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.

Depression, one of the most prevalent mental health disorders, has emerged as a critical focus in medical and neurobiological research, as well as a major challenge for global public health. The immune-inflammatory hypothesis has been confirmed to play a pivotal role in the pathogenesis and pathophysiology of depression, though its precise mechanisms remain to be fully elucidated. This article reviews the effects of key inflammatory factors, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and Toll-like receptors on depression. Additionally, it summarizes the effects of immune-inflammatory pathway invovled in the pathogenesis of depression, along with scientific clues related to inflammatory factors in this pathway. Findings from this review will provide new insights for antidepressant development and serve as a reference for evaluating the clinical efficacy of antidepressants.

Objective:To investigate the practicality and clinical significance of quantitative indicators related to wide QRS complex in the diagnosis of atrial fibrillation (AF) with wide QRS complex.Methods:A retrospective study was conducted to analyze the dynamic electrocardiogram data of 93 patients who visited Ankang People's Hospital from January 2021 to December 2023. Based on the type of arrhythmia, the patients were divided into two groups: AF with premature ventricular contraction (PVC) group ( n = 65) and AF with intraventricular conduction abnormality group ( n = 28). The traditional diagnostic indicators and newly introduced quantitative indicators were compared between the two groups to analyze the clinical significance of the new quantitative indicators in identifying AF with wide QRS complex. Results:There were statistically significant differences in the occurrence of cannon waves, QRS duration > 140 ms, QRS morphology in lead V1, the R wave or qR pattern, or the deepest point of R being greater than r or rS in lead V1 being > 60 ms, R/S ratio in lead V6 < 1 or displaying QS pattern, the presence of a notching, a slow decline, or a prominent R wave in the QRS beginning in lead aVR, Vi/Vt in lead aVR ≤ 1, and the data regarding the electrical axis in the no man's land between the two groups ( χ2 = 11.83, 37.59, 26.05, 27.33, 5.30, 49.46, 34.95, 4.90, all P < 0.05). The premature interval/coupling interval in the AF with PVC group was (1.38 ± 0.32), which was significantly lower than (1.84 ± 0.43) in the AF with intraventricular condection abnormality group ( t = -5.71, P < 0.001). The quasi-compensatory pause/coupling interval and quasi-compensatory pause/premature interval in the AF with PVC group were (1.71 ± 0.36) and (1.28 ± 0.25), respectively, which were significantly higher than those in the AF with intraventricular conduction abnormality group ( t = 5.48, 5.06, both P < 0.001). The areas under the curve for the premature interval/coupling interval, quasi-compensatory pause /coupling interval, and quasi-compensatory pause/premature interval, and the combined three indicators (using logistic regression) in distinguishing AF with wide QRS complex were 0.810, 0.788, 0.818, and 0.953, respectively. The area under the curve for the combined three indicators was significantly greater than that for each individual indicator ( Z = -3.10, -3.92, -3.09, all P < 0.05). Conclusions:Premature interval/coupling interval, quasi-compensatory pause/coupling interval, and quasi-compensatory pause/premature interval show good value in the diagnosis of AF with wide QRS complex, and the combined use of the three can significantly improve the diagnostic accuracy.

Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer.Methods A colitis-cancer model was established in C57BL/6 mice using azoxymethane(AOM)combined with dextran sulfate sodium(DSS).Samples were collected at 7,10,and 14 weeks post-modeling and the spleen index,colon length,mass,and colon mass per unit length were measured.Histopathological changes in the colon were observed by hematoxylin and eosin and Masson staining.Expression levels of the cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b,Lrp5,Axin2,and Znrf3 at different pathological stages were detected by reverse transcription quantitative real time PCR.Cancer-associated fibroblasts(FAP),CD44,the proliferation marker Ki67,and goblet cell MUC2 protein were detected by multiple immunofluorescence histochemistry(mIHC)and immunofluorescence.In addition,colon organoids were isolated from model mice at ten and fourteen weeks and cultured in vitro to observe changes in organoid morphology and marker expression.Results AOM/DSS-induced mice showed reduced,distorted,and branched colon crypt structures with a few collagen fibers at 7 weeks,and varying degrees of colon intraepithelial neoplasia,with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining at ten and fourteen weeks.mRNA levels of CD44 and Wnt2b in the colon were significantly increased(P＜0.05)and Axin2 was decreased(P＜0.01)in model mice compared with control mice at fourteen week,and levels of Wnt2b,Lrp5,and Znrf3 were increased compared with seven-week mice(P＜0.01,P＜0.05,P＜0.01),and Axin2 was decreased(P＜0.01).mIHC staining showed increased expression of FAP and CD44 in the colon in model mice at ten and fourteen weeks,with decreased MUC2 expression.Colon organoids showed cystic dilation,especially at fourteen weeks,with more prominent expression of Ki67 and CD44.Conclusions The AOM/DSS-induced mouse model exhibited chronic colonic inflammation,low-grade intraepithelial neoplasia,and high-grade intraepithelial neoplasia at seven,ten,and fourteen weeks,respectively.The pathological microenvironment was characterized by fibroblast activation and abnormal proliferation of epithelial cells.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To construct a classification management model on the basis of Kraljic matrix for electrocardiogram(ECG)monitoring equipment in emergency intensive care unit(ICU),so as to explore its application value in the management for ECG monitoring equipment in emergency ICU.Methods:The classification management model on the basis of index for ECG monitoring equipment in emergency ICU was constructed.According to two classification dimensions included the market supply risk and the self-value,an indicator system of classification management,which aimed at strategic materials with high value and high risk,leverage materials with high value and low risk,bottleneck materials with low value and high risk,and conventional materials with low value and low risk,was constructed.A total of fifty-one ECG monitoring equipment in the emergency ICU of The People's Hospital of Longhua of Shenzhen from January to December 2023 were selected,and they were managed respectively by conventional management mode(25 sets)and classification management mode(26 sets)according to different management modes.The standardization level of operation management for equipment,the occurrence of safety risk and the level of management for equipment of the two management modes were compared,and the satisfaction of 30 relative personnel,who used and managed these equipment,for classification management of equipment also were compared.Results:The average values of the percentage of standardization level of normality of equipment operation,disinfection and sterilization,maintenance and fault repair of using classification management mode were respectively(91.58±4.33)%,(92.1±3.28)%,(91.49±3.54)%and(92.58±3.32)%,all of which were higher than those of conventional management mode,and the differences were statistically significant(t=12.537,15.706,14.196,18.946,P<0.05),repsectively.The average incidences of the risk of pressure injury,electrical injury and body fluid extravasation of adopting classification management mode were respectively(2.54±0.87)%,(3.02±0.82)%and(1.29±0.65)%,all of which were lower than those of adopting conventional management mode,and the differences were statistically significant(t=22.825,17.453,24.424,P<0.05),respectively.The satisfaction scores of 30 relative management personnel,who used equipment on the process rationality,system standardization and quality effectiveness,of adopting classification management mode were respectively(94.26±3.54),(92.57±4.36)and(91.87±3.69),all of which were higher than those of conventional management mode,and the differences were statistically significant(t=14.052,13.991,13.551,P<0.05),respectively.The reasonable placement rate,recording rate of standardization,and intact rate of equipment in the 26 equipment by adopting classification management mode were respectively 92.31%,92.31%and 88.46%,all of which were significantly higher than those by adopting conventional management mode,and the differences were statistical significant(x2=12.052,10.398,11.338,P<0.05).Conclusion:The classification management model of ECG monitoring equipment in emergency ICU can increase the management efficiency for the equipment in operating room of hospital,and improve the operation quality of equipment,and enhance the safety of equipment in clinical use,and the standardization of operation management for equipment.

Narrow leaf 1 (NAL1) plays an important role in plant branching, while little is known about the roles of this gene in petunias. In this study, PhNAL1b was cloned from Petunia×hybrida cv. Mitchell Diploid, with a total length of 1 767 bp, encoding a protein composed of 588 amino acid residues and containing the peptidase S64 domain. The PhNAL1b promoter region contained several elements involved in the responses to auxin, jasmonic acid, abscisic acid, and light. The expression analysis showed that PhNAL1b had the highest expression level in roots and the lowest expression level in flowers, and its transcription could be inhibited by decapitation and cytokinin. The subcellular localization analysis showed that PhNAL1b was located in the nucleus and was a nuclear protein. Virus-induced gene silencing was employed to downregulate the expression of PhNAL1b, which resulted in significant increases in branch number and plant height. The results indicated that PhNAL1b played an important role in regulating the branching of petunias. This study lays a foundation for revealing the mechanism of NAL1 in regulating branch development and provides genetic resources for plant architecture improvement.
Petunia/growth & development* ; Plant Proteins/metabolism* ; Diploidy ; Gene Expression Regulation, Plant ; Cloning, Molecular ; Promoter Regions, Genetic

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Septic acute kidney injury (SAKI) is one of the most common complications of sepsis, and the occurrence of acute kidney injury (AKI) indicates that the patient's condition is critical with a poor prognosis. The traditional view holds that the main mechanism of SAKI is the reduction of renal blood flow, inadequate renal perfusion, inflammatory response, and microcirculatory dysfunction caused by sepsis, which subsequently leads to ischemia and necrosis of renal tubular cells. Recent research findings indicate that processes such as autophagy and other forms of programmed cell death play an increasingly important role. Autophagy is a programmed intracellular degradation process and is a form of programmed cell death. Cells degrade their cytoplasmic components via lysosomes, breaking down and recycling intracellular constituents to meet their metabolic needs, maintain intracellular homeostasis, and renew organelles. During SAKI, autophagy plays a crucial protective role through various mechanisms, including regulating inflammation and immune responses, clearing damaged organelles, and maintaining stability in the intracellular environment. In recent years, the role of autophagy in the pathogenesis and treatment of SAKI has received widespread attention. Research has confirmed that various intracellular signaling pathways and signaling molecules targeting autophagy [such as mammalian target of rapamycin (mTOR) signaling pathway, AMP-activated protein kinase (AMPK) signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and Sirtuins (SIRT), autophagy associated factor Beclin-1, and Toll-like receptor (TLR)] are involved in the development of SAKI. Due to the complex pathogenesis of SAKI, current treatment strategies include fluid management, infection control, maintenance of internal environment balance, and renal replacement therapy; however, the mortality remains high. In recent years, it has been found that autophagy plays a critical protective role in sepsis-mediated AKI. As a result, an increasing number of drugs are being developed to alleviate SAKI by regulating autophagy. This article reviews the latest advances in the role of autophagy in the pathogenesis and treatment of SAKI, with the aim of providing insights for the development of new drugs for SAKI patients.
Humans ; Acute Kidney Injury/etiology* ; Autophagy ; Sepsis/complications* ; Signal Transduction