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The lack of vascular tissue and the low metabolism and biological activity of mature chondrocytes lead to the low regeneration ability of articular cartilage. People try to solve this problem through various methods, but the effect is not very ideal. Inspired by the piezoelectric effect of collagen in cartilage tissue, this work focused on the design of a biomimetic hydrogel by introducing piezoelectric materials and silver nanowires into hydrogel to endow them with piezoelectric and antibacterial properties to promote tissue regeneration. Additionally, the mechanical and swelling properties of the material were adjusted to match natural articular cartilage. Based on bionic principles, a double-layer piezoelectric hydrogel was prepared and applied for the repair of osteochondral defects. An enhanced repair effect of osteochondral defects has been seen, which has demonstrated potential values for future application in bionics principle- and piezoelectric effect-based osteochondral tissue engineering. Furthermore, piezoelectric effect-induced degradation was observed. These results fully indicated the positive effect of the piezoelectric effect on promoting the regeneration of osteochondral tissue and in vivo degradation of materials.

Background: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma., Methods: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes., Findings: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause)., Interpretation: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients., Funding: Innovent Biologics., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests ZR has received honoraria as an advisor from Innovent Biologics, AstraZeneca, F Hoffmann-La Roche, and Merck Sharp & Dohme. YY, MC, YW. and HZ are employees of Innovent Biologics. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The epithelial-mesenchymal transition (EMT) process is a key priming activity of fibroblasts in pulmonary fibrosis during silicosis. Ets-like protein-1 (Elk-1) is a critical modulator that promotes functional changes in cells, and the effects are mediated by oxidative stress (OS). However, whether ELK-1 is involved in EMT of silicosis remains unclear. In addition, researchers have found that Elk-1 is involved in the expression of the gene zc3h12a, which encodes the protein MCPIP1, and MCPIP1 is a member of the zinc finger Cys-Cys-Cys-His (CCCH)-type protein family. A previous study from our lab showed that ZC3H4, which is also a member of the CCCH-type protein family, critically affected the regulation of EMT during silicosis. However, it has not yet been elucidated if ELK-1 acts at the promoter for zc3h4 to increase its expression in a mechanism that is similar to that of the zc3h12a gene and whether such regulation ultimately controls EMT. Therefore, we explored the correlation between ELK-1 and ZC3H4 expression and tested the underlying mechanisms affecting ELK-1 activation induced by silica. Our study identifies that SiO 2 -mediated EMT via ELK-1, with the upstream activity of OS and the downstream signaling of ZC3H4 expression resulting in enhanced EMT. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis.

Purpose: To screen novel candidate biomarkers in primary colorectal cancer (CRC), and indentify their clinical valuation in progress of colorectal cancer., Methods: By using antibody microarray, 274 target proteins in tissue samples from primary colorectal cancer patients were detected. Among differently expressed proteins in CRC tissues, As promising candidate biomarker, RANTES/CCL5 was validated by enzyme-linked immunosorbentassay and immunohistochemistry (IHC), and the clinical significance of CCL5 was analyzed., Results: Totally, 25 differentially expressed proteins were indentified between colorectal cancers and matched normal mucosa. CCL5 expression was significantly associated with adverse pathological progress, apt to lymph node metastasis and higher T stage., Conclusions: CCL5 may contribute to promoting tumor growth, and CCL5 is a promising target that may help in understanding the pathogenesis of CRC., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Objective: To investigate the effects and mechanism of salidroside(SAL) on model rats of diabetic nephropathy(DN)., Methods: Rats were divided into control, model, SAL(50 mg/kg), SAL(100 mg/kg) and SAL(200 mg/kg) groups. The rats beside in control group were injected with streptozotocin(STZ) combined with right nephrectomy. And rats in SAL(50, 100, 200 mg/kg) groups were received gavage with SAL(50, 100, 200 mg/kg). After 12 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for renal injury, the concentrations of urine protein, urine creatine(Ucr), blood urea nitrogen(BUN), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were measured by kits. Western blot was used to measure the protein levels of Collagen Ⅳ, fibronectin, E-cadherin, α-smooth muscle actin(α-SMA), N-cadherin, Smad2、Smad3, phosphorylated-Smad2(p-Smad2), p-Smad3 and transforming growth factor-β1(TGF-β1)., Results: Compared with control group, the renal injury of rats in model group was aggravated, the concentrations of urine protein, Ucr and BUN were elevated significantly, the apoptosis cells and positive cells of caspase-3 were increased; compared with model group, the renal injury of rats in SAL(100, 200 mg/kg) groups were alleviated markedly, the concentrations of urine protein, Ucr and BUN were reduced, the apoptosis cells and positive cells of caspase-3 were decreased notably. SAL(50 mg/kg) increased the concentration of SOD in DN model rats, SAL(100, 200 mg/kg) increased the concentrations of SOD and GSH-Px, decreased the level of MDA. Meanwhile, the inhibition of collagen Ⅳ, fibronrctin, α-SMA, and N-cadherin and the induction of E-cadherin in DN rats were induced by SAL(100, 200 mg/kg). In addition, SAL(100, 200 mg/kg) reduced the ratio of p-Smad2/Smad2, p-Smad3/Smad3 and the level of TGF-β1(P<0.05 or P<0.01)., Conclusion: SAL can inhibit renal fibrosis of STZ-induced DN model rats, and the mechanism may be related to inhibition of TGF-β1/Smad pathway.

The study aimed to investigate the metal compositions in indoor PM2.5 and the potential health risks they pose to residents of an urban area in China. A total of 41 and 54 households were surveyed in February and September 2013, respectively. The results showed that the indoor concentrations of metals varied depending on the types of cooking fuels used. All measured concentrations of metals were highest among households using coal for cooking. In the majority of households, non-carcinogenic risks were posed by the use of coal. The carcinogenic risks posed by chromium (VI) and arsenic were generally higher among households using coal for cooking than among those using gas or electricity. The multivariate linear regression model suggested a potential adverse effect from arsenic and cadmium on birth weight and gestational weeks. This study also found that cooking fuel was the most significant factor that contributed to the differences in concentrations of metals in indoor PM2.5 and highlighted the importance of using clean energy for cooking and heating.

Bone epithelioid angiosarcoma (EA) is rare and characterized by large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The tumors may arise in various locations in bone and the patients may present with unifocal or multifocal osseous disease. We present a unifocal lesion case of EA of the ilium in a 62-year-old woman. A needle biopsy of the ilium was performed and first diagnosed poorly differentiated adenocarcinoma based on CKpan and CK18 immunopositivity. The tumor was treated initially with curettage followed by chemotherapy. The final diagnosis on the surgical specimen was epithelioid angiosarcoma.

Air pollution contributes substantially to global health burdens; however, less is known about pollution patterns in China and whether they differ from those elsewhere. We evaluated temporal and spatial heterogeneity of air pollution in Lanzhou, an urban Chinese city (April 2009-December 2012), and conducted a systematic review of literature on air pollution and health in Lanzhou. Average levels were 141.5, 42.3, and 47.2 µg/m 3 for particulate matter with an aerodynamic diameter ≤10 µm (PM 10 ), NO 2 , and SO 2 , respectively. Findings suggest some seasonality, particularly for SO 2 , with higher concentrations during colder months relative to warmer months, although a longer time frame of data is needed to evaluate seasonality fully. Correlation coefficients generally declined with distance between monitors, while coefficients of divergence increased with distance. However, these trends were not statistically significant. PM 10 levels exceeded Chinese and other health-based standards and guidelines. The review identified 13 studies on outdoor air pollution and health. Although limited, the studies indicate that air pollution is associated with increased risk of health outcomes in Lanzhou. These studies and the high air pollution levels suggest potentially serious health consequences. Findings can provide guidance to future epidemiological studies, monitor placement programs, and air quality policies.

Objective: We screened and identified protease-producing bacterial strains from the Arctic, the results would help find cold-adapted protease., Methods: In total 68 protease-producing strains were screened from the Arctic using the casein-agar plate under low temperature. All strains were classified using the 16S rRNA gene-restriction fragment length polymorphism (RFLP) and traditional phenotypic test. One strain was chosen to be the representative strain from each group respectively and identified using 16S rRNA gene sequence analysis, GenBank database Basic Local Alignment Search Tool (BLAST), phylogenetic analysis and phenotypic features analysis. The enzymatic properties of the representative strains were determined., Results: The 68 strains belonged to 3 groups (54.41%, 42.65% and 2.94%), and strains 6, 11 and 52 were the representative strains respectively. The results of the 16S rRNA gene sequence analysis showed that: Strain 11 was most closely related to Chryseobacterium scophthalmum with 98.24% sequence similarity; strain 52 was most closely related to Stenotrophomonas rhizophila with 98.55% sequence similarity; strain 6 was most closely related to Stenotrophomonas rhizophila with 96.50% sequence similarity, which might represent a novel species of the genus. The phenotypic study showed that: strains 6, 11 and 52 were Gram negative, straight rod-shaped, did not produce extracellular lipase and amylase, possessed strong proteolytic activity. The optimal temperature and pH for the enzyme activity were 55 degrees C and 6.7 for the protease from strain 6, 40 degrees C and 8.5 for the protease from strain 11 and 65 degrees C and 7.4 for the protease from strain 52., Conclusion: The research firstly introduced the distribution of Stenotrophomonas and Chryseobacterium specieses in the Arctic marine water, extended the diversity of the protease-producing bacteria from the Arctic, and provided a useful basis for further study of cold-adapted protease.

Objective: To investigate potential pathogens in waters of Xiamen from Jiulong River, and to provide useful information for the prevention and control of potential pathogen infections., Methods: All samples were spread on Thiosulfate Citrate Bile Salts Sucrose (TCBS) agar plates, and then incubated at 26 +/- 1 degrees C for 24 +/- 2 h. In total 158 TCBS strains were isolated from TCBS agar plates and pure-cultivated on 2216E agar plates. All strains were identified using the 16S rRNA gene- Restriction fragment length polymorphism (RFLP), 16S rRNA sequence analysis, GenBank database Basic Local Alignment Search Tool (BLAST) and phylogenetic analysis., Results: The results show that 158 TCBS strains from the sediments of Jiulong River estuary were classfied as 7 genus, which were Pseudomonas (28%), Aeromonas (24%), Pseudoalteromonas (19%), Shewanella (13%), Bacillus (11%), Vibrio (4%) and Psychrobacter (1%). The composition and distribution of TCBS bacteria groups varied with stations. Non-halophilic or haloduric bacteria groups were dominant in the upper area of Jiulong River estuary, and halophilic and haloduric bacteria were dominant in the lower area, which characterized a typical estuary feature. The salinity played a key role in the distribution of TCBS groups. Vibrios did not constitute a significant proportion (6% - 19%) of the total TCBS strains at different stations, and most of the them distributed at the lower region., Conclusion: There were a lot of potential pathogens in Jiulong River estuary. Aeromonas, a typical genus of halotolerant bacteria, was the potentially terrigenous bacteria contamination to the waters of Xiamen. Most Vibrio specieses were marine aborigines, which was not directly contaminated from the runoff of Jiulong River.

A psychrotrophic Arthrobacter strain, GP3(T), was isolated from Adélie penguin guano from Antarctica and characterized. The 16S rRNA gene sequence of the novel strain showed the highest similarity (97.8 %) with that of Arthrobacter psychrolactophilus B7(T). The novel strain showed a morphological change from rod to coccus. The growth temperature range of strain GP3(T) was 0-25 degrees C, with optimal growth at 20 degrees C. The strain grew over a salinity range of between 0 and 3 % (w/v) NaCl and the optimal pH for growth was pH 6-8. Strain GP3(T) contained anteiso-C(15 : 0) as the major fatty acid. The major menaquinone was MK-9(H(2)). The cell-wall peptidoglycan type was of the A3alpha variant. The DNA G+C content of strain GP3(T) was 58.5 mol%. Strain GP3(T) was able to hydrolyse chitin, Tween 80, starch, cellulose and lactose, but not gelatin, lecithin or urea. In addition to these physiological characteristics, DNA-DNA hybridization studies clearly differentiated strain GP3(T) from A. psychrolactophilus. The combined results of phylogenetic, physiological and chemotaxonomic studies indicated that strain GP3(T) represents a novel species of the genus Arthrobacter. The name Arthrobacter psychrochitiniphilus sp. nov. (type strain GP3(T)=JCM 13874(T)=CGMCC 1.6355(T)) is proposed in recognition of the strain's strong chitin-utilizing ability.

In order to analyze the major factors contributing to malnutrition of children aged under five at 40 inspective spots, a cluster method was used and four patterns were set up in this study. Multiple logistic regression was applied in each pattern to identify the most important factor. The results showed that the problem of child malnutrition in urban areas has been solved, but the problem in rural is still severe. The attributable risk of education level of mother, breast feeding and water supply were the major factors contributing to the nutrition status of children and therefore, the synthetical measures should be take for improving the nutrition status of children.