Hepatobiliary and pancreatic tumors are common types of digestive system disorders， and their complex pathogeneses have led to difficulties in early diagnosis and a high metastasis rate， with persistently high incidence and mortality rates in China， which greatly affects the quality of life and prognosis of patients. Studies have shown that heparanase （HPSE）， as a key effector molecule in matrix remodeling， plays a crucial regulatory role in tumor invasion and metastasis and microenvironment remodeling， and it is significantly associated with clinical prognosis. This article reviews the molecular mechanism of HPSE in hepatobiliary and pancreatic tumors， in order to provide a strong scientific basis for developing diagnostic markers and targeted interventions for hepatobiliary and pancreatic tumors.

Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction， posing a serious threat to human health. The cyclic GMP-AMP synthase （cGAS）-stimulator of interferon genes （STING） signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development， progression， and treatment of various diseases such as viral hepatitis， nonalcoholic fatty liver disease， liver fibrosis， and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation， autophagy， antiviral response， and oxidative stress， analyzes its molecular function in liver diseases， and explores its application prospect as a potential target for the treatment of liver diseases， in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.

AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

Accurate prediction of drug-induced adverse drug reactions (ADRs) is crucial for drug safety evaluation, as it directly impacts public health and safety. While various models have shown promising results in predicting ADRs, their accuracy still needs improvement. Additionally, many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints, which can introduce bias. To address these challenges, we propose ToxBERT, an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system (SMILES) representations. Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve (AUROC) scores of 0.839, 0.759, and 0.664 for predicting drug-induced QT prolongation (DIQT), rhabdomyolysis, and liver injury, respectively, outperforming previous studies. Furthermore, ToxBERT can identify drug substructures that are closely associated with specific ADRs. These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

Accurate prediction of drug-induced adverse drug reactions(ADRs)is crucial for drug safety evaluation,as it directly impacts public health and safety.While various models have shown promising results in predicting ADRs,their accuracy still needs improvement.Additionally,many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints,which can introduce bias.To address these challenges,we propose ToxBERT,an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system(SMILES)representations.Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve(AUROC)scores of 0.839,0.759,and 0.664 for predicting drug-induced QT prolongation(DIQT),rhabdomyolysis,and liver injury,respectively,outperforming previous studies.Furthermore,ToxBERT can identify drug substructures that are closely associated with specific ADRs.These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

Objective To clarify the active ingredients and the potential molecular mechanism of Guben Qushi Huayu Prescription in treating psoriasis recurrence.Methods An ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was applied to analyze the whole formula and the constituents absorbed into blood of Guben Qushi Huayu Prescription,and molecular docking technology was used to study the binding affinity of the constituents absorbed into blood with psoriasis-related immunomodulatory proteins such as CD69 and CD103 proteins.Results Mass spectrometry analysis identified 21 active ingredients such as paeoniflorin in Guben Qushi Huayu Prescription,including several known anti-inflammatory and immunomodulatory compounds.Analysis of the constituents absorbed into blood identified 11 ingredients,including paeoniflorin,that may affect the course of psoriasis through blood circulation.Molecular docking studies revealed that the constituents absorbed into blood,including astilbin,isoastilbin,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,helicine,paeoniflorin,ononin,all had high binding affinities with CD69 and CD103 proteins.Conclusion This research reveals the main active ingredients of Guben Qushi Huayu Prescription and their potential mechanism for regulating the recurrence of psoriasis by mass spectrometry and molecular docking technology,contributing to providing scientific basis for further pharmacological research and clinical application.

Objective To identify the key influencing factors and role mechanisms of large-scale medical equip-ment allocation decision-making in public hospitals,and to provide a reference basis for optimizing resource alloca-tion strategies.Methods Through searching the literature related to large-scale medical equipment decision-making in public hospitals and combing the policies,the system of decision-making influencing factors was initially screened.The Delphi method and decision-making trial and evaluation laboratory method were used to obtain the key influencing factors of equipment allocation decision-making and to determine the interaction effects among the factors.Results A total of seven cause factors and nine effect factors were screened.Among them,cost-benefit analysis,equipment technical performance,and evaluation of similar equipment were the top three key drivers;leadership emphasis,equipment market price,and equipment supporting facilities were the top three key con-straints.Conclusion Priority be given to strengthening the management of driving factors,mainly by conducting a full-cycle assessment of cost-effectiveness,paying attention to the clinical value output of equipment technical performance,and monitoring regionally similar equipment.A dynamic response mechanism for constraints should be established,mainly to strengthen leadership decision-making,implement a centralized procurement price nego-tiation model and improve the pre-assessment system for ancillary facilities.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

Objective To identify the key influencing factors and role mechanisms of large-scale medical equip-ment allocation decision-making in public hospitals,and to provide a reference basis for optimizing resource alloca-tion strategies.Methods Through searching the literature related to large-scale medical equipment decision-making in public hospitals and combing the policies,the system of decision-making influencing factors was initially screened.The Delphi method and decision-making trial and evaluation laboratory method were used to obtain the key influencing factors of equipment allocation decision-making and to determine the interaction effects among the factors.Results A total of seven cause factors and nine effect factors were screened.Among them,cost-benefit analysis,equipment technical performance,and evaluation of similar equipment were the top three key drivers;leadership emphasis,equipment market price,and equipment supporting facilities were the top three key con-straints.Conclusion Priority be given to strengthening the management of driving factors,mainly by conducting a full-cycle assessment of cost-effectiveness,paying attention to the clinical value output of equipment technical performance,and monitoring regionally similar equipment.A dynamic response mechanism for constraints should be established,mainly to strengthen leadership decision-making,implement a centralized procurement price nego-tiation model and improve the pre-assessment system for ancillary facilities.