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.

Objective To systematically evaluate the therapeutic effects of video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracic surgery (RATS) in treating mediastinal tumors. Methods A computer search was conducted on PubMed, Embase, Cochrane Library, Web of Science, Wanfang, CNKI, CBM, VIP databases for literature comparing the clinical efficacy of VATS and RATS in treating mediastinal tumors, with the search time from inception to March 31, 2024. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included cohort studies, and Review Manager 5.4 software was used to perform a meta-analysis. Results A total of 32 articles were included, with 7868 patients. The NOS scores of the included cohort studies were all≥7 points. Meta-analysis results showed that compared with the VATS group, the RATS group had less intraoperative blood loss [MD=−16.71, 95%CI (−23.88, −9.54), P<0.001], lower conversion rate to open thoracotomy [OR=0.41, 95%CI (0.26, 0.67), P=0.003], lower overall postoperative complication rate [OR=0.66, 95%CI (0.48, 0.92), P=0.01], shorter postoperative drainage time [MD=−0.64, 95%CI (−0.92, −0.36), P<0.001], and shorter postoperative hospital stay [MD=−1.03, 95%CI (−1.28, −0.78), P<0.001]. There was no statistical difference between the two groups in terms of tumor size [MD=−0.06, 95%CI (−0.31, 0.19), P=0.64] or operation time [MD=5.52, 95%CI (−2.35, 13.40), P=0.17]. The RATS group had higher hospitalization costs than the VATS group [MD=1.69, 95%CI (1.26, 2.13), P<0.001]. Conclusion In mediastinal tumors resection, RATS is superior to VATS in terms of intraoperative blood loss, conversion rate to open thoracotomy, overall postoperative complication rate, postoperative drainage time, and postoperative hospital stay, but it increases hospitalization costs.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Esophageal cancer is a common malignancy with high incidence and poor prognosis. Conventional therapies fail to provide long-term benefits for patients, with postoperative recurrence and metastasis being the primary reasons for treatment failure. With the continuous development of nanomedicine, nanoparticle-based drug delivery has received widespread attention as a novel therapeutic approach. Among them, Fe3O4 magnetic nanoparticles have achieved a series of encouraging advancements in the treatment of esophageal cancer, owing to their unique superparamagnetism and biocompatibility. This paper provides a review of the relevant research on Fe3O4 magnetic nanoparticle-based drug delivery systems for the treatment of esophageal cancer.

Objective To evaluate the efficacy and safety of concurrent chemoradiotherapy versus sequential chemoradiotherapy in the treatment of locally advanced non-small cell lung cancer. Methods The relevant literature was searched in PubMed, Web of Science, CNKI and Wanfang databases from the inception to October 15, 2023, and the literature was screened according to the inclusion and exclusion criteria. Review Manager 5.3 software was used for meta-analysis of the literature, and the Cochrane bias risk assessment tool was used to evaluate the quality of the literature. Results Finally, 14 randomized controlled studies were included covering a total of 1048 patients. The results of meta-analysis showed that the overall response rate [OR=2.39, 95%CI (1.83, 3.11)], 1-year survival rate [OR=1.81, 95%CI (1.39, 2.35)], 2-year survival rate [OR=1.75, 95%CI (1.27, 2.42)] and 3-year survival rate [OR=2.33, 95%CI (1.49, 3.66)] were superior to sequential chemoradiotherapy (P<0.001). In terms of safety, concurrent chemoradiotherapy increased the incidence of radiation esophagitis (P<0.05), but there was no statistical difference in the incidence of leukopenia and radiation pneumonia (P>0.05). Conclusion For patients with locally advanced non-small cell lung cancer, the short-term efficacy of concurrent chemoradiotherapy is better than that of sequential chemoradiotherapy and can improve the 1-, 2- and 3-year survival rates, but the toxic side effects of the treatment are slightly greater than those of the sequential chemoradiotherapy.

Purpose Chemical exchange saturation transfer(CEST)imaging is used to study the changes of glutamate metabolism in the hippocampus of rats with chronic unpredictable mild stress(CUMS)model,so as to evaluate the clinical reference value of glutamate acid CEST(GluCEST)imaging results.Materials and Methods Twenty-two male SD rats were enrolled,and were divided into CUMS and healthy groups.Rats in CUMS group were further divided into the non-treatment group(n=7)and the ketamine treatment group(n=8).Seven healthy rats were randomly selected as control group.CEST imaging scans were performed using 7T small animal magnetic resonance and glutamate concentrations were measured in both hippocampi.The difference of hippocampal GluCEST value and glutamate concentration between control group and CUMS non-treatment group,CUMS ketamine treatment group and CUMS non-treatment group was analyzed,respectively.Results Compared with the control group,the hippocampal GluCEST value in CUMS non-treatment group was increased(left:t=2.8,P=0.015;right:t=3.0,P=0.011),while the hippocampal GluCEST value of rats in CUMS ketamine treatment group was decreased compared with CUMS non-treatment group(left:t=2.3,P=0.037;right:t=2.5,P=0.028).Conclusion GluCEST imaging can provide high spatial resolution images and accurately evaluate the changes of glutamate metabolism in hippocampus of rats with depression,which is conducive to monitoring the abnormal signals of hippocampal neurons caused by depression.

AIM To study the effect of Zuogui Pills on improving ovarian function in rats with premature ovarian failure(POF)by regulating autophagy.METHODS Seven rats were randomly selected as the blank group,and the remaining rats were injected with cisplatin(4.0 mg/kg)intraperitoneally to establish POF model.The success of the model was evaluated by observing the changes of estrous cycle.Twenty-one successful model of rats were randomly divided into model group and estradiol group(0.01 mg/mL)and Zuogui Pills group(1.85 g/kg),with 7 rats in each group,the drug was administered continuously for 21 days.Serum E2,FSH and LH levels were detected by ELISA;HE staining was used to observe the pathological morphology of ovarian tissue;immunohistochemical(IHC)method was used to detect the protein expressions of LC3B,SIRT1 and FoxO1 in ovarian tissues;RT-qPCR method was used to detect the mRNA expressions of LC3B,Beclin-1 and Atg5 in ovarian tissues;the protein expressions of SIRT1,FoxO1 and Ac-FoxO1 in ovarian tissue was detected by Western blot.RESULTS Compared with the blank group,the ovarian index of the model group decreased(P＜0.01);serum FSH and LH levels increased(P＜0.01)and E2 level decreased(P＜0.01);the structure of ovary is disordered,especially atresia follicle;the mRNA expressions of LC3B,Beclin-1 and Atg5 in ovarian tissue increased(P＜0.01),while the protein expressions of LC3B and Ac-FoxO1 increased(P＜0.01),while the protein expressions of SIRT1 and FoxO1 decreased(P＜0.01).Compared with the model group,the ovarian index of rats in estradiol group and Zuogui Pills group increased(P＜0.01);serum FSH and LH levels decreased(P＜0.01)and E2 level increased(P＜0.01);the number of primordial follicles in ovary increased and the number of atresia follicles decreased;the mRNA expressions of LC3B,Beclin-1 and Atg5 in ovarian tissue decreased(P＜0.01),while the protein expressions of LC3B and Ac-FoxO1 decreased(P＜0.01),while the protein expressions of SIRT1 and FoxO1 increased(P＜0.01).CONCLUSION Zuogui Pills may inhibit autophagy by activating SIRT1/FoxO1 signaling pathway,thus improving the pathological state of POF rats,regulating the level of sex hormones in rats,restoring endocrine balance,enhancing ovarian reserve function,promoting the normal development of follicles and delaying the progress of POF.

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.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.