Male Infertility Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In recent years，with the change in lifestyle and social environment and the increase in pressure in both life and work，male fertility has decreased significantly in China，and the incidence of male infertility has increased year by year，which has brought great challenges to andrologists. Traditional Chinese medicine （TCM） has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility，the China Association of Chinese Medicine （CACM） invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia，abnormal semen liquefaction，varicocele，immune infertility，improving success ratio of assisted reproductive technology，and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages，characteristics，disadvantages，diseases responding specifically，and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility，western medicine cannot achieve a good curative effect，while TCM，taking the holistic view as the core，specializes in improving functional diseases and can correspond to multiple targets and factors，with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists，increase mutual learning and communication between TCM and western physicians，provide patients with excellent and personalized treatment plans in clinical practice，and improve the curative effect of male infertility and fertility of males in China.

Advantages of Chinese Medicine in Treating Dominant Disease： Benign Prostatic Hyperplasia / 中国实验方剂学杂志

China Association of Chinese Medicine organized specialists in andrology of Chinese and western medicine to explore the population and treatment stage of benign prostatic hyperplasia （BPH） with Chinese medicine as the leading therapy. Chinese medicine has great advantages in the treatment of benign prostatic hyperplasia. However， it is necessary to make clear the stage when Chinese medicine or modern medical treatment can be used as the leading therapy， and the conditions under which Chinese and western medicine can be combined to achieve the best treatment efficacy. The specialists agreed Chinese medicine as the leading therapy for the treatment of BPH in the following populations or conditions： the elderly and weak patients with basic diseases， BPH symptoms， and cannot tolerate anesthesia and surgery， the patients with BPH symptoms and cannot tolerate the adverse reactions or the possible adverse reactions of western medicine； the patients with mild ［international prostatic symptom score （IPSS） ≤ 7］ or moderate lower urinary tract symptoms （IPSS ≥ 8） and the quality of life not significantly affected， the patients with bladder detrusor hypofunction， bladder dysfunction and cannot be treated surgically， or with incomplete bladder emptying after surgical treatment； the BPH patients with prostatitis as the main clinical manifestation， the patients with non-acute complications after operation. BPH is one of the dominant diseases in urology and andrology of Chinese medicine， and the symptoms， complications， and prognosis of BPH patients need to be fully considered during the clinical treatment. When Chinese medicine is taken as the leading therapy， it is essential to regularly review the serum level of prostate-specific antigen to exclude the possibility of prostate cancer， and apply Chinese medicine for full treatment course and cycle. At the same time， Chinese and western medicine can be combined to achieve the most effective， convenient， economical， and satisfactory treatment， which can carry forward the advantages of Chinese medicine in treating this disease.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61 / 中西医结合学报

OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Modified strict sperm morphology threshold aids in the clinical selection of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) / 亚洲男科学杂志(英文版)

For infertility treatment, the selection of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is decided by multiplying indicators (including fallopian tube factors, semen count, and semen motility), except for sperm morphology. In this study, we conducted a retrospective analysis, from implantation to birth, over a period of 5 years. A total of 1873 couples with primary or secondary fallopian tube factors and an increased defective sperm morphology rate (DSMR) were divided into different groups to receive IVF or ICSI cycles. By comparing the outcomes, we found that the F1 group (DSMR <96%, IVF group 1) had higher cleavage rate, biochemical pregnancy rate, clinical pregnancy rate, and live birth rate than the F3 group (DSMR >98%, IVF group 3; P < 0.05). In contrast, there was no significant difference in the ICSI subgroups. Furthermore, a comparison of the outcomes between IVF and ICSI showed that the S3 group (DSMR >98%, ICSI group 3) had higher cleavage rate (P < 0.001), biochemical pregnancy rate (P < 0.05), clinical pregnancy rate (P < 0.05) and live birth rate (P < 0.05) than the F3 group. However, the ICSI subgroup had a lower two pronuclei fertilization rate than the IVF subgroup (P < 0.05). Our data suggest that the sperm morphology should also be considered when selecting IVF or ICSI combined with other semen parameters before the first assisted reproductive technologies (ART) cycle, especially for males with severe sperm defects.

Vascular endothelial growth factor induces inflammatory injury of pancreatic tissue by activating autophagy in hyperlipidemic acute pancreatitis rats / 生理学报

This study was to investigate the changes of autophagy in pancreatic tissue cells from hyperlipidemic acute pancreatitis (HLAP) rats and the molecular mechanism of autophagy to induce inflammatory injury in pancreatic tissue cells. Male Sprague Dawley (SD) rats were intraperitoneally injected with caerulein to establish acute pancreatitis (AP) model and then given a high fat diet to further prepare HLAP model. The HLAP rats were treated with autophagy inducer rapamycin or inhibitor 3-methyladenine. Pancreatic acinar (AR42J) cells were treated with caerulein to establish HLAP cell model. The HLAP cell model were treated with rapamycin or transfected with vascular endothelial growth factor (VEGF) siRNA. The inflammatory factors in serum and cell culture supernatant were detected by ELISA method. The histopathological changes of pancreatic tissue were observed by HE staining. The changes of ultrastructure and autophagy in pancreatic tissue were observed by electron microscopy. The expression levels of Beclin-1, microtubule- associated protein light chain 3-II (LC3-II), mammalian target of rapamycin complex 1 (mTORC1), and VEGF were measured by immunohistochemistry and Western blot. The results showed that, compared with control group, the autophagy levels and inflammatory injury of pancreatic tissue cells from HLAP model rats were obviously increased, and these changes were aggravated by rapamycin treatment, but alleviated by 3-methyladenine treatment. In HLAP cell model, rapamycin aggravated the autophagy levels and inflammatory injury, whereas VEGF siRNA transfection increased mTORC1 protein expression, thus alleviating the autophagy and inflammatory injury of HLAP cell model. These results suggest that VEGF-induced autophagy plays a key role in HLAP pancreatic tissue cell injury, and interference with VEGF-mTORC1 pathway can reduce the autophagy levels and alleviate the inflammatory injury. The present study provides a new target for prevention and treatment of HLAP.

Research progress of micro-RNA in intervertebral disc degeneration / 中华骨科杂志

Low back pain is becoming an important factor affecting people's quality of life, while the age of its onset is getting younger and younger, and the social and economic losses caused by low back pain are huge every year. Intervertebral disc degeneration (IDD) is an important cause of low back pain. Due to multiple factors, biomechanical and structural changes occur in intervertebral disc tissue, including rupture of annulus fibrosus, protrusion of nucleus pulposus, which cause compression of spinal cord and nerve root, and lower back pain. Micro-RNA (miRNA) is a kind of single-stranded non-coding small molecule RNA, with 18-24 nucleotides in length, which exists widely in eukaryotes. As one of the important regulatory molecules of gene expression, it has been proved to play a key role in the initiation and progression of many diseases, and it may also play an important role in intervertebral disc degeneration. At present, the clinical treatment for IDD is mainly surgical treatment to alleviate clinical symptoms. Even if surgical treatment can achieve good results, it will bring great physical trauma and economic burden to patients. The role of miRNA in IDD is one of the hotspots in the current academic research. Studies have shown that miRNA has abnormal expression patterns in degenerative intervertebral disc tissues and participates in a variety of pathological processes of IDD. At present, some miRNAs have been proved to be related to a variety of pathological processes in IDD, including nucleus pulposus cell apoptosis and proliferation, extracellular matrix degradation, autophagy, inflammation and cartilage endplate degeneration. The comparative study of gene chip showed that there were significant differences in the expression of some miRNAs between degenerative and normal nucleus pulposus cells. These differentially expressed miRNAs may be involved in the process of nucleus pulposus cell degeneration by regulating their respective upstream or downstream pathways. Most of the regulatory pathways are crossed and parallel, thus constructing a huge miRNA regulatory network. Understanding the target genes and mechanisms of miRNA in the pathogenic process can provide an important reference for the origin, development and prognosis of IDD. In this article, the important role of miRNA in IDD and the potential significance of clinical treatment are reviewed. With the in-depth study of miRNA and the molecular biological mechanism can provide new ideas for the diagnosis and treatment of IDD, which is likely to become a new strategy for biological treatment of IDD.

Key genes in malignant transformation of lung epithelial cells induced by hexavalent chromium based on GEO database / 环境与职业医学

Background Hexavalent chromium [Cr(VI)] can induce malignant transformation of lung epithelial cells, but its molecular mechanism is still unclear. Objective This study aims to explore the key genes of Cr(VI)-induced malignant transformation of lung epithelial cells and the mechanism of the transformation by bioinformatics analysis. Methods High-throughput gene expression profile data related to Cr(VI)-induced toxic effect was downloaded from the Gene Expression Omnibus(GEO) database, and the co-expressed genes were obtained by the intersection of differentially expressed genes in each dataset. DAVID 6.8 was used to analyze the function enrichment of gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways of the selected differential expression genes. STRING, and Cytoscape 3.8.2 were applied to construct and visualize the protein-protein interaction network. The expressions of Hub genes in lung tumor were obtained by GEPIA2. Results A total of 234 differentially expressed genes were screened out from the GSE24025 and GSE36684 datasets, among which 99 genes were up-regulated while 135 genes were down-regulated. The results of GO and KEGG analyse were mainly concentrated in cell adhesion, negative regulation of cell proliferation, and transcription disorders. A rotein-protein interaction network was generated by STRING database and Cytoscape software. Four functional modules with high scores and 6 Hub genes were finally retrieved. The expression trend of FBLN1 in lung cancer subtypes was consistent with the results of transcriptome screening. Conclusion Cr(VI) exposure causes the differential expression of multiple genes in lung epithelial cells, involving cell morphology, movement, survival fate, phenotype function and signal pathway related to cancer development. FBLN1 may be the critical gene related to malignant cytopathy.

Chinese Expert's Perspectives on Andrological Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In recent years， the incidence rate of andrological diseases has shown a significant growth trend. Considering the unavailability of a perfect theoretical system for andrology in traditional Chinese medicine （TCM） and the complex pathogenesis despite of the limited types of andrological diseases， it is necessary to improve the clinical efficacy of andrological diseases so as to satisfy the needs of patients. Therefore， the China Association of Chinese Medicine （CACM） organized the andrologists of TCM and western medicine and the outstanding young clinicians to discuss the andrological diseases responding specifically to TCM or integrated TCM and western medicine， such as chronic prostatitis， male infertility， benign prostatic hyperplasia， erectile dysfunction， and premature ejaculation， determine their diagnostic criteria in western medicine， and standardize the specifications for TCM diagnosis and treatment based on syndrome differentiation， thus formulating recognized and integrated diagnosis and treatment protocols. Apart from proposing suggestions on the treatment of such andrological diseases with TCM and western medicine， the experts have also figured out the andrological diseases responding specifically to TCM， the optimal intervention time of TCM and western medicine， and the suitable measures including surgery. The resulting consensus helps to better guide the formulation of accurate， personalized， and optimized treatment plans in clinical practice and improve the diagnosis and treatment effects of andrological diseases by giving full play to the advantages of TCM， which will in turn contribute to further innovation and development of TCM.

Expert Consensus on Otorhinolaryngology Head and Neck Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） and western medicine have their respective advantages and limitations in the diagnosis and treatment of common otorhinolaryngology head and neck diseases. Although the integrated TCM and western medicine exhibits definite curative effects， there is no consensus on the otorhinolaryngology head and neck diseases responding specifically to TCM or integrated TCM and western medicine， as well as the diagnosis and treatment schemes. The China Association of Chinese Medicine （CACM） thus organized the otorhinolaryngology head and neck specialists of both TCM and western medicine to discuss the etiology， pathogenesis， and clinical diagnosis and treatment methods of common otorhinolaryngology head and neck diseases with the results of multiple clinical trials taken into account. The acute pharyngitis， chronic pharyngolaryngitis， paraesthesia pharyngis， hysterical aphasia， allergic rhinitis， subjective tinnitus， and otogenic vertigo were confirmed to respond specifically to TCM or integrated TCM and western medicine. Then a mutually agreed diagnosis and treatment scheme and recommendation with integrated TCM and western medicine was formulated as a reference for clinical practice， thus benefiting more patients.

Obstetric Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In recent years， with the change in life style， social environment， and national childbearing policy， the proportion of high-risk pregnant women has increased significantly， triggering the spectrum of obstetric diseases to constantly change， which has brought new challenges to the diagnosis and treatment of obstetrics. Traditional Chinese medicine （TCM） has been proved effective in dealing with a variety of obstetric diseases， and various treatment methods are available， which can serve as alternative means for solving refractory obstetric diseases. However， most obstetric clinicians are currently less aware of the therapeutic effects of TCM， which has significantly hindered its participation in clinical treatment. Therefore， the China Association of Chinese Medicine （CACM） organized the outstanding young obstetricians of TCM and western medicine to discuss 15 obstetric diseases responding specifically to TCM or integrated TCM and western medicine， including hyperemesis gravidarum， threatened abortion， ectopic gestation， cough during pregnancy， pregnancy-induced hypertension syndrome， maternal-fetal ABO incompatibility， postpartum hypogalactia， residual pregnancy tissue in uterine cavity， puerperal infection， pantalgia after childbirth， hematoma/undesirable healing after caesarean section， postpartum urinary retention， ileus after cesarean section， pelvic floor dysfunction， and postnatal depression. The suggestions for their treatment with TCM or integrated TCM and western medicine were also proposed， aiming to provide patients with effective and personalized treatments in clinical practice and improve the diagnosis and treatment effects of obstetric diseases， thus benefiting the public. At the same time， more obstetrical clinicians are expected to understand the therapeutic effects and advantages of TCM and draw on the strengths of both TCM and western， thereby promoting the establishment of an obstetric diagnosis and treatment system with Chinese characteristics.

Surgical management of lumbar brucella spondylitis by posterior short-segment internal fixation / 中华骨科杂志

Objective:To explore the clinical efficacy of posterior short-segment internal fixation for the treatment of brucella spondylitis (BS).Methods:The medical records of 34 patients with BS admitted from January 2014 to June 2019 were retrospectively analyzed. There were 22 males and 12 females; the age was 52.3±10.6 years (range 35-72 years). On the basis of standardized use of antibacterial drugs, the lumbar spine posterior short-segment internal fixation was used. Twenty-nine cases underwent simple internal fixation, and posterolateral bone graft fusion, while 5 cases underwent primary debridement, autologous bone grafting and interbody fusion. Monitor erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and test tube agglutination test (SAT) were used to assess inflammation control. Imaging examinations of patients before operation, 1 month after operation, 3 months after operation, 6 months after operation, 1 year after operation to the last follow-up were analyzed to evaluate the condition of intervertebral fusion. The clinical efficacy evaluation was based on the pain visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, modified MacNab grading, and American Spinal Injury Association (ASIA) grading, as well as surgery-related complications.Results:The operation time of 34 patients was 104.64±16.72 min (range 65-145 min), the average hospital stay was 16.49±7.41 days (range 7-38 d), and the average postoperative follow-up time was 20.2 months (range 12-34 months). At the last follow-up, the ESR and CRP fell to the normal range, and the SAT was negative. At 3 months postoperatively, 11 cases (32.35%) reached Bridwell fusion criteria of grade II, 23 cases (67.65%) of grade III; 3 cases (8.82%) of grade I fusion at 6 months after surgery, 31 cases reached grade II fusion (91.18%); all reached grade I fusion at the last follow-up. After the operation, the symptoms of the waist or lower extremities were significantly relieved. The VAS score was 6.3±1.4 before the operation, 4.1±1.2 at 1 month after the operation, 2.7±1.4 at 3 months after the operation, 1.6±1.0 at 6 months after the operation, and 1.2±0.8 at the last follow-up. The JOA score before surgery was 13.8±2.4, 1 month after surgery 17.6±2.6, 3 months after surgery 21.7±3.1, 6 months after operation 4.9±2.7, and at the last follow-up 25.7±1.8. Compared with the preoperative time nodes of the above indicators, the differences were statistically significant. At the last follow-up, of the 12 patients (2 cases of grade C, 10 cases of grade D) with preoperative neurological dysfunction, 2 cases recovered from grade C to grade D, and 10 cases recovered from grade D to E; the excellent and good rate of modified MacNab grading reached 97.06% (33/34). No extradural hematoma, nerve damage, cerebrospinal fluid leakage and other surgical complications occurred. Only 1 case had wound infection complication, and the prognosis was good after active treatment. There were no recurrences during the follow-up period.Conclusion:On the basis of standardized antimicrobial treatment, posterior lumbar short-segment internal fixation is a safe and effective method for the treatment of BS, and good clinical effects can be obtained.

Research progress of animal model of intervertebral disc degeneration / 中华骨科杂志

Intervertebral disc degeneration (IDD) refers to the biomechanical and structural changes of intervertebral disc tissues due to the effects of a variety of factors. Theses physical or chemical factors lead to the rupture of the annulus fibrous, protrusion of the nucleus pulposus tissue, compression of the spinal cord and nerve roots and causing the patient's back and leg pain ultimately. Degeneration of intervertebral disc is a common condition in clinical practice, which affects working ability and daily living quality of patients seriously. Due to the change of living habits, the population with IDD tend to be younger recently. The etiology, pathogenesis and diagnosis and interventions of IDD have always been hot topics in spinal surgery. Thus, animal models of IDD close to the human body has a of great clinical significance for exploring the etiology, pathological mechanism and non-surgical treatment of IDD. At present, the establishment of IDD model mainly includes two following aspects, in vitro model and in vivo model. There are two main in vitro models, cell culture and tissue or organ culture. There are seven kinds of in vivo models, which can be divided into two categories, namely spontaneous and induced model. Among them, the spontaneous degeneration model is also regarded as age-related degeneration, while the induced model refers to the construction of the animal model of IDD by injuring the structure of the intervertebral disc, changing the biomechanical structure of the vertebral body, development spinal instability caused by surgery or constructing nerve root compression and gene knockout. Although there are many methods of animal modeling and literature reports, each method has its own advantages and disadvantages. The advantages and disadvantages should be weighed when choosing the animal models.

Shexiang Tongxin Dropping Pill () Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats.@*METHODS@#Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg@*RESULTS@#The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01).@*CONCLUSION@#STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.

Screening of interacting proteins of idiopathic gonadotropin-releasing hormone deficiency pathogenic gene RNF216 / 中华医学遗传学杂志

OBJECTIVE@#To screen proteins interacting with ring finger protein 216(RNF216) through yeast two hybrid experiment, and further clarify the role of RNF216 in the pathogenesis of gonadotropin-releasing hormone deficiency.@*METHODS@#A recombinant expression vector pGBKT7-RNF216 was constructed and transformed into yeast Y2HGold, which was hybridized with a human cDNA library in order to screen proteins interacting with RNF216. The interaction was verified in yeast Y2HGold.@*RESULTS@#A recombinant expression vector pGBKT7-RNF216 was successfully constructed and expressed in yeast Y2HGold. Filamin B (FLNB) was identified by yeast two hybrid experiment, and their interaction was verified in yeast Y2HGold.@*CONCLUSION@#An interaction between FLNB and RNF216 was identified through yeast two hybrid experiment. RNF216 may affect the proliferation and migration of GnRH neurons by regulating FLNB or FLNB/FLNA heterodimers.

Mechanism of Huanglian Jiedu Decoction in Preventing and Treating Atherosclerosis by Regulating Macrophage Polarization / 中国药房

OBJECTIVE：To stu dy the regulation effects of Huanglian jiedu decoction on M 1 and M 2 macrophage polarization in atherosclerosis （AS）model mice ，and to elucidate its mechanism of AS prevention and treatment. METHODS ：Sixty ApoE －/－ male mice were randomly divided into blank control group ，model group ，simvastatin group [positive control ，5 mg/（kg·d）]， Huanglian jiedu decoction low-dose ，medium-dose and high-dose groups [ 5，10，20 mg/（kg·d），by crude drug] ，with 10 mice in each group. Except for blank control group ，other groups were given high-fat diet to induce AS model. After modeling ， administration groups were given relevant medicine intragastrically ；blank control group and model group were given normal saline intragastrially，once a day ，for consecutive 4 weeks. After medication ，the contents of triglyceride （TG），total cholesterol （TC）， low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） in serum were detected by automatic biochemical analyzer. Sirius red staining was used to observe the formation of collagen fibers in the aorta of mice. The serum contents of iNOS and CD 206 were determined by ELISA. mRNA expression levels of IL- 1β，iNOS，TNF-α，YM1 and Fizz1 in the aorta were detected by RT-PCR. RESULTS ：Compared with blank control group ，the serum contents of TC ，TG， LDL-C and iNOS ，mRNA expression levels of IL- 1β，iNOS，TNF-α in the aorta were significantly increased in model group（P＜ 0.05 or P＜0.01），while the serum contents of HDL-C and CD 206 and mRNA expression levels of IL- 10，YM1，Fizz1 in the aorta were significantly decreased （P＜0.01）. There was a thick layer of collagen fibers under the endothelium of aorta. Compared with model group ，above serum indexes of mice were improved significantly in administration groups （P＜0.05 or P＜0.01）；mRNA expression levels of IL- 1 ，iNOS and TNF-α in the aorta in Huanglian jiedu decoction medium-dose and high-dose groups were decreased significantly （P＜0.01），while mRNA expression levels of IL- 10，YM1 and Fizz 1 were increased significantly （P＜0.05 or P＜0.01）. The vascular endothelium was relatively smooth. CONCLUSIONS ：Huanglian jiedu decoction can inhibit the polarization of M 1 macrophages and promote the polarization of M 2 macrophages，reduce the inflammatory reaction ，maintain the stability of atherosclerotic plaque in artery ，so as to play the role of anti-AS.

Study on the Mechanism of Huanglian Jiedu Decoction Regulating Macrophage Polarization Based on Network Pharmacology / 中国药房

OBJECTIVE：To study the mechanism of H uanglian jiedu decoction （HJD）regulating macrophage polarization in order to explore its anti-inflammatory mechanism. METHODS ：The active components and predicted targets of HJD were screened through TCMSP and Swiss Target Prediction database ；the related targets of macrophage polarization were obtained by GeneCards and OMIM database ，and the network diagram of active ingredient-macrophage polarization target of HJD was drawn by using Cytoscape 3.6.0 software；protein interaction network was constructed by String database and core targets were extracted. Gene ontology（GO）enrichment analysis and Kyoto Encyclopedia of genes and genomes （KEGG）pathway enrichment analysis were carried out by using Cytoscape 3.6.0 software and DAVID website. Combined with the results of network pharmacology analysis ， RAW264.7 macrophage cells were divided into blank control group ，model group ，simvastatin group （10 μmol/L）and serum containing HJD group （obtained from the blood after the rats were given HJD at the dose of 10 g/kg）. Except the blank control group and model group were added culture medium ， the other groups were added with 100 μ L of relevant drug solution or serum containing drug. After 2 h of culture ，except for the blank control group ，LPS solution （100 μg/L）was added to the other groups for 24 h to induce inflammation. Western blot assay was used to detect the expression of AMPK. mRNA expression of M 1 type polarization factor （IL-1 β，iNOS）and M 2 type polarization factor （IL-10，Fizz1）were detected by RT-PCR. RESULTS ：A total of 50 active components of HJD （such as acacetin ，wogonin，quercetin，β-sitosterol）were screened ， which could regulate macrophage polarization through 12 GO items （such as anoikis ，astrocyte activation ），and 20 KEGG pathways（such as estrogen signaling pathway ，bladder cancer pathway ，AMPK signaling pathway ）. The results of cell test showed that compared with blank control group ，the expression of AMPK protein ，Fizz1 and IL- 10 mRNA in model group were significantly decreased （P＜0.01），while the expression of IL- 1β and iNOS mRNA were significantly increased（P＜0.01）； compared with model group ，the expression of AMPK protein ，Fizz1 and IL- 10 mRNA in serum containing HJD group and simvastatin group were significantly increased （P＜0.05 or P＜0.01），while the expression of IL- 1β and iNOS mRNA were significantly decreased （P＜0.01）. CONCLUSIONS ：HJD can regulate macrophage polarization through multiple targets and pathways；it can up regulate the expression of M 2-type polarization factors and down-regulate the expression of M 1-type polarization factors through AMPK signaling pathway ，regulate macrophage polarization and play an anti-inflammatory role.

Impact of socioeconomic status，population mobility and control measures on COVID-10 development in major cities of China / 浙江大学学报·医学版

:To evaluate the impact of socioeconomic status，population mobility，prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. : The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19，2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects，that is, socioeconomic status，population mobility，and control measures for the pandemic. : According to the analysis on the 51 cities，4 development patterns of COVID-19 were obtained，including a high-incidence pattern (in Xinyu)，a late high-incidence pattern (in Ganzi)，a moderate incidence pattern (in Wenzhou and other 12 cities)，and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. : There were relatively large difference on the COVID-19 development among different cities in China，possibly affected by socioeconomic status，population mobility and prevention and control measures that were taken. Therefore，a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.

JAK1/STAT3 pathwaycooperates with TGF-β/Smad2/3 pathway to regulate TSLP and promote the resorption process of herniated disc / 中华骨科杂志

Objective:Resorption can occur after lumbar disc herniation, and Thymic stromal lymphopoietin (TSLP) is considered to be a key factor mediating reabsorption. Studies have found that under the action of inflammatory factors like TNF-α, IL-6, etc,the expression of TSLP in intervertebral disc tissue was increased, and then mononuclear macrophage chemokine-1 (MCP-1) was induced to induce infiltration of macrophage to promote reabsorption. To determine the mechanism, we design the experiment to explore the mechanism of IL-6-mediated JAK/STAT pathway and TGF-β/Smad pathway to promote the reabsorption of intervertebral disc by regulating the expression of TSLP.Methods:Rat bone marrow mesenchymal stem cells (MSC) and rat nucleus pulposus cells (NPC) were cultured in vitro, treating the cells withrat IL-6 recombinant protein, STAT3inhibitor and Smad2/3 inhibitorrespectively, and use real-time quantitative PCR (qRT-PCR) technology to detect the expression of JAK1, STAT3, Smad2, TSLP mRNA under different conditions; Western blot to detect the expression of TSLP, Smad2 and phosphate STAT3 protein; using enzyme-linked immunosorbent assay (Elisa) to detect the expression of TGF-β in two rat cells under the treatment of IL-6.Results:After stimulation ofIL-6 (10 ng/ml or 100 ng/ml) the expression of JAK1in MSC (10 ng/ml: 5.13±1.21; 100 ng/ml: 5.23±0.35; control group: 0.97±0.03), STAT3 (10 ng/ml: 6.50±0.38; 100 ng/ml: 6.74±0.61; control group: 0.87±0.19) was significantly increased, and TSLP also showed high expression in MSC (10 ng/ml: 4.26±0.38; 100 ng/ml: 5.05±0.46; control group: 1.04±0.04).The expression of STAT3 (10 ng/ml: 2.91±0.08; control group: 1.12±0.11), TSLP (10 ng/ml: 7.32±0.37; control group: 1.03±0.03) in NPC also increased. After stimulation of IL-6, the expression of Smad2 increasing in MSC was observed (10 ng/ml: 15.92±0.62; 100 ng/ml: 20.28±0.58; control group: 0.96±0.08), and increased expression of Smad2 in NPC (10 ng/ml: 5.01±0.17; control group: 0.96±0.03). The expression of TSLP in MSC decreased after adding STAT3 inhibitor (BP group, BP group: 0.17±0.01; control group: 0.90±0.09), the expression of TSLP also decreased in NPC (BP group: 0.42±0.11; control group: 0.90±0.11). After adding Smad2/3 inhibitor (SB group), the expression of TSLP in MSC decreased (SB group: 0.33±0.01; control group: 1.02±0.02), and the expression of TSLP in NPC also decreased (SB group: 0.40±0.04; control group: 0.99±0.01).Conclusion:IL-6 up-regulates TSLP expression via the JAK1/STAT3 signaling pathway and promotes prominent intervertebral disc reabsorption. At the same time, IL-6 can activate the TGF-β/Smad2/3 pathway and up-regulate the expression of TSLP, which play a synergistic role in the reabsorption process.

Progress in clinical related research of Inflammatory factors and signaling pathways in lumbar degenerative diseases / 中华骨科杂志

Low back pain is becoming an important factor that affects people's quality of life today, and the social losses caused by lowback pain are hugeevery year. Lumbar disc herniation (LDH) is one of the main diseases that cause low back pain. The mechanism of lumbar disc herniation in the biomedical science is still controversial. Inflammatory factor is a cytokine secreted by tissue cells and involved in mediating the inflammatory response. Studies have shown that some factors stimulated by the extrusive nucleus pulposus, like inflammatory factors, degeneration-related genes and downstream expression products, can cause the degeneration of intervertebral disc. IL-1, IL-6, TNF-α, MMPs, and TGF-β have become the hot topicin disc degeneration. Signaling pathway is the main pathway for inflammatory factors to participate in the regulation of various biochemical reactions in cells. The inflammatory factors interact with different proteins to activate or inhibit different pathways, thereby achieving regulation of the cell cycle, regulates gene expression, induces immune inflammatory response, and apoptosis. Research on the role of various inflammatory factors in the body and related molecular signaling pathways will help us understand the mechanism of LDH. Most of the experimental studies only focus on the influence of a certain cytokine or single pathway on intervertebral disc degeneration, but different inflammatory factors and their signaling pathways often crosstalk with each other through special channels, forming a complex and precise signal transduction regulation network jointly regulates various physiological or pathological processes in the body, and the occurrence of disease is often accompanied by multiple factors. Studying the effect of a single signal network on the disease cannot fully explain the cause of the disease and related clinical manifestations. Therefore, clarifying the role of various inflammatory factors in IDD and exploring and analyzing the ways in which each factor regulates each other will provide ideas for understanding the mechanism of lumbar degeneration and exploring new methods for preventing and treating LDH in the future.

Mechanism of nuclear translocation of hypoxia-inducible factor-1α in influenza A (H1N1) virus infected-alveolar epithelial cells / 中华危重病急救医学

Objective:To investigate the molecule mechanism of nuclear translocation of hypoxia-inducible factor-1α (HIF-1α) in influenza A (H1N1) virus infected-alveolar epithelial cells.Methods:Human lung adenocarcinoma epithelial cells (A549 cells) were cultured in vitro, and cells in logarithmic growth phase were selected for experiments. ① Experiment 1: the A549 cell model with H1N1 virus infection was established by using H1N1 virus infected cells with multiplicity of infection (MOI) 1.0 for 24 hours (H1N1 virus infection group), and the blank control group was set up. Importin 4 and Importin 7 protein expressions were detected by Western Blot to investigate whether HIF-1α nuclear translocation depended on Importin 4 or Importin 7. ② Experiment 2: the A549 cells were infected with H1N1 virus under different MOI (0, 0.1, 0.5, 1.0, 2.0, 4.0) for 24 hours. Then the A549 cells were infected with H1N1 virus (MOI 1.0) for different time (0, 3, 6, 12, 18, 24, 36 hours). The septin 9 isoform 1 (SEPT9_i1) mRNA expression was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) to investigate the effect of different MOI and infection time on the expression of SEPT9_i1. ③ Experiment 3: a cell model with SEPT9_i1 silencing was established by transfection of small interfering RNA (siRNA) for 24 hours (siRNA-SEPT9_i1 group), and the blank control group and blank vector control group (siControl group) were set up. Then the cells in the three groups were infected with H1N1 virus (MOI 1.0) for 24 hours after 24-hour transfection, and the SEPT9_i1 mRNA expression was detected by real-time fluorescence quantitative RT-PCR to investigate the interference efficiency of siRNA-SEPT9_i1. ④ Experiment 4: the cells were divided into siControl group and siRNA-SEPT9_i1 group. The transfection methods of two groups was as the same as experiment 3, and then the cells were infected with H1N1 virus (MOI 1.0) after 24-hour transfection. The distribution of HIF-1α was detected by immunofluorescence at 24 hours after infection. The M gene expression of virus was detected by real-time fluorescence quantitative RT-PCR at 6, 12, 24, 36, 48 hours after infection. The effects of SEPT9_i1 on HIF-1α translocation and virus replication were explored. ⑤ Experiment 5: the cells were divided into blank control group (complete medium), SP600125 group [100 μmol/L c-Jun N-terminal kinase (JNK) signaling pathway inhibitor SP600125 for 2 hours], H1N1 virus infection group (H1N1 virus of MOI 1.0 for 24 hours), H1N1 virus+SP600125 group (pretreated with 100 μmol/L SP600125 for 2 hours before 24-hour H1N1 virus infection). Real-time fluorescence quantitative RT-PCR was used to detect the expressions of SEPT_i1 mRNA and viral M gene to investigate the effect of JNK signaling pathway on SEPT9_i1 expression and virus replication. Results:① Experiment 1: compared with the blank control group, the protein expressions of Importin 4 and Importin 7 in the H1N1 virus infection group had no significant changes [Importin 4 protein (Importin 4/GAPDH): 1.08±0.03 vs. 1.05±0.03, Importin 7 protein (Importin 7/GAPDH): 0.87±0.11 vs. 0.78±0.03, both P > 0.05]. These indicated that the HIF-1α nuclear translocation in A549 cells might not be independent of Importin 4 and Importin 7 during H1N1 virus infection. ② Experiment 2: the SEPT9_i1 mRNA expression in A549 cells was increased with the increase in MOI and infection time of H1N1 virus, and peaked at MOI 2.0 or 18 hours after infection, and the differences were statistically significant as compared with MOI 0 or 0 hour after infection (2 -ΔΔCT: 1.39±0.05 vs. 1.00±0.00 at MOI 2.0, 1.47±0.04 vs. 1.00±0.00 at 18 hours, both P < 0.01). This indicated that the SEPT9_i1 expression in A549 cells was related to the MOI and the infection time during H1N1 virus infection. ③ Experiment 3: compared with the blank control group, the SEPT9_i1 mRNA expression in A549 cells was significantly decreased in the siRNA-SEPT9_i1 group (2 -ΔΔCT: 0.38±0.11 vs. 1.00±0.00, P < 0.01), and there was no significant difference between the siControl group and blank control group (2 -ΔΔCT: 1.03±0.16 vs. 1.00±0.00, P > 0.05). This indicated that SEPT9_i1 silence could inhibit the expression of SEPT9_i1 mRNA in H1N1 virus-infected A549 cells. ④ Experiment 4: HIF-1α nuclear translocation in the H1N1 virus-infected A549 cells in the siRNA-SEPT9_i1 group was significantly reduced as compared with the siControl group. The virus M gene expression after H1N1 virus infection in the siControl group was gradually increased, and peaked at 48 hours. The expression of virus M gene in A549 cells in the siRNA-SEPT9_i1 group was significantly down-regulated, and showed a statistically significant difference at 48 hours as compared with the siControl group (2 -ΔΔCT: 3.47±0.66 vs. 8.17±0.38, P < 0.05). This indicated that HIF-1α nuclear translocation and virus replication in H1N1 virus-infected A549 cells were inhibited after silencing SEPT9_i1. ⑤ Experiment 5: the expressions of SEPT9_i1 mRNA and virus M gene in A549 cells in the H1N1 virus infection group were significantly higher than those in the blank control group. However, the expressions of SEPT9_i1 mRNA and viral M gene in A549 cells in the H1N1 virus+SP600125 group were significantly lower than those in the H1N1 virus infection group (2 -ΔΔCT: SEPT9_i1 mRNA was 0.12±0.10 vs. 1.53±0.14, viral M gene was 2.13±0.10 vs. 4.66±0.14, both P < 0.05). There was no significant difference in above indicators between the SP600125 group and the blank control group. This indicated that the JNK signaling pathway could regulate the expression of SEPT9_i1 in A549 cells during H1N1 virus infection, and the JNK signaling pathway inhibition could down-regulate the expression of SEPT9_i1 and inhibit virus replication. Conclusion:The H1N1 virus regulates the expression of SEPT9_i1 by activating the JNK signaling pathway, thus increase HIF-1α transport efficiency and H1N1 replication.