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.

AIM To investigate the protective effects and mechanisms of aqueous extract of Cimicifugae Rhizoma on intestinal mucosa in a mouse model of ulcerative colitis(UC).METHODS The UC mouse models established by sodium dextran sulfate were allocated into different groups and administered with sulfasalazine(200 mg/kg)or aqueous extract of Cimicifugae Rhizoma(3.9,7.8 g/kg)by gavage,respectively.The mice had their changes of body weight,defecation patterns,disease activity index(DAI)and colon length recorded;their colon tissue pathological alterations and goblet cell quantification analyzed through HE and AB-PAS staining;their ROS levels in colon tissue measured via ELISA;their mRNA expressions of inflammatory cytokines,Nrf2/HO-1 signaling pathway components and NLRP3/Caspase-1/GSDMD pathway regulators in colon tissue assessed by RT-qPCR;their protein expressions of Nrf2/HO-1 and NLRP3/Caspase-1/GSDMD pathway verified by immunohistochemistry;and their ZO1 and Occludin tight junction proteins in colon tissues quantified by Western blot analysis.RESULTS Compared to the model group,the high-dose Cimicifugae Rhizoma aqueous extract group demonstrated significantly increased body weight,colon length and DAI scores(P＜0.01);mitigated intestinal mucosal barrier damage;reduced ROS levels in colon tissue(P＜0.01);suppressed mRNA levels of pro-inflammatory factors IL-1β,IL-6 and TNF-α in colon(P＜0.01);elevated expressions of tight junction protein ZO1 and Occludin in colon tissue(P＜0.05);upregulated mRNA and protein expressions of Nrf2,NQO1 and HO-1 in colon tissue(P＜0.05,P＜0.01);downregulated mRNA and protein expressions of Keap1(P＜0.05);and reduced expressions of NLRP3 inflammasome components(ASC,Caspase-1,GSDMD)in mRNA and protein(P＜0.05,P＜0.01).CONCLUSION The aqueous extract of Cimicifugae Rhizoma exerts protective effects against UC through dual mechanisms involving redox regulation and pyroptosis inhibition by reducing ROS level via Nrf2/HO-1 pathway activation and attenuating NLRP3-mediated pyroptosis via Caspase-1/GSDMD pathway inhibition,and thereby synergistically preserves the structural and functional integrity of intestinal mucosal barrier and mitigates UC progression.

AIM To establish a GC-MS/MS method for the analysis of volatile components in Yinhu Ganmao Powder,and to determine the contents of α-pinene,camphene,sabinene,β-pinene,α-terpinene,(+)-limonene,p-cymene,1,8-cineole,linalool,L-menthol,terpinen-4-ol,DL-menthol,α-terpineol,tridecane,pulegone,caryophyllene,humulene,n-hexadecane and patchouli alcohol.METHODS The analysis was performed on a DB-624 UI capillary column(30 m×0.25 mm×1.40 μm ),and electron ionization source was adopted with multiple reaction monitoring mode.RESULTS Fifty volatile components and twenty-five liposoluble components were identified in volatile oils and medicinal material powder,respectively.Nineteen constituents showed good linear relationships within their own ranges(r ≥ 0.999 0),whose average recoveries were 84.43％-113.31％with the RSDs of less than 9.15％.CONCLUSION This stable,accurate and reproducible method can provide a reference for the quality evaluation of Yinhu Ganmao Powder.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To investigate the effects of remote ischemic preconditioning (RIPC) on myocardial injury after non-cardiac surgery (MINS) in elderly patients with hip fracture.Methods:A prospective randomized controlled trial was conducted on 78 elderly patients with hip fracture admitted to the Seventh Medical Center of the PLA General Hospital between October 2023 and September 2024. The patients were divided into RIPC group and non-RIPC group using a random number table. They were treated with closed reduction internal fixation, open reduction internal fixation, or hip arthroplasty for hip fracture under regional anesthesia. The RIPC group received RIPC intervention on the day before surgery and after entering the operating room on the day of surgery (3 cycles of 5-minute upper limb exsanguination followed by 5-minute reperfusion using an inflatable tourniquet cuff). The non-RIPC group received the same perioperative management as the RIPC group except RIPC. Plasma high-sensitivity cardiac troponin I (hs-cTnI) concentrations were measured at admission, immediately after surgery, on the morning of the first postoperative day, and on the morning of the third postoperative day and MINS incidence was calculated based on the hs-cTnI concentrations. The incidence of MINS within 3 days postoperatively and the intraoperative complications were compared in the overall cohort and in age-stratified groups (<80 years, ≥80 years). The local adverse reactions at the RIPC application sites were observed within 3 days after surgery.Results:Among the 78 elderly patients with hip fracture, including 21 males and 57 females, aged 60-99 years [79.5(70.0, 87.0)years], 40 were assigned to the RIPC group and 38 to the non-RIPC group. No significant difference was found in the general data of the two groups. There was no significant difference in the overall MINS incidence between the two groups ( P>0.05). In the patients aged <80 years, no MINS incidence was found (0/21) in the RIPC group, compared with 22% (4/18) in the non-RIPC group ( P<0.05), while in the patients aged ≥80 years, no significant difference in MINS incidence was observed between the two groups ( P>0.05). There were no significant differences in intraoperative complication rates in the overall cohort, patients aged <80 years, or patients aged ≥80 years ( P>0.05). None of the patients had local adverse reactions at the RIPC application sites. Conclusion:For elderly patients with hip fracture who received regional anesthesia, RIPC can significantly reduce the incidence of MINS in patients aged <80 years, but exerts no significant effect on MINS incidence in the overall cohort or in patients aged ≥80 years.

Objective:To investigate the methods and skills required for the safe and swift removal of primary or secondary sacral tumors located between the second (inclusive) and fourth sacral vertebrae.Methods:The clinical images, pathology reports, surgical procedures, operation durations, intraoperative bleeding volumes, and postoperative functional follow-up data of 26 patients undergoing sacral tumor resection at the First Affiliated Hospital of Zhengzhou University and Xinjiang Production and Construction Corps Hospital between May 2020 and February 2025 were retrospectively examined. Additionally, the safety measures for sacral tumor resection and techniques for expedited specimen removal were evaluated.Results:According to magnetic resonance imaging (MRI) findings, all 26 patients presented with sacral tumors located between the second (inclusive) and fourth sacral vertebrae. Specifically, 9 patients were diagnosed with primary sacral tumors, pathologically confirmed as chordomas, while 17 patients had secondary sacral tumors. Among the secondary tumor cases, 12 were attributed to recurrent rectal cancer invading the sacrum, and 5 were due to malignant teratomas invading the sacrum. The 26 patients underwent a treatment strategy that began with managing the relationship between the internal iliac artery, vein branches, and the tumor, followed by the resection of the sacrum. During surgery, the bilateral sciatic foramina were accurately positioned, and the presacral fascia was dissected subsequent to the fracture of the sacrum. Among the 26 patients, 9 underwent sacral tumor resection directly through the posterior sacral approach. The average operation time for these patients was (71.1±4.9) minutes, with average blood loss of (186.7±72.8) milliliters. On the other hand, 17 patients underwent sacral tumor resection by transitioning from the supine position to the prone knife position through a combined abdominal and sacral approach. The average operation time for this group was (213.5±19.3) minutes, with average blood loss of (480.0±93.0) milliliters, significantly longer than that of the posterior sacral approach. The follow-up period ranged from 1 to 48 months, with a median of 20 months, ending on March 31, 2025. During this time, 26 patients achieved autonomous defecation with the aid of medication. None of the patients reported any functional movement disorders or pain in their lower limbs. It was observed that two out of the 26 patients developed distant metastasis, while the remaining 24 patients survived without any tumors.Conclusion:By pretreated the relationship between the internal iliac vessels and sacral tumors prior to resecting sacral tumors, utilizing the approach of initially fracturing the sacrum followed by rupturing the presacral fascia, the tumor can be entirely eliminated, resulting in a brief surgical procedure, reduced intraoperative bleeding, and minimal postoperative complications.