BACKGROUND:For knee osteoarthritis,synovium inflammation and abnormal proliferation and activation of fibroblast-like synoviocytes caused by insuffcient apoptosis are important driving factors for disease progression.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway plays a key role in regulating inflammatory response and apoptosis of synovial cells.As a traditional Mongolian medicine component,Agiophyllum Oligo Saccharides has anti-inflammatory and immunomodulatory functions,but its specific molecular mechanism has not been fully revealed.OBJECTIVE:To explore the effects and mechanism of Agiophyllum Oligo Saccharides on lipopolysaccharide-induced inflammation and apoptosis of mouse synovial cells.METHODS:The mouse synovial cells were randomly divided into a control group,a model group,an Agiophyllum Oligo Saccharides group and a Bay 11-7082 group.Osteoarthritic synoviocyte model was prepared using 1.0 μg/mL lipopolysaccharide intervention for 36 hour.The Agiophyllum Oligo Saccharides group was treated with 1.0 μg/mL lipopolysaccharide and 32 μg/mL Agiophyllum Oligo Saccharides for 36 hours;and the Bay 11-7082 group was firstly incubated for 4 hours with 1 μmol/L NF-κB pathway inhibitor Bay 11-7082,and then 1.0 μg/mL lipopolysaccharide and 32 μg/mL Agiophyllum Oligo Saccharides for 36 hours.Western blot was used to detect TLR4,MyD88,NF-κBp65,p-NF-κBp65,and IκBα protein expression.The level of tumor necrosis factor-α and interleukin-1β in the supernatant were analyzed by ELISA.To detect the expressions of Bax and Bcl-2,western blot and immunofluorescence analysis were performed.The intracellular reactive oxygen species level was detected by DCFH-DA.RESULTS AND CONCLUSION:(1)Compared with the control group,the levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species,the protein expressions of TLR4,MyD88,Bcl-2,and p-NF-κBp65/NF-κBp65 increased(P<0.05),whereas the protein expressions of IκBα and Bax decreased(P<0.05)in the model group.(2)Compared with the model group,the levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species,the protein expressions of TLR4,MyD88,Bcl-2,and p-NF-κBp65/NF-κBp65 decreased(P<0.05),while the expressions of IκBα and BAX increased(P<0.05)in the Agiophyllum Oligo Saccharides group.(3)The levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species and the protein expression of Bcl-2 in the Bay 11-7082 group were higher than those in the Agiophyllum Oligo Saccharides group(P<0.05),but still lower than those in the model group(P<0.05),whereas the expression of Bax protein was lower than that in the Agiophyllum Oligo Saccharides group(P<0.05),but still higher than that in the model group(P<0.05).(4)Compared with the model group and the Agiophyllum Oligo Saccharides group,the protein expressions of TLR4,MyD88 and p-NF-κBp65/NF-κBp65 decreased(P<0.05),whereas the protein expressions of IκBα increased(P<0.05)in the Bay 11-7082 group.To conclude,Agiophyllum Oligo Saccharides could inhibit inflammation of mouse synovial cells and promote apoptosis of synovial cells with inflammation,and the mechanisms may be correlated with regulating the TLR4/NF-κB signaling pathway.

BACKGROUND:For knee osteoarthritis,synovium inflammation and abnormal proliferation and activation of fibroblast-like synoviocytes caused by insuffcient apoptosis are important driving factors for disease progression.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway plays a key role in regulating inflammatory response and apoptosis of synovial cells.As a traditional Mongolian medicine component,Agiophyllum Oligo Saccharides has anti-inflammatory and immunomodulatory functions,but its specific molecular mechanism has not been fully revealed.OBJECTIVE:To explore the effects and mechanism of Agiophyllum Oligo Saccharides on lipopolysaccharide-induced inflammation and apoptosis of mouse synovial cells.METHODS:The mouse synovial cells were randomly divided into a control group,a model group,an Agiophyllum Oligo Saccharides group and a Bay 11-7082 group.Osteoarthritic synoviocyte model was prepared using 1.0 μg/mL lipopolysaccharide intervention for 36 hour.The Agiophyllum Oligo Saccharides group was treated with 1.0 μg/mL lipopolysaccharide and 32 μg/mL Agiophyllum Oligo Saccharides for 36 hours;and the Bay 11-7082 group was firstly incubated for 4 hours with 1 μmol/L NF-κB pathway inhibitor Bay 11-7082,and then 1.0 μg/mL lipopolysaccharide and 32 μg/mL Agiophyllum Oligo Saccharides for 36 hours.Western blot was used to detect TLR4,MyD88,NF-κBp65,p-NF-κBp65,and IκBα protein expression.The level of tumor necrosis factor-α and interleukin-1β in the supernatant were analyzed by ELISA.To detect the expressions of Bax and Bcl-2,western blot and immunofluorescence analysis were performed.The intracellular reactive oxygen species level was detected by DCFH-DA.RESULTS AND CONCLUSION:(1)Compared with the control group,the levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species,the protein expressions of TLR4,MyD88,Bcl-2,and p-NF-κBp65/NF-κBp65 increased(P<0.05),whereas the protein expressions of IκBα and Bax decreased(P<0.05)in the model group.(2)Compared with the model group,the levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species,the protein expressions of TLR4,MyD88,Bcl-2,and p-NF-κBp65/NF-κBp65 decreased(P<0.05),while the expressions of IκBα and BAX increased(P<0.05)in the Agiophyllum Oligo Saccharides group.(3)The levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species and the protein expression of Bcl-2 in the Bay 11-7082 group were higher than those in the Agiophyllum Oligo Saccharides group(P<0.05),but still lower than those in the model group(P<0.05),whereas the expression of Bax protein was lower than that in the Agiophyllum Oligo Saccharides group(P<0.05),but still higher than that in the model group(P<0.05).(4)Compared with the model group and the Agiophyllum Oligo Saccharides group,the protein expressions of TLR4,MyD88 and p-NF-κBp65/NF-κBp65 decreased(P<0.05),whereas the protein expressions of IκBα increased(P<0.05)in the Bay 11-7082 group.To conclude,Agiophyllum Oligo Saccharides could inhibit inflammation of mouse synovial cells and promote apoptosis of synovial cells with inflammation,and the mechanisms may be correlated with regulating the TLR4/NF-κB signaling pathway.

ObjectiveTo analyze the polarized light microscopic characteristics， the composition of physical phases and their relative contents of Maifanitum from different origins， and to establish the Fourier characteristic fingerprint of Maifanitum powder crystals by X-ray diffraction（XRD）. MethodA total of 26 batches of Maifanitum samples were selected， and the microscopic characteristics of the sample powders and grinding flakes were observed by polarized light microscopy under single polarized light and orthogonal polarized light， and the main phase compositions and their relative contents were analyzed by powder crystal XRD technique， and the XRD Fourier characteristic fingerprint of Maifanitum was established. The incident light source of XRD was Cu target Kβ radiation， the light tube voltage and light tube current were 40 kV and 40 mA， respectively， the divergence slit was 1°， the scattering slit was 1°， the receiving slit was 0.2 mm， the scanning speed was 5°·min^-1 with continuous scanning and scanning range of 5-90°（2θ）， and the step length was 0.02°. ResultThe polarized light micrographs of powders and grinding flakes of Maifanitum were obtained， and the main phases were plagioclase， potassium feldspar and quartz， and a few samples also contained illite， pyrite， iron dolomite， calcite， iron amphibole and chlorite， etc. The relative total content of feldspar phases was 61.9%-82.4%， and the relative content of quartz was 12.6%-33.6%. The XRD Fourier fingerprint analysis method of Maifanitum with 13 common peaks as the characteristic fingerprint information was established， and the similarity calculated by the mean correlation coefficient method was 0.920 9-0.997 7， the similarity calculated by the mean angle cosine method was 0.940 5-0.998 4， the similarity calculated by the median correlation coefficient method was 0.921 1-0.997 5， and the similarity calculated by the median angle cosine method was 0.947 5-0.998 2. ConclusionThe polarized light microscopic identification characteristics of Maifanitum are mainly plagioclase， quartz and potassium feldspar， and the technique of powder crystal XRD Fourier fingerprint analysis can be used for the identification of Maifanitum.

Exploring the genetic basis of human infertility is currently under intensive investigation.However,only a handful of genes have been validated in animal models as disease-causing genes in infertile men.Thus,to better understand the genetic basis of human spermatogenesis and bridge the knowledge gap between humans and other animal species,we construct the FertilityOnline,a data-base integrating the literature-curated functional genes during spermatogenesis into an existing sper-matogenic database,SpermatogenesisOnline 1.0.Additional features,including the functional annotation and genetic variants of human genes,are also incorporated into FertilityOnline.By searching this database,users can browse the functional genes involved in spermatogenesis and instantly narrow down the number of candidates of genetic mutations underlying male infertility in a user-friendly web interface.Clinical application of this database was exampled by the identifi-cation of novel causative mutations in synaptonemal complex central element protein 1(SYCE1)and stromal antigen 3(STAG3)in azoospermic men.In conclusion,FertilityOnline is not only an integrated resource for spermatogenic genes but also a useful tool facilitating the exploration of the genetic basis of male infertility.

Objective:To evaluate early corneal biomechanical change, safety and effectiveness after small-incision lenticule extraction combined with ultraviolet A corneal collagen cross-linking (SMILE-CXL) for myopic eyes and compare with SMILE.Methods:A non-randomized controlled clinical study was performed.Forty-four myopic eyes of 25 patients were included in Hankou Aier Eye Hospital from December 2017 to July 2018.SMILE-CXL or SMILE was carried out for 22 eyes of 12 patients or 22 eyes of 13 patients, respectively, based on the normal posterior surface manifestation of Belin by Pentacam tomography or not.The posterior surface manifestation of Belin was normal in the SMILE group, and the posterior surface of Belin was yellow or red with Corvis biomechanical index and tomographic biomechanical index<0.3 (except keratoconus) in the SMILE-CXL group.The refractive diopter of the eyes was detected before and 6 months after surgery, including spherical diopter, cylindrical diopter and spherical equivalent (SE) with a comprehensive refractometer.The corneal biomechanical parameters of the eyes were detected before and 6 months after surgery with a Scheimpflug-based dynamic tonometry (Corvis ST). The safety index, a ratio of postoperative mean best corrected visual acuity (BCVA) to preoperative mean BCVA, and efficacy index, a ratio of postoperative uncorrected visual acuity (UCVA) to preoperative BCVA, were compared between SMILE-CXL group and SMILE group.BCVA and UCVA were examined using standard chart and converted to logarithm of the minimal angle of resolution (LogMAR) units.This protocol complied with the Declaration of Helsinki and was approved by an Ethics Committee of Hankou Aier Eye Hospital (No.WHS2017052701). Written informed consent was obtained from each patient prior to entering into the cohort.Results:The postoperative UCVA of the eyes in both groups was more than 1.0.There were no significant differences in safety index, efficacy index and SE change between the SMILE-CXL group and SMILE group (all at P≥0.05). At 6 months after surgery, the values of second applanation time (A2T), time from the start until the highest concavity (HC-Time) and DA ratio 2 mm were significantly increased in comparison with before operation in both SMILE-CXL group and SMILE group (all at P<0.05). The changes of A2T, HC-Time and DA ratio 2 mm in the SMILE-CXL group were significantly lowered than those in the SMILE group at the sixth month after surgery ( P=0.001, 0.001, 0.036). The deformation amplitude, maximum corneal velocity during the first applanation (Vin), distance between both non-deformed peaks and integrated radius during the maximum depression were significantly increased, and the central curvature radius at highest concavity, cord length of first applanation, cord length of second applanation, Ambrósio's relational thickness horizontal, stiffness parameter applanation 1 and biomechanical intraocular pressure during the maximum depression were significantly lower at the sixth month after surgery than those before surgery (all at P<0.05). There were no significant differences in the parameters mentioned above between the two groups (all at P<0.05). Conclusions:Compared with SMILE alone, SMILE-CXL shows a comparable safety and efficacy, and better corneal biomechanical properties.

The traditional teaching mode of "subject-centered" has many shortcomings such as knowledge separation and lack of integrity. In order to make up for the deficiencies of this mode, the organ-system integrated medical teaching mode has gradually become the trend of medical teaching reform. Taking "motor system" as an example, this paper discusses the practice of the organ-system integrated medical teaching mode from four aspects: teaching implementation, teaching quality supervision, supporting assessment system and teaching effectiveness.

OBJECTIVE： To systematically evaluate the efficacy and safety of cyclosporin combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid in the treatment of membranous nephropathy （MN）. METHODS： Retrieved from Embase， Medline， CNKI， VIP and Wanfang database， RCTs about cyclosporin combined with glucocorticoid （trial group） versus cyclophosphamide combined with glucocorticoid （control group） in the treatment of MN were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with Jadad scale. RESULTS： Totally 6 RCTs were included， involving 312 patients in total. Results of Meta-analysis showed that remission rate 3 months after treatment [OR＝3.42，95％CI（2.05，5.71），P＜0.000 01] and relapse rate [OR＝3.12，95％CI（1.45，6.70），P＝0.004]， leukocyte count 12 months after treatment [MD＝1.77，95％CI（0.96，2.58），P＜0.000 1] in trial group were significantly higher than control group. There was no statistical significance in remission rate 6 months after treatment [OR＝2.06，95％CI（0.80，5.30），P＝0.13] and remission rate 12 months after treatment [OR＝1.30，95％CI（0.68，2.48），P＝0.42]， blood creatinine level 3 months after treatment [MD＝－1.55，95％CI（－6.72，3.62），P＝0.56] and blood creatinine level 6 months after treatment [MD＝－1.21，95％CI（－5.96，3.54），P＝0.62]， cholesterol level 12 months after treatment [MD＝－0.77，   95％CI（－1.81，0.28），P＝0.15] or ALT level[MD＝－0.40，95％CI（－4.38，3.58），P＝0.98] between 2 groups. ADR were reported in 5 RCTs， but their results were different. CONCLUSIONS： Long-term efficacy of cyclosporine combined with corticosteroid is similar to that of cyclophosphamide combined with corticosteroid in the treatment of MN. Cyclosporin combined with glucocorticoid has a faster effect， but a higher relapse rate.

Objective To explore difference of neuropsychological tests between the remitted schizophrenia patients and the first-degree non-psychotic relatives of schizophrenia patients,and to explore the possible endophenotypes in cognitive function.Methods The MATRICSTM consensus cognitive battery was administered to 86 remittent schizophrenia patients (the patient group),86 first-degree non-psychotic relatives of schizophrenia patients (the relative group),and 86 healthy people (the control group).Results Compared with the control group,the patients group and the relative group showed poor performance on trail making test,brief assessment of cognition,hopkins verbal learning,mazes,category fluency,emotional intelligence test and continuous performance test (P＜0.05).There were significantly lower performances in the patient group than the relative groups on hopkins verbal learning,mazes,emotional intelligence test and continuous performance test (P＜0.05).Conclusion The remitted schizophrenia patients and their first-degree non-psychotic relatives have selective deficits in cognition function,among them,verbal leaning,attention/vigilance,reasoning and problem solving and social cognition may be potential endophenotypes for schizophrenia.

Objective To examine the difference of neurological soft signs (NSS) among the remittent schizophrenia patients,first-degree non-psychotic relatives of schizophrenia patients and healthy controls.Methods The Cambridge Neurological Inventory (CNI) (the Chinese version) was administered to 86 remittent schizophrenia patients (patient group),86 first-degree non-psychotic relatives of schizophrenia patients (relative group) and 86 healthy controls (control group).Results Compared with relative group,NSS total-score,the subscore of motor coordination and sensory integration were significantly higher in patient group (P＜0.01).Compared with control group,NSS total-score,the subscore of motor coordination and sensory integration were significantly higher in patient group (P＜0.01).Compared with control group,NSS total-score and the subscore of motor coordination were significantly higher in relative group (P＜0.01).Conclusions The levels of NSS in remittent schizophrenia patients and their first-degree non-psychotic relatives are higher than normal control,and the patients have more NSS than their relatives.The motor coordination nay be a potential endophenotype for schizophrenia.

Objective To study the effect of curcumin on the radiosensitivity of the human papillary thyroid cancer cell line TPC?1, to investigate the signaling pathway probably targeted by curcumin, and to provide new insights for the development of radiosensitizers for thyroid cancer. Methods The human papillary thyroid cancer cell line TPC?1 was treated with curcumin and radioactive iodine. CCK?8 assay, colony formation assay, and flow cytometry were used to evaluate cell proliferation, colony formation ability, and cell apoptosis, respectively. Western blot was used to measure the expression of p50, p65, and apoptosis?related proteins, Bcl?2 and Bax. Cell proliferation, colony formation ability, and cell apoptosis were determined again after the activity of the NF?κB signaling pathway was blocked by a NF?κB signaling pathway inhibitor PDTC. Results After treatment with curcumin and radioactive iodine, the human papillary thyroid cancer TPC?1 cells had reduced cell proliferation and colony formation, an elevated apoptosis rate, downregulated expression of anti?apoptotic Bcl?2, and upregulated expression of pro?apoptotic Bax in a dose?dependent manner. These results indicated that curcumin enhanced the radiosensitivity of TPC?1 cells. Curcumin inhibited the activation of the NF?κB signaling pathway in the TPC?1 cells treated with radioactive iodine. When the activity of the NF?κB pathway was blocked by PDTC, cell proliferation and colony formation were reduced and the apoptosis rate was increased, indicating an enhanced radiosensitivity of TPC?1 cells. Conclusions Curcumin is likely to target the NF?κB signaling pathway. It regulates the radiosensitivity of thyroid cancer cells by inhibiting the activity of the NF?κB signaling pathway.