Objective To explore the mechanism of NLRP3 gene knockout in relation to the abnormal mucosal barrier and inflammatory factors in ulcerative colitis(UC)mice.Methods Thirty-two NLRP3-knockout(NLRP3-/-)mice and 30 C57BL/6 wild-type(WT)mice were divided randomly into six groups:NLRP3-/-blank,NLRP3-/-model,NLRP3-/-mesalazine,WT blank,WT model,and WT mesalazine groups.Except for mice in the two blank groups,mice in the other groups were given 3％dextran sodium sulfate to drink freely for 5 days to establish an UC mouse model.After successful establishment of the model,mice in each group underwent intragastric administration of the respective solution for 7 consecutive days.The general condition,body weight,disease activity index(DAI)score,and colon length were observed and evaluated in each group.Histopathological changes in the colon were observed by hematoxylin and eosin staining.ZO-1,claudin-1,occludin,tumor necrosis factor(TNF)-αand interleukin(IL)-6 expression in colon tissue were detected by immunohistochemistry.Results(1)The DAI score was significantly higher in the NLRP3-/-model group compared with the WT model group on day 12,while colon length was significantly shorter and pathological injury of the intestinal mucosa was more serious.Expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower whereas expression levels of TNF-α and IL-6 were significantly higher in the NLRP3-/-model group compared with the WT model group.(2)Regarding the two mesalazine groups,the DAI score was significantly higher and expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower in the NLRP3-/-mesalazine compared with the WT mesalazine group on day 12.Conclusions Specific knockout of the NLRP3 gene makes mice more sensitive to UC.Compared with WT mice,NLRP3-/-UC mice have more severe mucosal barrier injury and release more inflammatory factors.Mesalazine could repair the mucosal barrier and reduce inflammation in NLRP3-/-and WT UC mice.Under the same experimental conditions,mesalazine repaired the mucosal barrier more effectively in WT compared with NLRP3-/-UC mice.

Objective To explore the mechanism of NLRP3 gene knockout in relation to the abnormal mucosal barrier and inflammatory factors in ulcerative colitis(UC)mice.Methods Thirty-two NLRP3-knockout(NLRP3-/-)mice and 30 C57BL/6 wild-type(WT)mice were divided randomly into six groups:NLRP3-/-blank,NLRP3-/-model,NLRP3-/-mesalazine,WT blank,WT model,and WT mesalazine groups.Except for mice in the two blank groups,mice in the other groups were given 3％dextran sodium sulfate to drink freely for 5 days to establish an UC mouse model.After successful establishment of the model,mice in each group underwent intragastric administration of the respective solution for 7 consecutive days.The general condition,body weight,disease activity index(DAI)score,and colon length were observed and evaluated in each group.Histopathological changes in the colon were observed by hematoxylin and eosin staining.ZO-1,claudin-1,occludin,tumor necrosis factor(TNF)-αand interleukin(IL)-6 expression in colon tissue were detected by immunohistochemistry.Results(1)The DAI score was significantly higher in the NLRP3-/-model group compared with the WT model group on day 12,while colon length was significantly shorter and pathological injury of the intestinal mucosa was more serious.Expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower whereas expression levels of TNF-α and IL-6 were significantly higher in the NLRP3-/-model group compared with the WT model group.(2)Regarding the two mesalazine groups,the DAI score was significantly higher and expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower in the NLRP3-/-mesalazine compared with the WT mesalazine group on day 12.Conclusions Specific knockout of the NLRP3 gene makes mice more sensitive to UC.Compared with WT mice,NLRP3-/-UC mice have more severe mucosal barrier injury and release more inflammatory factors.Mesalazine could repair the mucosal barrier and reduce inflammation in NLRP3-/-and WT UC mice.Under the same experimental conditions,mesalazine repaired the mucosal barrier more effectively in WT compared with NLRP3-/-UC mice.

Objective:To compare the diagnostic efficacy of the added 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT imaging (tomography imaging) after early or delayed planar imaging in different types of hyperparathyroidism, and to seek for the optimal timing of preoperative imaging. Methods:A total of 339 patients (148 males, 191 females, age (52±13) years) with primary or secondary hyperparathyroidism and pathological results from January 2016 to June 2024 in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. The patients were divided into primary early tomography imaging group ( n=63) and delayed tomography imaging group ( n=47), secondary early tomography imaging group ( n=89) and delayed tomography imaging group ( n=140). χ2 test was used to compare the diagnostic efficacies of early and delayed tomography imaging. Results:The difference of accuracy between primary delayed (98.40%(185/188)) and early tomography imaging (94.84%(239/252)) was statistically significant ( χ2=3.90, P=0.048). There were significant differences in sensitivity (77.29%(405/524) and 85.40%(275/322)), accuracy (75.89%(425/560) and 83.99%(299/356)) and negative predictive value (14.39%(20/139) and 33.80%(24/71)) between secondary delayed and early tomography imaging ( χ2 values: 8.33, 8.61, 10.70, all P<0.01). Conclusion:The optimal timing of preoperative 99Tc m-MIBI SPECT/CT imaging for primary and secondary hyperparathyroidism is after delayed planar imaging and after early planar imaging respectively.

Objective:To compare the diagnostic efficacy of the added 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT imaging (tomography imaging) after early or delayed planar imaging in different types of hyperparathyroidism, and to seek for the optimal timing of preoperative imaging. Methods:A total of 339 patients (148 males, 191 females, age (52±13) years) with primary or secondary hyperparathyroidism and pathological results from January 2016 to June 2024 in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. The patients were divided into primary early tomography imaging group ( n=63) and delayed tomography imaging group ( n=47), secondary early tomography imaging group ( n=89) and delayed tomography imaging group ( n=140). χ2 test was used to compare the diagnostic efficacies of early and delayed tomography imaging. Results:The difference of accuracy between primary delayed (98.40%(185/188)) and early tomography imaging (94.84%(239/252)) was statistically significant ( χ2=3.90, P=0.048). There were significant differences in sensitivity (77.29%(405/524) and 85.40%(275/322)), accuracy (75.89%(425/560) and 83.99%(299/356)) and negative predictive value (14.39%(20/139) and 33.80%(24/71)) between secondary delayed and early tomography imaging ( χ2 values: 8.33, 8.61, 10.70, all P<0.01). Conclusion:The optimal timing of preoperative 99Tc m-MIBI SPECT/CT imaging for primary and secondary hyperparathyroidism is after delayed planar imaging and after early planar imaging respectively.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Purpose: Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. Methods: This retrospective study included all patients with stage I–III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore.Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13–3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16–0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17–0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07–2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11–3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36–0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09–2.44; p = 0.018). Conclusion NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.

Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To construct an intervention program for diabetic retinopathy(DR)patients undergoing surgery based on the theory of'Timing It Right'.Methods Guided by the theory of'Timing It Right',based on literature review and semi-structured interview,the first draft of the intervention program was formulated.From December 2022 to February 2023,15 medical and nursing experts in ophthalmology and endocrinology from 5 provinces(cities)in Zhejiang,Sichuan,Shanxi,Chongqing and Shanghai were interviewed by Delphi expert for 2 rounds to seek their advice and revision,and the final draft was formed.Results The effective recovery rate of 2 rounds of expert consultations was 93.75％and 100％.The authority coefficients were 0.87.The importance and feasibility of Kendall'W coordination coefficients were 0.325,0.138 and 0.193,0.141 in 2 rounds,respectively(P＜0.001).The finalized intervention program consisted of 6 months,which included 5 first-level items,18 second-level items and 43 third-level items.Conclusion The intervention program for DR patients undergoing surgery based on the theory of'Timing It Right'is reliable,scientific,feasible and practical,and it can meet the needs of such patients,providing a reference for improving their self-management ability,improving their negative emotions and delaying disease progression.

OBJECTIVES: This study aimed to investigate the accuracy of model superimposition and automatic analysis for upper and lower dentition widths in iTero Progress Assessment during the clear aligner process. METHODS: Nineteen cases were included in this retrospective case control study. Pretreatment dental cast (T0) and post treatment dental cast after staged treatment (T1) were available for three-dimensional (3D) model superimposition. The movements of maxillary teeth in the horizontal plane (cross section) after staged treatment and the widths of upper and lower dentitions were measured by 3D model superimposition in real world and iTero Progress Assessment. The data collected from the two methods were compared. RESULTS: The movements [Median (upper and lower quartiles)] of maxillary teeth in the horizontal plane after staged treatment were 2.31 (1.59, 3.22) and 1.79 (1.21, 3.03) mm in iTero Progress Assessment and 3D model analysis, respectively. Significant difference was observed between the two groups (P<0.05). In the measurement of upper and lower dentition width, four indicators were measured, including intercanine width upper, intermolar width upper, intercanine width lower, and intermolar width lower. Before treatment, the measurement of iTero Progress Assessment were (35.78±2.49), (56.21±2.51), (27.43±1.38), (52.26±2.91) mm, respectively, and actual measurement were (35.77±2.53), (56.17±2.47), (27.40±1.41), (52.30±2.86) mm, respectively, without significant difference (P>0.05). After stage treatment, the measurement of iTero Progress Assessment were (37.37±2.86), (57.76±2.56), (28.89±2.00), (54.16±2.19) mm, respectively, and actual measurement were (37.29±2.94), (57.71±2.63), (28.88±2.05), (54.01±2.15) mm, respectively, and there was no significant difference (P>0.05). CONCLUSIONS The data from iTero Progress Assessment did not coincide with the model superimposition results with palate as reference. The accuracy of model superimposition in iTero Progress Assessment needs further investigation, whereas the arch width analysis is accurate. Therefore, iTero Progress Assessment results should be interpreted with caution by orthodontists in clinical applications.
Case-Control Studies ; Cuspid ; Dental Arch ; Orthodontic Appliances, Removable ; Retrospective Studies ; Humans