Photonic Source of Heralded Greenberger-Horne-Zeilinger States.

Generating large multiphoton entangled states is of main interest due to enabling universal photonic quantum computing and all-optical quantum repeater nodes. These applications exploit measurement-based quantum computation using cluster states. Remarkably, it was shown that photonic cluster states of arbitrary size can be generated by using feasible heralded linear optics fusion gates that act on heralded three-photon Greenberger-Horne-Zeilinger (GHZ) states as the initial resource state. Thus, the capability of generating heralded GHZ states is of great importance for scaling up photonic quantum computing. Here, we experimentally demonstrate this required building block by reporting a polarisation-encoded heralded GHZ state of three photons, for which we build a high-rate six-photon source (547±2 Hz) from a solid-state quantum emitter and a stable polarization-based interferometer. The detection of three ancillary photons heralds the generation of three-photon GHZ states among the remaining particles with fidelities up to F=0.7278±0.0106. Our results initiate a path for scalable entangling operations using heralded linear-optics implementations.

Jupiter's atmospheric jet streams extend thousands of kilometres deep.

The depth to which Jupiter's observed east-west jet streams extend has been a long-standing question. Resolving this puzzle has been a primary goal for the Juno spacecraft, which has been in orbit around the gas giant since July 2016. Juno's gravitational measurements have revealed that Jupiter's gravitational field is north-south asymmetric, which is a signature of the planet's atmospheric and interior flows. Here we report that the measured odd gravitational harmonics J3, J5, J7 and J9 indicate that the observed jet streams, as they appear at the cloud level, extend down to depths of thousands of kilometres beneath the cloud level, probably to the region of magnetic dissipation at a depth of about 3,000 kilometres. By inverting the measured gravity values into a wind field, we calculate the most likely vertical profile of the deep atmospheric and interior flow, and the latitudinal dependence of its depth. Furthermore, the even gravity harmonics J8 and J10 resulting from this flow profile also match the measurements, when taking into account the contribution of the interior structure. These results indicate that the mass of the dynamical atmosphere is about one per cent of Jupiter's total mass.

A suppression of differential rotation in Jupiter's deep interior.

Jupiter's atmosphere is rotating differentially, with zones and belts rotating at speeds that differ by up to 100 metres per second. Whether this is also true of the gas giant's interior has been unknown, limiting our ability to probe the structure and composition of the planet. The discovery by the Juno spacecraft that Jupiter's gravity field is north-south asymmetric and the determination of its non-zero odd gravitational harmonics J3, J5, J7 and J9 demonstrates that the observed zonal cloud flow must persist to a depth of about 3,000 kilometres from the cloud tops. Here we report an analysis of Jupiter's even gravitational harmonics J4, J6, J8 and J10 as observed by Juno and compared to the predictions of interior models. We find that the deep interior of the planet rotates nearly as a rigid body, with differential rotation decreasing by at least an order of magnitude compared to the atmosphere. Moreover, we find that the atmospheric zonal flow extends to more than 2,000 kilometres and to less than 3,500 kilometres, making it fully consistent with the constraints obtained independently from the odd gravitational harmonics. This depth corresponds to the point at which the electric conductivity becomes large and magnetic drag should suppress differential rotation. Given that electric conductivity is dependent on planetary mass, we expect the outer, differentially rotating region to be at least three times deeper in Saturn and to be shallower in massive giant planets and brown dwarfs.

Measurement of Jupiter's asymmetric gravity field.

The gravity harmonics of a fluid, rotating planet can be decomposed into static components arising from solid-body rotation and dynamic components arising from flows. In the absence of internal dynamics, the gravity field is axially and hemispherically symmetric and is dominated by even zonal gravity harmonics J2n that are approximately proportional to qn, where q is the ratio between centrifugal acceleration and gravity at the planet's equator. Any asymmetry in the gravity field is attributed to differential rotation and deep atmospheric flows. The odd harmonics, J3, J5, J7, J9 and higher, are a measure of the depth of the winds in the different zones of the atmosphere. Here we report measurements of Jupiter's gravity harmonics (both even and odd) through precise Doppler tracking of the Juno spacecraft in its polar orbit around Jupiter. We find a north-south asymmetry, which is a signature of atmospheric and interior flows. Analysis of the harmonics, described in two accompanying papers, provides the vertical profile of the winds and precise constraints for the depth of Jupiter's dynamical atmosphere.

[Clinical characteristics and efficacy analysis of various treatments for spontaneous carotid artery dissection].

Objective: To investigate the clinical features of spontaneous carotid artery dissection (SCAD) and the efficacy of different treatment methods. Methods: The clinical data of 164 patients with SCAD who were treated at the First Affiliated Hospital of Zhengzhou University from June 2018 to January 2023 were retrospectively analyzed. There were 127 males and 37 females, with a mean age of (49.5±11.1) years. They were divided into conservative treatment group (n=100) and surgical treatment group (n=64) according to whether they received surgical treatment. Patients were followed at 3, 6, and 12 months after discharge and annually thereafter through outpatient or inpatient visits. The incidence of cerebral ischemic events, cerebral hemorrhage events, and mortality rates during hospitalization and follow-up periods were analyzed in the two patient groups. To examine correlates of revascularization in SCAD, multifactorial logistic regression analysis was used. Results: Of the 164 patients, 18 patients had bilateral SCAD and a total of 182 carotid arteries were included in the study. Ischemic stroke (85 cases, 51.8%) and transient ischemic attack (31 cases, 18.9%) were the main clinical manifestations in SCAD patients. Hypertension (81 cases, 49.4%) and hyperlipidemia (39 cases, 23.8%) were the main comorbidities in SCAD patients. During hospitalization, 100 patients in the conservative treatment group received medication in 113 carotid arteries, no new cerebral ischemic events or symptomatic intracranial hemorrhage events occurred, and no death occurred. A total of 69 carotid arteries were surgically treated in 64 patients in the surgical treatment group. The success rate was 97.1% (67/69). In the surgical treatment group, the proportion of carotid stenosis degree≥90% was 47.8% (33/69), the proportion of type Ⅱ SCAD was 60.9% (42/69), and the proportion discharged from the hospital to receive antiplatelet therapy was 92.8% (64/69), which were higher than those in the conservative treatment group, which were 25.7% (29/113), 45.1% (51/113), and 73.5% (83/113), respectively (all P<0.05). The follow-up time [M(Q1, Q3)] in the conservative treatment group was 24 (13, 34) months, with an 8% (9/113) rate of ischemic events and a 7.1% (8/113) rate of readmission; in the surgical treatment group, the follow-up time was 24 (11, 38) months, and there were no new ischemic events or deaths. The results of multifactorial logistic regression analysis showed that the degree of true luminal stenosis<90% (OR=2.738, 95%CI: 1.067-7.026, P=0.036) and type Ⅰ dissections (OR=2.656, 95%CI: 1.189-5.935, P=0.017) were the correlates of complete revascularization. Conclusions: Ischemic stroke and transient ischemic attack are the main clinical manifestations in patients with SCAD. Pharmacological antithrombotic therapy remains the method of choice, and endovascular treatment after failure of conservative therapy reduces the risk of recurrent long-term cerebral ischemic events and the re-admission rate of patients.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

[Analysis of the efficacy of left subclavian artery laser in situ fenestration combined with hybrid arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection].

Objective: To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods: This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results: Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m2 vs.(26.9±1.9)kg/m2; t=2.766,P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion: Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

[Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis].

Objective: To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis. Methods: This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates. Results: All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%. Conclusion: For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient's condition,and the mid-and long-term outcomes are satisfactory.

[Study on risk factors of mycobacterium tuberculosis infection among health workers in medical institutions].

Objective: To understand the infection status of mycobacterium tuberculosis among health workers in tuberculosis designated medical institutions and explore the risk factors of infection. Methods: From September 2021 to June 2022, a questionnaire survey was conducted among health workers in relevant departments of 4 tuberculosis designated medical institutions by cluster stratified sampling, including the implementation of hospital infection control measures in medical institutions and occupational exposure of medical staff to mycobacterium tuberculosis. Peripheral blood interferon gamma release assays (IGRAs) and lung imaging examination were performed to determine the mycobacterium tuberculosis infection. Factors with statistical significance in univariate analysis were included in multivariate logistic regression to analyze the risk factors of mycobacterium tuberculosis infection. Results: A total of 657 people completed the lung imaging examination and questionnaire, of which 654 people had peripheral blood IGRAs detection, and the latent infection rate of tuberculosis was 39.45% (258/654) . Univariate analysis showed that age, sex, marital status, economic income, occupational category, professional title, length of service, and other variables had statistical significances in tuberculosis latent infection (P<0.05) . In terms of personal health status, there were statistically significant differences in the distribution of health workers in terms of their tuberculosis history, tuberculosis history of their immediate family members, previous tuberculin skin test (TST) (P<0.05) . Multivariate analysis showed that there were four risk factors related to tuberculosis, including professional title (X(1)) , years of tuberculosis related works (X(2)) , tuberculosis history (X(3)) and previous TST (X(4)) . The regression equation of the probability of tuberculosis among health workers was y=-1.920+0.246X(1)+0.046X(2)+1.231X(3)+0.478X(4). Conclusion: The latent infection rate of tuberculosis among health workers in tuberculosis designated medical institutions is high. It is necessary to strengthen the management of infection control, carry out regular screening, enhance the self-protection awareness of health workers, and reduce their exposure to mycobacterium tuberculosis and infection risk.

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.

[Single hydrogen-methane breath test for the diagnosis of small intestinal bacterial growth].

Objective: To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO). Method: The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH4 (methane) and H2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman's Rank correlation analysis,and the Z test were used for statistical analysis. Results: Based on the international recommended diagnostic criteria for SIBO,which are fasting CH4 ≥10 ppm (parts per million) or H2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH4 and H2 were higher in the case group than in the control group [CH4: 3(2,7) vs. 3(1,3) ppm, H2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH4 levels was statistically significant (Z=6.22,P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH4 alone,0.531 for H2 alone, and 0.620 for CH4 combined with H2. The cut-off values were fasting CH4≥4 ppm,fasting H2≥13 ppm,and fasting CH4 ≥5 ppm (or CH4≥4 ppm and H2≥24 ppm),respectively. Measuring CH4 alone and CH4 combined with H2 was effective for determining the presence of gastrointestinal symptoms (P<0.05). When CH4 alone or CH4 combined with H2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria (P>0.05). The specificity of CH4 alone was 79.9%,and the accuracy of CH4 alone was 68.8%. The specificity of CH4 combined with H2 was 85.0%,and the accuracy of CH4 combined with H2 was 71.7%. Conclusion: Rapid one-time determination of CH4 and H2 in exhaled breath may a viable diagnostic method for SIBO, and using CH4 combined with H2 (i.e.,fasting CH4≥5 ppm, or CH4 ≥4 ppm and H2 ≥24 ppm) as cutoff values may be feasible.

[Prevalence of frailty and associated factors among kidney transplant recipients].

Objective: To investigate the prevalence of frailty among kidney transplant recipients and to analyze the influential factors of frailty after kidney transplantation. Methods: We retrospectively included 201 kidney transplant recipients who were followed up in the Department of Urology, Beijing Chao-yang Hospital, Capital Medical University from November 2020 to May 2022. We investigated the prevalence of frailty based on the Fried Frailty Scale (including unexpected shrinking, slow walking speed, poor grip strength, low physical activity, and exhaustion). Then the logistic regression model and CART decision tree model were established separately to explore the influential factors of frailty after kidney transplantation. Results: Frail kidney transplant recipients accounted for 25.9% (n=52) of all participants. The age [M (Q1, Q3)] of the frailty group was higher than that of the non-frailty group, and the median ages of the two groups were 57(49, 62) and 46(38, 56) (P<0.001); the males accounted for 51.9% (n=27) and 62.4% (n=93), respectively. There was no significant difference in gender composition (P=0.244). Among the five components of Fried Frailty Scale, the incidence of unexpected shrinking was the lowest (19.4%, 39/201). In the frailty group, the frailty combination with the highest incidence was slow walking speed+low physical activity+exhaustion, which was 19.2% (10/52). The logistic regression model showed that advanced age (OR=1.062, 95%CI: 1.005-1.123), history of acute rejection (OR=16.776, 95%CI: 2.288-123.028), increased neutrophil/lymphocyte ratio (NLR) (OR=2.096, 95%CI: 1.158-3.792), and comorbidity (OR=10.600, 95%CI: 1.828-61.482) were risk factors for frailty among kidney transplant recipients, and high serum albumin level (OR=0.623, 95%CI: 0.488-0.795) was a protective factor. The CART decision tree grew in three layers with four terminal nodes, and three explanatory variables were screened out: serum albumin, NLR, and age. The accuracy, sensitivity, and specificity of the logistic regression model were 87.1% (95%CI: 82.5%-91.7%), 69.2% (95%CI: 54.7%-80.9%), and 93.3% (95%CI: 87.7%-96.6%), respectively. The area under the ROC curve (AUC) of the logistic regression model was 0.951 (95%CI: 0.923-0.978). The accuracy, sensitivity, and specificity of the CART decision tree model were 91.0% (95%CI: 87.0%-95.0%), 82.7% (95%CI: 69.2%-91.3%), and 94.0% (95%CI: 88.5%-97.0%), respectively. The AUC of the CART decision tree model was 0.883 (95%CI: 0.819-0.948). Conclusions: The prevalence of frailty among kidney transplant recipients in this study is 25.9%. Advanced age, history of acute rejection, low serum albumin level, increased NLR, and comorbidity are likely to be associated with the long-term frailty among kidney transplant recipients.

[Related factors of high-volume lymph node metastasis in multifocal papillary thyroid carcinoma].

Objective: To explore the related factors of high-volume lymph node metastasis (HVM) in multifocality papillary thyroid carcinoma (MPTC). Methods: The clinical and pathological data of multifocality papillary thyroid carcinoma (MPTMC, d≤10 mm) and MPTC (d>10 mm) collected from Hangzhou First People's Hospital from January 2010 to March 2023 were retrospectively analyzed. Univariate and multivariate logistic regression analysis were used to analyze the relevant factors of HVM. Results: Among 566 cases of MPTMC and 381 cases of MPTC, there were 72 males and 494 females in MPTMC, 106 males and 275 females in MPTC, respectively. The median age of the patients was 47 (39, 54) and 47 (34, 56) years, respectively, and the incidence of HVM was 4.6% (26/566) and 21.5% (82/381), respectively (χ2=64.588, P<0.001). Univariate analysis showed that in patients with MPTMC and MPTC, the incidence of HVM in males was higher than that in females [15.3% (11/72) vs 3.0% (15/494) (χ2=21.487, P<0.001) in MPTMC, 33.2% (35/106) vs 17.1% (47/275) (χ2=11.492, P=0.001) in MPTC]. The age of the HVM group was lower than that of the non-HVM group [41 (33, 50) vs 48 (39, 54) years (Z=-2.128, P=0.033) in MPTMC, 38 (29, 48) vs 48 (36, 57) years (Z=-4.987, P<0.001) in MPTC]. The maximum diameter of tumors in the HVM group were higher than those in the non-HVM group [7.0 (5.0, 10.0) mm vs 6.0 (5.0, 8.0) mm (Z=-2.558, P=0.011) in MPTMC, 17.5 (13.0, 25.0) mm vs 15.0 (12.0, 20.0) mm (Z=-2.871, P=0.004) in MPTC]. Multivariate logistic regression analysis showed that larger tumor size (OR=3.027, 2.378; 95%CI: 1.287-7.117, 1.404-4.030; P=0.011, 0.001), male (OR=5.398, 1.909; 95%CI: 2.284-12.758, 1.113-3.274; P<0.001, P=0.019), and younger age (OR=3.889, 3.136; 95%CI: 1.686-8.969, 1.837-5.355; P=0.001, P<0.001) were all risk factors for the occurrence of HVM in MPTMC and MPTC. Conclusion: The proportion of HVM in MPTC patients was higher than that in MPTMC, and larger maximum diameter, male gender and younger age are related factors for HVM in MPTMC and MPTC.

[Progress and application of liver organoids in the study of liver cancer].

The incidence rate of liver cancer has been rising in recent years. Traditional cell line culture and human patient-derived tumor xenograft models, which are commonly used tools to simulate the occurrence of human liver cancer, have deepened the understanding of tumor occurrence, development, and drug resistance mechanisms. However, they cannot reflect the accurate state of cancer cells, the tumor microenvironment, or spatial structural characteristics. Recently, more in vitro-produced physiological liver organoids have been applied in the study of liver cancer. Liver organoid models have made breakthroughs in the occurrence and development mechanisms of liver cancer, personalized drug screening and biomarker identification, immunotherapy, and regenerative medicine applications. This paper mainly summarizes the progress and application of liver organoids processed in the study of liver cancer.

[Status and challenges of neoadjuvant immunotherapy for hepatocellular carcinoma].

With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

[Efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma].

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(n=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(n=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,P=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,P=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P=0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,P=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.

Contour prognostic model for predicting survival after resection of colorectal liver metastases: development and multicentre validation study using largest diameter and number of metastases with RAS mutation status.

BACKGROUND: Most current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables. METHODS: A prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort. RESULTS: A total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases. CONCLUSION: The contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.

Down-regulation of betatrophin enhances insulin sensitivity in type 2 diabetes mellitus through activation of the GSK-3ß/PGC-1α signaling pathway.

OBJECTIVE: The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. Accumulating evidences have noted the significant role of betatrophin in the regulation of lipid metabolism and glucose homeostasis. In our study, we tried to figure out the underlying mechanism of betatrophin in insulin resistance (IR) in type 2 diabetes mellitus (T2DM). METHODS: First, fasting serum betatrophin, fasting blood glucose (FBG), insulin, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were detected in T2DM children. The homeostasis model assessment of insulin resistance (HOMA-IR), Gutt insulin sensitivity index (ISIG) and Matsuda insulin sensitivity index (ISIM) were calculated. A T2DM-IR mouse model was induced by high-fat diet, with the expression of GSK-3ß and PGC-1α detected. Besides, HepG2 cells were induced by a high concentration of insulin to establish an IR cell model (HepG2-IR). The cell viability, glucose consumption, liver glycogen content, inflammation, and fluorescence level of GSK-3ß and PGC-1α were analyzed. RESULTS: Betatrophin was highly expressed in serum of T2DM children and was positively correlated with FBG, insulin, TC, TG, LDL-C and HOMA-IR, while negatively correlated with ISIG and ISIM. Betatrophin and GSK-3ß in the liver tissues of T2DM-IR mice were increased, while the PGC-1α expression was decreased. Betatrophin expression was negatively correlated with PGC-1α and positively correlated with GSK-3ß. Silencing of betatrophin enhanced insulin sensitivity through the activation of GSK-3ß/PGC-1α signaling pathway. In vitro experiments also found that silencing of betatrophin promoted glucose consumption and glycogen synthesis while inhibited inflammation. CONCLUSION: Our findings concluded that silencing of betatrophin could enhance insulin sensitivity and improve histopathological morphology through the activation of GSK-3ß/PGC-1α signaling pathway.

H-FABP gene expression and genetic association with meat quality traits in domestic pigeons (Columba livia).

1. H-FABP (heart-type fatty acid-binding protein) is an important fatty acid-binding protein that participates in the metabolism and intracellular transportation of lipids. This study was designed to study the H-FABP gene expression and genetic association with meat quality traits in domestic pigeons.2. The spatio-temporal expression patterns showed that H-FABP was widely expressed in all eleven tissues in birds from hatching to 4 weeks of age, and the expression level in the liver was the highest, and spleen and subcutaneous fat showed relatively high levels at all time points, and increased markedly as squabs became older.3. Nine novel SNPs were found; three of them (g.42 C > T and g.123 C > T in exon 1 and g.3128 C > T in exon 2) were synonymous mutations, and six of them (g.3304 T > C, g.3305 G > A, g.3313A>G, g.3343 C > T, g.3372A>C, g.3410 T > C in exon 3) were located in the 3' untranslated region (UTR). In addition, four haplotypes and six diplotypes were formed and showed weak linkage disequilibrium. Association analysis showed that in the SNP of g.3305 G > A, the AB genotype showed higher (P < 0.05) inosinic acid concentrations in breast muscle than the BB genotype. In the SNP of g.3313A>G, the AA and AB genotypes showed significantly higher (P < 0.01) inosinic acid concentrations than the BB genotype, AA showed the highest intramuscular fat content, and the relative mRNA expression level of the AA genotype was the highest (P < 0.05).4. Association analysis of diplotypes showed no correlation with meat quality traits. Moreover, correlation analysis indicated that the H-FABP mRNA expression level was tightly related to intramuscular fat content (P < 0.01).5. This study suggested that the H-FABP gene may be a candidate gene in marker-assisted selection of pigeons for high-quality meat.