PKM2/Hif-1α signal suppression involved in therapeutics of pulmonary fibrosis with microcystin-RR but not with pirfenidone.

To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.

Eccrine porocarcinoma in the tempus of an elderly woman: A case report.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin tumor that mainly affects the elderly population. Tumors often present with slow growth and a good prognosis. EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry. However, surgical management alone may be inadequate if the tumor has metastasized. However, currently, surgical resection is the most commonly used treatment modality. CASE SUMMARY: A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area, with no obvious itching or pain, for more than four months. Histopathological examination showed small columnar and short spindle-shaped cells; thus, basal cell carcinoma was suspected. However, immunohistochemical analysis revealed the expression of cytokeratin 5/6, p63 protein, p16 protein, and Ki-67 antigen (40%), and EPC was taken into consideration. The skin biopsy was repeated, and hematoxylin and eosin staining revealed ductal differentiation in some cells. Finally, the patient was diagnosed with EPC, and Mohs micrographic surgery was performed. We adapted follow-up visits in a year and not found any recurrence of nodules. CONCLUSION: This case report emphasizes the diagnosis and differentiation of EPC.

Characteristics of pine wood nematode disease in Nankang District, Ganzhou, Jiangxi Province, China.

Pine wood nematode (PWN) disease is one of the major disasters in forests of southern China, causing substantial forest resources and ecological and economic losses. Based on field surveys and WFV image data from the GF-1 satellite, we constructed a spatial identification model of PWN disease with the random forest model to explore the relative influences of topography, human activities and stand factors on the occurrence of diseases and predict their spatial distribution. We then used the spatial autocorrelation analysis to assess the distribution characteristics of PWN disease at the regional scale. The results showed that the random forest model constructed in this study was effective in identifying pine nematode diseases (AUC value=0.99, overall accuracy=0.96). The norma-lized difference greenness index (NDGI), the distance to the highway, and normalized vegetation index (NDVI) were important factors in explaining the spatial variations of PWN disease occurrence. There was a positive spatial correlation in the occurrence of PWN disease (not randomly distributed but with obvious spatial aggregation characteristics). The high occurrence areas of pine wood nematode disease concentrated in Chitu Township, Zhufang Township and Shibatang Township, low occurrence areas concentrated in the vicinity of Rongjiang Street. The areas far away from the highway, low in elevation, and close to county roads were suffered to PWN disease. The results could serve the regional monitoring of pine nematode disease occurrence and provide practical guidance for PWN disease management.

Association Between the Diabetic Foot Ulcer and the Bacterial Colony of the Skin Based on 16S rRNA Gene Sequencing: An Observational Study.

Objective: Microorganisms have been the main cause of refractory and high recurrence of diabetic foot ulcer (DFU). This study attempted to observe the skin bacterial colony in healthy skin, diabetic skin and DFU skin. Methods: Forty-eight diabetes patients were recruited at Panyu Central Hospital from March 2021 to March 2022 and divided into DFU group (T group, n = 22), diabetes without foot ulcer group (TW group, n = 26). Besides, a healthy control group (H group, n = 10) was recruited at the same time. The swab samples of foot skin in the same position in the three groups were collected. The microorganisms obtained from the skin were analyzed by 16S rRNA gene sequencing. The composition of the skin microorganisms was determined, and the species diversity of the skin microbiota was analyzed by α and ß diversity. The species differences in the skin microbiota and the relative abundance of different operational taxonomic units (OUTs) with the most significant abundance were analyzed by linear discriminant analysis effect size (LEfSe). Results: Significant changes were found in the composition of the skin microbiota in the T and TW groups relative to the H group. However, the species diversity of the skin microbiota was significantly reduced in the T and TW groups, with the lowest one in the T group. The composition of microbial diversity in the T group was significantly different from that of the TW and H groups. Among the skin bacterial colonies, the abundance of Staphylococcus, Enhydrobacter, and Corynebacterium_1 was obviously reduced, while that of Escherichia coli and Pseudomonas was significantly increased. Conclusion: Changes in the abundance of Staphylococcus, Enhydrobacter, Corynebacterium_1, Escherichia coli and Pseudomonas in the skin bacterial colonies can be the main causative factors for DFU. This study indicates that altering the microbiota composition of wounds may help the treatment of DFU.

Immunogenicity and safety of a new hexavalent rotavirus vaccine in Chinese infants: A randomized, double-blind, placebo-controlled phase 2 clinical trial.

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.

[Cytogenetic and Clinical Characteristics of Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the cytogenetic characteristics and prognostic risk factors for elderly patients with newly diagnosed elderly acute myeloid leukemia(AML). METHODS: Cytogenetic test results of 76 elderly patients with AML admitted to the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) from April 2015 to December 2021 were retrospectively analyzed, and analyzed clinical characteristics of patients and risk factors influencing prognosis. RESULTS: According to cytogenetic risk stratification, 76 newly treated elderly AML patients were divided into the favorable, intermediate, and unfavorable groups with 6(7.9%), 58(76.3%), and 12(15.8%) cases, respectively. There was no significant difference in the patient's clinical characteristics and prognosis with the cytogenetics-risk classification groups. Correlation analysis showed that patients' objective response rate (ORR) was related to the age of onset and the mutation status of the CEBPA gene. Logistic regression analysis found that age ≥70 years was an independent risk factor for patients' ORR (OR=0.110, P=0.005). Remission determined the 1-year OS rate (OR=0.049, P=0.005). CONCLUSION: There is no significant difference in clinical characteristics among aged AML patients treated at initial treatment in different cytogenetic risk groups. The age of onset ≥70 years is the determinant of whether patients can obtain ORR, and the rate of ORR is closely related to the 1-year OS rate.

Successful outcome of neoadjuvant PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy for potentially unresectable esophagogastric junctional squamous cell carcinoma: a case report.

Background: Esophagogastric junctional squamous cell carcinoma (EJSCC) is quite rare among all gastric carcinoma, its potential resectable rate is low due to the late diagnosis. Recently, programmed death-1 (PD-1) blockade combined with anti-angiogenesis have gained accumulated clinical experiences in treating solid tumors. This is the first reported case with EJSCC who achieved a partial remission (PR) after neoadjuvant PD-1 blockade, vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor plus chemotherapy. Case Description: We present an EJSCC case treated with novel neoadjuvant treatment. A 64-year-old Chinese male had the symptom of chocking for 3 months. An enhanced abdominal computed tomography (CT) scan found a locally advanced, potentially unresectable esophagogastric junctional (EGJ) mass, and the preoperative immunohistochemistry result exhibited a highly positive programmed death-ligand 1 (PD-L1) expression, so the patient received three courses of neoadjuvant camrelizumab (200 mg/day), apatinib (750 mg/day), albumin paclitaxel (200 mg/day) and nedaplatin (70 mg/day), he was well tolerant without any adverse event, and he underwent radical surgery after a significant tumor shrinkage. The patient recovered well after surgery, and he has received four cycles of camrelizumab and apatinib as maintenance treatment. There is no recurrence 7 months after surgery. Conclusions: PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy is effective and safe for the patient with EJSCC.

[Spatial point pattern analysis of pine wilt disease occurrence and its influence factors]. / æ¾æçº¿è™«ç— å‘ç”Ÿç‚¹æ ¼å±€åŠå½±å“å› ç´ .

Pine wilt disease has caused huge losses in ecological and economic values in China, especially in the southern parts. Analyzing the spatial distribution of pine wilt disease and quantifying the impact of environmental factors on its occurrence were of great significance for its prevention and control. In this study, we examined the spatial pattern of pine wilt disease occurrence and its response to environmental variables in Nankang District, Ganzhou, Jiangxi Province, using kernel-smoothing density, Ripley's K function, and point process model. The results showed that the occurrence of pine wilt disease in the study region was not randomly distributed, but was obviously clustered at some areas. Terrain, vegetation, and human activity were the main factors affecting the heterogeneous distribution of pine wilt disease. Spatial point pattern analysis showed that altitude, slope, distance to the nearest road, road density, distance to nearest settlement, canopy closure, and vegetation type had significant effects on the occurrence of pine wilt disease. In addition to strengthening the control of disease transmission caused by human activities, we should also consider the effects of terrain and vegetation types for early warning and monitoring in forest disease management.

Case Report: Successful Repair of Primary Aortoesophageal Fistula With an Endovascular Stent Graft and an Esophageal Stent.

Aortoesophageal fistula (AEF), secondary to thoracic pseudoaneurysm as a result of upper gastrointestinal bleeding, is a rare condition and will be undoubtedly lethal without prompt surgical intervention. The estimated annual incidence of primary AEFs and secondary AEFs is about 0.0015% and 0.6%-2%, respectively. The challenges of the therapy posed by AEF are control of the hemorrhage, arterial reconstruction in an infection field, control of sepsis, and re-establishment of the alimentary tract. We present a case of a 58-year-old man who suffered from chest pain and hematemesis and was finally diagnosed with pAEF caused by descending thoracic pseudoaneurysm. Our team successfully deployed an endovascular stent graft and esophageal stent to seal ruptured thoracic aorta and esophageal defects, which provided a new surgical strategy for aortoesophageal fistula in the endovascular era.

[Relationship between surface dead fuel loadings and environmental factors in southern Jiangxi, China]. / èµ£å—åœ°åŒºæ£®æž—åœ°è¡¨æ­»å¯ç‡ƒç‰©è½½é‡ä¸ŽçŽ¯å¢ƒå› å­çš„å ³ç³».

The distribution pattern of forest fuel loading is driven by the interaction of environmental factors, such as terrain and vegetation. Based on field sampling data of surface dead fuels of seven main forest types in southern Jiangxi Province, and according to the classification standard of different time-lags, we constructed structural equation models to explore the relationship between surface fuel loadings and environmental factors such as terrain and vegetation etc. We analyzed the influence path of each factor and its direct, indirect, and total influence. The results showed that the coniferous and broad-leaved mixed forest had the highest loadings and the Phyllostachys heterocycla pure forest had the lowest loadings for all the 1, 10, and 100 h time-lag fuels. The influencing coefficient of environmental factors for 1 h time-lag fuels were ranked as: slope (0.40) > crown height (0.07) > tree species (-0.03) > canopy closure (0.01). For the 10 h time-lag fuels, the environmental factors were ranked as: diameter at breast height (0.15) >tree species (-0.09) > aspect (-0.08) > canopy closure (-0.06). For the 100 h time-lag fuels, the environmental factors were ranked as: aspect (0.25) > diameter at breast height (0.19) > canopy closure (-0.08) > tree species (0.02). The influencing coefficient of environmental factors for the total fuels were ranked as: slope (0.22) > tree species (-0.04), canopy closure (-0.04) > crown height (-0.01).