Objective To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with immune cell infiltration and patient prognosis. Methods Three ESCC datasets (GSE161533, GSE26886, and GSE23400) from the GEO database were analyzed to identify differentially expressed genes. CEACAM6 was identified as a key gene through survival analysis. Its expression, prognostic value, and relationship with immune cell infiltration were further explored using databases, such as TIMER. Tissue samples were collected from 162 patients with ESCC. Immunohistochemistry was performed to detect the expression of CEACAM6, immune cell markers (CD4, CD8, CD20, and CD56), and immune checkpoint molecules (HHLA2 and CD40LG). Correlations between CEACAM6 expression and clinicopathological features, immune cell infiltration, and immune checkpoints were analyzed. Results Bioinformatic analysis and clinical sample validation confirmed that CEACAM6 expression was significantly upregulated in ESCC tissues compared with adjacent nontumor tissues (P<0.05). High CEACAM6 expression was closely associated with advanced clinical stage (AJCC Ⅲ-Ⅳ), high T stage (T3-T4), lymph node metastasis, nonulcerative type, and poor prognosis. Furthermore, CEACAM6 expression levels were positively correlated with the infiltration density of CD8⁺ T cells, CD4⁺ T cells, and CD20⁺ B cells within the tumor microenvironment and with the expression of the immune checkpoint molecules HHLA2 and CD40LG (all P<0.05). Conclusion CEACAM6 serves as an independent poor prognostic factor for ESCC. Its high expression is implicated in the modulation of the tumor immune microenvironment by correlating with specific immune cell infiltration and immune checkpoint molecules, suggesting its potential as a novel prognostic biomarker and immunotherapeutic target for ESCC.

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 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.

Endothelial dysfunction is one of the early triggers of vascular remodeling during pulmonary hypertension (PH) with complex predisposing mechanisms, mainly via an unbalanced generation of vasoactive factors, increased expression of growth factors, prothrombotic elements, and inflammatory markers. Conventional treatment regimens are restricted to a single therapeutic pathway, which usually leads to limited clinical outcomes. Combination therapies targeting multiple cells and several signaling pathways are increasingly adopted in PH treatment. Herein, inspired by the cocrystal pleomorphism theory, we prepared rod-shaped nanococrystals of the endothelin-1 (ET-1) receptor antagonist (bosentan, BST) and the anti-inflammatory drug (andrographolide, AG) for targeting the pulmonary endothelium and alleviating PH. The 525 nm-sized co-delivery system displayed a rod-like morphology, preferentially accumulated in the pulmonary endothelium and alleviated pulmonary artery (PA) remodeling. A three-week treatment with the preparation significantly alleviated the monocrotaline (MCT)- or Sugen 5416/hypoxia (SuHx)-induced PH by reducing the pulmonary artery pressure, increasing the survival rate, improving the hemodynamics, and inhibiting vascular remodeling. Mechanistically, the nanococrystals collaboratively repaired endothelial dysfunction by suppressing the pathways of ET-1/NF-κB/ICAM-1/TNF-α/IL-6. In conclusion, the cocrystal-based strategy offers a promising approach for constructing co-delivery systems. The developed rod-shaped nanococrystals effectively target the pulmonary endothelium and relieve experimental PH.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.

Objective:To evaluate the association between postoperative delirium (POD) and preoperative frailty in elderly patients undergoing knee or hip arthroplasty.Methods:This nested case-control study utilized medical records from elderly patients who underwent knee or hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between September 2021 and May 2023. Participants were divided into 2 groups based on clinically diagnosed POD: POD group ( n=53) and non-POD group ( n=256). Univariate analysis was conducted on suspected influencing factors, and logistic regression analysis was utilized to identify the risk factors for POD. Receiver operating characteristic and clinical decision curves were plotted to evaluate the predictive performance of these risk factors for POD. Mediation analysis was performed, and a clinically applicable nomogram was constructed to achieve visual prediction of outcomes. Results:There were statistically significant differences in age, preoperative frailty, body mass index, American Society of Anesthesiologists Physical Status classification, Memorial Delirium Assessment Scale scores, and concentrations of Aβ 42, Aβ 40, phosphorylated tau protein (p-tau protein) and tau protein, Aβ 42/tau ratio and Aβ 42/p-tau ratio in cerebrospinal fluid (CSF) between non-POD group and POD group ( P<0.05). Preoperative frailty was a risk factor for POD ( P<0.05). Mediation analysis revealed that the association between preoperative frailty and POD was mediated by CSF tau protein concentrations. The area under the receiver operating characteristic curve of preoperative frailty and CSF biomarker concentrations in predicting POD was 0.974 ( P<0.05). The clinical decision curve demonstrated that the model combining the preoperative frailty and CSF biomarker concentrations predicted a higher net benefit ( P<0.05). The clinical decision curve showed that the model combining preoperative frailty and CSF biomarker concentrations predicted a higher net benefit. Conclusions:Preoperative frailty is a risk factor for POD in elderly patients undergoing knee or hip arthroplasty, and its combination with CSF biomarker concentrations can effectively predict the occurrence of POD. CSF tau concentration mediates the association between preoperative frailty and development of POD.

Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.