Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

The establishment of modern biliary surgery system, alongside pivotal scientific paradigm shifts, has heralded a new era featured by precision, personalization, life-cycle care, and multidisciplinary management in the treatment of both benign and malignant biliary diseases. However, two formidable challenges persist in haunting the treatment of biliary diseases: (1) The refinement of surgical techniques has reached a plateau in reducing the disability associated with benign biliary conditions and in improving survival outcomes in biliary tract cancers; (2) Traditional evidence-based clinical studies have shown limited power in addressing complex dilemmas, such as determining whether to excise or preserve pathological gallbladders or selecting the optimal biliary drainage strategy. Consequently, the authors propose the conceptual framework of “biliary ecosystem”. In this model, diverse and abundant cholangiocytes represent forest, while blood vessels, nerves, and lymphatic vessels serve as nurturing soil, biliary stem cells function as seeds, bile flows like river network, and hepatocytes mark the river′s origins. Both benign and malignant biliary diseases exhibit significant spatiotemporal dynamics. The bile ducts form the “macro” environment, bile constitutes the “sub-macro” environment, and diverse cellular niches create the microenvironment. Specific pathological biliary conditions are shaped by intricate regulatory mechanisms that operate across these three tiers. Within the biliary ecosystem, cellular subpopulations exist remarkable diversity with states of homeostasis, oscillation, perturbation, or imbalance, underpinned by complex signaling networks. This holistic approach allows us to reframe and critically examine the pressing scientific issues confronting biliary tract diseases. Based on this framework, the authors distill key scientific questions and offer preliminary recommendations for embracing the paradigm shift. The authors anticipate that this conceptual model will promote interdisciplinary integration and accelerate clinical and translational researches.

After 50 years of clinical development， endoscopic retrograde cholangiopancreatography （ERCP） has become the preferred method for the clinical diagnosis and treatment of cholangio-pancreatic duct diseases； however， the major postoperative complications of ERCP， such as pancreatitis， hemorrhage， and perforation， are still a difficult issue faced by clinicians， and postoperative perforation is associated with an extremely high risk of death. Therefore， it is very important to explore the risk factors for perforation after ERCP， make a definite diagnosis of perforation in a timely manner， and formulate precise prevention and treatment measures. By reviewing a large number of articles， this article summarizes the influencing factors for perforation after ERCP and related diagnosis and treatment measures.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

OBJECTIVE To further standardize the dispensing management standard of intravenous infusion drugs for clinical trials in pharmacy intravenous admixture services （PIVAS）， and provide reference for medical institutions to provide high-quality pharmaceutical services. METHODS Initiated by PIVAS Group， Hospital Pharmacy Professional Committee， Shanghai Pharmaceutical Association， jointly led by Longhua Hospital， Shanghai University of Traditional Chinese Medicine and Shanghai Geriatric Medical Center， a writing group was established by PIVAS experts from multiple medical institutions to discuss the basic requirements and dispensing process of intravenous infusion drugs for clinical trials in PIVAS. The experts from the leading unit sorted out， summarized， analyzed， fed back and revised the opinions， and finally reached Expert Consensus on Dispensing Management of Intravenous Infusion Drugs for Clinical Trials in PIVAS. RESULTS & CONCLUSIONS The main contents of this consensus include information management， operation process， fund management and document management of intravenous infusion drugs for clinical trials in PIVAS. This consensus establishes a more standardized model for dispensing management of intravenous infusion drugs for clinical trials in PIVAS， by standardizing clinical trail drug management operational procedures， accurately recording and preserving drug-related information， with the aim of achieving standardized and meticulous management of PIVAS’s receipt of clinical trial drugs.

The establishment of modern biliary surgery system, alongside pivotal scientific paradigm shifts, has heralded a new era featured by precision, personalization, life-cycle care, and multidisciplinary management in the treatment of both benign and malignant biliary diseases. However, two formidable challenges persist in haunting the treatment of biliary diseases: (1) The refinement of surgical techniques has reached a plateau in reducing the disability associated with benign biliary conditions and in improving survival outcomes in biliary tract cancers; (2) Traditional evidence-based clinical studies have shown limited power in addressing complex dilemmas, such as determining whether to excise or preserve pathological gallbladders or selecting the optimal biliary drainage strategy. Consequently, the authors propose the conceptual framework of “biliary ecosystem”. In this model, diverse and abundant cholangiocytes represent forest, while blood vessels, nerves, and lymphatic vessels serve as nurturing soil, biliary stem cells function as seeds, bile flows like river network, and hepatocytes mark the river′s origins. Both benign and malignant biliary diseases exhibit significant spatiotemporal dynamics. The bile ducts form the “macro” environment, bile constitutes the “sub-macro” environment, and diverse cellular niches create the microenvironment. Specific pathological biliary conditions are shaped by intricate regulatory mechanisms that operate across these three tiers. Within the biliary ecosystem, cellular subpopulations exist remarkable diversity with states of homeostasis, oscillation, perturbation, or imbalance, underpinned by complex signaling networks. This holistic approach allows us to reframe and critically examine the pressing scientific issues confronting biliary tract diseases. Based on this framework, the authors distill key scientific questions and offer preliminary recommendations for embracing the paradigm shift. The authors anticipate that this conceptual model will promote interdisciplinary integration and accelerate clinical and translational researches.

This article explored the strategies of promoting access to medicines for rare diseases with digital and intelligent transformation technology in China. It summarized the mature, global-oriented, digital and intelligent transformation supported platforms for promoting rare disease research, technology and product development, as well as diagnosis and treatment information sharing in typical countries and region. This was followed with analyses of the challenges of access to medicines for rare diseases in China. It also systematically reviewed a range of policies implemented in China intended to promote access to medicines for rare diseases, and the digital and intelligent solutions to promote access to medicines for rare diseases at national and regional levels. The authors proposed that the central government agencies and their technical support institutions take a lead to construct a patient-centered dynamic and decentralized national big data sharing platform for rare diseases registry and research, medicines development, production and supply, access to care and medicines, payment and security, utilization surveillance in China. With the support of digital and intelligent technologies, this national platform would be able to link multiple stakeholders to achieve integrated analysis of big data, as well as international sharing and exchange, which will help to effectively and efficiently promote access to medicines for rare diseases in China.

BackgroundCurrently， the problem of depressed mood in college students is becoming more prominent. The experience of childhood maltreatment is a significant contributor to depression among college students. Although the association between the two has been confirmed， the specific psychosocial mechanisms underlying how childhood maltreatment affects college students' mental health remain insufficiently evidenced. ObjectiveTo explore the mediating role of emotion regulation difficulties in the relationship between childhood maltreatment and depression among college students， and to investigate the moderated effects of psychological resilience and family socioeconomic status， aiming to provide references for improving depressive symptoms in college students. MethodsOn 14 March 2024， a cluster sampling method was employed to recruit 751 college students from a university in Heilongjiang Province. Participants were assessed with Childhood Trauma Questionnaire （CTQ）， Difficulties in Emotion Regulation Scale （DERS）， Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， 10-item Connor-Davidson Resilience Scale （CD-RISC-10） and Family Socioeconomic Status Questionnaire. Pearson correlation analysis was adopted to examine the correlation between the scores of scales. Model 4 and model 7 in Process 4.2 were used to test the mediating effects of emotional regulation difficulties and the moderated effects of psychological resilience and family socioeconomic status. Results① A total of 712 （94.81%） valid questionnaires were collected. ② College students' CTQ score was positively correlated with DERS score and PHQ-9 score （r=0.296， 0.507， P<0.01）， and negatively correlated with CD-RISC-10 score and Family Socioeconomic Status Questionnaire score （r=-0.148， -0.229， P<0.01）. ③ The indirect effect value of difficulties in emotion regulation on the relationship between childhood maltreatment and depression was 0.091 （95% CI： 0.018~0.046）， accounting for 17.95% of the total effect. ④ The first half of the mediation model "childhood maltreatment → difficulties in emotion regulation → depression" （childhood maltreatment → difficulties in emotion regulation） was moderated by psychological resilience （β=-0.030， t=-6.147， 95% CI： -0.040~-0.020） and family socioeconomic status （β=-0.051， t=-3.929， 95% CI： -0.077~-0.026）. ConclusionChildhood maltreatment exerts both a direct effect on college students' depression and an indirect effect through emotion regulation difficulties. The childhood maltreatment → emotion regulation difficulties pathway in this mediation model is moderated by psychological resilience and family socioeconomic status. ［Funded by Qiqihar Medical University Graduate Student Innovation Fund Project （number， QYYCX2023-48）； Special Research Fund Project for Young Doctors of Qiqihar Academy of Medical Sciences （number， QMSI2021B-08）］

This paper summarizes clinical experience in treating depression with a combined approach of acupuncture and herbal medicine under the guiding principle of deficiency and excess. Given the complex pathogenesis of depression， it is proposed that syndrome differentiation based on deficiency and excess should serve as the overarching principle. Acupuncture is prioritized， supplemented by Chinese herbal medicine. Acupuncture is based on the spirit-regulating protocol； for excess syndromes， it is combined with the calming and restoring protocol， while for deficiency syndromes， it is combined with the five zang organs tonification protocol. In cases of mixed deficiency and excess， the two protocols are alternated， and adjustments are made dynamically throughout the treatment based on syndrome evolution. Herbal prescriptions are also guided by the differentiation of deficiency and excess. For excess patterns， dispersion and clearance should be emphasized， focusing on soothing the liver， clearing heat， relieving irritability， regulating qi， transforming phlegm， and calming the mind； for deficiency patterns， tonification is emphasized， aiming to strengthen the spleen， nourish the blood， calm the spirit， tonify qi， and consolidate the root.

Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.