This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

Atherosclerosis （AS） is a chronic and inflammatory vascular disease. Macrophages are common immune cells and play an important role in the development of AS. In recent years， research has found that the formation of AS plaques is closely related to pathological and physiological processes such as macrophage polarization， energy metabolism， and lipid phagocytosis. This review aims to summarize the mechanism of macrophages in the development of AS， and to explore potential therapeutic methods for delaying AS by regulating macrophages， providing new ideas for the treatment and research of AS.

[摘 要] 目的：探讨环指蛋白8（RNF8）对子宫内膜癌（EC）细胞顺铂（CDDP）敏感性的影响及可能机制。方法：基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异；采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理，按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理，并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果：RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50，抑制克隆形成，并进一步增强CDDP诱导的凋亡；同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高，BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡，并降低细胞活力。结论：RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性；敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。

Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

BACKGROUND: The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients. METHODS: 104 EGFR-mutated NSCLC-LM patients who received IP treatment at Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School from January 2018 to June 2024 were analyzed retrospectively. Clinical parameters, treatment regimens, and survival outcomes were collected. The overall survival (OS), progression-free survival (PFS), clinical response rate and adverse events (AEs) were evaluated. RESULTS: The cohort demonstrated a median PFS of 9.6 months and OS of 13.0 months with 6-month and 1-year OS rates of 80.8% and 56.5%, respectively. Clinical response was observed in 77.9% of patients. The common AEs were myelosuppression (58.7%) and elevation of hepatic aminotransferases (25.0%). Nine (8.7%) patients experienced grade 4 myelosuppression and recovered to normal after receiving symptomatic treatment. Subgroup analyses revealed prolonged OS in patients with Karnofsky performance status (KPS) ≥60 versus <60 (14.4 vs 9.0 months, P=0.0022) and those receiving Bevacizumab therapy versus not (19.2 vs 10.5 months, P=0.0011). CONCLUSIONS IP exhibits promising efficacy and manageable toxicity in EGFR-mutated NSCLC-LM patients. When combined with Bevacizumab, it exerts synergistic antitumor effects with the potential to further improve clinical outcomes.
Humans ; Pemetrexed/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Male ; Female ; Middle Aged ; Lung Neoplasms/pathology* ; ErbB Receptors/genetics* ; Aged ; Mutation ; Adult ; Retrospective Studies ; Injections, Spinal ; Meningeal Neoplasms/genetics* ; Treatment Outcome ; Aged, 80 and over

BACKGROUND: Heavy metals are significant risk factors for kidney function. Numerous studies have shown that exposure to heavy metals negatively correlates with kidney function through oxidative stress pathways, and serum α-klotho is linked to oxidative stress. However, the role of α-klotho in the relationship between blood lead, mercury, and kidney function remains unclear. METHOD: This study evaluated the mediating role of alpha-klotho in the relationship between lead, mercury and renal function, using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) in U.S. adults aged 40-79. The sample included 11,032 participants, with blood lead, mercury, α-klotho, and other relevant covariates measured. Inductively coupled plasma mass spectrometry was used to assess blood lead and mercury levels, and enzyme-linked immunosorbent assay (ELISA) was employed to measure serum α-klotho. Kidney function was evaluated using estimated glomerular filtration rate (eGFR) based on creatinine levels. Multivariable linear regression was conducted to analyze the relationships between blood lead, mercury, α-klotho, and eGFR. A mediation analysis model was used to assess whether α-klotho influenced these associations. RESULTS: We observed a significant association between blood lead and eGFR. Mediation analysis revealed that α-klotho accounted for 12.76% of the relationship between serum lead and eGFR in the NHANES population. Subgroup analysis showed that α-klotho mediated 12.43%, 6.87%, 21.50% and 5.44% of the relationship between blood lead and eGFR in women, middle-aged adults (40-59 years old), without cardiovascular disease and hypertension, respectively. However, α-klotho did not mediate the relationship between blood mercury and eGFR in terms of gender or age. This newly identified pathway may provide valuable insights for the prevention and treatment mechanisms related to kidney function impairment. CONCLUSION We found that blood lead was associated with renal function. According to the results of subgroup analysis, for blood lead, serum α-klotho mediated the association in females, middle aged 60-79 years. The relationship between blood mercury and renal function was not clinically significant, and serum α-Klotho mediated the relationship between blood mercury and renal function without significant clinical significance.
Humans ; Middle Aged ; Lead/blood* ; Female ; Klotho Proteins ; Male ; Aged ; Adult ; Mercury/blood* ; Glomerular Filtration Rate ; Nutrition Surveys ; United States ; Kidney/physiology* ; Glucuronidase/blood* ; Environmental Pollutants/blood*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Objective:To construct a Harvard cancer index-based risk predictive model for perioperative venous thromboembolism (VTE) in elderly patients with femoral neck fracture and assess its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 610 elderly patients with femoral neck fracture admitted to Peking Union Medical College Hospital between January 2013 and December 2022, including 193 males and 417 females, aged 60-99 years [(77.3±9.0)years]. The patients were divided into VTE group ( n=125) and non-VTE group ( n=485) according to occurrence of VTE during the perioperative period. The two groups were compared in terms of gender, age, body mass index, smoking status, alcohol consumption, time from fracture to admission, surgical waiting time, comorbidities, perioperative electrolyte disorders, past or present history of malignancy, past history of deep vein thrombosis (DVT) or pulmonary embolism (PE), and preoperative use of oral anticoagulants. Univariate analysis and multivariable stepwise Logistic regression analysis were conducted to evaluate and identify independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. A perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed using the Harvard cancer index: (1) assigning a risk score to each variable according to the corresponding conversion criteria of the Harvard cancer index and risk score, based on the magnitude of their ORs; (2) determining the exposure rate of each risk factor based on the population distribution observed in this study; (3) calculating the average population risk score; (4) computing the individual VTE risk score; (5) deriving the ratio (X) of each individual ′s VTE risk score to the population average. Based on the Harvard cancer index classification criteria for disease risk levels, individual VTE risk categories were determined. The predictive performance of the risk stratification was evaluated by comparing the incidence of VTE across different risk levels. The predictive performance of the model was evaluated based on sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC). The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) test and internal validation was performed using the bootstrap resampling method with 1000 iterations. Results:Univariate analysis showed that gender, age, time from fracture to admission, surgical waiting time, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, history of DVT or PE, and preoperative use of oral anticoagulant drug were moderately associated with the occurrence of VTE in elderly patients with femoral neck fracture ( P<0.10). Multivariable stepwise logistic regression analysis demonstrated that female gender ( OR=2.26, 95% CI 1.34, 3.80, P<0.01), time from fracture to admission>1 day ( OR=3.70, 95% CI 2.24, 6.12, P<0.01), surgical waiting time>70 hours ( OR=2.06, 95% CI 1.29, 3.30, P<0.01), previous cerebral infarction ( OR=3.78, 95% CI 1.04, 13.76, P<0.05), stroke within the past month ( OR=11.57, 95% CI 1.21, 110.44, P<0.05), Alzheimer′s disease ( OR=3.26, 95% CI 1.12, 9.49, P<0.05), primary Parkinson ′s syndrome ( OR=3.47, 95% CI 1.22, 9.85, P<0.05), previous hysterectomy with bilateral adnexectomy ( OR=4.75, 95% CI 2.09, 10.80, P<0.01), perioperative electrolyte disorders ( OR=2.73, 95% CI 1.39, 5.35, P<0.01), and preoperative oral anticoagulant use ( OR=3.86, 95% CI 1.18, 12.67, P<0.05) were significantly associated with the occurrence of perioperative VTE in elderly patients with femoral neck fracture. Based on the above 10 risk factors, a perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed with the Harvard cancer index. The formula was as follows: X=[10×(female gender)+25×(time from fracture to admission>1 day)+10×(surgical waiting time>70 hours)+25×(previous cerebral infarction)+50×(stroke within the past month)+25×(Alzheimer′s disease)+25×(primary Parkinson′s disease)+25×(previous hysterectomy with bilateral adnexectomy)+10×(perioperative electrolyte disorders)+25×(preoperative use of oral anticoagulant drug)]/33. Individualized VTE risk was classified into five levels: very low, low, moderate, high, and very high, with corresponding VTE rates of 4.8%, 11.8%, 14.9%, 32.3%, and 73.5%, respectively ( χ2=87.71, P<0.01). The VTE risk predictive model demonstrated an AUC of 0.74 (95% CI 0.69, 0.79, P<0.01), with a sensitivity of 63.2% and specificity of 74.8%. The H-L goodness-of-fit test indicated satisfactory model calibration ( P>0.05). The internal validation with the bootstrap method confirmed that the AUC remained 0.74. Conclusions:Female gender, time from fracture to admission>1 day, surgical waiting time>70 hours, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, and preoperative use of oral anticoagulant drug are independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. Based on these factors, the perioperative VTE risk predictive model constructed using the Harvard cancer index demonstrates good clinical predictive value. Individualized VTE risk stratification can effectively identify high-, intermediate-, and low-risk populations, providing a valuable reference for tailoring anticoagulant prophylaxis strategies and enhancing postoperative surveillance.

Objective:To analyze the changes in the incidence trend of liver cancer in Taizhou of Jiangsu Province, from 2012 to 2020 and provide reference for tumor prevention and control and management.Methods:Liver cancer incidence data from 2012 to 2020 were extracted from the Taizhou Center for Disease Control and Prevention's tumor registry system. Demographic data were used to calculate the crude incidence rate, age-standardized incidence rate (ASIR), Chinese age-standardized incidence rate (CASIR; based on China's 2010 standard population), and world age-standardized incidence rate (WASIR; based on Segi's world standard population). The Joinpoint regression model was applied to identify inflection points in liver cancer incidence trends during 2012-2020, and annual percentage change (APC) with average annual percentage change (AAPC) were calculated.Results:In 2020, the crude incidence ratio (CIR) of liver cancer in Taizhou was 34.6 per 100 000, with CASIR and WASIR at 19.6 per 100 000 and 14.9 per 100 000, respectively. From 2012 to 2020, the male-to-female ratio of new liver cancer cases was 2.94∶1 (10 455 males vs. 3 559 females), with male incidence consistently higher than female. Overall liver cancer incidence in Taizhou initially increased and then decreased after 2017 (2012-2017: APC=6.4%, P=0.014; 2017-2020: APC=-9.5%, P=0.035), peaking at a CASIR of 26.2 per 100 000 in 2017. The trend in male incidence mirrored the overall pattern, rising before 2017 and declining thereafter (2012-2017: APC=6.2%, P=0.005; 2017-2020: APC=-9.0%, P=0.016). Female incidence remained relatively stable (2012-2016: APC=11.0%, P=0.054; 2016-2020: APC=-6.5%, P=0.130). Conclusions:Liver cancer incidence in Taizhou increased before 2017 and declined thereafter, with 2017 as the turning point. Amid population aging, liver cancer remains a persistent public health challenge requiring sustained attention.