Investigation on status of dyslipidemia in Chinese females aged 35 years or above / 中华心血管病杂志

Objective: To investigate the prevalence, awareness, treatment and control status of dyslipidemia among females aged ≥35 years old across China. Methods: Participants were selected by stratified multistage random sampling method in the "Twelfth Five-Year Plan" National Science and Technology Support Project "Survey on the Prevalence of Important Cardiovascular Diseases and Key Technology Research in China" project. This study is a retrospective, cross-sectional study. A total of 17 418 females aged 35 years and over were included in the current study. The basic information such as age, medical history and menopause was collected by questionnaire. The blood lipid parameters were derived from clinical laboratory examinations. The prevalence of dyslipidemia and the rate of awareness, treatment, and control of dyslipidemia were analyzed in females aged 35 years and over. Results: The age of participants was (56.2±13.0) years old, and the prevalence of dyslipidemia was 33.1% (5 765/17 418). The prevalence rates of high total cholesterol, hypertriglyceridemia, low HDL-C and high LDL-C were 9.7% (1 695/17 418), 11.1% (1 925/17 418), 10.9% (1 889/17 418) and 7.3% (1 262/17 418), respectively. The prevalence of dyslipidemia increased with age and the prevalence of dyslipidemia in women who were not married, Han, menarche age>16 years, obesity, central obesity, alcohol consumption, diabetes, hypertension and family history of cardiovascular disease were higher than those without such characteristics (P<0.05). There were 10 432 (59.9%) menopausal females in this cohort and prevalence of dyslipidemia of these participants was 38.8% (4 048/10 432), which was higher than that of non-postmenopausal females (24.6%, 1 717/6 986) (P<0.05). The awareness rates, treatment rates and control rates of dyslipidemia were 33.9% (1 953/5 765), 15.1% (870/5 765) and 2.5% (143/5 765) respectively among females aged 35 years and over in China. Conclusion: The prevalence of dyslipidemia in Chinese females aged 35 years and over is high, and its awareness, treatment, and control rates need to be optimized.

Mechanism of Gegen Qinliantang against Vulnerable Plaque of Atherosclerosis： Based on Macrophage Pyroptosis Mediated by NF-κB/NLRP3/Caspase-1 Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Gegen Qinliantang （GQL） on vulnerable plaque of atherosclerosis based on the macrophage pyroptosis mediated by nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1 pathway. MethodA total of 12 normal C57BL/6CNC mice were used as the control group， and 60 ApoE-/- mice of the same line were randomized into 5 groups： model group， low-dose， medium-dose， and high-dose GQL groups （GQL-D， GQL-Z， GQL-G groups， respectively）， and western medicine group. The control group and model group were given （ig） equal volume sterile distilled， and GQL-D， GQL-Z， GQL-G and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. Aortic plaques were observed based on hematoxylin and eosin （HE） staining. Serum levels of interleukin （IL）-1β and IL-18 were detected by enzyme-linked immunosorbent assay （ELISA）， protein levels of macrophage mannose receptor （CD206）/apoptosis-associated speck-like protein containing a CARD （ASC） and CD206/NLRP3 by double-labeling immunofluorescence， and C-terminal gasdermin D （GSDMD）， N-terminal GSDMD， NLRP3， pro-cysteinyl aspartate specific proteinase 1 （pro-Caspase-1） and NF-κB p65 by Western blot. ResultCompared with the control group， model group demonstrated serious pathological changes， rise of the levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and decrease of CD206 level （P<0.05）. As compared with model group， the administration groups showed alleviation of the lesions in aortic wall， decrease in levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and rise of CD206 level， with significant difference between some groups （P<0.05）. ConclusionGegen Qinliantang alleviates vulnerable plaque of atherosclerosis by regulating NF-κB/NLRP3/Caspase-1 pathway and further relieving macrophage pyroptosis.

Gegen Qinliantang Regulates Polarization Tendency of Macrophages to Intervene in Vulnerable Plaque in AS of ApoE-/- Mice / 中国实验方剂学杂志

ObjectiveTo explore the mechanism underlying the intervention of Gegen Qinliantang （GQL） in vulnerable plaques in atherosclerosis （AS） of ApoE-/- mice by regulating the polarization of macrophages. MethodTwelve normal C57BL/6CNC mice were used as the control group， and 60 ApoE-/- mice of the same line were randomized into 5 groups： model group， low-dose， middle-dose， and high-dose GQL groups （GQL-D， GQL-Z， and GQL-G groups， respectively）， and atorvastatin group （western medicine group）. High-fat diet was used for modeling. The control group and the model group were given （ig） equal volume of sterile distilled water， and GQL-D， GQL-Z， GQL-G， and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. The levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected with biochemical methods. The distribution of plaques in the aortic region was observed based on oil red O staining and hematoxylin-eosin （HE） staining. Serum levels of M1 pro-inflammatory factors tumor necrosis factor （TNF）-α and interleukin （IL）-6 and M2 anti-inflammatory factors IL-13 and transforming growth factor （TGF）-β were detected by enzyme-linked immunosorbent assay （ELISA）. Protein expression of macrophage mannose receptor CD206/arginase-1 （Arg-1） and CD206/inducible nitric oxide synthase （iNOS） was determined by double-labeling immunofluorescence， and mRNA expression of aortic Arg-1 and iNOS by real-time polymerase chain reaction （PCR）. ResultLevels of TG， TC， and LDL-C were significantly lower and HDL-C level was significantly higher in the GQL-Z， GQL-G， and western medicine groups than in the model group. As the concentration of GQL rose， the area with plaques gradually shrunk and the color became lighter. The staining areas of the GQL-G group and the western medicine group were the most scattered. The administration groups showed significant increase in the protein levels of Arg-1 and CD206， significant decrease in the protein level of iNOS， significant rise of Arg-1 mRNA level， and significant drop of iNOS mRNA level （P<0.05）. ConclusionGQL intervenes in the vulnerable plaques in AS by improving lipid metabolism， inhibiting macrophage M1 polarization， promoting macrophage M2 polarization， and further improving the inflammatory microenvironment.

Explore Potential Molecular Mechanism of Gegen Qinliantang in Intervention of Atherosclerosis Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveThis study aims to explore the potential molecular mechanism of Gegen Qinliantang （GQL） in the intervention of atherosclerosis （AS） based on network pharmacology and molecular docking. MethodThe active components and targets of each medicinal in GQL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and AS-related genes from 7 databases. Thereby， the anti-AS targets of GQL were screened out. Cytoscape 3.8.0 was employed to construct the "component-target" network， and STRING the protein-protein interaction （PPI） network. Core targets were screened out with CytoNCA. R clusterProfiler was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of target genes， which were then visualized. Finally， molecular docking of the top ten active components with the core targets of AS was performed and the binding affinity was compared with that between atorvastatin and the core targets. ResultIn the end， 150 active components of GQL， 20 289 AS targets， and 213 common targets were retrieved， and 48 core common targets were screened out. They were mainly involved in the GO terms of nuclear receptor activity， ligand activation， and transcription factor activity and the pathways of fluid shear force and AS， advanced glycation end products-receptor for advanced glycation end products （AGE/RAGE）， interleukin-17 （IL-17）， tumor necrosis factor （TNF）， Toll-like receptor pathways and other signaling pathways closely related to AS. The molecular docking results showed that the effective components of GQL had high binding affinity to core targets of AS， and the binding affinity was even higher than that between the atorvastatin and core targets. The five groups with high binding affinity were puerarin-TNF， baicalein-inducible nitric oxide synthase 2 （NOS2）， puerarin-NOS2， and formononetin-NOS2， wogonin-NOS2. ConclusionThe above result provides new ideas for further exploration of this classical decoction.

Chemical Compositions and Anti-tumor Effect of Tetrastigma hemsleyanum： A Review / 中国实验方剂学杂志

Due to the infinite proliferation， strong migration and loss of contact inhibition of tumor cells， tumor has become the most intractable diseases to be cured in the world. At present， the main treatments of tumor diseases are surgical resection， radiotherapy， chemotherapy， targeted-therapy and immunotherapy. Although these measures can inhibit or kill the tumor to a certain extent， they still cannot avoid adverse reactions and drug resistance. After thousands of years of clinical practice， traditional Chinese medicine （TCM） has the characteristics of good curative effect， few adverse reactions and significantly improving the quality of life in patients， which provides new ideas for the prevention and treatment of tumors. As an endemic and rare plant in China， Tetrastigma hemsleyanum has been listed in the 2015 edition of Zhejiang Provincial Processing Specification of TCM with the effects of heat-clearing and detoxification， detumescence and analgesia， dissipating phlegm and resolving masses. It has been reported that the chemical constituents of T. hemsleyanum are mainly flavonoids， polysaccharides， phenolic acids， terpenoids， steroids， volatile oils， alkaloids and so on. It can exert a broad spectrum of anti-tumor effects through various ways such as inhibiting proliferation， migration and invasion of tumor cells， inducing apoptosis of tumor cells， inhibiting angiogenesis of tumor cells， reversing multidrug resistance of tumor cells and regulating body autoimmunity. On the basis of reviewing relevant literature at home and abroad， this paper intends to systematically sort out the chemical and anti-tumor research of T. hemsleyanum， and in order to provide a new idea for its synergistic anti-tumor effect of multi-component， multi-pathway and multi-target， and finally provide theoretical basis for the research and development and clinical application of new anti-tumor drugs of T. hemsleyanum.

Analysis of CiteSpace knowledge map for traditional Chinese medicine prevention and treatment of cerebral small vessel diseases / 中国中药杂志

This study aims to analyze the research on the prevention and treatment of cerebral small vessel diseases(CSVDs) with traditional Chinese medicine(TCM) based on knowledge map, and to preliminarily explore the research hotspots and trends. To be specific, articles on TCM treatment of CSVDs in CNKI, Wanfang, and VIP(from establishment to November 2021) were retrieved, followed by bibliometric analysis. Then CiteSpace 5.7 R4 and Gephi were employed for generation of maps on annual number of articles, author cooperation, institution cooperation, keyword co-occurrence, keyword clustering, and keyword emergence. A total of 106 eligible articles were screened out, and the annual number of articles presented a steady upward trend. A total of 277 authors were included in the author cooperation network, among whom CHEN Zhigang published the most articles. A total of 87 institutions were included in the institution cooperation network, among which Dongfang Hospital of Beijing University of Chinese Medicine showed the most frequent cooperation with other institutions. Keyword clustering showed that research on the TCM treatment of CSVDs mainly focused on five aspects: related disease research, neurological function deficits, disease nature and location in TCM, TCM treatment methods, and formulas. The prevention and treatment of CSVDs with TCM in China has been developing steadily in the past ten years, and TCM has unique advantages in the prevention and treatment of this disease. The knowledge maps vividly demonstrated the development and research hotspots and trends in this field. The result is expected to provide a reference for further research in this field.

LncRNA-m18as1 competitively binds with miR-18a-5p to regulate follicle-stimulating hormone secretion through the Smad2/3 pathway in rat primary pituitary cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.

Synthesis and antibacterial activity of synephrine sulfonamide derivatives containing tetrazole and sulfuryl groups / 药学学报

Synephrine is a natural small-molecule alkaloid found in Aurantii fructus immaturus with versatile biological activities, but its derivatives have been rarely studied so far. Based on the multi-target drug design strategy, the phenolic hydroxyl and secondary amino group of synephrine were modified structurally by the molecular splicing method in this study and thus five intermediates and fifteen target molecules were designed and synthesized. These compounds were evaluated with certain human pathogenic bacteria and fungi, and found that the inhibitory activities of IM4 and IM5 against E.coli are comparable to those of eight fluoroquinolones; TM1n showed stronger inhibitory activity against drug-resistant C. trobicans and drug-resistant C. albicans than the positive control drug fluconazole. TM1d and TM1f against C. albicans ATCC90023, TM1o and TM1f against drug-resistant C. albicans, and TM1f against C. parapsilosis ATCC22019 are all comparable to fluconazole, all of which have the potential for in-depth research. In this study, synephrine derivatives with strong inhibitory activities against human pathogenic fungi were discovered for the first time, which provided a new idea for the further study of synephrine.

Progress in the mechanism of regulatory B cells and its role in human diseases / 中华微生物学和免疫学杂志

Regulatory B cells (Bregs) are a group of cells with immunoregulatory function. They can regulate the progression of diseases by inhibiting excessive inflammatory responses and serve as critical protective cells in immune disorders and other conditions. This article reviewed the source, function and mechanism of Bregs and its role in autoimmune diseases, infection and tumor.

The evolving progress of mitochondrial oxidative stress in the pathological mechanisms of diabetic microvascular complications / 中华内分泌代谢杂志

Diabetes complications are the primary cause of disability and mortality in diabetic patients. As the center of cell energy metabolism, mitochondria dysfunction is closely related to the occurrence and development of various microvascular complications. This review focuses on common complications, including diabetic ulcers, diabetic nephropathy and diabetic retinopathy, and on the research progress of mitochondrial function and oxidative stress involving pathological mechanisms of diabetic microvascular complications. We also conclude and update the theoretical basis for targeting mitochondrial oxidative stress in the treatment of these diseases.

Theoretical construction and practical research on the curriculum system of children's rehabilitation specialty in rehabilitation therapy / 中华医学教育探索杂志

This article takes the setting of children's rehabilitation specialty in the rehabilitation therapy of Xiamen Medical College as an example, and expounds that in the process of cultivating talents in children's rehabilitation, theoretically, a training model of "2.5+0.5+1" has been built closely around the training goals of "solid foundation, wide caliber and strong skills", highlighting basic pediatric courses, core skills courses for children's rehabilitation therapy and special courses for children's rehabilitation. In practice, the training of "early clinical practice and early probation" for children's rehabilitation skills is stressed. The results show that students have greatly improved their professional knowledge and practical ability, and the effect of "early clinical practice and early probation" is obvious. Among the students who choose the direction of children's rehabilitation, 95% of the students want to engage in the career of children's rehabilitation and believe that the curriculum system will be of great help to their future employment.

Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fourth Edition) / 中华实用儿科临床杂志

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.

The prevalence of depressive disorders in school students aged 6-16 years in Beijing / 中华实用儿科临床杂志

Objective:To investigate the prevalence of depressive disorders among school students aged 6-16 years in Beijing, the effect of age and gender on the prevalence, and the behavioral and emotional profiles of identified students with depressive disorders.Methods:The prevalence of depressive disorders in primary and secondary school students aged 6-16 years in Beijing from January 2012 to December 2014 was examined by a multistage stratified random sampling method.In the first stage, the Achenbach′s Child Behavior Checklist (CBCL) was used to identify high-risk children and adolescents.In the second stage, the high-risk group was further screened by Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), and then two psychiatrists made the final diagnosis according to the diagnostic criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-Ⅳ). This study was a prospective epidemiological investigation.The effect of age and gender on the disease prevalence was analyzed by Chi- square test. Results:About 2.29% (234/10 215 cases) of the school students aged 6-16 years in Beijing had depressive disorders.The incidence of depressive disorders was 1.80% (106/5 866 cases) in boys and 2.94% (128/4 349 cases) in girls.There is an age effect on the prevalence of depression.As the age increases, the morbidity of depressive disorders increases.The age of 12 years was a critical turning point, and the peak incidence was reached at around the age of 15 years.The emotional and behavioral problems of patients with depressive disorders mainly include social problems, withdrawal depressed, anxiety and depressed, somatic complaints, and aggressive behavior.Conclusions:The prevalence of depressive disorders among school students aged 6-16 years in Beijing is 2.29%.Depressive disorders occur in primary and middle school students of all ages.More attention should be paid to the mood of students before and after the entrance exams for junior high school and senior middle school, especially the girls′ mood.In the process of screening, diagnosis and treatment of depressive disorders, the atypical symptoms of depression need to be paid more attention.

Construction and practice of undergraduate training mode for clinical pharmacy specialty based on outcome-based education / 中国药房

OBJECTIVE To introduce the construction of undergraduate specialty of clinical pharmacy based on the concept of outcome-based education （OBE），and to provide new idea and enlightenment for the construction of undergraduate specialty of clinical pharmacy in Chinese universities. METHODS Through the establishment and construction of training objectives and graduation requirements ，teaching reform was designed and implemented ，and the construction of teaching support system and teaching quality assurance system were completed. RESULTS The clinical pharmacy department of our university established the training direction of clinical pharmacy talents under the guidance of post competence ，including clarifying the training needs of undergraduate talents based on the overall requirements of national undergraduate education ；defining the social and industrial needs of clinical pharmacy talents based on the normative documents or concepts of clinical pharmacy ；clarifying the post and ability needs of clinical pharmacy talents based on the investigation of graduates and clinical pharmacists ；clarifying the development needs of clinical pharmacy based on the current situation and trends at home and abroad ；forming characteristic training objectives combined with the regional characteristics and school positioning ， so as to construct training objectives and graduation requirements. The OBE concept was introduced into the undergraduate teaching reform of clinical pharmacy ；the pharmacy talent training direction were established under the guidance of post competence ；the training system was designed by reverse design method；a training mode of both innovation and practical ability was built so as to promote teaching reform ，strengthen the construction of grass-roots teaching organizations and teaching staff ， and improve the construction of teaching quality assurance system. CONCLUSIONS The undergraduate training mode of clinical pharmacy specialty based on the concept of OBE is helpful to improve students ’personal comprehensive quality and professional knowledge and skills. The established undergraduate training model of clinical pharmacy specialty is in line with the modern educational concept and social needs ，and provides theoretical basis and practical experience for the training mode of clinical pharmacy professionals.

Construction and mechanism of dry eye model in mice with ocular surface iron overload / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish a dry eye mouse model of iron overload by intraperitoneal injection of iron dextran and preliminarily explore its possible mechanism.METHODS: A total of 40 male C57BL/6 mice(taking the right eye as the experimental eye)were divided into 4 groups by random number table method: There were 10 mice in the control group, each time by intraperitoneal injection of 0.2mL of normal saline; Low-dose group, middle-dose group and high-dose iron group with 10 mice in each group were the model group. Each time, 0.2mL of iron dextran solution with concentrations of 12.5, 25, and 50 mg/mL was injected intraperitoneally. One injection 3d for a total of 28d. We observed the ocular surface inflammation index, corneal fluorescein staining, tear break-up time(BUT)and Schimer I test(SIt)on the 7, 14 and 28d after injection and evaluated the degree of dry eye and ocular surface inflammation. After 28d, the mice were sacrificed for cornea, conjunctiva and lacrimal glands tissue for HE staining, Prussian blue staining and tissue iron detection, to evaluate the inflammatory reaction and iron overload. The expression of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and matrix metallo proteinase-9(MMP-9)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS: Compared with the control group, the mice in the model group showed a series of dry eye symptoms, the inflammation index of ocular surface in mice were increased, the score of corneal fluorescein staining increased, the BUT shortened and the amount of tear secretion decreased(all P&#x003C;0.05). The cornea, conjunctiva and lacrimal gland tissues of the mice were damaged to varying degrees, the iron deposition on the eye surface of the model group was more serious than that of the control group, and the iron content of the tissue was significantly increased than the control group(all P&#x003C;0.01). The contents of inflammatory factors(IL-1β, TNF-α, MMP-9)in the cornea, conjunctiva and lacrimal gland tissue of the mice in the model group were significantly higher than those of the control group(all P&#x003C;0.01). With the increase of injection time and concentration of iron dextran, the degree of dry eye and ocular surface inflammation in mice gradually increased. CONCLUSION: The mouse iron overload dry eye model was successfully established by intraperitoneal injection of iron dextran, the mechanism may be related to the ocular surface inflammation aggravated by iron overload.

Efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore whether efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization. METHODS: A total of 50 healthy C57BL/6 male mice aged 6-8wk were randomly divided into normal control group, iron group, inhibitor group, enhancer group and solvent control group, with 10 mice in each group. The normal control group was injected intraperitoneally with 0.2mL of normal saline, and the other groups were injected intraperitoneally with 50mg/mL iron dextran of 0.2mL, once every 3d. From the 14d, the inhibitor group, the enhancer group and the solvent control group were injected intraperitoneally with the same volume(0.2mL)50mg/kg XMD8-92, 10mg/kg simvastatin and 50% DMSO solvent once a day, respectively. The anterior segment of the eyes was observed under slit lamp microscope on the 7, 14, 28d after intraperitoneal injection, and the ocular surface inflammation index and corneal fluorescein staining score were evaluated. The cornea, conjunctiva and lacrimal gland tissues were taken at 28d for the HE staining and immunofluorescence staining, and RT-PCR were used to detect the expression of macrophage polarization related indexes(CD86, CD206, iNOS, Arg-1); Western blot were used to detect the expression of efferocytosis related signal factors(Gas6, MerTK); ELISA was used to detect the expression of inflammatory factors(IL-1β, TNF-α, MMP-9).RESULTS: After injection for 28d, compared with the normal control group, the ocular surface inflammatory index and corneal fluorescein staining score were increased in the iron group and the solvent control group. HE staining showed incomplete corneal epithelium, reduced conjunctival goblet cells, unclear lacrimal gland structure and relatively disordered arrangement of cells. In all tissues, the expressions of polarization related indexes of M1 macrophages such as CD86 and iNOS were up-regulated, while those of M2 macrophages such as CD206 and Arg-1 were down-regulated, and the expressions of inflammatory factors such as IL-1β, TNF-α and MMP-9 were up-regulated(all P&#x003C;0.05). Compared with the iron group and the solvent control group, the ocular surface inflammation index and corneal fluorescein staining score of the inhibitor group were further increased. HE staining showed obvious exfoliation of corneal epithelium, further decrease or even disappearance of conjunctival goblet cells, disorder of lacrimal gland structure and irregular arrangement of cells. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was down-regulated(all P&#x003C;0.05), the expression of polarization related indexes of M1 macrophages such as CD86 and iNOS and the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 were further up-regulated(all P&#x003C;0.05). But the ocular surface inflammation index and corneal fluorescein staining score decreased in the enhancer group. HE staining showed the integrity of corneal epithelial, the increase of conjunctival goblet cells and the improvement of lacrimal gland structure and morphology. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was up-regulated(all P&#x003C;0.05), and the expression of polarization related indexes of M2 macrophages such as CD206 and Arg-1 was up-regulated, while the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 was down-regulated(all P&#x003C;0.05). CONCLUSION: High-iron environment induces macrophages polarize to M1, which aggravates ocular surface inflammation and tissue damage. Efferocytosis by regulating the polarization of macrophages impact the occurrence of ocular surface inflammation in high-iron environment.

The Great Imitator: Atypical Cutaneous Manifestations of Primary Syphilitic Chancre / 中国医学科学杂志(英文版)

Objective To analyze the reasons of misdiagnosis of primary syphilitic chancre and strengthen the understanding of atypical features of this disease. Methods A case series of twenty-seven challenging primary syphilis patients who were not immediately recognized as chancre was included in our study. The clinical data including the patients' age, sex, skin lesions, HIV status, syphilis serologic test results, treatment, and follow-up results were collected. Hematoxylin-eosin and immunohistochemistry staining of skin biopsy sections were reviewed. Results Four female cases with extragenital chancres presenting as erythema or erosive skin lesions on the nipple were misdiagnosed as Paget's disease or eczema. The disorder of missed or misdiagnosed male cases manifested as syphilitic balanitis or multiple chancres on the penis root and adjacent pubis rather than coronal sulcus or frenum. Patients with nonreactive nontreponemal tests at initial presentation were also easily missed or misdiagnosed. Conclusion Primary syphilis presenting as multiple lesions rather than a single chancre, at atypical locations, or with a nonreactive nontreponemal test result, tends to be missed or misdiagnosed.

Nivolumab-associated pulmonary toxicities： a retrospective study based on FARES database from 2016 to 2019 / 上海预防医学

Objective:Nivolumab is one of the most common programmed death 1 （PD-1） inhibitors used as an immune checkpoint inhibitor （ICI）. It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration （FDA） Adverse Event Reporting System （FAERS） database from January 1， 2016 to September 30， 2019. Two types of disproportionality analysis， information component （IC） and reporting odds ratio （ROR）， were applied in nivolumab-associated pulmonary adverse events （AEs） signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably， potent signals were detected in radiation pneumonitis （IC025： 3.99， ROR025： 17.25）， pneumonitis （IC025： 3.34， ROR025： 10.64） and bronchial fistula （IC025： 2.94， ROR025： 8.78）. Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea （IC025： 0.50， ROR025： 1.44）， pneumonia （IC025： 0.08， ROR025： 1.07） and pneumonitis （IC025： 3.34， ROR025： 10.64）. Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer （N=3 711， 32.13%）， malignant melanoma （N=1 658， 14.36%） and renal cell carcinoma （N=731， 6.33%）. Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus， it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.

Association between pulse pressure and new-onset diabetes in hypertensive patients / 中华心血管病杂志

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q1-Q4), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q1 group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q2 group(41-<51 mmHg) (n=8 196); Q3 group (51-<61 mmHg) (n= 8 270); Q4 group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

Evaluation of the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease based on various mouse models / 针灸推拿医学（英文版）

Objective: To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease (AD) based on various AD mouse models.Methods: Several representative types of mouse models were selected according to the pathophysiological causes of AD, including senescence accelerated mouse/prone (SAMP) mice, soluble amyloid-β protein (Aβ) injection mice/rats, amyloid precursor protein (APP) transgenic mice, and APP/PS1 double transgenic mice. Through the observation of behavioral changes and analysis of core items, the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored. Results: Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction; the major action mechanisms including increasing cerebral blood flow, improving the expressions of vital proteins in the hippocampus, preventing neuron cell apoptosis, promoting the clearance of Aβ deposition, activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor, tyrosine kinase receptor B, N- acetylaspartate and glutamic acid. Conclusion: Although the optimal mouse model is not determined, it is sure that acupuncture-moxibustion therapy can improve cognitive function. A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.