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.

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

Objective: To investigate the characteristics and risk factors of an outbreak of acute hemorrhagic conjunctivitis (AHC) in a boarding middle school in Guangdong Province, in order to provide a scientific evidence for effective prevention and control of campus AHC outbreaks. Methods: From September 1st to 28th 2023, case identification was conducted among 559 students and 60 faculty members using standardized definition. Descriptive analysis was conducted on the three distrubution patterns of the outbreak. Questionnaires were designed, and a case-control study was adopted to analyze the possible risk factors of the disease transmission. The propensity score matching (PSM) method was used to control the difference of baseline data. Results: A total of 269 cases of AHC were identified, with an attack rate of 43.46%. The pathogen was confirmed as Coxsackie virus A24 variant (CA24v). Among these, 264 cases were students (attack rate of 47.23%) and 5 were staff (attack rate of 8.33%). A total of 153 pairs of PSM were successfully matched. After PSM matching, there were no statistically significant differences in gender, grade and class between the case group and the control group ( χ 2=0.12, 5.41, 11.24, P >0.05). The results of multivariate Logistic regression analysis showed that middle school students whose towels contacted with others ( OR =1.81), and direct contact with other AHC cases recently ( OR =4.89) were more likely to have AHC; while wearing glasses ( OR =0.43) and frequent use of hand sanitizer ( OR = 0.37 ) were less likely to have AHC ( P <0.05). Conclusion The outbreak of AHC is caused by CA24v, demonstrating rapid spread and extensive impact within the school setting.

Objective To identify the key biomarkers for diagnosing chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH)using bioinformatics,and validate their clinical significance.Methods High-throughput sequencing data analysis was employed to identify differentially expressed genes(DEGs)in COPD-PAH.Functional enrichment analysis was then conducted to explore the biological functions of these DEGs.Machine learning methods,including least absolute shrinkage and selection operator(LASSO),random forest(RF),and support vector machine-recursive feature elimination(SVM-RFE),were utilized to screen 5 potential biomarkers.Single-cell analysis was performed to reveal the expression patterns of these key genes in macrophages.The clinical significance of these biomarkers was further validated using peripheral blood mononuclear cells(PBMC)data.A mouse model of COPD-PAH was established using hypoxia exposure.Sixteen mice(either sexes,8 weeks old,weighing 20～22 g)were randomly divided into a hypoxia group[O2(10.0±0.5)%,COPD-PAH,n=8]and a normoxia group(COPD,n=8).Immunofluorescence assay was used to label the key biomarkers,and their expression levels were quantified.Results A total of 28 DEGs(|Log2FC|≥2,P<0.05)were identified in COPD-PAH patients.Functional enrichment analysis indicated that DEGs in COPD were primarily associated with major histocompatibility complex(MHC)Ⅱ and cell division,and involved in lysosomes,oxidative phosphorylation,and cell cycle pathways(P<0.05).Machine learning identified 5 potential biomarkers(GRN,KLF4,SHTN1,LRP1,and GPNMB),and subsequent single-cell analysis revealed that these markers exhibited reverse expression patterns during disease progression.A nomogram model constructed based on PBMC data yielded an area under the curve(AUC)of 0.907 in diagnosing COPD-PAH.GRN,KLF4,SHTN1,LRP1 and GPNMB were significantly upregulated in the COPD-PAH group(P<0.05).Conclusion GRN,KLF4,SHTN1,LRP1 and GPNMB are identified as key biomarkers for the prediction and diagnosis of COPD-PAH,which providing new insights for the clinical and treatment of the condition.

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective:To investigate the effects of transhepatic arterial chemoembolization(TACE)combined with Endostar on CD4+/CD8+T cells,5-aminoketovalonate synthase 1(ALAS1)and HIPPO-YAP signaling pathway in patients with hepatocellular carcinoma(HCC).Methods:A total of 60 HCC patients admitted to Chengdu Third People's Hospital from January 2018 to December 2021 were enrolled and randomly divided into TACE treatment group(A)and TACE combined with Endostar treatment group(B),with 30 patients in each group.T lymphocyte,ALAS1 and indicators of HIPPO-YAP signaling pathway were observed in the two groups.Results:In group A,1 subject had complete remission,2 subjects had partial remission,2 subjects had stable remission,and 4 subjects had progress;in group B,2 subjects had complete remission,4 subjects had partial remission,4 subjects had stable remis-sion,and 1 subject had progress.The total effective rate in group B(33.33%)was significantly higher than that in group A(10.00%),with significant difference among groups(P=0.028).There were no significant differences in CD4+T cells,CD8+T cells and CD4+/CD8+T cells between the two groups before treatment(P=0.972,0.995,0.917).After treatment,level of CD4+T cells in the two groups was significantly increased(P<0.001),while level of CD8+T cells was significantly decreased(P<0.001).CD4+/CD8+T cells was significantly increased(P<0.001),and the changes in group B were significant compared with group A(P<0.001).There was no significant difference in content of ALAS1 between the two groups before treatment(P=0.975);after treatment,content of ALAS1 in liver cancer tissues of the two groups was significantly increased(P<0.001),which in group B was significantly higher than that in group A(P<0.05).Before treatment,there were no significant differences in mammalian STE20-like protein kinase 2(MST2),large tumor suppressor 1(LATS1)and Yes-associated protein(YAP)between the two groups(P=0.134,0.134,0.134).After treatment,mRNA relative expressions of MST2 and LATS1 were significantly increased(all P<0.001),while mRNA relative expression of YAP were significantly decreased(P<0.001),and changes of group B were significant compared with group A(all P<0.001).After treat-ment,there were 5 more cases of no adverse reactions in group B than in group A,and the total incidence of adverse reactions(16.67%)was significantly lower than that in group A(43.33%),with a significant difference between groups(P=0.024).Conclu-sion:TACE combined with Endostar has significant therapeutic effect on HCC patients,which can effectively regulate CD4+/CD8+T cells,promote ALAS1 secretion,and activate HIPPO-YAP signaling pathway.

Objective To summarize the clinical experience of the first case of sulbactam-durlobactam treatment for extensively drug-resistant Acinetobacter baumannii infection after lung transplantation in China.Methods A retrospective analysis was conducted on a case of a patient with severe chronic obstructive pulmonary disease who received sulbactam-durlobactam treatment after lung transplantation.Results A 68-year-old male patient with a history of drug-resistant Acinetobacter baumannii infection before surgery,experienced worsening infection and impaired renal function after lung transplantation,with sputum culture showing extensively drug-resistant Acinetobacter baumannii.After receiving combination treatment with sulbactam-durlobactam and meropenem,the infection was controlled,and the function of the transplanted lung was restored.Conclusions Sulbactam-durlobactam has potential therapeutic value for extensively drug-resistant Acinetobacter baumannii infection after lung transplantation and provides a new strategy for clinical practice.