[Vertebral fractures combined with prolonged activated partial prothrombin time: A case report].

With the development of modern medical standards, autoimmune diseases and their associated successive osteoporosis have received increasing attention in recent years. Patients with autoimmune diseases, due to the characteristics of the disease and the prolonged use of glucocorticoid hormone therapy, may affect the bone formation and bone absorption of the patient, followed by severe successive osteoporosis, thereby increasing the risk of osteoporotic vertebral fractures. Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures. Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases. Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures. However, due to the operation of spinal puncture during the operation, there are serious surgical risks such as bone cement leakage, spinal epidural hemorrhage, subdural hemorrhage, and subarachnoid hemorrhage in both PVP and PKP. As a result, it is necessary to evaluate the patient' s body before surgery carefully, especially in the case of blood coagulation. This article reports a case of autoimmune disease patient admitted to Peking University People' s Hospital due to lumbar 4 vertebral compression fracture combined with Sjögren' s syndrome. The patient' s preoperative examination showed that the activated partial thromboplastin time (APTT) was significantly prolonged. After completing the APTT extended screening experiment and lupus anticoagulant factor testing, the multi-disciplinary team (MDT) of Peking University People' s Hospital jointly discussed the conclusion that the patient' s test results were caused by an abnormal self-immunity anti-copulant lupus (LAC). Based on the results of the laboratory examination, the patient was considered to be diagnosed with combined antiphospholipid syndrome (APS). For such patients, compared with the patient' s tendency to bleed, we should pay more attention to the risk of high blood clotting in the lower limbs of the patient, pulmonary clots and so on. With timely anti-coagulation treatment, the patient safely passed the peripheral period and was successfully discharged from the hospital. Therefore, for patients with autoimmune diseases with prolonged APTT in the perioperative period, doctors need to carefully identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

Propionic Acid Driven by the Lactobacillus johnsonii Culture Supernatant Alleviates Colitis by Inhibiting M1 Macrophage Polarization by Modulating the MAPK Pathway in Mice.

In this study, we investigated the effects of Lactobacillus johnsonii on the mouse colitis model. The results showed that the supernatant of the L. johnsonii culture alleviated colitis and remodeled gut microbiota, represented by an increased abundance of bacteria producing short-chain fatty acids, leading to an increased concentration of propionic acid in the intestine. Further studies revealed that propionic acid inhibited activation of the MAPK signaling pathway and polarization of M1 macrophages. Macrophage clearance assays confirmed that macrophages are indispensable for alleviating colitis through propionic acid. In vitro experiments showed that propionic acid directly inhibited the MAPK signaling pathway in macrophages and reduced M1 macrophage polarization, thereby inhibiting the secretion of pro-inflammatory cytokines. These findings improve our understanding of how L. johnsonii attenuates inflammatory bowel disease (IBD) and provide valuable insights for identifying molecular targets for IBD treatment in the future.

Limosilactobacillus mucosae-derived extracellular vesicles modulates macrophage phenotype and orchestrates gut homeostasis in a diarrheal piglet model.

The diarrheal disease causes high mortality, especially in children and young animals. The gut microbiome is strongly associated with diarrheal disease, and some specific strains of bacteria have demonstrated antidiarrheal effects. However, the antidiarrheal mechanisms of probiotic strains have not been elucidated. Here, we used neonatal piglets as a translational model and found that gut microbiota dysbiosis observed in diarrheal piglets was mainly characterized by a deficiency of Lactobacillus, an abundance of Escherichia coli, and enriched lipopolysaccharide biosynthesis. Limosilactobacillus mucosae and Limosilactobacillus reuteri were a signature bacterium that differentiated healthy and diarrheal piglets. Germ-free (GF) mice transplanted with fecal microbiota from diarrheal piglets reproduced diarrheal disease symptoms. Administration of Limosilactobacillus mucosae but not Limosilactobacillus reuteri alleviated diarrheal disease symptoms induced by fecal microbiota of diarrheal piglets and by ETEC K88 challenge. Notably, Limosilactobacillus mucosae-derived extracellular vesicles alleviated diarrheal disease symptoms caused by ETEC K88 by regulating macrophage phenotypes. Macrophage elimination experiments demonstrated that the extracellular vesicles alleviated diarrheal disease symptoms in a macrophage-dependent manner. Our findings provide insights into the pathogenesis of diarrheal disease from the perspective of intestinal microbiota and the development of probiotic-based antidiarrheal therapeutic strategies.

Whole intestinal microbiota transplantation is more effective than fecal microbiota transplantation in reducing the susceptibility of DSS-induced germ-free mice colitis.

Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of inflammatory bowel disease (IBD). Previous studies have reported that compared with FMT, whole intestinal microbiota transplantation (WIMT) can more precisely replicate the community structure and reduce the inflammatory response of the host. However, it remains unclear whether WIMT is more effective in alleviating IBD. To examine the efficacy of WIMT and FMT in the intervention of IBD, GF (Germ-free) BALB/c mice were pre-colonized with whole intestinal microbiota or fecal microbiota before being treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by both WIMT and FMT, as demonstrated by the prevention of body weight loss and decreased the Disease activity index and histological scores in mice. However, WIMT's anti-inflammatory effect was superior to that of FMT. In addition, the inflammatory markers myeloperoxidase (MPO) and eosinophil peroxidase were dramatically downregulated by WIMT and FMT. Furthermore, the use of two different types of donors facilitated the regulation of cytokine homeostasis in colitis mice; the level of the pro-inflammatory cytokine IL-1ß in the WIMT group was significantly lower than that in the FMT group, while the level of the anti-inflammatory factor IL-10 was significantly higher than that in the FMT group. Both groups showed enhanced expression of occludin to protect the intestinal barrier in comparison with the DSS group, and the WIMT group demonstrated considerably increased levels of ZO-1. The sequencing results showed that the WIMT group was highly enriched in Bifidobacterium, whereas the FMT group was significantly enriched in Lactobacillus and Ochrobactrum. Correlation analysis revealed that Bifidobacterium was negatively correlated with TNF-α, whereas Ochrobactrum was positively correlated with MPO and negatively correlated with IL-10, which might be related to different efficacies. Functional prediction using PICRUSt2 revealed that the FMT group was considerably enriched in the L-arginine biosynthesis I and L-arginine biosynthesis IV pathway, whereas the WIMT group was enriched in the L-lysine fermentation to acetate and butanoate pathway. In conclusion, the symptoms of colitis were subsided to varying degrees by the two different types of donors, with the WIMT group being more effective than the FMT group. This study provides new information on clinical interventions for IBD.

Analysis of the effectiveness of the application of pelvic floor rehabilitation exercise and the factors influencing its self-efficacy in postoperative patients with cervical cancer.

Objective: To analyze the application effect of pelvic floor rehabilitation exercise in postoperative patients with cervical cancer and the factors influencing their self-efficacy. Methods: 120 postoperative patients with cervical cancer from January 2019 to January 2022 from the Department of Rehabilitation, Aeronautical Industry Flying Hospital, Bayi Orthopaedic Hospital and Southwest Medical University Affiliated Hospital of Traditional Chinese Medicine, and the Department of Obstetrics and Gynecology, Chengdu Seventh People's Hospital, and the Department of Oncology, Sichuan Provincial People's Hospital were selected for the study. They were divided into routine group (n=44, applied routine care) and exercise group (n=76, applied routine care + pelvic floor rehabilitation exercise) according to the different perioperative care programs. The perioperative indicators, bladder function recovery rate and urinary retention incidence, urodynamic indicators, and pelvic floor distress inventory-short form 20 (PFDI-20) scores were compared between the 2 groups. The general data, PFDI-20 scores and broome pelvic muscle self-efficacy scale (BPMSES) scores of patients in the exercise group were investigated and analyzed individually to investigate the factors influencing the self-efficacy of patients with pelvic floor rehabilitation exercise after cervical cancer surgery. Results: The time of first anal exhaust, urine tube retention and hospitalization after surgery were shorter in the exercise group than in the routine group (P<0.05). The bladder function grade I rate after surgery was more in the exercise group than in the routine group, and the urinary retention incidence was lower than that in the routine group (P<0.05). At 2 weeks after exercise, bladder compliance and bladder detrusor systolic pressure were higher in both groups than before exercise, and they were higher in the exercise group than in the routine group (P<0.05). There was no significant difference in urethral closure pressure within and between the two groups (P>0.05). At 3 months after surgery, the PFDI-20 scores were higher in both groups than before surgery, and the exercise group was lower than the routine group (P<0.05).The BPMSES score for the exercise group was (103.33 ± 9.16). Marital status, residence and PFDI-20 scores were influential factors in the self-efficacy level of patients undergoing pelvic floor rehabilitation exercise after cervical cancer surgery (P<0.05). Conclusion: Implementing pelvic floor rehabilitation exercise for postoperative patients with cervical cancer can speed up the recovery of pelvic organ function and reduce the occurrence of postoperative urinary retention. Marital status, residence and PFDI-20 scores were influential factors in the self-efficacy level of patients undergoing pelvic floor rehabilitation exercise after cervical cancer surger, medical staff need to incorporate these clinical features to provide targeted nursing interventions to enhance patient compliance with training and improve postoperative survival quality.

The complete mitochondrial genome of Pseudofabraea citricarpa (Dermateaceae: Helotiales) causing Citrus target spot.

Pseudofabraea citricarpa (Dermateaceae: Helotiales) is known as a significant pathogen causing Citrus target spot disease and results in profound yield loss. In the present study, the complete mitochondrial genome (mitogenome) determined based on next-generation sequencing technology. The circular mitogenome (56,935 bp) comprised 14 conserved protein-coding genes (PCGs), 16 ORFs, two ribosomal RNA genes (rns and rnl), one non-coding RNA gene (rnpB), one ribosomal protein S3 (rps3) and 28 transfer RNA (tRNA) genes. The overall base composition is as follows: 36.08% A, 35.25% T, 13.04% C, and 15.63% G, with a GC content of 28.70%. The phylogenetic analysis shows that P. citricarpa, belonging to Dermateaceae, forms a separate clade and is sister to Sclerotiniaceae. The mitogenome of P. citricarpa reported in this study provides more molecular data for further research on the evolutionary relationships of Helotiales.

Fecal bacteria-free filtrate transplantation is proved as an effective way for the recovery of radiation-induced individuals in mice.

Background: Ionizing radiation can cause intestinal microecological dysbiosis, resulting in changes in the composition and function of gut microbiota. Altered gut microbiota is closely related to the development and progression of radiation-induced intestinal damage. Although microbiota-oriented therapeutic options such as fecal microbiota transplantation (FMT) have shown some efficacy in treating radiation toxicity, safety concerns endure. Therefore, fecal bacteria-free filtrate transplantation (FFT), which has the potential to become a possible alternative therapy, is well worth investigating. Herein, we performed FFT in a mouse model of radiation exposure and monitored its effects on radiation damage phenotypes, gut microbiota, and metabolomic profiles to assess the effectiveness of FFT as an alternative therapy to FMT safety concerns. Results: FFT treatment conferred radioprotection against radiation-induced toxicity, representing as better intestinal integrity, robust proinflammatory and anti-inflammatory cytokines homeostasis, and accompanied by significant shifts in gut microbiome. The bacterial compartment of recipients following FFT was characterized by an enrichment of radioprotective microorganisms (members of family Lachnospiraceae). Furthermore, metabolome data revealed increased levels of microbially generated short-chain fatty acids (SCFAs) in the feces of FFT mice. Conclusions: FFT improves radiation-induced intestinal microecological dysbiosis by reshaping intestinal mucosal barrier function, gut microbiota configurations, and host metabolic profiles, highlighting FFT regimen as a promising safe alternative therapy for FMT is effective in the treatment of radiation intestinal injury.

Non-line-of-sight imaging and tracking of moving objects based on deep learning.

Detection of objects outside the line of sight remains a challenge in many practical applications. There have been various researches realizing 2D or 3D imaging of static hidden objects, whose aim are to improve the resolution of reconstructed images. While when it comes to the tracking of continuously moving objects, the speed of imaging and the accuracy of positioning becomes the priorities to optimize. Previous works have achieved centimeter-level or even higher precision of positioning through marking coordinates in intervals of 3 seconds to tens of milliseconds. Here a deep learning framework is proposed to realize the imaging and dynamic tracking of targets simultaneously using a standard RGB camera. Through simulation experiments, we firstly use the designed neural network to achieve positioning of a 3D mannequin with sub-centimeter accuracy (relative error under 1.8%), costing only 3 milliseconds per estimation in average. Furthermore, we apply the system to a physical scene to successfully recover the video signal of the moving target, intuitively revealing its trajectory. We demonstrate an efficient and inexpensive approach that can present the movement of objects around the corner in real time, profiting from the imaging of the NLOS scene, it is also possible to identify the hidden target. This technique can be ultilized to security surveillance, military reconnaissance, autonomous driving and other fields.

NH2-MIL-125(Ti) modified graphitic carbon nitride with carbon vacancy for efficient photocatalytic NO removal.

This paper reports the application of NH2-MIL-125(Ti) modified carbon nitride Cv-C3N4 with carbon vacancies in the removal of NO. We performed a series of characterizations of the complex and compared various ratios with the individual components. The results of UV spectrum analysis show that the composite's range of light absorption expanded due to the modification of Ti metal-organic framework. Furthermore, the results of photocurrent and electrical impedance indicate the compound has a better ability to generate and transfer electrons. The increase in the compound's NO removal efficiency (up to 63%) indicates that MOF has a positive effect on Cv-C3N4 modification-a good method for photocatalysis. Moreover, the compound can promote photocatalysis in a favorable direction.

Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.

In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.

Bi2WO6 quantum dots with oxygen vacancies combined with g-C3N4 for NO removal.

Semiconductor materials have been used for photocatalytic degradation since they were discovered to be useful for photocatalytic degradation. Many studies have been researched to improve the efficiency of photocatalytic degradation. Among them, the introduction of vacancies to improve the photocatalytic efficiency has been verified to be a more feasible method. In this study, we combined two-dimensional (2D) graphite carbon nitride (g-C3N4) nanosheets with oxygen-containing vacancy zero-dimensional (0D) Bi2WO6 (BWO-OV) quantum dots to prepare 2D-0D g-C3N4/Bi2WO6-OV composite catalyst. The use of Bi2WO6 containing oxygen vacancies enhanced the absorption of light and increased the generation of photogenerated carriers. In addition, the formation of heterojunction and the vacancy structure of Bi2WO6 promote the life of photogenerated carriers and improve the catalytic effect of the catalyst. This structure shows high efficiency in removing low concentration (0.5 ppm) of nitric oxide (NO) at room temperature. The efficiency of the composite catalyst is much higher than g-C3N4 or BWO-OV, and better than the composite g-C3N4/Bi2WO6 without oxygen vacancies. When applied to NO removal, the composite g-C3N4/Bi2WO6-OV-10 showed the best catalytic activity which was up to 61.2%. At the same time, five cycles of experiments show that the material has excellent stability.

Modification strategies to improve the membrane hemocompatibility in extracorporeal membrane oxygenator (ECMO).

ABSTRACT: Since extracorporeal membrane oxygenator (ECMO) has been utilized to save countless lives by providing continuous extracorporeal breathing and circulation to patients with severe cardiopulmonary failure. In particular, it has played an important role during the COVID-19 epidemic. One of the important composites of ECMO is membrane oxygenator, and the core composite of the membrane oxygenator is hollow fiber membrane, which is not only a place for blood oxygenation, but also is a barrier between the blood and gas side. However, the formation of blood clots in the oxygenator is a key problem in the using process. According to the study of the mechanism of thrombosis generation, it was found that improving the hemocompatibility is an efficient approach to reduce thrombus formation by modifying the surface of materials. In this review, the corresponding modification methods (surface property regulation, anticoagulant grafting, and bio-interface design) of hollow fiber membranes in ECMO are classified and discussed, and then, the research status and development prospects are summarized.

New Disubstituted Quindoline Derivatives Inhibiting Burkitt's Lymphoma Cell Proliferation by Impeding c-MYC Transcription.

The c-MYC oncogene is overactivated during Burkitt's lymphoma pathogenesis. Targeting c-MYC to inhibit its transcriptional activity has emerged as an effective anticancer strategy. We synthesized four series of disubstituted quindoline derivatives by introducing the second cationic amino side chain and 5-N-methyl group based on a previous study of SYUIQ-5 (1) as c-MYC promoter G-quadruplex ligands. The in vitro evaluations showed that all new compounds exhibited higher stabilities and binding affinities, and most of them had better selectivity (over duplex DNA) for the c-MYC G-quadruplex compared to 1. Moreover, the new ligands prevented NM23-H2, a transcription factor, from effectively binding to the c-MYC G-quadruplex. Further studies showed that the selected ligand, 7a4, down-regulated c-MYC transcription by targeting promoter G-quadruplex and disrupting the NM23-H2/c-MYC interaction in RAJI cells. 7a4 could inhibit Burkitt's lymphoma cell proliferation through cell cycle arrest and apoptosis and suppress tumor growth in a human Burkitt's lymphoma xenograft.

Conformation Selective Antibody Enables Genome Profiling and Leads to Discovery of Parallel G-Quadruplex in Human Telomeres.

G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel single-chain variable fragment (scFv) antibody, D1, with high binding selectivity for parallel G-quadruplexes in vitro and in vivo. Genome-wide chromatin immunoprecipitation using D1 and deep-sequencing revealed the consensus sequence for parallel G-quadruplex formation, which is characterized by G-rich sequence with a short loop size (<3 nt). By using D1, telomeric parallel G-quadruplex was identified and its formation was regulated by small molecular ligands targeting and telomere replication. Together, parallel G-quadruplex specific antibody D1 was found to be a valuable tool for determination of G-quadruplex and its conformation, which will prompt further studies on the structure of G-quadruplex and its biological implication in vivo.

Quinazoline derivative QPB-15e stabilizes the c-myc promoter G-quadruplex and inhibits tumor growth in vivo.

The ribozyme-sensitive element NHE-III1 in the P1 promoter region of the important proto-oncogene c-myc contains many guanine (G)-rich sequences. Induction and stabilization of the G-quadruplex formed by NHE-III1 can downregulate c-myc expression. In the present study, we found that QPB-15e, a quinazoline derivative designed and synthesized by our laboratory, binds to and stabilizes the c-myc G-quadruplex in vitro, thereby inhibiting double-stranded DNA replication, downregulating c-myc gene expression and arresting cancer cell proliferation. PCR termination experiments showed that QPB-15e blocked double-stranded DNA replication by inducing or stabilizing the c-myc G-quadruplex. FRET-melting further confirmed that QPB-15e improved the stability of the G-quadruplex, and CD spectroscopy indicated that the compound interacted directly with the G-rich sequence. In competitive dialysis experiments, QPB-15e bound preferentially to quadruplex DNA in various structures, especially the G-quadruplex within the c-myc promoter region. Moreover, QPB-15e reduced the weights and volumes of tumors transplanted into nude mice. These findings strongly suggest that QPB-15e is a c-myc G-quadruplex ligand with anti-tumor properties, and may be efficacious for treating cancer in humans.

New quinazoline derivatives for telomeric G-quadruplex DNA: effects of an added phenyl group on quadruplex binding ability.

To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [17]. These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond. Studies showed that these quinazoline derivatives were effective and selective telomeric G-quadruplex ligands. With this encouragement, here we synthesized a series of N-(2-(quinazolin-2-yl)phenyl)benzamide (QPB) compounds as modified quinazoline derivatives. In this modification, a phenyl group was introduced to the aromatic core. The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G-quadruplex DNA than LZ-11, the most potential compound of reported quinazoline derivatives. Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied.

Disubstituted quinazoline derivatives as a new type of highly selective ligands for telomeric G-quadruplex DNA.

A series of 2,4-disubstituted quinazoline derivatives found to be a new type of highly selective ligand to bind with telomeric G-quadruplex DNA, and their biological properties were reported for the first time.Their interactions with telomeric G-quadruplex DNA were evaluated by using fluorescence resonance energy transfer (FRET) melting assay, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and molecular modeling. Our results showed that these derivatives could well recognize G-quadruplex and have high selectivity toward G-quadruplex over duplex DNA. The structure-activity relationships (SARs) study revealed that the disubstitution of quinazoline and the length of the amide side chain were important for its interaction with the G-quadruplex. Furthermore, telomerase inhibition of the quinazoline derivatives and their cellular effects were studied.