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.

Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

Objective: To analyze the characteristics and key risk factors of abnormal blood disposal throughout the 2024-2025 blood collection and supply process based on nationwide multi-site monitoring data, develop a comprehensive prevention and control strategy across the entire chain, reduce preventable blood waste, and ensure clinical blood safety. Methods: According to the Guidelines for Haemovigilance (T/CSBT 001-2026), we extracted 74 cases of abnormal blood disposal events reported by the China Blood Transfusion Association′s Blood Safety Monitoring System from January 1 2024, to December 31 2025, and conducted descriptive statistical analysis on the distribution of events, types of deviations, root causes, and classifications of disposal manifestations. Results: A total of 664 adverse events related to blood collection and supply were reported over two years, with 74 cases involving discarded abnormal blood units, accounting for 11.1% of the total. Among these, blood component preparation (40.5%) and blood collection (37.8%) remained traditional high-risk stages. The proportion of blood waste occurring during storage, distribution, and transportation increased from 7.7% in 2024 to 34.3% in 2025. Deviations from standard operating procedures (SOP) by personnel were the primary cause, accounting for 74.3% of cases. Discarded blood units were categorized into four types: compromised closed blood bag systems (40 cases), mainly due to inadequate heat sealing, physical damage, or dropped bags; blood out of the cold chain (12 cases), primarily resulting from blood being left at work sites; imbalanced proportion of preservation solution (10 cases), mostly caused by blood collection volumes exceeding the standard capacity of blood bags; and other causes (12 cases). Conclusion: Human operational errors are the core cause of abnormal blood waste. The collection and preparation stages have long been at high-risk, and the risks in the storage and transportation stages have been increasing year by year. We should focus on standardizing personnel management, improving specialized operation norms such as heat sealing, transportation, and storage, establishing a full-process intelligent cold chain monitoring and multi-node visual verification mechanism, and systematically reducing the occurrence rate of abnormal blood waste through a closed-loop quality intervention system, thereby improving the utilization efficiency of voluntary blood donation resources.

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

The development of antiviral drugs targeting SARS-CoV-2 remains a major strategy for the prevention and treatment of COVID-19 infection. Current anti-SARS-CoV-2 agents mainly act on key viral protein targets involved in the viral life cycle, such as the main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp). However, these drugs are insufficient to address the challenges posed by the rapid mutation rate and drug resistance of SARS-CoV-2. In recent years, viral RNA has demonstrated to be a highly promising therapeutic target. Small-molecule drugs that target viral RNA possess distinct advantages, featuring novel mechanisms of action and the potential for broad-spectrum antiviral activity as well as the ability to overcome drug resistance. Such agents provide a new avenue for combating coronavirus threats. This review systematically summarizes recent advances in the development of small-molecule inhibitors targeting conserved SARS-CoV-2 RNA structures, including the frameshift stimulation element (FSE), stem-loops (SL), G-quadruplexes (G-4), and RNA-targeting chimeras (RNATAC), aiming to provide some insight to guide future.

Objective To investigate the status quo of health management behaviors in elderly patients with type 2 diabetes mellitus(T2DM)complicating chronic complications and the influencing factors based on health ecology theory.Methods The convenience sampling method was used to select elderly patients with T2DM complicating chronic complications in the Shanghai City from January to July 2022 as the respondents.Based on the health ecology theory,the five aspects of personality traits,psychological and behavioral traits,family and community interpersonal networks,living and working conditions and policy environment were in-vestigated.The Pearson correlation coefficient was used to analyze the correlation of various variables.The hi-erarchical linear regression was used to analyze the influencing factors of health management behaviors in eld-erly patients with T2DM complicating chronic complications.Results A total of 272 questionnaires were dis-tributed and 264 valid questionnaires were recovered,with an effective recovery rate of 97.06％(264/272).There were statistically significant differences in DSMB-Oscores among the patients with different chronic complications number,sleep quality,per capita monthly household income and medical payment methods(P＜0.05).The DSMB-Oscore in elderly patients with T2DM complicating chronic complications was positively correlated with HLSCP,DES,PACIC and CIRS scores(P＜0.05),and negatively correlated with the PAID-5 score(P＜0.05).Conclusion The health management behaviors of elderly patients with T2DM complicating chronic complications is jointly affected and acted by many factors,and it is necessary to identify and manage the related influencing factors from different aspects and different levels.

Objective To investigate the clinical efficacy of modified Wuzi Yanzong Pills combined with sequential therapy for the treatment of patients with premature ovarian failure(POF)of yang deficiency of spleen and kidney type,and to observe their effects on sex hormones and ovarian ultrasound indicators.Methods From September 2022 to September 2023,a total of 62 patients with POF of yang deficiency of spleen and kidney type who attended Huizhou Hospital of Traditional Chinese Medicine were selected as the study objects.The patients were randomly divided into the control group and the observation group by using a table of random numbers,with 31 patients in each group.The control group was treated with estrogen-progestin sequential therapy,and the observation group was treated with modified Wuzi Yanzong Pills on the basis of treatment for the control group.The two groups were treated for three menstrual cycles.Before and after treatment,the changes of serum sex hormones,uterine and ovarian ultrasonography and hemodynamic indicators,traditional Chinese medicine(TCM)syndrome scores,Kupperman score of the two groups were observed.The ovulation rate and therapeutic efficacy of the two groups were compared,and the safety of the therapeutic regimen for the two groups was evaluated.Results(1)Two cases fell off during the study period,and a total of 60 patients were eventually included in the study,of which 30 patients in each group.(2)After three menstrual cycles of treatment,the total effective rate of the observation group was 90.00％(27/30)and that of the control group was 76.67％(23/30),and the total effective rate of the observation group was significantly higher than that of the control group(P＜0.05).(3)After treatment,the serum follicle-stimulating hormone(FSH)and luteinizing hormone(LH)levels of the two groups of patients were decreased compared with those before treatment(P＜0.05),and the serum estradiol(E2)level was increased compared with that before treatment(P＜0.05),the decrease of the serum FSH and LH levels and the increase of the serum E2 level in the observational group were significantly superior to those of the control group(P＜0.01).(4)After treatment,ultrasonographic indicators such as endometrial thickness(EM),ovarian volume averaged(OVA),mean ovarian diameter(MOD)at the maximum transverse section of the ovary,and antral follicle count(AFC)in the two groups were increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the peak systolic velocity(PSV)of the two groups was increased compared with that before treatment(P＜0.05),and the ovarian resistance index(RI)and ovarian pulsatility index(PI)were decreased compared with those before treatment(P＜0.05),and the increase of PSV and the decrease of RI and the PI in the observation group were significantly superior to those of the control group(P＜0.01).(6)After treatment,the Kupperman score and TCM syndrome scores of the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(7)After three menstrual cycles of treatment,the ovulation rate of the observation group was 30.00％(9/30),and that of the control group was 10.00％(3/30).The comparison between the two groups showed that the ovulation rate of the observation group was significantly superior to that of the control group(P＜0.05).(8)The incidence of adverse reactions in the control group was 6.67％(2/30)and that in the observation group was 6.67％(2/30).The comparison between the two groups showed that there being no statistically significant difference(P＞0.05).Conclusion The modified Wuzi Yanzong Pills combined with estrogen-progestin sequential therapy can effectively regulate the sex hormone levels of patients with POF of yang deficiency of spleen and kidney type,promote the follicular development,significantly improve the ovarian microcirculation,increase the ovulation rate,and relieve symptoms and signs,with good safety.

BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

Objective:To explore the clinical efficacy, safety and possible neuroimaging mechanism of deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) in the treatment of refractory migraine.Methods:Thirty patients with refractory migraine were selected from the Department of Neurology, Affiliated Hospital of North Sichuan Medical College from October 2022 to August 2023. The patients were randomly divided into dTMS group ( n=10), rTMS group ( n=10) and sham stimulation group ( n=10). The dTMS group was treated with H7 coil and the rTMS group with "8" coil, and the sham stimulation group was treated with sham stimulation rTMS with the frequency of 10 Hz. The stimulation site was the contralateral primary motor cortex (M1) of headache, which was treated for 2 weeks (3 600 pulses per time, 5 times per week, 10 times in total). Visual Analogue Scale (VAS) and Headache Impact Test-6 (HIT-6) evaluations were performed before treatment, on the first day after treatment, and 1, 3 and 6 months after treatment. The resting-state functional magnetic resonance images of the 3 groups of patients before and after treatment were collected and analyzed by MATLAB2018b, SPM12 and RESTPLUS softwares, and the brain regions with different regional homogeneity (ReHo) before and after treatment were obtained. The general clinical data and scale scoring data were analyzed and processed by SPSS 26.0 version software. Results:There were significant differences in VAS scores among the dTMS group (before treatment 6.70±0.68, the first day after treatment 5.60±0.70, 1 month after treatment 5.00±0.82, 3 months after treatment 3.50±0.85, 6 months after treatment 3.90±1.45), the rTMS group (before treatment 6.90±0.74, the first day after treatment 5.90±0.74, 1 month after treatment 5.30±0.82, 3 months after treatment 5.30±0.82, 6 months after treatment 6.80±0.63) and the sham stimulation group (before treatment 6.60±0.97, the first day after treatment 6.70±0.95, 1 month after treatment 6.90±1.10, 3 months after treatment 6.70±0.68, 6 months after treatment 7.10±0.88; F=16.054, P<0.001), VAS scores among different time points ( F=34.292, P<0.001), and the interaction between groups and time ( F=24.136, P<0.001). Compared with those before treatment, VAS scores in the dTMS group and the rTMS group decreased on the first day after treatment, 1 month and 3 months after treatment (all P<0.05); VAS scores decreased in the dTMS group 6 months after treatment ( P<0.05). Compared with the sham stimulation group, the VAS scores of the dTMS group were lower at the same time points after treatment (all P<0.05), and the VAS scores of the rTMS group were lower on the first day after treatment, 1 month and 3 months after treatment (all P<0.05). Compared with the rTMS group, VAS scores were lower at 3 and 6 months after dTMS treatment (both P<0.05). There were significant differences in HIT-6 scores among groups ( F=13.173, P<0.001), HIT-6 scores among different time points ( F=60.788, P<0.001), and interaction between groups and time ( F=35.576, P<0.001). Compared with those before treatment, the HIT-6 scores in the dTMS group decreased on the first day after treatment ( P<0.05); the HIT-6 scores in the dTMS group and the rTMS group decreased 1 month and 3 months after treatment (both P<0.05); the HIT-6 scores decreased in the dTMS group 6 months after treatment ( P<0.05). Compared with the sham stimulation group, the HIT-6 scores were lower in the dTMS group at the same time points after treatment (all P<0.05), and the HIT-6 scores were lower in the rTMS group at 1 and 3 months after treatment (both P<0.05). Compared with the rTMS group, HIT-6 scores were lower at 3 and 6 months after dTMS treatment (both P<0.05). Analysis of ReHo results: compared with those before treatment, the ReHo values of the right cerebellar angle area 1 increased in the dTMS group and the sham stimulation group, decreased in the rTMS group. The ReHo values of the right middle occipital gyrus, left dorsolateral superior frontal gyrus and right cerebellar area 8 increased in the dTMS group, but decreased in the rTMS group and the sham stimulation group. The ReHo values of the left precentral gyrus and left superior temporal gyrus decreased in the dTMS group, while those in the rTMS group and the sham stimulation group increased. There were no obvious adverse reactions in the 3 groups during the treatment and follow-up period. Conclusions:dTMS and rTMS may help to improve the headache degree and quality of life of patients with refractory migraine, and they are safe, which may be related to the changes of brain network in the right cerebellar angle area 1, right middle occipital gyrus, left dorsolateral superior frontal gyrus, left precentral gyrus, left superior temporal gyrus and right cerebellar area 8.