BACKGROUND: The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients. METHODS: 104 EGFR-mutated NSCLC-LM patients who received IP treatment at Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School from January 2018 to June 2024 were analyzed retrospectively. Clinical parameters, treatment regimens, and survival outcomes were collected. The overall survival (OS), progression-free survival (PFS), clinical response rate and adverse events (AEs) were evaluated. RESULTS: The cohort demonstrated a median PFS of 9.6 months and OS of 13.0 months with 6-month and 1-year OS rates of 80.8% and 56.5%, respectively. Clinical response was observed in 77.9% of patients. The common AEs were myelosuppression (58.7%) and elevation of hepatic aminotransferases (25.0%). Nine (8.7%) patients experienced grade 4 myelosuppression and recovered to normal after receiving symptomatic treatment. Subgroup analyses revealed prolonged OS in patients with Karnofsky performance status (KPS) ≥60 versus <60 (14.4 vs 9.0 months, P=0.0022) and those receiving Bevacizumab therapy versus not (19.2 vs 10.5 months, P=0.0011). CONCLUSIONS IP exhibits promising efficacy and manageable toxicity in EGFR-mutated NSCLC-LM patients. When combined with Bevacizumab, it exerts synergistic antitumor effects with the potential to further improve clinical outcomes.
Humans ; Pemetrexed/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Male ; Female ; Middle Aged ; Lung Neoplasms/pathology* ; ErbB Receptors/genetics* ; Aged ; Mutation ; Adult ; Retrospective Studies ; Injections, Spinal ; Meningeal Neoplasms/genetics* ; Treatment Outcome ; Aged, 80 and over

OBJECTIVE To investigate the distribution of Candida and predict the detection trend in the southern and northern campuses of Affiliated Hospital of Jiangnan University,Wuxi,between 2021 and 2024.METHODS A total of 27 056 patients with common Candida infections from the southern and northern campuses of Affiliated Hospital of Jiangnan University between 2021 and 2024 were selected to analyze the distribution of Candida species and predict the detection trend.RESULTS Among the 27 056 patients,there were 11 061 males and 15 995 fe-males,aged from 1 to 101 years,with a median age of 68 years.Over the past four years,the top five most com-monly detected Candida species in the hospital were Candida albicans,Candida glabrata,Candida tropicalis,Candida parapsilosis and Candida krusei.Statistically significant differences were found in infection characteris-tics among patients with C.albicans and C.glabrata in terms of gender,age,specimen source and related diseases(P＜0.05).From 2021 to 2024,the number of detected cases declined in 2022 and then rebounded(P＜0.001).Among the detected patients,those aged 70 and above accounted for the highest proportion.Regarding the distribution of specific diseases,the top three were vaginitis(4 176 cases,15.43％),bacterial pneumonia(1 842 cases,6.81％)and cancer(1 279 cases,4.73％).Patients with vaginitis were mainly infected with C.albicans,while patients with bacterial pneumonia were predominantly infected with C.albicans and C.glabrata.The LSTM model showed a good fit to the training set,with an root-mean-square error(RMSE)of 145.03 and an mean absolute error(MAE)of 131.19.Model predictions indicated that the number of patients with Candida in-fections in the hospital would remain low from Jan.to May 2025,which was basically consistent with actual clini-cal observations(RMSE=94.71,MAE=84.00).CONCLUSIONS The common diseases associated with Candi-da infections in the hospital include vaginitis,bacterial pneumonia and cancer.C.albicans and C.glabrata are the main pathogenic species,and the infection situation is relatively severe.The LSTM model performs well in short-term prediction and dynamic analysis of Candida detection trends.

In June 2018,sows at a pig farm in Jiamusi,Heilongjiang Province,suffered a large num-ber of miscarriages,and subsequently weaned piglets at the farm began to show persistent high fe-ver symptoms at around 35 days of age,with some pigs having a fever of more than 41.5 ℃.In or-der to determine the cause of this outbreak,63 clinical samples from this farm were tested.The re-sults showed that 60 out of 63 samples were positive for the porcine reproductive and respiratory syndrome virus(PRRSV)antigen.Subsequently,PRRSV antigen-positive plasmid was transfected into African green monkey embryonic kidney cells(Marc-145),and after three generations of blind transmission,indirect immunofluorescence assay(IFA)was performed.The results showed that one PRRSV strain,named HLJ38,was successfully isolated.Then the whole genome of HLJ38 strain was sequenced and then analyzed in detail by bioinformatics software.Sequence analysis showed that there were three deletions of 131 amino acids(323-433 aa,483 aa and 504-522 aa)in the derived sequence of Nsp2 gene of HLJ38 strain,which was consistent with the molecular ge-netic marker of NADC30 PRRSV.The phylogenetic tree analysis showed that HLJ38 and NADC30 PRRSV in GenBank belong to lineage 1 subgroup,and the nucleotide homology of HLJ38 and NADC30 PRRSV in GenBank was only 85.2％and 84.6％.Recombinant analysis showed that HLJ38 was a recombinant NADC30-like PRRSV,and the recombinant gene fragments were de-rived from multiple strains,among which the fragment of 1-201 nt was provided by VR2332 strain and fragment of 6 641-8 061 nt derived from the HP-PRRSV strain.In summary,the re-sults showed that the outbreak in this pig farm may be caused by the recombination of PRRSV strains among different lineages,and the recombinant circulating strains not only have certain pathogenicity but also suggest that the existing commercial vaccines provide limited cross-protec-tion against them.Recombination between different lineages increases the genetic diversity of PRRSV and aggravates the difficulty of prevention and control of PRRS in pig farms.Therefore,it is necessary to continuously monitor the epidemic dynamics of PRRSV in pig farms and take effec-tive measures in time to curb the spread of PRRS.

OBJECTIVE To investigate the distribution of Candida and predict the detection trend in the southern and northern campuses of Affiliated Hospital of Jiangnan University,Wuxi,between 2021 and 2024.METHODS A total of 27 056 patients with common Candida infections from the southern and northern campuses of Affiliated Hospital of Jiangnan University between 2021 and 2024 were selected to analyze the distribution of Candida species and predict the detection trend.RESULTS Among the 27 056 patients,there were 11 061 males and 15 995 fe-males,aged from 1 to 101 years,with a median age of 68 years.Over the past four years,the top five most com-monly detected Candida species in the hospital were Candida albicans,Candida glabrata,Candida tropicalis,Candida parapsilosis and Candida krusei.Statistically significant differences were found in infection characteris-tics among patients with C.albicans and C.glabrata in terms of gender,age,specimen source and related diseases(P＜0.05).From 2021 to 2024,the number of detected cases declined in 2022 and then rebounded(P＜0.001).Among the detected patients,those aged 70 and above accounted for the highest proportion.Regarding the distribution of specific diseases,the top three were vaginitis(4 176 cases,15.43％),bacterial pneumonia(1 842 cases,6.81％)and cancer(1 279 cases,4.73％).Patients with vaginitis were mainly infected with C.albicans,while patients with bacterial pneumonia were predominantly infected with C.albicans and C.glabrata.The LSTM model showed a good fit to the training set,with an root-mean-square error(RMSE)of 145.03 and an mean absolute error(MAE)of 131.19.Model predictions indicated that the number of patients with Candida in-fections in the hospital would remain low from Jan.to May 2025,which was basically consistent with actual clini-cal observations(RMSE=94.71,MAE=84.00).CONCLUSIONS The common diseases associated with Candi-da infections in the hospital include vaginitis,bacterial pneumonia and cancer.C.albicans and C.glabrata are the main pathogenic species,and the infection situation is relatively severe.The LSTM model performs well in short-term prediction and dynamic analysis of Candida detection trends.

In June 2018,sows at a pig farm in Jiamusi,Heilongjiang Province,suffered a large num-ber of miscarriages,and subsequently weaned piglets at the farm began to show persistent high fe-ver symptoms at around 35 days of age,with some pigs having a fever of more than 41.5 ℃.In or-der to determine the cause of this outbreak,63 clinical samples from this farm were tested.The re-sults showed that 60 out of 63 samples were positive for the porcine reproductive and respiratory syndrome virus(PRRSV)antigen.Subsequently,PRRSV antigen-positive plasmid was transfected into African green monkey embryonic kidney cells(Marc-145),and after three generations of blind transmission,indirect immunofluorescence assay(IFA)was performed.The results showed that one PRRSV strain,named HLJ38,was successfully isolated.Then the whole genome of HLJ38 strain was sequenced and then analyzed in detail by bioinformatics software.Sequence analysis showed that there were three deletions of 131 amino acids(323-433 aa,483 aa and 504-522 aa)in the derived sequence of Nsp2 gene of HLJ38 strain,which was consistent with the molecular ge-netic marker of NADC30 PRRSV.The phylogenetic tree analysis showed that HLJ38 and NADC30 PRRSV in GenBank belong to lineage 1 subgroup,and the nucleotide homology of HLJ38 and NADC30 PRRSV in GenBank was only 85.2％and 84.6％.Recombinant analysis showed that HLJ38 was a recombinant NADC30-like PRRSV,and the recombinant gene fragments were de-rived from multiple strains,among which the fragment of 1-201 nt was provided by VR2332 strain and fragment of 6 641-8 061 nt derived from the HP-PRRSV strain.In summary,the re-sults showed that the outbreak in this pig farm may be caused by the recombination of PRRSV strains among different lineages,and the recombinant circulating strains not only have certain pathogenicity but also suggest that the existing commercial vaccines provide limited cross-protec-tion against them.Recombination between different lineages increases the genetic diversity of PRRSV and aggravates the difficulty of prevention and control of PRRS in pig farms.Therefore,it is necessary to continuously monitor the epidemic dynamics of PRRSV in pig farms and take effec-tive measures in time to curb the spread of PRRS.

Objective:To isolate and identify SARS-CoV-2 epidemic strains and analyze the sequence characteristics of the virus strains following serial passages.Methods:Eleven nasopharyngeal swabs positive for SARS-CoV-2 antigen were collected from December 2022. Quantitative real-time PCR was used to detect SARS-CoV-2 nucleic acid, and positive specimens were inoculated onto Vero cells for virus isolation. The isolated strains were identified by Western blot and indirect immunofluorescence assay. The morphology of the isolated strains was observed using transmission electron microscopy. Nucleic acid was extracted from the isolates and passaged viruses for further sequencing and analysis.Results:All 11 specimens tested positive for SARS-CoV-2 using quantitative real-time PCR. SARS-CoV-2 strains were successfully isolated from seven specimens, and could be adaptively cultured, passaged, and expanded on Vero cells, achieving a peak titer exceeding 10 6.25 50% cell culture infectious dose (CCID 50)/ml. Western blot and indirect immunofluorescence results showed that the isolates could be specifically recognized by monoclonal antibodies and convalescent serum against SARS-CoV-2. Transmission electron microscopy revealed oval-shaped viral particles with diameters of approximately 100 nm. Next-generation sequencing of the viral isolates demonstrated a sequence homology greater than 99.50% with the Wuhan-Hu-1 reference strain (NC_045512) and 99.98% among the seven isolated strains, and all of the isolates belonged to the Omicron BF.7 variant. Sequence analysis after continuous passage and plaque purification of the BJ-NVSI-20230005 isolate showed that compared with passages 1-3, passages 4-6 had one nucleotide site mutation (C→T) in the ORF1ab gene and a deletion of 3 bp in the E gene, which resulted in a change from leucine to phenylalanine and the deletion of valine, respectively. Polymorphisms were observed in the sequences of plaque-purified clones. Conclusions:The seven successfully isolated SARS-CoV-2 strains all belong to the SARS-CoV-2 BF.7 variant, which is consistent with the prevalence trend in mainland China in December 2022.

Objective To assess the clinical and cranial CT/MR features of leptomeningeal metastasis(LM)from lung adenocar-cinoma with non-enhanced T2-fluid attenuated inversion recovery(T2-FLAIR)hyperintensity on the brainstem surface.Methods Eleven cases with LM from lung adenocarcinoma with non-enhanced T2-FLAIR hyperintensity on the brainstem surface confirmed by cere-brospinal fluid cytology were analyzed retrospectively.The clinical features included the pathological classification of the primary tumor,genetic testing results,and treatment methods.The imaging features included lesion location,MRI(T1 and T2)signals,diffusion weighted imaging(DWI)signal,enhancement patterns,CT density characteristics.Results The features of non-enhanced T2-FLAIR hyperintensity on the brainstem surface of 11 cases among 98 patients(11.2％)with LM from lung adenocarcinoma were reviewed.All patients were lung adenocarcinomas with epidermal growth factor receptor(EGFR)gene mutation and were diagnosed with LM after receiving EGFR-tyrosine kinase inhibitors(EGFR-TKIs)targeted therapy.There were 5 cases located in the pons,2 cases in the midbrain and pons,and 4 cases involving the midbrain,pons and medulla oblongata with the symmetrical band-like high signal on non-enhanced T2-FLAIR imaging.On T1WI,1 case showed slightly high signal,10 cases showed equal signal.On DWI,4 cases showed high signal,7 cases showed equal signal,and on enhanced T1WI,1 case showed mild enhancement,and 10 cases showed no enhancement.Additionally,on cranial CT scans,1 case showed calcification on the brainstem.Conclusion Non-enhanced T2-FLAIR hyperintensity on the brainstem surface may be more common among LM patient from lung adenocarcinoma with EGFR gene muta-tions and TKIs treatment,with the most frequent site being the pons.The features may include non-enhanced T2-FLAIR high signal,non-enhancement on enhanced T1 WI,restricted diffusion on DWI,and calcifications on CT imaging.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

Human enterovirus 71 (EV71) is one of the major causative agent of hand,foot and mouth disease (HFMD) in infant.Clinical studies find that EV71 infection can cause a variety of clinical manifestations,from mild HFMD to fatal neurogenic pulmonary edema and even death,but the reasons remain unclear.The capsid protein VP1 of EV71 plays a key role in the processes of viral recognizing,binding and entering into the targeted cells and viral particles assembling.VP1 variation is a major determinant to EV71 fitness and immunogenicity.This study reviews the research progress of the structure,functions and associated antiviral vaccines and drugs of VP1,which further provides a theoretical basis for developing new and more effective antiviral vaccine and drugs.

Objective To evaluate the BALB/c murine infective effects in different concentrations and different aerosol challenge times by Bordetella pertussis.Methods Four experiment groups according to different concentrations and different aerosol challenge times were designed.BALB/c murines were challenged by aerosol way.Group 1: 1010cfu/mL Bordetella pertussis challenge 15 min, group 2: 1010cfu/mL challenge 30 min, group 3: 109cfu/mL challenge 30 min, group 4: 1011cfu/mL challenge 30 min, using the normal saline challenge 30 min as control.At 0d,3d,7d,14d and 21d after challenge, the WBCs of all groups were measured and lung tissues were homogenized to calculate the bordetella pertussis clone in lung.Results After 3 days of challenge, WBCs in all groups were slightly increased.The WBCs of group 1, group 2, group 3 and group 4 were significantly increased after 7 days, with the average numbers of 8.52×109 per/L, 1.74×1010per/L, 1.15×1010per/L and 5×1010per/L, respectively.After 14 days, they were 1.77×1010per/L, 1.67×1010per/L, 1.27×1010per/L and 3.84×1010per/L respectively.WBCs in all groups were dramatically declined after 21 days.The WBC of negative control group had no obvious change during the whole process with the stable number of 3.4~7.0×109per/L.Bordetella pertussis were detected in lung of all experimental groups in each sampling point.The CFU in lung wase at peak at 7d or 14d after challenge, which was obviously decreased at 21d.Conclusion This aerosol challenge method can establish a bordetella pertussis infection mouse model successfully.