Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

Objective:To investigate the regulatory effect of zinc finger transcription factor 580 (ZNF580) gene on autophagy and extracellular matrix (ECM) secretion in human pancreatic cancer cells PANC1.Methods:PANC1 cells were transfected with 500 ng/ml short hairpin RNA-ZNF580 (shRNA-ZNF580) and a ZNF580 expression vector with a green fluorescent protein reporter gene (GFP-ZNF580) using lentiviral transfection to establish the ZNF580-silenced group and ZNF580-overexpression group, respectively. PANC1 cells were treated with 10 mmol/L rapamycin (RA), a cell autophagy inducer, and the autophagy inhibitor LY294002 for 2 hours to construct the autophagy-induced group and autophagy-inhibited group, respectively. The autophagy inhibition+ZNF580 silencing group was established by transfecting PANC1 cells with 500 ng/ml sh-ZNF580 using lentiviral transfection while simultaneously adding 10 mmol/L LY294002. PANC1 cells cultured in conventional medium served as control group. The expression levels of ZNF580 protein and autophagy-related proteins ATG7 and LC3 in PANC1 cells from each group were detected by Western blot. The expression changes of ECM secretion-related markers type I collagen (Col-Ⅰ), Col-Ⅲ, fibronectin (FN), and tumor necrosis factor-α (TNF-α) in PANC1 cells were measured by ELISA.Results:Compared with control group, the protein expression levels of ATG7, LC3-Ⅰ, and LC3-Ⅱ in PANC1 cells of the ZNF580-silenced group were significantly decreased (0.40±0.04 vs 0.81±0.13, 0.66±0.08 vs 2.0±0.45, 0.78±0.10 vs 1.89±0.23), while they were significantly increased in the ZNF580-overexpression group (2.07±0.17 vs 0.83±0.09, 1.21±0.37 vs 0.88±0.09, 0.77±0.16 vs 0.37±0.06). The protein expression level of ZNF580 in PANC1 cells of the autophagy inhibition group was significantly down-regulated compared with the control group (0.40±0.15 vs 1.07±0.18), while it was significantly up-regulated in the autophagy induction group (1.59±0.25 vs 0.67±0.09). Compared with the control group, the levels of extracellularly secreted Col-Ⅰ, Col-Ⅲ, FN, and TNF-α in PANC1 cells were significantly decreased in the ZNF580-silenced group (5.02±0.81 vs 8.38±0.83, 6.17±0.83 vs 10.73±1.69, 28.66±2.47 vs 45.20±4.31, 10.09±1.32 vs 19.48±2.77), which were significantly increased in the ZNF580-overexpression group (19.28±2.05 vs 8.38±0.83, 28.29±5.96 vs 10.73±1.69, 103.22±6.37 vs 45.20±4.31, 46.78±6.96 vs 19.48±2.77), significantly decreased in the autophagy inhibition group (5.10±0.66 vs 9.01±1.24, 7.22±0.67 vs 11.83±1.71, 28.45±2.82 vs 43.51±4.38, 12.16±2.13 vs 20.53±3.65, respectively), and significantly increased in the autophagy induction group (20.49±3.68 vs 9.01±1.24, 26.58±3.96 vs 11.83±1.71, 73.18±7.15 vs 43.51±4.38, 41.11±8.87 vs 20.53±3.65). Compared with the autophagy inhibition group and the ZNF580-silenced group, the levels of extracellularly secreted Col-Ⅰ, Col-Ⅲ, FN, and TNF-α in PANC1 cells of the autophagy inhibition+ZNF580 silencing group were significantly decreased (Col-Ⅰ: 3.36±1.25 vs 5.73±0.62 and 5.57±0.35; Col-Ⅲ: 4.15±0.16 vs 6.24±0.90 and 6.71±0.34; FN: 18.31±2.00 vs 26.46±1.18 and 27.09±2.01; TNF-α: 6.81±0.46 vs 9.96±1.87 and 10.62±0.65). All the above differences were statistically significant (all P value <0.05). Conclusions:The transcription factor ZNF580 could positively regulate the levels of autophagy and ECM secretion in PANC1 cells. The combined application of ZNF580 gene silencing and autophagy inhibitors can significantly inhibit ECM secretion in PANC1 cells.

Objective:To investigate the regulatory effect of zinc finger transcription factor 580 (ZNF580) gene on autophagy and extracellular matrix (ECM) secretion in human pancreatic cancer cells PANC1.Methods:PANC1 cells were transfected with 500 ng/ml short hairpin RNA-ZNF580 (shRNA-ZNF580) and a ZNF580 expression vector with a green fluorescent protein reporter gene (GFP-ZNF580) using lentiviral transfection to establish the ZNF580-silenced group and ZNF580-overexpression group, respectively. PANC1 cells were treated with 10 mmol/L rapamycin (RA), a cell autophagy inducer, and the autophagy inhibitor LY294002 for 2 hours to construct the autophagy-induced group and autophagy-inhibited group, respectively. The autophagy inhibition+ZNF580 silencing group was established by transfecting PANC1 cells with 500 ng/ml sh-ZNF580 using lentiviral transfection while simultaneously adding 10 mmol/L LY294002. PANC1 cells cultured in conventional medium served as control group. The expression levels of ZNF580 protein and autophagy-related proteins ATG7 and LC3 in PANC1 cells from each group were detected by Western blot. The expression changes of ECM secretion-related markers type I collagen (Col-Ⅰ), Col-Ⅲ, fibronectin (FN), and tumor necrosis factor-α (TNF-α) in PANC1 cells were measured by ELISA.Results:Compared with control group, the protein expression levels of ATG7, LC3-Ⅰ, and LC3-Ⅱ in PANC1 cells of the ZNF580-silenced group were significantly decreased (0.40±0.04 vs 0.81±0.13, 0.66±0.08 vs 2.0±0.45, 0.78±0.10 vs 1.89±0.23), while they were significantly increased in the ZNF580-overexpression group (2.07±0.17 vs 0.83±0.09, 1.21±0.37 vs 0.88±0.09, 0.77±0.16 vs 0.37±0.06). The protein expression level of ZNF580 in PANC1 cells of the autophagy inhibition group was significantly down-regulated compared with the control group (0.40±0.15 vs 1.07±0.18), while it was significantly up-regulated in the autophagy induction group (1.59±0.25 vs 0.67±0.09). Compared with the control group, the levels of extracellularly secreted Col-Ⅰ, Col-Ⅲ, FN, and TNF-α in PANC1 cells were significantly decreased in the ZNF580-silenced group (5.02±0.81 vs 8.38±0.83, 6.17±0.83 vs 10.73±1.69, 28.66±2.47 vs 45.20±4.31, 10.09±1.32 vs 19.48±2.77), which were significantly increased in the ZNF580-overexpression group (19.28±2.05 vs 8.38±0.83, 28.29±5.96 vs 10.73±1.69, 103.22±6.37 vs 45.20±4.31, 46.78±6.96 vs 19.48±2.77), significantly decreased in the autophagy inhibition group (5.10±0.66 vs 9.01±1.24, 7.22±0.67 vs 11.83±1.71, 28.45±2.82 vs 43.51±4.38, 12.16±2.13 vs 20.53±3.65, respectively), and significantly increased in the autophagy induction group (20.49±3.68 vs 9.01±1.24, 26.58±3.96 vs 11.83±1.71, 73.18±7.15 vs 43.51±4.38, 41.11±8.87 vs 20.53±3.65). Compared with the autophagy inhibition group and the ZNF580-silenced group, the levels of extracellularly secreted Col-Ⅰ, Col-Ⅲ, FN, and TNF-α in PANC1 cells of the autophagy inhibition+ZNF580 silencing group were significantly decreased (Col-Ⅰ: 3.36±1.25 vs 5.73±0.62 and 5.57±0.35; Col-Ⅲ: 4.15±0.16 vs 6.24±0.90 and 6.71±0.34; FN: 18.31±2.00 vs 26.46±1.18 and 27.09±2.01; TNF-α: 6.81±0.46 vs 9.96±1.87 and 10.62±0.65). All the above differences were statistically significant (all P value <0.05). Conclusions:The transcription factor ZNF580 could positively regulate the levels of autophagy and ECM secretion in PANC1 cells. The combined application of ZNF580 gene silencing and autophagy inhibitors can significantly inhibit ECM secretion in PANC1 cells.

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2016 to December 2017. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI) 2019. WHONET 5.6 was used to analyze data.Results:During the study period, 8 154 bacterial strains were collected from 33 hospitals, of which 2 325 (28.5%) were Gram-positive bacteria and 5 829 (71.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (34.7%), Klebsiella pneumoniae (15.8%), Staphylococcus aureus (11.3%), coagulase-negative Staphylococci (7.4%), Acinetobacter baumannii (4.6%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.8%), Streptococci (2.9%), Enterobacter cloacae (2.7%) and Enterococcus faecalis (2.5%). Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) accounted for 34.2%(315/922) and 77.7%(470/605), respectively. No vancomycin-resistant Staphylococcus was detected. The resistance rate of Enterococcus faecium to vancomycin was 0.6%(2/312), and no vancomycin-resistant Enterococcus faecium was detected. The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus were 55.7%(1 576/2 831), 29.9%(386/1 289) and 38.5%(15/39), respectively. The incidences of carbapenem-resistance in Escherichia coli, Klebsiella pneumoniae were 1.2%(33/2 831), 17.5%(226/1 289), respectively. The resistance rates of Acinetobacter baumannii to polymyxin and tigecycline were 14.8%(55/372) and 5.9%(22/372) respectively, and those of Pseudomonas aeruginosa to polymyxin and carbapenem were 1.3%(4/315) and 18.7%(59/315), respectively. Conclusion:The surveillance results from 2016 to 2017 showed that the main pathogens of blood stream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen; the MRSA incidence was lower than other surveillance data in the same period in China; carbapenem-resistant Escherichia coli was at a low level during this surveillance, while carbapenem-resistant Klebsiella pneumoniae is on the rise.

Objective: To observe the effects of oxymatrine(OM) on the expression and release of high mobility group box 1(HMGB1) in rat pancreatic acinar cell line AR42J stimulated by hydrogen peroxide. Methods: MTT method was used to detect the effects of H₂O₂ in different concentrations on the survival of AR42J cells. AR42J cells cultured in vitro were divided into control group, H₂O₂ group and H₂O₂+ OM group. An equal volume of H₂O₂(final concentration 0.16 mmol/L) was added in H₂O₂ group and H₂O₂+ OM group, respectively, while an equal volume of triple distilled water was added in control group. In H₂O₂+ OM group, OM(final concentration 0.5 g/L)was added 0.5 h before the addition of H₂O₂, and cell samples and supernatant were collected after 24 h culture. The expression of HMGB1 protein was detected by Western blotting, the level of HMGB1 protein in cell supernatant was detected by enzyme-linked immunosorbent assay, and the intracellular distribution of HMGB1 protein was detected by immunofluorescence. Results: In the H₂O₂ group, the expression of HMGB1, the secretion of HMGB1 in the supernatant and the proportion of cytoplasmic HMGB1 in the total HMGB1 were significantly higher than those in the control group[1.04±0.04 vs 0.69±0.02, (4.84±0.13)μg/L vs (2.68±0.07)μg/L, (35.7±2.5)% vs (10.7±1.9)%], and all the differences were statistically significant (all P<0.05). After OM intervention, HMGB1 protein expression, secretion and cytoplasmic proportion were [0.82±0.02, (3.97±0.10)μg/L and (27.3±1.7)%], respectively, which were obviously lower than those in the H₂O₂ group, and all the differences were statistically significant (all P<0.05). Conclusions H₂O₂ can induce the expression and release of HMGB1 in rat pancreatic acinar cells; OM treatment could alleviate the severity of oxidative stress injuries induced by H₂O₂ in AR42J cells.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.