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.

ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

Ankylosing spondylitis is a chronic immunoinflammatory disease that mainly affects the spine and the sacroiliac joint， the mechanism of which is closely related to signaling pathways， such as osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， phosphoinositide 3- kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）. Traditional Chinese medicine has the characteristics of multiple components and targets， and is widely used for the treatment of autoimmune diseases due to its low toxicity， strong specificity， and high efficacy. This review found that monomers and compounds of traditional Chinese medicine can exert anti ankylosing spondylitis effects by intervening in the aforementioned signaling pathways， regulating immune inflammatory responses， and inhibiting biological processes such as bone destruction， ectopic osteogenic differentiation， cell apoptosis， and autophagy.

AIM: To analyze the factors affecting non-contact intraocular pressure(IOPNCT)measurements after femtosecond laser-assisted small incision lenticule extraction(SMILE), explore the correlation of IOPNCT with central corneal thickness(CCT)and corneal curvature after SMILE, and construct the corresponding regression model which will provide scientific basis for clinical evaluation of the true IOP of patients after SMILE.METHODS: Data from a retrospective analysis of 107 myopic patients(206 eyes)who underwent SMILE and 107 myopic patients(201 eyes)received femtosecond laser-assisted in situ keratomileusis(FS-LASIK)surgery from June 2023 to May 2024 were examined. IOPNCT, CCT, and corneal curvature before surgery and at 1 and 3 mo were collected. The preoperative and postoperative IOPNCT, CCT and corneal curvature were analyzed by ANOVA and Pearson correlation analysis, and multiple linear regression models were constructed to evaluate the association of postoperative changes of IOPNCT, CCT and corneal curvature.RESULTS: There were significant differences in IOPNCT, CCT, and corneal curvature of both SMILE and FS-LASIK patients(all P<0.001), there was no significant difference between two groups and interaction effects(all P>0.05), and the IOPNCT, CCT and corneal curvature at 1 and 3 mo post-surgery were significantly lower than preoperative(all P<0.05). Pearson correlation analysis showed a positive correlation between IOPNCT and CCT at 1 and 3 mo after SMILE(r=0.261, 0.267, all P<0.001), but no significant correlation with corneal curvature(all P>0.05). Multiple linear regression analysis of IOPNCT with CCT and corneal curvature at 1 mo after SMILE indicated that the regression equation was: Y=3.426+0.019X1-0.058X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistical significant difference in the equation(F=7.654, P=0.001); the regression equation for 3 mo after surgery was: Y=2.056+0.020X1-0.038 X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistically significance in the equation(F=7.903, P<0.001). The regression equation of postoperative IOPNCT change(△IOPNCT)and intraoperative cutting corneal thickness(△CCT)and corneal curvature at 1 mo was Y=-2.252+0.008X1+0.587X2(Y represents △IOPNCT, X1 stands for the △CCT, X2 represents the corneal curvature change value), with statistical significant difference in the equation(F=17.550, P<0.001); the regression equation for 3 mo after surgery was: Y=-2.168+0.024X1+0.281X2(Y represents △IOPNCT, X1 represents △CCT, X2 indicates the corneal curvature change values), with statistical significant difference in the equation(F=16.030, P<0.001).CONCLUSION: After SMILE and FS-LASIK surgery, the IOPNCT value of patients was mainly affected by CCT compared with preoperative surgery, and the short-term use of hormone eye drops, fluorometholone, did not cause a significant increase in IOP; both the IOP correction formula at 1 and 3 mo postoperatively can be used clinically to evaluate and correct actual IOP in patients after SMILE.

AIM: To analyze the factors affecting non-contact intraocular pressure(IOPNCT)measurements after femtosecond laser-assisted small incision lenticule extraction(SMILE), explore the correlation of IOPNCT with central corneal thickness(CCT)and corneal curvature after SMILE, and construct the corresponding regression model which will provide scientific basis for clinical evaluation of the true IOP of patients after SMILE.METHODS: Data from a retrospective analysis of 107 myopic patients(206 eyes)who underwent SMILE and 107 myopic patients(201 eyes)received femtosecond laser-assisted in situ keratomileusis(FS-LASIK)surgery from June 2023 to May 2024 were examined. IOPNCT, CCT, and corneal curvature before surgery and at 1 and 3 mo were collected. The preoperative and postoperative IOPNCT, CCT and corneal curvature were analyzed by ANOVA and Pearson correlation analysis, and multiple linear regression models were constructed to evaluate the association of postoperative changes of IOPNCT, CCT and corneal curvature.RESULTS: There were significant differences in IOPNCT, CCT, and corneal curvature of both SMILE and FS-LASIK patients(all P<0.001), there was no significant difference between two groups and interaction effects(all P>0.05), and the IOPNCT, CCT and corneal curvature at 1 and 3 mo post-surgery were significantly lower than preoperative(all P<0.05). Pearson correlation analysis showed a positive correlation between IOPNCT and CCT at 1 and 3 mo after SMILE(r=0.261, 0.267, all P<0.001), but no significant correlation with corneal curvature(all P>0.05). Multiple linear regression analysis of IOPNCT with CCT and corneal curvature at 1 mo after SMILE indicated that the regression equation was: Y=3.426+0.019X1-0.058X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistical significant difference in the equation(F=7.654, P=0.001); the regression equation for 3 mo after surgery was: Y=2.056+0.020X1-0.038 X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistically significance in the equation(F=7.903, P<0.001). The regression equation of postoperative IOPNCT change(△IOPNCT)and intraoperative cutting corneal thickness(△CCT)and corneal curvature at 1 mo was Y=-2.252+0.008X1+0.587X2(Y represents △IOPNCT, X1 stands for the △CCT, X2 represents the corneal curvature change value), with statistical significant difference in the equation(F=17.550, P<0.001); the regression equation for 3 mo after surgery was: Y=-2.168+0.024X1+0.281X2(Y represents △IOPNCT, X1 represents △CCT, X2 indicates the corneal curvature change values), with statistical significant difference in the equation(F=16.030, P<0.001).CONCLUSION: After SMILE and FS-LASIK surgery, the IOPNCT value of patients was mainly affected by CCT compared with preoperative surgery, and the short-term use of hormone eye drops, fluorometholone, did not cause a significant increase in IOP; both the IOP correction formula at 1 and 3 mo postoperatively can be used clinically to evaluate and correct actual IOP in patients after SMILE.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

OBJECTIVE To establish a clinical comprehensive evaluation framework for direct oral anticoagulants （DOACs） in the prevention of cancer-associated venous thromboembolism （CAVTE）， providing a methodological reference for the rational prevention and treatment of CAVTE as well as for the formulation and adjustment of macro-management strategies for anticoagulant drugs. METHODS Through literature retrieval， evaluation indicators were collected and organized to establish a preliminary indicator pool. The selection of evaluation indicators was carried out through two rounds of Delphi surveys using average score of indicator importance≥3.5 and a coefficient of variation （CV） ＜0.25 as the screening criteria. Analytic hierarchy process （AHP） was employed to finalize the indicator weights. RESULTS The authority levels （C）r of the two rounds of expert consultations were 0.877 and 0.943， with CV of 0.24 and 0.18， respectively. The Kendall concordance coefficients were 0.331 and 0.535 （P＜0.05）. After expert validation， six primary indicators and forty-six secondary indicators were finalized for inclusion in the evaluation framework. The primary indicators and their weightings， ranked in descending order， were as follows：“ effectiveness” （38.86%）， “safety” （38.86%），“ cost-effectiveness” （10.67%），“ accessibility” （5.51%），“ suitability” （3.48%）， and “innovation” （2.64%）. The secondary indicators exhibited a weight range from 0.02% to 20.25%， with the top five secondary indicators being：“ incidence of intracranial hemorrhage” （20.25%）， “reduction in all-cause mortality” （15.29%）， “decrease in the incidence of pulmonary embolism” （8.82%）， “reduction in the incidence of deep vein thrombosis” （7.25%）， and “drug contraindications” （4.74%）. CONCLUSIONS This study has established an authoritative， scientific， and reliable comprehensive clinical evaluation framework for the use of DOACs in the prevention of CAVTE.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.