OBJECTIVE To provide empirical basis for promoting the dynamic adjustment of the pharmaceutical care catalogue and the formulation of policies such as hierarchical payment of medical insurance. METHODS A multicenter cross- sectional survey method was adopted to conduct a questionnaire survey among 424 inpatients in 22 tertiary medical institutions in 12 prefecture-level cities of Hubei Province to evaluate their demand for pharmaceutical care， willingness to pay and preference for service forms. Combined with univariate and multivariate Logistic regression analysis， the influencing factors and key factors that affect patients’ willingness to pay for pharmaceutical care were identified. RESULTS Only 39.86% of the patients were aware of pharmaceutical care or pharmacists， and 89.62% of the patients hope to receive pharmaceutical care. Among the 16 types of pharmaceutical care， the patients surveyed had a relatively high recognition rate for guidance on drug usage and dosage， notification of medication precautions， and the identification， prevention and handling of adverse drug reactions. 96.70%， 95.30%， and 94.12% respectively expressed strong approval and approval. The demand for services such as insurance-related policy consultation， popular science on the mechanism of drug action， and assessment of the combined use of traditional Chinese and Western medicines was relatively low， with 61.65%， 68.47%， and 68.47% expressing strong approval and approval respectively. The positive influencing factors of willingness to pay were household monthly income ＞ 5 000 yuan （OR＝1.742）， awareness of pharmaceutical care or pharmacists （OR＝3.620）， and the desire to receive pharmaceutical care （OR＝4.686） （P＜0.05）， while self-rating health as “good” （OR＝0.390） was a negative influencing factor （P＜0.05）. Cardiovascular and cerebrovascular diseases （54.48%） and antihypertensive drugs （45.05%） were the service scenarios that the surveyed patients most hope to be covered. 85.14% of the patients preferred “service when xiaochnye@126.com needed”， with a single service duration of less than 10 minutes being appropriate （84.43%）， and the willingness to pay within 20 yuan being the main type （85.38%）. CONCLUSIONS Based on the characteristics of patients’ needs and payment behaviors， it is suggested that our country could consider establishing a hierarchical payment mechanism for pharmaceutical care， and focus on differentiated design in combination with diseases and medication situations. At the same time， the rights， responsibilities and service standards of resident pharmacists in the links such as medication reorganization and medical order review should be further clarified to comprehensively enhance the clinical value and policy operability of pharmaceutical care.

ObjectiveTo understand the status of parasitic infection in the food sold on market in Qingpu District of Shanghai, and to provide an evidence for the development of prevention and control strategies for parasitic infection applicable to Qingpu District. MethodsAquatic products, meat products and other foodstuffs sold on online shops, at farm product markets, supermarkets/foodstores and restaurants were sampled in Qingpu District, Shanghai, during 2015‒2023, based on the administrative division of Qingpu District. The parasitic infection in the food samples were examined using pressing method and digestion for detecting metacercariae in freshwater products and pickled products, using dissection microscopy for Anisakis larvae in seawater products, Taenia cysticercus and Trichinella encysted larvae in meat products. ResultsA total of 1 079 samples of food products were examined during 2015‒2023, with a total parasite infection rate of 13.44%. The total parasite infection rate of freshwater fish products was 3.40% (16/471), and the difference of parasite infection rates between different freshwater fish species was statistically significant (χ²=229.609, P=0.001). The total infection rate of Clonorchis sinensis was 3.18% (15/471), which had been detected in Pseudorasbora parva, Cyprinidae rhodeus, and Carassius auratus, with a positive rate of 77.78% (7/9), 50.00% (5/10) and 3.90% (3/77), respectively. Metorchis orientalis was detected in in Pseudorasbora parva, with a positive rate of 33.33% (3/9). The positive rate of Gnathostoma spinigerum (third-stage larvae) was 0.81%. Paragonimus metacercariae were not detected in the freshwater shrimps and crabs. The infection rate of seawater fish products was 26.46%. The difference of parasite infection rate in seawater fishes was statistically significant (χ²=109.181, P=0.001). A total of 53 pork and beef samples were tested, none was detected with Trichinella larva cysts, Taenia solium metacercariae, and Taenia saginata metacercariae. The total infection rate of pickled yellow mud snail products was 58.11% (43/74). Paragonimus metacercariae was not detected in any of the pickled aquatic product samples. ConclusionThere are different degrees of parasitic infection in freshwater products, seawater products and pickled aquatic products in Qingpu District of Shanghai. The risk of parasite infection from raw or undercooked foods is high. Health education on healthy dietary practices such as throughly cooked food should be strengthened for local residents.

Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues, and it constitutes a major global public health concern. Methylation modifications, including DNA methylation, histone methylation, and RNA m6A modification, represent reversible processes coordinately regulated by methyltransferases, demethylases, and binding proteins. In periodontitis, aberrant methylation modifications suppress Toll-like receptor 2 expression, leading to oral microbial dysbiosis. These modifications further disrupt normal immune regulatory functions through C-C motif chemokine ligands, Fc-γ receptor-mediated phagocytosis, and NF-κB signaling pathways, resulting in localized immune-inflammatory imbalance in periodontal tissues. In addition, various methylation modifications regulate the expression of Runt-related transcription factor 2 (RUNX2), osteoblast-specific transcription factor Osterix (OSX), and receptor activator of nuclear factor-κB ligand (RANKL), thereby interfering with osteoclast and osteoblast differentiation, disrupting bone homeostasis, and ultimately driving alveolar bone resorption. Methylation-related biomarkers demonstrate promising potential for periodontitis screening and prognostic evaluation. While numerous abnormally methylated sites have been identified in periodontitis, the precise signaling pathways and comprehensive epigenetic regulatory networks remain to be fully elucidated. This review systematically summarizes the functional roles of DNA methylation modifications in the pathogenesis of periodontitis and explores their potential value in etiological studies, diagnostic biomarker discovery, and targeted therapeutic interventions, with the aim of providing novel perspectives for periodontitis prevention and treatment strategies.

Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Rheumatoid arthritis (RA) represents a persistent autoimmune condition distinguished by a multifaceted etiology that encompasses both genetic and environmental factors. Recent progress in understanding the mechanisms behind RA pathogenesis has delved into the critical role of epigenetic regulatory processes, including DNA methylation, histone modifications, and the regulation by microRNAs (miRNAs). These findings provide new insights into the intricate nature of RA and pave the way for innovative therapeutic strategies. This review consolidates the latest developments in the epigenetic regulation of RA, concentrating on how these mechanisms affect the dysregulated signaling pathways associated with the disease. We analyze the roles of specific proteins that function as 'writers', 'erasers', and 'readers' in epigenetic modifications, highlighting their potential as targets for therapeutic intervention. Additionally, in view of the significance of miRNAs in the pathogenesis of RA, we deliberate on their involvement in disease progression and explore miRNA-based treatment strategies. By integrating these diverse epigenetic dimensions, this review offers a comprehensive epigenetic perspective on RA pathogenesis and identifies promising avenues for future research and therapeutic interventions.

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Purpose To establish and evaluate a high-speed fragment-induced penetrating liver injury model in pigs assisted by portable ultrasound.Materials and Methods With the aid of portable ultrasound,the lower edge of the liver at the end of expiration and the lower edge of the right chest at the end of inspiration of 10 Landrace pigs were positioned on the body surface.Then the sighting line was traced to determine the direction of projection and the sighting point.High-speed(about 627 m/s)fragments were projected through an experimental ballistic gun to induce penetrating liver injury.Blood pressure,heart rate,respiratory rate,pulse oxygen saturation and other physiological indexes were measured 15 minutes before shooting and 20 minutes after shooting.20 minutes after injury,the liver injury and the degree of injury were examined by ultrasound.After injury,the liver injury and abdominal fluid accumulation were observed by on-site portable ultrasound,and the size of liver trauma,liver injury grade,abdominal fluid accumulation location and maximum depth were recorded.The degree of liver injury was evaluated by comparison with the gross pathological results.Results Nine out of ten pigs were successfully modeled.The success rate of penetrating liver injury induced by fragments was 90%(9/10),other organ injury in abdominal cavity was 22.22%(2/9),and diaphragm penetrating injury was 22.22%(2/9),which did not occur obvious hemopneumothorax.After injury,the systolic blood pressure,diastolic blood pressure,and pulse oxygen saturation of the pigs decreased[(132.44±12.65)mmHg vs.(103.33±33.43)mmHg,(96.44±12.27)mmHg vs.(70.89±24.21)mmHg,(89.44±8.49)%vs.(76.00±13.41)%;t=2.440,2.651,4.084,all P<0.05],and the heart rate increased[(94.00±17.39)times/min vs.(139.89±37.21)times/min;t=3.534,P<0.05].Within 20 minutes after modeling,portable ultrasound images showed that the liver injury was a patchy,heterogeneous,slightly strong echo area with clear and irregular boundary,and the continuity of the local liver capsule was interrupted.The ascites appeared in the abdominal cavity with the maximum depth of(4.16±1.35)cm.The American association for the surgery of trauma(AAST)liver injury grading of gross pathology after the animals were killed showed that there were 6 cases of grade Ⅱ and 3 cases of grade Ⅲ.Along the fragment projection direction,the short diameter measured by ultrasound was positively correlated with the depth of gross pathological laceration(r=0.945,P<0.001).Compared with the gross specimen,the accuracy rate of ultrasonic AAST grading of liver injury was 88.89%(8/9).Conclusion The model of high-speed fragment-induced liver injury in pigs assisted by portable ultrasound is accurate and stable,and portable ultrasound can effectively evaluate the penetrating liver injury,which provides a basis for the treatment of liver firearm injury.

Objective:To investigate the association between plasma anti-Müllerian hormone(AMH) levels and ischemic stroke.Methods:In this case-control study, 93 ischemic stroke patients were randomly selected as the case group from a study on the prevention and treatment of metabolic syndrome, which was conducted in 2018-2019 in Changshu, Jiangsu Province, while 372 nonischemic stroke patients were selected as the control group according to the principle of 1∶4 matching.An enzyme-linked immunosorbent assay was used to measure plasma AMH levels.The conditional logistic regression model and restricted cubic spline were used to analyze the relationship between AMH levels and ischemic stroke.Results:A total of 465 subjects with an average age of (68.7±7.4)years were included in this study, of whom 215(46.2%)were men and 250(53.8%)were women.According to our conditional Logistic regression analysis, the risk of ischemic stroke was reduced by 44% for every unit increase in the log-AMH level( OR=0.56, 95% CI: 0.37-0.85)in the overall population after multivariate adjustment.Compared with the tertile with the lowest AMH level, the risk of ischemic stroke in the tertile with the highest AMH level decreased significantly( OR=0.37, 95% CI: 0.19-0.69). When subgrouped by sex, the tertiles with the highest AMH levels were associated with a 66% lower risk of ischemic stroke in men( OR=0.34, 95% CI: 0.13-0.88)and a 64% lower risk of ischemic stroke in women( OR=0.36, 95% CI: 0.15-0.87), compared with the tertiles with the lowest AMH levels.The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between plasma AMH levels and ischemic stroke both in the general population and in male or female population( Pvalues for linear trends were 0.0002, 0.008 and 0.007, respectively). Conclusions:Higher plasma AMH levels decrease the risk of ischemic stroke with a dose-response pattern.