Kidney transplant recipient (KTR) faces significant challenges in long-term survival, with the incidence of post-transplant malignancies being 2 to 3 times higher than that of the general population, making it the second leading cause of death in KTR. Immune checkpoint inhibitors (ICI) represent an important breakthrough in malignancy treatment, significantly improving the prognosis of some malignancy patients by blocking co-inhibitory signaling molecules and activating T lymphocyte activity. However, due to concerns about the risk of rejection, solid organ transplant recipients, including KTR, are usually excluded from ICI clinical trials. Existing evidence shows that the incidence of rejection during ICI treatment can be as high as 40%-50%, with the specific mechanisms not yet clear. Therefore, how to enable KTR to effectively benefit from the anti-tumor effects of ICI while avoiding rejection is crucial. This article focuses on the core contradiction of ICI in the treatment of post-transplant malignancies in KTR, that is, the dual effects of activating anti-tumor immunity and inducing transplant kidney rejection. It systematically reviews the current clinical application status and challenges, and explores optimization strategies for the delicate balance between restoring anti-tumor immunity and triggering rejection.

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Hematopoietic stem cell transplantation (HSCT) is currently an effective method to cure hematologic malignancies and bone marrow failure diseases, and can restore hematopoietic function destroyed by hematologic malignant diseases. In recent years, HSCT has developed rapidly in China, but pulmonary chronic graft-versus-host disease after transplantation has seriously affected the quality of life and long-term survival of patients. Therefore, this article aims to describe the risk factors, clinical classification, and early diagnosis and treatment strategies of pulmonary chronic graft-versus-host disease, and proposes that lung transplantation is the only effective therapeutic intervention when medical treatment proves ineffective for end-stage pulmonary cGVHD.

Whole-genome sequencing, serotype typing, MLST typing, population genetic structure analysis, and core-genome single nucleotide polymorphism (cgSNP) analysis were performed on 23 strains of mucoid Haemophilus influenzae collected from the Laboratory Center of Hunan Children′s Hospital from January 2021 to December 2022. Drug susceptibility tests were conducted using the automated microbial identification and susceptibility analysis system AF-600, and virulence genes and drug resistance genes were analyzed based on the whole-genome sequences. Based on the serotype typing of whole-genome sequencing, all 23 strains were Haemophilus influenzae type b (Hib). MLST analysis revealed that the 23 strains belonged to six ST types, among which 10 strains (43.5%) were ST386, 5 strains (21.7%) were ST18, and 2 strains (8.7%) were the newly discovered ST2887. Bayesian population structure analysis (BAPS) showed three distinct populations. The results of the virulence gene analysis showed that the carriage rates of genes encoding capsule-related proteins and those associated with bacterial immune regulation and inflammatory signaling pathways were all 100%. However, the ompP5 gene related to bacterial adhesion, and the hgpC and hxuA genes related to bacterial protein metabolism were all present in the newly discovered ST2887. The in vitro drug susceptibility test results of 23 strains of mucoid Hib showed that the resistance rates to ampicillin, cefuroxime, and Trimethoprim-sulfamethoxazole were 13.0%(3 strains), 13.0%(3 strains), and 87.0%(20 strains), respectively. They were sensitive to other beta-lactam drugs. All the 23 strains of mucoid Haemophilus influenzae infected children were Hib, and the main ST types were ST386 and ST18. It is very important to advocate Hib vaccination.

Lung transplantation is a key therapeutic approach for patients with end-stage lung diseases. Although its clinical outcomes have significantly improved, multidimensional injuries sustained by donor lungs during procurement, preservation, and transplantation remain major challenges affecting graft survival and long-term prognosis. This article proposes the "Guangzhou Classification" for full-course management of donor lung injury, characterized by spatiotemporal dynamics. Based on the progression of disease stages, donor lung injuries are systematically divided into three types: primary injuries (including donor ICU-related lung injury, pathogen colonization, and cold ischemia injury), secondary injuries (such as ventilator-induced lung injury after transplantation, ischemia-reperfusion inflammatory storm, and early rejection), and accompanying injuries (organ toxicity caused by accumulation of postoperative sedatives, analgesics, and vasoactive drugs). Drawing on previous studies and the clinical experience of our center, this paper elaborates the temporal evolution, key risk factors, and prevention and treatment strategies of each injury category, and discusses future research directions. By targeting critical injury factors at each stage, this classification aims to optimize both short-term and long-term outcomes of lung transplantation.

Objective To explore the early diagnostic value of serum heat shock protein 70(HSP70),periosten combined with low-dose spiral CT(LDCT)for lung cancer.Methods From July 2022 to June 2024,103 lung cancer patients admitted to our hospital were regarded as the lung cancer group,and 87 patients with benign pulmonary nodules were selected as the benign group.ELISA kit was used to measure serum HSP70 and Periostin.Multivariate logistic regression was applied to analyze the influencing factors of lung cancer.Four grid table method was applied to calculate the sensitivity,specificity,and accuracy of LDCT combined with serum HSP70 and Periostin in the diagnosis of lung cancer.Kappa test was applied to evaluate the consistency between LDCT,serum HSP70,Periostin combined with LDCT and pathological diagnosis of lung cancer.Results Compared with the benign group,the lung cancer group had greatly higher levels of serum HSP70 and Periostin(P＜0.05).Compared to the benign group,the lung cancer group had higher proportions of lobulation and spiculation signs(P＜0.05).Multivariate logistic regression showed that HSP70(OR=1.569),Periostin(OR=1.427),lobulation sign(OR=2.015),and spiculation sign(OR=1.946)were all independent risk factors for lung cancer(P＜0.05).The sensitivity,specificity,and accuracy of LDCT in diagnosing lung cancer were 85.44％,88.51％,and 86.84％,respectively;the sensitivity,specificity,and accuracy of serum HSP70 and Periostin combined with LDCT in diagnosing lung cancer were 93.20％,80.46％,and 87.37％,respectively.Kappa test showed that the consistency between serum HSP70,Periostin combined with LDCT had high consistency with pathology in the diagnosis of lung cancer(Kappa value=0.743).Conclusion The serum levels of HSP70 and Periostin are higher in lung cancer patients.The combination of serum HSP70 and Periostin with LDCT has better diagnostic efficacy for lung cancer.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.