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.

Through evidence mapping, this paper systematically summarized the research evidence on the use of traditional Chinese medicine(TCM) in treating renal anemia, displaying the distribution of evidence in this field. A systematic search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, Springner, PubMed, Engineering Village, and Web of Science, targeting studies published up to June 30, 2024. The research evidence was summarized and displayed through a combination of graphs, tables, and text. A total of 264 interventional studies, 37 observational studies, and 7 systematic reviews were included. The annual publication volumes related to TCM treatment in renal anemia showed an overall upward trend, with most studies involving sample sizes between 60 and 120 participants(224 articles, 74.42%). Intervention measures were categorized into 21 types, with oral TCM decoctions being the most common medicine(171 times, 56.81%). The use of self-made prescriptions was the most common TCM intervention method. The intervention duration was mainly between 8 weeks and 3 months(239 articles, 79.40%). The most frequently reported TCM syndrome was spleen and kidney Qi deficiency. The top 2 outcome indicators were the anemia indicators and renal injury/renal function markers. However, several issues were identified in these studies, such as insufficient attention to the sources, social/geographical information, and temporal continuity of research subjects in observational research. Randomized controlled trials mostly had a high risk of bias, mainly due to issues such as randomization bias, blinding bias, and failure to register research protocols. The methodology quality of systematic reviews was generally low, mainly due to inadequate inclusion of literature, failure to specify funding sources, and lack of pre-registrations. While the report quality of systematic review was acceptable, there were significant gaps in the reporting of protocols, registration, and funds. The results show that these issues affect the quality of research and the reliability of findings on TCM in treating renal anemia, underscoring the need to address them to conduct higher-quality research and provide more reliable medical evidence for TCM in treating renal anemia.
Humans ; Anemia/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/drug therapy*

OBJECTIVE: To assess the mid-term clinical efficacy of the direct anterior approach for window decompression and bone grafting surgery in the treatment of early to mid-stage osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was performed on 40 patients (40 hips) diagnosed with osteonecrosis of the femoral head (ONFH), classified as types L1 and L2 according to the China-Japan Friendship Hospital (CJFH) classification system, and at stagesⅡ, ⅢA, and ⅢB based on the Association Research Circulation Osseous (ARCO) staging system. All patients underwent head-neck junction fenestration decompression and bone grafting via the direct anterior approach between January 2015 and May 2022, with complete follow-up data available for a minimum of three years. The ages of the patients ranged from 35 to 69 years old, with a mean of (49.13±6.14 ) years old;their body mass index (BMI) ranged from 20.02 to 27.94 kg·m^-2, with a mean of (23.65±1.69) kg·m^-1;the duration of the disease ranged from 13 to 36 months, with a mean of (24.55±4.14) months. Preoperative and 3-year postoperative X-ray parameters were collected, including the anterior preserved angle(APA), lateral preserved angle (LPA), and combined preserved angle (CPA). Additionally, hip joint disability and osteoarthritis outcome scores (HOOS) and Harris hip scores (HHS) were recorded. RESULTS: Forty patients were followed up for a period ranging from 36 to 59 months, with a mean duration of (47.18±6.18) months. At 3 years postoperative, none of the patients underwent hip replacement surgery. The APA (73.15±19.35)°, LPA (75.35 ±21.48)°, and CPA (136.25±26.78)° at the 3-year postoperative significantly improved compared to preoperative measurements (61.93±20.54)°, (59.46±22.67)°, and (116.58±32.47)°, with statistical significance (P<0.05). The HOOS (20.37±1.39) and HHS (89.74±3.28) scores at the 3-year postoperative were significantly improved from preoperative scores (12.36±1.58) and (50.27±6.15), respectively, with statistical significance (P<0.05). CONCLUSION The direct anterior approach for window decompression and bone grafting surgery can relieve joint pain, improve joint function, and enhance X-ray preserved angles, effectively preventing femoral head collapse, making it an effective surgical method for treating ONFH classified as L1, L2 according to CJFH and stagesⅡ, ⅢA, ⅢB according to ARCO.
Humans ; Middle Aged ; Male ; Female ; Adult ; Decompression, Surgical/methods* ; Bone Transplantation ; Femur Head Necrosis/surgery* ; Follow-Up Studies ; Aged ; Retrospective Studies

Objective:To study genotype analysis and influence factors analysis of hepatitis B virus(HBV)deoxyribonucleic acid(DNA)positive samples of negative hepatitis B surface antigen(HBsAg)donors in blood donors without compensation in Nan'an area.Methods:A total of 62,000 HBsAg fast-screened blood donor samples from January 2021 to June 2024 were selected as the study objects.HBV infection,viral load and genotype of HBV DNA positive samples,single factor and influencing factor of HBV DNA positive samples were detected and analyzed.Results:Among the 62000 HBsAg fast-screened blood donor samples,the results were negative by HBsAg screening,moreover,285 cases(0.46％)were HBsAg positive and 61715 cases(99.54％)were negative.NAT positive 180 cases and 118 cases were positive for HBV DNA.The HBV DNA positive rate of HBsAg negative donors was 0.19％(118/62000).HBV DNA of the viral load of positive specimens with＜20 IU/mL was higher than those with 20 to 99 IU/mL and ≥ 100 IU/mL(P＜0.05).HBV DNA of C style of the genotype of positive specimens was higher than B style and unsamples(P＜0.05).Univariate analysis found that HBV DNA positivity was mainly related to the history of intravenous drug use and risky sexual behavior,as well as the history of hepatitis B vaccination and blood transfusion(P＜0.05).According to the Logistic regression analysis,history of intravenous drug use and risky sexual behavior,and blood transfusion were risk factors for positive HBV DNA(OR＞1,P＜0.05),vaccination of hepatitis B vaccine was a protective factor for HBV DNA positivity(OR＜1,P＜0.05).Conclusion:The proportion of HBsAg in Nan'an area is relatively high,but there are still a small number of positive samples,the main genotype was type C,and history of intravenous drug use and risky risk behaviors,as well as history of blood transfusion were all risk factors for positive HBV DNA,vaccination of hepatitis B vaccine is protective factor for HBV DNA positivity.

Objective To explore the effect of sequential therapy with butylphthalide on the risk of post-stroke epilepsy(PSE)in patients with cerebral infarction.Methods The clinical data of patients with cerebral infarction hospitalized in Langfang People's Hospital from October,2016 to October,2022 were selected and analyzed.Patients receiving butylphthalide sequential treatment were included in the butylphthalide group,patients who were hospitalized at the same time with matching gender,age(±5 years),basic disease,clinical drug treatment scheme and follow-up period but did not receive butylphthalide treatment were included in the control group.The general clinical data,laboratory examination results on admission,and incidence of PSE in the two groups were compared,and multivariate Logistic regression was used to analyze the correlation between sequential therapy with butylphthalide and PSE occurrence in patients with cerebral infarction.Results A total of 1,200 patients were included,with 600 patients in each group.There was no significant difference in general clinical data such as sex,age,complications and living habits between the two groups(P＞0.05).There were no significant differences between the two groups in the patients distribution of TOAST classification,NIHSS score(P＞0.05).The incidence of PSE in butylphthalide group was significantly lower than that in control group(4.17％vs.7.83％,P＜0.05).The application of sequential treatment with butylphthalide was a protective factor for PSE occurrence in patients with cerebral infarction[OR=0.352,95％CI(0.151,0.821),P=0.016].Conclusion Sequential treatment with butylphthalide can reduce the risk of post-stroke epilepsy in patients with cerebral infarction.

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.

Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature