[Endoscopic ultrasonography features of benign esophageal stenosis in children]. / å„¿ç«¥é£Ÿç®¡è‰¯æ€§ç‹­çª„çš„è¶ å£°å† é•œç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children. METHODS: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children. RESULTS: A total of 42 children with benign esophageal stenosis were included. Among these children, 19 (45%) had anastomotic stenosis after surgery for esophageal atresia, with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS, and had 0-12 sessions of endoscopic treatment (average 2.1 sessions); 5 children (12%) had corrosive esophageal stenosis and 1 child (2%) had physical esophageal stenosis, with unclear stratification of the esophageal walls on EUS, and they had 2-9 sessions of endoscopic treatment (average 5.3 sessions); 1 child (2%) had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology; 16 children (38%) had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS, among whom 6 received endoscopic treatment. During follow-up, 95% (40/42) of the children had significant alleviation of the symptoms such as vomiting and dysphagia. CONCLUSIONS: For benign esophageal stenosis in children, EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions, possible etiologies, and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications, thereby helping to optimize the treatment regimen.

Cluster-Centered Excited-State-Induced Bright Low-Energy Emissive Hybrid Copper Iodide Constructing Stable White LEDs.

Herein, we successfully synthesized a stable copper iodide hybrid with a 0D structure, (C20H20P)2Cu2I4, in which [Cu2I4]2- dimers with a short Cu-Cu distance (2.64 Å) are isolated and surrounded by [C20H20P]+ organic cations. Bright broadband yellow emission (576 nm) featuring a wide excitation range from 240 to 450 nm was achieved, along with a large Stokes shift (211 nm), long-lived lifetime (1.99 µs), and zero self-absorption. The results combined with crystal structure, spectroscopy analysis, and theoretical studies reveal that a cluster-centered excited state is responsible for this yellow emission. Importantly, the structure of (C20H20P)2Cu2I4 remains unchanged even after soaking in water for 30 days or heating at 80 °C for 240 h due to the intermolecular interaction. Furthermore, a stable white LED showing a naturally correlated color temperature (CCT) of 6573 K and CIE color coordinate of (0.31, 0.37) was also demonstrated. This work demonstrates efficient light emitters based on lead-free and stable metal halides for lighting, providing an important reference for the development of stable, high-performance metal halide phosphors.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

IgG4-related kidney disease complicated with retroperitoneal fibrosis: A case report.

BACKGROUND: IgG4-related disease (IgG4-RD) is a chronic fibrotic disease mediated by immunity recognized by clinicians in recent years. When the kidney is involved, it is called IgG4-related kidney disease (IgG4-RKD). IgG4-related tubulointerstitial nephritis (IgG4-TIN) is a representative manifestation of IgG4-RKD. IgG4-TIN can cause obstructive nephropathy complicated by retroperitoneal fibrosis (RPF). Cases of IgG4-TIN complicated with RPF are rare. Glucocorticoids are the first-line therapeutic medication for IgG4-RD and can significantly improve renal function. CASE SUMMARY: Herein, we report the case of a 56-year-old man with IgG4-RKD complicated with RPF. The patient presented to the hospital with complaints of elevated serum creatinine (Cr), nausea, and vomiting. During hospitalization, Cr was 1448.6 µmol/L, and serum IgG4 was increased. A total abdominal computed tomography (CT) scan and enhanced CT scan obviously indicated RPF. Although this patient had a long course and renal insufficiency, we performed a kidney biopsy. Renal biopsy showed that the renal tubulointerstitium had focal plasma cell infiltration and increased lymphocyte infiltration accompanied by fibrosis. After combining the biopsy results with immunohistochemistry, it was found that the absolute number of positive IgG4+ cells per high power field exceeded 10, and the ratio of IgG4/IgG was over 40%. Finally, the patient was diagnosed with IgG4-TIN complicated with RPF and given glucocorticoids as long-term maintenance therapy, helping him keep out of dialysis. After a follow-up of 19 mo, the patient had recovered well. Previous literature on IgG4-RKD and RPF was retrieved from PubMed to characterize the clinical and pathological features and to identify the diagnosis and treatment of IgG4-RKD. CONCLUSION: Our case report demonstrates the clinical characteristics of IgG4-RKD complicated with RPF. Serum IgG4 is a favorable indicator for screening. Performing renal biopsy actively plays a vital role in diagnosis and treatment, even if the patient has a long course and manifests with renal insufficiency. It is remarkable to treat IgG4-RKD with glucocorticoids. Hence, early diagnosis and targeted therapy are essential for reversing renal function and improving extrarenal manifestations in patients with IgG4-RKD.

CDK5RAP3, an essential regulator of checkpoint, interacts with RPL26 and maintains the stability of cell growth.

PURPOSE AND MATERIALS: CDK5RAP3 (CDK5 regulatory subunit associated protein 3) was originally identified as a binding protein of CDK5. It is a crucial gene controlling biological functions, such as cell proliferation, apoptosis, invasion, and metastasis. Although previous studies have also shown that CDK5RAP3 is involved in a variety of signalling pathways, however, the mechanism of CDK5RAP3 remains largely undefined. This study utilized MEFs from conditional knockout mice to inhibit CDK5RAP3 and knockdown CDK5RAP3 in MCF7 to explore the role of CDK5RAP3 in cell growth, mitosis, and cell death. RESULTS: CDK5RAP3 was found to be widely distributed throughout the centrosome, spindle, and endoplasmic reticulum, indicating that it is involved in regulating a variety of cellular activities. CDK5RAP3 deficiency resulted in instability of cell growth. CDK5RAP3 deficiency partly blocks the cell cycle in G2 /M by downregulating CDK1 (Cyclin-dependent kinase 1) and CCNB1 (Cyclin B1) expression levels. The cell proliferation rate was decreased, thereby slowing down the cell growth rate. Furthermore, the results showed that CDK5RAP3 interacts with RPL26 (ribosome protein L26) to regulate the mTOR pathway. CDK5RAP3 and RPL26 deficiency inhibited mTOR/p-mTOR protein and induce autophagy, resulting in an upregulation of the percentage of apoptosis, and the upregulated percentage of apoptosis also slowed cell growth. CONCLUSIONS: Our experiments show that CDK5RAP3 interacts with RPL26 and maintains the stability of cell growth. It shows that CDK5RAP3 plays an important role in cell growth and can be used as the target of gene medicine.

High Human Papillomavirus Vaccine Acceptability and Cost-Effectiveness of the Chinese 2-Valent Vaccine Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Despite the insupportable burden caused by the human papillomavirus (HPV) and high vaccine acceptability, vaccination programs are not currently available for men who have sex with men (MSM). We aimed to assess HPV infection by examining the willingness for vaccination among MSM and cost-effectiveness of the Chinese 2-valent HPV vaccine. Methods: We recruited MSM in Shenyang, China between July and December 2020 to conduct anal HPV testing and an online survey regarding HPV-related knowledge and vaccine acceptability. We performed a cost-effectiveness analysis to evaluate the incremental cost-effectiveness ratios (ICERs) of the Chinese 2-valent HPV vaccine. Results: A total of 234 participants completed the online survey; of those, 203 were successfully tested for HPV. The median age was 30 years [interquartile range (IQR): 23-38 years]. Most participants had at least undergraduate education (136/234, 58.1%). The acceptability rate for the free HPV vaccine was 57.7% (135/234). The prevalence of HPV types 16 and 18 was 14.9% (18/121) and 26.8% (22/82) in the willing and unwilling to vaccinate groups, respectively (P > 0.05). The prevalence of high-risk HPV among participants aged <30 and ≥50 years was 48.6 and 38.9%, respectively. Using the Chinese per capita gross domestic product (GDP) as a threshold, the Chinese 2-valent HPV vaccine would be a "very cost-effective" strategy, with an ICER value of USD 4,411. This evidence showed that the Chinese 2-valent HPV vaccine was more cost-effective than other imported vaccines. Conclusions: Targeted strategies should be utilized in MSM with different rates of vaccine acceptability. A pilot HPV vaccination program based on the Chinese 2-valent HPV vaccine for MSM is urgently warranted to reduce the burden of HPV and anal cancer.

Prevention and control of HIV/AIDS in China: lessons from the past three decades.

ABSTRACT: In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Assisted Partner Notification and Uptake of HIV Testing among Men Who Have Sex with Men: A Randomized Controlled Trial in China.

BACKGROUND: Assisted partner notification (PN) is an effective approach for increasing HIV testing among heterosexual partners. There is sparse evidence on its effect among sexual partners of men who have sex with men (MSM). METHODS: A randomized controlled trial was conducted to compare the effect of assisted PN and passive PN interventions on uptake of HIV testing among male and female sexual partners of newly HIV-diagnosed MSM. In the passive PN group, participants were encouraged to disclose their HIV status and refer and persuade sexual partners to access HIV testing services (HTS). In the assisted PN group, participants were further provided with HIV self-testing kits for sexual partners to take a test at home or allow a community health worker from MSM-serving community-based organization (CBO) to anonymously refer and persuade their sexual partners to access HTS. The primary outcome was the proportion of index cases who had any sexual partner accessing HTS within four months after randomization. This trial is registered with chictr.org.cn, ChiCTR1800017813. FINDINGS: Between August 2017 and January 2019, 187 MSM newly diagnosed with HIV in a large city Shenyang in northern China were enrolled in the study and randomly assigned to either passive PN (n=90) or assisted PN (n=97) study groups. The proportion of index cases who disclosed their HIV status to any sexual partners within three months of randomization was similar between passive PN (57%, 95% confidence interval [CI]: 46-67%) and assisted PN groups (58%, 95% CI: 48-68%). During four months of follow-up, the number of sexual partners named, referred to HTS, tested and testing positive per index case was 3•2, 0•7, 0•2 and 0•03 in the passive PN group, and 4•0, 1•0, 0•5 and 0•10 in the assisted PN group. Thirty-five percent of index cases in the assisted PN group had any sexual partners accessing HIV testing compared to 17% in the passive PN group (P = 0•004); 49% sexual partners who were disclosed by index cases in the assisted PN group had access HTS compared to 28% in the passive PN group (P = 0•007). INTERPRETATION: The assisted PN strategy incorporating HIV self-testing and CBO outreach can increase uptake of HIV testing among sexual partners of MSM who were recently diagnosed with HIV. FUNDING: National Science and Technology Major Project of China, National Natural Science Foundation of China, and Project for Overseas Visiting Research of Liaoning Province.

Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

Preference for daily versus on-demand pre-exposure prophylaxis for HIV and correlates among men who have sex with men: the China Real-world Oral PrEP Demonstration study.

INTRODUCTION: This study explores the preference for daily versus on-demand pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in developing countries when both regimens are available. METHODS: From 11 December 2018 to 19 October 2019, we recruited MSM for an open-label real-world PrEP demonstration study in four major cities in China. Subjects selected their preferred PrEP (oral tenofovir/emtricitabine) regimen (daily vs. on-demand) at recruitment and underwent on-site screening before initiation of PrEP. We used logistic regression to assess preference for daily PrEP and correlates. RESULTS: Of 1933 recruited MSM, the median age was 29 years, 7.6% was currently married to or living with a female; the median number of male sexual partners was four and 6.1% had used post-exposure prophylaxis (PEP) in the previous six months. HIV infection risk was subjectively determined as very high (>75%) in 7.0% of subjects, high (50% to 75%) in 13.3%, moderate (25% to 49%) in 31.5% and low or none (0% to 24%) in 48.1%. On average, participants preferred on-demand PrEP over daily PrEP (1104 (57.1%) versus 829 (42.9%)) at recruitment. In multivariable analysis, currently being married to or living with a female was associated with 14.6 percentage points lower preference for daily PrEP (marginal effect = -0.146 [95% CI: -0.230, -0.062], p = 0.001); whereas the number of male sexual partners (marginal effect = 0.003 [95% CI: 0.000, 0.005], p = 0.034) and a subjective assessment of being very high risk of HIV infection (vs. low and no risk, marginal effect size = 0.105 [95% CI: 0.012, 0.198], p = 0.027) were associated with increased preference for daily versus on-demand PrEP. Among the 1933 potential participants, 721 (37.3%) did not attend the subsequent on-site screening. Lower-income, lower education level, lower subjective expected risk of HIV infection risk and younger age positively correlated with the absence of on-site screening. CONCLUSIONS: MSM in China prefer both daily and on-demand PrEP when both regimens are provided free. Social structural factors and subjective risk of HIV infection have significant impacts on PrEP preference and use. The upcoming national PrEP guideline should consider incorporating both regimens and the correlates to help implement PrEP in China.

Disparity of human immunodeficiency virus incidence and drug resistance in college student, non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China.

BACKGROUND: Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM. METHODS: We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance. RESULTS: Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8). CONCLUSIONS: College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

A Chromatographic Method for Separation of Tungsten (W) from Silicate Samples for High-Precision Isotope Analysis Using Negative Thermal Ionization Mass Spectrometry.

A new chromatographic method for isolation of W from large masses of silicate samples (>1 g) for ultrahigh precision isotopic analysis was developed. The purification of W was achieved through two stages of rapid chromatographic separations. In the first step, Ti, Zr, Hf, and W were separated collectively from the sample matrix through an AG1-X8 (100-200 mesh) column with a 10 mL resin volume. Subsequently, W was rapidly separated from Ti and Zr-Hf with high purity by a two-step extraction chromatographic method using 0.6 and 0.3 mL TODGA resin columns (50-100 µm particle size), respectively. The total yield of W, including the anion exchange and the TODGA chromatographic separation steps, is greater than 90%. The procedure was employed to isolate W from rock reference materials GSJ JB-3 and USGS BHVO-2; the separated W was analyzed by TRITON Plus TIMS, yielding a 182W/184W of 0.864898 ± 0.000005 (n = 8, 2 SD) for JB-3 and 182W/184W of 0.864896 ± 0.000006 (n = 5, 2 SD) for BHVO-2, which are in agreement with previously reported values within analytical errors.

Theoretical prediction of the impact sensitivities of energetic C-nitro compounds.

In order to design high-energetic and insensitive explosives, the frontier orbital energy gaps, surface electrostatic potentials, nitro group charges, bond dissociation energies (BDEs) of the C-NO2 trigger bonds, and intermolecular interactions obtained by the M06-2X/6-311++G(2d,p) method were quantitatively correlated with the experimental drop hammer potential energies of 10 typical C-nitro explosives. The changes of several information-theoretic quantities (ITQs) in the density functional reactivity theory were discussed upon the formation of complexes. The BDEs in the explosives with six-membered ring are larger than those with five-membered ring. The frontier orbital energy gaps of the compounds with benzene ring are larger than those with N-heterocycle. The models involving the intermolecular interaction energies and the energy gaps could be used to predict the impact sensitivity of the C-nitro explosives, while those involving ΔSS, ΔIF, and ΔSGBP are invalid. With the more and more ITQs, the further studies are needed to seek for a good correlation between impact sensitivity measurements and ITQs for the energetic C-nitro compounds. The origin of sensitivity was revealed by the reduced density gradient method.

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.

A retrospective pilot study to examine the feasibility of real-time navigation for laparoscopic liver resections in intrahepatic cholangiocarcinoma using fusion indocyanine green fluorescence imaging.

BACKGROUND AND OBJECTIVES: Recently, PINPOINT, a novel laparoscopic fusion indocyanine green fluorescence imaging (IGFI) system has become available for laparoscopic liver resection. This study aims to characterize fluorescence patterns of intrahepatic cholangiocarcinoma (ICC) using the negative counterstaining method in laparoscopic anatomical hepatectomies of ICC. METHODS: Eleven consecutive patients, diagnosed with intrahepatic cholangiocarcinoma and underwent laparoscopic liver resection between April 2017 and December 2018, were retrospectively reviewed. A laparoscopic IGFI navigation system was used to characterize fluorescence patterns of ICC with intraoperative liver segment demarcation by means of negative counterstaining. RESULTS: Fusion IGFI of ICC was successfully obtained from all 11 patients from the surgical specimens. The fluorescence patterns of ICC can be categorized into rim-type fluorescence and segmental fluorescence, depending on tumor growth. In eight patients, indocyanine green fluorescence imaging was used to identify the hepatic lobes or segments by negative counterstaining. In six cases, a valid and persistent demarcation was achieved intraoperatively. CONCLUSION: Laparoscopic IGFI system could identify different types of ICC lesions and may facilitate real-time navigation for laparoscopic anatomic liver resection of ICC.

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.

BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.