In recent years, remarkable advances have been made in lung transplantation regarding donor evaluation, perioperative support, and immune regulation, laying a foundation for improving the long-term survival of recipients. The rational application of extended criteria donor lungs and the popularization of ex vivo lung perfusion technology have enhanced the utilization efficiency and safety of marginal donor lungs. Refined assessment of risk factors such as donors’ smoking history and infectious status has reduced the incidence of primary graft dysfunction and postoperative infection. In terms of recipient management, individualized assessment systems have been gradually optimized. The standardized application of intraoperative extracorporeal membrane oxygenation and the development of minimally invasive surgical techniques have effectively alleviated perioperative injuries. The optimization of postoperative immunosuppressive regimens and advances in rejection monitoring technologies have further improved the long-term survival of grafts. Nevertheless, chronic graft dysfunction and recurrent or refractory infections remain the major bottlenecks restricting long-term prognosis. Future research should focus on expanding donor sources, improving the repair quality of marginal donor lungs, promoting precise immunosuppression and anti-infection strategies, and comprehensively enhancing the long-term survival rate and quality of life of lung transplant recipients.

ObjectiveTo establish and evaluate a rat model of chronic obstructive pulmonary disease (COPD) associated with the traditional Chinese medicine (TCM) phlegm-dampness syndrome. MethodsEighteen SPF-grade 8-week-old male SD rats were randomly assigned to a control group (n=8) and a model group (n=10). The modeling procedure lasted for 19 weeks. Rats in the control group received no intervention. Lipopolysaccharide (LPS; 40 μg per rat per instillation) was instilled intratracheally into rats in the model group at 09:00 on the first day of weeks 1, 5, 9, 13, and 17, for a total of five instillations. Except for the instillation weeks, rats were exposed daily to cigarette smoke in a self-made high-humidity smoke exposure chamber (15 cigarettes/session before week 9 and 20 cigarettes/session from week 9 onward; 30 min/session/day). Body weight was recorded weekly, and general signs and manifestations of TCM phlegm-dampness syndrome were observed. On the day after modeling, rats were anesthetized for pulmonary ventilatory function testing. Tumor necrosis factor-α (TNF-α) and mucin 5AC (MUC5AC) levels in serum and bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay (ELISA). Lung tissues were subjected to hematoxylin and eosin (HE) and alcian blue and periodic acid-Schiff staining (AB-PAS) to assess lung tissue morphology and goblet cell hyperplasia. Western blotting was performed to determine TNF-α and MUC5AC protein expression in lung tissue. ResultsGeneral signs and overall condition: Compared with the control group, body weight in the model group was significantly decreased from week 3 onward (P<0.01). Rats showed yellowish fur, sluggish activity, reduced movement, rapid/labored breathing, and increased oral/nasal secretions. Pulmonary ventilatory function: Compared with the control group, minute ventilation and tidal volume (both P<0.01) and dynamic compliance (P<0.05) were decreased, whereas elastic resistance was markedly increased (P<0.01) in the model group. Inflammatory factors and mucus-related proteins: Compared with the control group, TNF-α and MUC5AC levels in serum and BALF, as well as their protein levels in lung tissue, were significantly elevated in the model group (all P<0.01). Histopathology: HE staining showed obvious alveolar dilatation and rupture with partial coalescence into bullae, and inflammatory cell infiltration in bronchiolar lumens. AB-PAS staining revealed increased goblet cells in bronchiolar mucosal epithelium and mucus plug formation in the lumen. ConclusionThis protocol can reproduce a COPD rat model with manifestations consistent with TCM phlegm-dampness syndrome, reduced pulmonary ventilation function, and pathological features of emphysema, inflammation, and chronic bronchitis, thereby providing reliable support for subsequent studies on TCM treatment of COPD with phlegm-dampness syndrome.

Objective:To analyze the clinical characteristics of tigecycline-related adverse reactions and provide the basis for the safe and rational use of the drug.Methods:Adverse reaction reports with suspected drug as tigecycline from Beijing Adverse Drug Reaction Monitoring Center from January 1st, 2019 to June 30th, 2024 were collected. The adverse reaction reports were standardized using the preferred term (PT) and system organ class (SOC) in the Chinese updated edition (2015 version) of the World Health Organization Adverse Reaction Terminology. The patients' general condition, tigecycline use, and adverse reaction occurrence (including latency, severity, treatment, outcome, and correlation evaluation) were descriptively and statistically analyzed. Results:A total of 408 tigecycline-related adverse reaction reports were entered, including 153 females (37.5%) and 255 males (62.5%). The age was (68±21) years, ranging from 2 to 99. The main reasons for tigecycline use were infections of lung, blood flow, skin and skin soft tissue, etc. The pathogens were mainly Klebsiella pneumoniae, Acinetobacter baumanii, Escherichia coli, etc. The usage and dosage of tigecycline in most patients were in line with the instructions. Four hundred and eight adverse event reports involved 11 SOCs and 580 PTs. The top 3 SOCs were gastrointestinal diseases (195 case times, 33.62%), vascular, bleeding and coagulation diseases (183 case times, 31.55%), and hepatobiliary diseases (142 case times, 24.48%). The main clinical manifestations were nausea, vomiting, diarrhea, etc. The main laboratory abnormalities were decreased plasma fibrinogen, decreased platelet count, increased alanine aminotransferase, increased aspartate aminotransferase, and increased bilirubin. There were 27 case times of adverse reactions that were not recorded in the instructions, mainly including leukopenia, abdominal distension, fever, dysbacteriosis, etc. The latency of adverse reactions ranged from 5 min to 65 days, with a median time of 5 days. The grade of adverse reactions was general in 379 patients (92.89%) and severe in 29 patients (7.11%). The top 3 SOCs involved in 53 case times of severe adverse reactions were hepatobiliary diseases (30 case times, 56.60%), vascular, bleeding and coagulation diseases (8 case times, 15.09%), and urinary tract diseases (4 case times, 7.55%), the main clinical manifestations were elevated liver enzymes, coagulation disorders, pancreatitis, etc. After the occurrence of adverse reactions, all patients stopped tigecycline, and received symptomatic treatments such as liver protection, intravenous infusion of human fibrinogen, intravenous infusion of platelets, and antidiarrheal therapy. Among 408 patients, 66 (16.18%) were cured, 297 (72.79%) were improved, 20 (4.90%) were not improved, and 25 cases' outcome (6.13%) were unknown. The shortest time for recovery or improvement was 0.5 hour, the longest was 44 days, with a median time of 5 days. The correlation between tigecycline and adverse reactions was probable in 132 patients (32.35%), and possible in 276 patients (67.65%). Conclusions:Tigecycline-related adverse reactions involve multiple organ systems, mainly including gastrointestinal diseases, vascular, bleeding and coagulation diseases, and hepatobiliary diseases, etc. which can lead to severe adverse reactions such as acute pancreatitis and coagulation disorders. After drug withdrawal and symptomatic treatments, most patients had a good prognosis.

OBJECTIVE To report a case of hepatitis B virus （HBV） reactivation induced by iparomlimab and tuvonralimab， summarize the clinical characteristics and potential mechanisms of such adverse reactions induced by immune-checkpoint inhibitors （ICIs）， and provide references for clinical application. METHODS From the perspective of a clinical pharmacist， a retrospective analysis was conducted on the treatment course of a patient with metastatic cervical cancer who experienced HBV reactivation after receiving iparomlimab and tuvonralimab. Additionally， an analysis of the correlation with adverse reactions was performed， and the clinical characteristics， risk factors， potential mechanisms， key points of treatment approaches and pharmaceutical care associated with HBV reactivation induced by ICIs were summarized. RESULTS & CONCLUSIONS The patient developed HBV reactivation and severe liver injury after using iparomlimab and tuvonralimab. The condition improved following drug discontinuation， and symptomatic treatment such as glucocorticoids. According to Naranjo’s Assessment Scale and China’s Measures for the Reporting and Monitoring of Adverse Drug Reactions， the association between iparomlimab and tuvonralimab and HBV reactivation was judged as “highly probable”， and it was identified as a new adverse reaction； the correlation between iparomlimab and tuvonralimab， paclitaxel and liver injury was “highly probable”. HBV reactivation in hepatitis B patients receiving standardized antiviral therapy is very rare after ICIs treatment； HBV reactivation is related to the overactivation of the immune system and disruption of immune balance induced by ICIs. For such patients， glucocorticoids should be administered for treatment， accompanied by pharmaceutical care， including pre- medication risk assessment and monitoring of relevant indicators during treatment.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Diagnosis and treatment of refractory hydrocephalus are the keys in reflecting the overall level of diagnosis and treatment of hydrocephalus. However, there is currently no clear definition of refractory hydrocephalus; moreover, treatment of these patients is difficult, with high failure rate. This article focuses on the definition, common causes and classification of refractory hydrocephalus, the treatment strategies of infectious refractory hydrocephalus, the treatment dilemmas of negative pressure or low-pressure hydrocephalus, and treatment future directions of refractory hydrocephalus, in order to attract attention of clinicians to the diagnosis and treatment of refractory hydrocephalus.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Objectives:To assess the impact of intravascular ultrasound(IVUS)guidance for drug-eluting stent(DES)implantation on the long-term outcomes in coronary artery disease(CAD)patients with chronic kidney disease(CKD).Methods:A retrospective study was conducted on 1 800 CAD and CKD patients who underwent coronary DES implantation at Nanjing First Hospital from January 2018 to December 2022.Patients were divided into IVUS-guided group(IVUS group,n=333)and angiography-guided group(angiography group,n=1 467).Propensity score matching(PSM)was performed at a 1:2 ratio to adjust for differences in baseline clinical and angiographic characteristics between the two groups.Major adverse cardiovascular events(MACE),including cardiac death,target vessel myocardial infarction,and clinically driven target vessel revascularization,were evaluated over a 2-year follow-up.Cox proportional hazards regression was performed to identify independent predictors of MACE.Results:After propensity score matching,333 patients in the IVUS group were matched with 666 patients in the angiography group.Following matching,there were no significant differences in clinical characteristics and angiographic data between the two groups(all P>0.05).Regarding procedural data,IVUS group had a higher number of stents implanted,longer total stent length,larger average stent diameter,more frequent use of post-dilation balloons,larger post-dilation balloon diameter,and greater contrast agent usage(all P<0.05).MACE rate was significantly higher in the angiography group than that in the IVUS group(23.9%vs.18.0%,P=0.037).The difference was mainly attributed to a higher rate of cardiac death in the angiography group(16.1%vs.10.8%,P=0.013).Additionally,patients in angiography group had a significantly higher all-cause mortality rate compared to IVUS group(19.7%vs.13.8%,P=0.022).Multivariate cox regression analysis showed that IVUS guidance(HR=0.73,95%CI:0.55-0.99,P=0.042)was an independent protective factor,while hypertension(HR=1.60,95%CI:1.13-2.26,P=0.008),type 2 diabetes(HR=1.56,95%CI:1.19-2.05,P=0.001),acute coronary syndrome(HR=1.92,95%CI:1.12-3.30,P=0.018),and moderate to severe calcification(HR=1.55,95%CI:1.18-2.04,P=0.002)were independent risk factors for MACE at 2 years after DES implantation in CKD patients.Conclusions:Patients with CAD and CKD,IVUS-guided DES implantation is associated with a reduced risk of MACE and all-cause mortality at 2 years post-procedure compared to coronary angiography-guided implantation.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.