Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.

The complex pathophysiological mechanisms between diabetes mellitus and cardiovascular diseases have not yet been fully elucidated， becoming one of the challenges in clinical care. Glucagon-like peptide-1 receptor agonist （GLP1-RA） and sodium glucose cotransporter-2 inhibitors （SGLT2） are clinically used to reduce the cardiovascular risk of patients with diabetes mellitus. Traditional Chinese medicine has diverse biological activities and unique advantages in the treatment of chronic complex diseases due to its multi-component and multi-target effects. Based on recent reports， this paper reviewed the common risk factors of diabetes mellitus and cardiovascular diseases （e.g.， hyperglycemia， insulin resistance， and inflammation）， related targets such as apolipoprotein C-Ⅲ （APOC3）， S100 calcium-binding protein A8/A9 （S100A8/A9）， growth/differentiation factor-15 （GDF-15）， and NACHT， LRR， and PYD domains-containing protein 3 （NLRP3）， advanced glycation end products， insulin resistance， endothelial dysfunction， endoplasmic reticulum stress， mitochondrial dysfunction， and intestinal flora disorder. In addition， this paper summarized the research progress in the treatment of cardiovascular diseases in diabetes mellitus with the active ingredients （e.g.， baicalein， puerarin， curcumin， notoginsenoside， and tanshinone Ⅱ_A）， single herbal medicines （e.g.， Astragali Radix， Ginseng Radix et Rhizoma， Sophorae Flavescentis Radix， Cinnamomi Cortex， and Corni Fructus）， and compound formulas （e.g.， Buzang Tongluo Fang， Yiqi Yangyin Huoxue Fang， Shenqi Fang， Huangqisan， Danggui Buxue Tang， and Liuwei Dihuang Wan） of traditional Chinese medicine. Traditional Chinese medicine mainly treats cardiovascular diseases in diabetes mellitus by reducing inflammation and oxidative stress， ameliorating dyslipidemia and insulin resistance， protecting islet β cell function， repairing endothelial damage， inhibiting smooth muscle cell proliferation， foam cell formation， macrophage polarization， and cardiac hypertrophy and fibrosis， and regulating intestinal flora disorder. These processes involve insulin receptor substrate/ phosphatidylinositol 3-kinase/protein kinase B （IRS/PI3K/Akt）， peroxisome proliferator-activated receptor α/γ （PPAR α/γ）， nuclear factor-kappa B （NF-κB）， adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， hypoxia-inducible factor-1-BCH domain-containing protein （HIF-1-BNIP）， vascular endothelial growth factor/hypoxia-inducible factor-1α （VEGF/HIF-1α） and other signaling pathways. This review is expected to provide a theoretical basis and reference for the treatment of cardiovascular diseases in diabetes mellitus with traditional Chinese medicine.

Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.

Objective:To investigate the application and effectiveness of slit-lamp microscope demonstration combined with supervisory clinical teaching in ophthalmology training for general practice residents.Methods:Sixty general practice residents who underwent ophthalmology training in Fifth Affiliated Hospital of Sun Yat-sen University from March 2021 to March 2023 were randomly assigned to 2 groups. In the traditional teaching group ( n=29), the teaching was primarily led by the instructors, and trainees observed and recorded the clinical findings under their guidance; while in the combined teaching group ( n=31), the trainees received integrated slit-lamp microscope demonstration and supervisory outpatient teaching. Both groups underwent a unified exit examination after the training, with the scores based on knowledge, diagnostic skills, comprehensive evaluation and overall performance. Additionally, satisfaction with the teaching process was assessed through questionnaires completed by both trainees and instructors. Results:There were no significant differences in gender composition, age and initial exam scores between the two groups (all P>0.05). Upon completion of the training, the combined teaching group scored higher in ophthalmology knowledge, outpatient diagnostic skills, and overall performance compared to the traditional teaching group (all P<0.05). Satisfaction scores from both trainees and instructors were also higher in the combined teaching group compared to the traditional teaching group (all P<0.05). Conclusion:The use of slit-lamp microscope demonstration combined with supervisory outpatient teaching can significantly enhance the effectiveness of ophthalmology training for general practice residents.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Objective:To explore the clinical feasibility of finger-pressing therapy based on the theory of treating impotence alone with Yang Ming to reduce incidence of ICU acquired weakness (ICU-AW) in critically ill children and provide a feasible nursing plan for ICU acquired asthenia in critically ill children.Methods:A quasi-experimental study was conducted. A total of 73 critically ill children were admitted to the PICU of Kunming Children′s Hospital from January 1 to April 30, 2021. According to the random number table, the subjects were divided into the observation group (37 cases) and the control group (36 cases). Children in the control group received routine PICU nursing. The children in the observation group were treated with PICU routine nursing and finger-pressing therapy based on the theory of treating impotence alone with Yang Ming. The two groups were compared in terms of limb muscle strength score (MRC-Score), incidence of ICU-AW, basic activities of life (Barthel Index, BI), limb muscle thickness.Results:After intervention, the MRC-Score of the observation group was 50 (46, 52) points, which was higher than 46 (40, 48) points of the control group, and the difference between the two groups was statistically significant ( Z=-3.70, P<0.05). The incidence of ICU-AW in the observation group was 32.43% (12/37), and the incidence of ICU-AW in the control group was 72.22% (26/36). The difference between the two groups was statistically significant ( χ2=11.58, P<0.05). The BI score of the observation group was 63 (50, 70), which was higher than 44 (40,60) of the control group, and the difference between the two groups was statistically significant ( Z=-3.94, P<0.05). The reduction degree of quadriceps femoris thickness in the observation group at D3-D1 was (-0.381 ± 0.131) cm, which was lower than (-0.762 ± 0.182) cm in the control group, and the difference between the two groups was statistically significant ( t=10.29, P<0.05). Conclusions:The application of finger-pressing therapy guided by theory of treating impotence alone with Yang Ming in the early rehabilitation of critically ill children can enhance muscle strength, prevent muscle atrophy and reduce the incidence of ICU-AW in critically ill children.

Objectives:The risk factors affecting the blood perfusion of side branch(SB)in coronary bifurcation lesions were explored by the three-dimensional quantitative coronary angiography(3D-QCA)and the Murray's law based quantitative flow ratio(μQFR),and a risk prediction model affecting SB perfusion disorders was established to provide reference for the percutaneous coronary intervention(PCI)strategies of bifurcation lesions. Methods:From October 2022 to April 2023,393 bifurcation lesions were evaluated by coronary angiography in Hunan Provincial People's Hospital.The general clinical evaluation index of the patient,the anatomical index of coronary bifurcation lesion,and the μQFR representing branch perfusion in bifurcation lesion were collected.All samples were randomly divided into training set and test set at the 8:2 ratio.Univariate logistic regression was used to determine filter variables,and the influencing factors of branch perfusion in bifurcated lesions were evaluated by multivariate logistic regression analysis.A risk prediction model was established,and the accuracy of the model was further verified in the test set. Results:The maximum area stenosis rate,maximum lumen diameter stenosis rate of the bifurcation nucleus,ostia diameter stenosis rate,as well as the branch maximum diameter stenosis rate,and length of the bifurcation lesion are independent predictors of SB perfusion disorders(SB μQFR<0.8),P<0.05.A SB perfusion disorder risk prediction model was established based on the above five independent risk factors.The area under the ROC curve of the model was 0.926(95%CI:0.896-0.958),the sensitivity was 0.864(95%CI:0.818-0.910),and the specificity was 0.850(95%CI:0.780-0.920).This model was applied to the test set,the results showed that the area under the ROC curve of this model was 0.897(95%CI:0.817-0.976),the sensitivity was 0.870(95%CI:0.756-0.936),and the specificity was 0.923(95%CI:0.759-0.986). Conclusions:The blood perfusion of branches in coronary bifurcation lesions is mainly related to multiple anatomical factors of the main branch and SB.Among them,the maximum area stenosis rate,maximum lumen diameter stenosis rate of the bifurcation nucleus,ostia diameter stenosis rate,branch maximum diameter stenosis rate and length of the bifurcation lesion are independent predictors of perfusion disorders in the SB.Future studies are needed to validate the clinical value of the established risk prediction model of the SB perfusion disorders in daily clinical practice.

Objective:To analyze the clinical efficacy of different treatment modalities and prognostic factors of patients with Masaoka-Koga stage Ⅲ thymoma.Methods:Clinical data of patients diagnosed with Masaoka-Koga stage Ⅲ thymoma admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2000 to December 2018 were analyzed retrospectively. A total of 133 patients had complete treatment and follow-up data. Kaplan-Meier method was used to calculate the cumulative survival rate, log-rank method was used to compare the survival between two groups, and Cox regression model was used for multivariate analysis.Results:The median follow-up time was 50 months (3-221 months). The median overall survival (OS) was 51 (3-221) months, and the median disease-free survival (DFS) was 45 (2-221) months. The survival rate in the radical surgery group was better than that in the palliative surgery group. The 5- and 10-year OS rates in radical surgery group were 88.2% and 74.4% respectively, while in palliative surgery group were 51.8% and 32.4% respectively ( P<0.001). The 5- and 10-year DFS rates in radical surgery group were 72.2% and 45.5%, respectively, while in palliative surgery group were 32.3% and 16.1% respectively ( P=0.001). The OS in the surgery combined with radiotherapy group was better than that in the surgery alone group. The 5- and 10-year OS rates in the radical surgery group were 82.8% and 64.2% respectively, while in the palliative surgery group were 55.8% and 50.2% ( P=0.033). There was no significant difference in DFS between two groups ( P=0.176). Multivariate analysis showed that age < 50 years old ( HR=0.264, P=0.001), radical resection ( HR=0.134, P<0.001), surgery combined with radiotherapy ( HR=2.778, P=0.009) were independently associated with better OS. Age < 50 years old ( HR=0.550, P=0.046), radical resection ( HR=0.555, P=0.042), and invasion of single organ ( HR=0.111, P=0.003) were independently associated with better DFS. Conclusions:OS and DFS in patients undergoing radical surgery are significantly better than those in their counterparts treated with palliative surgery, which is the most important factor affecting prognosis. Surgery combined with radiotherapy yields better OS. It is necessary to design a rigorous and reasonable multicenter prospective study to evaluate the efficacy of various treatment modalities and prognostic factors.

Pigs are considered as ideal donors for xenotransplantation because they have many physiological and anatomical characteristics similar to human beings. However, antibody-mediated immunity, which includes both natural and induced antibody responses, is a major challenge for the success of pig-to-primate xenotransplantation. Various genetic modification methods help to tailor pigs to be appropriate donors for xenotransplantation. In this study, we applied transcription activator-like effector nuclease (TALEN) to knock out the porcine α-1, 3-galactosyltransferase gene GGTA1, which encodes Gal epitopes that induce hyperacute immune rejection in pig-to-human xenotransplantation. Meanwhile, human leukocyte antigen-G5 gene HLA-G5, which acts as an immunosuppressive factor, was co-transfected with TALEN into porcine fetal fibroblasts. The cell colonies of GGTA1 biallelic knockout with positive transgene for HLA-G5 were chosen as nuclear donors to generate genetic modified piglets through a single round of somatic cell nuclear transfer. As a result, we successfully obtained 20 modified piglets that were positive for GGTA1 knockout (GTKO) and half of them expressed the HLA-G5 protein. Gal epitopes on the cell membrane of GTKO/HLA-G5 piglets were completely absent. Western blotting and immunofluorescence showed that HLA-G5 was expressed in the modified piglets. Functionally, the fibroblasts from the GTKO/HLA-G5 piglets showed enhanced resistance to complement-mediated lysis ability compared with those from GTKO-only or wild-type pigs. These results indicate that the GTKO/HLA-G5 pigs could be a valuable donor model to facilitate laboratory studies and clinics for xenotransplantation.
Animals ; Animals, Genetically Modified ; Gene Knockout Techniques ; HLA Antigens ; Humans ; Nuclear Transfer Techniques ; Swine ; Transplantation, Heterologous

Objective:To analyze the failure patterns and influencing factors of stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (ES-NSCLC).Methods:113 cases of ES-NSCLC treated with SABR from 2012 to 2020 in our hospital were retrospectively analyzed. The failure patterns, recurrence time, recurrence site and influencing factors were analyzed. Kaplan-Meier method was used to calculate the local recurrence rate, regional lymph node recurrence rate and distant metastasis rate. Univariate analysis was performed by Log-rank test, and multivariate analysis was performed by Cox model.Results:The median follow-up time was 58 months (range: 6-108 months), and a total of 45 patients (39.8%) recurred. The median recurrence time was 36 months. Distant metastasis (DM) occurred in 31 patients (27.4%) and DM alone in 24 patients (21.2%). Local recurrence (LR) was developed in 12 patients (10.6%) and LR alone in 7(6.2%). Regional lymph node recurrence (RR) occurred in 11 patients (9.7%) and RR alone in 6 patients (5.3%). LR combined with RR was observed in 1 case (0.9%), LR combined with DM in 3(2.7%), LR combined with RR and DM in 1(0.9%), and RR combined with DM in 3(2.7%). The 1-, 2-, 3-, 4-and 5-year recurrence rates were 5.4%, 16.6%, 27.5%, 44% and 51.2%, respectively. Univariate and multivariate analyses suggested that EGFR mutation was an influencing factor of high recurrence rate.Conclusion:ES-NSCLC patients treated with SABR alone have a high recurrence rate, and DM is the most common mode of failure. Follow-up consolidation therapy is recommended, especially for EGFR mutation-positive NSCLC patients.