Breast cancer is a malignant tumor that occurs in the glandular epithelium of the breast, and it is one of the most common tumors that seriously affect the physical and mental health of women. With the aggravation of population aging, the incidence of breast cancer in the elderly has increased year by year in recent years. Elderly patients with breast cancer often have a variety of underlying diseases, and their prognosis is usually related to many factors such as cancer staging, cancer classification, treatment status and health status, with a significant difference in survival rate among patients. Due to the unique clinical and pathological characteristics of elderly patients with breast cancer compared to young and middle-aged patients, there are many studies on the treatment of elderly breast cancer patients in the past, and there are few reviews on the influencing factors of prognosis in elderly patients. This paper reviews the research progress of influencing factors of prognosis in elderly patients with breast cancer from the aspects of clinicopathological factors, treatment options and prognosis factors, in order to provide a reference for clinical determination of treatment options for elderly patients with breast cancer in the future.

Objective: To assess the effect of 12-year-old children s pit and fissure sealants on the health of first permanent molars, so as to provide evidence for optimizing caries prevention strategies among children. Methods: In March 2025, a cluster random sampling method was used to conduct oral examinations on 965 students aged 12 from Chengdu s 2021 Comprehensive Intervention Program for Pediatric Oral Diseases. Data from the Comprehensive Intervention System for Children s Oral Diseases were referenced. Participants were divided into a sealed group ( n =755) and an unsealed group ( n =210) based on whether they had received sealants on their first permanent molars. Chi square test or analysis of variance were used to compare indicators such as caries incidence, new caries detection rate, and new caries mean (DMFT increment) between the two groups Results: The sealed group showed significantly lower caries incidence, new caries detection rate, and new caries mean (33.38%, 17.65%, 0.59±1.00) compared to the unsealed group (43.81%, 24.70%, 0.87±1.22)( χ 2/F =7.79, 18.26, 9.55, all P <0.05). However, no significant difference was found in the filled teeth ratio between the two groups (20.38% , 20.16%; χ 2=0.01, P =0.94). In girls, the sealed group exhibited significantly lower caries incidence, new caries detection rate, and new caries mean (36.78%, 20.99%, 0.69± 1.10 ) than the unsealed group (57.55%, 33.52%, 1.15±1.29) ( χ 2/F =14.42, 23.76, 10.92, all P <0.05), whereas no significant differences were observed between boys in the sealed (30.47%, 14.85%, 0.50±0.89) and unsealed groups (29.81%, 16.18%, 0.59± 1.08) ( χ 2/F =0.02, 0.41, 0.74, all P >0.05). Boys had significantly lower new caries detection rates and new caries means than girls in both groups ( χ 2/F =16.20, 6.94; 29.93, 11.84, all P <0.05). In urban areas, the sealed group had lower new caries detection rates and new caries means (19.37%, 0.68±1.04) than the unsealed group (24.66%, 0.90±1.20) ( χ 2/F =6.86, 3.94, both P <0.05). In suburban areas, all indicators for the sealed group (24.71%, 13.77%, 0.42±0.87) were significantly lower than those for the unsealed group (38.81%, 24.77%, 0.82±1.28) ( χ 2/F =5.28, 15.36, 6.00, all P <0.05). Indicators from specialized dental institutions (11.25%, 4.81%, 0.16±0.56) were significantly lower than those from county level or above general hospitals (33.33%, 19.11%, 0.38±1.00) and primary healthcare institutions (37.59%, 19.24%, 0.67±1.05) ( χ 2/F =20.99, 34.31, 21.08 , all P <0.01). Conclusions The 12-year-old children s pit and fissure sealants effectively reduce the caries incidence in first permanent molars, particularly showing significant effectiveness in girls and suburban children. Intervention strategies should be optimized according to gender.

We examined the longitudinal hypothalamic morphology in the progression of mild cognitive impairment (MCI). We used multivariable linear modelling to differentiate the structural volumetric change in the hypothalamic nuclei in nine females who developed MCI after 5 years and 61 healthy controls. We found significantly decreased left anterior-inferior (p<0.01), left anterior-superior (p<0.05), and left posterior (p<0.01) hypothalamic regions among females with MCI compared to healthy controls. There was also a significant asymmetry at the anterior-superior hypothalamus (p<0.05) in MCI females than in healthy controls. Thus, the degradation of the specific left hypothalamic subregions and leftward lateralization over time highlight the impact of early- stage MCI on the morphology of hypothalamus.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

OBJECTIVE To provide a reference for pharmaceutical care in patients with ulcerative colitis （UC） and ankylosing spondylitis （AS） who developed pustular psoriasis induced by infliximab. METHODS Clinical pharmacists participated in the pharmaceutical care process of a patient with UC and AS who developed pustular psoriasis after using infliximab. The clinical pharmacists determined， using Naranjo’s Scale， that the correlation between the patient’s pustular psoriasis and infliximab was “likely”. Regarding the patient’s development of pustular psoriasis after using infliximab， the clinical pharmacists recommended discontinuing infliximab and switching to Upadacitinib extended-release tablets. For the patient’s skin allergic reaction after using upadacitinib， the clinical pharmacists advised continuing the use of upadacitinib and closely monitoring any potential adverse reactions during the treatment period. RESULTS The clinicians adopted the clinical pharmacists’ recommendation. Following the treatment， the patient’s symptoms were significantly alleviated， and the patient was discharged with medication. The follow-up after discharge showed that the treatment was effective and well-tolerated. CONCLUSIONS The clinical pharmacists analyzed the causal relationship between infliximab and pustular psoriasis. Through pharmaceutical care measures such as dynamic monitoring of skin lesions， evaluation of treatment responses， and optimization of drug regimens， they assisted the physicians in formulating an individualized medication plan， ensuring the safety and efficacy of the patient’s medication use.

BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

OBJECTIVE:Although wearable electronic devices have demonstrated potential utility as intervention tools to enhance physical activity,comprehensive evaluations of their specific effects on the healthy adolescent population remain scarce.Consequently,this article aims to systematically explore and summarize the impact of interventions based on wearable electronic devices on the physical activity and sedentary behavior of healthy adolescents,thereby providing more precise and reliable evidence-based support for public health practices. METHODS:Randomized controlled trials assessing the effects of wearable electronic device-based interventions on the physical activity and sedentary behavior of healthy adolescents were retrieved from databases including Web of Science,PubMed,Scopus,The Cochrane Library,and EBSCO.Meta-analysis was conducted using Review Manager 5.4 and Stata 17,evaluating the effects of interventions on physical activity and sedentary behavior through the standardized mean difference.To ensure the robustness of the research findings,a Leave-One-Out sensitivity analysis was conducted,and subgroup analyses were carried out to explore the potential influence of different factors on the results.The review protocol was registered with the International Prospective Register of Systematic Reviews(CRD42023406645). RESULTS:(1)Twelve publications were ultimately included,consisting of three randomized controlled trials and nine cluster-randomized controlled trials,involving a total of 4 933 healthy adolescents.(2)Meta-analysis results revealed that interventions based on wearable electronic devices had a positive effect on moderate to vigorous physical activity[standardized mean difference(SMD)=0.10;95%confidence interval(CI):0.04 to 0.17;P<0.05).However,the interventions did not significantly improve low-intensity physical activity(SMD=-0.15;95%CI:-0.32 to 0.02;P>0.05),daily step count(SMD=0.13;95%CI:-0.65 to 0.91;P>0.05),and sedentary behavior(SMD=0.00;95%CI:-0.09 to 0.09;P>0.05).(3)Subgroup analyses indicated that short-term interventions(≤12 weeks)(SMD=0.11;95%CI:0.03 to 0.18;P=0.008),studies using pedometers worn at the waist or hip(SMD=0.10;95%CI:0.04 to 0.17;P=0.002),and experiments registered at clinical trial centers(SMD=0.11;95%CI:0.04 to 0.17;P=0.001)had a more significant effect on enhancing daily moderate to vigorous physical activity. CONCLUSION:The current evidence suggests that interventions based on wearable electronic devices possess certain advantages in enhancing the daily moderate-to-vigorous physical activity of healthy adolescents.It is recommended that interventions not exceeding 12 weeks and utilizing pedometers positioned at the waist or hip may yield more favorable results.However,the effects of these interventions on daily step count,low-intensity physical activity,and sedentary behavior exhibit some limitations.Consequently,future investigations necessitate higher-quality,larger-scale randomized controlled trials for further validation.