Objective To evaluate the cost–utility of lecanemab and donanemab in the treatment of early Alzheimer’s disease （AD） in China. Methods A Markov model was developed from a societal perspective to compare standard of care （SOC）, lecanemab plus SOC, and donanemab plus SOC in terms of costs, quality-adjusted life years （QALY）, and incremental cost–utility ratios （ICUR）. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. Results Both intervention strategies increased QALY compared with SOC but were associated with substantially higher costs, and neither was cost-effective under the current willingness-to-pay threshold. Conclusion Lecanemab and donanemab may be more appropriately considered within a multi-tiered healthcare reimbursement framework in China rather than relying solely on basic medical insurance.

Objective To evaluate the cost-utility of risdiplam in the treatment of pediatric spinal muscular atrophy （SMA） and analyze changes in patients’ out-of-pocket economic burden under the medical insurance scenarios. Methods A Markov model was developed from the healthcare system perspective to compare the long-term costs and quality-adjusted life years （QALYs） of risdiplam treatment versus conventional therapy. The incremental cost-utility ratio （ICUR） was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the model. On this basis, health insurance scenarios were simulated to evaluate patients’ individual economic burden. Results Base-case analysis showed that risdiplam treatment generated additional health benefits but substantially increased medical costs. The resulting ICUR did not demonstrate a clear cost-utility advantage under the current willingness-to-pay threshold. Sensitivity analyses indicated that the model results were relatively robust, with drug costs and key utility parameters being the main drivers of economic outcomes. Health insurance scenario analysis demonstrated that increasing reimbursement levels and reducing patient copayment rates could significantly alleviate patients’ financial burden. Conclusion Risdiplam for pediatric SMA faces economic challenges under the current health insurance payment framework in China. However, optimizing health insurance reimbursement policies and developing multi-tiered healthcare security mechanisms may improve its affordability and accessibility.

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome. METHODS: From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded. RESULTS: Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment. CONCLUSIONS The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Rhinitis, Allergic/drug therapy* ; Female ; Adult ; Double-Blind Method ; Quality of Life ; Qi ; Middle Aged ; Loratadine/therapeutic use* ; Medicine, Chinese Traditional ; Syndrome ; Lung/drug effects* ; Young Adult ; Treatment Outcome

Organophosphorus pesticide(OP)is one of the most widely used pesticides in the world with the largest dosage.Acute organophosphorus pesticide poisoning(AOPP)is a common clinical disease,and AOPP accounts for 20%-50%of poisoning cases in China every year,with case fatality rate of 3%-40%.Bromophos(BDF)is a long-acting anticoagulant rodenticide,which inhibits vitamin K epoxide reductase and interferes with the synthesis of coagulation factorsⅡ,Ⅶ,Ⅸ and Ⅹ,leading to coagulation dysfunction.This article discusses the multidisciplinary diagnosis and treatment(MDT)process of a patient with combined poisoning of dichlorvos and bromadiolone.The article explores blood purification,management of coagulation abnormalities,secondary infection,atropinization and altered consciousnes in patients with organophosphorus poisoning and anticoagulant rodenticide compound poisoning,with the aim of providing clinicians with references for early diagnosis and treatment.

Objective:To construct a lentiviral interference plasmid targeting collapse response regulatory protein 1(CRMP1)gene,to establish a human neuroblastoma cell line(SH-SY5Y)with stable CRMP1 knockdown,and to investigate its impact on expression of NLRP3 inflammasome protein.Methods:Double-stranded shRNA was designed and synthesized targeting h-CRMP1 mRNA sequence,and cloned into PLKO.1 vector.Recombinant shCRMP1 plasmids were constructed correctly,which was transfected into HEK-293T cells for lentiviral packaging.Obtained lentivirus supernatant was concentrated and then infected into SH-SY5Y cells.The interference effect of shCRMP1 plasmid and protein expressions of NLRP3 inflammasome components in SH-SY5Y cells were detected by Western blot.Results:DNA sequencing results showed that insertion sequences of recombinant interference plasmids pLKO.1-shCRMP1 were consistent with designed sequences,which confirmed successful construction of shCRMP1 lentivirus interfering plasmids and transfected into HEK-293T cells for lentivirus packaging,and protein level of CRMP1 in HEK-293T cells were decreased.SH-SY5Y cells were infected with lentivirus concentrate obtained from packaging and screened with puromycin.Western blot results showed that shCRMP1 recombinant lentiviral plasmids could significantly down-regulate CRMP1 protein expression in SH-SY5Y cells.It was also found that in SH-SY5Y cell line with stable CRMP1 knockdown,inhibition of CRMP1 expression could effectively inhibit NLRP3 inflammasome activation under MPP+induction.Conclusion:pLKO.1-shCRMP1 lentiviral interfering plas-mids have been successfully constructed,and interference with CRMP1 can inhibit activation of NLRP3 inflammasome in MPP+-in-duced SH-SY5Y cells.This study provides guidance for further research on mechanism of CRMP1 in neurodegenerative diseases such as Parkinson's disease.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To evaluate the clinical value of three-dimensional(3D) printing-assisted fenestrated/branched endovascular aortic repair (F/B-TEVAR) for the treatment of endoleak after open surgery for type A aortic dissection.Methods:A multi-center retrospective case series analysis was conducted on 16 patients with anastomotic leakage following Stanford type A aortic dissection open repair, admitted to 12 medical centers between January 2019 and December 2023. All surgeries were led by the vascular surgery team from Department of Vascular Surgery, Nanjing Drum Tower Hospital. The study included 12 males and 4 females, with an age of (58.1±8.2) years (range: 42 to 75 years). Preoperative patient-specific 3D-printed models or 3D parametric surface topological guides were created based on aortic CT angiography data. These models assisted intraoperative external positioning of fenestration sites, combined with stent diameter selection and inner branch techniques to complete endovascular repair. Surgical procedures, complications, and clinical outcomes were evaluated, with follow-up CT imaging to assess efficacy.Results:All patients successfully underwent surgery without conversion to open repair. One patient had distal stent migration from a prior open repair, requiring intraoperative coverage of the main stent window and conversion to an in situ fenestration procedure. The mean operative time was (332.6±111.2)minutes (range: 80 to 460 minutes). No renal failure, paraplegia, or branch artery loss occurred. Postoperative follow-up ( M(IQR)) was 18(18) months(range: 6 to 36 months), with follow-up rates of 16/16 at 6 months, 10/16 at 12 months, 8/16 at 24 months, and 2/16 at 36 months. During follow-up, endoleak occurred in 3 patients, cerebral infarction in 1 patient, and death in 1 patient. The remaining patients demonstrated stable stent positioning, patent branches, and no endoleak. Conclusion:3D technology-guided F/B-TEVAR shows favorable mid-to short-term outcomes in treating anastomotic leakage after open repair of type A aortic dissection.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.