Comparative study on pathological characteristics of four different antigen-induced rheumatoid arthritis mouse models / 药学学报

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

Intervention effect of Qufeng Gutong Cataplasm on myofascial pain syndrome in rats and its mechanism / 中国中药杂志

This paper aims to investigate the intervention effect of Qufeng Gutong Cataplasm(QFGT) on myofascial pain syndrome(MPS) in rats and to preliminarily explain its mechanism from the perspective of improving muscle inflammation and pain. Male SD rats were divided into 6 groups, namely normal group, model group, positive control drug(Huoxue Zhitong Ointment, HXZT) group, and low, medium, and high-dose QFGT groups(75, 150, and 300 mg·d~(-1)). The rat model of MPS was established by striking combined with centrifugation for 8 weeks, during which QFGT and HXZT were used for corresponding intervention. Standard VonFrey fiber was used to evaluate the mechanical pain threshold, and acetone was used to detect the cold pain threshold. The electrophysiological activity of muscle at trigger point was detected, and the electromuscular analysis of trigger point was performed. CatWalk gait analyzer was used to detect pain-induced gait adaptation changes. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in muscle and skin tissues at the trigger point of rats. Immunohistochemistry was used to detect the expression of capsaicin receptor transient receptor potential vanilloid 1(TRPV1) in muscle tissues and interleukin(IL)-33 in skin tissues at the trigger point. The protein expression levels of TRPV1, protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), IL-1β, and tumor necrosis factor-α(TNF-α) in muscle tissues at the trigger point were detected by Western blot. The results showed that as compared with the model group, the mechanical pain threshold and cold pain threshold of rats in other groups were increased after treatment with QFGT. The spontaneous electromyography(EMG) activity was observed in the model group, but QFGT alleviated the EMG activity in a dose-dependent manner. Gait analysis showed that standing duration, average intensity, swing speed, maximum contact point, maximum contact area, paw print length, paw print width, and paw print area were significantly improved in all QFGT groups. Pathological results showed that the disorder of muscle arrangement at the trigger point was decreased, muscle fiber adhesion and atrophy were reduced, and inflammatory cell infiltration was alleviated after treatment with QFGT. In addition, QFGT and HXZT both inhibited the protein expression of TRPV1, PI3K, Akt, p-Akt, IL-1β, and TNF-α in the muscle tissues of rats with MPS. However, there was no significant difference in the pathological structure and expression of IL-33 in the treated skin as compared with the normal group. The related results have proved that QFGT can inhibit the release of inflammatory factors by inhibiting the TRPV1/PI3K/Akt signaling pathway in the muscle trigger point of rats with MPS and finally attenuate the atrophy and adhesion of local muscles and inflammatory infiltration, thereby relieving the muscle pain of rats with MPS, and local administration has no skin irritation.

A decade of liver organoids: Advances in disease modeling

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.

Current progress in the treatment of nonarteritic anterior ischemic optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Nonarterial anterior ischemic optic neuropathy(NAION)is a group of common optic nerve diseases that seriously endanger visual function. It is resulted from insufficient perfusion of the posterior ciliary artery, which causes acute ischemia, structural and functional disorders of the optic nerve, and ultimately leads to hypopsia and even vision loss. The etiology and pathogenesis of this disease is complex. It is nowadays considered that multiple factors including local anatomy, risk of systemic vascular cause this disease together, which result in no clear, unified and recognized treatment. Early detection, diagnosis and treatment are of great significance in the prognosis of NAION. Possible therapeutic methods include etiological treatment, drug therapy, traditional Chinese medicine(TCM)treatment, combined medication, optic nerve sheath decompression, adjuvant treatments and exosomes. With the continuous development and application of various anti-NAION drugs in recent years, a variety of therapeutic methods have been proposed, especially with the exosomes as the research focus. In order to better treat NAION with improvement of the cure rate and guidance for clinical work, this paper mainly reviews the progress in the treatment of NAION in recent years.

Efficacy of Conbercept combined with laser photocoagulation in the treatment of macular edema secondary to ischemic BRVO / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe and analyze the efficacy of Conbercept combined with 577nm yellow subliminal micropulse laser photocoagulation in the treatment of macular edema(ME)secondary to ischemic branch retinal vein occlusion(BRVO).<p>METHODS: Totally 71 patients(71 eyes)diagnosed as ME secondary to ischemic BRVO during the period from March 2016 to March 2019 were retrospectively included, and they were divided into laser group(<i>n</i>=33, 33 eyes)and combined group(<i>n</i>=38, 38 eyes)according to the different treatment methods. The patients in the laser group all received 577nm yellow subliminal micropulse laser photocoagulation, and the patients in the combined group all received Conbercept combined with 577nm yellow subliminal micropulse laser photocoagulation. The best corrected visual acuity(BCVA), central macular thickness(CMT)and total macular volume(TMV)were compared between the two groups before treatment and at 1, 2, 3, 6, 9 and 12mo after surgery, and the therapeutic efficacy was observed and the occurrence of complications were recorded.<p>RESULTS:There were statistically significant differences in the BCVA, CMT and TMV between the two groups before and after treatment(<i>P</i><0.05), and the BCVA, CMT and TMV in the two groups at 1, 2, 3, 6, 9 and 12mo after treatment were significantly lower than those before treatment(<i>P</i><0.05), and the differences between the two groups were statistically significant(<i>P</i><0.05). During follow-up, there were 30 eyes with once laser photocoagulation, 7 eyes with twice and 1 eye with 3 times in combined group, and there were 16 eyes with once laser photocoagulation, 14 eyes with twice and 3 eyes with 3 times in laser group(<i>Z</i>=2.670, <i>P</i><0.05). There were 3 eyes of corneal epithelial exfoliation on the 1d after vitreous injection in combined group, and the symptoms disappeared after symptomatic treatment. All patients did not have serious complications such as persistent intraocular pressure increase, retinal detachment and intraocular inflammation.<p>CONCLUSION: Conbercept combined with 577nm yellow subliminal micropulse laser photocoagulation has a significant efficacy in the treatment of ME secondary to ischemic BRVO, and it can effectively improve the visual acuity and promote the macular edema absorption, and it is safe and reliable.

An investigation of the prevalence of tea-drinking-borne endemic fluorosis in Tianzhu Tibetan Autonomous County, Gansu Province / 中华地方病学杂志

Objective:To further investigate the prevalence of tea-drinking-borne endemic fluorosis in Tianzhu Tibetan Autonomous County (referred to as Tianzhu) Gansu Province, to accurately master the information of patients with tea-drinking-borne endemic fluorosis, and to provide scientific basis for popularizing low fluoride brick tea and carrying out patient rescue and treatment.Methods:From 2019 to 2020, according to the "Investigation Plan of Tea-drinking-borne Endemic Fluorosis in Gansu Province in 2019", in the administrative villages with the habit of drinking and selling tea, drinking water samples of local residents were collected to detect the fluorine content of water in Tianzhu, 10 families were randomly selected in each village, basic situation of each family member and the drinking situation of tea were investigated, and tea samples were collected to determine the fluorine content. At the same time, all children aged 8 - 12 in the investigation village were examined for dental fluorosis; clinical examination of bone and joint symptoms and signs was conducted for permanent residents over the age of 25 in the investigation village (excluding 25 years old), X-ray examination of bone and joint was conducted for patients with clear clinical symptoms or signs of skeletal fluorosis, and urine samples were collected to detect urinary fluorine. Ion selective electrode method was used to detect fluorine in water, tea and urine, and dental fluorosis was diagnosed by "Diagnosis of Dental Fluorosis" (WS/T 208-2011), and the "Diagnostic criteria for Endemic Skeletal Fluorosis" (WS 192-2008) was used for the diagnosis of skeletal fluorosis.Results:A total of 161 water samples were collected, and the fluorine content in water was from 0.07 to 0.68 mg/L, which met the domestic drinking water standard ( < 1.0 mg/L). A total of 1 644 side-tea samples were collected, and the annual per capita consumption of side-tea of permanent residents over 16 years old was 1.05 kg. The average fluoride content of tea was 601.99 - 991.38 mg/kg. According to the detection results of tea fluorine, 16 administrative villages with an average daily intake of tea fluorine more than 3.5 mg/d were screened, the lowest intake was 4.91 mg/d in Tuta Village Danma Township, and the highest intake was 18.98 mg/d in Huashan Village Maozang Township. A total of 253 children aged 8 - 12 years old in 14 administrative villages were investigated. There were 3 cases of very mild dental fluorosis, 2 cases of mild dental fluorosis, and 1 case of moderate dental fluorosis. The overall prevalence of dental fluorosis was 4.74% (12/253). The clinical examination of bone and joint symptoms and signs was carried out for 3 100 permanent adults over the age of 25 (excluding the age of 25) in 15 administrative villages. The X-ray examination of bone and joint was carried out for 104 patients with definite clinical symptoms and/or signs of skeletal fluorosis. Six patients with skeletal fluorosis were diagnosed, including 3 mild and 3 severe, aged 56 - 76 years. The average urinary fluorine in the investigated villages was 0.73 - 4.74 mg/L (the number of investigated was 3 100). According to the determination and classification standards of tea-drinking-borne fluorosis area, Tuta Village Danma Township, Xiding Village Dahonggou Township and Daiqian Village Zhuaxixiulong Township were determined to be in the mild area of tea-drinking-borne endemic fluorosis, while Nannigou Village Zhuaxixiulong Township was in the moderate area of tea-drinking-borne endemic fluorosis.Conclusion:Tea-drinking-borne endemic fluorosis is prevalent in Tianzhu, Gansu Province, and targeted prevention methods and control measures need to be taken.

Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid / 中国中药杂志

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Protective Effect of Tongluo Shenggu Capsule on Function Damage of Human Umbilical Vein Endothelial Cells Induced by Glucocorticoid / 中国实验方剂学杂志

Objective:To observe the effect of Tongluo Shenggu capsule （TLSGC） on glucocorticoid-induced vascular endothelial cell functional damage， and to preliminally explore the mechanism of action through MEK-ERK signaling pathway. Method:The blood vessel of aorta rings of normal SD rats were induced <italic>in vitro</italic> intervention with methylprednisolone sodium succinate （MPS， 0.04 g·L^-1） and/or vascular endothelial growth factor （VEGF， 20 μg·L^-1）， and were treated with TLSGC（12.5， 25， 50 μg·L^-1） continuously for 5 days to observe the number， length and area of microvascular ring buds．In addition， human umbilical vein endothelial cells （HUVEC） induced by VEGF（20 μg·L^-1） were added into MPS（0.04 g·L^-1） and TLSGC （12.5， 25， 50 μg·L^-1） were added. Then， Transwell migration， Transwell invasion and lumen formation experiments were used to detect the migration， invasion and lumen formation ability of HUVEC， respectively. The content of nitric oxide（NO） in the cell supernatant was detected by nitrate reductase method， the content of endothelin 1（ET-1） in the cell supernatant was detected by dry powder method. Moreover， the protein contents of vascular endothelial growth factor receptor 2 （VEGFR2）， extracellular signal-regulated kinase （ERK）， phospho-extracellular signal-regulated kinase （p-ERK）， mitogen extracellular kinase1（MEK） and phosphorylated mitogen extracellular kinase1（p-MEK） in the cells were determined by Western blot. Result:Compared with the normal group， MPS could significantly inhibit the number， length and area of VEGF-induced rat thoracic aortic ring microvessels， HUVEC cell migration， invasion and lumen formation ability. It could reduce NO content and increase ET-1 content. MPS could also significantly reduce the protein content of VEGF-induced VEGFR2， p-MEK and p-ERK in HUVEC（<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， TLSGC could dose-dependently increase the number， length and area of MPS-induced abnormally reduced rat thoracic aortic ring microvessels， promote MPS-induced abnormally decreased HUVEC cell migration， invasion and lumen formation ability. It could increase the protein contents of NO， VEGFR2， p-MEK and p-ERK in HUVEC， and reduce abnormally increased ET-1 content（<italic>P</italic><0.05<italic>，P</italic><0.01）. Conclusion:TLSGC has a protective effect on the damage of angiogenesis and secretion of vascular endothelial cells induced by glucocorticoid， and the mechanism may be related to the activation of MEK/ERK signaling pathway.

Effect and Mechanism of Yuxuebi Tablet Against Collagen-Induced Arthritis of Rats / 中国实验方剂学杂志

Objective:To explore the intervention effect of Yuxuebi tablet （YXB） on collagen-induced arthritis （CIA） in rats and its anti-inflammatory mechanism. Method:Following CIA modeling， the rats in the drug administration groups were separately treated with intragastric administration of YXB （0.1， 0.2， and 0.4 g·kg^-1） and methotrexate （MTX， 0.4 mg·kg^-1）， once a day. The incidence of CIA， mechanical pain threshold （MPT） and cold pain threshold （CPT） were evaluated once every three days. After continuous administration for 30 days， the peripheral blood of rats was collected for the determination of platelet （PLT） count and fibrinogen （FIB） content. The hematoxylin-eosin （HE） staining was conducted to analyze the pathological changes in joint tissues. The protein expression levels of interleukin （IL）-1<italic>β</italic>， IL-8， nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） p65， phosphorylated NF-<italic>κ</italic>B （p-NF-<italic>κ</italic>B） p65， Ras， and Raf-1 in joint tissues of CIA rats were detected by immunohistochemistry （IHC） and Western blot. The rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were induced by tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>， 10 μg·L^-1） <italic>in vitro</italic> and then subjected to transwell migration/invasion assay， followed by the detection of protein expression levels of Ras， Raf-1， and p-NF-<italic>κ</italic>B p65 in RA-FLS by Western blot. Result:Compared with the control group， the model group exhibited an increased incidence of CIA， significantly decreased MPT （<italic>P</italic><0.05，<italic>P</italic><0.01）， elevated CPT （<italic>P</italic><0.01） and PLT and FIB in the peripheral blood， worsened histopathological score of joints， enhanced RA-FLS migration and invasion， and up-regulated inflammatory factors （<italic>P</italic><0.01）. The comparison with the model group revealed that YXB at different doses obviously reduced the incidence of CIA， increased MPT， down-regulated CPT and PLT and FIB in the peripheral blood （<italic>P</italic><0.05，<italic>P</italic><0.01）， ameliorated the pathological changes like synovial hyperplasia and bone and cartilage destruction （<italic>P</italic><0.05，<italic>P</italic><0.01）， and inhibited RA-FLS migration and invasion. Besides， the low-， medium-， and high-dose YXB reversed the IL-1<italic>β</italic>， IL-8， Ras， Raf-1， and p-NF-<italic>κ</italic>B p65 expression in joint tissues of CIA rats to different extents， as well as the protein expression of Ras， Raf-1 and p-NF-<italic>κ</italic>B p65 in RA-FLS （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:YXB reduces the incidence of CIA， ameliorates the clinical symptoms of RA and the pathological changes in joint tissues， and inhibits the formation of synovium， which may be attributed to its inhibition against Ras/Raf-1/NF-<italic>κ</italic>B signaling pathway.

Effect of Panlongqi Tablet on Cervical Spondylosis of Vertebral Artery Type in Rats / 中国实验方剂学杂志

Objective:To establish a model of cervical spondylosis of vertebral artery type （CSA） in rats by mixed modeling method， and observe the intervention effect of Panlongqi tablet （PLQT） on CSA rats. Method:SD rats were divided into a normal control group， a model group， low- （0.16 g·kg^-1）， medium- （0.32 g·kg^-1）， and high-dose （0.64 g·kg^-1） PLQT groups， and a Jingfukang granule （JFK， 1.35 g·kg^-1） group. The rats were treated correspondingly 24 hours after modeling for eight weeks， and those in the normal control group received an equal volume of normal saline by gavage. The limb movement was tested by the inclined plate assay， vertebral artery flow volume by multi-mode high-frequency sound wave for small animals， and microcirculatory blood flow in the pia mater by the laser Doppler. The imaging of the cervical spine was recorded and scored by X-ray micro-computed tomography （Micro CT）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of endothelin-1 （ET-1）， nitric oxide （NO）， tissue plasminogen activator （t-PA）， and plasminogen activator inhibitor （PAI）. Result:Compared with the normal control group， the model group showed decreased limb movement， vertebral artery flow volume， and microcirculatory blood flow in the pia mater， and increased imaging of the cervical spine and score （<italic>P</italic><0.05，<italic>P</italic><0.01）. PLQT could dose-dependently improve the motor function， increase the vertebral artery flow volume and microcirculatory blood flow in the pia mater， and reduce the degree and score of imaging of the cervical spine in CSA rats（<italic>P</italic><0.05，<italic>P</italic><0.01）. The serum levels of NO and t-PA were decreased and those of ET-1 and PAI were increased in the model group as compared with those in the normal control group， while such changes were reversed by PLQT treatment（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:PLQT can enhance the limb movement， promote the vertebral artery flow volume and microcirculatory blood flow in the pia mater， improve the degree of imaging of the cervical spine， regulate the vasomotor function， and improve the coagulation and fibrinolysis system of CSA rats， which shows good potential for the treatment of CSA.

SNP Panel Analysis of Ancestry Inference in East Asian Populations / 法医学杂志

Objective To develop an SNP Panel for East Asian population, which has a high individual identification rate and the capability of ancestry analysis. Methods The 55 SNP Panel by Professor KIDD of Yale University and the 128 SNP Panel by Professor SELDIN of Davis School of California University, 170 SNP Panel in total was used as the basis and its test data in the East Asian population was collected. The genetic parameters of SNP loci were calculated and combined with the results of heatmap analysis to screen SNP loci suitable for East Asian population. Some Tibetan and Han samples were tested. The possibility of using the SNP loci in ancestry inference was analyzed by means of STRUCTURE analysis, principal component analysis and heatmap analysis. Results A Panel with 45 SNPs （45 SNP Panel） was screened out, and the average genetic parameters of each SNP were better than 170 SNP Panel, with the same ancestry analysis and inference ability. Conclusion In terms of ancestry inference information, the 45 SNP Panel can completely replace the 170 SNP Panel and achieve the same ancestry analysis and inference ability. In genetic parameters, 45 SNP Panel is better than 170 SNP Panel in the East Asian population, which shows its important potential forensic application value.

Identification of New Psychoactive Tryptamines 4-OH-MET and 4-AcO-DMT Using High Resolution Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy / 法医学杂志

Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and 1H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.

Development in methods and application of healthy life expectancy / 上海预防医学

With the development of social economy and improvement of people's health condition， life expectancy continues to extend and people are more concerned about the quality of life. Nowadays people's attention has shifted from living longer lives to living healthier lives. Life expectancy can only reflect the length of life， but not the health condition and quality of life. Meanwhile， healthy life expectancy contains death and disability information， which comprehensively reflects the length and quality of life and evaluates the health status of the population comprehensively. Through literature search and review， the article summarized the research on healthy life expectancy in recent years， including the concept proposal， index development， calculation， and application progress of health life expectancy. The research methods of healthy life expectancy are summarized in order to provide academic reference for further research.

Analysis of the epidemiological characteristics and survival rate of cancer in Qingpu District， Shanghai from 2012 to 2016 / 上海预防医学

Objective:To analyze the incidence and death characteristics of cancer and survival rate of residents in Qingpu District， Shanghai from 2012 to 2016， and to provide a scientific basis for subsequent cancer prevention and treatment. Methods:The malignant tumor incidence and death data were collected by the Shanghai Malignant Tumor Case Registration System. Based on these data， the crude incidence and mortality rate of cancer， the standardized rate， the order of incidence and death of the top 10 cancers， and the overall survival rate were calculated using the life table method. The relative survival rate for 1 to 5 years was calculated using the Ederer II method according to survival probability in the abbreviated life table for the same period. The annual percentage change （APC） was calculated by Joinpoint software， and the trend of morbidity and mortality was analyzed. Results:A total of 10 893 new malignant tumor cases were diagnosed in the region from 2012 to 2016. The crude incidence rate of cancer in the whole region was 464.68/100 000 （502.06/100 000 for men and 428.57/100 000 for women）， and the standardized incidence rate was 224.61/100 000 （235.52/100 000 for men， and 217.98/100 000 for women）. A total of 5 820 people died of cancer， the crude mortality rate of cancer in the whole region was 248.28/100 000 （321.92/100 000 for men and 177.13/100 000 for women）， and the standardized mortality rate was 97.08/100 000 （133.14/100 000 for men and 66.38/100 000 for women）. Patients with malignant tumors diagnosed in Qingpu District in 2012 showed higher 5-year relative survival for breast cancer （87.03%）， malignant tumors of brain and central nervous system （73.62%）， and colorectal cancer （58.22%）. A relative low 5-year survival rate was observed in patients with pancreatic cancer （3.76%）， esophageal cancer （10.55%）， and liver cancer （15.79）. Conclusion:Lung cancer and malignant tumors of the digestive system （including gastric cancer and colorectal cancer） are the main types of cancer threatening the health of residents in Qingpu District. The survival rates of breast cancer， malignant tumors of brain and central nervous system， and colorectal cancer have reached or approached the level of developed countries. However， the overall survival rate of malignant tumors in Qingpu District is lower than that in the city， and needs to be further improved.

Serological detection and clinical manifestations of brucellosis in the key occupational population in Baotou City / 中国职业医学

OBJECTIVE: To analyze the serological positive results of brucellosis and its clinical manifestations in the key occupational population in Baotou City. METHODS: A total of 9 937 individuals from eight districts who were engaged in livestock breeding, grazing, slaughtering, processing, and selling from 2018 to 2019 in Baotou City were selected as the study subjects by a cluster sampling method. Blood samples were collected and serological tests of brucellosis were performed. The demographic characteristics and clinical manifestations of these subjects were investigated by a questionnaire. RESULTS: The seropositive rate of brucellosis in the study subjects was 2.7%(273/9 937). The average age of the individuals with serological positive reaction of brucellosis was(44±13) years. The seropositive rate of brucellosis was higher in males than females(4.8% vs 1.2%, P<0.05). In the brucellosis seropositive population, the regional distribution was the highest in Damao Qi district and the lowest in Qingshan district; the mainly occupation distribution was farmers, herdsmen and workers in beef and mutton processing plants. The exposure ways were mainly slaughtering animals and delivering lambs. The main clinical manifestations were fatigue(54.2%), followed by fever(48.7%). CONCLUSION: The characteristics of brucellosis serological positive reaction are young age, males, and farmers and herdsmen in key occupational group in Baotou City. The prevention and control of brucellosis should be focused on young male farmers and herdsmen engaged in slaughtering animals and delivering lambs.

HPLC characteristic chromatograms and quantitative analysis of Kunxian Capsules / 中草药

Objective: In order to provide a scientific basis for the quality control of Kunxian Capsules (KC), HPLC characteristics chromatogram combined with multi-components determination was established. Methods: The analysis was performed on Agilent Zorbax SB-C18 column (250 mm × 4.6 mm, 5 μm), using acetonitrile and 0.1% phosphoric acid solution as the mobile phase at a flow rate of 0.8 mL/min for gradient elution, the column temperature was 33 ℃, and the detection wavelength was 270 nm. The fingerprints of 15 batches of KC were established and evaluated by the similarity evaluation system of TCM (2012A version), hierarchical cluster analysis and discriminant analysis of partial least squares. Furthermore, the content of hyperoside, epimedin A, epimedin B, epimedin C, icariin and baohuoside Ⅰ were determined. Results: The HPLC fingerprint with 21 common peaks of KC was established, and the similarities of samples were over 0.9. The linearity relationships separated with hyperoside, epimedin A, epimedin B, epimedin C, icariin and baohuoside Ⅰ were good, and the contents of the above-mentioned components in 15 batches of preparations were 2.817-7.527, 7.287-9.103, 8.730-18.675, 33.377-70.371, 35.297-50.291 and 4.059-9.079 mg/g, respectively. Conclusion: The combination methods of HPLC characteristic chromatograms and simultaneous determinations of multiple components are rapid, simple and reproducible, which can provide methodological reference for the quality control of KC.

Overexpression of miR-31 regulates TLR4/NF-κB signaling pathway and apoptotic protein in colitis model mice / 中国应用生理学杂志

To investigate the effects of miR-31 on TLR4/NF-κB signaling pathway and apoptosis-related proteins in dextran sulfate sodium (DSS) induced mouse colon colitis. Methods: ① Mouse model of colon colitis: 1% DSS was used to induce mouse ulcerative colitis (UC). Fourteen FVB non-transgenic mice were randomly divided into control group (n= 6), DSS group (n= 8), and 16 FVB miR-31 transgenic mice were randomly divided into miR-31 overexpression group (n= 8), miR-31 overexpression +DSS group (n= 8). DSS was dissolved in water and administered to mice by drinking water. The DSS group and miR-31+DSS group drank 1% DSS water in the first week, normal sterilized water in the second week, and 1% DSS water in the third week, after 5 weeks, the modeling was completed, then the colon tissues of the mice were collected. Western blot and IHC were used to detect the expressions of NF-κB p65, TLR4, Bax and Bcl-2 proteins in mouse colon tissue, TUNEL was used to detect apoptosis of mouse colon tissues. ② Cell culture experiments: Transfection of miR-31mimic and inhibitor by lipofectamine resulted in overexpression or knockdown of miR-31 in human colon epithelial cell line HCT 116 cells, each group was repeated three times and cells were collected 48 h later, Western blot was used to detect the expressions of NF-κB p65 and TLR4 protein. ① In animal experiments, compared with the control group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the DSS group and miR-31 overexpression group in mouse colon tissue were significantly increased (P＜0.05 or P＜0.01), and the Bcl-2 / Bax ratio was significantly reduced (P＜0.05 or P＜0.01); and compared with the DSS group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the miR-31+DSS group were significantly increased (P＜0.01), while the Bcl-2/Bax ratio was significantly decreased (P＜0.01). ② In cell experiments, compared with the control group, the expression levels of NF-κB p65 and TLR4 protein in the over-expressed miR-31 group of HCT 116 cells were significantly increased (P＜0.05 or P＜0.01), the expressions of NF-κB p65 and TLR4 protein in miR-31 knockdown group were decreased (P＜0.05). miR-31 promotes the development of colitis by promoting TLR4/NF-κB signaling pathway and mediating apoptosis of intestinal epithelial cells.

"Medium and Long-term Plan for the Prevention and Control of Chronic Non-communicable Diseases in Shanghai(2018-2030)" in the perspective of public health / 上海预防医学

The "Medium and Long-term Plan for the Prevention and Control of Chronic Non-communicable Diseases in Shanghai (2018-2030)" was officially released in August 2018.From the perspective of public health, this paper analyzes the background of the plan from the epidemic situation, response and challenges Shanghai City is facing, expounds the comprehensive prevention and control system of chronic diseases including four functional systems, and explains the key preventive and control measures on the different stages of chronic diseases, comparing the evaluation indicators with those of the national plan.This paper will help to better understand the new blueprint for the prevention and control of chronic diseases in Shanghai in the next ten years.

Analgesic Effect of Panlongqi Tablet on Rats with Chronic Inflammatory Pain / 中国实验方剂学杂志

Objective:To observe the analgesic effect of Panlongqi tablet（PLQT） on rats with chronic inflammatory pain， and to explore mechanism of the action preliminarily from the perspective of the nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）and mitogen-activated protein kinase（MAPKs） signaling pathways. Method:Rats were induced to establish model of chronic inflammatory pain by complete Freund adjuvant（CFA）， which was divided into normal group， model group， the PLQT 0.16，0.32，0.64 g·kg-1 group， and the ibuprofen 0.05 g·kg-1 group（also positive group）， give the medicine once a day by gavage. Standard Von Frey fiber was used to evaluated the mechanical pain threshold， acetone was used to stimulated rats inflammatory foot to get the cold-induced response score， with the mechanical pain threshold and cold-induced response score to be observed at 1， 2， 3， 4 and 6 h before and after administration on day 1， and at 4 h after administration on day 3-7. The content of PGE2， IL-1， TNF-α in serum， inflammatory foot and 4-5 lumbar spinal cord was detected by enzyme-linked immunosorbent assay（ELISA）. The protein level of MAPKs （p-p38， p-ERK， p-JNK） in lumbar spinal cord 4-5 was detected by Western blot. The expression of NF-κB p65 in the lumbar spinal cord was detected by IFA. Result:Model group had lower mechanical pain threshold and higher cold-induced response score than these in normal group（P<0.01）， while the mechanical pain threshold and cold-induce response score of the model rats were dose-dependent better regulated after administration of PLQT 0.16， 0.32， 0.64 g·kg-1·d-1（P<0.05，P<0.01）， these effect lasted 6 h， of which PLQT groups get the most significant effect on 4 h， however the effect of IBP was similar to that of PLQT medium dose group. In addition， PLQT reduced the abnormal increase of PGE2， IL-1 and TNF-α contents in serum， inflammatory foot and spinal cord of rats in model group， decreased the protein phosphorylation levels of ERK and JNK in spinal cord， and decreased the protein expression of NF-κB p65， that was significant in the PLQT high-dose group（P<0.01）. Conclusion:PLQT had significant analgesic effect on chronic inflammatory pain model rats， which may be related to the inhibition of NF-κB and MAPKs signaling pathways in spinal cord.