ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

To summarize the perioperative nursing experience of a premature infant with ABO hemolytic disease who underwent resection of giant Altman type Ⅰ sacrococcygeal teratoma at 43 hours after birth.Key points of preoperative nursing care include the cooperative blood transfusion to correct anemia,and the protection of tumor body,the prevention of rupture and bleeding.Key points of intraoperative nursing care include the personalized postural safety management,the target-oriented fluid therapy to maintain circulation stability,and composite insulation measures to prevent hypothermia.Key points of postoperative nursing care include sequential fluid replenishment to treat neonatal capillary leakage syndrome;protective ventilation strategies to maintain effective breathing;precision wound care,prevention and control of postoperative infection;progressive mixed feeding;to empower family members and improve the quality of continuous rehabilitation.After careful treatment and nursing care,the patient was discharged 18 days after surgery.During the 7-month follow-up,the growth and development were normal.

Objective To explore the effects of high-intensity interval training on fatigue sensation and prognosis in patients with chronic obstructive pulmonary disease(COPD).Methods Sixty patients with COPD treated in outpatient and inpatient departments of our hospital from January to December 2024 were enrolled and randomly divided into a control group and an experimental group using a random number table method,with 30 patients in each group.The control group received conventional rehabilitation training,while the experimental group received high-intensity interval training on the basis of conventional rehabilitation training.Before and after the intervention,the pulmonary function indices(forced expiratory volume in the first second(FEV1),FEV1/forced vital capacity(FVC),diffusing capacity of the lung for carbon monoxide(DLCO)),exercise capacity(6-minute walk test(6MWT),peak oxygen uptake,and load power),subjective fatigue sensation(Fatigue Severity Scale,FSS),and serum level of interleukin-6(IL-6)of the two groups were measured,and the number of acute exacerbations during the 12-week intervention was counted.Results Compared with pre-intervention levels,the post-intervention experimental group showed significant improvements in FEV1 absolute value,percentage of FEV1 to FVC,DLCO,6MWT,peak oxygen uptake,and load power,along with reduced FSS scores and IL-6 levels(P<0.05).In the control group,only load power changed significant-ly(P<0.05),while other indicators showed no significant improvement(P>0.05).The experimental group had fewer acute exacerbations than the control group.Correlation analysis revealed positive correlation be-tween FSS scores and IL-6 levels(r=0.47,P<0.01).Conclusion High-intensity interval training can im-prove fatigue status,pulmonary function,exercise capacity,and inflammatory levels in COPD patients while reducing acute exacerbation risk.Fatigue sensation scores may serve as a potential indicator for assessing COPD disease progression and prognosis.

Objective To analyze the characteristics and drug resistance of pathogenic bacteria isolated from patients undergoing solid organ transplantation(SOT)at West China Hospital,Sichuan University in re-cent years,in order to provide a basis for empirical anti infective treatment after SOT surgery.Methods A retrospective analysis was conducted on the isolation of major pathogens and their resistance to common anti-biotics from various specimens collected from patients undergoing kidney transplantation(KT),liver trans-plantation(LTx),and lung transplantation(LT)at West China Hospital,Sichuan University from 2017 to 2022.Results A total of 1 077 non-duplicate strains of pathogens were isolated from the samples of patients with infections after SOT surgery during the 6-year period,of which approximately 74.8％(806/1 077)were Gram negative bacteria and 25.2％(271/1 077)were Gram positive bacteria.There were differences in the distribution of pathogenic bacteria among different types of SOT groups and different specimens.Compared to E.coli isolated from urine specimens,the strains of E.coli isolated from non-urinary specimens exhibited a higher resistance rate to common antimicrobial drugs(P＜0.05).The resistance rate of E.coli to β-lactam/β-lactamase inhibitor combinations(cefoperazone/sulbactam and piperacillin/tazobactam)in the LTx group was significantly higher than that in the KT group(P＜0.05).The overall proportion of multidrug-resistant bac-teria after SOT surgery was 11.3％(122/1 077).The proportion of carbapenem resistant Acinetobacter bau-mannii and carbapenem resistant Pseudomonas aeruginosa among the same group and type of pathogens in the LTx group(93.8％,37.5％)was significantly higher than that in the KT group(55.8％,9.2％).Conclusion The specimen types and strain distribution of pathogenic bacteria after different types of SOT surgery are different.The same pathogenic bacteria have different antibiotic resistance among different types of SOT groups and specimens.Therefore,it is necessary to strengthen the pathogen examination after different types of SOT and optimize the anti infection treatment plan related to transplantation based on drug sensitivity re-sults.

To summarize the perioperative nursing experience of a premature infant with ABO hemolytic disease who underwent resection of giant Altman type Ⅰ sacrococcygeal teratoma at 43 hours after birth.Key points of preoperative nursing care include the cooperative blood transfusion to correct anemia,and the protection of tumor body,the prevention of rupture and bleeding.Key points of intraoperative nursing care include the personalized postural safety management,the target-oriented fluid therapy to maintain circulation stability,and composite insulation measures to prevent hypothermia.Key points of postoperative nursing care include sequential fluid replenishment to treat neonatal capillary leakage syndrome;protective ventilation strategies to maintain effective breathing;precision wound care,prevention and control of postoperative infection;progressive mixed feeding;to empower family members and improve the quality of continuous rehabilitation.After careful treatment and nursing care,the patient was discharged 18 days after surgery.During the 7-month follow-up,the growth and development were normal.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Objective:To investigate the relationship between the virulence and the carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection,and to identify carbapenem-resistant and hypervirulent Klebsiella pneumoniae(CR-HVKP)strains.Methods:A total of 192 Klebsiella pneumoniae strains were isolated from blood culture of patients with bloodstream infections from 2016 to 2019,of which 96 isolates were carbapenem-resistant Klebsiella pneumoniae(CRKP)and 96 were carbapenem-sensitive Klebsiella pneumoniae(CSKP).The drug susceptibility was detected by VITEK-2 automatic microbial analyzer;carbapenemase genes,virulence genes and capsule typing were detected by polymerase chain reaction;the high viscosity phenotype of strains was detected by string test,and the genome characteristics of CR-HVKP were detected by whole genome sequencing.Serum killing and biofilm formation test were used to further verify the virulence of CR-HVKP.Results:There were significant differences in drug resistance to common antibiotics,except for minocycline between CSKP and CRKP isolates(all P<0.05).92 out of 96 CRKP isolates carried carbapenemase genes,mainly blaKPC-2.The string tests were positive in 4 isolates of CRKP and 36 isolates of CSKP(P<0.05).The detection rates of virulence genes Kfu,aerobictin,iutA,ybtS,rmpA,magA,allS,and capsule antigen K1 and K2 in CSKP group were significantly higher than those in CRKP group(all P<0.05).One HVKP strain was detected in the CRKP group(CR-HVKP)and 36 HVKP was detected in the CSKP group(P<0.05).The CR-HVKP strain belonged to the MLST412,serotype K57,expressed iutA,entB,mrkD,fimH,and rmpA virulence genes,and showed strong biofilm formation and significantly increased serum resistance.Whole genome sequencing results showed that this CR-HVKP isolate carried blaSHV-145,blaTEM-1,blaCTX-M-3,fosA6,oqxA5,oqxB26,and aac(3)-Ⅱd resistance genes,accompanied by abnormalities in outer membrane protein K(OmpK)35 and OmpK36.Conclusions:The drug resistance of CRKP is significantly higher than that of CSKP,while CRKP carrying fewer virulence genes in both number and types compared to CSKP.A new MLST type of carbapenem-resistant and hypervirulent Klebsiella pneumoniae strain has been detected,which requires clinical awareness and epidemiological monitoring.

Objective To analyze the distribution of ocular bacterial pathogens and their antibiotic resistance status at a tertiary-care hospital and to provide a reference for the appropriate use of antibiotics.Methods Retrospective analysis was conducted with bacteria isolated from the ophthalmic samples sent for lab analysis at a tertiary-care hospital from 2012 to 2021.The suspected bacterial strains were identified with automated systems for microbial identification and susceptibility analysis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer.VITEK 2 Compact,an automated microbial identification and antibiotic susceptibility analysis system,was used for antimicrobial susceptibility testing.Results A total of 1556 ophthalmology bacteria culture samples were collected,574 of which showed bacterial growth,presenting an overall positive rate of 36.89%.Of the isolated bacteria,Gram-positive cocci,Gram-positive bacilli,Gram-negative bacilli,and Gram-negative cocci accounted for 63.15%(377/597),18.76%(112/597),17.09%(102/597),and 1.00%(6/597),respectively.Among the bacteria isolated in different years over the course of a decade,Gram-positive cocci always turned out to be the main cause of eye infections.Of the Gram-positive cocci,73.47%(277/377)were isolated from patients with endophthalmitis,with the most important species being Staphylococcus epidermidis,which was followed by Streptococcus viridans.The rest,or 26.53%(100/377),of the Gram-positive cocci were isolated from patients with external eye infections,with the main isolated strains being Staphylococcus epidermidis,Streptococcus viridans,and Staphylococcus aureus.More than 70%of Staphylococcus epidermidis isolated from both endophthalmitis and external eye infections were resistant to methicillin.No strains resistant to vancomycin,linezolid,or tigecycline were detected.Staphylococcus epidermidis isolated from patients with external eye infections had a low rate of resistance to levofloxacin(2/27 or 7.41%),whereas those isolated from patients with endophthalmitis had a higher resistance rate(43/127 or 33.86%).The difference in drug resistance rate between the two groups was statistically significant(P<0.05).Conclusion The chief ocular bacterial pathogens identified in a tertiary-care hospital were Gram-positive cocci,among which,Staphylococcus epidermidis was the most common species.The Staphylococcus epidermidis identified in the hospital had a high rate of resistance to oxacillin,but remained highly sensitive to vancomycin,linezolid,and tigecycline.The endophthalmitis caused by Staphylococcus epidermidis in the hospital can be treated empirically with vancomycin and then the treatment plan can be further adjusted according to the results of the drug susceptibility test.However,the establishment of the breakpoint of drug susceptibility test is mainly based on the model of bloodstream infection and has limited reference value for the treatment of eye infection.The required drug distribution concentration at the infection site can be achieved by dose increase or local administration.

Objective To study the distribution and drug resistance characteristics of pathogenic bacteria in the elderly population of China by collecting and analyzing the standardized case data on the pathogens of infections in elderly patients,and to facilitate the establishment of a standardized layered surveillance system for pathogenic bacteria in China.Methods We collected the case data of elderly patients(≥65 years old)from 62 sentinel hospitals across the country in 2021.Then,we statistically analyzed the data by patient age,their geographical region,the distribution of pathogenic bacteria,and the drug resistance characteristics of main pathogens.Results A total of 3468 cases from across the country were included in the study.The top three sources of patients were the intensive care unit(13.2%),the department of respiratory medicine(11.2%),and the department of general surgery(8.4%).The top three types of specimens were urine(25.5%),sputum(20.6%),and blood(18.7%).A total of 3468 strains of pathogens were isolated,among which,78.9%were gram-negative bacteria and 21.1%were gram-positive bacteria.The top five types of bacteria were Escherichia coli(20.9%),Klebsiella pneumoniae(18.3%),Pseudomonas aeruginosa(11.2%),Staphylococcus aureus(9.0%),and Acinetobacter baumannii(7.0%).The isolation rates of common important drug-resistant bacteria were 38.0%for methicillin-resistant Staphylococcus aureus(MRSA),68.7%for carbapenem-resistant Acinetobacter baumannii(CRAB),and 38.2%for carbapenem-resistant Pseudomonas aeruginosa(CRPA),20.1%for carbapenem-resistant Klebsiella pneumoniae(CRKP),5.2%for carbapenem-resistant Escherichia coli(CRECO),and 2.1%for vancomycin-resistant Enterococcus(VRE).There were differences in the isolation rates of CRAB and CRKP in clinical care in the elderly population in seven geographical regions of China(P＜0.05).Klebsiella pneumoniae is the most important pathogen in the elderly population≥85 years old,and the isolation rates of CRKP showed significant differences in different age groups(P＜0.05).Conclusion There are significant differences in the drug resistance of pathogenic bacteria in the elderly populations of different regions and age groups in China.Therefore,monitoring the distribution and drug resistance of pathogenic bacteria in the elderly population and formulating targeted treatment plans according to the characteristics of the specific regions and age groups are of great significance to the improvement in the treatment outcomes and prognosis of the elderly population.