p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Objective:To investigate the clinical efficacy of intraoperative regional lymph-adenectomy and extended lymphadenectomy in resectable hilar cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 187 patients of hilar cholangiocarcinoma who were admitted to Henan University People′s Hospital from January 2014 to January 2018 were collected. There were 105 males and 82 females, aged (57±9)years. Of the 187 patients, 62 patients undergoing hilar cholangiocarcinoma resection with extended lymphadenectomy were divided into the extended group, and 125 patients under-going hilar cholangiocarcinoma resection with regional lymphadenectomy were divided into the regional group. Observation indicators:(1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) follow-up. Comparison of measurement data with normal distribu-tion between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. The Kaplan-Meier method was used to plot calculate survival rate and survival curve. The Log-rank test was used for survival analysis. Propen-sity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.1. Results:(1) Propen-sity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 187 patients, 104 patients were success-fully matched, with 52 cases in each of the extended group and the regional group. After propensity score matching, the elimination of tumor diameter, neural invasion, Bismuth classification, and TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After pro-pensity score matching, the operation time of the extended group was (341±83)minutes, the number of lymph node dissected was 12.3±4.5, the number of positive lymph node dissected was 2.2±0.7, cases of postoperative new lymphadenectasis was 17. The above indicators of the regional group were (311±73)minutes, 9.2±3.4, 1.5±0.5, 44, respectively. There were significant differences in the above indica-tors between patients of the two groups ( t=-1.99, -3.92, -5.57, χ2=31.18, P<0.05). (3) Follow-up. After propensity score matching, all 104 patients were followed up after surgery, with the follow-up time of 29(range, 3-49)months. The postoperative 3-year overall survival rate was 44.2% of the extended group, versus 30.8% of the regional group, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusions:The perioperative safety of regional lymphadenec-tomy and extended lymphadenectomy in the radical resection of hilar cholangiocarcinoma are com-parable. Extended lymphadenectomy can increase the number of positive lymph node detected and improve the postoperative survival rate of patients.

Objective:To construct a questionnaire to measure parents′ behavioral and social drivers (BeSD) in administering rotavirus vaccine to their children, and to test the reliability and validity of the questionnaire.Methods:A questionnaire was constructed to investigate the BeSD of rotavirus vaccination among parents based on the WHO BeSD questionnaire. A survey was conducted among parents of children aged 0-3 years old in vaccination clinics from 15 community health service centers in Nanjing City of Jiangsu Province, Yuhuan and Kaihua Counties of Zhejiang Province, Anqing City of Anhui Province, and Yangpu District of Shanghai City from April to May in 2024. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to analyze the reliability (internal consistency reliability, combination reliability and split half reliability) and validity (structural validity, convergence validity and discriminative validity) of the questionnaire.Results:A total of 850 questionnaires were collected, of which 614 were valid, with an effective response rate of 72.20%. The EFA resulted in the refinement of the rotavirus vaccine BeSD questionnaire from 37 to 35 items (including 24 core items), and suggested a five-factor structure including the perceptions of vaccine, confidence in vaccine, social process of vaccination, motivation for vaccination, and practical problems of vaccination. The cumulative variance contribution rate reached 56.27%. The CFA confirmed an ideal five-factor model fit (GFI=0.82,CFI=0.86,PNFI=0.67,RMSEA=0.07). The AVE of each dimension was greater than 0.50. The AVE square root of each dimension of the questionnaire was greater than its correlation coefficient. The Cronbach′s α coefficient of the total questionnaire was 0.79.Conclusion:The developed BeSD questionnaire of rotavirus vaccine has good reliability and validity, and can be used to measure parents′ behavioral and social factors in administering rotavirus vaccine to their children.

Objective:To investigate the immuno-inflammatory regulatory effects of the Qing Gan San Jie Xiao Ying Formula(QGSJXYF)on Hashimoto's thyroiditis(HT)by modulating thyroid cell-derived exosomes to provide experi-mental evidence for its immunomodulatory mechanisms.Methods:Nthy-ori-3-1 thyroid cells were treated with QGSJXYF-medicated serum,with untreated cells serving as controls.Exosomes from both groups were extracted and analyzed using nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and Western blot to assess concentration,size distribution,morphology,and the expression of characteristic exosomal markers.An inflammatory model of human T lymphocytes(H9)was established and co-incubated with normal exosomes(EXO-C group)or QGSJXYF-treated exosomes(EXO-T group).The levels of inflammatory cytokines in H9 cells were measured using Western blot(WB)and ELISA.Results:Exosome characterization showed that the particle concentration of Nthy-ori-3-1 cell-derived exosomes in both the control and QGSJXYF groups ranged from 1×109 to 1×1011/mL,with particle diameters between 80～300 nm.The exosomes exhibited a typical spherical or cup-shaped morphology with positive expression of TSG101,CD63,and HSP70.Compared with the inflammation model group and the EXO-C group,the EXO-T group significantly reduced the intracellular expression of IL-17A protein in H9 cells(P<0.05)and suppressed IL-17 and IL-6 levels in the cell supernatant(P<0.01).Conclusion:QGSJXYF may exert its anti-inflammatory and thyroid-protective effects by modulating the functional state of thyroid cell-derived exosomes,regulating the inflamma-tory microenvironment,and inhibiting the expression of inflammatory cytokines associated with Hashimoto's thyroiditis.

Objective:To analyze the willingness and related factors of pregnant women in Shanghai City to receive influenza vaccines during pregnancy.Methods:An online questionnaire survey was conducted among pregnant women who registered in maternal and child health hospitals in 16 districts of Shanghai. The basic information, health status during pregnancy, attitude towards influenza vaccination, and knowledge of influenza and influenza vaccine were collected, and χ2 test and multivariate logistic regression analysis were used to analyze the willingness and related factors of pregnant women to receive influenza vaccines during pregnancy. Results:A total of 3 219 valid questionnaires were received, with 10.90% of pregnant women willing to receive influenza vaccination during pregnancy, 57.50% unwilling to receive vaccination and 31.59% holding an uncertain attitude. Among the pregnant women who were willing to receive the vaccine, 82.91% would take the initiative to know the relevant information about the influenza vaccine, and 87.18% understood the transmission routes of the flu. 32.09% believed that pregnant women could receive the influenza vaccination at any stage of pregnancy. Among those who were unwilling and held an uncertain attitude, the proportions of the above three questions were 47.06%, 83.95% and 17.80%, respectively. Among pregnant women who were unwilling to receive vaccination and held an uncertain attitude, the main reason for their vaccine hesitation was the concern about the safety of the vaccine for pregnant women and fetuses during pregnancy. Multivariate logistic regression analysis showed that pregnant women with higher education ( OR=3.278, 95% CI: 1.678-6.406, P=0.001), second trimester ( OR=1.542, 95% CI: 1.159-2.054, P=0.003), third pregnancy ( OR=2.318, 95% CI: 1.008-5.331, P=0.048), and previous influenza vaccination ( OR=1.552, 95% CI: 1.119-2.152, P=0.008) had a higher willingness to receive influenza vaccines during pregnancy. Conclusion:Pregnant women in Shanghai have a relatively low willingness to receive influenza vaccines during pregnancy, mainly due to concerns about vaccine safety.

Objective To construct a medical consumables selection indicator system based on analytic hierarchy process(AHP)and fuzzy cluster method.Methods Firstly,a medical consumables selection indicator system was established preliminarily with the literature research results and actual situation of hospital consumables management;secondly,13 experts in related fields were selected to execute two rounds of online questionnaires,the expert weights were determined with AHP,the importance of each selection indicator was scored by the expert evaluation method and fuzzy cluster method,and consistency analysis was carried out on the two rounds of expert evaluation results;finally,the final medical consumables selection indicator system was built with the 100-point scale.Results The constructed medical consumables selection indicator system was composed of 5 primary indicators,12 secondary indicators and 38 tertiary indicators.The primary indicators included consumables quality,clinical demand,cost-effectiveness,supply capacity and after-sales service,with the percentage-based scores being 27,25,14,26 and 8,respectively.Conclusion The medical consumables selection indicator system based on AHP and fuzzy cluster method with high reliability provides effective and reliable references for medical institutions to select medical consumables.