Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Objective:To recheck the Histoplasma capsulatum and Coccidioides sp. strains of the past by molecular identification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS). Methods:The phylogenetic relationships among the ten Histoplasma capsulatum isolates and reference strains were analyzed by multilocus sequence typing (MLST). Based on the Coi region, Coccidioides posadasii was distinguished from Coccidioides immitis accurately. MALDI-TOF MS was used to set up the MALDI-TOF MS database of Histoplasma capsulatum and Coccidioides sp. for rapid identification. In addition, hierarchical clustering of spectra was compared with MLST. Results:An unrooted dendrogram constructed with MLST showed that ten individuals of Histoplasma capsulatum were divided into three clades: Eurasia clade, Australia clade and North American class 2 clade, in agreement with the establishment by MALDI-TOF MS cluster analysis. All individuals of Coccidioides sp. were identified as Coccidioides posadasii with Coi region primers. The in-house MALDI-TOF MS database of Histoplasma capsulatum and Coccidioides posadasii was expanded and reached an identified accuracy of 100%. Conclusions:We improve the recognition of Histoplasma capsulatum and Coccidioides posadasii by molecular pathways which shows the major species or clades in Chinese mainland. The in-house MALDI-TOF MS database of Histoplasma capsulatum and Coccidioides posadasii can provide a new efficient way to identify those pathogens rapidly.

Humans ; Retroperitoneal Neoplasms ; Liposarcoma ; Calcium-Binding Proteins ; Mixed Function Oxygenases ; Membrane Proteins ; Muscle Proteins

Transcription, Genetic

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.

Objective    To investigate the effect of optimized arterial perfusion strategy on total arch replacement for acute type A aortic dissection (AAAD) with malperfusion syndrome (MPS). Methods    From 2017 to 2019, 51 patients with AAAD and MPS who had received total arch replacement with optimized arterial perfusion strategy in our hospital were included in the optimized perfusion group, including 40 males and 11 females, with an average age of 47.43±13.39 years. A total of 40 patients with AAAD and MPS who had been treated with traditional Sun's surgery were taken as the traditional control group, including 31 males and 9 females, with an average age of 50.66±12.05 years. The perioperative clinical data of the two groups were compared. Results    The preoperative baseline data of the two groups were basically consistent (P>0.05). The comparison of operative data between the optimized perfusion group and the traditional control group showed that in the optimized perfusion group, the extracorporeal circulation time, aortic occlusion time, and circulation-out cerebral perfusion time were significantly less than those in the traditional control group (223.64±65.13 min  vs. 266.77±87.04 min, 114.48±27.28 min vs. 138.20±39.89 min, 8.28±3.81 min vs. 50.53±23.60 min, all P≤0.05). The lowest intraoperative nasopharyngeal temperature in the optimized perfusion group was significantly higher than that in the traditional control group (27.10±1.18℃ vs. 23.6±3.30℃, P=0.000). Postoperative wakefulness time of the optimized perfusion group was earlier than that of the traditional control group (4.50±1.35 h vs. 5.27±1.15 h, P=0.019). The volume of blood transfusions in the optimized perfusion group was significantly less than that in the traditional control group (13.25±9.06 U vs. 16.95±7.53 U, P=0.046). There was no significant difference in ICU time and invasive ventilation time between the two groups (P>0.05). Postoperative complications of the two groups showed that the incidence of postoperative continuous renal replacement therapy in the optimized perfusion group was significantly lower than that in the traditional control group, with a statistically significant difference (21.6% vs. 42.5% P=0.003). The incidence of postoperative delirium, coma, low cardiac row syndrome and limb ischemia in the optimized perfusion group was lower than that in the traditional control group, but the difference was not statistically significant (P>0.05). The incidence of postoperative hemiplegia, sepsis, and secondary thoracotomy in the optimized perfusion group was higher than that in the traditional control group, and the difference was not statistically significant (P>0.05). Postoperative mortality in the optimized perfusion group was significantly lower than that in the traditional control group (13.7% vs. 27.5%), but the difference was not statistically significant (P=0.102). Conclusion    Optimized arterial perfusion strategy and its related comprehensive surgical technique reduce surgical trauma, shorten the operation time, reduce perioperative consumption of blood products. Postoperative wakefulness is rapid and the incidence of complications of nervous system, kidney and limb ischemia is low. Optimized arterial perfusion strategy is suitable for operation of AAAD with MPS by inhibiting the related potential death risk factors to reduce operation mortality.

Objective:To analyze the operative outcomes and postoperative pathological features of retroperitoneal leiomyosarcoma(RPLMS) undergoing surgeries.Methods:Medical records of RPLMS patients admitted to Peking University International Hospital from Jan 2015 through Dec 2020 were retrospectively reviewed.Results:Ninety-seven patients undergoing resectional surgeries were included in the study. Of whom, 49 cases were primary RPLMS. Others were recurrent sarcomas or sarcomas with incomplete resection in the first surgical intentions. The most frequent symptoms were abdominal pain and distention (30 cases) as well as lower back pain (23 cases). All patients underwent resectional surgeries with a R 0/R 1 rate of 84.5%. Sixty-four cases received extended surgeries with combined organs resection. External iliac artery resection with reconstruction were performed on 2 cases. And 19 patients underwent partial IVC resection in combination of sarcoma resection. The general postoperative morbidity was 26.8%, including 4 intestinal fistulas, 1 pancreatic fistula, 1 vesicovaginal fistula, 1 urinary fistula, 1 biliary fistula, 2 abdominal major bleeding, 7 IVC thrombosis, 3 gastroplegiaetc. One patient deceased within post-operative 30 d due to massive bleeding.Pathology found that spindle and pleomorphic cell types were most common subtypes of RPLMS. Conclusions:Surgery remains the mainstay in the treatment of RPLMS which often presents with atypical symptoms. Extended surgeries combining with multiple organ and major vascular resections could be only suggested in experienced sarcoma centers due to high risk of severe postoperative complications.

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

Objective: To analyze effect of fractured file removal from the middle third root canal on root fracture resistance using finite element analysis, which provides a theoretical basis for clinical prognosis evaluation. Methods: Two finite-element models were established, the fractured file removal model (fractured file located in the middle third of root canals, followed by ultrasonic file removal and root canal preparation) and the control model (root canal preparation only), and compressive displacement dependencies on compressive force was computed and compared with experimental data for validation. The validated finite-element models were used to analyze the stress distribution differences during the initiation, propagation and completion of the crack between fractured file removal specimen and control one. Results: The critical breaking force of the fractured file removal specimen was 406 N, and the finite element simulation result was 396 N. The critical breaking force of the control specimen was 502 N, and the finite element simulation result was 483 N. The position of crack initiation in the finite element simulation was basically consistent with that in the experiment. The experimental data of compressive test and the results of finite-element computation were in agreement, thus validating the finite-element model. In the process of continuous pressure, the stress distribution of the control root is relatively uniform, and the location of crack initiation and the direction of propagation have a certain unpredictability. Compared with the control root, the stress concentration on the root with fracture file removal was obvious, especially on edges, and the number of cracks are much more. Because of the thinner radicular wall, the crack propagation rate is faster too. Therefore, the overall root fracture resistant is decreased obviously. Conclusions During the fractured file removal procedure, amount of dentine removed should be minimized, and the edges and corners which caused by fractured file removal should be shaped to smooth in order to reduce the stress concentration and prevent the root from fracture.

A 55-year-old male patient presented with plaques on the face for more than 20 years,and no immunodeficiency diseases were diagnosed.Skin examination showed large areas of pink plaques on the nose,bilateral cheeks and upper oral lips with slight desquamation,verrucous hyperplasia on the dorsal area of the nose,and a bean-sized verrucous protuberance on the tip of the nose.Histopathological examination of the skin lesions revealed pseudoepitheliomatous hyperplasia in the epidermis and hyphae-like structures in the stratum corneum.Moreover,there was diffuse infiltration of inflammatory cells in the dermis,which mainly included neutrophils,lymphocytes,histiocytes and multinucleated giant cells.Periodic acid-Schiff (PAS)-positive spore-like structures were observed in the multinucleated giant cells.Culture of the lesional tissues on Sabouraud dextrose agar (SDA) medium showed grey-brown villous colonies.Microculture on the potato dextrose agar (PDA) medium yielded dark septate hyphae and pycnidia filled with a large number of spores.Microsphaeropsis arundinis was identified by fungal molecular biological techniques.The patient was diagnosed with cutaneous phaeohyphomycosis caused by Microsphaeropsis arundinis.The patient was treated with CO2 laser for the removal of verrucous protuberance on the tip of the nose,and oral itraconazole capsules at a dose of 200 mg twice a day.After 3-month treatment,the skin lesions subsided and the drug was withdrew.During 6-month follow-up,no relapse occurred.