Pezizomycotina species associated with rotten plant materials in Guizhou Province, China.

Nine Pezizomycotina strains were isolated from rotten dead branches and leaves collected from Guizhou Province. To obtain their accurate taxonomic placement, we provided the morphological characteristics of conidiophore cells and conidia. Phylogenetic relationships, based on ITS, rpb2, SSU, LSU and tub2 gene sequences, confirmed our strains represented three novel species, Peglioniafalcata, Neoascochytapseudofusiformis and Neomicrosphaeropsiscylindrica. Peglioniafalcata produced falcate conidia and Neoa.pseudofusiformis generated fusiform conidia, while Neom.cylindrica possessed cylindrical conidia. The phylogenetic results also supported them as novel taxa. All the new species in the present study were found as saprophytic on forest litter with high rainfall, which suggest they may have a certain effect on nutrient decomposition and redistribution in forest ecosystems. Thus, it opened a way for further research on related ecological roles and their application production.

Intrauterine chilled saline instillation reduces endometrial impairment on MRI after ultrasound-guided percutaneous microwave ablation of uterine adenomyosis.

OBJECTIVE: To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. METHODS: An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. RESULTS: The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2-139.6%) and 99.7 ± 15.7% (range: 71.5-129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort. CONCLUSION: Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis. CRITICAL RELEVANCE STATEMENT: This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice. KEY POINTS: Endometrial impairment occurs in the PMWA treatment of adenomyosis. Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis. An intrauterine catheter is a practical endometrial protecting method during thermal ablation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090 .

SMIM1 absence is associated with reduced energy expenditure and excess weight.

BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Cdk5 activation promotes Cos-7 cells transition towards neuronal-like cells.

Objectives: Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear. Methods: Cdk5 kinase activity was measured by [γ-32P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa. Results: P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression. Conclusion: p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.

Ultrasound-guided percutaneous microwave ablation for adenomyosis with abnormal uterine bleeding: clinical outcome and associated factors.

OBJECTIVE: To investigate the factors affecting the efficacy of ultrasound (US)-guided percutaneous microwave ablation (PMWA) for adenomyosis with abnormal uterine bleeding (AUB-A). METHODS: Baseline data of patients with AUB-A who underwent US-guided PMWA treatment between October 2020 and October 2021, including demography characteristics, laboratory and imaging examination results were retrospectively analyzed. 3D reconstruction of magnetic resonance imaging (MRI) was applied to quantitatively assess the local treatment responses, including ratio of non-perfusion volume to adenomyosis volume (NPVr), ablation rate of the endometrial-myometrial junction (EMJ), and surface area (SA) of the ablated part of the EMJ. Patients were followed up at 3, 6, and 12 months after treatment, and divided into two groups: group with complete relief (CR), and group with partial relief (PR) or no relief (NR). Data were compared between them. RESULTS: Thirty-one patients were analyzed with a mean age of 38.7 ± 6.8 years (range: 24-48): 48.4% (15/31), 63.3% (19/30), and 65.5% (19/29) achieved CR at 3, 6, and 12 months, respectively. In univariate analysis, compared with the PR/NR group, serum CA125 levels were significantly lower in CR group at 3 months, while ablation rates of EMJ and SA of the ablated part of the EMJ were significantly higher at the three time points. Other baseline characteristics and NPVr did not differ between the two groups. CONCLUSION: Baseline CA125 and ablation rate of the EMJ and SA of the ablated part of the EMJ are associated with the outcome of AUB-A patients after US-guided PMWA treatment.

Uterine artery embolization combined with percutaneous microwave ablation for the treatment of prolapsed uterine submucosal leiomyoma: A case report.

BACKGROUND: Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia. However, an alternative treatment approach is needed for patients who cannot tolerate general anesthesia. We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia. CASE SUMMARY: A 46-year-old female suffered from abnormal uterine bleeding, severe anemia, and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma. She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency. A new individualized combined treatment, consisting uterine artery embolization (UAE), percutaneous microwave ablation (PMWA) of the pedicle and the endometrium, and transvaginal removal of the leiomyoma by twisting, was performed. The lesion was completely removed successfully under local anesthesia without any major complications. The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life. CONCLUSION: UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.

Efficacy and safety of percutaneous microwave ablation for adenomyosis in the posterior uterine wall.

OBJECTIVE: To evaluate the efficacy and safety of percutaneous microwave ablation (PMWA) for treating adenomyosis in the posterior uterine wall. METHODS: Thirty-six patients with symptomatic adenomyosis in the posterior uterine wall who had been subjected to PMWA were retrospectively enrolled in this study. 20 patients who had no ideal transabdominal puncture path due to the retroverted or retroflexed uterine position were treated with PMWA combined with Yu's uteropexy (Group 1). The other 16 patients were treated with PMWA only (Group 2). The non-perfused volume (NPV) ratio, symptomatic relief rate, recurrence rate, changes in clinical symptom scores, economic cost, and complications were compared. RESULTS: The mean NPV ratio for the 36 patients was 90.2±18.3%, and the percentage of patients who obtained complete relief of dysmenorrhea and menorrhagia was 81.3% (26/32), and 69.6% (16/23) respectively. The recurrence rate was 11.1% (4/36). No major complication was observed. Minor complications included lower abdominal pain, fever, vaginal discharge, nausea, and/or vomiting after ablation, with incidences of 55.6%, 41.7%, 47.2%, and 19.4% respectively. Subgroup analysis showed no significant difference in the median value of NPV ratio, symptomatic relief rate of dysmenorrhea and menorrhagia, changes in clinical symptom scores, recurrence rate and economic cost between the two groups (all p > 0.05). CONCLUSION: PMWA is an effective and safe treatment for adenomyosis in the posterior uterine wall. ADVANCES IN KNOWLEDGE: This study focused on the ultrasound-guided PMWA treatment for adenomyosis in the posterior uterine wall. Yu's uteropexy, a new ancillary technique allowing safe PMWA for deep posterior uterine wall lesions in retroverted uterus, expanded the indications of PMWA for symptomatic adenomyosis.

Monitoring the in vivo siRNA release from lipid nanoparticles based on the fluorescence resonance energy transfer principle.

The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization. However, the in vivo distribution and release of siRNA still cannot be effectively monitored. In this study, based on the fluorescence resonance energy transfer (FRET) principle, a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds (Au-DR-siRNA), which were then wrapped with lipid nanoparticles (LNPs) for monitoring the release behaviour of siRNA in vivo. The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells, the fluorescence of Cy5 would change from quenched state to activated state, showing the location and time of siRNA release. Besides, the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds. Therefore, this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA, but also a siRNA delivery system for treating and diagnosing tumors.

Clinical and pathological characteristics of primary IgA nephropathy patients with different blood types / 中国医师杂志

Objective:To investigate the differences of clinical data and pathological changes in patients with primary IgA nephropathy (IgAN) with different blood types.Methods:The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the People's Hospital of Ningxia Hui Autonomous Region from May 2016 to May 2021 were collected. They were divided into groups A, O, B and AB according to blood group. The clinical manifestations and pathological changes of the four groups during renal biopsy were analyzed.Results:A total of 258 patients with primary IgAN were included, including 87 cases of type A, 74 cases of type O, 72 cases of type B and 25 cases of type AB. The male to female ratio was 1.34∶1, and the median age was 36 (29, 47) years old. There was no significant difference in age, sex, blood pressure, hemoglobin and renal function among the four groups (all P>0.05). Neutrophil gelatinase-associated lipocalin (NGAL) in patients with type A and B was higher than other groups (all P<0.05). There were no significant differences in mesangial cell hyperplasia (M), capillary cell hyperplasia (E), glomerular segmental sclerosis (S), renal tubule atrophy/interstitial fibrosis (T), crescent body (C) lesions and proportion of sclerosed glomeruli among the four groups (all P>0.05). Subgroup analysis by gender showed that the hemoglobin, uric acid and creatinine of male patients were higher than those of female patients (all P<0.05), but the estimated glomerular filtration rate (eGFR) and urinary protein had no statistical significance (all P>0.05). Women with blood type A and O were heavier than men under microscope. The pathological manifestations of M, E, S and C lesions in women with type A blood were heavier than those in men, and S and T lesions in men with type B blood were heavier than those in women. There was no significant difference in the general baseline data, inflammation and kidney indexes between the four groups of men and women (all P>0.05). Pathologically, the M lesions of men with B blood group were more severe than those of other blood groups, while the S and T lesions of women with B blood group were less severe than those of other blood groups. Conclusions:The clinical and pathological manifestations of IgAN women with type A are heavier, the pathological manifestations of IgAN women with type B are lighter, but the pathological lesions of IgAN men with type B are heavier.

Lipid nanoparticles produce chimeric antigen receptor T cells with interleukin-6 knockdown in vivo.

Chimeric receptor T cells (CAR-T) can effectively cure leukemia; however, there are two limitations: a complicated preparation process ex vivo and cytokine release syndrome (CRS). In this study, we constructed a lipid nanoparticle system modified by CD3 antibody on the surface, loading with the plasmid containing the combination gene of interleukin 6 short hairpin RNA (IL-6 shRNA) and CD19-CAR (AntiCD3-LNP/CAR19 + shIL6). The system targeted T cells by the mediation of CD3 antibody and stably transfected T cells to transform them into CAR-T cells with IL-6 knockdown, thus killing CD19-highly expressed leukemia tumor cells and reducing CRS caused by IL-6. In vivo experiments showed that AntiCD3-LNP/CAR19 + shIL6 could stably transfect T cells and produce CAR-T within 90 days to kill the tumor. This significantly prolonged the survival time of leukemia model mice and demonstrated the prepared LNP exhibited the same anti-tumor effect as the traditional CAR-T cells prepared ex vivo. In this study, CAR-T cells were directly produced in vivo after intravenous injection of the lipid nanoparticles, without the need of using the current complex process ex vivo. Additionally, IL-6 expression was silenced, which would be helpful to reduce the CRS and improve the safety of CAR-T therapy. This method improves the convenience of using CAR-T technology and is helpful in further promoting the clinical application of CAR-T.

Ultrasound-guided microwave ablation for symptomatic abdominal wall endometriosis and treatment response evaluation with contrast-enhanced imaging: The first experience.

INTRODUCTION: Abdominal wall endometriosis (AWE) is a relatively uncommon condition associated with diagnostic and therapeutic difficulties among all the extra pelvic endometriosis. The main therapies include surgery and oral contraceptive administration. Percutaneous cryoablation and high intensity focused ultrasound (HIFU) are also proven to be valid alternatives. Microwave ablation (MWA) as one of the thermal ablation methods has not been applied in the treatment of AWE yet. Herein the feasibility of ultrasound (US) -guided MWA for AWE was explored and treatment response evaluation was carried out using contrast-enhanced imaging. METHODS: Three consecutive patients who underwent US-guided MWA for AWE with typical symptoms were included in this retrospective study. US, magnetic resonance imaging (MRI), laboratory tests, and US-guided core-needle biopsy were conducted for pre-treatment assessment and ruling out malignancy. The interventional procedure was carried out under local anesthesia with MWA and the output power was 60w. Post-treatment contrast-enhanced ultrasound (CEUS) was performed to evaluate the instant treatment response. The follow-up intervals were 1 month, 6 months, and 12 months after treatment. The clinical symptoms and condition of AWE lesions were recorded in each follow-up. RESULTS: The MWA procedure was completed in all the patients with no blood perfusion inside each lesion by instant CEUS after treatment. The mean ablation time was 687 seconds (s) for a single patient (ranged from 660s to 742s). Clinical symptoms were relieved evidently at the end of the follow-up. The pain according to the visual analogue scale (VAS) decreased from 4-6 before treatment to 0-2 after treatment. Mild to moderate complications included slightly abdominal pain and fat liquefaction occurred. In terms of technical outcomes, the volume of all six lesions reduced in different degrees at the end of follow-up (ranged: 16.6% to 100%). CONCLUSION: US-guided MWA may be a feasible and promising approach for symptomatic AWE.

Sequential thermal ablation in combination with sclerotherapy using lauromacrogol as a successful translative therapy for an unresectable huge biliary cystadenocarcinoma: The first experience assisted by contrast-enhanced ultrasound.

Biliary cystadenocarcinoma (BCAC) is an extremely rare intrahepatic cystic tumor. Patients usually present with nonspecific symptoms such as abdominal pain, abdominal distention, and abdominal mass. This tumor occurs most commonly in the left hemiliver and is thought to mainly develop from a benign biliary cystadenoma (BCA). At present, the disease is mainly diagnosed by ultrasound, CT, MR, and other imaging methods, and the main treatment is radical surgical resection. We reported a 75-year-old female with an unresectable huge BCAC (i.e., 161×145×122 mm in three orthogonal directions) and poor general condition (40 in Karnofsky Performance Status, KPS) who received sequential thermal ablation (i.e., cryoablation and microwave ablation) in combination with sclerotherapy using lauromacrogol. The diagnosis of intrahepatic BCAC was confirmed pathologically. Preablation grayscale US showed the BCAC with a clear boundary, regular shape, and cystic-solid mixed echogenicity, which appeared as a huge multilocular cystic lesions with thick internal sepatations. Preablation contrast-enhanced ultrasound (CEUS) showed honeycomb-like hyper-enhancement of the thick internal sepatations and cystic wall in the arterial and portal phase, and sustained enhancement of the thick internal sepatations and cystic wall in the late phase. 6-month postablation CEUS showed non-enhancement in most parts of the lesion in the arterial phase and 6-month postablation MRI showed the volume reduction ratio (VRR) was about 70%. The abdominal pain and abdominal distension were relieved remarkably, and her quality of life was greatly improved (70 in KPS). In conclusion, sequential thermal ablation in combination with sclerotherapy provides a successful translative therapy for this unresectable huge BCAC with a poor general condition, which makes subsequent curative surgery or ablation possible.

Ultrasound-guided percutaneous microwave ablation for uterine fibroids: mid-term local treatment efficiency and associated influencing factors.

OBJECTIVE: To investigate the mid-term local treatment efficiency of ultrasound-guided percutaneous microwave ablation (MWA) for uterine fibroids (UFs) and the associated influencing factors. METHODS: From July 2020 to October 2021, a total of 28 patients with 52 UFs who had undergone ultrasound-guided MWA were retrospectively included in this study. Pre-treatment clinical characteristics, conventional ultrasound and contrast-enhanced ultrasound (CEUS) features were analyzed to explore their correlation with volume reduction ratios (VRRs) of sufficient ablation (i.e. a VRR of at least 50% at the 3 month follow-up). The patients were assessed at 1-, 3-, 6 month follow-up after MWA treatment and the assessment included VRR, adverse events, uterine fibroid symptom (UFS) and quality of life (QoL) scores, and clinical symptoms. RESULTS: The procedures of percutaneous MWA for UFs were tolerated well and no major complications occurred in all patients. At the 1-, 3-, 6 month follow-up, the median VRRs of UFs were 30.1%, 46.9%, and 65.8%, respectively. At the 3 month follow-up, 44.4% of fibroids obtained sufficient ablation while the remaining 55.6% obtained partial ablation (i.e. a VRR of <50%). Non-enhancing area during the early phase (i.e. within 30 s after injecting contrast agent) on pre-treatment CEUS was present in 22.2% UFs, which was associated with sufficient ablation at the 3 month follow-up (p < 0.05). In addition, the relevant clinical symptoms of all patients were alleviated or removed. The UFS and QoL score after MWA decreased significantly in comparison with those after MWA (p = 0.04 and p = 0.057, respectively), indicating a remarkable improvement of clinical symptom and QoL. CONCLUSION: Ultrasound-guided MWA is an effective and safe method to treat patients with UFs. Non-enhancing area during the early phase on pretreatment CEUS is associated with mid-term local treatment efficiency, which might be used to predict treatment outcome. ADVANCES IN KNOWLEDGE: Non-enhancing area during the early phase on pretreatment CEUS is an important factor associated with mid-term local treatment efficiency. This is the first study finding that CEUS feature can be used as a marker for the prediction of mid-term local treatment response.

CAR T cells equipped with a fully human scFv targeting Trop2 can be used to treat pancreatic cancer.

PURPOSE: Chimeric antigen receptor (CAR) T cell therapy has demonstrated clinical success in treating haematologic malignancies but has not been effective against solid tumours thus far. Trop2 is a tumour-related antigen broadly overexpressed on a variety of tumours and has been reported as a promising target for pancreatic cancers. Our study aimed to determine whether CAR T cells designed with a fully human Trop2-specific single-chain fragment variable (scFv) can be used in the treatment of Trop2-positive pancreatic tumours. METHODS: We designed Trop2-targeted chimeric antigen receptor engineered T cells with a novel human anti-Trop2 scFv (2F11) and then investigated the cytotoxicity, degranulation, and cytokine secretion profiles of the anti-Trop2 CAR T cells when they were exposed to Trop2 + cancer cells in vitro. We also studied the antitumour efficacy and toxicity of Trop2-specific CAR T cells in vivo using a BxPC-3 pancreatic xenograft model. RESULTS: Trop2-targeted CAR T cells designed with 2F11 effectively killed Trop2-positive pancreatic cancer cells and produced high levels of cytotoxic cytokines in vitro. In addition, Trop2-targeted CAR T cells, which persistently circulate in vivo and efficiently infiltrate into tumour tissues, significantly blocked and even eliminated BxPC-3 pancreatic xenograft tumour growth without obvious deleterious effects observed after intravenous injection into NSG mice. Moreover, disease-free survival was efficiently prolonged. CONCLUSION: These results show that Trop2-targeted CAR T cells equipped with a fully human anti-Trop2 scFv could be a potential treatment strategy for pancreatic cancer and could be useful for clinical evaluation.

Nanoengineered Neutrophils as a Cellular Sonosensitizer for Visual Sonodynamic Therapy of Malignant Tumors.

The rapid evolution of cell-based theranostics has attracted extensive attention due to their unique advantages in biomedical applications. However, the inherent functions of cells alone cannot meet the needs of malignant tumor treatment. Thus endowing original cells with new characteristics to generate multifunctional living cells may hold a tremendous promise. Here, the nanoengineering method is used to combine customized liposomes with neutrophils, generating oxygen-carrying sonosensitizer cells with acoustic functions, which are called Acouscyte/O2 , for the visual diagnosis and treatment of cancer. Specifically, oxygen-carried perfluorocarbon and temoporfin are encapsulated into cRGD peptide modified multilayer liposomes (C-ML/HPT/O2 ), which are then loaded into live neutrophils to obtain Acouscyte/O2 . Acouscyte/O2 can not only carry a large amount of oxygen but also exhibits the ability of long circulation, inflammation-triggered recruitment, and decomposition. Importantly, Acouscyte/O2 can be selectively accumulated in tumors, effectively enhancing tumor oxygen levels, and triggering anticancer sonodynamics in response to ultrasound stimulation, leading to complete obliteration of tumors and efficient extension of the survival time of tumor-bearing mice with minimal systemic adverse effects. Meanwhile, the tumors can be monitored in real time by temoporfin-mediated fluorescence imaging and perfluorocarbon (PFC)-microbubble-enhanced ultrasound imaging. Therefore, the nanoengineered neutrophils, i.e., Acouscyte/O2 , are a new type of multifunctional cellular drug, which provides a new platform for the diagnosis and sonodynamic therapy of solid malignant tumors.

Hepatic macrophage targeted siRNA lipid nanoparticles treat non-alcoholic steatohepatitis.

HMGB1 is an inflammatory factor produced by macrophages after liver injury, which plays a key role in promoting NASH progression and further developing into liver fibrosis and cirrhosis. In this study, a mannose-modified HMGB1-siRNA loaded stable nucleic acid lipid particle delivery system (mLNP-siHMGB1) was constructed to target liver macrophages with mannose receptor mediation, thereby silencing HMGB1 protein expression and treating NASH. We also examined the effect of co-administration with docosahexaenoic acid (DHA), a kind of unsaturated fatty acid, on NASH. The results showed that mLNP-siHMGB1 could target macrophages through mannose receptors, effectively silence HMGB1 gene, reduce the release of HMGB1 protein in the liver, regulate liver macrophages to be an anti-inflammatory M2 phenotype, effectively reduce hepatic lobular inflammation and bullous steatosis in the liver, and restore the liver function of NASH model mice to a normal level. After 8 weeks of combined treatment with mLNP-siHMGB1 and DHA, the liver function of NASH model mice recovered rapidly and the hepatic steatosis returned to normal level. In view of inflammation, a key factor in the progression of NASH, we provided an actively targeted siRNA delivery system in this study, and clarified the important role of the delivery system in phenotypic regulation of liver macrophages in NASH. In addition, we also demonstrated the effectiveness of DHA co-administration in NASH treatment. This study provided a useful idea and scientific basis for the development of therapeutic strategies for NASH in the future.

The first experience of ultrasound-guided percutaneous microwave ablation for extracranial schwannoma of the cervical vagus nerve in carotid space and treatment response evaluation with contrast-enhanced imaging: A case report.

Schwannoma is a benign tumor that originates from Schwann cells in the nerve sheathing of cranial, other peripheral, or autonomic nerves. Patients often present with painless mass as the chief complaint. The main symptoms of this tumor are related to its size and specific nerve origin. At present, the pretreatment diagnosis is mainly made by ultrasound, CT, MR, or biopsy, and the main treatment is surgical resection. We reported a new treatment method for cervical schwannoma in a 65-year-old woman with a history of non-small cell lung cancer (NSCLC). When the patient's neck mass was initially found with hoarseness and severe cough, it was considered as cervical lymph node metastasis of lung cancer due to her medical history. And she was diagnosed with schwannoma by core-needle biopsy after chemotherapy failed and the tumor shrank after the radiotherapy with no improvement of the clinical symptoms. After considering the physical condition, the patients were treated in our department for minimal invasiveness treatment. The patient was definitively diagnosed with cervical vagus schwannoma and was treated with ultrasound-guided microwave ablation of schwannoma under general anesthesia with systematic evaluation and improved preoperative examination. Her condition was stable, and the symptoms of severe cough disappeared after anesthesia resuscitation and the ablation. The tumor continued to shrink after the operation with no recurrence of cough symptoms. Ultrasound-guided percutaneous microwave ablation (MWA) for cervical vagus schwannomas might be a minimally invasive, effective, and relatively safe alternative to conventional treatment for those patients with severe symptoms.

Two new Botryosphaeria (Botryosphaeriales, Botryosphaeriaceae) species in China.

Five ascomycetous strains were isolated from dead branches and leaves of Salix (Salicaceae) and Osmanthusfragrans (Oleaceae), respectively. BLAST searches with ITS sequences in GenBank suggested a high degree of similarity to Botryosphaeriadothidea. To accurately identify these strains, we further analysed their morphological characteristics of asci, ascospores, all conidiophore cells and conidia. Phylogenetic relationships, based on ITS, rpb2, tef1 and tub2 gene sequences, confirmed our strains represented two novel species, which are introduced here as B.salicicola and B.osmanthuse spp. nov.

Four new Phragmidium (Phragmidiaceae, Pucciniomycetes) species from Rosaceae plants in Guizhou Province of China.

In this study, four new species of Phragmidium were proposed based on morphological and molecular characters. In morphology, Phragmidiumrosae-roxburghii sp. nov. was distinguished to related taxa by its unique square to diamond-shaped urediniospores; Ph.rubi-coreani sp. nov. differed from Ph.barclayi and Ph.cibanum because of teliospores with fewer cells and shorter pedicels; urediniospores of Ph.potentillae-freynianae sp. nov. were bigger than Ph.duchesneae-indicae; and Ph.rosae-laevigatae sp. nov. produced bigger urediniospores than Ph.jiangxiense. The phylogenetic analyses based on the combination of two loci (ITS and LSU) also supported our morphological conclusion. In the meantime, three previously known species were also described herein.

Efficacy and safety of allopurinol in the treatment of chronic kidney disease: a meta-analysis / 中国医师杂志

Objective:To evaluate the efficacy and safety of allopurinol in the treatment of chronic kidney disease.Methods:The databases of Embase, PubMed and the Cochrane library were searched for randomized controlled trials of allopurinol in patients with chronic kidney disease. According to the Cochrane system evaluation method, two evaluators independently screened the literature and extracted the data, and analyzed the results with Revman 5.3 software.Results:Finally, 10 articles were included, including 940 patients (472 in the experimental group and 468 in the control group). Meta analysis showed that allopurinol treatment could reduce blood uric acid ( MD=-2.40, 95% CI: -2.74--2.05, P<0.01), 24-hour urinary protein ( MD=-0.61, 95% CI: -1.17--0.06, P=0.03) and increase estimation of glomerular filtration rate(eGFR) ( MD=2.51, 95% CI: 1.86-3.17, P<0.01). There was no significant difference in adverse events between the experimental group and the control group ( OR=1.40, 95% CI: 0.61-3.19, P=0.42), but allopurinol treatment could reduce the risk of cardiovascular events ( OR=0.58, 95% CI: 0.38-0.89, P=0.01). Conclusions:Allopurinol treatment of chronic kidney disease can reduce urinary protein, improve eGFR, and reduce the risk of cardiovascular events.