Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China / 生物医学与环境科学（英文）

OBJECTIVE@#The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.@*METHODS@#We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.@*RESULTS@#Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.@*CONCLUSION@#HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.

Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism.@*METHODS@#Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice.@*RESULTS@#Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05).@*CONCLUSION@#BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

Role of GDC-0449 in a rat model of liver fibrosis induced by carbon tetrachloride combined with 2-acetylaminofluorene / 临床肝胆病杂志

Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.

Analysis and comparison of metabolic processes of salvianolic acid A and salvianolic acid B in rats based on UHPLC-LTQ-Orbitrap MS technology / 中国中药杂志

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.

Prescription Research and Clinical Application of Yiguanjian / 中国实验方剂学杂志

By systematically sorting out the ancient medical books and modern clinical literature of Yiguanjian， the historical evolution of this formula， including its source， composition， origin， processing， dosage， preparation and usage， functions and indications， evolution of prescription meaning， is textual so as to clarify the historical evolution and clinical application of Yiguanjian. On the basis of fully considering the actual demand of development of famous classical formula preparation and the usage habit of modern clinical practice， the feasible development suggestions were put forward. Yiguanjian is composed of six herbs， which is derived from Yifang Jiedu (《医方絜度》) . It is an ancient book of traditional Chinese medicine edited by QIAN Min-jie in Qing dynasty. The original medicinal plants and medicinal parts of the formula were basically the same as those recorded in the 2020 edition of Chinese Pharmacopoeia. The raw products should be selected for decoction pieces and processed according to the methods recorded in the 2020 edition of Chinese Pharmacopoeia. The reference dose of the medicine in this formula is set out in Yifang Jiedu. According to dosage of one Qian（钱）=3.73 g， the dosages of Glehniae Radix， Ophiopogonis Radix and Angelicae Sinensis Radix were 5.60 g， the dosages of Lycii Fructus and Rehmanniae Radix were 11.19 g， the dosage of Toosendan Fructus was 7.46 g. These decoction pieces were boiled and warm decoction was taken. According to ancient medical records， the formula always has the effect of nourishing Yin and relieving Qi of liver. It is used to treat syndrome of stagnation of liver-Qi and deficiency of liver-Yin and kidney-Yin， which can be seen with pain in chest， stomach and flank， acerbity and vomiting， dry throat and mouth， red tongue， weak pulse or deficiency of string and hernia. Here， the source， processing and others of Yiguanjian were clarified， providing a literature reference for the development and application of this famous classical formula.

Expression of lymphocyte-activation gene 3, programmed cell death protein 1 and its ligand 1 in decidual lymphocytes of women with preeclampsia / 中华围产医学杂志

Objective:To investigate the expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1(PD-L1), and lymphocyte-activation gene 3(LAG-3) in different subsets of lymphocytes and their relationship with the immunologic imbalance in preeclampsia.Methods:We enrolled 25 cases of singleton pregnant women with preeclampsia who were delivered by cesarean section in the Shandong Provincial Hospital Affiliated to Shandong First Medical University from May 2019 to January 2020 as the preeclampsia group. According to the allocation ratio of 1∶1 matched for the date of cesarean section and pregnancy week at delivery, another 25 healthy singleton pregnant women underwent elective cesarean section were selected as the normal group. The decidua tissue was obtained during cesarean section. The expression levels of PD-1, PD-L1, and LAG-3 on decidual T cells, natural killer (NK), and natural killer T (NKT) cells were measured by flow cytometry and compared between the two groups using two independent samples- t test. Results:(1) The expression of PD-1 on decidual T cells and NK cells of the preeclampsia group were lower than those of the normal group (37.84±3.82 vs 57.02±3.89, t=3.529, P<0.001; 3.28±0.48 vs 5.69±0.99, t=2.184, P=0.034), but did not differ significantly in the expression on decidual NKT cells ( P=0.461). PD-L1 expression on decidual NK cells of preeclampsia group was lower than that of the normal group (0.60±0.11 vs 1.32±0.19, t=3.319, P=0.002), but showed no significant difference in the expression level on T cells and NKT cells (both P>0.05). The preeclampsia group was noted for a lower expression of LAG-3 on decidual T cells and NKT cells compared with the normal group (2.32±0.36 vs 4.09±0.67, t=2.335, P=0.024; 35.40±4.97 vs 56.27±4.49, t=3.282, P=0.002), while showed no significant difference in the expression level of NK cells ( P=0.112). Conclusions:The decreased expression of PD-1, PD-L1, and LAG-3 in the decidual lymphocyte subsets may be involved in the immunologic imbalance of preeclampsia through the over-activation of immunocytes at the maternal-fetal interface.

Advances in Neuropathologic Research of Hypoglycemic Brain Damage Caused by Insulin Overdose / 法医学杂志

The number of death from insulin overdose, including accidental poisoning, suicide and homicide, is increasing these years. The forensic diagnosis of death from insulin overdose is a tough task. Glucose is the main energy source of the brain. Therefore, hypoglycemic brain damage is considered to be the main reason of death from insulin overdose. Recently, research of hypoglycemic brain damage caused by insulin overdose is gradually being paid attention in the field of forensic medicine. This paper summarizes the neuropathologic changes, pathophysiologic process and potential neural molecular markers of hypoglycemic brain damage caused by insulin overdose in terms of forensic neuropathology, providing reference for the research and practice in forensic medicine related fields.

RGFP966 inactivation of the YAP pathway attenuates cardiac dysfunction induced by prolonged hypothermic preservation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4-6 h. The aim of this study was to investigate whether the histone deacetylase 3 (HDAC3) inhibitor RGFP966 could protect against cardiac injury induced by prolonged hypothermic preservation. Rat hearts were hypothermically preserved in Celsior solution with or without RGFP966 for 12 h followed by 60 min of reperfusion. Hemodynamic parameters during reperfusion were evaluated. The expression and phosphorylation levels of mammalian STE20-like kinase-1 (Mst1) and Yes-associated protein (YAP) were determined by western blotting. Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation. RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated (p)-Mst1/Mst1 and p-YAP/YAP ratios, prevented a reduction in total YAP protein expression, and increased the nuclear YAP protein level. Verteporfin (VP), a small molecular inhibitor of YAP-transcriptional enhanced associate domain (TEAD) interaction, partially abolished the protective effect of RGFP966 on cardiac function, and reduced lactate dehydrogenase activity and malondialdehyde content. RGFP966 increased superoxide dismutase, catalase, and glutathione peroxidase gene and protein expression, which was abolished by VP. RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cleaved caspase-3, increased Bcl-2 mRNA and protein expression, and reduced cardiomyocyte apoptosis. The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP. The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction. The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.

Digital language markers distinguish the pathological effect of Alzheimer′s disease and mild cognitive impairment from the aging effect / 中华神经科杂志

Objective:To characterize the digital language markers in Alzheimer′s disease (AD) and mild cognitive impairment (MCI) patients, and to explore the pathological effect and aging effect on these markers.Methods:AD ( n=14) and MCI ( n=16) patients from memory clinic in Peking Union Medical College Hospital, age-matched cognitively normal elderly adults ( n=18) and youthful adults ( n=19) as controls participated in the study. The digital speech data of animal fluency test were collected. Novel language markers such as response time, semantic similarity and word frequency were analyzed in addition to the traditional word production, clustering and switching indicators by trained professionals. Multiple linear regression analysis with multiple comparison was used to test the associations of language markers with the cognitive status, adjusting for education. Results:The results of multiple regression analysis showed that, after adjusting for the years of education, statistically significant differences existed in 11 language markers among the four groups ( P<0.001), except for the effective word production in the last 15 s, cluster size, the first word response time and the average semantic similarity. Compared to other three groups, AD group differed significantly in effective word production, effective rate, repetitive rate, effective word production in the first 15 s, the number of subcategories, single word production time and inter-subcategory switching interval ( P<0.001). In addition, compared to cognitively normal youthful group, AD group had less number of switching and shorter semantic maximum distance ( P=0.001, P<0.001); both AD and MCI groups had longer intra-subcategory switching interval ( P<0.001, P=0.001); AD, MCI and cognitively normal elderly groups had significantly higher word frequency ( P<0.001); MCI group had significantly less number of effective word production and subcategories ( P=0.002, P=0.003); both MCI and cognitively normal elderly groups had significantly longer single word production time ( P<0.001). Conclusions:The performance of AD patients on the semantic fluency test task was affected by both pathological effect and normal aging effect. Pathological indicators included effective word production, effective rate, repetition rate, effective word production in the first 15 s, the number of subcategories, inter-subcategory switching interval and single word production time. These results provide a new approach to identify the specific effects of AD dementia.

An FT 3/FT 4 ratio greater than 0.4 is helpful in differentiating Graves′ disease from subacute thyroiditis / 中华内分泌代谢杂志

Objective:To search for the clinical indicators in differentiating Graves′ disease from subacute thyroiditis (SAT).Methods:Retrospective analysis was performed on thyroid function measurement of 265 cases of newly diagnosed Graves′ disease, 76 cases of SAT with thyrotoxicosis, 100 cases of non-toxic thyroid nodules, 105 cases of autoimmune thyroid diseases with normal thyroid function, and 151 cases of outpatients with normal thyroid function and without thyroid diseases.Results:Free triiodothyronine(FT 3)/free thyroxine(FT 4) ratio of Graves′ disease patients was significantly higher than that of SAT patients with thyrotoxicosis (0.65±0.29 vs 0.32±0.75, P<0.05). Receiver operating characteristic curve(ROC curve) analysis of FT 3/FT 4 ratio between Graves′ disease group and SAT group showed that FT 3/FT 4 ratio greater than 0.4 with a sensitivity of 98.11% and a specificity of 83.81% for diagnosis of Graves′ disease. Conclusion:FT 3/FT 4 ratio greater than 0.4 is helpful for differentiating Graves′ disease from subacute thyroiditis with thyrotoxicosis.

Analysis of carnosic acid metabolites in rats by UHPLC-Q-Exactive MS / 中国中药杂志

A method of ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field Obitrap high-resolution mass spectrometry(UHPLC-Q-Exactive MS) was established to comprehensively identify the metabolites of carnosic acid in rats. After oral gavage of carnosic acid CMC-Na suspension in rats, urine, plasma and feces samples were collected and pretreated by solid phase extraction(SPE). Acquity UPLC BEH C_(18 )column(2.1 mm×100 mm, 1.7 μm) was used with 0.1% formic acid solution(A)-acetonitrile(B) as the mobile phase for the gradient elution. Biological samples were analyzed by quadrupole/electrostatic field Obitrap high-resolution mass spectrometry in positive and negative ion mode. Based on the accurate molecular mass, fragment ion information, and related literature reports, a total of 28 compounds(including carnosic acid) were finally identified in rat samples. As a result, the main metabolic pathways of carnosic acid in rats are oxidation, hydroxylation, methylation, glucuronide conjugation, sulfate conjugation, S-cysteine conjugation, glutathione conjugation, demethylation, decarbonylation and their composite reactions. The study showed that the metabolism of carnosic acid in rats could be efficiently and comprehensively clarified by using UHPLC-Q-Exactive MS, providing a reference for clarifying the material basis and metabolic mechanism of carnosic acid.

Analysis of 4 Cases of Electrocution due to Direct Current Electronic Hunter / 法医学杂志

Objective To summarize the characteristics of cases of electrocution due to direct current （DC） electronic hunter, and to provide references for forensic identification. Methods Four cases of electrocution due to DC electronic hunter were collected. Statistical analysis was carried out from the perspective of the scene and electric marks distribution, damage characteristics and histopathological changes. Results All the 4 cases of electrocution were accidental events. There were multiple electric marks, most of which were located in the lower limbs with serious damage. Some strip type electric marks were visible. Conclusion The distribution, morphological characteristics and severity of the electric marks caused by DC electronic hunter are different from those of the ordinary low-voltage alternating current damage. It is alerting that there would be actions of destroying the scene and abandoning the corpse in such cases.

CTHRC1 promotes proliferation of gastric cancer cells by overexpression of COL1A1 / 解放军医学杂志

Objective To investigate the proliferation and potential mechanism of CTHRC1 on gastric cancer cells. Methods The cancer tissues and adjacent tissues were collected of 8 gastric cancer patients diagnosed by pathology from Jun. 2017 to Jun. 2018 in Guangzhou Zengcheng People's Hospital. Human gastric mucosal GES-1 cells, and gastric cancer SGC-7901, BGC-823, BGC-803, MKN-45, and MKN-28 cells were purchased from Shanghai Cell Bank of Chinese Academy of Sciences. Western blotting was used to detect the expression of CTHRC1 protein in gastric cancer tissues, paracancerous tissues and gastric cancer cell lines SGC-7901, BGC-823, BGC-803, MKN-45, MKN-28 and human gastric mucosal GES-1 cells. After transfection of gastric cancer SGC-7901 cells with si-CTHRC1 and si-COL1A1, cell proliferation was detected by MTT assay, and the apoptosis rate was detected by flow cytometry. The target gene of CTHRC 1 was predicted by STRING database. Western blotting and immunofluorescence were performed to detect the expression of CTHRC1 and COL1A1 proteins in gastric cancer SGC-7901 cells transfected with si-CTHRC1. The expressions of CTHRC1 and COL1A1 proteins in gastric cancer tissues and the prognosis of gastric cancer patients were analyzed by Kaplan-Meier. Results The expression of CTHRC1 protein was significantly higher in gastric cancer tissues (0.87±0.13) than in adjacent tissues (0.31±0.20, P<0.05). The expression of CTHRC1 protein was higher in gastric cancer cell lines than in human gastric mucosa GES-1 cells with significant difference (P<0.05). The cell proliferation of gastric cancer SGC-7901 cells transfected by si-CTHRC1 decreased significantly. The cell vitality of gastric cancer SGC-7901 cells co-transfected by si-CTHRC1 and si-COL1A1 was lower (0.40±0.07) than those only transfected by si-CTHRC1 (0.87±0.05) or by si-COL1A1 groups (0.83±0.13, P<0.05). The apoptosis rate of gastric cancer SGC-7901 cells transfected by si-CTHRC1 (6.77%±1.55%) was higher than that in NC group (4.80%±1.93%) with statistical significance (P<0.05). The STRING database predicted that COL1A1 was a target gene for CTHRC1. For gastric cancer SGC-7901 cells transfected by si-CTHRC1, the relative expressions of CTHRC1 and COL1A1 proteins were 0.92±0.16 and 1.08±0.23, which were higher than those in NC group (0.55±0.15 and 0.65±0.12) with significant difference (P<0.05). Immunofluorescence showed that the expressions of CTHRC1 and COL1A1 proteins decreased significantly after transfection of si-CTHRC1 into gastric cancer SGC-7901 cells. Kaplan-Meier analysis showed that the 5-year survival rate of patients with high CTHRC1 expression in gastric cancer tissues was significantly lower (27.4%) than that of patients with low CTHRC1 expression (38.4%); The 5-year survival rate of patients with high COL1A1 expression in gastric cancer tissues (20.4%) was significantly lower than that in low expression patients (49.3%), the difference was statistically significant (P<0.001). Conclusion CTHRC1 promotes the proliferation of gastric cancer cells by overexpressing COL1A1 protein.

Relationship between serum uric acid level and subclinical target organ damage / 上海交通大学学报（医学版）

Objective: To explore the correlation between serum uric acid level and subclinical target organ damage. Methods: A cohort of 333 patients were recruited at the Department of Examination Center of Ruijin Hospital North in July 2017, who were divided into two groups, normal (n=248) and high levels (n=85, males >420 µmol/L, females >360 µmol/L) of serum uric acid. Subclinical target organ damage indexes included glomerular filtration rate (eGFR), left ventricular mass index (LVMI) and other indicators. Results: Systolic pressure (P=0.006), diastolic pressure (P=0.000), serum creatinine (P=0.000) and LVMI (P=0.028) in the high uric acid group were significantly higher than those in the normal uric acid group, and eGFR was significantly lower than that of the control group (P=0.000). Pearson correlation analysis showed that the serum uric acid level was significantly correlated with systolic pressure (r=0.149, P=0.007), diastolic pressure (r=0.269, P=0.000), LVMI (r=0.172, P=0.002) and serum creatinine (r=0.569, P=0.000), and negatively correlated with glomerular filtration rate (r=-0.383, P=0.000). After adjusting to sex, age, and BMI, there was a significant positive correlation with diastolic pressure (r=0.170, P=0.013), and a significant negative correlation with glomerular filtration rate (r=-0.332, P=0.000). After further adjusting to blood pressure, there was a significant negative correlation with glomerular filtration rate (r=-0.291, P=0.000). Multivariate linear regression analysis showed that serum uric acid was independent of diastolic pressure and glomerular filtration rate (β=0.162, P=0.000; β=-0.058, P=0.004). Conclusion: Serum uric acid is positively correlated with diastolic blood pressure, and is negatively correlated with glomerular filtration rate.

Comparison of the Biological Functions between Human Bone Marrow Derived CD106 Mesenchymal Stem Cells and CD106 Subgroup / 中国医学科学院学报

Objective To analyze the differences in biological functions between bone marrow(BM)-derived CD106 mesenchymal stem cells(MSCs)and the CD106 subgroup. Methods The MSCs from normal BM were isolated and expanded.The subgroups of CD106 and CD106 MSCs were sorted.The cell proliferation and adhesion functions,chemotactic activities,adipogenic and osteogenic potentials,senescence,and senescence protein 21(p21)were detected.The capacity of translocation into nucleus of nuclear factor-kappa B(NF-κB)when stimulated by tumor necrosis factor(TNF-α)was measured. Results The proliferative ability was higher in CD106 MSCs than that in CD106 MSCs.In 48 hours,the value of optical density(OD)was significantly higher in CD106 MSCs than that in CD106 subgroup(1.004±0.028 0.659±0.023,=3.946,=0.0225).In 72 hours,this phenomenon was even more pronounced(2.574±0.089 1.590±0.074,=11.240,=0.0000).The adhesive capacity of CD106 MSCs was significantly stronger than that of CD106 subgroup(0.648±0.018 0.418±0.023,=7.869,=0.0002).Besides,the metastasis ability of CD106 MSCs were significantly stronger than that of CD106 subgroup(114.500±4.481 71.000±4.435,=6.900,=0.0005).The CD106 MSCs had signifcnatly lower proportions of senescent cells.The expression of aging protein p21 in CD106 MSCs was significantly lower than that in CD106 MSCs [(17.560±1.421)% (45.800±2.569)%,=9.618,=0.0000].Furthermore,there were no visible pigmenting cells after β-galactosidase staining in CD106 MSCs subgroup.However,in CD106 MSCs,some colored green cells were detected.The rate of NF-κB translocation into nucleus after stimulated by TNF-α was significantly higher in CD106 MSCs than CD106 MSCs [(37.780±3.268)% (7.30±1.25)%,=8.713,=0.0001]. Conclusion Bone marrow-derived CD106 MSCs possess more powerful biological functions than CD106 MSCs.

Application of omics approaches in Sclerotinia sclerotiorum / 生物工程学报

Sclerotinia sclerotiorum is a typical necrotrophic plant pathogenic fungus that distributes worldwide and causes severe diseases on a broad-range of plant species. Studies on S. sclerotiorum have been mainly focused on biology and pathology. The development of high-throughput technologies enabled multi-omics approaches for systems biology. This review summarizes current researches on S. sclerotiorum and proposes systemic strategies for understanding its biology and pathology, to provide novel insights and references for further investigation on molecular biology and pathogenesis of the pathogenic fungi and the pathosystems.

Establishment of physical fingerprint of Shengmai Injection and its quality evaluation / 中草药

Objective To establish the physical fingerprint of Shengmai Injection and evaluate its quality. Methods The physical fingerprint was visually showed by the radar map consisting of eight indexes (conductivity, pH, turbidity, refractive index, solid content, relative density, kinematic viscosity, and osmolality). Correlation coefficient method was used to calculate the similarity between the fingerprints and the control fingerprints. Results The products physical fingerprints and parameters of the same species from different manufacturers were quite different. In some companies, the quality of the same product was also unstable among different batches and specifications, mainly reflected in the three indicators of osmolality, conductivity, and turbidity. Conclusion Physical fingerprints can be used to evaluate the quality of Shengmai Injection and provide some ideas for the quality re-evaluation of Chinese medicine injection.

Research advances in the relationship between iron deficiency and neurodevelopment in preterm infants / 中国当代儿科杂志

Iron deficiency (ID) is the most common micronutrient deficiency in children. Due to insufficient iron storage at birth and rapid catch-up growth after birth, preterm infants tend to have a high incidence rate of ID. During the critical period of brain development, ID alters iron-dependent neurometabolism, neurochemistry, neuroanatomy, and gene/protein profiles. This affects the central nervous system and causes the change in neurocognitive and behavioral development. Iron supplementation in infancy cannot reverse neurodevelopmental impairment caused by perinatal ID. The influence of ID on neurodevelopment is time- and region-specific, and in the high-risk population, early diagnosis and optimal iron treatment may help with the recovery of brain function and improve quality of life and long-term prognosis in preterm infants.