Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

Objective:To investigate the clinical characteristics of patients with multiple myeloma(MM)complicated by bone lesions and the risk factors associated with bone lesions.Methods:The clinical data of 294 newly diagnosed MM patients in Gansu Provincial Hospital from January 2017 to June 2021 were retrospectively analyzed.The patients were divided into the bone lesion group(154 cases)and the non-bone lesions group(140 cases)based on the presence of absence of bone lesions at diagnosis.The general data and laboratory parameters were compared between the two groups.The risk factors for bone lesions in MM patients were analyzed by logistic regression analysis,and the characteristic(ROC)curves were plotted to assess the predictive value of each risk factor for the occurrence of bone lesions in MM patients.Results:Compared to the non-bone lesion group,the bone lesion group had significantly higher serum calcium levels and significantly greater proportions of patients with Durie-Salmon(DS)stage Ⅲ,and bone pain(all P＜0.05).Logistic regression analysis showed that elevated serum calcium(OR=5.135,95％CI:1.931-13.653,P=0.001),DS stage Ⅲ(OR=1.841,95％CI:1.019-3.328,P=0.043),and bone pain(OR=8.208,95％CI:4.761-14.151,P＜0.001)were independent risk factors for bone lesions in MM patients.ROC curve analysis showed that serum calcium(AUC=0.619,95％CI:0.555-0.683,P＜0.001)and bone pain(AUC=0.743,95％CI:0.692-0.793,P＜0.001)had predictive value for bone lesions in MM patients.Conclusion:MM patients have a high incidence of bone lesions,and active monitoring and management of risk factors may improve treatment outcomes and prognosis.

Objective To elucidate the correlation between specific nucleocapsid(N)protein mutant of the SARS-CoV-2 B.1.1.7 variant and clinical stratification in COVID-19 patients,revealing their impact on N protein liquid-liquid phase separation(LLPS)and host innate immune response.Methods Based on whole-genome sequencing data of the SARS-CoV-2 B.1.1.7 lineage from the GISAID database,non-synonymous mutation sites significantly associated with mild/severe clinical phenotypes were screened.For high-frequency N protein mutant,IFN-β promoter transcriptional activity was quantitatively measured using a dual-luciferase reporter system.qPCR was used to detect the mRNA expression levels of interferon(IFN)-β,interleukin(IL)-6 and tumor necrosis factor(TNF)-α.LLPS characteristics were observed by confocal microscopy.The ubiquitination status of host MAVS was detected by Western blot assay.Results A total of 17 640 non-synonymous mutation sites were identified,among which 65 were associated with mild cases and 20 were related to severe cases,with a mutation frequency>1%.The N protein mutation sites associated with severe cases were D3L,M234I and R203K-G204R-T205I.N protein and the mutants NM234I,NR203K-G204R-T205I inhibited the promoter activity of IFN-β(P＜0.05).Compared to the wild type N protein,NR203K-G204R-T205I mutation significantly reduced the mRNA levels of IFN-β,IL-6 and TNF-α(P＜0.05),and altered the phase separation state by dispersing the formation of LLPS condensates.However,N mutant did not affect the ubiquitination modification of host MAVS.Conclusion N protein mutants of the SARS-CoV-2 B.1.1.7 variant can influence the clinical prognosis of COVID-19 patients by altering LLPS status and suppressing the innate immune responses.These finding provides a theoretical basis for the design of antiviral drugs targeting the N protein.

BACKGROUND:In the repair of large bone defects,a variety of factors such as seed cell passaging can cause senescence of osteoblasts,leading to a reduction in osteogenic differentiation activity after implantation of tissue-engineered bone.In recent years,a novel mechanism involving primary cilia in cell senescence has been widely studied,but the primary cilia-related mechanism of"passage senescence-reduced osteogenic activity"is not fully understood.OBJECTIVE:To explore the possible mechanisms by which primary cilia regulate the senescence of MC3T3-E1 cells.METHODS:The osteoblast precursor cell lines MC3T3-E1 were passaged to 10th generation cells(early passage)and 40th generation cells(late passage).siRNA was used to silence IFT88 to inhibit primary cilia formation.The cells were than grouped into passage 10 group,passage 40 group,passage 10+siRNA IFT88 group,and passage 40+siRNA IFT88 group.RT-PCR and western blot assays were used to detect the expression of the aging marker P16(CDKN2A),the osteogenic activity markers bone morphogenetic protein 2 and alkaline phosphatase,and the Hedgehog pathway IHH expression.Alizarin red staining and primary cilia immunofluorescence staining were performed.Spearman correlation analysis was conducted to analyze primary cilia positive rate and IHH and bone morphogenetic protein 2 expression.RESULTS AND CONCLUSION:(1)The expression of CDKN2A(P16)in the passage 10 group was significantly higher than in the passage 40 group,but the difference disappeared after siRNA IFT88 intervention.(2)Meanwhile,the positive rate of primary cilia cells in the passage 10 group were higher than in the passage 40 group,while siRNA IFT88-significantly inhibited the expression of primary cilia in both passage 10 and passage 40 cells.(3)The transcriptional activity and protein expression of bone morphogenetic protein 2 and alkaline phosphatase in the passage 10 group were higher than those in the passage 40 group.After inhibiting the expression of primary cilia with siRNA,the above differences were reduced or disappeared.(4)The positive rate of primary cilia cells was correlated with IHH and bone morphogenetic protein 2 protein expression.To conclude,primary cilia mediate the replicative senescence of osteogenic MC3T3-E1 cells and regulate osteogenic differentiation ability.

Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P＜0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P＜0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P＜0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P＜0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

Objective To propose a dynamic electrical impedance tomography imaging algorithm based on complementary information fusion network(CIFN)to enhance image quality of dynamic electrical impedance imaging.Methods There were three modules for initialization,multi-frame complementary information extraction and information fusion involved in the CIFN.Firstly,multi-frame dynamic conductivity distribution images were obtained by the initialization module;secondly,spatial complementary information was extracted from the images by using the multi-frame complementary information extraction module;finally,the fusion of lesion target distribution information and target re-reconstruction were realized by the information fusion module to aquire high-quality EIT images.With a 16-electrode multilayer cranial simulation model,the CIFN-based imaging method was compared with Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm in terms of imaging results of types of lesions to verify its performance.Results Compared with the Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm,the proposed CIFN-based algorithm exhibited the lowest mean absolute error(MAE)and the highest structural similarity(SSIM)when used to image different lesion targets,which accurately reconstructed the distribution of lesion targets and gained high imaging stability under common noise levels.Conclusion The proposed CIFN-based imaging algorithm obtains high imaging quality on a cranial simulation model and reconstruction results close to the real model distribution,which provides algorithmic support for subsequent clinical studies on electrical impedance imaging.[Chinese Medical Equipment Journal,2025,46(6):1-6]

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS 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.