Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

Methods:A total of 160 Wistar neonatal rats were assigned into normoxia group, HPH group, normoxia+PDGF-BB group, HPH+PDGF-BB group and HPH+PDGF-BB inhibitor (STI571) group using random number table method (32 rats in each group), each group was further assigned into 4 subgroups on d3, d7, d14 and d21 (8 rats in each subgroup). HPH model was established using nitrogen-oxygen mixture with an oxygen concentration of 10%±0.5%. PDGF-BB groups were injected with adenovirus encoding PDGF-BB in the tail vein. HPH+STI571 group was given STI571 intragastrically. On d3, d7, d14 and d21 after modeling, mean right ventricular systolic pressure (RVSP) was examined. Morphological changes of small pulmonary arteries were observed using HE staining and indicators of pulmonary vascular remodeling calculated. Immunohistochemistry was used to determine the protein levels of PDGF-BB, HIF-1α and proliferation-associated protein nuclear protein Ki67 in the pulmonary vasculature of each group. RT-qPCR was used to determine the mRNA levels of PDGF-BB, HIF-1α and Ki67 in lung tissue.Results:At all time points, RVSP was higher in the HPH group than the normoxia group ( P<0.05), higher in the HPH+PDGF-BB group than the HPH group ( P<0.05), and lower in the HPH+STI571 group than both the HPH+PDGF-BB group and the HPH group ( P<0.05). On d3 after modeling, pulmonary vascular remodeling occurred in the HPH+PDGF-BB group; on d7, pulmonary vascular remodeling occurred in the PDGF-BB group and the HPH group. Pulmonary vascular remodeling appeared later and to a lesser extent in the HPH+STI571 group than the other hypoxic groups. On d3, d7 and d21 after modeling, protein and mRNA levels of PDGF-BB, HIF-1α and Ki67 in the HPH+PDGF-BB group were higher than the other groups ( P<0.05). The protein and mRNA expression levels of PDGF-BB, HIF-1α and Ki67 in the HPH+STI571 group were lower than the HPH+PDGF-BB group and the HPH group at all timepoints ( P<0.05). Conclusions:PDGF-BB up-regulates HIF-1α expression, participates in PASMC proliferation, exacerbates pulmonary vascular remodeling and increases pulmonary artery pressure in neonatal rats with HPH.Obiective:To study the roles of platelet-derived growth factor-BB (PDGF-BB) in hypoxic pulmonary hypertension (HPH) and the mechanisms of regulating hypoxia-inducible factor-1α (HIF-1α) expression, promoting the proliferation of pulmonary arterial smooth muscle cells (PASMC) and participating in the remodeling of pulmonary vessels.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective To observe the value of habitat model based on lung CT for predicting brain metastasis(BM)of lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation.Methods Data of plain lung CT of 198 lung adenocarcinoma patients with EGFR-mutant were retrospectively analyzed.The patients were divided into training set(n=138)and test set(n=60)at the ratio of 7∶3,and further divided into BM subgroup and non-BM subgroup in each set.Then a logistic regression(LR)clinical model was constructed using variables being statistically different between subgroups in training set.For features extracted from tumor and subregion of tumor,radiomics models and habitat models were constructed based on random forest,Gaussian process(GP)and support vector machine(SVM)algorithms,and the best radiomics and habitat models with generalization ability were screened.LR combined model was constructed based on the predicted values of the best radiomics and habitat models with generalization ability,as well as the clinical model.Then receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting BM of lung adenocarcinoma with EGFR-mutant.Spearman correlation analysis was performed to observe the correlations between Ki-67 and habitat features of lung adenocarcinoma with EGFR-mutant.Results AUC of LR clinical model,GP radiomics model,SVM habitat model and LR combined model for predicting BM of lung adenocarcinoma with EGFR-mutant was 0.700,0.726,0.801 and 0.834 in training set,0.754,0.600,0.715 and 0.848 in test set,respectively.AUC of LR combined model was higher than that of LR clinical model in training set(P＜0.001),also higher than that of GP radiomics model in test set(P=0.010).Compared with GP radiomics model and SVM habitat model,the performance of LR combined model was significantly and positively improved in training set(integrated discrimination improvement index[IDI]=8.60%,8.55%,both P＜0.001).Ki-67 level of EGFR-mutant lung adenocarcinoma was lowly and positively correlated with habitatmap_original_glszm_lalgle extracted from habitat map(│rs│=0.201,P=0.004).Conclusion The habitat model based on lung CT could be used to predict BM of lung adenocarcinoma with EGFR-mutant effectively.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Urban traffic is closely related to the daily life of the public,and air pollution in the traffic microenvironment has become a public health problem that cannot be ignored.This paper reviews the comparative studies of air pollutant exposure levels among different modes of transportation in multiple cities in China.By com-paring the exposure levels of pollutants among different modes of transportation,this paper provides a reference for protecting the health of the public in daily transportation and selecting targeted control measures.

Objective: To investigate the epidemiological characteristics of human brucellosis in Jiaxing City from 2010 to 2021, so as to provide insights into the development of the brucellosis control strategy. Methods: The epidemiological and clinical data of brucellosis patients and epidemiological data of brucellosis outbreaks in Jiaxing City from 2010 to 2021 were collected from Chinese Disease Control and Prevention Information System, and the epidemiological features and outbreaks of brucellosis were analyzed descriptively. Results: Totally 160 brucellosis patients were reported in Jiaxing City from 2010 to 2021, and the incidence of brucellosis appeared a tendency towards a rise (χ2trend=28.564, P=0.002), with annual mean incidence of 0.29/105. No deaths due to brucellosis occurred in Jiaxing City from 2010 to 2021. Brucellosis cases were reported each month, which were concentrated in the first and second quarters, and the greatest number was seen in May (27 cases, 16.88%). The brucellosis cases were predominantly reported in Tongxiang City (114 cases, 71.25%), and 75.00% were male (120 cases) and 70.63% were occupational populations (113 cases). The patients had a median (interquartile range) age of 57 (12) years at onset, and the median duration (interquartile range) from onset to definitive diagnosis was 18 (28) days. The clinical manifestations mainly included fever and weakness, and a total of 18 Brucella melitensis isolates and one B. bovis isolate were cultured. Conclusions The incidence of brucellosis was rising in Jiaxing City from 2010 to 2021. The brucellosis patients were predominantly reported in Tongxiang City in the first and second quarters, and young, middle-aged men and occupational populations were at a high risk of brucellosis.

Objective:To evaluate the efficacy of endoscopic ultrasound-guided drainage (EUS-GD) and percutaneous drainage (PD) for the treatment of pancreatic pseudocyst (PPC) by meta-analysis.Methods:The key words were pancreatic pseudocyst, endoscopic ultrasonography, percutaneous drainage, endoscopic ultrasound-guided, EUS and EUS-guided, and the databases of CNKI, Wanfang, PubMed and Web of science were searched from the establishment to October 1, 2021 for the retrospective cohort studies on PD, endoscopic ultrasonography and PPC. The article were screened and the quality was evaluated according to the pre-set inclusion and exclusion criteria; and important data were extracted. The software REVMAN5.3 was used for meta-analysis.Results:14 articles were finally included, and a total of 843 patients with PPC were enrolled (485 in the EUS-GD group and 358 in the PD group). Mesh meta-analysis showed that in the incidence of technical success rate, clinical success rate and complication rate, there were no significant differences between PD group and EUS-GD group ( OR=0.69, 95% CI 0.32-1.46; OR=1.31, 95% CI 0.88-1.95; OR=1.01, 95% CI 0.70-1.47, all P value >0.05); but the incidence of the recurrence rate and reintervention rate in EUS-GD group were significantly lower than those in the PD group and the differences were statistically significant ( OR=0.45, 95% CI 0.23-0.85; OR=0.51, 95% CI 0.28-0.93, all P value <0.05). Conclusions:Compared with PD, EUS-GD can significantly reduce recurrence rate and complication rate, and it has more advantages than PD for the treatment of PPC.