Objective: To analyze the trends in incidence and mortality of colorectal cancer in Jinhua City, Zhejiang Province from 2016 to 2024, and to predict the incidence and mortality from 2025 to 2027, so as to provide the evidence for improving regional colorectal cancer prevention and control strategies. Methods: Data on incidence and mortality of colorectal cancer in Jinhua City from 2016 to 2024 were collected through the Zhejiang Chronic Disease Surveillance Information Management System. The crude incidence and crude mortality were calculated, and standardized using the data from the Sixth National Population Census in 2010. Trends in incidence and mortality of colorectal cancer from 2016 to 2024 were analyzed using the average annual percent change (AAPC). A grey Markov model was constructed to predict the incidence and mortality of colorectal cancer from 2025 to 2027. Results: From 2016 to 2024, the crude incidence and standardized incidence of colorectal cancer in Jinhua City were 46.90/100 000 and 30.69/100 000, respectively, showing upward trends (AAPC=4.594% and 2.051%, both P<0.05). The crude mortality and standardized mortality were 17.47/100 000 and 10.36/100 000, respectively, and the trends were not statistically significant (both P>0.05). The standardized incidence and standardized mortality of colorectal cancer in males were higher than those in females (35.38/100 000 vs. 25.68/100 000, 11.96/100 000 vs. 8.57/100 000, both P<0.05). The crude incidence and crude mortality of colorectal cancer in the ≥80 years age group were the highest, at 220.04/100 000 and 186.86/100 000, respectively. From 2016 to 2024, the standardized incidence of colorectal cancer in males and females showed upward trends (AAPC=5.069% and 3.965%, both P<0.05), while the trends in standardized mortality were not statistically significant (all P>0.05). The crude incidence in the 70-<80 years age group showed an upward trend (AAPC=1.320%, P<0.05), and the crude mortality in the 40-<50 years age group showed a downward trend (AAPC=-3.756%, P<0.05). Trends in other age groups were not statistically significant (all P>0.05). The prediction results of the grey Markov model showed that the predicted values of crude incidence and crude mortality of colorectal cancer in the whole population would increase from 58.20/100 000 and 20.04/100 000 in 2025 to 61.70/100 000 and 21.26/100 000 in 2027. Conclusions From 2016 to 2024, the incidence of colorectal cancer in Jinhua City showed upward trends, while the mortality trend was stable. Males and the elderly aged ≥80 years are high-risk populations for colorectal cancer incidence and mortality. It is predicted that both crude incidence and crude mortality will increase from 2025 to 2027.

Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Objective To investigate the impact of closed negative pressure drainage in combination with Ilizarov transverse tibial bone transport on oxidative stress and inflammatory response in patients with severe diabetic foot.Methods A total of 60 patients with severe diabetic foot who were admitted to the hospital from July 2019 to March 2023 were recruited as the research subjects.These patients were randomly allocated into a control group(n=30)and an observation group(n=30).The control group received Ilizarov tibial transverse bone transport alone,whereas the observation group was treated with closed negative pressure drainage in conjunction with Ilizarov tibial transverse bone transport.The following parameters were compared between the two groups of patients:the reduction rate of wound size,the healing rate,growth factors[Epidermal Growth Factor(EGF),Transforming Growth Factor(TGF),Vascular Endothelial Growth Factor(VEGF)],oxidative stress indicators[Advanced Protein Oxidation Products(AOPP),Malondialdehyde(MDA),Superoxide Dismutase(SOD)],inflammatory factors[Procalcitonin(PCT),Interleukin-18(IL-18),C-reactive Protein(CRP)],adverse reactions,and the amputation rate.Results The shrinkage rate and healing rate of patients in the observation group were both significantly higher than those in the control group(P<0.05).Post-treatment,the improvement in growth factor levels,including EGF,TGF,and VEGF,in the observation group was more pronounced compared to that in the control group(P<0.05).Regarding serum AOPP,MDA,and SOD levels,the improvement in the observation group was superior to that in the control group(P<0.05).Moreover,the improvement in inflammatory factor levels such as serum PCT,IL-18,and CRP in the observation group was more notable than that in the control group(P<0.05).The incidence of adverse reactions such as redness,swelling,pain,and bleeding in the observation group was 6.67%.When compared with the incidence of 11.67%in the control group,no statistically significant difference was observed(P>0.05).The amputation rate of patients in the observation group was 3.33%,which was significantly lower than 23.33%in the control group(P<0.05).Conclusions Closed negative pressure drainage combined with Ilizarov tibial transverse bone transport demonstrates better efficacy in the treatment of severe diabetic foot.This treatment modality can effectively promote wound healing,enhance oxidative stress regulation,and inhibit the inflammatory response,presenting a relatively high safety profile.Therefore,the application of closed negative pressure drainage combined with Ilizarov tibial transverse bone transport in the treatment of severe diabetic foot merits clinical reference and promotion.

Objective To analyze the application of outcome indicators and measurement tools in randomized controlled trials(RCTs)of TCM treatment for coronary heart disease(CHD)complicated with anxiety and depression in recent years;To facilitate the construction of core outcome set in this field.Methods The RCTs of TCM treatment for CHD complicated with anxiety and depression were retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase,Cochrane Library,and the included RCTs were evaluated for bias risk,data extracted and analyzed.Results A total of 163 articles were included,with 157 outcome indicators categorized into 6 indicator domains according to their functional attributes.The application rates in descending order were symptoms and signs(98.16%),physiological and chemical tests(58.90%),TCM syndromes(48.47%),safety events(44.17%),quality of life(39.88%),and long-term prognosis(9.20%).By analyzing the frequency and distribution of outcome indicators,indicator combinations,measurement time points and tools found that the experimental design and the registration of study protocols were ignored,and the diagnosis and evaluation criteria of anxiety and depression and TCM diagnosis/syndrome differentiation were not standardized.The selection of outcome indicators was characterized by lack of comorbidity between CHD and anxiety and depression,no separation of primary and secondary,excessive number of indicators,irregular composite indicators,inconsistent application of TCM-specific indicators,lack of long-term prognosis,safety indicators and health economics evaluation.Conclusion There are some limitations in the RCT design and outcome indicators in the TCM treatment of CHD complicated with anxiety and depression.It is imperative to establish a core outcome set and standardize trial designs to enhance research quality.

Objectives:To evaluate the incidence of neurological complications following left ventricular assist device(LVAD)implantation and to investigate related risk factors.Methods:A retrospective analysis was conducted on 151 patients who underwent LVAD implantation at Fuwai Hospital between June 2017 and September 2024.Clinical characteristics and postoperative survival outcomes were compared between patients with and without neurological complications.Results:Neurological complications occurred in 21 patients(13.9%)postoperatively,15 cases were ischemic strokes,5 cases were symptomatic intracranial hemorrhages or subarachnoid hemorrhages,and 1 case was transient ischemic attack(TIA).The total incidence of neurological complications was 0.08 events per person-year(EPPY),ischemic stroke was 0.06 EPPY and hemorrhagic stroke was 0.02 EPPY.Compared with patients without neurological complications,patients with neurological complications had a higher proportion of preoperative aortic regurgitation and tricuspid regurgitation,lower triglyceride levels,a lower rate of concurrent left atrial appendage resection and a higher rate of concurrent aortic valve replacement surgery.Multivariate cox regression analysis revealed that higher preoperative triglyceride levels(HR=0.21,95%CI:0.08-0.56,P=0.002)were associated with neurological complications.The median follow-up time was 508.0(186.5,931.5)days,12 out of 15 cases of ischemic stroke experienced no long-term sequelae,while 3 patients had varying degrees of residual deficits.All 5 patients with hemorrhagic stroke died,with 2 deaths directly attributed to hemorrhage.Kaplan-Meier survival curve analysis indicated that patients with neurological complications had a significantly lower survival rate(log-rank P=0.005).Conclusions:Neurological complications after LVAD implantation are predominantly ischemic strokes.Although less frequent,hemorrhagic strokes are associated with worse outcomes.Higher preoperative triglyceride levels is associated with neurological complications.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Cardiac troponin I (cTnI), a widely used biomarker for assessing cardiovascular risk, can provide a window for the evaluation of drug-induced myocardial injury. Label-free biosensors are promising candidates for detecting cell secretomes, since they do not require labor-intensive processes. In this work, a label-free electrochemical aptasensor is developed for in situ monitoring of cardiac cell secretomes in cell culture media based on target-induced strand displacement. The aptasensing system contains an aptamer-functionalized signal nanoprobe facing trimetallic metal-organic framework nanosheets and a gold nanoparticle-based detection working electrode modified with DNA nanotetrahedron-based complementary DNA for indirect target detection. The signal nanoprobes (termed CAHA) consisted of copper-based metal-organic frameworks, AuPt nanoparticles, horseradish peroxidase, and an aptamer. When the aptasensor is exposed to cardiac cell secretomes, cTnI competitively binds to the aptamer, resulting in the release of signal nanoprobes from the biorecognition interface and electrochemical signal changes. The aptasensor exhibited rapid response times, a low detection limit of 0.31 pg/mL, and a wide linear range of 0.001-100 ng/mL. We successfully used this aptasensor to measure cTnI concentrations among secreted cardiac markers during antitumor drug treatment. In general, aptasensors can be used to monitor a variety of cardiac biomarkers in the evaluation of cardiotoxicity.

Objective To analyze the application of outcome indicators and measurement tools in randomized controlled trials(RCTs)of TCM treatment for coronary heart disease(CHD)complicated with anxiety and depression in recent years;To facilitate the construction of core outcome set in this field.Methods The RCTs of TCM treatment for CHD complicated with anxiety and depression were retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase,Cochrane Library,and the included RCTs were evaluated for bias risk,data extracted and analyzed.Results A total of 163 articles were included,with 157 outcome indicators categorized into 6 indicator domains according to their functional attributes.The application rates in descending order were symptoms and signs(98.16%),physiological and chemical tests(58.90%),TCM syndromes(48.47%),safety events(44.17%),quality of life(39.88%),and long-term prognosis(9.20%).By analyzing the frequency and distribution of outcome indicators,indicator combinations,measurement time points and tools found that the experimental design and the registration of study protocols were ignored,and the diagnosis and evaluation criteria of anxiety and depression and TCM diagnosis/syndrome differentiation were not standardized.The selection of outcome indicators was characterized by lack of comorbidity between CHD and anxiety and depression,no separation of primary and secondary,excessive number of indicators,irregular composite indicators,inconsistent application of TCM-specific indicators,lack of long-term prognosis,safety indicators and health economics evaluation.Conclusion There are some limitations in the RCT design and outcome indicators in the TCM treatment of CHD complicated with anxiety and depression.It is imperative to establish a core outcome set and standardize trial designs to enhance research quality.

Objective To investigate the impact of closed negative pressure drainage in combination with Ilizarov transverse tibial bone transport on oxidative stress and inflammatory response in patients with severe diabetic foot.Methods A total of 60 patients with severe diabetic foot who were admitted to the hospital from July 2019 to March 2023 were recruited as the research subjects.These patients were randomly allocated into a control group(n=30)and an observation group(n=30).The control group received Ilizarov tibial transverse bone transport alone,whereas the observation group was treated with closed negative pressure drainage in conjunction with Ilizarov tibial transverse bone transport.The following parameters were compared between the two groups of patients:the reduction rate of wound size,the healing rate,growth factors[Epidermal Growth Factor(EGF),Transforming Growth Factor(TGF),Vascular Endothelial Growth Factor(VEGF)],oxidative stress indicators[Advanced Protein Oxidation Products(AOPP),Malondialdehyde(MDA),Superoxide Dismutase(SOD)],inflammatory factors[Procalcitonin(PCT),Interleukin-18(IL-18),C-reactive Protein(CRP)],adverse reactions,and the amputation rate.Results The shrinkage rate and healing rate of patients in the observation group were both significantly higher than those in the control group(P<0.05).Post-treatment,the improvement in growth factor levels,including EGF,TGF,and VEGF,in the observation group was more pronounced compared to that in the control group(P<0.05).Regarding serum AOPP,MDA,and SOD levels,the improvement in the observation group was superior to that in the control group(P<0.05).Moreover,the improvement in inflammatory factor levels such as serum PCT,IL-18,and CRP in the observation group was more notable than that in the control group(P<0.05).The incidence of adverse reactions such as redness,swelling,pain,and bleeding in the observation group was 6.67%.When compared with the incidence of 11.67%in the control group,no statistically significant difference was observed(P>0.05).The amputation rate of patients in the observation group was 3.33%,which was significantly lower than 23.33%in the control group(P<0.05).Conclusions Closed negative pressure drainage combined with Ilizarov tibial transverse bone transport demonstrates better efficacy in the treatment of severe diabetic foot.This treatment modality can effectively promote wound healing,enhance oxidative stress regulation,and inhibit the inflammatory response,presenting a relatively high safety profile.Therefore,the application of closed negative pressure drainage combined with Ilizarov tibial transverse bone transport in the treatment of severe diabetic foot merits clinical reference and promotion.