A 75-year-old male patient with non-small cell lung cancer in the lower lobe of the left lung underwent left lobectomy, followed by 4 cycles of adjuvant chemotherapy with paclitaxel and platinum, 4 cycles of chemotherapy with docetaxel and cisplatin, and immunotherapy with sintilimab, 13 cycles of immunotherapy with sintilimab monotherapy, and 5 cycles of endostatin and sintilimab, spanning a total of 5 years. Due to disease progression, he received the monotherapy with anlotinib, 42 days later, the patient developed intestinal perforation, and laparoscopic ileal perforation repair surgery was performed. During the operation, a perforation with a diameter of about 1 cm was observed in the ileum, indicating the outflow of digestive fluid and a large amount of purulent fluid accumulation in the pelvic cavity; no signs of gastrointestinal tumor metastasis were observed. After surgery, the patient developed abdominal infection and peritonitis, and was given symptomatic and supportive treatments such as anti-infection for 7 days. However, the patient developed severe complications such as lung infection, heart failure, sepsis, and respiratory failure, and died.

Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

Objective:To explore the mediating role of cyber self-efficacy between technological anxiety and the willingness to use tele-rehabilitation among patients with chronic obstructive pulmonary disease (COPD) .Methods:From September 2023 to May 2024, a convenience sampling method was used to select COPD patients receiving treatment in the Inpatient Department of Zhoushan Hospital as the research subjects. A General Information Questionnaire, the Scale of Willingness to Use Tele-Rehabilitation for COPD Patients, the Technological Anxiety Scale, and the Cyber Self-Efficacy Questionnaire were used to collect data.Results:A total of 312 questionnaires were distributed, and 305 valid questionnaires were retrieved, with an effective recovery rate of 97.76%. The average score of the Scale of Willingness to Use Tele-Rehabilitation for the 305 COPD patients was (76.52±5.30) , and the average item score was (2.94±0.20) . Cyber self-efficacy played a partial mediating role between technological anxiety and the willingness to use tele-rehabilitation, accounting for 8.21% of the total effect (-0.048/-0.585) .Conclusions:The level of willingness to use tele-rehabilitation among COPD patients needs to be enhanced. The professional values of COPD patients not only directly affect their level of willingness to use tele-rehabilitation, but also influence their technological anxiety, which in turn affects their cyber self-efficacy, ultimately having an indirect impact on the willingness to use tele-rehabilitation. Nursing staff should strengthen the professional values of COPD patients, help them overcome technological anxiety, and enhance their cyber self-efficacy, so as to increase their willingness to use tele-rehabilitation.

Objective To investigate the correlation between thyroid hormone(TH)sensitivity and diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 949 T2DM patients with normal thyroid function were selected from the National Standardized Metabolic Disease Management Center database of our hospital between May 2020 and October 2024.All the patients were divided into DKD group(n=466)with urinary albumin/creatinine ratio(UACR)≥30 mg/g and simple T2DM group(n=483)with UACR<30 mg/g.Free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),thyroid feedback quantification index(TFQI),thyroid stimulating hormone resistance index(TT4RI),thyroid stimulating hormone index(TSHI),FT3/FT4 were compared between the two groups.Results Body mass index(BMI),DM duration,subcutaneous fat area(SFA),blood urea nitrogen(BUN),serum creatinine(Scr),UACR,TSHI and FT4 were higher(P<0.05 or P<0.01),while FT3,TFQI was lower in DKD group than in T2DM group(P<0.05).Spearman correlation analysis showed that TT4RI was positively correlated with Scr(P<0.05),and FT3/FT4 was negatively correlated with UACR(P<0.05)in DKD group.TT4RI was positively correlated with UACR in T2DM group(P<0.05).Logistic regression analysis showed that FT3,BUN and BMI were influencing factors for DKD.The model formula was established as follows:DKD=0.711+0.102×BMI-0.002×SFA+0.138×BUN+0.007×Scr-0.578×FT3-0.089×FT4+0.750×TFQI-0.277×TSHI,which can forecasted the risk of DKD occurrence by 10%.The receiver operator characteristic curve evaluated the area under the curre of the above model formula as 0.705,the sensitivity was 49.1%,the specificity was 80.3%,and the cut-off value was 0.464.Conclusions With normal thyroid function,impaired central and peripheral TH sensitivity is correlated with T2DM combined with DKD,and elevated FT3 is a protective factor for T2DM combined with DKD.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

The aim of this study was to establish a rapid,highly sensitive,and specific nucleic acid detection method for the H5N6 and H9N2 avian influenza virus(AIV)subtypes by using reverse transcription-recombinase polymerase amplification(RT-RPA)combined with clustered regularly interspaced short palindromic repeats(CRISPR)-Cas13a proteins.The conserved regions were selected to design specific RT-RPA primers and crRNA sequences of H5,H6,H9,and N2 genes.RT-RPA tech-nology combined with CRISPR-Cas13a detection was used to evaluate the sensitivity and specificity of AIV nucleic acid detec-tion.The detection was performed on avian influenza environmental samples and compared with the results of fluorescence quantitative RT-PCR,to evaluate the effectiveness of the RT-RPA technology combined with CRISPR-Cas13a.AIV H5,H9,and N2 subtypes were detected with a sensitivity as high as 1 copy/μL,and AIV N6 subtypes were detected with a sensitivity of 10 copies/μL.Plasmid samples with differing copy numbers showed fluorescence under blue LED transillumination.The four AIV subtypes showed high specificity and did not cross-react with the other AIV subtypes.The detection of avian influenza ex-ternal environmental samples containing AIV H5,N6,and H9 subtypes was consistent with the results of fluorescence quanti-tative RT-PCR,with 100％accuracy.For AIV N2 subtypes,one additional negative sample was detected with 97.9％accuracy.The established RT-RPA technology combined with CRISPR-Cas13a detection enabled sensitive,specific visual detection of AIV H5N6 and H9N2 subtypes.This study provides a new nucleic acid detection method for AIV surveillance and subtype clas-sification.

Copper is one of the essential elements in the human body,playing various physiological roles.Maintai-ning copper homeostasis is crucial for health.Recent researches have uncovered that copper homeostasis imbalance is closely associated with the occurrence,progression,prognosis,and drug resistance of gynecological malignancies.The employment of copper and its complexes in antitumor therapy has emerged as a promising novel approach,attracting considerable research attention.Based on the relationship between copper homeostasis imbalance and gynecological tumors,this paper provides a concise review of the current status and progress of copper and its complexes in the treat-ment of gynecological tumors.

This study was aimed at comprehensively understanding the epidemic status of acute hemorrhagic conjunctivitis(AHC)and influencing factors related outbreak in Fujian Province,to provide valuable insights for AHC prevention and control in this region.We conducted a descriptive statistical analysis of epidemiological data for AHC cases.Additionally,clinical samples collected from a 2023 outbreak were subjected to pathogen detection,determination of full-length nucleotide sequences within the VP1 region,genotype identification,and comprehensive analysis.The peak incidence of AHC in 2023 was observed in September and accounted for a substantial proportion(86.39%,5 205/6 025)of the total cases throughout the year.The three areas with the highest incidence rates were Sanming(118.57/100 000),Longyan(53.83/100 000)and Zhangzhou(16.02/100 000).From 2011 to 2022,the inci-dence of AHC in Longyan City was the highest for consecutive 12 years.During the peak AHC outbreak period in Fujian Province in 2023,all 62 conjunctival swabs collected were identified as CVA24v,and 60 complete VP1 sequences were obtained through se-quencing.The nucleotide sequence identity among these 60 sequences ranged from 98.7%to 100%,whereas the amino acid identity ranged from 98.4%to 100%.The highest nucleotide sequence identity was observed for the 2023 strain isolated from Zhongshan,Guangdong Province(rang:99.0%～100%).The 2023 strains in Fujian Province belonged to the GIV genotype,and L16I represented a potential unique amino acid variation within the sequence.CVA24v was the causative agent responsible for this AHC epidemic,and its GIV genotype is currently the dominant type in China.Future efforts should prioritize AHC prevention and control measures cen-tered in key cities.Monitoring and early warning of AHC in the whole province should be strengthened before September each year,and the variation of pathogen nucleic should also be tracked in time.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.