OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

On August 31， 2025， the Asian Pacific Association for the Study of the Liver （APASL） updated and released management of acute variceal bleeding： updated APASL guidelines （2025 edition）， which systematically elaborates on the definition， diagnosis， assessment， and treatment of acute variceal bleeding. This article gives an excerpt of the recommendations in this guideline.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Background In the Global Burden of Disease research, it has been found that atmospheric fine particulate matter (PM_2.5) pollution significantly harms human health. Currently, there is limited research on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) that exhibit high toxicity effects in PM_2.5 . Objective By studying the spatiotemporal distribution and variation characteristics of PCDD/Fs in PM_2.5 in Pudong area of Shanghai, to assess the associated population health risk. Methods This study set up 28 sampling points in Pudong area. One sample of PM_2.5 was collected during winter (February 2022) and summer (July 2022) at each site, with a sampling period lasting 24 h. The concentration of PM_2.5 was measured by membrane filter method, and the content of 17 kinds of 2,3,7,8-substituted chlorinated PCDD/Fs in the samples was analyzed using isotope dilution. Seasonal variations (winter and summer) in the concentrations of PM_2.5 and PCDD/Fs were evaluated, sources of PCDD/Fs pollution were tracing by principal component analysis, and health risks to the population from respiratory exposure to PCDD/Fs were estimated by VLIER-HUMAAN model. Results The PM_2.5 concentrations in the 28 samples ranged from 10 to 126 μg·m⁻³, while the concentrations of PCDD/Fs in PM_2.5 ranged from 58 to 2625 fg·m⁻³. The concentration of PM_2.5 during winter (11-126 μg·m⁻³) was higher than that during summer (10-60 μg·m⁻³). The concentration range of PCDD/Fs in winter was from 58 to 2625 fg·m⁻³, which corresponded to a range of toxic equivalent quantity (WHO-TEQ) concentration from 2.99 to 40.97 fg·m⁻³ when taking World Health Organization's toxic equivalency factor (WHO-TEQ); the concentration range of PCDD/Fs in summer was from 72 to 446 fg·m⁻³, which corresponded to a range of WHO-TEQ concentration from 2.66 to 16.61 fg·m⁻³. This range in summer was significantly lower than that observed in winter. The results of principal component analysis revealed that waste incineration was the primary source of PCDD/Fs in winter PM_2.5 in the area, whereas traffic emissions emerged as the main source in summer. The assessment of Pudong residents' respiratory exposure to PCDD/Fs in PM_2.5 showed significantly higher exposure of children in summer and winter than that of adults, indicating higher susceptibility of children to air pollutants. Both the hazard ratios (HR) for children and adults were below 1, while the cancer risks (CR) ranged from 8.41×10⁻⁸ to 2.35×10⁻⁶. Notably, during winter, the CR at 4 locations slightly exceeds 1×10⁻⁶, indicating a potential carcinogenic risk. Conclusion The overall pollution level of PCDD/Fs in PM_2.5 in Pudong area is relatively low, but it shows clear seasonal patterns. Waste incineration and traffic are the main sources of PCDD/Fs in PM_2.5 in the area. Although the cancer risk of exposure to PCDD/Fs in PM_2.5 for children or adults is relatively low, there is a certain risk at some locations in winter, necessitating additional monitoring and control.

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.

Objective:To observe the value of superb microvascular imaging(SMI)combined with contrast-enhanced ultrasound(CEUS)in the differential diagnosis of benign and malignant superficial enlarged lymph nodes.Methods:A total of 82 patients with superficial enlarged lymph nodes who admitted to the Fourth Hospital of Qinhuangdao City from March 2020 to June 2022 were selected.All patients underwent SMI and CEUS examinations,and the ultrasound-guided needle biopsy was used as the"gold standard",and Kappa values was used to analyze the consistencies of single SMI and CEUS,and the combination of them with the"gold standard"in diagnosing benign and malignant superficial enlarged lymph nodes.Results:The results of ultrasound-guided needle biopsy showed that 34 superficial enlarged lymph nodes were benign lymph nodes and 63 superficial enlarged lymph nodes were malignant lymph nodes in 97 superficial enlarged lymph nodes of 82 patients.The results of SMI examination showed that 37 superficial enlarged lymph nodes were benign lymph nodes and 60 superficial enlarged lymph nodes were malignant lymph nodes in 97 superficial enlarged lymph nodes.The results of consistency analysis indicated that SMI has favorable value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,which has better consistency with needle biopsy(Kappa=0.712).The results of CEUS examination showed that 36 cases of the 97 superficially enlarged lymph nodes were benign lymph nodes and 61 cases were malignant lymph nodes.The results of consistency analysis indicated that CEUS has better value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,which has higher consistency with needle biopsy(Kappa=0.821).The results of SMI combined with CEUS examination showed that 35 cases of 97 superficial enlarged lymph nodes were benign lymph nodes and 62 cases were malignant lymph nodes.The result of consistency analysis indicated that SMI combined with CEUS has better value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,and has higher consistency with needle biopsy(Kappa=0.886).Conclusion:Both SMI and CEUS examinations have better value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,and the combination of them can further improve the consistency with result of pathological examination,and enhance the diagnostic value,which has a certain guidance significance in clinical screening malignant lymph nodes.