Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell lymphoma, and its pathogenesis remains unclear. Recent studies have uncovered high-frequency chromosomal copy number variations in MF, such as gain of chromosomes7q,1q,17q and loss of 9p21,10q,17p, which lead to the gain of proto-oncogenes and loss of tumor suppressor genes, and finally result in tumor development and progression. Moreover, low-frequency single-nucleotide variants have been found in MF, and these mutated genes are mostly enriched in the pathways associated with cell cycle regulation, cell apoptosis, chromatin remodeling as well as T cell activation. Gene-fusion variation is rarely reported in MF. In addition, large cell transformation may occur in some MF cases, and often indicates poor prognoses such as disease progression and drug resistance. In conclusion, MF is a complex disease with highly molecular genetic heterogeneity, and more extensive and intensive researches on its pathogenesis are needed in the future.

Objective To investigate the role of autophagy in podocyte damage,and the intracellular mechanism of autophagy activation through passive Heymann nephritis (PHN) animal model.Methods Male Sprague-Dawley rats (n=40) were studied on day 0,2,4,7,and 21 after induction of PHN by injection of anti-Fx1A.Podocyte morphology and autophagosomes were observed by transmission electron microscopy.Podocyte numerical density was estimated by Weibel-Gomez =method.Cell apoptosis was detected by TUNEL assay and caspase-3 immunohistochemical staining.Expressions of autophagy markers and endoplasmic reticulum stress (ERS)-associated proteins were analyzed by Western blotting.Results (1) In PHN rats,immunohistochemical staining showed that C5b-9 deposited along glomerular basement membrane on day 4 to day 21.Small subepithelial electron -dense deposits and a part of foot process fusion were detected in the glomerulus of PHN rats on day 4 by transmission electron microscope,and podocyte damage was aggravated on day 21.Furthermore,compared with control,the urinary protein levels of PHN rats began to increase on day 3,and reached the top on day 21 [(50.6±6.0) mg/24 h].(2) The number of podocytes significantly decreased in PHN rats compared with control group on day 21(P ＜ 0.05).(3) In PHN rats,apoptotic podocytes were found by caspase-3 immunohistochemical staining and TUNEL assay on day 21.(4) The expression of autophagy marker LC3 Ⅱ was markedly increased on day 7 and 21,but down-regulated on day 21 compared with day 7.Moreover,accumulated autophagosomes in podocytes were detected on day 7 and 21 by transmission electron microscope.(5) The level of GRP78 was significantly increased on day 2 and 7 but reduced to baseline on day 21.At the same time,the downstream pathways (ATF6α,p-PERK and p-JNK) of unfolded protein response were also up-regulated in the early process of PHN and down-regulated later.Conclusions Autophagy is an important way to protect against immunemediated podocyte injury in membranous nephropathy.Autophagy activation is mainly related to endoplasmic reticulum stress induced by complement attack.This provides an important basis for a thorough understanding of the role of autophagy in the process of podocyte damage and the pathogenesis of membranous nephropathy.

AIM: To determine the effect of rapamycin on the progression of passive Heymann nephritis (PHN), and whether autophagy is involved in this process .METHODS:Male Sprague-Dawley rats (n=24) were ran-domly divided into 3 groups:control group , PHN group and rapamycin treatment group .The rat PHN model was induced by injection of anti-Fx1A serum through penile vein , and all rats were sacrificed on day 21.Automatic biochemical analyzer was used to detect 24 h urine protein , blood urea nitrogen and serum creatinine .Renal damage was observed through per-iodic acid-silver methenamine staining .The number of podocyte was estimated by Weibel-Gomez method .The glomerular deposition of C5b-9, the expression of caspase-3 and expression of autophagy marker LC 3 in glomeruli were examined by immunofluorescence staining , immunohistochemical staining and Western blotting , respectively.RESULTS: Rapamycin significantly reduced proteinuria in the PHN rats (P<0.05), while the renal functions in 3 groups were normal, without significant difference .Although rapamycin limited weight gain in the rats , the health of the rats during drug treatment was not affected .Rapamycin retarded glomerular basement membrane thickening in the PHN rats .Rapamycin significantly re-duced the podocyte deletion by preventing podocyte apoptosis .Rapamycin enhanced the level of autophagy of glomerular in-herent cells .CONCLUSION:In the disease process of PHN , appropriate strength of autophagy plays a protective role . Rapamycin appropriately enhances autophagy and prevents podocyte apoptosis , thus reducing nephropathy and proteinuria . This may be one of the important mechanisms of rapamycin to slow down the progress of PHN .

AIM:In podocytes , autophagy occurs at a high basal level and dysregulated autophagy is associa -ted with a variety of podocytopathies .This paper is to investigate the role of autophagy in sublytic C 5b-9-induced podocyte injury.METHODS: Sublytic complement C5b-9 stimulation was used as an in vitro model.Autophagosomes were con-firmed using monodansylcadaverine (MDC) staining.Immunoblotting was used to measure the change of autophagy-related markers.Cellular morphological changes were observed by Wright-Giemsa staining.Immunofluorescence staining and con-focal microscopy were used to detect the expression and distribution of nephrin .The cell viability was assessed by methylth-iazol tetrazolium (MTT) assay.The cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate/PI staining.RE-SULTS:For ensuring sublytic complement injury , the maximal amounts of anti-podocyte antiserum and 160 ×-diluted nor-mal human serum were used without inducing cell lysis (defined as >5%LDH release).Sublytic C5b-9 promoted autoph-agy of podocytes in vitro.The proautophagic effect of sublytic C 5b-9 manifested in the form of accumulated MDC-labeled vesicles and enhanced the expression of LC 3-Ⅱ.Autophagy inhibitor 3-methyladenosine (3-MA) promoted sublytic C5b-9-induced podocyte morphological abnormalities .Compared with the sublytic C5b-9-injured podocytes, 3-MA exposure further decreased the expression of nephrin .3-MA enhanced sublytic C5b-9-induced podocyte apoptosis .CONCLUSION: Sub-lytic C5b-9 attack induces autophagy , which may play a protective role against complement-mediated podocyte injury .

Objective To investigate the effects of inhibitor of growth 5 (ING5) gene on the proliferation, apoptosis, migration and cell cycle of human breast cancer Bcap-37 cells.Methods The eukaryotic ING5-expressing plasmid and GFP-empty plasmid were steadily transfected in Bcap-37 cells, the expression of green fluorescent protein was measured with fluorescence microscopy, and the high expression of ING5 was measured by real time-PCR. Bcap-37-ING5 cells served as the experimental group, Bcap-37-GFP cells as the mock group and Bcap-37 as the control group. The effects of ING5 on the proliferation were detected by MTT, the cell cycle and apoptosis were detected by Flow cytometry, and the cell migration was detected by cell wound scratch assay and Transwell experiment.Results Bcap-37 cell lines steadily expressing ING5 protein with GFP-tag were acquired by stable transfection. ING5 over-expression inhibited the proliferation and led to G2 arrest of Bcap-37 cells, increased cells apoptosis and decreased the cell migration ability (P<0.05).Conclusion ING5 over-expression may have reverse effect for malignant phenotype of breast cancer cells, and may be employed to indicate the biomarker of prognosis of breast cancer patients and regarded as a target of gene therapy.

AIM:To study the effect of Hand2 (one of basic helix-loop-helix proteins’ transcription factors) expression on the development of the cardiac tissues in the fetal rats from gestational diabetes mellitus ( GDM) parents, and to investigate the potential pathogenesis of GDM-induced congenital cardiac defects in rats.METHODS: The adult Spra-gue-Dawley female rats were randomly divided into blank control group (n=24), GDM group (n=30), negative control group ( n=30) and insulin intervened group ( n=30) .The GDM model was established by intraperitoneal injection of 2%streptozotocin (STZ, 40 mg/kg body weight) to the pregnant rats on the successive day.The rats in insulin intervened group were injected with intermediate-acting insulin in order to keep the fasting blood glucose in the normal range.The rats in negative control group were injected with citric acid-sodium citrate buffer solution in the same position.Blood glucose and body weight were examined every day 72 h after STZ injection.On E12, E15 and E19, the rats were anesthetized and the embryonic cardiac tissues were collected after caesarean section.The histopathological changes of the cardiac tissues were observed under microscope with HE staining.The expression of Hand2 was analyzed by the method of immunohisto-chemistry.The expression of Hand2 in the cardiac tissues at mRNA and protein levels was determined by real-time fluores-cence quantitative PCR and Western blotting.RESULTS:During the development of embryonic heart, the protein expres-sion of Hand2 in the cardiac tissues was showed dynamic changes.Observed on E12, obviously increased on E15, and at the highest level on E19.Compared with the other 3 groups, the protein and mRNA expression of Hand2 in GDM group was decreased at the time points of E12 and E15.CONCLUSION:The morbidity of fetal cardiac malformation is significantly increased in GDM group, suggesting that Hand2 may be involved in the development of cardiac malformation in GDM.

Objective To determine the effect of rapamycin on sublytic C5b-9-induced podocyte adhesion damage,and whether autophagy is involved in this progression.Methods Sublytic complement C5b-9 stimulation was used in vitro.Autophagosomes were viewed using electron microscopy.Western blotting was used to measure the change of autophagy-related markers.Attachment assay was used to assess the adhesion of podocyte.Confocal microscopy was used to explore the expression patterns of cytoskeletal protein F-actin.Flow cytometry was used to measure the level of adhesion-associated protein integrin α3.Results (1) For ensuring sublytic complement injury,the maximal amounts of anti-podocyte antiserum and 160×-diluted normal human serum were used without inducing cell lysis (defined as ＞ 5％ LDH release).(2) Sublytic C5b-9 promoted autophagy in podocyte in vitro.The proautophagic effect of sublytic C5b-9 manifested in the form of accumulated autophagosomes and enhanced expression of LC3-lⅡ.(3) Inhibition of autophagy by 3-methyadenine enhanced the effect of sublytic C5b-9-induced podocyte injury,including serious cytoskeleton damage and markedly reduced adhesion of podocyte.(4) Rapamycin treatment significantly improved the above lesions.(5) Rapamycin enhanced autophagy induced by sublytic C5b-9 in podocyte.Conclusions In summary,rapamycin can improve sublytic CSb-9-induced podocyte adhesion damage by appropriate autophagy activation.These findings provide important information for the development of appropriate protocols for the application of mTOR (mammalian target of rapamycin) inhibitors in podocytopathy.

The basic diagnostic and treatment principles of traditional Chinese medicine are the pattern-differentiation-deduced pathogenesis and treatment based on examination of the pathogenesis.Shanghan Lun established a system of pattern differentiation of six meridians,systematically summarized the evolution laws of exogenous febrile disease,and discussed miscellaneous diseases as exogenous diseases.It contains 112 classic formulas and advocates that"those whose disease corresponds to the formulas should take them accordingly",combining disease differentiation and pattern differentiation,containing not only the knowledge of treatment based on pattern identification,but also the profundity of pattern-differentiation-deduced pathogenesis.Based on the original meaning of"pathogenesis",from the three angles of"subtle meaning","core meaning",and"appropriate meaning",this paper exemplifies the concept of pattern differentiation for six meridians in Shanghan Lun,analyzes the relationship and connotation of formula patterns of classical formulas in Shanghan Lun by"taking pattern with formulas",and explores the concept of pattern-differentiation-deduced pathogenesis in Shanghan Lun.This paper emphasizes that during the clinical practice of traditional Chinese medicine,it is important(i)to deduce the pathogenesis based on pattern differentiation,understand symptoms upon first onset,and deduce the pathogenesis before symptoms appear,thereby treating the disease at an early stage;(ii)to identify the most important concepts,solve complications with simple method,discern the core of the disease,and treat the entire body;and(iii)to optimize timing,act quickly,take advantage of opportunities,accept outcomes,and provide judicious guidance to patients.This paper serves to interpret Shanghan Lun based on pattern-differentiation-deduced pathological mechanism and provides ideas and inspiration for applying the theory of Shanghan Lun to guide clinical practice.

Objective: To investigate the influence of maternal age on the health status of pregnant women and the pregnant outcomes. Methods: Data obtained from "Beijing perinatal health management registration system" was analyzed, 263 157 pregnant women with age information were included from October 1st, 2015 to September 30th, 2016, in which 43 594 women delivered at the age of 35 or above (advanced age) . According to the age of maternal age, there were 5 groups. (1) Proper age: 219 563 (83.43%, 219 563/263 157) cases of the age of 18-34 years, including 122 735 cases (46.64%, 122 735/263 157) in the ≤29 years old group and 96 828 cases (36.79%, 96 828/263 157) in 30-34 years old group. (2) Advanced age: there were 43 594 cases (16.57%, 43 594/263 157) ≥35 years old, including 37 395 cases (14.21%, 37 395/263 157) in the 35-39 years old group, 5 790 cases (2.20%, 5 790/263 157) in the 40-44 years old group and 409 cases (0.16%, 409/263 157) in the ≥45 years old group. The trend-based chi-square test and logistic regression were used to analyze the effects of different age groups on maternal complications and pregnant outcomes. Results: (1) The total incidence of high risk pregnancy (HRP) : in advanced age women, the incidence of HRP was 67.83% (29 571/43 594) which was 56.73% (124 550/219 563) in proper age women, the difference was statistically significant (χ²=1 848.91, P<0.000) . In advanced age women, the incidence of severe HRP was 7.64% (3 329/43 594) which was 6.18% (13 571/219 563) in proper age women, the difference was statistically significant (χ²=128.211, P<0.000) . In advanced age women, the incidence of very severe HRP was 1.76% (769/43 594) which was 0.84% (1 838/219 563) in proper age women, the difference was statistically significant (χ²=318.58, P<0.000) . (2) Comparison of the incidence of HRP in 5 groups:the total incidence of HRP increased through the following age group ≤29 years, 30-34 years, 35-39 years, 40-44 years, ≥45 years (53.28%, 61.09%, 67.41%、70.09%, 74.57% respectively) , the difference was statistically significant (linear by linear χ²=3 165.72, P<0.000) . The incidence of very severe HPR increased (0.66%, 1.06%, 1.66%, 2.35%, 2.93% respectively) , the difference was statistically significant (linear by linear χ²=218.31, P<0.000) . The incidence of severe HPR increased (5.77%, 6.70%, 7.48%, 8.34%, 11.49% respectively) , the difference was statistically significant (linear by linear χ²=422.20, P<0.000) . The incidence of general HPR increased (46.84%, 53.34%, 58.26%, 59.40%, 60.15% respectively) , the difference was statistically significant (linear by linear χ²=1 947.51, P<0.000) . (3) As the maternal age group increased, the incidence of adverse pregnancy outcomes increased (5.54%, 6.85%, 8.77%, 9.90%, 18.09%, linear by linear χ²=674.57, P<0.000) . The incidence of perinatal death, premature birth and low birth weight also presented the above trends (perinatal death: linear by linear χ²=34.79, P<0.000; premature birth: linear by linear χ²=692.87, P<0.000; low birth weight: linear by linear χ²=379.20, P<0.000) . (4) Logistic regression analysis with the assisted reproductive technology and multiple pregnancy considered showed the same trend (P<0.000) . Conclusion The maternal age has an impact on the maternal health status and pregnancy outcomes, and the risk of various types of pregnancy complications and adverse pregnancy outcomes increase with the maternal age group, antenatal care and management should be emphasized in women with advanced maternal age, especially for women ≥40 years old.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.