Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.

BACKGROUND: The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. METHODS: We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. RESULTS: Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. CONCLUSION: Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.

Applications of Near-Infrared Fluorescence Imaging and Angiography of Inferior Vesical Artery in Laparoscopic Lateral Lymph Node Dissection: A Prospective Nonrandomized Controlled Study.

BACKGROUND: Near-infrared imaging with indocyanine green has been used to guide lateral lymph node dissection, yet its efficacy and benefits need further investigation. OBJECTIVE: To investigate the efficacy and feasibility of near-infrared fluorescence imaging and angiography of the inferior vesical artery in laparoscopic lateral lymph node dissection. DESIGN: A prospective nonrandomized controlled study. SETTINGS: Single-center study. PATIENTS: Patients with lower rectal cancer who underwent total mesorectal excision plus lateral lymph node dissection. MAIN OUTCOME MEASURES: A cohort of 108 patients was enrolled. After propensity score matching, 29 patients in the near-infrared group and 50 patients in the non-near-infrared group were matched. The total number of harvested lateral lymph nodes, positive lateral lymph nodes, inferior vesical artery preservation, and postoperative urinary function were compared. RESULTS: After propensity score matching, both groups had similar baseline characteristics. The total number of harvested lateral lymph nodes in the near-infrared group was significantly higher (12 vs 9, p = 0.013), but positive lateral lymph nodes were similar between the 2 groups (1 vs 1, p = 0.439). The inferior vesical artery preservation ratio was significantly increased with the aid of indocyanine green angiography (93.1% vs 56.0%, p < 0.001). The non-near-infrared group required more days for urinary catheter removal than the near-infrared group (5 vs 4, p = 0.046). Urinary recatheterization tended to occur more frequently in the non-near-infrared group, with a marginally significant trend (16% vs 0%, p = 0.059). The non-near-infrared group tended to have more cases with residual urine volume ≥50 mL than the near-infrared group (20.0% vs 3.4%, p = 0.087), especially in the bilateral dissection subgroup (41.2% vs 0%, p = 0.041). LIMITATIONS: Small sample size. CONCLUSIONS: Near-infrared imaging increased the number of harvested lateral lymph nodes, whereas real-time indocyanine green fluorescence angiography ensured the preservation of the inferior vesical artery and tended to improve postoperative urinary function.

Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

Risk factors and outcomes in patients who switched from peritoneal dialysis to physician-oriented or patient-oriented kidney replacement therapy.

BACKGROUND: We aimed to compare the cardiovascular events and mortality in patients who underwent either physician-oriented or patient-oriented kidney replacement therapy (KRT) conversion due to discontinuation of peritoneal dialysis (PD). METHODS: Patients with end-stage kidney disease who were receiving PD and required a switch to an alternative KRT were included. They were divided into physician-oriented group or patient-oriented group based on the decision-making process. Logistic regression analysis was used to explore the influencing factors related to KRT conversion in PD patients. The association of physician-oriented or patient-oriented KRT conversion with outcomes after the conversion was assessed by using Cox proportional hazards models. RESULTS: A total of 257 PD patients were included in the study. The median age at catheterization was 35 years. 69.6% of the participants were male. The median duration of PD was 20 months. 162 participants had patient-oriented KRT conversion, while 95 had physician-oriented KRT conversion. Younger patients, those with higher education levels, higher income, and no diabetes were more likely to have patient-oriented KRT conversion. Over a median follow-up of 39 months, 40 patients experienced cardiovascular events and 16 patients died. Physician-oriented KRT conversion increased nearly 3.8-fold and 4.0-fold risk of cardiovascular events and death, respectively. After adjusting for confounders, physician-oriented KRT conversion remained about a 3-fold risk of cardiovascular events. CONCLUSION: Compared to patient-oriented KRT conversion, PD patients who underwent physician-oriented conversion had higher risks of cardiovascular events and all-cause mortality. Factors included age at catheterization, education level, annual household income, and history of diabetes mellitus.

Characterization of VOC emissions and health risk assessment in the plastic manufacturing industry.

Volatile organic compounds (VOCs) significantly contribute to ozone pollution formation, and many VOCs are known to be harmful to human health. Plastic has become an indispensable material in various industries and daily use scenarios, yet the VOC emissions and associated health risks in the plastic manufacturing industry have received limited attention. In this study, we conducted sampling in three typical plastic manufacturing factories to analyze the emission characteristics of VOCs, ozone formation potential (OFP), and health risks for workers. Isopropanol was detected at relatively high concentrations in all three factories, with concentrations in organized emissions reaching 322.3 µg/m3, 344.8 µg/m3, and 22.6 µg/m3, respectively. Alkanes are the most emitted category of VOCs in plastic factories. However, alkenes and oxygenated volatile organic compounds (OVOCs) exhibit higher OFP. In organized emissions of different types of VOCs in the three factories, alkenes and OVOCs contributed 22.8%, 67%, and 37.8% to the OFP, respectively, highlighting the necessity of controlling them. The hazard index (HI) for all three factories was less than 1, indicating a low non-carcinogenic toxic risk; however, there is still a possibility of non-cancerous health risks in two of the factories, and a potential lifetime cancer risk in all of the three factories. For workers with job tenures exceeding 5 years, there may be potential health risks, hence wearing masks with protective capabilities is necessary. This study provides evidence for reducing VOC emissions and improving management measures to ensure the health protection of workers in the plastic manufacturing industry.

Cobaltosic oxide-polyethylene glycol-triphenylphosphine nanoparticles ameliorate the acute-to-chronic kidney disease transition by inducing BNIP3-mediated mitophagy.

Accumulating evidence highlights mitochondrial dysfunction as a crucial factor in the pathogenesis of acute kidney injury (AKI); thus, novel therapeutic strategies maintaining mitochondrial homeostasis are highly anticipated. Recent studies have shown that cobaltosic oxide has peroxidase-like catalytic activities, although its role and mechanism remain elusive in AKI. In the present study, we synthesized and identified cobaltosic oxide-polyethylene glycol-triphenylphosphine (COPT) nanoparticles by conjugating cobaltosic oxide with polyethylene glycol and triphenylphosphine, to improve its biocompatibility and mitochondria-targeting property. We found that COPT preferentially accumulated in the kidney proximal tubule cells, and significantly alleviated ischemic AKI in mouse models and gentamicin induced-AKI in the zebrafish model. COPT also inhibited the transition from AKI to chronic kidney disease (CKD), with few side effects. Further studies demonstrated that COPT localized in the mitochondria, and ameliorated hypoxia-reoxygenation-mediated mitochondrial damage through enhancing mitophagy in vitro and in vivo. Mechanistically, COPT dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 attenuated COPT-induced mitophagic flux and mitochondrial protection. Thus, our findings suggest that COPT nanoparticles ameliorate AKI and its progression to CKD through inducing BNIP3-mediated mitophagy, indicating that COPT may serve as a promising mitochondria-targeting therapeutic agent against AKI.

The Molecular Mechanism and Therapeutic Strategy of Cardiorenal Syndrome Type 3.

Cardiorenal syndrome type 3 (CRS3) is defined as acute kidney injury (AKI)-induced acute cardiac dysfunction, characterized by high morbidity and mortality. CRS3 often occurs in elderly patients with AKI who need intensive care. Approximately 70% of AKI patients develop into CRS3. CRS3 may also progress towards chronic kidney disease (CKD) and chronic cardiovascular disease (CVD). However, there is currently no effective treatment. Although the major intermediate factors that can mediate cardiac dysfunction remain elusive, recent studies have summarized the AKI biomarkers, identified direct mechanisms, including mitochondrial dysfunction, inflammation, oxidative stress, apoptosis and activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS), inflammasome, as well as indirect mechanisms such as fluid overload, electrolyte imbalances, acidemia and uremic toxins, which are involved in the pathophysiological changes of CRS3. This study reviews the main pathological characteristics, underlying molecular mechanisms, and potential therapeutic strategies of CRS3. Mitochondrial dysfunction and inflammatory factors have been identified as the key initiators and abnormal links between the impaired heart and kidney, which contribute to the formation of a vicious circle, ultimately accelerating the progression of CRS3. Therefore, targeting mitochondrial dysfunction, antioxidants, Klotho, melatonin, gene therapy, stem cells, exosomes, nanodrugs, intestinal microbiota and Traditional Chinese Medicine may serve as promising therapeutic approaches against CRS3.

Ruthenium and Iron Co-doped Molybdenum Carbide as a Stable Hydrogen Evolution Electrocatalyst in Harsh Electrolyte.

Electrocatalytic water splitting is one of the most commercially valuable pathways of hydrogen production especially combined with renewable electricity; however, efficient and durable electrocatalysts are urgently needed to reduce electric energy consumption. Here, we reported a Ru and Fe co-doped Mo2 C on nitrogen doped carbon via a controllable two-step method, which can be used for efficient and enduring hydrogen evolution reaction. At 10, 100 and 200 mA cm-2 in acidic electrolyte, the resultant Ru-Fe/Mo2 C@NC delivered low overpotentials of 31, 78 and 103 mV, respectively, which are comparable to that of the commercial Pt/C (20 wt %). At an applied current density of 100 mA cm-2 , stable hydrogen production was conducted for 120 h without obvious degradation. In alkaline media, Ru-Fe/Mo2 C@NC can also deliver a current density of 100 mA cm-2 for more than 100 h. Furthermore, the Ru-Fe/Mo2 C@NC electrocatalyst was used as cathode in an anion exchange membrane water electrolyzer under industrial environments for robust hydrogen production. The characterization and electrochemical results prove the synergism effects between Ru, Fe dopants and Mo2 C for promoting hydrogen evolution activity. This work would pave a new avenue to fabricate low-cost, high-performance hydrogen evolution electrocatalysts for industrial water electrolyzers.

The tumor characteristics, treatment strategy, and prognosis in colorectal cancer patients with synchronous liver metastasis in China and the USA.

PURPOSE: This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA. METHODS: The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period. RESULTS: Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment (P = 0.237). CONCLUSIONS: Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade.

Potential influence of fine aerosol chemistry on the optical properties in a semi-arid region.

The current understanding regarding the potential influence of aerosol chemistry on the optical properties does not satisfy accurate evaluation of aerosol radiative effects and precise determination of aerosol sources. We conducted a comprehensive study of the potential influence of aerosol chemistry on the optical properties in a semi-arid region based on various observations. Organic matter was the main contributor to the scattering coefficients followed by secondary inorganic aerosols in all seasons. We further related aerosol absorption to elemental carbon, organic matter, and mineral dust. Results showed that organic matter and mineral dust contributed to >40% of the aerosol absorption in the ultraviolet wavelengths. Therefore, it is necessary to consider the absorption of organic matter and mineral dust in addition to that of elemental carbon. We further investigated the potential influence of chemical composition, especially of organic matter and mineral dust on the optical parameters. Mineral dust contributed to higher absorption efficiency and lower scattering efficiency in winter. The absorption Ångström exponent (AAE) was mostly sensitive to organic matter and mineral dust in winter and spring, respectively; it was relatively high (i.e., 1.68) in winter and moderate (i.e., 1.42) in spring. Unlike in the other seasons, mineral dust contributed to higher mass absorption efficiency in winter. This work reveals the complexity of the relationship between aerosol chemistry and optical properties, and especially the influence of organic matter and mineral dust on aerosol absorption. The results are highly important regarding both regional air pollution and climate.

Lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation: can it be a powerful supplement tool for predicting the status of lateral pelvic lymph nodes in advanced lower rectal cancer.

BACKGROUND: An innovative instrument for laparoscopy using indocyanine green (ICG) allows easy detection of sentinel lymph nodes (SLNs) in lateral pelvic lymph nodes (LPLNs). Here, we investigated the safety and efficacy of lateral pelvic SLN biopsy (SLNB) using ICG fluorescence navigation in advanced lower rectal cancer and evaluated the sensitivity and specificity of this technique to predict the status of LPLN. METHODS: From April 1, 2017 to December 1, 2020, we conducted lateral pelvic SLNB using ICG fluorescence navigation during laparoscopic total mesorectal excision and lateral pelvic lymph node dissection (LLND) in 23 patients with advanced low rectal cancer who presented with LPLN but without LPLN enlargement. Data regarding clinical characteristics, surgical and pathological outcomes, lymph node findings, and postoperative complications were collected and analyzed. RESULTS: We successfully performed the surgery using fluorescence navigation. One patient underwent bilateral LLND and 22 patients underwent unilateral LLND. The lateral pelvic SLN were clearly fluorescent before dissection in 21 patients. Lateral pelvic SLN metastasis was diagnosed in 3 patients and negative in 18 patients by frozen pathological examination. Among the 21 patients in whom lateral pelvic SLN was detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLN. CONCLUSION: This study indicated that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure for advanced lower rectal cancer with good accuracy, and no false-negative cases were found. No metastasis in SLNB seemed to reflect all negative LPLN metastases, and this technique can replace preventive LLND for advanced lower rectal cancer.

Comparative short-term and survival outcomes of three specimen extraction techniques in laparoscopic low rectal cancer surgery: does it affect ileostomy closure?

INTRODUCTION: This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. MATERIALS AND METHODS: A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. RESULTS: In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P < 0.001), more intraoperative bleeding (P < 0.001), longer length of abdominal incision (P<0.001), longer time to first flatus (P < 0.001), longer time to first defecation (P < 0.001), longer time to first eat (P < 0.001), and longer postoperative hospital stays (P = 0.005) than the EXSI and EVER groups. The primary postoperative complication rate in the EXAI and EVER group was significantly higher than in the EXSI group (P = 0.005). In loop ileostomy closure, EXAI group had significantly longer operative time (P = 0.001), more bleeding volume, and longer postoperative hospital stays (P < 0.001) than the EXSI and EVER groups. For survival outcomes, the 3-year local recurrence-free survival (LRFS) is 92.6% for all patients. The 3-year LRFS for patients in EXAI, EXSI, and EVER were 90.1%, 95.4%, and 92.7%, with P = 0.476. CONCLUSIONS: Our single-center results found that in LAR-PLI surgery for low rectal cancer, the short-term outcomes of specimen extraction through the stoma incision or anus were better than that through the auxiliary incision, but the 3-year LRFS was no statistically different.

Laparoscopic radical transverse colectomy with transrectal specimen extraction: A novel natural orifice specimen extraction procedure: A case report.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Chemical characteristics and regional transport of submicron particulate matter at a suburban site near Lanzhou, China.

Lanzhou, which is a valley city on the Loess Plateau, frequently suffered from aerosol pollution in recent years, especially in winter. However, the lack of understanding of factors governing aerosol pollution limits the implementation of effective emission policies in and around Lanzhou. To help solve this problem, an intensive field campaign was conducted at the SACOL site, which is a suburban site near Lanzhou, in winter 2018. The chemical characteristics and sources of submicron particulate matter (PM1) were investigated, and the influence of the topography around Lanzhou on aerosol pollution was examined. In the present study, the average PM1 mass concentration reached 25.6 ± 12.8 µg m-3, with 41.0% organics, 16.1% sulfate, 19.7% nitrate, 10.7% ammonium, 3.1% chloride, and 9.4% black carbon (BC). Three organic aerosol (OA) factors were identified with the positive matrix factorization (PMF) algorithm, including a biomass burning OA (BBOA, 13.6%), a coal combustion OA (CCOA, 34.2%), and an oxygenated OA (OOA, 52.2%). The significant relationships between organics, BC, and chloride and wind pattern suggested that the SACOL site was strongly influenced by regionally transported aerosols. Further analysis suggested that these aerosol regional transport events were caused by topography. Due to the limitation of the valley, aerosols accumulated in the valley. These accumulated aerosols were then transported to the SACOL site along the valley by prevailing winds. Our study highlights enhanced aerosol regional transport in valleys, which provides a new perspective for future studies on aerosol pollution in basins and valleys.

Changes in physical and chemical properties of urban atmospheric aerosols and ozone during the COVID-19 lockdown in a semi-arid region.

The synergistic response of urban atmospheric aerosols and ozone (O3) to reduction of anthropogenic emissions is complicated and still needs further study. Thus, the changes in physical and chemical properties of urban atmospheric aerosols and O3 during the Coronavirus Disease 2019 (COVID-19) lockdown were investigated at three urban sites and one rural site in Lanzhou with semi-arid climate. Fine particulate matter (PM2.5) decreased at four sites by âˆ¼ 20% while O3 increased by >100% at two urban sites during the COVID-19 lockdown. Both primary emissions and secondary formation of PM2.5 decreased during the lockdown. Significant increase in both sulfur and nitrogen oxidation ratios was found in the afternoon, which accounted for 48.7% of the total sulfate and 40.4% of the total nitrate, respectively. The positive matrix factorization source apportionment revealed increased contribution of secondary formation and decreased contribution of vehicle emissions. Aerosol scattering and absorption decreased by 33.6% and 45.3%, resulting in an increase in visibility by 30% and single scattering albedo (SSA) at 520 nm slightly increased by 0.02. The enhanced O3 production was explained by increased volatile organic compounds to nitrogen oxides ratio, decreased aerosol, as well as increased SSA. The primary emissions of secondary aerosol precursors significantly decreased while Ox (i.e., NO2 and O3) exhibited little change. Consequently, Ox to CO ratio, PM2.5 to elemental carbon (EC) ratio, secondary inorganic aerosols to EC ratio, and secondary organic carbon to EC ratio increased, confirming enhanced secondary aerosol production efficiency during the lockdown. Positive feedback among O3 concentration, secondary aerosol formation, and SSA was revealed to further promote O3 production and secondary aerosol formation. These results provide scientific guidance for collaborative management of O3 and particulate matter pollution for cities with semi-arid climate.

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.

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.

B7-H3 immune checkpoint expression is a poor prognostic factor in colorectal carcinoma.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.

Safety and survival outcomes of transanal natural orifice specimen extraction using prolapsing technique for patients with middle- to low-rectal cancer.

OBJECTIVE: The transanal approach to specimen collection, combined with the prolapsing technique, is a well-established and minimally invasive surgery for treating rectal cancer. However, reports on outcomes for this approach are sparse. We compared short- and long-term outcomes of conventional laparoscopic surgery (CLS) vs. transanal natural orifice specimen extraction (NOSE) using the prolapsing technique for patients with middle- to low-rectal cancer. METHODS: From January 2013 to December 2017, we enrolled consecutive patients with middle- to low-rectal cancer undergoing laparoscopic anterior resection. Totally, 50 patients who underwent transanal NOSE using the prolapsing technique were matched with 50 patients who received CLS. Clinical parameters and survival outcomes between the two groups were compared. RESULTS: Estimated blood loss (29.70±29.28 vs. 52.80±45.09 mL, P=0.003), time to first flatus (2.50±0.79 vs. 2.86±0.76, P=0.022), time to liquid diet (3.62±0.64 vs. 4.20±0.76 d, P<0.001), and the need for analgesics (22%vs. 48%, P=0.006) were significantly lower for the NOSE group compared to the CLS group. The incidences of overall complications and fecal incontinence were comparable in both groups. After a median follow-up of 44.52 months, the overall local recurrence rate (6% vs. 5%, P=0.670), 3-year disease-free survival (86.7% vs. 88.0%, P=0.945) and 3-year overall survival (95.6% vs. 96.0%, P=0.708), were not significantly different. CONCLUSIONS: For total laparoscopic rectal resection, transanal NOSE using the prolapsing technique is effective and safe, and associated with less trauma and pain, a faster recovery, and similar survival outcomes compared to CLS.