Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

[Post-transcriptional regulation mechanism and antiviral strategy of hepatitis B virus RNA].

Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle, there is a lack of effective drugs to cure chronic hepatitis B. During HBV replication, covalently closed circular DNA (cccDNA) serves as the template for viral replication and can be transcribed to produce five viral RNAs of 3.5, 2.4, 2.1 kb and 0.7 kb in length, which are translated to produce HBeAg, core protein, polymerase (P) protein, HBsAg and HBx proteins, respectively. Among them, the 3.5 kb pregenomic RNA (pgRNA) is also the template for viral reverse transcription. Polymerase protein recognizes and binds to the capsid assembly signal on the pgRNA to initiate capsid assembly and reverse transcription. Recent studies have revealed that the processes of splicing, nuclear export, stability, translation, and pgRNA encapsidation of HBV RNAs are regulated by a post-transcriptional regulatory network within the host cell and depend on unique post-transcriptional regulatory elements in the HBV RNA structure. The aim of this review is to overview the post-transcriptional regulatory mechanisms of HBV RNA and their applications in the study of HBV antiviral therapeutics, with the aim of providing new ideas for the development of new drugs targeting HBV RNA.

Erratum: Momentum-Resolved Observation of Thermal and Quantum Depletion in a Bose Gas [Phys. Rev. Lett. 117, 235303 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.235303.

Primary human thyrocytes maintained the function of thyroid hormone production and secretion in vitro.

PURPOSE: Thyroid cell lines are useful tools to study the physiology and pathology of the thyroid, however, they do not produce or secrete hormones in vitro. On the other hand, the detection of endogenous thyroid hormones in primary thyrocytes was often hindered by the dedifferentiation of thyrocytes ex vivo and the presence of large amounts of exogenous hormones in the culture medium. This study aimed to create a culture system that could maintain the function of thyrocytes to produce and secrete thyroid hormones in vitro. METHODS: We established a Transwell culture system of primary human thyrocytes. Thyrocytes were seeded on a porous membrane in the inner chamber of the Transwell with top and bottom surfaces exposed to different culture components, mimicking the 'lumen-capillary' structure of the thyroid follicle. Moreover, to eliminate exogenous thyroid hormones from the culture medium, two alternatives were tried: a culture recipe using hormone-reduced serum and a serum-free culture recipe. RESULTS: The results showed that primary human thyrocytes expressed thyroid-specific genes at higher levels in the Transwell system than in the monolayer culture. Hormones were detected in the Transwell system even in the absence of serum. The age of the donor was negatively related to the hormone production of thyrocytes in vitro. Intriguingly, primary human thyrocytes cultured without serum secreted higher levels of free triiodothyronine (FT3) than free thyroxine (FT4). CONCLUSION: This study confirmed that primary human thyrocytes could maintain the function of hormone production and secretion in the Transwell system, thus providing a useful tool to study thyroid function in vitro.

Global burden of neoplasms attributable to specific occupational carcinogens over 30 years: a population-based study.

OBJECTIVES: The study aimed to analyze the global burden of occupational neoplasms from various epidemiological perspectives. STUDY DESIGN: In this cross-sectional study, secondary analyses were conducted to assess the burden of neoplasms attributable to occupational carcinogens and their distribution characteristics using data from GBD 2019 and the World Bank database. METHODS: Based on the GBD 2019 and the World Bank database, we analyzed the global burden of occupational neoplasms including the age-period-cohort model, decomposition analysis, health inequality analysis, and panel model. All analyses were conducted in R (version 4.0.3) and Joinpoint (version 4.9.1). RESULTS: The absolute number of neoplasms burden attributable to occupational carcinogens has continued to rise over 30 years. In 2019, occupational neoplasms caused 333,867 [95% uncertainty interval (UI): 263,491 to 404,641] mortalities and 6,964,775 (95% UI: 5,467,884 to 8,580,431) disability-adjusted life years (DALYs) globally. Greenland, Monaco, the Netherlands, and Andorra suffered the highest burden. The burden was higher in countries with a higher sociodemographic index. The age effect was prominent in the elderly, and the 1925 birth cohort had the highest cohort effect. Population growth was the most significant driver of the mortalities (89%) and DALYs (111%) change. Moreover, the proportion of urban population was significantly positively associated with the disease burden, while GDP per capita was negatively correlated with the disease burden. CONCLUSIONS: The burden of occupational neoplasms was unevenly distributed across locations and populations. The need for rational allocation of healthcare resources was urgent.

[Analysis of different protein expression levels in peripheral blood circulating tumor cells from patients with diffuse large B-cell lymphoma and their predictive efficiency for recurrence].

Objective: To analyze the expression levels of differentiation cluster 47 (CD47), signal regulatory protein α (SIRP-α), proto-oncogene (MYC) and proliferating cell associated antigen (Ki67) proteins in peripheral blood circulating tumor cells (CTC) from patients with diffuse large B-cell lymphoma and their predictive efficiency for tumor recurrence. Methods: The data of 82 patients with diffuse large B-cell lymphoma who were confirmed by histopathology and were in remission after chemotherapy in the Hematology Department of Linyi People's Hospital from January 2018 to January 2021 were retrospectively analyzed. There were 44 males and 38 females, and aged from 50 to 75 (63.8±4.6) years. The patients were divided into recurrent group (n=36) and non-recurrent group (n=46) according to their recurrence within 1 year after remission. The fasting peripheral venous blood samples (4 ml) from patients in the morning were collected, and the CTC were isolated. The expression levels of CD47, SIRP-α, MYC and Ki67 proteins in CTC were detected by Western blotting. The correlations between CD47 expression level and SIRP-α, MYC and Ki67 expression levels were analyzed by Pearson correlation analysis. The predictive efficiency of CD47, SIRP-α, MYC and Ki67 expression levels on tumor recurrence was evaluated by receiver operating characteristic (ROC) curves, and the areas under the curve (AUC) were calculated. Results: The expression levels of CD47, SIRP-α, MYC and Ki67 in recurrent group were 2.24±0.23, 1.17±0.12, 1.98±0.20 and 2.63±0.27, while those in non-recurrent group were 2.04±0.21, 1.31±0.13, 1.53±0.16 and 2.24±0.25. The expression levels of CD47, MYC and Ki67 in the recurrent group were higher than those in the non-recurrent group, while the expression levels of SIRP-α were lower than those in the non-recurrent group (all P<0.001). In 82 patients, the expression levels of CD47, SIRP-α, MYC and Ki67 were 2.13±0.22, 1.25±0.13, 1.73±0.18 and 2.41±0.26, respectively. The expression level of CD47 was negatively correlated with the expression level of SIRP-α (r=-0.308, P=0.005), but positively correlated with the expression level of MYC and Ki67 (r=0.484 and 0.332, P=0.012 and 0.003). The sensitivity of CD47, SIRP-α, MYC and Ki67 expression levels in predicting recurrence of diffuse large B-cell lymphoma was 66.7%, 72.2%, 72.2% and 66.7%, with the specificity of 67.4%, 71.7%, 67.4% and 71.7%, and AUC (95%CI) of 0.694 (0.582-0.791), 0.693 (0582-0.790), 0.714 (0.603-0.808) and 0.709 (0.598-0.804), respectively. The sensitivity of the combined detection of the above four indicators was 83.3%, with the specificity of 78.3% and the AUC (95%CI) of 0.864 (0.771-0.930), which was higher than those of the individual detection of each indicator (all P<0.05). Conclusions: The expression level of CD47 was negatively correlated with the expression level of SIRP-α, but positively correlated with the expression level of MYC and Ki67. The expression levels of CD47, SIRP-α, MYC and Ki67 have certain predictive value for tumor recurrence in patients with diffuse large B-cell lymphoma, and the predictive efficiency of combined detection is higher than single indicator detection.

[Predictive value of low-density lipoprotein cholesterol/remnant cholesterol coordination on cardiovascular and cerebrovascular events in elderly patients with hypertension].

Objective: To explore the predictive value of serum low-density lipoprotein cholesterol/residual cholesterol (LDL-C/RC) coordination on major adverse cardiovascular events (MACE) in elderly hypertensive patients. Methods: This is a prospective cohort study. Elderly hypertensive patients hospitalized in Beijing Anzhen Hospital from June 2018 to June 2020 were prospectively enrolled. According to the coordination of baseline LDL-C/RC, patients were divided into four groups: low LDL-C and low RC (LDL-C<2.6 mmol/L, and RC<0.62 mmol/L), low LDL-C and high RC (LDL-C<2.6 mmol/L, and RC≥0.62 mmol/L), high LDL-C and low RC (LDL-C≥2.6 mmol/L, and RC<0.62 mmol/L), and high LDL-C and high RC (LDL-C≥2.6 mmol/L, and RC≥0.62 mmol/L). Patients were followed up until June 2022. The primary outcome was MACE, including non-fatal acute coronary syndrome, non-fatal acute heart failure, non-fatal stroke and death. Kaplan-Meier survival analysis was used to evaluate MACE among the four groups, and Cox regression analysis was performed to evaluate the related factors of MACE. Results: A total of 847 hypertensive patients were enrolled. There were 453 males (53.5%), mean age was (72.4±8.8) years. There were 207, 162, 263, 215 patients in the low LDL-C and low RC, low LDL-C and high RC, high LDL-C and low RC and high LDL-C and high RC group, respectively. During a median follow-up of 37 months, 196 patients (23.1%) had MACE, including 77 cases (9.1%) of ACS, 56 cases (6.6%) of acute heart failure, 34 cases (4.0%)of non-fatal stroke, 29 cases(3.4%) of all-cause mortality, and 16 cases (1.9%) of cardiovascular death. Risk of MACE of the four groups was significantly different (log-rank P<0.001). Compared with low LDL-C and low RC groups, high LDL-C and high RC groups had the highest incidence of MACE (HR=2.237, 95%CI 1.328-3.783, P=0.004), followed by low LDL-C and high RC groups (HR=1.745, 95%CI 1.220-2.527, P=0.003) and high LDL-C and low RC groups (HR=1.393, 95%CI1.048-1.774, P=0.022). In addition, the risk of nonfatal ACS among the four groups was also statistically significant (P=0.037), while the risk of nonfatal acute heart failure, nonfatal stroke, all-cause mortality and cardiovascular death were similar (all P>0.05). Multivariate Cox regression analysis showed that age (HR=1.271), duration of hypertension (HR=1.339), diabetes (HR=1.415), hyperlipidemia (HR=1.348), serum creatinine (HR=1.263), N-terminal pro-B-type natriuretic peptide (HR=1.316), LDL-C (HR=1.205), RC (HR=1.302), low LDL-C and high RC (HR=1.745), high LDL-C and low RC (HR=1.393), high LDL-C and high RC (HR=2.237) were independently associated with the occurrence of MACE. Conclusion: The coordination of LDL-C/RC affects the risk of MACE in elderly hypertensive patients, and the risk of MACE is the highest in patients with high LDL-C and high RC.

[Effects of postoperative urine protein levels on predicting acute kidney injury in critically ill patients undergoing non-cardiac surgery].

Objective: To investigate the predictive value of postoperative urine protein level in critically ill patients undergoing non-cardiac surgery with acute kidney injury (AKI). Methods: A total of 661 critically ill patients undergoing non-cardiac surgery, who visited the Department of Critical Care Medicine of Peking University First Hospital from May 20, 2019 to November 24, 2020, were enrolled in this prospective study. The clinical data of the patient's age, gender, body mass index, laboratory examination, surgical status, etc. were collected. AKI diagnostic criteria of the 2012 KDIGO guidelines were used to diagnose the occurrence of AKI after surgery. The independent predictors of AKI were determined by multivariate logistic regression. Results: The age of this patient cohort was (69±15) years. The prevalence of AKI was 45.4% (300/661). Multivariate logistic regression showed that urine protein semi-quantitative ≥2+(OR=2.62, 95%CI: 1.05-6.56, P=0.039) was independent factor for postoperative AKI in critically ill patients undergoing non-cardiac surgery, other independent factors include higher age (OR=1.04, 95%CI: 1.02-1.06, P=0.001), higher body mass index (BMI) (OR=1.12, 95%CI: 1.04-1.21, P=0.004), lower plasma hemoglobin level (OR=0.98, 95%CI: 0.97-1.00, P=0.019), lower central venous pressure (OR=0.89, 95%CI: 0.83-0.97, P=0.005) and lower total hypotension time (OR=1.01, 95%CI: 1.00-1.01, P=0.041). Conclusions: Urine protein semi-quantitative ≥2+after surgery is an independent predictive factor for the occurrence of postoperative AKI in critically ill patients undergoing non-cardiac surgery. It is important to check urine routine immediately after surgery to detect and deal with high-risk patients.

[Advancement in endovascular therapy of aortoiliac occlusive disease].

Aortoiliac occlusive disease (AIOD) refers to the stenosis and occlusion of the distal abdominal aorta and(or) bifurcation of the aortoiliac artery,which is mainly caused by atherosclerosis,leading to pelvic and lower limb ischemia.Open surgery has always been the main treatment for complex AIOD.However,in recent years,with the development of endovascular surgery technologies and medical instruments,its treatment concept has been greatly changed.More and more clinical evidence has proved that the long-term efficacy of endovascular therapy is not inferior to that of traditional open surgery,so minimally invasive endovascular therapy has become the preferred treatment for AIOD.

[Comparison on the clinical characteristics of patients with Takotsubo syndrome from China and from Europe/North America].

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, ß-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.

Photoluminescence and magnetism integrated multifunctional black phosphorus probes through controllable PO bond orbital hybridization.

Biological probes with integrated photoluminescence and magnetism characteristics play a critical role in modern clinical diagnosis and surgical protocols combining fluorescence optical imaging (FOI) with magnetic resonance imaging (MRI) technology. However, traditional magnetic semiconductors can easily generate a spin splitting at the Fermi level and half-metallic electronic occupation, which will sharply reduce the radiation recombination efficiency of photogenerated carriers. To overcome this intrinsic contradiction, we propose a controllable oxidation strategy to introduce some particular PO bonds into black phosphorus nanosheets, in which the p orbital hybridization between P and O atoms not only provides some carrier recombination centers but also leads to a room-temperature spin polarization. As a result, the coexistence of photoluminescence and magnetism is realized in multifunctional black phosphorus probes with excellent biocompatibility. This work provides a new insight into integrating photoluminescence and magnetism together by intriguing atomic orbital hybridization.

[A comparative study on the construction methods of animal models of aortic arch dissection].

Objective: To compare the effectiveness and safety of different methods to construct animal models of aortic arch dissection (AAD), and explore safe and effective methods for constructing AAD animal models. Methods: Twenty-four healthy mongrel dogs were divided into 4 groups by random number table (n=6). Group A: Venous incision needle high pressure water flow impact method; Group B: Venous incision needle non-high pressure water flow impact method; Group C: Transarterial sheath non-high pressure water flow impact method; Group D: Two-way balloon expansion combined with elastase perfusion method. Imaging examinations were performed immediately and 7 days after operation, aortic tissue biopsy and pathological staining were performed 15 days after operation to observe the formation of AAD. The operation time, aortic blood flow block time, model construction success rate, dissection tear length, postoperative survival rate and survival time of four groups of experimental dogs were collected to compare the effectiveness and safety of different construction methods. Results: There were no significant difference of the gender, age and weight between four groups of experimental dogs (all P>0.05). The operation time of four groups of experimental dogs were (111.6±8.0), (168.0±17.4), (164.4±13.9), (202.8±21.5)min, and the difference was statistically significant (F=39.973, P<0.001). The operation time of group A was significantly lower than group B, C and D (all P<0.001). The aortic blood flow block time of four groups of experimental dogs were (5.2±1.8), (19.6±3.8), (20.6±3.9), and (18.6±3.0) min, and the difference was statistically significant (all P<0.001). The aortic blood flow block time of group A was significantly lower than group B, C and D (F=27.598, P<0.001). The four groups of experimental dogs had 5, 5, 4, and 1 model were successfully constructed, respectively, and the difference was statistically significant (P=0.008). The successful rate of model construction in group A was significantly higher than that in group D (P=0.040). The dissection tear length of four groups were (14.4±3.0), (11.3±4.2), (7.0±2.3), (4.7±0.6) cm,and the difference was statistically significant (F=8.103, P=0.003). The dissection tear length of group A was significantly longer than group C, D (all P<0.05). The postoperative survival time were 15.0(10.0, 15.0), 5.0(3.0, 10.0), 3.5(1.5, 4.8), 10.0(2.8, 15.0) days, and the difference was statistically significant (χ2=7.825,P=0.036). The postoperative survival time of group A was significantly higher than group B, C (all P<0.05). There was no significant difference in the survival rate of the four groups (P=1.000). The pathological staining results showed that the elastic fiber at the tearing point of AAD was destroyed, and the elastic fiber on the outer wall of the false cavity was over-stretched, which was consistent with the pathological changes of aortic dissection. Conclusion: Transvenous incision needle high-pressure water flow impact modeling method is easy to operate. The aortic blood flow block time is short, the dissection tear length is wide, and the postoperative survival time is long, can be used as the preferred method of animal AAD model construction.

[The comparison of prognosis and risk factors after radical resection for pancreatic ductal adenocarcinoma between China Pancreas Data Center and SEER].

Objectives: To compare the prognosis of patients underwent radical resection for pancreatic ductal adenocarcinoma(PDAC) in Surveillance, Epidemiology, and End Results(SEER) and China Pancreas Data Center(CPDC), and to compare the prognostic factors for PDAC in both databases. Methods: The data of patients underwent radical resection for PDAC in CPDC database from January 2016 to December 2017 and SEER database from January 2014 to December 2015 were retrospectively analyzed. The prognosis of patients in both databases was analyzed by the Kaplan-Meier method, Log-rank method, and propensity score matching, and the Cox proportional hazard regression was used to analyze the independent prognosis factors for PDAC. Results: There were 1 977 cases and 2 220 cases of pancreatic cancer that underwent radical resection from CPDC and SEER, respectively. There were more male patients(60.90%,1 204/1 977) than female patients(39.10%,773/1 977) in CPDC, while nearly 1∶1 ratio(male:1 112 cases,female:1108)was observed between male and female in SEER(χ²=48.977,P<0.01). The proportion of patients under 45 years old was the smallest in both databases, and the age group with the most significant proportion was 60 to 74 years old. The ratio of patients over 75 years old in the SEER(24.28%,539/2 220) was higher than that of CPDC(7.89%,156/1 977)(χ²=202.090,P<0.01), while the proportion of patients between 45 and 59 years old in CPDC(33.69%,666/1 977) was higher than that in SEER(19.77%,439/2 220)(χ²=103.640,P<0.01). There were more pancreatic head cancers than body and tail cancers in both databases, and no statistical difference was found in tumor size between the two databases (W=2 181 502,P=0.740). More positive and examined lymph nodes were found in SEER patients (W=3 265 131,W=2 954 363,all P<0.01); and the proportion of patients who had at least 15 lymph nodes dissected was higher in SEER(63.24%,1 404/2 220)(χ²=532.130,P<0.01). There were more patients without neoadjuvant or adjuvant therapy in CPDC(57.16%,1 130/1 977) than that in SEER(24.91%,553/2 220)(χ²=451.390,P<0.01). After propensity score matching, the overall survival for CPDC was better than that for SEER(Log-rank test:χ²=4.500,P=0.034), and the median overall survival was 24 months and 23 months respectively. Cox regressional analysis showed the common independent prognosis factors in both databases were ≥75 years old, pancreatic head cancer, poorly differentiated and undifferentiated tumors, T stage, N stage(All P<0.05). Neoadjuvant or adjuvant therapy was a protective factor in both databases(CPDC:Wald=27.082;SEER:Wald=212.285, all P<0.01) and 45 to 59 years old was protective factor in the SEER database(Wald=5.212,P=0.020). Conclusions: The data in both databases have a good consistency. However, in terms of data quality, examined lymph nodes count, and neoadjuvant/adjuvant therapy rate, the CPDC differs greatly from the SEER.

[Advances in indocyanine green fluorescence imaging during hepatectomy].

While surgical operation is the preferred treatment for liver malignancies,the postoperative recurrence rate remains high. In the early 21st century,Japanese scientists first reported the use of indocyanine green(ICG) in liver resection. Follow-up studies also found its potential applications such as identifying tumors,determining surgical margins,delineating segmental boundaries,and preventing bile leakage. At present,ICG fluorescence imaging is applied to some types of hepatectomy with excellent effect and is expected to assist in generating surgical strategies for liver malignancies. However,its safety and efficacy still need further studies to evaluate.

[Drug-coated balloons versus bare metal stent for treatment of femoropopliteal lesions:36 month follow-up results of single center].

Objective: To examine the therapeutic effects of drug-coated balloon (DCB) and bare metal stent (BMS) on primary femoropopliteal disease (FPAD) in the real world. Methods: This was a retrospective analysis of single-center follow-up results at 12,24,and 36 months of patients with FPAD lesions that were treated with DCB and BMS at Department of Aortic and Vascular Surgery, Fu Wai Hospital.One-to-one propensity score matching(PSM) was performed to balance the covariance between DCB group (137 cases) and BMS group (100 cases). Freedom from clinically driven target lesion reintervention rate(fCD-TLR) was determined by Kaplan-Meier curve.Log-rank test was used to compare the rates of fCD-TLR between DCB and BMS groups at 12,24,36 months post-operation. Results: After PSM, there were both 71 patients in each group,aged (68.0±9.6) years(range: 46 to 90 years) and (68.8±7.3) years(range: 48 to 87 years),lesion lengths were (119.6±14.2)mm(range:40 to 380 mm) and (110.8±13.1)mm(range:40 to 400 mm). The median follow-up period were 24.3 months (range:5.8 to 55.1 months).There was no death,amputation or reintervention within the 30 days after operation.The rates of fCD-TLR for DCB group at 12,24 and 36 months were 97.2%,85.9%,69.1%, and 95.8%,83.1%,59.2% for BMS group.There was no statistical difference between the two groups by Log-rank test (P=0.551). Conclusion: DCB and BMS can both maintain favorable clinical effects in FPAD patients at 12,24,36 months post-operation.

[Study on the expression of non-coding microRNA-376b-3p in serum exosomes of patients with malignant glioma and the mechanism of anti-angiogenesis].

Objective: To screen the different microRNAs in the serum exosomes of patients with malignant glioma, to explore the effect of non-coding microRNA-376b-3p (miR-376b-3p) on the proliferation, invasion and tumor vasculogenic mimicry of glioma cells, and to verify its targeting effect on HOXD10. Methods: HiSeq/MiSeq high-throughput sequencing was used to screen the different microRNA expression profiles, target genes and action pathways in the serum exosomes of patients with malignant glioma. Samples were used to evaluate the expression of candidate microRNAs in serum exosomes of high-grade gliomas. The effects of miR-376b-3p on the proliferation, invasion and angiogenesis of glioma cells were detected by MTT assay, Transwell migration assay and Matrigel vasculogenic mimicry assay. The mRNA and protein expression of HOXD10 were detected to evaluate the regulatory effect of miR-376b-3p on it. Results: There were 144 different expression microRNAs in the serum exosomes between malignant glioma and the normal control. Focal adhesion and tumor protein polysaccharides were involved in the regulation of glioma enriched by KEGG(Kyoto Encyclopedia of Genes and Genomes). MiR-376b-3p was down regulated in malignant glioma, and AUC of malignant glioma was 0.85 (P<0.01). MTT test showed that the proliferation ability of miR-376b-3p inhibitor group was higher than that of the control group, and that of miR-376b-3p mimic group was lower than that of the control group. Transwell migration test showed that the number of transmembrane cells in miR-376b-3p inhibitor group was higher than that in NC inhibitor group, and the number of transmembrane cells in miR-376b-3p mimic group was lower than that in NC mimic group. The number of tubes of vasculogenic mimicry in miR-376b-3p mimic group was lower than that in NC mimic group. MiR-376b-3p inhibitor decreased the expression level of HOXD10 mRNA and protein, and miR-376b-3p mimic increased the expression level of HOXD10 mRNA and protein. Conclusions: MiR-376b-3p is down-regulated in the serum exosomes of malignant glioma patients. The up-regulated miR-376b-3p can reduce the proliferation and invasion of glioma cells, inhibit the formation of vasculogenic mimicry, and increase the expression of HOXD10, which is expected to inhibit the formation of two forms of angiogenesis at the same time. MiR-376b-3p may be a new therapeutic target of anti-angiogenesis for malignant glioma.

[Manual suture or stapler closure: management of pancreatic stump during distal pancreatectomy].

Postoperative pancreatic fistula is the most common complication after distal pancreatectomy.With the update of the domestic and international guidelines or consensuses, the definition of pancreatic fistula has become more standardized.And the classification of pancreatic fistula is able to represent the severity of clinical outcomes more accurately.Currently, the determination of risk factors of pancreatic fistula after distal pancreatectomy, the establishment of prediction model, and the surgical closure mode of pancreatic stump still remain the major topics.With the rapid development of laparoscopic and robotic surgery in pancreatectomy, there are more and more selectionsin transection and managing the pancreatic stump after distal pancreatectomy for prevention of pancreatic fistula.However, there has not been a uniform fashion in terms of manual suture or stapler use to close the pancreatic stump.Herein the current status and development of pancreatic fistula after distal pancreatectomy are reviewed.The strategy of managing the pancreatic stump after distal pancreatectomy should be adopted individually according to the texture and thickness of pancreatic parenchyma.

[Surgical treatment of total subclavian artery occlusion: a single center experience of 67 cases].

Objective: To examine the outcomes of surgical repair for patients with total subclavian artery occlusion. Methods: A retrospective analysis was performed on 67 patients with subclavian artery occlusion disease admitted at Ward 1 of Aortic and Vascular Surgery Center, Fuwai Hospital from January 2016 to July 2019. The age was, and There were 51 male patients and 16 females with an age of (61.7±8.2) years (range: 37 to 79 years). The t-test, Mann-Whitney U-test, χ(2) test, and Fisher's exact test were used to analyze the factors related to the technique success. The Kaplan-Meier curve was used to calculate the cumulative patency rate and plot the corresponding survival curves, and the Log-rank test was used for comparison. The length from the subclavian artery ostial to the occlusion area was used as a variable to plot the receiver operating characteristic curve, and the optimal cut-off value was determined by the Youden index. Results: Eighteen patients received open surgery. Forty-nine patients with subclavian artery occlusion accepted endovascular repair, of which 38 patients succeeded (31 cases on left side and 3 cases on right side). Fifteen patients failed with endovascular therapy, of which 10 cases received elective surgery and 5 cases received conservative therapy. The success rate of endovascular repair was 69.4%(34/49). Among them, the success rate of left subclavian artery occlusion was 81.6%(31/38), while the right side was 3/11. Patients with the length from the subclavian artery ostial to the occlusion area ≥6 mm were more likely to get success (23/34 vs. 4/15, χ(2)=5.506, P=0.019). In the endo-group, one patient had hemorrhage in the left chest. In the open-group, one patient had lymphatic leakage. Follow-up period ranged from 3 to 46 months with a median of 22 months. The patency of endovascular repair group and the open surgery group was 92.6% and 90.8% at 12-month, while 82.9% and 84.3% at 24-month, respectively. The cumulative patency rates of smoking patients and non-smoking patients after endovascular treatment were 70.2% vs. 100% (P=0.048) at 24-month. No independent prognosis factors were identified through the Cox proportional risk model which significantly affected postoperative patency rates for patients with subclavian artery occlusion. Conclusions: Part of patients with subclavian artery occlusion can be treated by endovascular therapy. The success rate of left subclavian artery occlusions is higher than right sides. The length from the subclavian artery ostial to the occlusion area affected the success rate of repair.

Effect of centrifugal force on the development of articular neocartilage with bovine primary chondrocytes.

A lot has been invested into understanding how to assemble cartilage tissue in vitro and various designs have been developed to manufacture cartilage tissue with native-like biological properties. So far, no satisfactory design has been presented. Bovine primary chondrocytes are used to self-assemble scaffold-free constructs to investigate whether mechanical loading by centrifugal force would be useful in manufacturing cartilage tissue in vitro. Six million chondrocytes were laid on top of defatted bone disks placed inside an agarose well in 50-ml culture tubes. The constructs were centrifuged once or three times per day for 15 min at a centrifugal force of 771×g for up to 4 weeks. Control samples were cultured under the same conditions without exposure to centrifugation. The samples were analysed by (immuno)histochemistry, Fourier transform infrared imaging, micro-computed tomography, biochemical and gene expression analyses. Biomechanical testing was also performed. The centrifuged tissues had a more even surface covering a larger area of the bone disk. Fourier transform infrared imaging analysis indicated a higher concentration of collagen in the top and bottom edges in some of the centrifuged samples. Glycosaminoglycan contents increased along the culture, while collagen content remained at a rather constant level. Aggrecan and procollagen α1(II) gene expression levels had no significant differences, while procollagen α2(I) levels were increased significantly. Biomechanical analyses did not reveal remarkable changes. The centrifugation regimes lead to more uniform tissue constructs, whereas improved biological properties of the native tissue could not be obtained by centrifugation.

[Induction of specific CD8(+) T cells against hepatocellular carcinoma-associated neoantigens].

Objective: To predict the tumor neoantigen peptides in hepatocellular carcinoma (HCC), and examine their specific immune effects against the tumor cells without injury to normal cells. Methods: The data of whole-genome sequencing and exome sequencing of HCC tumor and matched non-tumor liver tissues were analyzed to confirm the HCC-associated somatic mutations. Based on the HLA phenotype of the patients, we used NetMHC software to predict the neoantigen epitopes with high binding affinity to their MHC-I molecules. The predicted peptides with mutation sites included were synthesized. GPL10687 platform was applied to examine the gene expression difference between tumor and normal tissues of the selected genes in GSE25097, one of the GEO databases. The quantitative real-time PCR (qRT-qPCR) and immunohistochemistry were used to confirm the expressions in tumors and normal tissues of the selected genes. By using the predicted peptides, we induced the generation of antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) and examined their specific effects against tumor cells. Results: The mutation frequency of TP53 (tumor protein p53) was 40%, and LAMA3 (Laminin Subunit Alpha 3) was 8% in the analyzed HCC tissues. In GSE25097 database, TP53 and LAMA3 mRNA levels in tumors were 1.57±0.02 and 1.37±0.10, which were significantly increased than those in matched no-tumor tissue (0.54±0.01 and 0.36±0.01, P<0.05). The differences of expression levels of TP53 and LAMA3 in tumor and no-tumor tissues were validated by using qRT-qPCR and immunohistochemistry in 10 HCC tissues. The mRNA levels of TP53 and LAMA3 in tumors were 0.24±0.03 and 0.13±0.06, which were significantly elevated than those in matched no-tumor tissue (0.11±0.01 and 0.01±0.01, P<0.05). Among the Chinese population, HLA-A2 and HLA-A11 and HLA-A24 accounted for 70%, representing the major MHC-I molecules. The CTLs induced by predicted peptides showed cytotoxicity to the targets pulsed with mutated peptide, with no effect on the target pulsed with normal peptide and on normal cells. Conclusions: TP53 and LAMA3 existed relative higher mutation frequency in HCC, and expressed higher in tumor tissues. The induced CTLs by predicted peptides derived from mutation-associated protein could specific kill the target cells without injury to normal cells.