Prognostic value of preoperative white blood cell to hemoglobin ratio and fibrinogen to albumin ratio in patients with colorectal cancer.

The prognostic value of preoperative white blood cell to hemoglobin ratio (WHR) and fibrinogen to albumin ratio (FAR) in colorectal cancer (CRC) is unknown. The purpose of this study was to analyze the correlation between preoperative WHR and FAR and the prognosis of CRC patients. The retrospective study analyzed the medical records of 207 patients with colorectal cancer who were admitted to Linyi People's Hospital between June 1, 2017 and June 1, 2021. The receiver operator curve was used to determine the cutoff value of 4.604 for WHR and 0.086 for FAR, and the patients were divided into high and low groups for comparative analysis of clinical data. Cox proportional hazards regression models were used to assess independent risk factors for disease-free survival (DFS) and overall survival (OS) in univariate and multifactorial analyses. Kaplan-Meier methods were used for survival analysis and logrank tests were used to assess survival differences. Multifactorial Cox analysis showed that tumor pathological stage (HR = 6.224, 95% CI:3.063-12.647, P < .001), and WHR (HR = 3.681, 95% CI:1.768-7.401, P < .001) were the independent risk factors for DFS in CRC patients. Tumor pathological stage (HR = 4.080, 95% CI:1.992-8.360, P < .001), and WHR (HR = 3.397, 95% CI:1.662-6.940, P = .001) were independent risk factors for OS. High levels of WHR and high levels of FAR were associated with lower DFS (P < .001) and OS (P < .001).CRC patients with both higher WHR and FAR had significantly lower DFS (P < .001) and OS (P < .001). DFS and OS may be shorter in CRC patients with high WHR and high FAR, perhaps associated with poor prognosis in CRC patients, and WHR and FAR may be potential CRC prognostic markers.

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2.

Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the "common cold" but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV. Mice are an ideal experimental animal model for such studies, but are resistant to HCoV-229E and HCoV-NL63 infections. Here, we generated 229E and NL63 mouse models by exogenous delivery of their receptors, human hAPN and hACE2 using replication-deficient adenoviruses (Ad5-hAPN and Ad5-hACE2), respectively. Ad5-hAPN- and Ad5-hACE2-sensitized IFNAR-/- and STAT1-/- mice developed pneumonia characterized by inflammatory cell infiltration with virus clearance occurring 7 d post infection. Ad5-hAPN- and Ad5-hACE2-sensitized mice generated virus-specific T cells and neutralizing antibodies after 229E or NL63 infection, respectively. Remdesivir and a vaccine candidate targeting spike protein of 229E and NL63 accelerated viral clearance of virus in these mice. 229E- and NL63-infected mice were partially protected from SARS-CoV-2 infection, likely mediated by cross-reactive T cell responses. Ad5-hAPN- and Ad5-hACE2-transduced mice are useful for studying pathogenesis and immune responses induced by HCoV-229E and HCoV-NL63 infections and for validation of broadly protective vaccines, antibodies, and therapeutics against human respiratory coronaviruses including SARS-CoV-2.

Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease.

SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential inhibitors have been identified in vitro. However, the detailed mechanism of action and structure-activity relationship require further studies. Here, we investigated the structure-activity relationships of the series of derivatives of tanshinone IIA sulfonate sodium (TSS) and chloroxine based on biochemical analysis and molecular dynamics simulation. We found that compound 7, a derivative of chloroxine, can disrupt PLpro-ISG15 interaction and exhibits an antiviral effect for SARS-CoV-2 variants (wild type, delta, and omicron) at the low micromolar level. These studies confirmed that inhibiting PLpro-ISG15 interaction and, thus, restoring the host's innate immunity are effective methods for fighting against viral infection.

Mapping and role of T cell response in SARS-CoV-2-infected mice.

Virus-specific T cells play essential roles in protection against multiple virus infections, including SARS-CoV and MERS-CoV. While SARS-CoV-2-specific T cells have been identified in COVID-19 patients, their role in the protection of SARS-CoV-2-infected mice is not established. Here, using mice sensitized for infection with SARS-CoV-2 by transduction with an adenovirus expressing the human receptor (Ad5-hACE2), we identified SARS-CoV-2-specific T cell epitopes recognized by CD4+ and CD8+ T cells in BALB/c and C57BL/6 mice. Virus-specific T cells were polyfunctional and were able to lyse target cells in vivo. Further, type I interferon pathway was proved to be critical for generating optimal antiviral T cell responses after SARS-CoV-2 infection. T cell vaccination alone partially protected SARS-CoV-2-infected mice from severe disease. In addition, the results demonstrated cross-reactive T cell responses between SARS-CoV and SARS-CoV-2, but not MERS-CoV, in mice. Understanding the role of the T cell response will guide immunopathogenesis studies of COVID-19 and vaccine design and validation.

Current research and perspective of microplastics (MPs) in soils (dusts), rivers (lakes), and marine environments in China.

In this study, we first reviewed the current research progress regarding the presence of environmental microplastics (MPs) in environment in China from 2010 to 2019. Results showed that: (1) current research has primarily focused on river and marine environments rather than soils and dusts, mainly located in eastern China, i.e., the Yangtze river, Poyang lake, Dongting lake, Yellow sea, and Bohai sea; (2) the abundance of MPs found in water bodies (sediments) of the rivers in China ranged from 3.9 to 7900 items·m-3 (19.0 × 103-13600.5 × 103 items·km-2), and 20-24300 items·kg-2 (170-5500 × 106 items·km-2) in the sediments, respectively; in lake water the range was 340-8900 items·m-3 (5 × 103-340 × 105 items·km-2) and 8 to 1200 items·m-2/25-300 items·kg-1 in the sediments, respectively; in marine water the range was 0.003-540 items·m-3 (0-380,100 item·km-2) and 1.3-14700 item·kg-1 in the sediments, respectively; in fish, shellfish, and natural planktons from ocean and freshwater, the range was 0-57 items·individuals-1 (0-168 items·g-1); (3) The absorption and toxicological effects of MPs in freshwater and oceans have mainly focused on polyethylene (PE), polypropylene (PP), and polystyrene (PS); (4) the sources of microplastics in soils and dusts primarily come from urban/town activities; for rivers and lakes (estuary), they primarily come from urban activities; for coastal waters, fishing gear and nets, and the maritime activities were the main sources.

Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.

COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.

Pollution assessment and health risk evaluation of eight (metalloid) heavy metals in farmland soil of 146 cities in China.

Heavy metals are the most important indicator for farmland soil; however, in China, few provincial and national scales of studies have been done on heavy metals. Herein, by retrieving published studies, we calculated the spatial distribution characters and evaluated the health risks of Cu, Zn, Cd, Ni, Pb, Cr, As, and Hg in the farmland soil of 146 cities in China. Results showed that (1) the range (mean) values of eight (metalloid) heavy metals were as follows in mg/kg: Cu 0.236-251.015 (44.604), Zn 0.151-1547.060 (154.203), Cd 0.014-39.100 (1.497), Ni 0.709-554.420 (41.968), Pb 0.327-495.400 (55.143), Cr 0.078-333.510 (70.093), As 0.836-60.000 (12.207), and Hg 0.008-12.190 (0.371). The coefficient of variation values of Cu, Cr, and As displayed moderate variation, and Zn, Cd, Ni, Pb, and Hg displayed high variation (142.148-364.960%). (2) the Igeo values of As, Cu, Cd, Ni, Zn, Cr, Pb, and Hg were - 4.329 to 1.837, - 7.166 to 2.888, - 3.378 to 8.070, - 5.831 to 3.780, - 9.527 to 3.797, - 10.120 to 1.866, - 6.899 to 3.667, and - 3.681 to 6.966, respectively; in many cities, there was some degree of heavy metal pollution of the farmland soil such as Zn in Pingdu, Pb in Huludao, and Hg in Tongguan, Funshun, Huludao, and Qinglong (Igeo > 3); there were no obvious spatial patterns of Cr, Ni, and As, and Zn, Cu, but Cd, Ni, Pb, and Hg mainly located in some cities in the southwest, central or eastern parts of China. (3) Health risk assessment showed that with the exception of Cd, Cr, and As by the respiration route and Ni, Cr, and As through skin exposure, the average amount of daily exposure of the eight (metalloid) heavy metals all showed values for children > adults, and the HQ and HI values were all lower than 1.0, indicating noncarcinogenic risks; calculation of carcinogenic risks showed there were no carcinogenic risks for As, Cr, Ni, and Cd; however, the value for Cr was the maximum and contributed 98.505% of the total.

A study of synchronous measurement of liable phosphorous and iron based on ZrO-Chelex (DGT) in the sediment of the Chaiwopu Lake, Xinjiang, Northwest China.

The water-sediment interface of lakes is an important and unique area of the water environment; the geochemical behavior of nutrients in this area has a significant impact on the quality of the water environment and ecosystems, especially in shallow lakes. However, most studies do not provide direct in situ evidence for this in shallow lakes in arid regions; in order to explore the coupling relationship between phosphorus (P) and iron (Fe) in a sediment profile, we conducted a high-resolution analysis of liable Fe and P in sediments taken from the Chaiwopu Lake using ZrO-Chelex thin film diffusion gradient technology (ZrO-Chelex DGT). The results show that (1) the vertical spatial distribution trend of the liable P and Fe in the sediments from each sampling site is essentially similar. The contents of the liable P and Fe ranged from 0.004-0.125 mg/L and 0.050-0.190 mg/L, respectively, and the synchronous distribution of the micro-interface concentration reflects the coupling relationship between them. (2) The correlation analysis of the liable P and Fe concentrations showed that there were significant linear correlations between them (P < 0.05, bilateral). (3) The diffusion fluxes of P and Fe were - 51.76~65.12 µg (m2 d)-1 and - 451.27~457.06 µg (m2 d)-1, respectively, and were shown to be negative at the sediment-water interface for most of the samples, which showed that P and Fe were released from the overlying water into the sediments. (4) This research showed that the diffusive fluxes at the different sites are quite different, which indicates that the phosphorus and iron pollution in the sediments of the Chaiwopu Lake is affected by exogenous inputs. There was no significant correlation between P release flux and pH, ORP, conductivity (EC), the TDS of the overlying water, or the pH, salinity (Ca2+, Mg2+), and nutrient (organic matter) content of the sediment. The release flux of Fe is affected by the pH of the sediment. The results of this study provide references for the research of elements in the water-sediment interface of shallow lakes in arid regions, as well as other areas.

Laparoscopic transabdominal preperitoneal technique versus open surgery with the ULTRAPRO Hernia System for the repair of female primary femoral hernias-an observational retrospective study.

Femoral hernias (FHs), predominantly seen in females, require surgery for cure. To date, surgical repair of primary FHs in female patients with either open surgery or laparoscopic operation has been poorly documented. We retrospectively investigated the treatment of female primary FHs with open surgery using the ULTRAPRO Hernia System (UHS procedure) or the laparoscopic procedure, namely, the transabdominal preperitoneal (TAPP) technique. A total of 41 female patients with primary FHs who had undergone UHS or TAPP were included in this study. The procedural parameters, post-surgical complications, treatment expense, and follow-up results were analyzed. The vast majority of patients (39/41) underwent elective operations: 15 received UHS (including 2 emergency cases) and 26 had TAPP (P = .08). The UHS group had a greater average age, due to the fact that FHs occur often in people with advanced age who tend to have systemic disease, limiting the use of general anesthesia required for TAPP. Compared with UHS, TAPP took a significantly shorter time to complete and patients undergoing TAPP had a dramatically shorter hospital stay. While no recurrence was observed in both groups, post-procedure pain and foreign body sensation were reported by significantly more patients in UHS group. The cost was greater with TAPP. Taken together, we concluded that both UHS and TAPP are effective in the management of female FHs. In view of the advantages and disadvantages between the open and the laparoscopic operation, surgeons can select a procedure according to their skills and patients' situation.