Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Objective:To study the clinicopathological, immunophenotypic and molecular genetic characteristics of nodular fasciitis (NF) in unusual sites.Methods:A total of 50 cases of NF diagnosed between January 2015 and January 2021 were reviewed in the Department of Pathology, Henan Provincial People′s Hospital, and the clinical and pathologic data were analyzed. Among them, 14 cases from unusual sites were included in this study. Immunohistochemical (IHC) staining was used to detect the expression of related proteins, and fluorescence in situ hybridization (FISH) was used to detect the breakage of the USP6 gene.Results:There were seven males and seven females in the 14 NF respectively. The lesions were located in the extremities, perineum, breast, wrist joints, the gap between lumbar vertebra 4/5, and in eight cases there was involvement of unusual tissues (six cases in skeletal muscle, one case in nerve root, and one case was intravascular). The tumor boundary was unclear with infiltrating growth. Spindle-shaped myofibroblasts were arranged in bundles or chaotically, with mild pleomorphic, small nucleoli and various mitotic figures. The tumor stroma showed collagenization to myxoid degeneration with erythrocyte extravasation and infiltration of inflammatory cells. IHC staining showed that the spindle cells expressed SMA focally or partially, and p16 diffusely and strongly. FISH showed that 12 of 14 cases had USP6 gene breakage, and two of them occurred in the intrathoracic skeletal muscle with the red signal amplification of USP6 gene.Conclusions:NF in unusual sites shows similar clinicopathological and genetic characteristics to classic NF, but the tumor mostly has infiltrating borders, non-specific and strong expression of p16, and USP6 red signal amplification. The pathological diagnosis of NF in rare sites should be highly vigilant.

Objective:To investigate the clinicopathological features, immunophenotypic and molecular genetic characteristics and differential diagnosis of fibrous hamartoma of infancy (FHI).Methods:Thirty-three cases of surgically removed FHI were collected from the Department of Pathology, Henan Provincial People′s Hospital from October 2011 to December 2020, the clinical and pathologic data with follow-up were collected and analyzed. Next-generation sequencing (NGS) and quantitative real time polymerase chain reaction (q-PCR) were used to study the molecular genetics.Results:The FHI cases occurred in 21 males and 12 females (mean age 16.7 months, range 6 months to 6 years). The sites included trunk ( n=21), limb ( n=11), and neck (n=1). All patients had painless solitary superficial soft tissue masses, the size was 1.5-9.0 cm (mean 3.8 cm). Microscopically, they were composed of mature adipose tissue, fibroblast/myofibroblast bundle and primitive mesenchymal cells in different proportions; giant cell fibroblastoma-like areas were seen in 14 cases. Immunohistochemistry showed variable expression of EGFR in the spindle cells and primitive mesenchymal components. In most cases, the spindle cells were positive for CD34 and SMA; giant cell fibroblastoma-like areas were strongly positive for CD34; and S-100 protein was expressed by adipocytes in all cases. Ki-67 labeling index ranged 1%-5%. There were recurrent somatic EGFR exon 20 insertion/duplication mutations in six cases tested by NGS, and there were three different mutation types: p.Asn771_His773dupAsnProHis, p.Pro772_His773insProProHis, and p.His773_Val774insThrHis. All the above 6 and another 15 tested cases showed EGFR exon 20 insertion/duplication mutations by q-PCR. Conclusions:FHI is a rare benign fibroblast/myofibroblast tumor. The characteristic histologic feature is organoid triphasic morphology, and the molecular feature is somatic mutation of EGFR exon 20 (insertion/duplication).

The plant root-associated microbiomes include root microbiome and rhizosphere microbiome, which are closely related to plant life activities. Nearly 30% of photosynthesis products of plants are used to synthesize root compounds, there is evidence that root compounds regulate and significantly affect the root microbiome Tanshinones are the main hydrophobic components in Salvia miltiorrhiza. In order to study whether these compounds can regulate the root-associated microbiomes of S. miltiorrhiza, our study first identified a white root S. miltiorrhiza(BG) which contains little tanshinones. Retain of the fifth intron of tanshinones synthesis key enzyme gene SmCPS1 leading to the early termination of the SmCPS1 gene, and a stable white root phenotype. Further, wild type(WT) and BG were planted in greenhouse with nutrient soil(Pindstrup, Denmark) and Shandong soil(collected from the S. miltiorrhiza base in Weifang, Shandong), then high-throughput sequencing was used to analyze the root-associated microbiomes. The results showed that the tanshinones significantly affected the root-associated microbiomes of S. miltiorrhiza, and the impact on root microbiomes was more significant. There are significant differences between WT and BG root microbiomes in species richness, dominant strains and co-occurrence network. Tanshinones have a certain repelling effect on Bacilli which belongs to Gram-positive, while specifically attract some Gram-negative bacteria such as Betaproteobacteria and some specific genus of Alphaproteobacteria. This study determined the important role of tanshinones in regulating the structure of root-associated microbiomes from multiple angles, and shed a light for further improving the quality and yield of S. miltiorrhiza through microenvironment regulation.
Abietanes ; Microbiota ; Plant Roots ; Salvia miltiorrhiza

Objective:To investigate the role of DDX3 up-regulation in the proliferation of human cervical cancer cells and its correlation with clinical prognosis.Methods:Expression levels of DDX3 in the 59 specimens of cervical cancer and adjacent non-neoplastic tissue collected at Henan Provincial People′s Hospital from April 2012 to March 2013 were detected using immunohistochemistry. A lentivirus-mediated DDX3-over-expression cell line was constructed based on HeLa cells of cervical cancer. CCK-8 assay was used to evaluate cell survival rate. Boyden chamber was used to measure the cell migration and invasion. Real-time fluorescence quantitative PCR was used to detect DDX3 expression level and Western blot was used to detect the expression of EMT and PI3K/Akt signal pathway-related proteins. Results:DDX3 overexpression was associated with FIGO stage, depth of cervical invasion and lymph node metastasis ( P<0.05). Kaplan-Meier analysis revealed that cervical cancer patients with high expression of DDX3 had a poor overall survival ( P<0.05). Compared with the cells transfected with pLVX-Con vector, the expression of DDX3 protein and mRNA was significantly increased in the cells transfected with pLVX-DDX3 (all P<0.01). Cell proliferation was significantly increased following transfection with pLVX-DDX3 for 72 h in HeLa cells compared with that transfected with pLVX-Con ( P<0.05). Compared with the controls, DDX3 overexpression significantly promoted the migration and invasion of HeLa cells ( P<0.05), and increased the expression of N-Cadherin, vimentin and Snail in HeLa cells ( P<0.05). In pLVX-DDX3 group, the expression levels of β-catenin, phosphorylated Akt, and pAkt′s downstream target p-GSK3β were significantly higher than those of pLVX-Con group ( P<0.05). The expression levels of p-Akt, p-GSK3β and β-catenin were decreased when the PI3K/Akt pathway was blocked using the PI3K inhibitor LY294002 ( P<0.05), and the expression levels of N-Cadherin, vimentin and Snail were also significantly decreased ( P<0.05). Conclusions:DDX3 overexpression promotes proliferation, migration and invasion of cervical cancer cells, and induces epithelial-mesenchymal transition (EMT). Its mechanism may be related to activation of the PI3K/Akt signaling pathway.

Objective:To evaluate the efficacy of Qingpeng ointment in the treatment of early herpes zoster neuralgia.Methods:From January to June 2019, sixty patients with herpes zoster (34 males and 26 females, aged 12 to 48 years, onset time of 1 to 7 days) were randomly divided into experimental group and control group. Both groups were given the same antiviral and neurotrophic therapy after admission. The experimental group was treated with Qingpeng ointment for external use in addition. The numerical rating scale (NRS), sleep score (AIS) and adverse reactions of the two groups were evaluated at pre-treatment, 3, 5, 7, 15 and 30 days after treatment.Results:Compared with pre-treatment, the NRS and AIS scores of the experimental group were significantly reduced at each time from day 3, and the difference was statistically significant. The NRS and AIS scores of the control group were reduced at each time from day 7, and the difference was statistically significant. Compared with control group, the NRS scores of the experimental group on the 3rd, 5th, and 7th days and the AIS scores on the 3rd and 5th days after treatment were lower than those of the control group, and the difference was statistically significant. There were no serious adverse reactions in the two groups.Conclusions:External application of Qingpeng ointment can quickly relieve early neuralgia in patients with herpes zoster, improve the patients＇ sleep, and there is no obvious adverse reaction.

Objective: To investigate the clinicopathological characteristics, histogenesis, immunophenotypes, molecular genetic characteristics, diagnosis and differential diagnosis of calcifying fibrous tumors (CFT). Methods: A total of 32 cases of CFT (22 cases from Henan Provincial People′s Hospital and 10 cases from PLA Army Medical Center) diagnosed between June 2009 and February 2019 were reviewed. The clinical and pathologic data were analyzed. Results: There were 12 male and 20 female patients, aged from 15 to 63 years (mean 40.8 years). Eleven cases occurred in stomach, four cases in retroperitoneum, four cases in ovary, two cases in scrotum, two cases in mediastinum, two cases in head and neck, one case each in thoracic cavity, lung, adrenal gland, kidney, sigmoid colon, epididymis and mesosalpinx. All the tumors were solid masses with clear boundaries. The maximal dimension of the tumors ranged from 0.6 to 10.0 cm. Microscopically, there was hypocellular stromal sclerosis and wavy storiform coarse collagen with superimposed scattered or patchy lymphocytes and plasma cells; calcification or gravel formation were also detected. Immunohistochemistry showed that spindle cells were positive for vimentin and some were positive for CD34; and they were negative for calponin, SMA, desmin, S-100 protein, SOX10, STAT6, β-catenin, ALK, CD117, DOG1, CKpan, and EMA. No ALK rearrangement was detected by FISH in all cases. No C-KIT and PDGFRA mutation was detected in all the tested 11 cases of stomach, four cases of retroperitoneal and one case of sigmoid colon CFT. MDM2 was not amplified by FISH in all four tested cases of retroperitoneal CFT. Conclusions CFT is a rare benign tumor of fibroblastic cell origin. The diagnosis mainly depends on histomorphologic analysis and immunophenotyping. CFT should be differentiated from other benign and malignant spindle cell mesenchymal tumors.

Objective: To study rhizosphere soil fungal community composition and diversity of Salvia miltiorrhiza,in order to explain the changes of the rhizosphere microenvironment of S.miltiorrhiza,and provide theoretical basis for revealing the reasons for the formation of continuous obstacles.Method: Based on the high-throughput sequencing technology,three kinds of soil samples were collected,namely soil of non-plant (CK),soil for cultivating for one year (Y1) and soil for cultivating for two years (Y2),respectively.According to the sequencing of the internal transcribed space of nuclear ribosomal DNA (ITS) region of fungal rRNA gene,14 153,19 024 and 7 622 valid sequences were obtained and annotated as 1 027,1 095 and 712 varieties of OTUs.The diversity of fungal communities showed a trend of decreasing first and then increasing.Agaricomycetes,Leotiomycetes and Tremellomycetes were the dominant bacterial communities at the class level,their orders in three treatments were Y1 > CK > Y2,Y2 > Y1 > CK,CK > Y2 > Y1.At the genus level,Guehomyces was dominant species in CK,and both Y1 and Y2 had a decrease of 96.13% and 90.21%,respectively.Wickerhamomyces had a significantly increase in Y2(6.64%),250.59% and 564.00% compared with CK and Y1,respectively.Result: The results of cluster analysis showed that CK and Y1 had a higher similarity at the genus level in soil fungal community composition compared with Y2.Conclusion: Cryptosporiopsis and other pathogenic fungal communities were dominant genuses according to the heatmap analysis in Y2,suggesting a correlation with the incidence of S.miltiorrhiza.The findings provide theoretical basis for the formation of continuous cropping obstacle.

Objective To investigate the effectiveness of endovascular technique in treatment of acute arterial hemorrhage of abdominal organs.Methods Totally 159 cases (145 patients) acute arterial hemorrhage of abdominal organs were enrolled.All patients underwent emergency transarterial angiography.Endovascular treatment by spring coil,gelatin sponge,or covered stent were in 40 cases.The success rate of immediate and long-term hemostasis was judged by the postoperative radiography,symptoms and the changes of vital signs and laboratory results.Results The positive signs in angiography were observed in 47 among the total 159 cases (47/159,29.56％).Seventy-seven postoperative hemorrhage cases underwent angiography and 29 cases (29/77,37.66 ％) were positive,82 non-operative hemorrhage cases underwent angiography and 18 cases (18/82,21.95％) were positive.The difference was statistical significant (P＜0.05).Endovascular treat ment were performed in 40 cases (33 by spring coils,4 by gelatin sponge and 3 by covered stent).Hemorrhages were con trolled immediately in all the 40 cases after embolization and the success rate were 100％.Conclusion Endovascular tech nique is minimal invasive,and it is an effective method for treatment of acute arterial hemorrhage in abdominal organs.

Objective To evaluate the safety and efficacy of the endovascular treatment of subclavian artery stenosis.Methods From January 2010 to December 2015,the clinical data of 93 patients with subclavian artery stenosis were analyzed retrospectively.All the patients were received angiography and endovascular treatment.Results The technical success rate was 97.9％.Clinical symptom remission rate was 97.8％ after the treatment.There was no procedure related death.During the procedure,limited arterial dissection was encountered in two cases.One patient had minor cerebellar hemorrhage.The follow-up time was 12 to 60 months.Median follow-up time was 36 months.Restenosis was occurred in nine cases.The patency rate of 5 years was 81.0％.Conclusions Endovascular treatment was a safe and effective treatment as the result of our data.It should be used as the preferred treatment of choice for subclavian artery stenosis.