Histone H3.3 phosphorylation amplifies stimulation-induced transcription.

Complex organisms can rapidly induce select genes in response to diverse environmental cues. This regulation occurs in the context of large genomes condensed by histone proteins into chromatin. The sensing of pathogens by macrophages engages conserved signalling pathways and transcription factors to coordinate the induction of inflammatory genes1-3. Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription4-7. However, how chromatin is regulated at induced genes, and what features of H3.3 might enable rapid and high-level transcription, are unknown. The amino terminus of H3.3 contains a unique serine residue (Ser31) that is absent in 'canonical' H3.1 and H3.2. Here we show that this residue, H3.3S31, is phosphorylated (H3.3S31ph) in a stimulation-dependent manner along rapidly induced genes in mouse macrophages. This selective mark of stimulation-responsive genes directly engages the histone methyltransferase SETD2, a component of the active transcription machinery, and 'ejects' the elongation corepressor ZMYND118,9. We propose that features of H3.3 at stimulation-induced genes, including H3.3S31ph, provide preferential access to the transcription apparatus. Our results indicate dedicated mechanisms that enable rapid transcription involving the histone variant H3.3, its phosphorylation, and both the recruitment and the ejection of chromatin regulators.

[Research progress in the regulation of pathogenesis and the transformation of chronic liver disease by short-chain fatty acids].

Short-chain fatty acids are metabolites of the intestinal flora and serve as the main energy source for intestinal epithelial cells. At the same time, as important signaling molecules, it regulate a variety of cellular inflammatory responses and homeostatic proliferation through receptor-dependent and independent pathways. Short-chain fatty acids regulate the gut-liver axis and thereby directly act on the liver, participating in the pathogenesis and transformation of various liver diseases, including alcoholic liver disease, metabolic dysfunction-related liver disease, autoimmune liver disease, liver fibrosis, and hepatocellular carcinoma. In addition, short-chain fatty acids can inhibit HBV DNA replication. This article reviews the research progress on the role of short-chain fatty acids in aspects of the pathogenesis and transformation of chronic liver diseases.

Morin protects chicks with T-2 toxin poisoning by decreasing heterophil extracellular traps, oxidative stress and inflammatory response.

1. Fusarium tritici widely exists in a variety of grain feeds. The T-2 toxin is the main hazardous component produced by Fusarium tritici, making a serious hazard to poultry industry. Morin, belonging to the flavonoid family, can be extracted from mulberry plants and possesses anticancer, antioxidant and anti-inflammatory compounds, but whether morin protects chicks with T-2 toxin poisoning remains unclear. This experiment firstly established a chick model of T-2 toxin poisoning and then investigated the protective effects and mechanism of morin against T-2 toxin in chicks.2. The function of liver and kidney was measured by corresponding alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (Cre) and uric acid (UA) kits. Histopathological changes were observed by haematoxylin-eosin staining. The status of oxidative stress was measured by MDA, SOD, CAT, GSH and GSH-PX kits. The mRNA levels of TNF-α, COX-2, IL-1ß, IL-6, caspase-1, caspase-3 and caspase-11 were measured by quantitative real-time PCR. Heterophil extracellular trap (HET) release was analysed by immunofluorescence and fluorescence microplate.3. The model with T-2 toxin poisoning in chicks was successfully established. Morin significantly decreased T-2 toxin-induced ALT, AST, ALP, BUN, Cre and UA, and improved T-2 toxin-induced liver cell rupture, liver cord disorder and kidney interstitial oedema. Oxidative stress analysis showed that morin ameliorated T-2 toxin-induced damage by reducing malondialdehyde (MDA), increasing superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-PX). The qRT-PCR analysis showed that morin reduced T-2 toxin-induced mRNA expressions of TNF-α, COX-2, IL-1ß, IL-6, caspase-1, caspase-3 and caspase-11. Moreover, morin significantly reduced the release of T-2 toxin-induced HET in vitro and in vivo.4. Morin can protect chicks from T-2 toxin poisoning by decreasing HETs, oxidative stress and inflammatory responses, which make it a useful compound against T-2 toxin poisoning in poultry feed.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[Update points for the 2022 edition of the European Association for the Study of Liver Diseases Clinical Practice Guidelines for the Management of Hepatic Encephalopathy and comparison with China's 2018 edition guidelines].

The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.

[The efficacy of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery].

Objective: To examine the safety and effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). Methods: The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up. Results: The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth and that the false lumen disappeared or weakened. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively (W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively (W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion: The use of thin struct bare stents for SIDSMA is safety and efficacy.

[Protection of side-branch ostium by the jailed balloon technique validated by three-dimensional optical coherence tomography].

Objective: To evaluate the protective effect of jailed balloon technique on side branch (SB) ostium using three-dimensional optical coherence tomography(OCT). Methods: This is a retrospective study. Consecutive coronary disease patients with coronary artery bifurcation lesions who underwent percutaneous coronary intervention (PCI) and completed pre-and post-procedural OCT examinations at the Chinese People's Liberation Army General Hospital from September 2019 to March 2022 were enrolled. Patients were divided into the jailed balloon technique group and the unprotected group according to the options applied for the SB. The SB ostium area difference was calculated from OCT images (SB ostium area difference=post-PCI SB ostium area-pre-PCI SB ostium area). The SB ostium area differences were compared between the two groups and compared further in the subgroup of true bifurcation lesions and non-true bifurcation lesions. In the jailed balloon group, the SB ostium area difference was compared between the active jailed balloon technique and the conventional jailed balloon technique, between the jailed balloon>2.0 mm diameter and the jailed balloon≤2.0 mm diameter, and between the higher balloon pressure (>4 atm, 1 atm=101.325 kPa) and the lower balloon pressure (≤4 atm). Multivariate linear regression analysis was used to explore the correlation between the technical parameters of the jailed balloon technique and the SB protection effect. Results: A total of 176 patients with 236 bifurcation lesions were enrolled, aged (60.7±9.3) years, and there were 128 male patients (72.7%). There were 67 patients in the jailed balloon technique group with 71 bifurcation lesions and 123 patients in the unprotected group with 165 bifurcation lesions. Fourteen patients had 2 to 3 lesions, which were treated in different ways, so they appeared in the unprotected group and the jailed balloon technique group at the same time. The area difference in SB ostium was greater in the jailed balloon group than in the unprotected group (0.07 (-0.43, 1.05)mm2 vs.-0.33 (-0.83, 0.26)mm2, P<0.001), and the results were consistent in the true bifurcation lesion subgroup (0.29 (-0.35, 0.96)mm2 vs.-0.26 (-0.64, 0.29)mm2, P=0.004), while the difference between the two groups in the non-true bifurcation lesion subgroup was not statistically significant (P=0.136). In the jailed balloon technique group, the SB ostium area difference was greater in patients treated with the active jailed balloon technique than in those treated with the conventional jailed balloon technique ((0.43±1.36)mm2 vs. (-0.22±0.52)mm2, P=0.013). The difference in SB ostium area was greater in those using>2.0 mm diameter jailed balloons than in those using≤2.0 mm diameter jailed balloons (0.25 (-0.51, 1.31) mm2 vs.-0.01 (-0.45, 0.63) mm2, P=0.020), while SB ostium area difference was similar between those endowed with higher balloon pressure (>4 atm) compared to those with lower balloon pressure (≤4 atm) (P=0.731). Multivariate linear regression analysis showed that there was a positive correlation between jailed balloon diameter and SB ostium area difference (r=0.344, P=0.019). Conclusions: The jailed balloon technique significantly protects SB ostium, especially in patients with true bifurcation lesions. The active jailed balloon technique and larger diameter balloons may provide more protection to the SB.

Effect of the compound bacterial agent on microbial community of the aerobic compost of food waste.

In our study, we used 16SrRNA and ITS to investigate the microbial community composition and the effect of compound bacterial agent on the microbial community composition in the aerobic composting process of food waste (FW). At the bacterial level, the main phyla of Group A (compost naturally) were Proteobacteria and Firmicutes, and the main species were Pseudomonas_sp._GR7, Bacillus licheniformis and Pediococcus acidilactici. The main phyla of Group B (compost with compound bacterial agent) were Proteobacteria, Firmicutes and Streptophyta, and the main species were Klebsiella pneumoniae, Cronobacter sakazakii, Macrococcus caseolyticus, Enterococcus faecalis, Citrobacter freundii and Bacillus velezensis. It is worth noting that M. caseolyticus may be able to improve the effect of odour which is an important sensory index during aerobic composting. At the fungal level, the main phylum of both Groups A and B was Ascomycota, and the main species of Group A were Paecilomyces variotii, Byssochlamys spectabilis and Aspergillus fumigatus. The main species of Group B were Ogataea polymorpha and Millerozyma farinosa. Finally, the degradation rate of Group B was 81% that was about 15% higher than that of Group A, indicating that the compound bacterial agent could effectively improve the degradation rate and the composting process, while the low abundance of the compound bacterial agent in the composting process might be due to the small initial addition or the inhibition of other bacteria or fungi in the composting process.

[Occurrence and recovery of adverse drug reactions of preventive treatment in elderly population with latent tuberculosis infection].

Objective: To evaluate the occurrence and recovery of adverse drug reactions (ADRs) of preventive treatment in the elderly population with latent tuberculosis infection (LTBI). Methods: A total of 2 583 elderly patients with LTBI were recruited in Zhongmu, Henan Province from July 1 to October 17, 2015. Face-to-face surveys and physical examinations were used to obtain the basic information of the participants, and the body mass index (BMI) was calculated. Fasting venous blood was collected from the participants for blood biochemical and routine blood tests. The random numbers were generated by Excel 2010, and the participants were divided into group A (1 284 cases) and group B (1 299 cases) by simple randomization. Both group A and group B received combination treatment of isoniazid and rifapentine. Group A was treated for 8 weeks with weekly doses of isoniazid at 15 mg/kg and 900 mg for those with body weight ≤50 and>50 kg, respectively, and the doses of rifapentin were 750 and 900 mg, respectively. Group B was treated twice a week for 6 weeks, the doses of isoniazid in patients with body weight ≤50 and>50 kg were [600-(50-body weight)×15] (rounded up) and 600 mg, respectively, and the doses of rifapentin were 600 and 450 mg, respectively. During the treatment period, doctors observed, inquired about and recorded symptoms related to ADRs, and blood biochemical and routine blood tests were performed at 4 weeks after taking the drug, the end of the treatment, and 3 months after the end of the treatment. The patients with ADRs were treated accordingly by severity. The ADRs and graded treatment outcomes of LTBI patients in group A and group B were compared. Results: The ageï¼»M（Q1，Q3）］of the participants was 60 (55,65) years old, and 54.7% (1 412/2 583) were males. There were no statistical differences in age, gender, BMI and baseline biochemical indexes between groups A and B (all P values>0.05). The incidence of ADRs in group A and group B were 18.5% (237/1 279) and 16.3% (209/1 279), respectively, and those with alanine aminotransferase (ALT)≥5 ULN accounted for 0.8% (7/931) and 1.1% (11/987), aspartate aminotransferase (AST)≥5 ULN accounted for 0.3% (3/931) and 0.3% (3/987), respectively, and there were no statistically significant differences (all P values>0.05). There were 7 and 11 patients with ALT≥5 ULN in group A and group B, respectively, and 3 patients with AST≥5 ULN for each group, respectively. After treatment, except for 2 patients with ALT≥5 ULN in group B, ALT and AST levels in all the other patients returned to normal. There were 15 and 10 patients with abnormal white blood cell count in group A and group B, respectively, and 10 and 9 patients returned to normal after treatment. Conclusion: LTBI preventive treatment has a high incidence of adverse drug reactions, but it can be effectively controlled through active monitoring and graded management.

[Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs].

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.