Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

VDR restores the expression of PINK1 and BNIP3 in TECs of streptozotocin-induced diabetic mice.

Defective mitophagy in renal tubular epithelial cells is one of the main drivers of renal fibrosis in diabetic kidney disease. Our gene sequencing data showed the expression of PINK1 and BNIP3, two key molecules of mitophagy, was decreased in renal tissues of VDR-knockout mice. Herein, streptozotocin (STZ) was used to induce renal interstitial fibrosis in mice. VDR deficiency exacerbated STZ-induced renal impairment and defective mitophagy. Paricalcitol (pari, a VDR agonist) and the tubular epithelial cell-specific overexpression of VDR restored the expression of PINK1 and BNIP3 in the renal cortex and attenuated STZ-induced kidney fibrosis and mitochondrial dysfunction. In HK-2 cells under high glucose conditions, an increased level of α-SMA, COL1, and FN and a decreased expression of PINK1 and BNIP3 with severe mitochondrial damage were observed, and these alterations could be largely reversed by pari treatment. ChIP-qPCR and luciferase reporter assays showed VDR could positively regulate the transcription of Pink1 and Bnip3 genes. These findings reveal that VDR could restore mitophagy defects and attenuate STZ-induced fibrosis in diabetic mice through regulation of PINK1 and BNIP3.

A systematic comparison of salt removal efficiency in washing treatment by using fly ashes from 13 MSWI plants in China.

Municipal solid waste incineration (MSWI) fly ash contains large amounts of Ca, Si, and other elements, giving it the potential to be used as a raw material for cement production. However, fly ash often contains a high content of salts, which greatly limits its blending ratio during cement production. These salts are commonly removed via water washing, but this process is affected by the nature and characteristics of fly ash. To clarify the influence of the ash characteristics on salt removal, a total of 60 fly ash samples from 13 incineration plants were collected, characterized, and washed. The ash characterization and cluster analysis showed that the incinerator type and flue gas purification technology/process significantly influenced the ash characteristics. Washing removed a high percentage of salts from fly ash, but the removal efficiencies varied significantly from each other, with the chlorine removal efficiency ranging from 73.76% to 96.48%, while the sulfate removal efficiency ranged from 6.92% to 51.47%. Significance analysis further revealed that the salt removal efficiency varied not only between the ash samples from different incinerators, but also between samples collected at different times from the same incinerator. The high variance of the 60 ash samples during salt removal was primarily ascribed to their different mineralogical and chemical characteristics. Mineralogical analysis of the raw and washed ash samples showed that the mineralogical forms and proportion of these salts in each ash sample greatly influenced their removal. The presence of less-soluble and insoluble chloride salts (e.g., CaClOH, Ca2Al(OH)6(H2O)2Cl etc.) in fly ash significantly affected the chlorine removal efficiency. This study also found that Fe, Mn, and Al in fly ash were negatively correlated with the dechlorination efficiency of fly ash. In summary, the different physical and chemical properties of fly ash caused great discrepancies in salt removal. Consequently, it is suggested to consider the potential impact of the ash source and ash generation time on salt removal to ensure a reliable treatment efficiency for engineering applications.

Hypomethylation-Mediated Upregulation of NFE2L3 Promotes Malignant Phenotypes of Clear Cell Renal Cell Carcinoma Cells.

This work aimed to study the effect of NFE2 like bZIP transcription factor 3 (NFE2L3) on clear cell renal cell carcinoma (ccRCC) cells and whether NFE2L3 expression was mediated by DNA methylation. Twenty-one ccRCC patients were collected. The gene methylation and expression data of TCGA-KIRC were accessed from TCGA. Candidate methylation driver genes were identified by "MethylMix" package, and finally, NFE2L3 was selected as the target gene. The methylation of NFE2L3 was assayed by Ms PCR and QMSP. mRNA level of NFE2L3 was analyzed by qRT-PCR. Protein level of NFE2L3 was measured by Western blot. Demethylation was performed with methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). Proliferative, migratory, and invasive abilities of ccRCC cells were assayed via cell colony formation assay, scratch healing assay, and transwell assay, respectively. Analysis of TCGA database presented that DNA hypomethylation occurred in the NFE2L3 promoter region in ccRCC tissues. NFE2L3 was significantly upregulated in ccRCC tissues and cells. Its expression in cells treated with 5-Aza-CdR was proportional to the concentration of methylation inhibitor. In cell function experiments, overexpressing NFE2L3 or demethylation could stimulate proliferation, migration, and invasion abilities of ccRCC and normal cells. 5-Aza-CdR treatment rescued repressive impact of knockdown NFE2L3 on malignant phenotypes of ccRCC and normal cells. DNA hypomethylation could induce high expression of NFE2L3 and facilitate malignant phenotypes of ccRCC cells. These results may generate insights into ccRCC therapy.

Chloroplast Genome Comparison and Phylogenetic Analysis of the Commercial Variety Actinidia chinensis 'Hongyang'.

Actinidia chinensis 'Hongyang', also known as red yangtao (red heart kiwifruit), is a vine fruit tree native to China possessing significant nutritional and economic value. However, information on its genetic diversity and phylogeny is still very limited. The first chloroplast (cp) genome of A. chinensis 'Hongyang' cultivated in China was sequenced using de novo technology in this study. A. chinensis 'Hongyang' possesses a cp genome that spans 156,267 base pairs (bp), exhibiting an overall GC content of 37.20%. There were 132 genes that were annotated, with 85 of them being protein-coding genes, 39 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. A total of 49 microsatellite sequences (SSRs) were detected, mainly single nucleotide repeats, mostly consisting of A or T base repeats. Compared with 14 other species, the cp genomes of A. chinensis 'Hongyang' were biased towards the use of codons containing A/U, and the non-protein coding regions in the A. chinensis 'Hongyang' cpDNA showed greater variation than the coding regions. The nucleotide polymorphism analysis (Pi) yielded nine highly variable region hotspots, most in the large single copy (LSC) region. The cp genome boundary analysis revealed a conservative order of gene arrangement in the inverted repeats (IRs) region of the cp genomes of 15 Actinidia plants, with small expansions and contractions of the boundaries. Furthermore, phylogenetic tree indicated that A. chinensis 'Hongyang' was the closest relative to A. indochinensis. This research provides a useful basis for future genetic and evolutionary studies of A. chinensis 'Hongyang', and enriches the biological information of Actinidia species.

Determination of the effects of pre-harvest bagging treatment on kiwifruit appearance and quality via transcriptome and metabolome analyses.

Bagging is an effective cultivation strategy to produce attractive and pollution-free kiwifruit. However, the effect and metabolic regulatory mechanism of bagging treatment on kiwifruit quality remain unclear. In this study, transcriptome and metabolome analyses were conducted to determine the regulatory network of the differential metabolites and genes after bagging. Using outer and inner yellow single-layer fruit bags, we found that bagging treatment improved the appearance of kiwifruit, increased the soluble solid content (SSC) and carotenoid and anthocyanin levels, and decreased the chlorophyll levels. We also identified 41 differentially expressed metabolites and 897 differentially expressed genes (DEGs) between the bagged and control 'Hongyang' fruit. Transcriptome and metabolome analyses revealed that the increase in SSC after bagging treatment was mainly due to the increase in D-glucosamine metabolite levels and eight DEGs involved in amino sugar and nucleotide sugar metabolic pathways. A decrease in glutamyl-tRNA reductase may be the main reason for the decrease in chlorophyll. Downregulation of lycopene epsilon cyclase and 9-cis-epoxycarotenoid dioxygenase increased carotenoid levels. Additionally, an increase in the levels of the taxifolin-3'-O-glucoside metabolite, flavonoid 3'-monooxygenase, and some transcription factors led to the increase in anthocyanin levels. This study provides novel insights into the effects of bagging on the appearance and internal quality of kiwifruit and enriches our theoretical knowledge on the regulation of color pigment synthesis in kiwifruit.

A framework to validate fluorescently labeled DNA-binding proteins for single-molecule experiments.

Due to the enhanced labeling capability of maleimide-based fluorescent probes, lysine-cysteine-lysine (KCK) tags are frequently added to proteins for visualization. In this study, we employed an in vitro single-molecule DNA flow-stretching assay as a sensitive way to assess the impact of the KCK tag on the property of DNA-binding proteins. Using Bacillus subtilis ParB as an example, we show that, although no noticeable changes were detected by in vivo fluorescence imaging and chromatin immunoprecipitation (ChIP) assays, the KCK tag substantially altered ParB's DNA compaction rates and its response to nucleotide binding and to the presence of the specific sequence (parS) on the DNA. While it is typically assumed that short peptide tags minimally perturb protein function, our results urge researchers to carefully validate the use of tags for protein labeling. Our comprehensive analysis can be expanded and used as a guide to assess the impacts of other tags on DNA-binding proteins in single-molecule assays.

Strategies for fertilizer management to achieve higher yields and environmental and fertilizer benefits of rice production in China.

The challenge in China is to retain high yields while lowering greenhouse gas (GHG) emissions in the context of the increasing global and Chinese demand for rice yield. Better fertilizer management is a key factor that favors intensive rice systems toward more intensive, diverse, and sustainable development to obtain higher yield and environmental benefits. Thus, we used a data-intensive approach to estimate yield, fertilizer productivity (FP) and GHG emissions based on fertilizer and soil characteristics across major Chinese rice-producing regions. The common rice production model showed medium yield, low emission intensity and FP, and low or high GHG emissions. Approximate 41 % and 10 %, 34 % and 3 %, 8 % and 2 %, and 8 % and 1 % probabilities for medium and high yield (MY and HY)-low emission intensity (LI)-low GHG emissions (LG)-high FP (HF) (MY-LI-LG-HF and HY-LI-LG-HF) were achieved in Northeast, South, Southwest, Central and East China, respectively, by adjusting basal, tillering and panicle fertilization and soil pH, N, P and K. Our results provide insights for adjusting soil nutrient traits and fertilizer inputs according to regional production potentials for higher yields and FP and lower GHG emissions in China.

[Effects of Reservoir Water Depth on Different Plankton Communities and Keystone Species of Network Interaction].

In order to understand the impacts of the reservoir construction on the diversity and ecological network of different microbial communities, seven sampling sites were set up in the Hengshan Reservoir in 2021. Water samples were collected from the surface and bottom of the reservoir. After filtering and extracting total DNA samples, high-throughput sequencing was carried out based on 16S and 18S rDNA to investigate the response of community structure, molecular ecological network, and keystone species of different microbial groups to water environment changes. The results showed that the Richness, Simpson, Shannon, and Pielou's Evenness indices of bacterial community in the surface and bottom layers were higher than those in the eukaryote community. The dominant community of bacteria included Proteobacteria, Actinobacteria, and Bacteroidetes, and the eukaryote community included Arthropoda, Ciliophora, Ochrophyta, etc. Moreover, the density and average clustering coefficient of the microbial networks in the surface waters of different phytoplankton communities were higher than those in the bottom waters. It was also observed that the microbial ecological networks in the surface waters were more closely related, and the number of nodes and edges, as well as the number of keystone species, of bacterial communities in the surface and bottom layers were significantly higher than those in the eukaryote microbial communities, indicating that the bacterial community network was larger, and the cooperative relationship and network connectivity between species were stronger. The interaction between bacterial community and eukaryote community in different water depths was dominated by positive correlation, and the negative correlation of the two groups in the bottom layer was slightly greater than that in the surface, indicating that the competition between bottom-layer species was greater than that between surface-layer species. In addition, the environmental impact factors of all species and keystone species of the community in surface water were basically the same, but they differed greatly in deep water, indicating that the influence mechanism of water depth change on keystone species was not the same as that of all species. The results further revealed the effects of reservoir construction on the stability and interspecific interactions of different microbial communities and provided a theoretical basis for predicting variations in microbial community and material cycling in reservoirs.

Vitamin D receptor attenuate ischemia-reperfusion kidney injury via inhibiting ATF4.

Activating transcription factor 4 (ATF4) is one of the key effectors of endoplasmic reticulum stress (ERS), ATF4/CHOP pathway-mediated ERS plays an important role in the progression of acute kidney disease (AKI). We have previously reported that Vitamin D receptor (VDR) exert renoprotection in rodent AKI models. However, whether ATF4, as well as ERS, is involved in the protective effect of VDR in ischemia-reperfusion (I/R) induced AKI is unknown. Herein, we showed that VDR agonist paricalcitol and VDR overexpression alleviated I/R-induced renal injury and cells apoptosis with decreased ATF4 and attenuated ERS, while VDR deletion significantly resulted in further increased ATF4, more drastic ERS and renal injury in I/R mice models. In addition, paricalcitol remarkably reduced Tunicamycin (TM) induced ATF4 and ERS with attenuated renal injury, while VDR deletion aggravated the above changes in TM mice models. Moreover, overexpression of ATF4 partially abolished the effect of paricalcitol against TM-induced ERS and apoptosis, while inhibition of ATF4 enhanced the protective effect of paricalcitol. Bioinformatics analysis indicated potential VDR binding sites on ATF4 promotor sequence which were further confirmed by ChIP-qPCR and dual-luciferase reporter gene assay. In conclusion, VDR attenuated I/R-induced AKI by suppressing ERS partly via transcriptional regulation of ATF4.

The optimal dose of oxycodone in PCIA after laparoscopic surgery for gastrointestinal cancer in elderly patients: A randomized controlled trial.

Objective: To explore the optimal bolus dose of oxycodone for patient controlled intravenous analgesia (PCIA) without background dose in elderly patients after laparoscopic surgery for gastrointestinal cancer. Methods: In this prospective, randomized, double-blind, parallel-controlled study, we recruited patients aged 65 years or older. They underwent laparoscopic resection for gastrointestinal cancer and received PCIA after surgery. Eligible patients were randomly divided into 0.01, 0.02, or 0.03 mg/kg group according to the bolus dose of oxycodone in PCIA. The primary outcome was VAS scores of pain on mobilization at 48 h after surgery. Secondary endpoints included the VAS scores of rest pain, the total and effective numbers of press in PCIA, cumulative dose of oxycodone used in PCIA, the incidence of nausea, vomiting and dizziness, as well as patients' satisfaction at 48 h after surgery. Results: A total of 166 patients were recruited and randomly assigned to receive a bolus dose of 0.01 mg/kg (n = 55), 0.02 mg/kg (n = 56) or 0.03 mg/kg (n = 55) of oxycodone in PCIA. The VAS scores of pain on mobilization, the total and effective numbers of press in PCIA in 0.02 mg/kg group and 0.03 mg/kg group were lower than those in 0.01 mg/kg group (P < 0.05). Cumulative dose of oxycodone used in PCIA and patients' satisfaction in 0.02 and 0.03 mg/kg groups were more than those in 0.01 mg/kg group (P < 0.01). The incidence of dizziness in 0.01 and 0.02 mg/kg groups was lower than that in 0.03 mg/kg group (P < 0.01). There were no significant differences in VAS scores of rest pain, the incidence of nausea and vomiting among three groups (P > 0.05). Conclusion: For elderly patients undergoing laparoscopic surgery for gastrointestinal cancer, 0.02 mg/kg bolus dose of oxycodone in PCIA without background infusion may be a better choice.

A novel near-infrared fluorescent probe for the imaging of viscosity in cells and tumor-bearing mice.

A near-infrared fluorescent probe (IC-V) for detecting viscosity is constructed. The probe has a large Stokes shift (170 nm) and an about 180-fold increase in fluorescence intensity at 700 nm. In addition, IC-V can not only distinguish cancer cells from normal cells, but also monitor viscosity in normal mice and tumor-bearing mice.

Enhanced removal of metal-cyanide complexes from wastewater by Fe-impregnated biochar: Adsorption performance and removal mechanism.

Metal-cyanide complexes are common contaminants in industrial wastewater. Removal of these refractory contaminants is essential before their discharge into the environment. This study investigated a biochar (BC)-based sorbent material that could be applied for the efficient removal of metal-cyanide complexes from wastewater. In consideration of the strong electrostatic repulsion of the pristine BC toward anions, iron-modified BC (Fe-BC) composites were fabricated by a one-step co-pyrolysis of corn straw and FeCl3 at 600-800 °C. The adsorption performance and corresponding sorption mechanisms of representative metal-cyanide complexes (ferricyanide [Fe(CN)6]3- and tetracyanonickelate [Ni(CN)4]2-) onto the Fe-BC composites were investigated. The results indicated that the Fe-BC composites had significantly high affinity toward the metal-cyanide complexes, reaching a maximum sorption capacity of 580.96 mg/g for [Fe(CN)6]3- and 588.86 mg/g for [Ni (CN)4]2-. A mechanistic study revealed that Fe-impregnation during BC fabrication could effectively alter the negatively charged BC surface, forming more functional groups that could interact with the metal-cyanide complexes. Moreover, the transformation of carbon structure promoted the carbothermal reduction process, leading to the formation of various reductive-Fe minerals in the resulting Fe-BC composites. These modification-induced alterations to the surface and structural characteristics of BC were expected to facilitate the adsorption/precipitation of target contaminants. Different sorption mechanisms were proposed for the two metal-cyanide complexes that were the focus of this study. For [Fe(CN)6]3-, precipitation by Fe-bearing species in the Fe-BC composites was the major factor controlling [Fe(CN)6]3- removal, while for [Ni(CN)4]2- hydrogen bonding interactions between surface functional groups (especially hydroxyl (-OH) and carboxyl (-COOH)) and [Ni(CN)4]2- were the main factors controlling removal.

Preoperative ultrasound can accurately predict the diameter of double-stranded peroneus longus tendon autografts.

PURPOSE: This study aimed to determine the correlation between the intraoperative diameter of double-stranded peroneus longus tendon (2PLT) and length of the PLT autograft and preoperative ultrasound (US) measurements, as well as radiographic and anthropometric measurements. The hypothesis was that US can accurately predict the diameter of 2PLT autografts during operation. METHODS: Twenty-six patients underwent ligament reconstruction with 2PLT autografts were included. Preoperative US was used to calculate the in situ PLT cross-sectional area (CSA) at seven levels (0, 1, 2, 3, 4, 5, 10 cm proximal to the harvest start point). Femoral width, notch width, notch height, maximum patellar length, and patellar tendon length were determined on preoperative radiographs. Intraoperative measurements of PLT were made, including all fiber lengths of PLT and diameters of 2PLT using sizing tubes calibrated to 0.5 mm. RESULTS: CSA at 1 cm proximal to the harvest site had the highest correlation with the diameter of 2PLT (r = 0.84, P < 0.001). Calf length had the highest correlation with PLT length (r = 0.65, P < 0.001). The diameter of the 2PLT autografts could be predicted by the following formula: 4.6 + 0.2 × [sonographic CSA of PLT at 1 cm level]; the length of PLT could be predicted by the following formula: 5.6 + 0.5 × Calf length. CONCLUSION: The diameter of 2PLT and length of PLT autografts can be accurately predicted by preoperative US and calf length measurements, respectively. Accurate preoperative prediction of the diameter and length of autologous grafts can provide the most suitable and individualized graft for patients. LEVEL OF EVIDENCE: IV.

Clinical characteristics and prognostic characterization of endometrial carcinoma: a comparative analysis of molecular typing protocols.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common gynecological malignancies in China and globally, accounting for the fourth-prevalent cancer in women. Although numerous studies have confirmed prognostic value of The Cancer Genome Atlas (TCGA) molecular subgroups, it is unclear how they are combined with histological features. The main objective of this study was to compare ProMisE and TCGA classification for the rapid and accurate prediction of prognosis within EC patients, together with the provision of a revised strategy for individualized diagnosis and treatment of patients. METHODS: Within this study, 70 patients with EC from Beijing Tsinghua Changgeng Hospital (affiliated to Tsinghua University) were retrospectively examined between July 2015 and December 2021. Samples were processed for determination of clinical markers, together with ProMisE and TCGA classification. RESULTS: Comparative analysis across four TCGA types (POLE, Low-CN, High-CN, and MSI-H) and age, was statistically significant (χ²= 7.000, p = 0.029). There was no significant difference observed among the four TCGA types and FIGO stage, vascular invasion and depth of invasion, or lymph node metastasis and tumor area. There was no significant association between the expression of Vimentin, Ki-67, PTEN, MSH2, PAX-8, ß-catenin, CD10, ER, PR, P16, MLH1, and PMS2 with the four TCGA types. In addition, p63 expression (χ²= 11.09, p = 0.029) and p53 expression (χ²= 11.585, p = 0.005) were statistically significant. Numerous models demonstrated that patients with POLE mutations and low-CN had higher progression free survival (PFS) and overall survival (OS), whereas those with high-CN had lowest values. The log-rank test revealed that the survival rate of PR-positive and ER-positive patients was significantly higher (p < 0.001). CONCLUSION: Overall, these results can be of additional benefit for clinical applications, in comparison to the ProMisE classification method. In addition, PR, ER, vascular infiltration, hyperlipidemia and atherosclerosis were found to be the key factors affecting EC prognosis.

Vitamin D-VDR (vitamin D receptor) alleviates glucose metabolism reprogramming in lipopolysaccharide-induced acute kidney injury.

Background: Our previous study showed that vitamin D (VD)-vitamin D receptor (VDR) plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI. Objective: To investigate the role of VD-VDR in glucose metabolism reprogramming in LPS-induced AKI. Methods: We established a model of LPS-induced AKI in VDR knockout (VDR-KO) mice, renal proximal tubular-specific VDR-overexpressing (VDR-OE) mice and wild-type C57BL/6 mice. In vitro, human proximal tubular epithelial cells (HK-2 cells), VDR knockout and VDR overexpression HK-2 cell lines were used. Results: Paricalcitol (an active vitamin D analog) or VDR-OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in VDR-KO mice. In in vitro experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-PDHA1). Moreover, paricalcitol activated the phosphorylation of AMP-activated protein kinase (AMPK), and an AMPK inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells. Conclusion: VD-VDR alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of PDHA1 phosphorylation via the AMPK pathway.

Using DNA flow-stretching assay as a tool to validate the tagging of DNA-binding proteins for single-molecule experiments.

Due to the enhanced labeling capability of maleimide-based fluorescent probes, lysine-cysteine-lysine (KCK) tags are frequently added to proteins for visualization. In this study, we employed in vitro single-molecule DNA flow-stretching assay as a sensitive way to assess the impact of the KCK-tag on the property of DNA-binding proteins. Using Bacillus subtilis ParB as an example, we show that, although no noticeable changes were detected by in vivo fluorescence imaging and chromatin immunoprecipitation (ChIP) assays, the KCK-tag substantially altered ParB's DNA compaction rates, its response to nucleotide binding and to the presence of the specific sequence (parS) on the DNA. While it is typically assumed that short peptide tags minimally perturb protein function, our results urge researchers to carefully validate the use of tags for protein labeling. Our comprehensive analysis can be expanded and used as a guide to assess the impacts of other tags on DNA-binding proteins in single-molecule assays.

Case report: A case of complete clinical response in a patient experiencing high microsatellite instability unresectable colon cancer being treated with a PD-L1 inhibitor after interstitial pneumonia.

Immune checkpoint inhibitors (ICI) have dramatically transformed the treatment landscape for metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) or high microsatellite instability (MSI-H). Envafolimab, a novel programmed death-1 ligand 1 (PD-L1) inhibitor, has been reported to be efficient and safe for the management of advanced MSI-H/dMMR solid tumors. Here, we report the case of a 35-year-old female patient with MSI-H/dMMR mCRC who was treated with envafolimab following mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) plus bevacizumab. While suffering from interstitial pneumonia after chemotherapy, the patient achieved a complete clinical response with the use of envafolimab without additional adverse events. Thus, PD-L1 inhibitors may be potential candidates for treating patients with MSI-H/dMMR mCRC.

Intraoperative dexmedetomidine use is associated with lower incidence of acute kidney injury after non-cardiac surgery.

BACKGROUND: Previous studies have shown that perioperative dexmedetomidine could reduce the incidence of postoperative AKI in cardiovascular surgery, however, its effectiveness in the non-cardiovascular surgery patient population has not been reported. The aim of this study was to investigate the effect of intraoperative dexmedetomidine on the incidence of postoperative AKI and postoperative ICU admissions in patients undergoing non-cardiovascular surgery. DESIGN AND SETTING: A single-center retrospective cohort study obtained from the database of the Center for Anesthesia and Surgery, the Third Xiangya Hospital. PATIENTS: Inpatients between 18 and 75 years of age who were admitted to our hospital for non-cardiovascular surgery from 2012 to 2019. RESULTS: Overall 2391 patients who used dexmedetomidine intraoperatively were analyzed in comparison to 4552 patients who did not use dexmedetomidine after one-to-two matching. The two cohorts had similar baseline values and demographic characteristics. The incidence of AKI was lower in patients with intraoperative dexmedetomidine use than in the nonuse group (OR 0.60, p < .001). The rate of severe renal failure needing dialysis was also lower than in the nonuse group (ß = -0.02, p < .05). After adjusting for confounding factors, the rate of AKI was still lower in the dexmedetomidine group. The rate of postoperative ICU admissions and in-hospital deaths were similar in the two groups (p > .05). CONCLUSION: For non-cardiovascular surgery patient population, intraoperative use of dexmedetomidine was associated with a lower incidence and less severity of postoperative AKI. However, there was no significant correlation with postoperative ICU occupancy or in-hospital mortality. Further prospective RCTs are needed in the future.

Exploring the contributions of major emission sources to PM2.5 and attributable health burdens in China.

Ambient fine particulate matter (PM2.5) pollution is the principal environmental risk factor for health burdens in China. Identifying the sectoral contributions of pollutant emissions sources on multiple spatiotemporal scales can help in the formulation of specific strategies. In this study, we used sensitivity analysis to explore the specific contributions of seven major emission sources to ambient PM2.5 and attributable premature mortality across mainland China. In 2016, about 60% of China's population lived in areas with PM2.5 concentrations above the Chinese Ambient Air Quality Standard of 35 µg/m3. This percentage was expected to decrease to 35% and 39% if industrial and residential emissions were fully eliminated. In densely populated and highly polluted regions, residential sources contributed about 50% of the PM2.5 exposure in winter, while industrial sources contributed the most (29-51%) in the remaining seasons. The three major sectoral contributors to PM2.5-related deaths were industry (247,000 cases, 35%), residential sources (219,000 cases, 31%), and natural sources (87,000, 12%). The relative contributions of the different sectors varied in the different provinces, with industrial sources making the largest contribution in Shanghai (65%), while residential sources predominated in Heilongjiang (63%), and natural sources dominated in Xinjiang (82%). The contributions of the agricultural (11%), transportation (6%), and power (3%) sources were relatively low in China, but emissions mitigation was still effective in densely populated areas. In conclusion, to effectively alleviate health burdens across China, priority should be given to controlling residential emissions in winter and industrial emissions all year round, taking additional measures to curb emissions from other sources in urban hotspots, and formulating air pollution control strategies tailored to local conditions.