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Objective: To develop and validate clinical and radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI of dual-phenotype hepatocellular carcinoma (DPHCC) for preoperative differential diagnosis. Methods: Two hundred and fifty inpatients of hepatocellular carcinoma (HCC) confirmed by postoperative pathology, who underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. A total of 172 inpatients (72 DPHCC and 100 non-DPHCC) were included in Institution 1 (the First Affiliated Hospital of Soochow University) as a training cohort (between January 2020 and July 2023) and 78 inpatients (44 DPHCC and 34 non-DPHCC) were included in Institution 2 (the Third People's Hospital of Nantong) as an external validation cohort(between January 2019 and July 2023). The regions of interest of the tumor were delineated layer by layer in noncontrast phase, arterial phase (AP), portal venous phase (PP) and hepatobiliary phase (HBP) images. The software of FAE was used to extract the radiomics features of the images. Pearson correlation analysis and recursive feature elimination were used for feature selection. Each phase and combined radiomics models were established using logistic regression, linear discriminant analysis and support vector machine. Receiver operating characteristic curve and the areas under the curve (AUC) were used to evaluate and select the dominant radiomics model. The dominant radiomics model was combined with clinically independent predictors to construct a clinical radiomics model. Delong test was used to compare the performance of the models. Results: The age of the training cohort was (59.6±10.4) years, in which there were 135 men (78.5%). In the external validation cohort, the age was (57.8±9.2) years, including 56 men (71.8%). The maximum diameters of the lesions [M (Q1, Q3), 4.7 (2.6, 7.5) vs 2.7 (1.8, 4.4) cm, P<0.001] and the proportion of the multiple lesions (39.5% vs 16.7%, P<0.001) in the training cohort were higher than those in the external validation cohort. In the training group, the proportion of patients with hepatitis B virus (HBV) infection in the DPHCC subgroup (66.7%,48/172) was higher than that in non-DPHCC subgroup (49.0%,49/78,P=0.021). In the external validation cohort, the AUC (95%CI) of the PP [0.835 (0.733-0.937)] and combined radiomics models [0.786 (0.681-0.891)] were significantly higher than that of noncontrast phase [0.451 (0.319-0.584)], AP [0.566 (0.435-0.696)] and HBP models [0.496 (0.363-0.629)] (all P<0.05). There was no significant difference in AUC between PP radiomics model and combined radiomics model (P=0.189). The AUC between the radiomics models and clinical-radiomics models, which were brought into clinically independent variable HBV, showed no significant difference (all P>0.05). Conclusion: Gd-EOB-DTPA-enhanced MRI radiomics model based on portal venous phase may be available for discriminating DPHCC from non-DPHCC before operation.

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BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. RESULTS: Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

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The article "Resveratrol protects myocardial apoptosis induced by ischemia-reperfusion in rats with acute myocardial infarction via blocking P13K/Akt/e-NOS pathway", by X. Zhang, L.-F. Huang, L. Hua, H.-K. Feng, B. Shen, published in Eur Rev Med Pharmacol Sci 2019; 23 (4): 1789-1796-DOI: 10.26355/eurrev_201902_17142-PMID: 30840305 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/6A6E686494A160FBE7A1725E5CE30C) regarding figure duplication in Figures 1 and 2A, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The journal investigation revealed a figure duplication between the panels AMI and AMI+RSV+LY of Figure 1. The authors were informed about the journal's investigation but remained unresponsive and did not provide the study's raw data. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17142.

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Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

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Objective: To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP). Methods: This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the 1 211 patients,440 cases were in the robot-assisted group(173 males and 267 females),with an age(M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ2 test,while multivariate analysis utilized binary logistic regression. Results: After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor:χ2=1.200,P=0.952;malignant tumor:χ2=0.391,P=0.532). The surgical duration of the RDP group (Z1=15.113,P1<0.01; Z2=4.232, P2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss (Z1=12.530,P1<0.01;Z2=2.550,P2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group (Z1=10.947, P1<0.01), but not different from that in the laparoscopic group (P2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender(χ2=12.048,P=0.001),history of smoking (χ2=6.327,P=0.012),history of alcohol consumption (χ2=17.597,P<0.01),manual pancreas division (χ2=9.839,P=0.002),early elevation of amylase in drainage fluid (Z=5.187,P<0.01),and delayed gastric emptying (χ2=4.485,P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption(P=0.002,95%CI: 0.112 to 0.623), manual pancreas division(P=0.001,95%CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml(P<0.01,95%CI:0.151 to 0.438),and delayed gastric emptying (P=0.020, 95%CI: 1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusion: Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

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Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 µg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

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Magnetic monopoles, despite their ongoing experimental search as elementary particles, have inspired the discovery of analogous excitations in condensed matter systems. In chiral condensed matter systems, emergent monopoles are responsible for the onset of transitions between topologically distinct states and phases, such as in the case of transitions from helical and conical phase to A-phase comprising periodic arrays of skyrmions. By combining numerical modeling and optical characterizations, we describe how different geometrical configurations of skyrmions terminating at monopoles can be realized in liquid crystals and liquid crystal ferromagnets. We demonstrate how these complex structures can be effectively manipulated by external magnetic and electric fields. Furthermore, we discuss how our findings may hint at similar dynamics in other physical systems and their potential applications.

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Integrators are critical instruments used for magnetic measurement systems (MMSs) in tokamaks, and, currently, the Experimental Advanced Superconducting Tokamak (EAST) has over 600 deployed. However, these integrators, designed with real-time drift compensation, will not be able to support longer pulse operations in the near future due to saturation and drift. To address these issues, this paper proposes a new alternating integration system combining analog integration with drift digital rectification. This system utilizes a microcontroller unit (MCU) to control two parallel analog integrators to work alternatively, compensate their drifts based on their respective error characteristics, and assemble the two integration segments together. The designed architecture provides highly flexible capabilities in operation modes and error correction, which make the system operation and maintenance highly automated. Performance tests on the EAST experiment site show that the prototype integrator can meet the requirements of real-time plasma control for a duration of hour-level.

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OBJECTIVE: To investigate the role of angiotensin-converting enzyme (ACE) in the reproduction of Culex pipiens pallens, so as to provide insights into selection of targets for controlling mosquito vector populations. METHODS: Cx. pipiens pallens was collected from Tangkou County, Shandong Province in 2009. Female and male mosquitoes were selected at 72 hours post-eclosion, and quantitative real-time reverse transcription PCR (qPCR) assay was used to detect the expression of ACE gene in the whole body and reproductive tissues of male mosquitoes and fertilized female mosquitoes before (0 h) and after blood meals (24, 48, 72 h), respectively. Then, 150 female and 150 male mosquitoes at 0 to 4 hours post-eclosion were selected and divided into the wild-type group (WT group), small interfering RNA-negative control group (siNC group) and small interfering RNA-ACE group (siACE group), of 50 mosquitoes in each group. Mosquitoes in the WT group were given no treatment, and mosquitoes in the siNC and siACE groups were given microinjection of siNC and siACE into the hemolymph at a dose of 0.3 µg per mosquito. The knockdown efficiency was checked using qPCR assay, and the reproductive phenotype of mosquitoes was observed. RESULTS: The relative ACE gene expression was higher in the whole body of male mosquitoes (5.467 ± 1.006) relative to females (1.199 ± 0.241) (t = 5.835, P = 0.004) at 72 h post-eclosion, and the highest ACE expression was seen in reproductive tissues of male mosquitoes (199.100 ± 24.429), which was 188.3 times higher than in remaining tissues (1.057 ± 0.340) (t = 6.602, P = 0.002). Blood meal induced high ACE expression in all body tissues of fertilized female mosquitoes, with peak expression at 24 h after blood meals (14.957 ± 2.815), which was 14.8 times higher than that before blood meals (1.009 ± 0.139) (P = 0.002). The transcriptional level of ACEs continued to increase in the ovaries of female mosquitoes after blood meals during the vitellogenesis phase, peaking at 48 h after blood meals (5.500 ± 0.734), which was 5.1 times higher than that before blood meals (1.072 ± 0.178) (P = 0.002). Small RNA interference targeting ACE resulted in a 57.2% reduction in ACE expression in female mosquitoes in the siACE group (0.430 ± 0.070) relative to the siNC group (1.002 ± 0.070) (P = 0.001), and a 41.1% reduction in male mosquitoes in the siACE group (0.588 ± 0.067) relative to the siNC group (1.008 ± 0.131) (P = 0.016). Knockdown of ACE expression resulted in a 48.0% decrease in the number of eggs laid by female mosquitoes in the siACE group [(94.000 ± 27.386) eggs] relative to the siNC group [(180.800 ± 27.386)] (P < 0.001), and a 45.0% decrease in the number of eggs laid by wild female mosquitoes mated with males in the siACE group [(104.500 ± 20.965) eggs] relative to the siNC group [(190.050 ± 10.698) eggs] (P < 0.001). CONCLUSIONS: Reduced ACE expression may inhibit the fecundity of male and female mosquitoes, and ACE may be as a potential target for mosquito vector population suppression.

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The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.

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BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

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With the discovery that 48% of cholera infections in rural Bangladesh villages could be prevented by simple filtration of unpurified waters and the detection of Vibrio cholerae aggregates in stools from cholera patients it was realized V. cholerae biofilms had a central function in cholera pathogenesis. We are currently in the seventh cholera pandemic, caused by O1 serotypes of the El Tor biotypes strains, which initiated in 1961. It is estimated that V. cholerae annually causes millions of infections and over 100,000 deaths. Given the continued emergence of cholera in areas that lack access to clean water, such as Haiti after the 2010 earthquake or the ongoing Yemen civil war, increasing our understanding of cholera disease remains a worldwide public health priority. The surveillance and treatment of cholera is also affected as the world is impacted by the COVID-19 pandemic, raising significant concerns in Africa. In addition to the importance of biofilm formation in its life cycle, V. cholerae has become a key model system for understanding bacterial signal transduction networks that regulate biofilm formation and discovering fundamental principles about bacterial surface attachment and biofilm maturation. This chapter will highlight recent insights into V. cholerae biofilms including their structure, ecological role in environmental survival and infection, regulatory systems that control them, and biomechanical insights into the nature of V. cholerae biofilms.

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Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

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BACKGROUND: Initial dose adjustment is recommended for patients with known UGT1A1∗28 homozygosity for both conventional irinotecan and liposomal irinotecan (nal-IRI). A recent population pharmacokinetic (PK) study showed that Asian patients had a lower prevalence of UGT1A1∗28 homozygosity but a significantly higher maximum blood concentration of SN-38 (SN-38 Cmax) and a higher incidence of grade ≥3 neutropenia after nal-IRI administration than Caucasian patients. The current study investigated the association of UGT1A1 polymorphisms, including the Asian prevalent UGT1A1∗6, PK and toxicities of nal-IRI-based therapy in the Asian population. PATIENTS AND METHODS: A total of 162 patients with nal-IRI-based therapy and available UGT1A1∗6 and UGT1A1∗28 genotyping were included, with 82 Asian patients from six previous phase I or II studies of nal-IRI (cohort 1) and another 80 patients with nal-IRI + 5-fluorouracil/leucovorin every 2 weeks as real-world practice in a single institute in Taiwan (cohort 2). RESULTS: The frequency of UGT1A1∗6 or UGT1A1∗28 homozygosity/compound heterozygosity was 9.3%, with UGT1A1∗6/∗6 in 2.5%, UGT1A1∗28/∗28 in 1.9% and UGT1A1∗6/∗28 in 4.9%. Among the 53 patients in cohort 1 with available PK data, all 7 patients with homozygosity/compound heterozygosity harbored UGT1A1∗6 and had a significantly higher level of median dose-normalized area under the concentration-time curve (AUC) and Cmax of SN-38 than those with single heterozygosity/wild type. Of the entire study population, the incidence of grade ≥3 neutropenia and diarrhea was significantly higher in patients with homozygosity/compound heterozygosity than in those with single heterozygosity/wild type, 73.3% versus 38.1% (P = 0.012, Fisher's exact test) and 33.3% versus 9.5% (P = 0.018, Fisher's exact test), respectively. CONCLUSION: The results suggest that the recommendation of a lower starting dose of nal-IRI for patients with UGT1A1∗28 homozygosity should be extended to include patients with UGT1A1∗6 homozygosity/compound heterozygosity.

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Active nematics are the nonequilibrium analogue of passive liquid crystals. They consist of anisotropic units that consume free energy to drive emergent behaviour. Like liquid crystal molecules in displays, ordering and dynamics in active nematics are sensitive to boundary conditions. However, unlike passive liquid crystals, active nematics have the potential to regulate their boundaries through self-generated stresses. Here, we show how a three-dimensional, living nematic can actively shape itself and its boundary to regulate its internal architecture through growth-induced stresses, using bacterial biofilms confined by a hydrogel as a model system. We show that biofilms exhibit a sharp transition in shape from domes to lenses upon changing environmental stiffness or cell-substrate friction, which is explained by a theoretical model that considers the competition between confinement and interfacial forces. The growth mode defines the progression of the boundary, which in turn determines the trajectories and spatial distribution of cell lineages. We further demonstrate that the evolving boundary and corresponding stress anisotropy define the orientational ordering of cells and the emergence of topological defects in the biofilm interior. Our findings may provide strategies for the development of programmed microbial consortia with emergent material properties.

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Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

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OBJECTIVE: To investigate the effect of hydronidone on CCl4-induced liver fibrosis in rats and explore the possible mechanism. METHODS: Sixty-six male SD rats were randomized into 5 groups, including a control group (n=10), a liver fibrosis model group (n=20), 2 hydronidone dose groups (100 and 250 mg/kg; n=12), and a pirfenidone (250 mg/kg) treatment group (n= 12). Rat models of liver fibrosis were established by subcutaneous injection of CCl4 in all but the control group. Hydronidone and pirfenidone were given daily at the indicated doses by intragastric administration for 6 weeks. After the treatments, serum samples were collected from the rats for detecting liver function parameters, and hydroxyproline content in the liver tissue was determined. Inflammation and fibrosis in the liver tissue were observed using HE staining and Sirius Red staining. In the cell experiment, human hepatic stellate cell line LX-2 was stimulated with TGF-ß1 and treated with hydronidone or pirfenidone, and the expression levels of α-SMA, collagen type I and phosphorylated Smad3, phosphorylated p38, phosphorylated ERK1/2 and phosphorylated Akt were detected with Western blotting. RESULTS: In the rat models of liver fibrosis, treatment with hydronidone obviously improved the liver functions, reduced the content of hydroxyproline in the liver tissue, and significantly alleviated liver fibrosis (P < 0.05). In LX-2 cells, hydronidone dose-dependently decreased the expression levels of α-SMA and collagen type I. In TGF- ß1-stimulated cells, the phosphorylation levels of Smad3, P38, ERK, and Akt increased progressively with the extension of the treatment time, but this effect was significantly attenuated by treatment with hydronidone (P < 0.05). CONCLUSION: Hydronidone can inhibit the phosphorylation of the proteins in the TGF-ß signaling pathway, thereby preventing TGF-ß1-mediated activation of hepatic stellate cells, which may be a possible mechanism by which hydronidone alleviates CCl4-induced liver fibrosis in rats.

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We present the magnetically shielded room (MSR) for the n2EDM experiment at the Paul Scherrer Institute, which features an interior cubic volume with each side of length 2.92 m, thus providing an accessible space of 25 m3. The MSR has 87 openings of diameter up to 220 mm for operating the experimental apparatus inside and an intermediate space between the layers for housing sensitive signal processing electronics. The characterization measurements show a remanent magnetic field in the central 1 m3 below 100 pT and a field below 600 pT in the entire inner volume, up to 4 cm to the walls. The quasi-static shielding factor at 0.01 Hz measured with a sinusoidal 2 µT peak-to-peak signal is about 100 000 in all three spatial directions and increases rapidly with frequency to reach 108 above 1 Hz.