasive group, the robotic group shows satisfactory efficacy and can effectively reduce postoperative pain and intraoperative bleeding, and shorten postoperative mechanical ventilation time.

Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Objective To explore factors associated with early postoperative hormonal remission in patients with prolactinoma and to develop prediction models based on clinical and radiological features. Methods Data from 107 patients with prolactinoma who underwent transsphenoidal surgery at The First People’s Hospital of Huai’an, Nanjing Medical University between January 2020 and December 2024 was collected, included general clinical characteristics, preoperative laboratory indicators, and imaging features. Based on whether early postoperative prolactin (PRL) levels normalized, patients were divided into a remission group (n=76) and a non-remission group (n=31). Univariate logistic regression was used for preliminary evaluation of candidate variables, followed by LASSO regression for feature selection. Multiple machine learning models were constructed, including logistic regression, random forest, support vector machine, K-nearest neighbors, naive Bayes, decision tree, neural network, and gradient boosting decision tree (GBDT). All models were trained and evaluated using ten-fold cross-validation, with comprehensive assessment of model performance based on the area under the ROC curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score. Results The maximum diameter of tumors in the non remission group was larger than that in the remission group (P=0.019), and the incidence of tumor stroke and preoperative PRL levels were significantly higher than those in the remission group (P＜0.001). Univariate analysis showed that sex, maximum tumor diameter, tumor stroke, and preoperative PRL levels were influencing factors for early postoperative hormone response in patients with prolactinoma (P＜0.05). The comparison results of machine learning models show that the neural network model performs the best (AUC=0.921) and has good clinical application value, followed by the GBDT model (AUC=0.893) and the support vector machine model (AUC=0.884). Other models also show certain predictive ability. Conclusions Sex, preoperative PRL levels, maximum tumor diameter, Hounsfield unit value, and tumor stroke are important factors affecting early hormone response after prolactinoma surgery. The machine learning model constructed based on the above variables has good predictive performance, and performs the best and has good clinical application value.

OBJECTIVE To analyze the incidence of cyclosporine （CsA）-associated acute kidney injury （AKI） in hospitalized patients， identify influencing factors， and construct a risk prediction model. METHODS A single-center retrospective study was conducted， enrolling clinical data from hospitalized patients treated with CsA at the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital from January 2018 to July 2024. The patients were classified into AKI group and non-AKI group based on the occurrence of CsA-related AKI. Univariate analysis and multivariate Logistic regression analysis were used to identify independent risk factors for CsA-related AKI， and a risk prediction model was constructed and its performance was evaluated. RESULTS A total of 439 patients were included， of whom 54 developed CsA-related AKI， with an incidence rate of 12.30%. The occurrence of CsA-associated AKI was positively correlated with concurrent bacterial pulmonary infection， cytomegalovirus viremia， respiratory failure， renal insufficiency， gastrointestinal bleeding， and peripheral central venous catheterization （odds ratios of 763.750， 16.944， 41.933， 236.806， 17.537 and 212.789， respectively； P ＜0.05）； while uric acid， prealbumin， and calcium levels were negatively associated with it （odds ratios of 0.983， 0.967 and 0.058， respectively； P ＜0.05）. The prediction model constructed based on the above factors yielded a χ 2 value of 10.254 （ P ＞0.05） in the Hosmer-Lemeshow test. The average area under the curve （AUC） from 10-fold cross-validation was 0.885. The AUC of the receiver operating characteristic curve was 0.883， with a sensitivity of 84.3% and a specificity of 80.4%， respectively， at the optimal cutoff value of 0.1. CONCLUSIONS Six factors， including concurrent bacterial pulmonary infection and cytomegalovirus viremia， are positively associated with the occurrence of CsA-related AKI； while uric acid， prealbumin， and calcium levels are negatively associated. The Logistic regression model constructed based on these factors demonstrates good predictive performance and can assist clinic in conducting early risk assessment and personalized interventions.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

OBJECTIVE: To compare the registration accuracy of cone beam computed tomography (CBCT) images while registering to virtual craniodentofacial patients based on soft tissue and the dentition registration method. METHODS: Virtual dentofacial patients out of 13 selected participants who needed CBCT scanning were established by impression with a registered-block impression (RBI) based on digital dental images, three-dimensional (3D) facial images and maxillofacial CBCT images. CBCT images were processed in the Mimics software program, establishing the craniofacial virtual patients based on CBCT images (CCTs). Registration between virtual patients from RBI and CCT, using the soft tissue in lower half face (STE) and dentition (DTN) as the reference area, respectively, forming two kinds of virtual craniofacial patients based on digital dental images, 3D facial images and skeletal images of CBCT (hiding the soft tissue and dental casts from CBCT). Three-dimensional deviation analysis was performed in the upper half face and lower half face of facial images from CBCT between two kinds of virtual craniodentofacial patients and compared with 3D facial images from RBI and recorded as root mean square error (RMSE). Paired-t test was used to compare the deviations of RMSEs between the upper and lower half of the face and the upper half of the face of facial images from CCT, respectively, between the two kinds of virtual craniodentofacial patients based on STE and DTN methods. RESULTS: Paired-t tests showed that there was no statistically significant difference between the upper and lower half faces of facial images from CCT between STE and DTN (P>0.05), but the deviation of RMSEs of the upper half face of facial images from CCT in STE was smaller than those in DTN [(1.696±0.420) mm vs. (1.752±0.424) mm, P < 0.01]. CONCLUSION The registration accuracy of CBCT registered in virtual craniodentofacial patients using soft tissue as the reference area was higher.
Humans ; Cone-Beam Computed Tomography/methods* ; Imaging, Three-Dimensional/methods* ; Male ; Face/anatomy & histology* ; Female ; Adult ; Image Processing, Computer-Assisted/methods* ; Young Adult ; User-Computer Interface

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

The mandibular condyle is a critical growth center in craniofacial bone development, especially during postnatal stages. Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks. Plagl1, which encodes a zinc finger transcription factor, is a paternally expressed gene. We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell (CNCC)-derived lineage cells in mouse condyles. Using the CNCC-derived lineage-specific Plagl1 knockout mouse model, we evaluate the function of PLAGL1 during postnatal mouse condyle development. Our findings show that PLAGL1 contributes significantly to osteoblast differentiation, and its deficiency impairs osteogenic lineage differentiation, which consequently disrupts mandibular condyle development. Mechanistically, insulin-like growth factor 2 (IGF2) in complex with IGF-binding proteins (IGFBPs) has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis. Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway, leading to disordered glucose metabolism, defective extracellular matrix organization, and impaired ossification. Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency. In conclusion, the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.
Animals ; Osteogenesis/genetics* ; Insulin-Like Growth Factor II/metabolism* ; Mice ; Transcription Factors/metabolism* ; Mice, Knockout ; Cell Differentiation ; DNA-Binding Proteins/genetics* ; Mandibular Condyle/growth & development* ; Osteoblasts/cytology* ; Signal Transduction ; Neural Crest/cytology*