Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Comparative analysis of fractional CO 2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions / 中国医师杂志

Objective:To investigate the effects of fractional CO 2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions. Methods:A prospective study was conducted on 126 patients with white lesions of the vulva admitted to Hainan Cancer Hospital from August 2018 to December 2020. They were divided into drug group, focused ultrasound group and fractional CO 2 laser group by random number table method, with 42 patients in each group. The drug group was treated with mometasone furoate cream or dexamethasone acetate cream, and the focused ultrasound group was treated with focused ultrasound; the fractional CO 2 laser group was treated with fractional CO 2 laser. The serum interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and human epidermal growth factor (EGF) levels before and after treatment, and Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) scores of the three groups were compared. Results:Before treatment, there was no significant difference in the levels of IL-2, TNF-α, CRP and EGF among the three groups (all P>0.05). After treatment, the levels of IL-2, TNF-α, CRP and EGF in the three groups were significantly decreased, and the levels of IL-2, TNF-α, CRP and EGF in the focused ultrasound group and fractional CO 2 laser group were lower than those in the drug group, with statistically significant difference (all P<0.05). Before treatment, there was no significant difference in the white lesions, dry pruritus, sexual pain and chapped skin scores of the three groups (all P>0.05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO 2 laser were lower than those of the drug group, with statistical significance (all P<0.05). Before treatment, there was no significant difference in the scores of symptoms and feelings, daily activities and interpersonal relationship of the three groups (all P>0.05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO 2 laser were lower than those of the drug group, with statistical significance (all P<0.05). Conclusions:Fractional CO 2 laser has a remarkable effect in the treatment of gynecological vulva white lesions, which can reduce the level of inflammatory factors in patients, improve the pain condition, and improve the quality of life.

Exploration of pathological technology training for professional postgraduates of pathology / 中华医学教育探索杂志

Combined with teaching practice, this study summarizes the teaching contents, methods and effect evaluation of pathological technology for professional postgraduates majoring in pathology. According to the basic conditions of postgraduates, the pathological technology training program has been formulated, student-centered heuristic teaching is carried out by using diversified teaching methods such as flipped classroom, interactive theoretical teaching is carried out by using the intelligent teaching platform, and practical teaching is carried out by using the problem-based learning mode, aiming to improve the theoretical literacy and practical level of pathological technology of professional postgraduates majoring in pathology, improve their clinical research thinking, and lay a foundation for clinical pathological diagnosis and scientific research in the future.

C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery / 中华外科杂志

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Influencing factors of early activity in patients with acute ischemic stroke based on social ecological model: A qualitative study / 中南大学学报(医学版)

OBJECTIVES@#Acute ischemic stroke (AIS) is one of the main causes of disability in middle-aged and elderly people, and early activity plays an important role in functional recovery. This study aims to understand the factors that affect the implementation of early activity in patients with AIS and to provide reference for promoting early activity implementation and developing intervention strategies for AIS patients.@*METHODS@#Using purposive sampling, 19 AIS patients and their caregivers who visited at Stroke Center in the Third Xiangya Hospital of Central South University and the Third Hospital of Changsha from June to December 2021, as well as 19 medical staff, hospital administrators, or community workers providing medical health services to stroke patients, were selected as interviewes. A semi-structured interview was conducted based on the social ecological theory model, and the Colaizzi seven-step method was used to analyze the interview data.@*RESULTS@#According to qualitative interview results, the factors affecting early activity in AIS patients were summarized into 4 themes and 12 sub-themes: medical staff factors (insufficient knowledge and skills, insufficient knowledge of early activity, unclear division of responsibilities), patient factors (severity of the disease, lack of knowledge, psychological pressure, fear of falling), social environmental factors (lack of social support, shortage of human resources and rehabilitation equipment, insufficient medical insurance support), and evidence and norms (the evidence for early activity needs improvement, lack of standardized early activity procedures).@*CONCLUSIONS@#Early activity in AIS patients is impacted by factors at multiple levels, including medical staff, patients, social environment, and evidence and norms. Developing comprehensive intervention strategies to address these factors can promote early activity implementation in AIS patients.

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Huanglian Jiedutang Treats Acute Gouty Arthritis via NLRP3 Inflammasome and TLR4/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Huanglian Jiedutang on the inflammatory injury in the mouse model of acute gouty arthritis （AGA） and to explore the mechanism of Huanglian Jiedutang in treating AGA. MethodForty male C57BL/6J mice were randomized into blank， model， colchicine （0.83 mg·kg-1）， and Huanglian Jiedutang （5 g·kg-1） groups. The mouse model of AGA was established by injecting monosodium urate （MSU） crystals into the ankle joint. The swelling degree of the right ankle joint of each mouse was measured every day for 7 days， and the pathological changes of the ankle joint were detected by hematoxylin-eosin （HE） staining after 7 days. The other 40 C57BL/6J mice were grouped as above. After 18 hours of modeling， the right ankle joint was collected， and real-time polymerase chain reaction was employed to measure the mRNA levels of interleukin （IL）-1β， tumor necrosis factor （TNF）-α， IL-6， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The expression levels of IL-1β， TNF-α， and IL-6 were measured by the enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of NLRP3 inflammasome， Toll-like receptor 4 （TLR4）， and nuclear factor-κB （NF-κB）. ResultCompared with the blank group， the model group showed swelling right ankle joint （P<0.01）， obvious foreign body granuloma in the ankle joint with inflammatory cell infiltration. After the treatment with Huanglian Jiedutang， the ankle joint swelling was relieved （P<0.05， P<0.01）， and the size of foreign body granuloma was reduced. Compared with the blank group， the model group showed up-regulated mRNA levels of IL-1β， TNF-α， and IL-6 in the ankle joint tissue （P<0.01）， up-regulated mRNA levels of NLRP3 and Caspase-1 in the NLRP3 inflammasome （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05， P<0.01）. Huanglian Jiedutang down-regulated the mRNA levels of IL-1β， TNF-α， IL-6， NLRP3， and Caspase-1 （P<0.05， P<0.01） and the protein levels of IL-1β， TNF-α， IL-6， NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05 or P<0.01）. ConclusionInjecting MSU crystal resulted in local inflammatory injury of the joints in the mouse model of AGA. The treatment with Huanglian Jiedutang may alleviate the inflammatory injury by regulating the NLRP3 inflammasome and TLR4/NF-κB signaling pathway.

An anterolateral thigh perforator chimeric flap combined with calcium sulfate impregnated with vancomycin for treatment of chronic fracture-related infection complicated with extensive soft-tissue defects / 中华创伤骨科杂志

Objective:To investigate the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate in the treatment of chronic infection after internal fixation of calf fracture with soft tissue defects.Methods:Retrospectively analyzed were the data of 16 patients with chronic infection combined with extensive soft tissue defects after internal fixation of calf fracture who had been admitted to Department of Orthopedics, Shenzhen Hospital Affiliated to Peking University from September 2008 to November 2020. There were 11 males and 5 females, aged from 16 to 62 years (average, 37 years). Infection sites: the upper tibia in 4 cases, the middle and lower tibia in 10 cases, and the middle fibula in 2 cases. According to the Cierny-Mader classification, all patients were anatomical type III and by the host classification, there were 14 cases of type B and 2 cases of type C type. The areas of soft tissue defects ranged from 6 cm × 4 cm to 23 cm × 14 cm. All patients were treated by transplantation of an anterolateral thigh chimeric perforator flap combined with vancomycin-loaded calcium sulfate therapy. At the last follow-up, the curative efficacy was evaluated according to the Paley fracture union scoring.Results:All patients were followed up for 8 to 24 months (mean, 16 months). Complete flap survival was achieved in 15 flaps and partial survival in one. According to the Paley fracture union scoring at the last follow-up, the curative efficacy was evaluated as excellent in 15 cases and as good in one. Both the grafted artificial bone and the tibia and fibula achieved bone union after 6 to 12 months (mean, 8.9 months). Infection with chronic sinus tract pus recurred in one case at post-operative one year. After re-debridement, the infection was controlled and the wound healed. The plate internal fixation was replaced by the unilateral or annular external fixator in 14 patients and retained in 2 patients. The lengths of the bone defects averaged 2.4 cm and the time for the external fixation 10.5 months (from 8 to 14 months).Conclusion:In the treatment of chronic infection after internal fixation of calf fracture with extensive soft tissue defects, the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate is satisfactory, because the flap can fully cover the bone and soft tissue defects while the vancomycin-loaded calcium sulfate can effectively control the infection.

Huanglian Jiedutang Regulates Inflammatory Immunity to Relieve Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effects of Huanglian Jiedutang on pathological and immune damage in collagen-induced arthritis （CIA） model mice， and to explore the possible mechanism of Huanglian Jiedutang in relieving rheumatoid arthritis. MethodTwenty-four DBA/1 mice were randomly divided into normal group， model group， methotrexate group and Huanglian Jiedutang group， with six mice in each group. The CIA mice model were established using type Ⅱ collagen induction. The administration groups were respectively treated with Huanglian Jiedutang （5 g·kg-1） and methotrexate （0.5 mg·kg-1）. The joint swelling symptoms of the mice were observed， and the arthritis index was scored every 3 days. Flow cytometry was employed to detect granulocytes， monocytes， and T lymphocytes in peripheral blood. The expression of inflammatory cytokines in joint was determined by real-time polymerase chain reaction （Real-time PCR）. The ankle joint was scanned by micro-computed tomography （Micro-CT）， and the histopathological changes were observed through hematoxylin-eosin （HE） staining. ResultCompared with the normal group， the modeling led to joint swelling， elevated the joint index score （P<0.05）， increased the proportion of granulocytes （P<0.05） and decreased that of monocytes and T lymphocytes （P<0.01） in peripheral blood， and raised the neutrophil-to-lymphocyte ratio （NLR） （P<0.01）. Further， it up-regulated the expression of inflammatory cytokines such as tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 in joint （P<0.01）. Micro-CT showed obvious bone destruction in the ankle joint， and pathological examination revealed the infiltration of a large number of inflammatory cells and the synovial hyperplasia of joint tissue. Compared with the model group， Huanglian Jiedutang alleviated the symptoms of joint swelling， lowered the score of arthritis index （P<0.05）， increased the proportion of T lymphocytes and lowered NLR （P<0.01）. Moreover， it down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in joint （P<0.01） and alleviated the bone destruction and pathological injury of joint tissue. ConclusionType Ⅱ collagen caused systemic and local inflammatory immune damage in CIA mice. Huanglian Jiedutang alleviates such injury， especially for that in local joint， thereby inhibiting joint injury and bone destruction in CIA mice.

Ginkgo diterpene lactone improves depression-like behaviors and affects cytokine and neurotransmitter levels in a rat model of chronic unpredictable mild stress / 中华微生物学和免疫学杂志

Objective:To investigate the effects of Ginkgo diterpene lactone on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS) and its mechanism.Methods:Forty SD rats were randomly divided into five groups, which were control group, CUMS group, CUMS+ low-dose Ginkgo diterpene lactone group (1.5 mg·kg -1·d -1), CUMS+ medium-dose Ginkgo diterpene lactone group (3 mg·kg -1·d -1) and CUMS+ high-dose Ginkgo diterpene lactone group (6 mg·kg -1·d -1). CUMS rat model was established by continuous stress for six weeks, and the rats were given corresponding treatment in the last three weeks. Sucrose preference test was performed during the stress and drug administration, and behavior tests were performed after the stress and drug administration. After behavior tests, hippocampus, hypothalamus and serum samples were collected to detect inflammatory factors and neurotransmitter. Results:Chronic stress caused depression-like behaviors in rats, while continuous treatment with Ginkgo diterpene lactone could effectively improve sucrose preference, forced swimming immobility time and open field test scores in CUMS rats. It was found that Ginkgo diterpene lactone could significantly improve the decreased secretion of IL-1β and IFN-γ in plasma, and significantly increase the secretion of IL-10 and IL-4 caused by CUMS. In addition, CUMS caused hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis in rats, which manifested as increased secretion of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (COR). The negative feedback of HPA hypermodulated the release of neurotransmitters in the hippocampus, causing the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) in the brain of CUMS rats to decrease. However, Ginkgo diterpene lactone could significantly inhibit HPA axis hyperfunction and increase neurotransmitter levels in the brain.Conclusions:Ginkgo diterpene lactone can effectively improve the depression-like behaviors of CUMS rats through regulating the immune environment, inhibiting the HPA axis hyperfunction and increasing neurotransmitter release.

Modified Banxia Baizhu Tianmatang Combined with Acupuncture for Migraine (Wind-phlegm Upset Syndrome) Observe / 中国实验方剂学杂志

Objective:To observe theclinical efficacy of modified Banxia Baizhu Tianmatang combined with acupuncture on migraine with wind phlegm disturbance syndrome， and the regulatory effect on neurovasoactive peptide and vascular endothelial activator. Method:Two hundred and fifty patients were randomly divided into control group （75 cases） and observation group （75 cases）. Patients in Two group got acupuncture for 6 times， 1 time/day， after a day of rest， they got placebogranules of Banxia Baizhu Tianmatang， 10 g/time， 2 times/day. Patients in observation group got Banxia Baizhu Tianmatang， 1 dose/day， and also the same acupuncture with the therapyof control group. And the treatment lasted for 4 weeks. At the half， 1^st， 2^nd， 6^th， 12^th， 24^th， and 48^th hour after treatment， VAS were scored， rate of pain relief within 6， 12， and 24 hours， disappearance rate and recurrence rate of pain within 72 hours， migraine attack times， headache duration and headache degree before 4 weeks of treatment， during the treatment and after the treatment were recorded. Before and after treatment， accompanying symptoms， wind phlegm disturbance syndrome， headache impact test version-6 （HIT-6） and the migraine disability assessment questionnaire （MIDAS） were scored. And levels of calcitonin gene-related peptide （CGRP）， nitric oxide （NO）， endothelin-1 （ET-1）， pituitary adenylate cyclase activating peptide （PACAP）， S100B protein， substance P（SP）， von Willebrand factor （vWF） and fibrinogen （FIB） were detected. And safety was evaluated. Result:VAS in two groups decreased at different time points （<italic>P<</italic>0.01）， and VAS in observation group at 6^th， 12^th， 24^thand 48^th hour after treatment were lower than those in control group （<italic>P<</italic>0.01）. The rate of pain relief in observation group at 6^th and 12^th hours after treatment and the disappearance rate of pain at 72^th hour were 67.14%（47/70）， 87.14% （61/70） and 92.86% （65/70）， which were higher than 50.00% （34/68）， 70.59% （48/68） and 79.41% （54/68） in control group. The recurrence rate of pain in observation group was 21.43% （15/70）， which was lower than 39.71% （27/68） in control group （<italic>P<</italic>0.05）. During the treatment and drug withdrawal， times of migraine attack， headache duration and headache degree were all less than those in control group （<italic>P<</italic>0.01）. Scores of accompanying symptoms， wind phlegm disturbance syndrome， HIT-6 and MIDAS were all lower than those in control group （<italic>P<</italic>0.01）. The clinical effect was better than that in control group （<italic>Z</italic>=2.106， <italic>P<</italic>0.05）. Levels of CGRP， PACAP， S100B protein， SP， ET-1， vWF and FIB were lower than those in control group， while level of NO was higher than control group （<italic>P<</italic>0.01）. Conclusion:Modified Banxia Baizhu Tianmatang combined with acupuncture had a better instant analgesic effect， with a significant effect on continuing analgesia and reducing headache recurrence. It can also alleviate migraine symptoms and accompanying symptoms， andreduce the impact of migraine on daily life and the degree of disability. Its mechanism may be related to the regulation of neurovasoactive peptides and vascular endothelial substances. It is worth for further study.

Effect of Guizhitang on Atherosclerosis by Regulating Immune and Intestinal Flora / 中国实验方剂学杂志

Objective:To observe the effect of Guizhitang （GZT） on peripheral blood monocytes， intestinal flora and AS plaque formation of ApoE^-/- mice induced by Western diet （WD）. Method:In this study， 40 12-week-old homozygous female ApoE^-/- mice were randomly divided into chow diet （CD） group （ApoE^-/-+CD）， WD group （ApoE^-/-+WD）， GZT group （ApoE^-/-+WD+GZT， 7.83 g·kg^-1） and atorvastatin （Atr） group （ApoE^-/-+WD+Atr， 3.33 mg·kg^-1）. And 10 matched C57BL/6 mice were set as wild CD control group （C57BL/6+CD）. Except the CD group， the rest groups were given WD to induce models. Treatment groups were given Guizhitang or atorvastatin orally in addition to WD， while ApoE^-/-+CD and ApoE^-/-+WD model groups were treated with the same volume of double steam water at the same time. After 4 weeks of intervention， 5 mice in each group were selected to collect the eyeball blood samples. The levels of plasma lipids were detected by automatic biochemical analyzer， and the proportion of peripheral blood mononuclear cells and its subtypes， and the expression levels of surface receptors toll like receptor 4 （TLR4） and CD36 were detected by flow cytometry， the intestinal flora of mice was detected by 16S rDNA sequencing. The remaining 5 mice in each group were intervened for 12 weeks， and the aorta was taken to detect the formation of aortic plaque by oil red O staining. Result:After intervention for 4 week， compared with C57BL/6+CD group， the levels of plasma total cholesterol （TC） and low-density lipoprotein （LDL） levels in ApoE^-/-+CD and ApoE^-/-+WD groups were increased （<italic>P</italic><0.01）. ApoE^-/-+WD group showed increase in the proportion of monocytes， their inflammatory subtypes Ly6C^__， and TLR4 expression on monocyte surface in blood （<italic>P</italic><0.05）. ApoE^-/-+WD group induced the imbalance of intestinal flora， with increase of Firmicutes and decrease of Verrucomicrobia in ileum of ApoE^-/-mice. Compared with ApoE^-/-+WD group， there was no significant change in blood lipid level and monocyte proportion in ApoE^-/-+WD+GZT group， but with decrease in the proportion of Ly6C^__， increase in the proportion of anti-inflammatory subtype Ly6C^-， and decrease in the expression of TLR4 and CD36 on monocyte surface （P<0.05）. ApoE^-/-+WD+GZT group showed decrease of Firmicutes and increase of Bacteroidetes and Verrucomicrobia in ileum of ApoE^-/-mice. After 12 weeks of intervention， ApoE^-/-+WD group showed increase in the number and area of aortic plaques in ApoE^-/-mice. ApoE^-/-+WD+GZT group showed decrease of the area of aortic AS plaques. Conclusion:GZT can reduce the immune damage and imbalance of intestinal flora caused by WD， then inhibit the formation of AS plaque.

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC

Recurrent thrombocytopenia with hemolytic anemia in a boy aged 3 years / 中国当代儿科杂志

A boy, aged 3 years and 8 months, had recurrent thrombocytopenia with hemolytic anemia for more than 3 years. The physical examination showed no enlargement of the liver, spleen, and lymph nodes or finger deformities. Laboratory results showed a negative result of the direct antiglobulin test, normal coagulation function, and increases in bilirubin, lactate dehydrogenase and reticulocytes. The results of von Willebrand factor-cleaving protease ADAMTS13 activity assay showed extreme deficiency, and antibody assay showed negative ADAMTS13 inhibitory autoantibodies. Next-generation sequence showed compound heterozygous mutation in the

Clinical effect of multicenter multidisciplinary treatment in children with renal malignant tumors / 中国当代儿科杂志

OBJECTIVE@#To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors.@*METHODS@#A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children.@*RESULTS@#Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%.@*CONCLUSIONS@#Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.

Identification of small molecule sirtuin-1 inhibitors for treating acute myeloid leukemia based on molecular docking, quantitative structure-activity relationships and molecular dynamics / 药学学报

The purpose of this study was to discover novel inhibitors of sirtuin-1 (SIRT1) that could be used in the treatment of acute myeloid leukemia (AML). Eight potential SIRT1 inhibitors were identified from 231 511 natural drug-like molecules by virtual screening-based molecular docking and molecular mechanics-generalized Born surface area (MM-GBSA) calculation of binding free energies. Using existing SIRT1 inhibitor molecules as training and test sets, a series of quantitative structure-activity relationship models were established, and the best quantitative structure-activity relationship (QSAR) model was used to predict the IC50 of these 8 potential inhibitor molecules for SIRT1. Subsequently, molecular dynamics simulations were performed to verify the binding mode and stability of these complexes of potential inhibitors and SIRT1 protein. Finally, the activity of these potential SIRT1 inhibitors was verified by cell proliferation assays of OCI-AML2, OCI-AML3 and MV4-11 cells and SIRT1 enzyme activity assays, and it was found that 5 compounds could inhibit AML cell proliferation. Among them, the most active compound, ZINC000001774455, had an IC50 of 2.29 ± 0.09 μmol·L-1 with OCI-AML2 cells, and at a concentration of 1 μmol·L-1, the inhibitory ratio of this compound on SIRT1 protein activity was 65.33%. ZINC000001774455 can be used as a lead compound for the development of new AML treatments.

A review of isolation methods, structure features and bioactivities of polysaccharides from Dendrobium species / 中国天然药物

Dendrobium, orchid, is a traditional Chinese herb medicine applied extensively as tonic and precious food for thou-sands of years recorded in ancient Chinese medical book "Shen Nong's Materia Medica". It's well known that bioactivities are usually related to the ingredients' basis. Based on the previous research, Dendrobium species contain amino acid, sesquiterpenoids, alkaloids and polysaccharides. As the bioactive substances, carbohydrate shows extensive activities in antitumor, antiglycation, immune-enhancing, antivirus, antioxidant, antitumor and etc. Therefore, as the main biologically active substance, the exact structures and latent activities of polysaccharides from Dendrobium species are widely focused on. In this review, we focus on the advancements of extraction methods and diversity of structures and bioactivities of polysaccharides obtained from Dendrobium species.

HIV/AIDS related frailty syndrome in the elderly and related research progress / 中华流行病学杂志

Frailty syndrome, caused by degenerative changes in the body and the body vulnerability due to a variety of chronic diseases, is associated with adverse outcomes, such as fall, disability and mortality. With the development of antiretroviral therapy, the average life span of HIV/AIDS patients is extended, the number of elderly living with HIV/AIDS has increased, resulting the increase of the incidence of frailty syndrome in this population. The incidence of frailty syndrome in the elderly is associated with HIV infection and adverse reaction of antiretroviral therapy. Early assessment and intervention of frailty syndrome in elderly HIV/AIDS patients can reduce adverse clinical events and improve the quality of life.

HIV/AIDS related frailty syndrome in the elderly and related research progress / 中华流行病学杂志

Frailty syndrome, caused by degenerative changes in the body and the body vulnerability due to a variety of chronic diseases, is associated with adverse outcomes, such as fall, disability and mortality. With the development of antiretroviral therapy, the average life span of HIV/AIDS patients is extended, the number of elderly living with HIV/AIDS has increased, resulting the increase of the incidence of frailty syndrome in this population. The incidence of frailty syndrome in the elderly is associated with HIV infection and adverse reaction of antiretroviral therapy. Early assessment and intervention of frailty syndrome in elderly HIV/AIDS patients can reduce adverse clinical events and improve the quality of life.

Isolation and Biological Characterization of Lung Cancer Stem Cells / 中国医学科学院学报

To explore the methods of screening and biological characteristics of lung cancer stem cells. We selected the ABCG2 and ABCG2 cells from SPC-A-1/adriamycin(ADM)cell line induced by ADM and analyzed the tumorigenicity of ABCG2 and ABCG2 cells by flow cytometry and transplantation in nude mice. The average fluorescence intensity of SPC-A-1 cells was(1.001±0.014)×10 ,which was significantly lower than that of SPC-A-1/ADM cells [(10.257±0.023) ×10 ](=17.320,=0.001);the difference was also statistically significant between the ABCG2/BCRP-FITC treatment group and the SPC-A-1 control group(=5.269,=0.021) and the SPC-A-1 control group(=6.869, =0.012) and between the SPC-A-1/ADM cell control group and the SPC-A-1/ADM cell homotype control group(=8.112,=0.015).The positive rate of SPC-A-1/ADM cells treated with ABCG2/BCRP-FITC was 9.8%,39.84 times higher than that of SPC-A-1 cells;it showed significant difference between the ABCG2/BCRP-FITC group and the SPC-A-1/ADM group(=9.120,=0.005) and the SPC-A-1/ADM group(=8.257,= 0.006).The positive rate of group B cells was 684 times that of group A cells,and the difference was statistically significant(=11.235,=0.001),and the fluorescence intensity of group B cells was strong.The average tumorigenic volume of the mice inoculated with SPC-A-1 cells,group A cells,and group B cells was(6.96±1.82),(6.70±2.55),and(9.17±2.41) mm ,respectively.Among them,group B was the highest,but there was no significant difference among these three groups(=2.362,=0.086).The tumorigenic rate of group B cells was 75.00%,which was significantly higher than that of SPC-A-1 cells and group A cells(=19.780,=0.002). ABCG2 cells from human lung adenocarcinoma SPC-A-1/ADM cell line can be isolated by ABCG2 antibody combined with immunomagnetic beads sorting method,and the tumor formation rate in nude mice can be observed to explore the identification and biological characterization of lung cancer stem cells.