OBJECTIVE Identify the incentive and constraint factors of artificial intelligence （AI） application in the pharmaceutical field， and promote the application of AI in the field of pharmacy. METHODS Based on the technology acceptance model （TAM）， technology-organization-environment （TOE） framework， and diffusion of innovation theory （DOI）， a TAM-TOE-DOI integrated framework was constructed through a four-stage research process of “theoretical review → dimension mapping → mechanism integration → proposition development”. Combining the analytical pathways of the above three theories in AI application in pharmacy with the integration mechanisms and core propositions of the TAM-TOE-DOI， literature review and deductive reasoning were employed to systematically identify the incentive and constraint factors of AI application in pharmacy from three levels：micro （TAM）， meso （TOE）， and macro （DOI）， and to propose optimization strategies. RESULTS & CONCLUSIONS At the micro level， the efficiency transformation and quality improvement brought by AI technology were the main incentive factors for perceived usefulness， while technological complexity and algorithmic opacity were the main constraint factors for perceived ease of use. At the meso level， the completeness of technological infrastructure， the strength of top management support and innovation climate， as well as external institutional pressure and competitive driving forces were the core incentive factors， whereas scarcity of organizational resources and talent shortage were the main constraint factors. At the macro level， relative advantage and observability were typical incentive factors， while technological complexity was a typical constraint factor. China’s health administration， medical insurance authorities， and other relevant departments should coordinate efforts at the macro， meso， and micro levels to advance AI application in pharmacy： optimizing human-computer interaction and implementing tiered training programs at the micro level； reinforcing organizational support systems and capacity building at the meso level； dismantling data barriers and building social trust at the macro level. Differentiated implementation pathways should be developed for medical institutions at different tiers.

OBJECTIVE To systematically analyze the trends in the volume and value of out-licensing deals by Chinese biopharmaceutical companies over the past two decades， and to quantitatively identify factors associated with deal value， thereby providing an evidence base for policymakers and corporate managers. METHODS Based on the PharnexCloud database， information on out-licensing deals disclosed by Chinese biopharmaceutical companies between January 1， 2005 and December 31， 2025 was collected， and executed deals with disclosed specific financial terms were included for analysis. Descriptive statistical analyses of deal value， product characteristics and deal characteristics were performed using Stata SE 18.0； with the natural logarithm of deal value as the dependent variable， stepwise multiple regression models were constructed to examine the associations of product and deal characteristics with deal value. RESULTS A total of 210 out-licensing deals were included， with a cumulative deal value of approximately 214.151 billion dollars and a mean deal value of 1.020 billion dollars . The trading market expanded rapidly from 2020 onward， with the annual deal value reaching a record 95.687 billion dollars in 2025. Multiple regression analysis showed that the deal value of products at the drug discovery stage was significantly lower than that at the preclinical stage [regression coefficient （ β ） ＝－1.995， 95% confidence interval （CI）： －3.256 to －0.734， P ＜0.05 ] ； the deal value of oncology products was significantly higher than that of other therapeutic areas （ β ＝0.828， 95%CI： 0.224 to 1.431， P ＜0.05）； global licensing （ β ＝1.690， 95%CI： 1.107 to 2.273， P ＜0.05） and co-development arrangements （ β ＝0.849， 95%CI： 0.084 to 1.615， P ＜0.05） were significantly associated with higher deal value. CONCLUSIONS Out-licensing deals by Chinese biopharmaceutical companies have achieved significant growth in both volume and value over the past two decades. Oncology products， global licensing， and co-development arrangements are significantly and positively associated with higher deal value.

Objective:To investigate potential factors associated with nephrocalcinosis in children with X-linked hypophosphatemic rickets (XLH).Methods:A case-control study was conducted involving XLH children who were regularly followed up at Children′s Hospital of Nanjing Medical University, from January 2016 to January 2024.Patients diagnosed with nephrocalcinosis were assigned to the case group, and those without nephrocalcinosis served as controls.A retrospective analysis was performed to examine the correlation between nephrocalcinosis and laboratory parameters, as well as the diagnostic value of relevant factors.Multivariable Logistic regression was used to identify factors associated with nephrocalcinosis in children with XLH.Receiver operating characteristic (ROC) curves were plotted for the significant factors, and the areas under the curve (AUC) were compared using Delong′s test to evaluate differences in predictive performance.Results:Univariate analysis revealed significant differences between the case and control groups in serum calcium, urinary calcium, urinary calcium/creatinine ratio, urinary phosphorus, and renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmPi/GFR) (all P<0.05).However, multivariate logistic regression analysis identified only urinary calcium ( B=0.489, P=0.001) and TmPi/GFR ( B=-0.886, P=0.007) as independent predictors, while the urinary calcium/creatinine ratio was not statistically significant.The sensitivity, specificity, optimal cutoff value, and AUC for urinary calcium in predicting nephrocalcinosis were 0.842, 0.833, 0.614 mmol/L, and 0.851 ( P<0.01), respectively.For TmPi/GFR, the corresponding values were 0.900, 0.877, 0.573 mmol/L, and 0.875 ( P<0.01).The Delong test showed no significant difference in AUC between the combined indicator and TmPi/GFR ( Z=-1.555, P=0.120) or urinary calcium alone ( Z=-1.598, P=0.110). Conclusions:Urinary calcium and TmPi/GFR are significantly associated with nephrocalcinosis in children with XLH and demonstrate good predictive performance for early detection.The combination of these two indicators does not outperform either individual marker in diagnostic accuracy.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Objective:To investigate the different clinical characteristics and prognosis of patients with diabetic nephropathy (DN) accompanied by IgA deposition diagnosed by renal biopsy.Methods:The study was a retrospective cohort study. Clinical and pathological data of patients diagnosed with DN through renal biopsy in Beijing Anzhen Hospital affiliated to Capital Medical University from January 1, 2010 to March 31, 2023 were retrospectively collected. The clinical and pathological characteristics and prognosis of DN patients with IgA deposition and DN control group patients without IgA deposition were compared. Immunofluorescence staining was used to detect the intensity of galactose-deficient IgA1 (Gd-IgA1) staining in renal tissue of DN patients with DN IgA deposition, and grouping was performed according to whether the staining intensity was≥2+. Enzyme linked immunosorbent assay was used to detect the serum level of Gd-IgA1 in patients. A 50% decrease in estimated glomerular filtration rate (eGFR) from baseline or progression to end-stage renal disease within 5 years was defined as a renal endpoint event, and Kaplan-Meier survival analysis and Log-rank test were used to compare the difference in cumulative incidence of renal endpoint events between two groups of patients.Results:A total of 101 DN patients were enrolled in this study, including 68 males (67.3%) and 33 females (32.7%), with age of (52.2±10.3) years and a median follow-up time of 13.5(4.8, 26.3) months. There were 44 patients with IgA deposition (43.6%) and 57 patients without IgA deposition (56.4%). Compared with DN control group, Kaplan-Meier analysis showed that DN patients with IgA deposition had a higher cumulative incidence of renal endpoint within 5 years ( χ2=6.473, P=0.011). The proportion of positive glomerular Gd-IgA1 (KM55) staining in the DN patients with IgA deposition was 54.5% (24/44), and immunofluorescence examination showed consistent distribution of Gd-IgA1 and IgA in the glomerular mesangial and capillary regions. The serum level of Gd-IgA1 in the glomerular Gd-IgA1 positive patients was significantly higher than that in those negative patients [(6 296.4± 1 535.4) μg/L vs. (4 057.4±1 082.0) μg/L, t=-3.037, P=0.010]. In DN patients with IgA deposition, the age of the subgroup with endpoint events was younger [(42.8±6.9) years vs. (53.3±9.4) years, t=-3.440, P=0.002], the duration of proteinuria was shorter [6.0(1.0, 22.0) months vs. 12.0(10.0, 36.0) months, Z=-2.150, P=0.032], and the proportion of patients with glomerular Gd-IgA1 staining intensity ≥2+ was higher [Fisher'exact test, 30.8%(4/13) vs. 0(0/20), P=0.017]. Kaplan-Meier survival analysis showed that patients with glomerular Gd-IgA1 staining intensity≥2+ had a significantly higher cumulative incidence of renal endpoint events ( χ2=4.846, P=0.028). Conclusion:DN patients with glomerular IgA deposition and Gd-IgA1 positivity may be associated with worse prognosis.

Developmental dysplasia of the hip(DDH)is a common bone and joint disease in infants,the key to its prognosis lies in early diagnosis and treatment.Imaging is the main diagnostic modality for DDH.In recent years,artificial intelligence(AI)has developed rapidly,and the combination of AI and imaging techniques can be used for section positioning,automatic measurement of biological indicators,classification diagnosis and selection of treatment,it can improve diagnostic efficiency,develop treatment plans and effectively improve patient prognosis.This article will explain the progress of AI in the application of imaging technology for DDH.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

The number of patients with eye diseases in China is enormous,and the negative effects of these conditions,such as impaired visual function,psychological burdens,and restricted social participation,are becoming increasingly severe.Due to the limited and unevenly distributed ophthalmic resources,and the significant limitations of traditional diagnostic and therapeutic approaches in terms of accuracy and efficiency,there is an urgent need for more sensitive and efficient modalities.With the rapid advancement of artificial intelligence technology,ophthalmic diagnosis has entered a new stage of intelligent transformation.Facial photos,as a noninvasive and convenient medium,show unique advantages in eye disease diagnosis.Artificial intelligence systems based on facial photo analysis have been applied to the screening and diagnosis of conditions such as myopia,strabismus,ptosis,and thyroid eye disease,showing promising results.This review introduces the workflow of intelligent diagnosis for ocular diseases based on facial photographs,with a focus on recapitulating relevant research findings both domestically and internationally in recent years.It summarizes the innovative features and application advantages of intelligent diagnosis systems for eye diseases based on facial photos,analyzes the current technical bottlenecks and challenges in application,proposes corresponding countermeasures,and discusses future development directions,aiming to provide references and new insights for the intelligent screening and diagnosis of eye diseases.