ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Objective: To analyze the prognostic factors of transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients treated with cyclosporine A (CsA) and androgen. Methods: Clinical data of 77 consecutive TD-NSAA patients treated with CsA and androgen were retrospectively analyzed between 2010 and 2013. We obtained clinical manifestations and baseline parameters of routine blood test from responders, and compared those with non-responders. All data were analyzed by univariate analysis and multivariate analysis. Results: In 77 patients, there were 43 (55.8%) patients achieved hematological response after 6 months'treatment, and 53 (68.8%) patients got response after 12 months. Univariate analysis showed that platelets baseline was the only factor related to hematological response [19 (6-61) ×10(9)/L vs 13.5 (5-45) ×10(9)/L, P=0.001] after 6 months therapy. After 12 months, the statistical differences were maintained, which were platelets baseline [18 (6-61) ×10(9)/L vs 10.5 (5-45) ×10(9)/L, P<0.001], absolute reticulocytes [0.03 (0.01-0.06) ×10(12)/L vs 0.029 (0.02-0.06) ×10(12)/L, P=0.043], transfusion-dependent of platelet (P=0.007) , transfusion-dependent of platelet and erythrocyte (P=0.012) . Multivariate analysis showed that platelets baseline could be an independent prognostic factor of hematological response (P=0.010 or 0.009) . Cutoff value of platelets by receiver operating characteristic curve was 15.5×10(9)/L. Conclusion: Baseline of higher platelets, higher reticulocyte, and no transfusion dependence of platelet are favorable prognostic factors. When platelets baseline is higher than 15.5×10(9)/L, CsA and androgen regimen is rational.
Androgens/therapeutic use* ; Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum ; Cyclosporine/therapeutic use* ; Drug Combinations ; Humans ; Immunosuppressive Agents ; Prognosis ; Retrospective Studies ; Treatment Outcome

To study and analyze prevalence condition of hypertension and complicated cardiovascular risk factors in north Fujian rural area .Methods : By cluster sampling , an epidemiological questionnaire and physical ex‐amination were performed among 1784 residents using standardized survey method , who were ≥35 years from six towns and eight villages in north Fujian rural area from Jun 2013 to Mar 2014. Hypertension was diagnosed accord‐ing to The 2010 Chinese Guideline for the Prevention and Treatment of Hypertension , multivariate Logistic regres‐sion was used to analyze independent risk factors for hypertension in these subjects .Results : Prevalence rate of hy‐ pertension was 17.43% (31／1784 ) in north Fujian rural area .After population standardization , it＇s 23. 21%(18.66% in men and 16. 13% in women) , there was no significant difference in prevalence rate of hypertension be‐tween men and women in any age layer , P＞0. 05 all.Multivariate Logistic regression analysis indicated that age , overweight (BMI≥24 kg／m2 ) , high triglyceride and fasting blood glucose were independent risk factors for hyper‐tension in north Fujian rural area (OR＝1.107－2.096 , P＜0. 05 or ＜0. 01).Conclusion : Prevalence rate of hyper‐tension is high in north Fujian rural area , age , overweight , smoking , high triglyceride and fasting blood glucose are the main risk factors .

As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.

OBJECTIVE: To elucidate the action mechanism of Xingnaojing Injection (, XNJI) for sepsis, and to target screen the potential bioactive ingredients. METHODS: An integrated protocol that combines in silico target screen (molecular docking) and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target (C-T) interaction network. The XNJI's bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-lipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. RESULTS: Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. CONCLUSIONS The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.
Arachidonate 5-Lipoxygenase ; metabolism ; Computer Simulation ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Injections ; Phytochemicals ; therapeutic use ; Receptor, Adenosine A2A ; metabolism ; Reproducibility of Results ; Sepsis ; drug therapy ; metabolism

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are adult stem cells with multipotential differentiation, which can be induced to differentiate into bone, cartilage and other connective tissues. Meanwhile, as a highly specific marker of tenocytes, Scleraxis is involved in aggregation and differentiation of tendon progenitor cells as well as the formation of tendon extracellular matrix. OBJECTIVE: To investigate whether hAMSCs have the ability of differentiation into tenocytes by ectopic expression of Scleraxis. METHODS: Agreed by puerpera, the amniotic membrane from the full-term placenta was separated, and hAMSCs were isolated by a two-step enzyme digestion, observed under inverted phase contrast microscope, and identified by flow cytometry. Passage 3 cells were induced via plasmid-mediated Scleraxis overexpression in overexpression group. Untransfected cells cultured in normal medium served as blank control group, and those with empty plasmid transfection were defined as empty plasmid group. Cell proliferation was tested in each group using cell counting kit-8 within 7 days of culture. Real-time quantitative PCR and western blot were used to assess the tenogenic differentiation of hAMSCs in each group at 3 and 7 days of culture. RESULTS AND CONCLUSION: Findings from the cell counting kit-8 indicated that the cell viability had no significant differences among the groups within 7 days of culture (P > 0.05). Western blot results showed the protein expression of Scleraxis in the treatment group was significantly higher than that in the other two groups (P < 0.05). Real-time PCR results showed, at 3 days of culture, the expression of collagen type I, collagen type III, Fibronectin and Tenascin-C in the overexpression group was significantly higher than that in the empty plasmid group (P < 0.05), but the expression of Tenomodulin had no difference (P > 0.05); at 7 days of culture, the expressions of collagen type I, collagen type III, Fibronectin, Tenascin-C and Tenomodulin in the overexpression group were significantly higher than those in the empty plasmid group (P < 0.05). In summary, hAMSCs can be differentiated into tenocytes by ectopic expression of Scleraxis.

Objective: To investigate the clinical effects of traditional Chinese medicine (TCM) fumigation on type ⅢA prostatitis with the symptoms of damp heat and blood stasis. METHODS: We randomly divided 72 cases of type ⅢA prostatitis with the symptoms of damp heat and blood stasis into an experimental and a control group of equal number, the former treated with TCM fumigation plus oral Levofloxacin while the latter with oral Levofloxacin only. After 4 weeks of treatment, we compared the National Institute of Health Chronic Prostatitis Symptom Index (NIHCPSI) score, TCM symptoms score, maxinum flow rate (Qmax), and average urinary flow rate (Qave) between the two groups of patients. RESULTS: The total effectiveness rate was significantly higher in the experimental than in the control group (91.7% vs 61.1%, P< 0.01), while the NIHCPSI score in the experimental group was markedly decreased after treatment as compared with the baseline (14.5 ± 8.2 vs 26.5 ± 9.3, P< 0.05) and significantly lower than that in the control (14.5 ± 8.2 vs 20.6 ± 7.9, P< 0.05). Qmax was remarkably increased in the experimental group after treatment in comparison with the baseline (［21.2 ± 4.3］ vs ［15.8 ± 3.6］ ml/s, P< 0.05) and the control group, and so was Qave as compared with pretreatment (［16.3 ± 3.5］ vs ［10.5 ± 2.8］ ml/s, P< 0.05) and the control. However, the patients of the control group showed no statistically significant differences before and after treatment either in Qmax (［15.4 ± 3.4］ vs ［16.1 ± 2.9］ ml/s, P>0.05) or in Qave (［10.9 ± 2.4］ vs ［11.1 ± 2.9］ ml/s, P>0.05). CONCLUSIONS TCM fumigation combined with Levofloxacin is an effective therapy for type ⅢA prostatitis with the symptoms of damp heat and blood stasis, which can significantly improve the symptoms, reduce the NIHCPSI score, and increase the Qmax and Qave of the patient.
Anti-Bacterial Agents ; administration & dosage ; Chronic Disease ; Drugs, Chinese Herbal ; administration & dosage ; Fumigation ; Hot Temperature ; Humans ; Levofloxacin ; administration & dosage ; Male ; Medicine, Chinese Traditional ; Prostatitis ; drug therapy ; pathology ; Severity of Illness Index ; Symptom Assessment ; methods

Objective To investigate mechanical characteristics of the spirochete flagella with tight-fitting ribbon configuration in micro-periplasmic space. Methods The 2D model of two parallel plates was used to simplify the periplasmic space, and the effects of flagellum spacing and eccentricity on force and torque acted on the spirochete flagella, and wall shear stress acted on the spirochete protoplasmic cylinder were studied by using numerical simulation method. Results (1) The relationship between the flagellum horizontal force and eccentricity was presented as a parabolic curve, and the peak value of the flagellum horizontal force was mainly caused by the gradual increase of pressure difference at two sides of the cylinder and the resistance viscous force as well. Flagellum spacing had no significant influence on flagellum horizontal force. (2) The relationship between the flagellum torque and eccentricity was presented as an exponential curve, and smaller flagella spacing would cause bigger flagella torque. (3) Flagellum spacing had no significant effect on wall shear stress of the protoplasmic cylinder, but it would be increased with the number of flagella and the eccentricity increasing. Conclusions Numerical simulation results in this study can qualitatively reflect mechanical characteristics of the spirochete flagella, and also provide references for further understanding the morphology of spirochete as well as its kinematic mechanism and pathogenic characteristics.

OBJECTIVETo evaluate the efficacy of electrocorticographic (ECoG) monitoring and the application of different surgical approaches in the surgical treatment of solitary supretentorial cavernous malformations with secondary epilepsy.

METHODSThis study enrolled a consecutive series of 36 patients with solitary supratentorial cavernous malformations and secondary epilepsy who underwent surgery with intraoperative ECoG monitoring in the Department of Neurosurgery between January 2004 and January 2008. The patients were composed of 15 males and 21 females, aged between 8 and 52 years (mean age 27.3±2.8 years) at the time of surgery. Epilepsy history, the type of epilepsy at the presentation, lesion location, the incidence of residual epileptiform discharges, and postoperative outcomes were evaluated.

RESULTSHistopathological examination indicated cavernous malformations and hippocampal sclerosis in 36 and 5 cases, respectively. Neuronal degeneration, glial cell proliferation, and neurofibrillary tangles were found in all the resected cerebral tissues of extended lesionectomy of residual epileptic foci. Lesionectomy, anterior temporal lobectomy, anterior temporal lobectomy plus cortical thermocoagulation, extended lesionectomy, extended lesionectomy plus cortical thermocoagulation were performed in 4, 4, 1, 14, and 13 cases, respectively. Residual epileptiform discharges were captured in 9 out of the 14 patients who had additional cortical thermocoagulation. According to Engle class for postoperative outcomes, 27 cases were class I (75.00%), 5 were class II (13.89%), 2 were class III (5.56%), and 2 were class IV (5.56%), thus the total effective rate (class I+class II) was 88.89%. Neither of epilepsy history, the type of epilepsy, and the location of cavernous malformation was significantly related to outcomes (P>0.05). A significant relationship was found between the incidence of residual epileptiform discharges and outcomes (P=0.041).

CONCLUSIONSIntraoperative ECoG monitoring, the application of different surgical approaches, and the resection of residual epileptic foci could produce good result in the surgical treatment of supratentorial cavernous malformation with secondary epilepsy. Postoperative residual epileptiform discharges could be a useful predictor for evaluating the outcomes.

Adolescent ; Adult ; Brain ; abnormalities ; physiopathology ; Child ; Electroencephalography ; methods ; Epilepsy ; complications ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Young Adult

Objective To evaluate the efficacy of electrocorticographic (ECoG) monitoring and the application of different surgical approaches in the surgical treatment of solitary supretentorial cavernous malformations with secondary epilepsy.
Methods This study enrolled a consecutive series of 36 patients with solitary supratentorial cavernous malformations and secondary epilepsy who underwent surgery with intraoperative ECoG monitoring in the Department of Neurosurgery between January 2004 and January 2008. The patients were composed of 15 males and 21 females, aged between 8 and 52 years (mean age 27.3±2.8 years) at the time of surgery. Epilepsy history, the type of epilepsy at the presentation, lesion location, the incidence of residual epileptiform discharges, and postoperative outcomes were evaluated.
Results Histopathological examination indicated cavernous malformations and hippocampal sclerosis in 36 and 5 cases, respectively. Neuronal degeneration, glial cell proliferation, and neurofibrillary tangles were found in all the resected cerebral tissues of extended lesionectomy of residual epileptic foci. Lesionectomy, anterior temporal lobectomy, anterior temporal lobectomy plus cortical thermocoagulation, extended lesionectomy, extended lesionectomy plus cortical thermocoagulation were performed in 4, 4, 1, 14, and 13 cases, respectively. Residual epileptiform discharges were captured in 9 out of the 14 patients who had additional cortical thermocoagulation. According to Engle class for postoperative outcomes, 27 cases were class I (75.00%), 5 were class II (13.89%), 2 were class III (5.56%), and 2 were class IV (5.56%), thus the total effective rate (class I+class II) was 88.89%. Neither of epilepsy history, the type of epilepsy, and the location of cavernous malformation was significantly related to outcomes (P>0.05). A significant relationship was found between the incidence of residual epileptiform discharges and outcomes (P=0.041).
Conclusions Intraoperative ECoG monitoring, the application of different surgical approaches, and the resection of residual epileptic foci could produce good result in the surgical treatment of supratentorial cavernous malformation with secondary epilepsy. Postoperative residual epileptiform discharges could be a useful predictor for evaluating the outcomes.