[Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City].

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

[Comprehensive clinical evaluation of bedaquiline in the treatment of multidrug-resistant tuberculosis].

Objective: To assess the clinical value of bedaquiline in five dimensions: effectiveness, safety, economics, appropriateness, and social benefits, to provide a reference for medical and health insurance-related decisions. Methods: A total of 792 patients with multidrug-resistant tuberculosis who were hospitalized at Wuhan Pulmonary Hospital, Ganzhou Fifth People's Hospital and Jiangxi Chest Hospital between January 2018 and December 2020 were included in the study. Based on a retrospective survey of case data, and each evaluation dimension of bedaquiline was statistically analyzed by causal analysis or chi-square test, using linezolid as the reference drug. Results: In terms of effectiveness, bedaquiline significantly increased treatment success by 23.9% (95%CI:4.8%-43.0%) and shortened treatment duration by 64 days(95%CI:18-109 days). In terms of safety, the incidence of adverse reactions to bedaquiline and the discontinuation rate of adverse reactions (5.11%,4.55%) were significantly lower than those for linezolid (22.49%,15.24%), with statistically significant differences (χ2=27.50,P<0.001;χ2=14.09,P<0.001). In terms of economics, patients treated with bedaquiline had a significantly higher anti-TB drug course cost of RMB 48 209.4 Yuan(95%CI: 28 336.0-68 082.8 Yuan). In terms of appropriateness, the proportion of bedaquiline in patients' initial treatment regimens was lower than that of linezolid (16.7% vs. 86.5%) in the 2020 observation sample, with a statistically significant difference (χ2=238.96,P<0.001). In terms of social benefits, the infection control rate was significantly increased by 27.8% (95%CI:8.2%-47.5%) in patients using bedaquiline. Conclusions: Bedaquiline performed well in terms of efficacy, safety, and social benefits. However, it was less economical and the actual use rate of bedaquiline in clinical practice was lower than that of its counterpart drug, linezolid. Price reductions might be needed to increase the clinical use and performance of bedaquiline in the future.

[The 497th case: fever, anterior hypopituitarism, lymphadenopathy].

A 57-year-old woman was admitted to hospital with fever. She still had fever treated with multiple antibiotics, and no definite evidence for infection was found. Hypothermia and hypotension developed, and magnetic resonance imaging (MRI) examination showed enlarged anterior pituitary and multiple small nodular lesions with mild enhancement on the left side. Hormone replacement and anti-infection treatment were administrated, but fever did not improve. Remarkable lymphadenopathy was found in left supraclavicular area. The pathology of lymph node biopsy indicated peripheral T-cell lymphoma (not otherwise specified, NOS). Positron emission tomography-computed tomography (PET-CT) revealed hypermetabolism in multiple lymph nodes, infiltration of the liver and spleen. The final diagnosis were peripheral T-cell lymphoma with involvement of liver and spleen (stage Ⅳ) and anterior hypopituitarism. After chemotherapy, fever alleviated and the function of anterior pituitary recovered gradually.

[Effects of insulin glargine at different times on organ oxidative stress in burned rats with delayed resuscitation].

Objective: To examine the antioxidant effect of low dosage insulin glargine intervention at different time in rats with delayed resuscitation after burn, in order to acquire a better time of antioxidant intervention during delayed resuscitation following burn injury. Methods: With 10 rats in each group, 50 male SD rats were assigned to sham injury group, delayed resuscitation group, immediate post-burn insulin glargine treatment group (immediate treatment group), 2 hours post-burn insulin glargine treatment group(2 h treatment group), and 6 hours post-burn insulin treatment group(6 h treatment group) with random number table. Each treatment group received subcutaneous injections of insulin glargine (1.0 U·kg-1·d-1) immediately, two hours and six hours after the burn, while the delayed resuscitation group received the same amount of normal saline six hours after the burn. To imitate delayed fluid resuscitation, the delayed resuscitation group and each therapy group were intraperitoneally injected with normal saline (40 ml/kg) 6 hours after injury. No medicine and fluid resuscitation was administered to the sham injury group. Rats in the sham injury group had their abdominal aortic blood, hearts, and kidney tissues collected immediately after injury, while rats in the other groups had their blood and tissues collected 24 hours later. To analyze the timing of antioxidant intervention, the activities of CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), xanthine oxidase (XOD) and myeloperoxidase (MPO) in blood glucose and myocardial and renal tissues were measured by spectrophotometry. Results: Compared with the sham group, blood glucose levels in the delayed resuscitation group increased [(10.72±0.80) vs (6.57±0.82)mmol/L,P<0.001], while in the myocardium and kidney, the activities of CuZn-SOD, CAT, GSH-Px and T-AOC decreased (all P<0.05) and the activities of XOD and MPO increased (all P<0.05). Compared with the delayed resuscitation group, blood glucose decreased in the immediate, 2 h, and 6 h treatment groups (all P<0.05). In the immediate and 2 h treatment group, the activities of CuZn-SOD, CAT, GSH-Px and T-AOC in the myocardium and kidney increased(all P<0.05). In the 6 h treatment group, only the activities of GSH-Px in myocardium, CAT and GSH-Px in kidney increased (all P<0.05). Compared with the delayed resuscitation group, in the immediate treatment group, the activities of MPO and XOD in myocardial tissue and XOD in renal tissue decreased (all P<0.05). The activities of MPO and XOD in myocardial and renal tissues of the 2 h treatment group both decreased (all P<0.05). In the 6 h treatment group, the activities of MPO in myocardial tissue and XOD in renal tissue both decreased (all P<0.05). Compared with the immediate treatment group, the activity of GSH-Px in myocardial tissue increased (P<0.05), and the activities of CuZn-SOD, CAT, GSH-Px and T-AOC in renal tissue increased in the 2 h treatment group (all P<0.05). The activities of CuZn-SOD, CAT, GSH-Px and T-AOC in myocardium of 6 h treatment group decreased (all P<0.05). Compared with the immediate treatment group, the activities of XOD and MPO in myocardial tissue and XOD in renal tissue of the 2 h treatment group had no significant difference (all P>0.05), but the activity of MPO in renal tissue decreased (P<0.05). The activities of XOD and MPO in myocardial tissue of the 6 h treatment group increased (all P<0.05). Compared with the 2 h treatment group, the activities of CuZn-SOD, CAT and GSH-Px and T-AOC in myocardium and kidney tissues in the 6 h treatment group decreased (all P<0.05), while the activities of XOD and MPO in myocardium and kidney tissues increased [myocardium: (374±8) vs (290±19) U/g, (0.021 8±0.003 9) vs (0.010 7±0.002 4) U/g, kidney: (157±6) vs (128±9) U/g, (0.026 8±0.004 3) vs (0.013 4±0.003 1) U/g, all P<0.05]. Conclusions: The timing of the intervention is related to the antioxidant effect of insulin glargine during delayed burn resuscitation. The intervention immediately and 2 hours after burn could have a better antioxidant effect compared to the intervention at 6 hours after burn.

[Two-dimensional equivalent mechanical modeling and finite element analysis of normal female pelvic floor system].

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH2O (1 cmH2O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

[Analysis on the epidemic characteristics and genetic characteristics of varicella in Beijing from 2019 to 2021].

The reported incidence of varicella in Beijing from 2019 to 2021 were 63.8/100 000, 32.2/100 000 and 38.6/100 000, respectively. There were two VZV epidemics in Beijing each year, one peaked in May and the other in November. However, the first VZV epidemic almost disappeared in 2020. Among the cases involved in the varicella outbreaks in school, the proportion of the students with no history of vaccine immunization, 1 dose of immunization and 2 doses of immunization were 33.12%, 44.79% and 22.08%, respectively. The major body of VZV breakthrough cases was children aged 6-14 years (523/755, 69.27%). The proportion of moderate- or severe-rash were 55.32%, 39.06%, 29.96% in the three groups of cases with no immunization history, 1 dose of immunization and 2 doses of immunization, respectively (P<0.001). A total of 1 089 varicella samples were collected, and 837 (76.86%) were confirmed to be PCR-positive for VZV and were identified as VZV wild strains. 311 VZV strains were sequenced successfully, and 307 strains were clade 2 (98.72%), 1 clade 3 (0.32%) and 3 Clade 5 (0.96%). Compared with the representative strains, the nucleotide similarities of ORF22 fragments were between 99.4% and 100%, and amino acid similarities were between 99.4% and 100%.

[The diagnostic potential of Golgi protein 73 for cirrhosis in patients with chronic hepatitis C].

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.

Prognostic analysis of Behçet's disease with aortic regurgitation or involvement.

BACKGROUND: Aortic regurgitation is the most common cardiovascular damage in Chinese patients with Behçet's disease (BD) and is usually associated with aortic disease. These patients are easily misdiagnosed, and their prognosis is poor, even after surgical treatment. This study aimed to analyse potential factors that can improve the prognosis of BD patients with aortic regurgitation and/or aortic involvement. METHODS: Twenty-two patients with diagnosed or suspected BD as well as aortic regurgitation and/or aortic involvement in our hospital from 2012 through 2017 were collected in this study. Their clinical characteristics were listed, and the diagnosis of BD was evaluated by two different criteria sets. The influences of surgical treatment and immunosuppressive therapy (IST) on their prognosis were also explored. RESULTS: The diagnostic positive rate of the International Criteria for Behçet's Disease was higher than that of the International Study Group criteria (kappa value 0.31, p < 0.05), indicating that the diagnostic consistency between the criteria sets was poor. There was no significant difference in survival between patients who had undergone ≤ 1 operation and those with ≥ 2 operations. Aortic valve replacement alone or in combination with aortic root replacement had no significant effect on the incidence of reoperation or death, but IST did significantly reduce this incidence (p < 0.05). However, there was no significant difference in the occurrence of reoperation or death between preoperative and postoperative IST versus postoperative IST only. CONCLUSION: IST significantly improved the prognosis of BD patients with aortic regurgitation and/or aortic involvement.

New α-Emitting Isotope

A new α-emitting isotope ^{214}U, produced by the fusion-evaporation reaction ^{182}W(^{36}Ar,4n)^{214}U, was identified by employing the gas-filled recoil separator SHANS and the recoil-α correlation technique. More precise α-decay properties of even-even nuclei ^{216,218}U were also measured in the reactions of ^{40}Ar, ^{40}Ca beams with ^{180,182,184}W targets. By combining the experimental data, improved α-decay reduced widths δ^{2} for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N=126 are deduced. Their systematic trends are discussed in terms of the N_{p}N_{n} scheme in order to study the influence of proton-neutron interaction on α decay in this region of nuclei. It is strikingly found that the reduced widths of ^{214,216}U are significantly enhanced by a factor of two as compared with the N_{p}N_{n} systematics for the 84≤Z≤90 and N<126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the π1f_{7/2} and ν1f_{5/2} spin-orbit partner orbits, which is supported by the large-scale shell model calculation.

Effect of culture conditions on conidia production and enhancement of environmental stress resistance of Esteya vermicola in solid-state fermentation.

AIMS: Esteya vermicola is an endoparasitic fungus producing lunate conidia, which kill pine wood nematode (PWN), and PWN could cause pine wilt disease (PWD). The aims of this study were to increase production and confirm the resistance (temperature and UV irradiation) of lunate conidia, and further determine the effective concentrations of conidia infecting PWN. METHODS AND RESULTS: In this study, rice was used as a carrier to absorb conidial suspension to propagate conidia. The optimal conditions for lunate conidia production were 25°C temperature, 9 days of culture time, 2 : 1 rice/distilled water ratio and 10% inoculum size. The germination rate of E. vermicola cultured on potato dextrose agar was influenced by UV irradiation, similar to growth on rice. Esteya vermicola cultured on rice under heat stress might be more suitable for application in the field. The concentration (1 × 108 conidia per ml) to kill PWN had the highest infectivity among the four conidia concentrations tested after 3 days of inoculation. CONCLUSIONS: This study showed a rice substrate-supported high-quality conidia production and the optimal infectivity concentration of E. vermicola. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide the necessary process of an economical and efficient biological control strategy against PWD.

Lactobacillus plantarum inhibited the inflammatory response induced by enterotoxigenic Escherichia coli K88 via modulating MAPK and NF-κB signalling in intestinal porcine epithelial cells.

AIMS: To investigate the effects of Lactobacillus plantarum on inflammatory responses induced by ETEC K88 and explore the underlying molecular mechanisms. METHODS AND RESULTS: Intestinal porcine cells (IPEC-1) were incubated with 0 or 1 × 108  CFU per well L. plantarum for 4 h, and then these cells were challenged with 0 or 1 × 108  CFU per well ETEC K88 for 2 h. The results showed that pre-treatment of IPEC-1 cells with L. plantarum prevented the increases in the transcript abundance of interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) (P < 0·05) caused by ETEC K88. Additionally, L. plantarum inhibited the reduction in peroxisome proliferator-activated receptor-γ (PPAR-γ) expression caused by ETEC K88 (P < 0·05). Moreover, L. plantarum pre-treatment downregulated the phosphorylation levels of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases 1 and 2 (ERK1/2) and p38 and the nuclear concentration of nuclear factor kappa B p65 (NF-κB p65) (P < 0·05) compared with ETEC K88 group. Silencing experiment further supported that the protective effect of L. plantarum P might mediated by suppression of ETEC-provoked activation of MAPK and NF-κB signalling pathways. CONCLUSIONS: Lactobacillus plantarum inhibited the inflammatory response induced by ETEC K88 in IPEC-1 cells via modulating MAPK and NF-κB signalling. SIGNIFICANCE AND IMPACT OF THE STUDY: This study elucidated the underlying mechanism in which probiotics protect against intestinal inflammation caused by ETEC K88.

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial.

BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579.

CCL3/CCR1 mediates CD14+CD16- circulating monocyte recruitment in knee osteoarthritis progression.

OBJECTIVES: Monocyte-derived macrophages, as the predominant immune cell type that is increased in inflamed synovium, play a vital role during knee osteoarthritis (KOA) progression. However, the mechanisms underlying the recruitment of circulating monocytes to osteoarthritic knees remain uncertain. Based on previous data obtained from plasma, we investigated the contributions of CCL2, CCL3, CCL4 and their cognate receptors in circulating monocyte chemotaxis and KOA development. METHODS: Using flow cytometry staining, we characterized the expression patterns of the chemokine receptors in CD14+CD16- circulating monocytes from KOA patients and healthy volunteers. The expression of chemokines in synovial fluids, synovium and cartilage was investigated in KOA patients and in patients without KOA. The role of chemokines and their cognate receptors in the chemotaxis of CD14+CD16- circulating monocytes was assessed using chemokine neutralizing antibodies (NA) and receptor antagonists in vitro and in vivo. RESULTS: The majority of CD14+CD16- circulating monocytes were CCR1-and CCR2-positive. CCL2, CCL3 and CCL4 were elevated in synovial fluid of KOA patients compared with that of controls. The most likely source of these chemokines is inflamed synovium and cartilage in the osteoarthritic knee. The CCL3/CCR1 and CCL2/CCR2 axes showed substantial ability to recruit CD14+CD16- monocytes in transwell assays. Similar results were confirmed in a mouse model of collagenase-induced KOA (CIA) in which blocking either the CCL3/CCR1 axis or the CCL2/CCR2 axis reduced synovial hyperplasia and F4/80+ macrophage infiltration. CONCLUSIONS: Our findings suggested that, analogous to the CCL2/CCR2 axis, CCL3 produced in osteoarthritic knees can chemoattract circulating monocytes to the inflamed synovium through CCR1.

Occult Tumour Cells in Lymph Nodes from Gastric Cancer Patients: Should Isolated Tumour Cells Also Be Considered?

INTRODUCTION: Regional lymph node metastasis is an important prognostic factor for patients with gastric cancer. Occult tumour cells (OTCs), including either micrometastases (MMs) or isolated tumour cells (ITCs), may be a key factor in the development of cancer recurrence in pN0 patients. AIMS: We aimed to determine the frequency and prognostic significance for disease recurrence of OTCs. MATERIALS AND METHODS: This retrospective cohort study included all consecutive patients with pN0 gastric adenocarcinoma between January 2000 and December 2011 (n = 73). Immunohistochemistry using the pan-cytokeratin antibody AE1/AE3 was used to detect OTCs in 1257 isolated lymph nodes. RESULTS: OTCs were identified in 30 patients (41%), including 20 cases with MMs (27%) and 10 cases with ITCs (14%). Disease recurrence and cancer-related death were observed in 24 (33%) and 20 patients (27%), respectively, and both were significantly associated with the detection of OTCs. A significant difference was also observed for the mean survival time between patients with OTCs and those without OTCs [100 vs 158 months (p = 0.015)]. The presence of OTCs was statistically significantly associated with the Lauren classification, tumour size and lymphatic permeation. Multivariate analyses revealed that only age, T stage and the presence of ITCs in lymph nodes were independent factors for recurrence. The presence of ITCs increased the risk for recurrence by 11.1-fold. CONCLUSIONS: In a significant proportion of patients diagnosed as stage pN0, OTCs may be identified in lymph nodes if carefully searched for, which can negatively affect their prognosis. The presence of ITCs was found to be an independent factor for recurrence and after proper validation should be considered during lymph node assessment for prognosis definition.

Imaging Fluorescence of He_{2}

We show unequivocal evidence for formation of He_{2}^{*} excimers in liquid He II created by ionizing radiation produced through neutron capture. Laser beams induce fluorescence of the excimers. The fluorescence is recorded at a rate of 55.6 Hz by a camera. The location of the fluorescence is determined with an uncertainty of 5 µm. The technique provides an opportunity to record the flow of He_{2}^{*} excimers in a medium with very small viscosity and enables measurement of turbulence around macroscopic liter size objects or vortex matter in three dimensions.

DR10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.

PURPOSE: Both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) belong to the incretin family. This study aimed to investigate the pharmacokinetics and pharmacodynamics of DR10601, a fully recombinant hybrid peptide with dual GLP-1/GCG receptor agonistic activity. METHODS: The agonistic ability of DR10601 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary cells transfected with GLP-1R or GCGR in vitro. Following s.c. administration, the plasma pharmacokinetics of DR10601 were analysed in male Sprague-Dawley rats. The antiobesity effects and improved glycaemic control of DR10601 in vivo were evaluated by administering DR10601 to high-fat DIO mice and ICR mice as a single dose or repeated s.c. doses once every 4 days for 24 days. RESULTS: DR10601 exhibits dual agonistic activity on GLP-1 and glucagon receptors. The plasma half-life of DR10601 in Sprague-Dawley rats following s.c. administration was 51.9 ± 12.2 h. In an IPGTT, a single s.c. dose of DR10601 (30 nmol/kg) produced similar glycaemic control effects and a longer duration of action compared to dulaglutide (10 nmol/kg). Compared with that achieved with liraglutide (40 nmol/kg) s.c. administered daily, DR10601 administered s.c. once every 4 days at 90 nmol/kg exerted a nearly equivalent effect on food intake and significantly reduced the body weights of high-fat DIO mice at 24 days. CONCLUSIONS: Repeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.

Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene.

PURPOSE: T4-binding globulin (TBG) is the main thyroid hormone (TH) transporter present in human serum. Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG (SERPINA7) gene, which is located on the X chromosome. This study was performed to report and evaluate coding region mutations in TBG gene for partial thyroxine-binding globulin deficiency. METHODS: A pedigree spanning four generations is described in this study. The proband is a female with partial TBG deficiency. All members of this pedigree underwent thyroid function tests, while Sanger sequencing was used to identify the TBG gene mutations. Bioinformatics databases were used to evaluate the deleterious effects of the mutation(s). Two hundred and seven unrelated individuals were used to evaluate the thyroid function of individuals with different TBG mutations. A one-way ANOVA was used to analyze the impact of the TBG mutations on thyroid function. RESULTS: TBG gene sequencing results revealed that the proband had a novel mutation in codon 27 leading to alanine to valine substitution (p.A27V). This mutation was associated with lower serum T4 levels (p < 0.0001) when compared to the groups that did not carry the mutation. The previously reported p.L283F mutation was also found in the proband. The hemizygous p.L283F individuals presenting with lower T4 serum and TBG levels (p < 0.001) when compared to wildtype males and females. Both mutations were deleterious upon SIFT and PolyPhen-2 evaluation. CONCLUSION: Associated with partial thyroxine-binding globulin deficiency, this study reports a novel p.A27V mutation in the TBG gene.

[Clinical factors of pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer].

Objective: To explore the feasibility of clinical factors to predict the pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer. Methods: A retrospective analysis was performed on clinical factors of 162 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy in the General Hospital of People's Liberation Army from January 2011 to December 2018.According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) group and non-pathological complete response group (non-pCR group) to check the predictive clinical factors for pCR. Results: Twenty-eight cases achieved pCR after neoadjuvant chemoradiation (17.3%, 28/162). Univariate analysis showed that patients with higher differentiation (P=0.024), tumor occupation of the bowel lumen≤1/2 (P=0.006), earlier clinical T stage (P=0.013), earlier clinical N stage (P=0.009), the time interval between neoadjuvant chemoradiotherapy and surgery>49 days (P=0.006), and maximum tumor diameter≤5 cm (P=0.019) were more likely to obtain pCR, and the differences werestatistically significant. Multivariate analysis showed that tumor occupation of the bowel lumen≤1/2 (P=0.01), maximum tumor diameter≤5 cm (P=0.035), and the interval>49 days (P=0.009) were independent factors in predicting pCR after neoadjuvant therapy. Conclusion: Tumor occupation of the bowel lumen, maximum tumor diameter, and the time interval between neoadjuvant chemoradiotherapy and surgery can predict the pCR in rectal cancer.

[Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia].

Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of Ace2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.

[Establishment and preliminary application of serum Golgi protein 73 based noninvasive diagnostic model for compensated stage hepatitis B cirrhosis].

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.