Adverse childhood experiences (ACEs) refer to traumatic events such as abuse and neglect experienced before the age of 18 years, which have negative impacts on an individual's physical and mental health. Studies have shown that ACEs not only increase the risk of health-harming behaviors such as smoking and alcohol abuse, but are also risk factors for depression and anxiety. The influence of ACEs on depression and anxiety exhibits type-specificity, cumulative effects, and temporal dynamics. The impact of ACE types on depression and anxiety varies across populations and genders, a dose-response relationship exists between the number of ACEs and depression/anxiety, and the phase, trajectory, and frequency of ACEs also significantly influence depression and anxiety. This article collected literature on ACEs and depression/anxiety from January 1995 to June 2024 by searching the CNKI and PubMed databases. It provides a comprehensive review of the associations between different ACEs types, quantities, categories, timing, trajectories, frequencies, and the risks of depression and anxiety, while also exploring the underlying mechanisms of these associations. The findings aim to offer references for the prevention and intervention of ACEs and the improvement of mental health.

OBJECTIVES: To analyze the disease burden and inequalities of lower extremity peripheral artery disease (LEPAD) among people aged 40 and above in the Belt and Road partner countries from 1990 to 2021. METHODS: Data were retrieved from the Global Burden of Disease 2021 database. The age-standardized prevalence rates, mortality rates, and the annual rate of years lived with disability (YLDs) of LEPAD were analyzed. Trends were measured using the estimated annual percentage change (EAPC), and the slope index of inequality (SII) and concentration index were used to quantify the absolute and relative inequalities. RESULTS: In 2021, the age-standardized prevalence and mortality rates of LEPAD were 3168.26/10⁵ and 3.09/10⁵, increasing by 4.30% and 19.31% compared to 1990, while YLDs rates decreased by 4.00%. Females had higher age-standardized prevalence and YLDs rates, while males had higher mortality rates. The EAPC for prevalence rates was slightly higher in males (0.22%) than in females (0.17%); while the EAPC of age-standardized mortality rate was 2.02% for females, compared to 1.45% for males. From 1990 to 2021, the age-standardized YLDs rates decreased from 16.23/10⁵ to 15.58/10⁵, with a faster decline in females (－0.12%) than in males (－0.06%). LEPAD prevalence varied across countries, with higher burden in Europe and faster growth in Gulf states. Higher socio-demographic index countries had higher prevalence. Inequity improved, with the SII at 52.90/10⁵ and concentration index at 0.038 in 2021. Gender disparities persisted, with concentration index increased to 0.058 in females and reduced to －0.026 in males. CONCLUSIONS LEPAD prevalence and mortality among people aged 40 and above in the Belt and Road partner countries increased, while YLDs rates decreased from 1990 to 2021. Significant differences among people exist depending on gender and country, highlighting the need for enhanced screening, health education, and shared public health strategies across the Belt and Road partner countries.
Humans ; Peripheral Arterial Disease/mortality* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Prevalence ; Lower Extremity/blood supply* ; Global Burden of Disease ; Cost of Illness

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Background and objective Lung adenocarcinoma(LUAD)is a highly morbid and fatal cancer.De-spite advancements in modern medical treatment,the 5-year survival rate of patients remains suboptimal.Our previous study revealed that zinc finger SWIM-type containing 1(ZSWIM1),a novel protein,promotes the proliferation,migration,and inva-sion of LUAD cells.The aim of this study is to investigate the impact ofE3 ubiquitin ligase tripartite motif protein 21(TRIM21)on ZSWIM1-mediated cell proliferation and migration.Methods The interaction and co-localization between TRIM21 and ZSWIM1 were verified using co-immunoprecipitation(Co-IP)and immunofluorescence(IF).The effects of TRIM21 and ZSWIM1 on the proliferation and migration of LUAD cells were assessed through MTT and Transwell assays,respectively.Western blot(WB)analysis was conducted to evaluate the impact of TRIM21 and ZSWIM1 on the expression of epithelial-mesenchymal transition(EMT)markers in LUAD cells.The influence of TRIM21 on the ubiquitination of ZSWIM1 was exam-ined using Co-IP combined with WB.Results TRIM21 was found to interact and co-localize with ZSWIM1.Overexpression of TRIM21 inhibited the proliferation and migration of LUAD cells.Overexpression of TRIM21 reduced the promoting effect of ZSWIM1 on the proliferation,migration,and invasion of lung adenocarcinoma cells,and reversed the impact of ZSWIM1 on the expression of E-cadherin and Vimentin.Conversely,knockdown of TRIM21 further enhanced the promoting effect of ZSWIM1 on the proliferation and migration of LUAD cells.Mechanistically,we observed that overexpression of TRIM21 significantly en-hanced the ubiquitination level of ZSWIM1,leading to a decrease in ZSWIM1 protein expression.Conclusion TRIM21 binds to and promotes the ubiquitination of ZSWIM1,resulting in reduced protein expression of ZSWIM1,which leads to the inhibition of ZSWIM1-mediated promotion of proliferation,migration,and invasion in LUAD cells.

In recent years, artificial intelligence-related technologies have been deeply combined with many medical fields, and the intersection of medicine and engineering has become a hot topic. There are problems with heavy data and difficulty making decisions in orthopedic disease diagnosis and treatment. Machine learning is an important method of artificial intelligence. Since it can automatically analyze and predict medical big data, it is widely used in the field of orthopedics. It also assists physicians in completing disease diagnosis and treatment efficiently. In this review paper, the application and progress of machine learning in preoperative, intraoperative, and postoperative diagnosis and treatment in orthopedics are reviewed, providing new ways for exploring more rational diagnosis and treatment strategies.

OBJECTIVE To establish an evaluation syste m of clinical effec tiveness of Drug Selection Guideline for Medical Institutions，and to provide reference for drug selection in medical institution. METHODS Retrieved from relevant Chinese government websites ，PubMed，Embase，CBM and CNKI ，etc.，from the inception to Sept. 14th 2021，related contents of clinical effectiveness related to three secondary indicators ，such as “recommended level and strength of guideline ”“clinical pathway ”and “evidence and level of efficacy ”were extracted respectively ；evaluation system was construction for the clinical effectiveness. RESULTS A total of 5，4 and 17 policy documents or literatures were included according to “recommended level and strength of guideline”“clinical pathway ”and“evidence and level of efficacy ”，respectively.“The recommended level and strength of drug guideline”could reflect the clinical effectiveness of drugs ，and the evaluation content referred to the recommended level and strength of the selected drugs in the guidelines for corresponding indications. “Clinical pathway ”was the embodiment of drug effectiveness, and the evaluation content referred to the clinical path of whether the selected drugs were included in the corresponding indications. The evaluation contents of “evidence and level of efficacy ”were different between chemical medicine/ biological agent and Chinese patent medicine ；evidence and quality level of efficacy research for chemical medicine/biological agent referred to GRADE system ，while those for Chinese patent medicine referred to classic works or clinical experience inheritance. Therefore，the evaluation contents of this index system were the evidence and quality level of the efficacy research related to selected drugs. CONCLUSIONS The evaluation system of clinical effectiveness of drugs constructed from the perspective of drug selection in medical institutions can lay the foundation of evaluation system for the construction of Drug Selection Guideline for Medical Institutions ，and also provide reference for drug selection in medical institutions.

Objective:To analyze the trend of medication use in patients with ulcerative colitis (UC) in recent ten years in at Xijing Hospital, Air Force Military Medical University.Methods:From 2010 to 2019, the clinical data of 1 425 patients diagnosed with UC in the Department of Gastroenterology at Xijing Hospital, Air Force Medical University, were retrospectively collected. According to the period of medication, the UC patients were divided into year 2010 to 2014 group and year 2015 to 2019 group. The general information and the medication trend of year 2010 to 2014 group and year 2015 to 2019 group were analyzed. And then according to gender and age (<40 years old and ≥40 years old), patients were divided into subgroups and analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The number of UC patients of year 2010 to 2014 group and year 2015 to 2019 group was 369 and 1 056, respectively. The percentages of patients in remission of the two groups were 9.5% (35/369) and 12.0% (127/1 056), respectively; the percentages of mild patients were 40.4% (149/369) and 41.6% (439/1 056), respectively; the percentages of moderate patients were 37.4% (138/369) and 28.9% (305/1 056), respectively; the percentages of severe patients were 12.7% (47/369) and 17.5% (185/1 056), respectively. There was no significant difference in the proportion of UC patients with different degrees between year 2010 to 2014 group and year 2015 to 2019 group ( P>0.05). There were no significant differences in the age and proportion of female between the year 2010 to 2014 group and year 2015 to 2019 group ((46.2±15.3) years old vs. (44.6±30.6) years old; 45.8%, 169/369 vs. 44.8%, 473/1 056; both P>0.05). The utilization rates of 5-aminosalicylic acid (5-ASA), glucocorticoid, immunosuppressants, and biological agents of the year 2015 to 2019 group were all higher than those of the year 2010 to 2014 group (96.8%, 1 022/1 056 vs. 90.0%, 332/369; 29.9%, 316/1 056 vs. 14.6%, 54/369; 8.4%, 89/1 056 vs. 2.4%, 9/369; 4.8%, 51/1 056 vs. 0.5%, 2/369, respectively), and the differences were all statistically significant ( χ2=26.766, 33.256, 15.315 and 14.038, all P<0.01). Within each of the year 2010 to 2014 group and the year 2015 to 2019 group, there were no significant differences between the female and male in the age, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents ((47.2±13.6) years old vs. (45.3±16.5) years old, (43.1±12.9) years old vs. (45.8±39.5) years old, 88.8%, 150/169 vs. 91.0%, 182/200; 96.8%, 458/473 vs. 96.7%, 564/583; 13.6%, 23/169 vs. 15.5%, 31/200; 28.3%, 134/473 vs. 31.2%, 182/583; 2.4%, 4/169 vs. 2.5%, 5/200; 7.0%, 33/473 vs. 9.6%, 56/583; 0 vs. 1.0%, 2/200; 5.3%, 25/473 vs. 4.5%, 26/583; all P>0.05). In the patients aged≥40 years old of the year 2010 to 2014 group, the proportion of females was higher than that of the patients aged <40 years old (50.2%, 121/241 vs. 37.5%, 48/128), and the utilization rate of 5-ASA in patients aged ≥40 years old was lower than that of patients aged <40 years old (85.9%, 207/241 vs. 97.7%, 125/128), and the differences were statistically significant ( χ2=5.438 and 12.824, P=0.020 and P<0.01). In the year 2010 to 2014 group, there were no statistically significant differences in the utilization rates of glucocorticoid, immunosuppressants and biological agents between patients aged ≥40 years old and patients aged <40 years old (13.7%, 33/241 vs. 16.4%, 21/128; 2.1%, 5/241 vs. 3.1%, 4/128; 0 vs. 1.6%, 2/128; all P>0.05). In the year 2015 to 2019 group, the utilization rate of biological agents in patients aged≥40 years old was lower than that in patients aged<40 years old (3.7%, 23/630 vs. 46.5%, 198/426), and the difference was statistically significant ( χ2=4.721, P=0.030). In the year 2015 to 2019 group, there were no statistically significant differences in female proportion, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents between patients aged≥40 years old and patients aged <40 years old (43.7%, 275/630 vs. 46.5%, 198/426; 96.0%, 605/630 vs. 97.9%, 417/426; 29.7%, 187/630 vs. 30.3%, 129/426; 8.6%, 54/630 vs. 8.2%, 35/426; all P>0.05). Conclusions:Compared with year 2010 to 2014, the number of UC patients remarkably increased in the year 2015 to 2019 in the Department of Gastroenterology, Xijing Hospiatal, Air Force Medical University. The utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents all increased in UC patients. The medication trends of UC patients with different gender were almost the same. The medication trends of UC patients with different age were different.

Laccases (EC 1.10.3.2), a group of multi-copper oxidases (MCOs), play multiple biological functions and widely exist in many species. Fungal laccases have been extensively studied for their industrial applications, however, there was no database specially focused on fungal laccases. To provide a comparative genomics platform for fungal laccases, we have developed a comparative genomics platform for laccases and MCOs (http://laccase.riceblast.snu.ac.kr/). Based on protein domain profiles of characterized sequences, 3,571 laccases were predicted from 690 genomes including 253 fungi. The number of putative laccases and their properties exhibited dynamic distribution across the taxonomy. A total of 505 laccases from 68 genomes were selected and subjected to phylogenetic analysis. As a result, four clades comprised of nine subclades were phylogenetically grouped by their putative functions and analyzed at the sequence level. Our work would provide a workbench for putative laccases mainly focused on the fungal kingdom as well as a new perspective in the identification and classification of putative laccases and MCOs.