Theoretical Exploration of Cancer-related Fatigue in Malignant Tumors Guided by Luobing Theory / 中国实验方剂学杂志

Patients with cancer-related fatigue are prone to symptoms and signs such as anorexia， weight loss， and abdominal distension， which seriously reduces the quality of life and becomes an independent risk factor affecting the survival rate of patients with malignant tumors. Therefore， it is urgent to find effective treatment strategies and drugs. In the past， the academic viewpoint of improving syndromes—a new strategy for tumor treatment was proposed based on the guidance of the Luobing theory. Based on this， this article proposes the pathogenesis of cancer-related fatigue is characterized by spleen and kidney deficiency， stasis and toxin internal obstruction， as well as the treatment method of strengthening the spleen and tonifying the kidney， resolving blood stasis and detoxification guided by the core theory of the Qiluo doctrine of Chengzhi Tiaoping. The representative drug Yangzheng Xiaoji capsules has been developed， not only has good therapeutic effect on solid tumors， but also shows good advantages in treating cancer-related fatigue， which can help to restore the homeostasis of tumor bearing survival in patients with malignant tumors and provide new drug choices for the clinical treatment of cancer-related fatigue.

Characteristics of HIV-1 CRF01_AE molecular network in Yunnan Province / 中华微生物学和免疫学杂志

Objective:To investigate the molecular network of HIV-1 CRF01_AE in Yunnan Province and the factors influencing it.Methods:Demographic data and plasma samples of HIV/AIDS patients in Yunnan drug resistance monitoring database from 2018 to 2021 were collected. HIV-1 pol gene fragments (protease and reverse transcriptase region) were amplified using RT-PCR and then sequenced. The optimal gene distance was selected and a molecular network was constructed based on the sequences of CRF01_AE genotype. Results:In this study, a total of 967 sequences of CRF01_AE genotype were obtained by sequencing. At the optimal gene distance threshold of 1.75%, a total of 320 sequences were involved in the network with a rate of 33.1%, and 84 clusters were identified. In the regional distribution, one cluster dominated by multiple regions, one cluster dominated by Zhaotong, one cluster dominated by Honghe and five clusters dominated by Wenshan were formed in the network. In the network, 75.8% of heterosexual men were connected with other heterosexual men and 54.1% were connected with heterosexual women. There was potential transmission among 66.7% of men who have sex with men (MSM). HIV/AIDS patients in Chuxiong, Dali, Dehong, Honghe, Lincang, Pu′er, Wenshan, Yuxi and Zhaotong were more likely to be involved in the network that those in Kunming. People who were 50 years old and above were more likely to be involved in the network than those less than 25 years old. Factors influencing HIV/AIDS patients with HIV-1 CRF01_AE infection to become high-risk transmitters in Yunnan were not found and further study on this subject was needed.Conclusions:HIV-1 CRF01_AE strains had spread actively in different regions of Yunnan Province and the transmission network was complex. Dynamic monitoring of CRF01_AE strains should be strengthened and a precise intervention for high-risk transmitters should be performed to reduce new infections.

Analysis of pretreatment drug resistance and polymorphic sites in CRF08_BC strains among HIV-1 patients / 中华微生物学和免疫学杂志

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

Effect of chemogenetic manipulation of PVN corticotropin-releasing factor-expressing neurons on excitability of presympathetic neurons in SHR / 中国药理学通报

Aim To observe the effect of corticotropin-releasing factor ( CRF) -expressing neurons on presympathetic neurons in hypothalamic paraventricular nucleus ( PVN) of normotensive Wistar Kyoto ( WKY) rats or spontaneously hypertensive rats (SHR) , and to elucidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability. Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot. Meanwhile, the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining. Adult WKY rats and SHR were used in this study. By microinjection of Cre-dependent ade-no-associated viruses ( AAV) that specifically recognized the CRF promoter and AAV of chemogenetics into the PVN, CRF-expressing neurons expressed designer receptors exclusively activated by designer drugs (DREADDs). Human M3 muscarinic DREADD coupled to Gq receptor ( hM3 Dq) was specifically expressed in PVN CRF-expressing neurons in WKY rats, while human M4 muscarinic DREADD coupled to Gi receptor ( hM4Di) was specifically expressed in PVN CRF-expressing neurons in SHR. Clozapine-N-oxide (CNO) , as a designer ligand, would couple to excitatory hM3Dq or inhibitory hM4Di to regulate the excitability of PVN CRF-expressing neurons. Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column (IML) of spinal cord. Lastly, whole cell patch clamp was used to determine the effect of CNO (10 jjumol L~ ) on spontaneous excitatory postsynaptic currents ( sEPSCs) and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR. Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats, and the activity and number of CRF-expressing neurons in the PVN of SHR were increased. PVN CRF-expressing neurons were expressed with chemogenetic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR. In SHR expressed with chemogenetic inhibitory hM4Di-mCherry of PVN CRF-expressing neurons, bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency, but no change in their amplitude of labeled PVN presympathetic neurons. In contrast, in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons, CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neurons. Furthermore, bath application of CNO had no significant effect on current-evoked firing of PVN presympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons. Conclusions The activity and number of PVN CRF-expressing neurons are increased in SHR, and CRF-expressing neurons enhance the excitability of presympathetic neurons, which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.

Epidemiological characteristics and molecular evolution analysis of HIV-1 CRF07_BC in Nanjing from 2015 to 2019 / 中华微生物学和免疫学杂志

Objective:To investigate the epidemiology, evolution and transmission characteristics of HIV-1 CRF07_BC in Nanjing between 2015 and 2019 to provide scientific basis for precise prevention and control of HIV-1 transmission.Methods:Pol gene sequences of 319 patients with HIV-1 CRF07_BC infection in Nanjing were amplified and sequenced and a maximum likelihood phylogenetic tree was then constructed. Markov Chain Monte Carlo sampling method was used to generate Maximum Clade Credibility Tree. Bayesian Skyline Plot was used to reconstruct the changing trend of the effective population size. Pairwise gene distance method was used to construct molecular network to investigate the transmission features. Results:Among the 319 patients, 303 (95.0%) were male; 264 (82.8%) had multiple sexual partners; only 14 (4.4%) had been using condoms. Most of the infections were occurred in men who have sex with men (MSM), accounting for 77.4%. The maximum likelihood phylogenetic analysis of HIV-1 CRF07_BC revealed two clusters: Cluster1 and Cluster2. Cluster1 mainly contained the strains isolated from MSM and Cluster2 mainly consisted of the strains isolated from heterosexual patients. The most recent common ancestor was 2002.47(1999.91, 2005.43) year for Cluster1 and 1996.38(1992.55, 1999.76) year for Cluster2. The evolutionary rates (95% highest posterior density, 95%HPD) of Cluster1 and Cluster2 were 1.73×10 -3 (1.36×10 -3-2.16×10 -3) substitutions·site -1·year -1 and 2.09×10 -3 (1.50×10 -3 -2.79×10 -3 ) substitutions·site -1·year -1, respectively. The effective population sizes of Cluster1 and Cluster2 tended to be stable after 2002 and 2003, respectively. In addition, Cluster1 and Cluster2 formed eleven and eight unique branches, respectively, suggesting the possibility of divergent epidemics of this genotype. A total of 35 propagation clusters were formed in the molecular propagation network, including 92 Nanjing sequences with an average degree of 4.3. Males, MSM and people with multiple sexual partners were more likely to be connected to the network. Students and young patients were more likely to be connected to the network. Conclusions:HIV-1 CRF07_BC infection was characterized by low age, multiple sexual partners, unprotected behaviors and transmission among MSM in Nanjing from 2015 to 2019. It was recommended to pay more attention to students and young people, to formulate more effective prevention and control measures for high-risk sexual behaviors, and to carry out continuous molecular monitoring of CRF07_BC strain, so as to provide scientific basis for the prevention and control of HIV CRF07_BC.

Based on Theory of "Deficiency of Qi and Stagnation" to Explore Pathogenesis of Chronic Renal Failure "Micro-inflammatory State" and Progress of Traditional Chinese Medicine Prevention and Treatment / 中国实验方剂学杂志

Chronic renal failure （CRF） is generally characterized by micro-inflammatory state， which can aggravate the CRF process in severe cases， leading to the deterioration of renal function， malnutrition， anemia and other complications. Therefore， it is of great significance to improve the micro-inflammatory state of CRF. "Deficiency of Qi and stagnation" is the basic pathogenesis of the micro-inflammatory state of CRF， which runs through the whole process of the disease and affects the formation and outcome of CRF in different forms. Traditional Chinese medicine （TCM） has unique advantages in improving the micro-inflammatory state and enhancing the immunity of the body due to its advantages of syndrome differentiation and treatment， strengthening the righteousness and eliminating pathogenic factors. Therefore， the author systematically sorted out the relationship between micro-inflammatory state and CRF， understanding of micro-inflammatory state of CRF and its prevention and treatment of TCM by referring to relevant literature， based on the theory of "deficiency of Qi and stagnation"， and proposed that spleen and kidney failure （deficiency of Qi） is the origin of micro-inflammatory state of CRF， and blood stasis and poisonous evil （stagnation） is the target of its onset. Deficiency of Qi and stagnation adhered to each other， acted as cause and effect， and developed in a spiral manner throughout the development of the disease. TCM has the effects of nourishing the spleen and kidney， removing blood stasis and turbidity. By down-regulating C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor alpha （TNF-α） and other micro-inflammatory indicators， it can eliminate the pathological wastes derived from spleen and kidney deficiency， reduce the micro-inflammatory state， restore the balance of Yin and Yang in the body to achieve the purpose of eliminating pathogens and protecting renal function， providing guidance for the clinical treatment of CRF.

Automatic labeling and extraction of terms in natural language processing in acupuncture clinical literature / 中国针灸

The paper analyzes the specificity of term recognition in acupuncture clinical literature and compares the advantages and disadvantages of three named entity recognition (NER) methods adopted in the field of traditional Chinese medicine. It is believed that the bi-directional long short-term memory networks-conditional random fields (Bi LSTM-CRF) may communicate the context information and complete NER by using less feature rules. This model is suitable for term recognition in acupuncture clinical literature. Based on this model, it is proposed that the process of term recognition in acupuncture clinical literature should include 4 aspects, i.e. literature pretreatment, sequence labeling, model training and effect evaluation, which provides an approach to the terminological structurization in acupuncture clinical literature.

Cardiorespiratory fitness as a mediator in the relationship between lung function and blood pressure in adults

It is unclear whether physical activity and cardiorespiratory fitness (CRF) are pathways that link low pulmonary function (LPF) to increased blood pressure (BP). Therefore, we investigated the extent to which CRF and moderate-to-vigorous physical activity (MVPA) mediate the relationship between LPF and high BP in adults. We conducted a cross-sectional study with 1,362 participants that underwent cardiopulmonary exercise testing (CPET), spirometry, and wore an accelerometer to determine physical activity patterns. We performed mediation analyses using structural equations considering peak oxygen uptake (V̇O2) and MVPA as mediators, forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) as independent variables, and systolic and diastolic blood pressure (SBP, DBP) as dependent variables. The probability of alpha error was set at 5%. We found a significant total effect of FVC on SBP and DBP considering V̇O2 as mediator (P<0.01). Indirect effects were also significant, with 42.6% of the total effect of FVC on SBP and 77% on DBP mediated by V̇O2 (P<0.01). We did not observe a direct effect of FVC on SBP and DBP. Considering FEV1 as an independent variable, the total effect on SBP was also significant, as were the indirect effects, mediated by V̇O2 at 14.8% for SBP and 7.6% for DBP (P<0.01). We did not find an indirect effect of FVC or FEV1 considering the MVPA as a mediator. CRF mediates the pathway that links LPF and elevated BP. Therefore, CRF is more sensitive to variations in FVC and FEV1 than MVPA.

High occurrence of felid alphaherpesvirus 1 and feline calicivirus in domestic cats from southern Brazil / Alta ocorrência de alphaherpesvirus felideo e calicivirus felino em gatos domésticos no Sul do Brasil

Felid alphaherpesvirus 1 (FeHV-1) and feline calicivirus (FCV) affect cats worldwide. The aim of this study was to evaluate the frequency of occurrence of FeHV-1 and FCV in cats with clinical signs of respiratory, oral and/or ocular disease. Samples were collected from cats cared for in veterinary ambulatory and clinics and submitted to molecular detection and viral isolation. Of the 49 cats evaluated, 45 (92%) were positive for at least one of the viruses; 82% (40/49) were positive for FeHV-1 and 41% (20/49) for FCV. Of these, 31% (15/49) were coinfection cases. For FeHV-1, 45% (18/40) of the cats tested were positive from the collection of eye swab, and the same percentage (9/20) was obtained for the FCV by the oral swab. FeHV-1 and/or FCV were isolated in 35% (17/49) of the samples. The main clinical sign observed was ocular secretion in 71% (35/49) of cats, characterized as mild serous, purulent or serosanguineous, and in some cases associated with ocular injury and marked chemosis. Our findings demonstrate the high occurrence of FeHV-1 and FCV in domestic cats in southern Brazil and indicate that measures should be implemented to improve the diagnostic, prevention and management against of these important diseases.(AU)

Alphaherpesvírus felídeo 1 (FeHV-1) e calicivírus felino (FCV) afetam gatos mundialmente. O objetivo deste estudo foi identificar a frequência de ocorrência de FeHV-1 e FCV em gatos com sinais clínicos de doença respiratória, oral e/ou ocular. Amostras foram coletadas de gatos atendidos em ambulatório e clínicas veterinárias e submetidas à detecção molecular e isolamento viral. Dos 49 gatos avaliados, 45 (92%) foram positivos para ao menos um dos vírus; 82% (40/49) foram positivos para o FeHV-1 e 41% (20/49) para o FCV. Destes, 31% (15/49) foram casos de coinfecção. Para o FeHV-1, 45% (18/40) dos gatos foram positivos na coleta do swab ocular, e o mesmo percentual (9/20) foi obtido para o FCV a partir do swab oral. FeHV-1 e/ou FCV foram isolados em 35% (17/49) das amostras. O principal sinal clínico observado foi secreção ocular em 71% (35/49) dos gatos, caracterizada como serosa, purulenta ou serossanguinolenta e, em alguns casos, associada à lesão e quemose. Nossos resultados demonstram a alta ocorrência de FeHV-1 e FCV em gatos domésticos na região Sul do Brasil e indicam que devem ser implementadas medidas para melhorar o diagnóstico, a prevenção e o manejo contra essas importantes doenças.(AU)

Corticotropin-releasing factor receptor signaling and modulation: implications for stress response and resilience

Abstract Introduction In addition to their role in regulation of the hypothalamic-pituitary-adrenal-axis, corticotropin-releasing factor (CRF) and its related peptides, the urocortins, are important mediators of physiological and pathophysiological processes of the central nervous, cardiovascular, gastrointestinal, immune, endocrine, reproductive, and skin systems. Altered regulation of CRF-mediated adaptive responses to various stressful stimuli disrupts healthy function and might confer vulnerability to several disorders, including depression and anxiety. Methodology This narrative review was conducted through search and analysis of studies retrieved from online databases using a snowball method. Results This review covers aspects beginning with the discovery of CRF, CRF binding protein and their actions via interaction with CRF receptors type 1 and type 2. These are surface plasma membrane receptors, activation of which is associated with conformational changes and interaction with a variety of G-proteins and signaling pathways. We also reviewed the pharmacology and mechanisms of the receptor signaling modulatory activity of these receptors. Conclusion This review compiles and presents knowledge regarding the CRFergic system, including CRF related peptides, CRF binding protein, and CRF receptors, as well as some evidence that is potentially indicative of the biological roles of these entities in several physiological and pathophysiological processes.

Postoperative Healing in Renal Failure Patients after Teeth Extraction

Aim: To compare the postoperative course between the CRF patients and the control group in terms ofpostoperative pain, bleeding, and healing.Materials and Methods: Prospective cohort study. Study group: CRF patients referred for dental extraction whofit the inclusion criteria. Control group: healthy patients referred for teeth extraction. Perioperative managementwas recorded, and postoperative pain, bleeding, and healing were assessed on postoperative days 2, 4, and 7 asoutcomes.Results: forty patients were included in the study. Demographic variables were comparable between control andstudy patients; pain, bleeding, and healing were not statistically different between the two groups. Only thenumber of dialysis sessions per week was linked to improved healing in the study group.Conclusion: When prophylactic antibiotic and local hemostatic measures are used in CRF patients undergoingextraction, postoperative healing is comparable with healthy controls. Within the CRF group number ofhemodialysis sessions per week is linked to improved healing outcomes.

Effect of acupuncture on patients with cancer-related fatigue and serum levels of CRP, IL-6, TNF-α and sTNF-R1 / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism.@*METHODS@#A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups.@*RESULTS@#①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (<0.05), while there was no significant difference in the control group (<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (<0.05), score of social support dimension was increased after the treatment (<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all <0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (<0.05), while the serum levels of CPR and IL-6 were increased in the control group (<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (<0.05).@*CONCLUSION@#①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.

Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014 / 中华流行病学杂志

Objective To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China,and to provide guidance for the implementation of precise intervention.Methods A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014.Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters.Transmission network was constructed by Cytoscape 3.6.0,which was further used for exploring of the major risk factors.Results Of the 2 094 sequences,12.18％ (255/2 094) were in clusters.A total of 82 transmission clusters were identified.The numbers of clusters and contained sequences in intra-provincial transmission (61,173) were significantly more than those in inter-provincial transmission (21,82).The ratio of transmission clustering in MSM increased over time from 2.41％ (2/83) during 1996-2008 to 23.61％ (72/305) during 2013-2014,showing a significant upward trend (x2 =27.800,df=1,P =0.000).The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters,which increased from 0.67％ (2/297) during 1996-2008 to 6.36％(30/472) during 2013-2014,showing a significant upward trend (x2=20.276,df=1,P=0.000).The transmission rate in homosexuals of the inter-transmission clusters (86.59％,71/82) was higher than that of intra-provincial transmission clusters (56.65％,98/173),and the difference was statistically significant (x2=22.792,P=0.000).The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33％,7/21) was higher than that of intra-provincial clusters (13.11％,8/61),and the difference was statistically significant (x2=4.273,P=0.039).Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22％,42/82) was significantly higher than that with intra-provincial transmission clusters (26.59％,46/173),and the difference was statistically significant (x2=14.932,P=0.000).Inter-provincial clusters were mainly detected in and and MSM.Conclusions Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China.Inter-provincial transmission clusters increased rapidly,MSM played an important role in the wide spread of the strain.More researches in transmission networks are needed to guide the precision intervention.

Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014 / 中华流行病学杂志

Objective To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China,and to provide guidance for the implementation of precise intervention.Methods A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014.Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters.Transmission network was constructed by Cytoscape 3.6.0,which was further used for exploring of the major risk factors.Results Of the 2 094 sequences,12.18％ (255/2 094) were in clusters.A total of 82 transmission clusters were identified.The numbers of clusters and contained sequences in intra-provincial transmission (61,173) were significantly more than those in inter-provincial transmission (21,82).The ratio of transmission clustering in MSM increased over time from 2.41％ (2/83) during 1996-2008 to 23.61％ (72/305) during 2013-2014,showing a significant upward trend (x2 =27.800,df=1,P =0.000).The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters,which increased from 0.67％ (2/297) during 1996-2008 to 6.36％(30/472) during 2013-2014,showing a significant upward trend (x2=20.276,df=1,P=0.000).The transmission rate in homosexuals of the inter-transmission clusters (86.59％,71/82) was higher than that of intra-provincial transmission clusters (56.65％,98/173),and the difference was statistically significant (x2=22.792,P=0.000).The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33％,7/21) was higher than that of intra-provincial clusters (13.11％,8/61),and the difference was statistically significant (x2=4.273,P=0.039).Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22％,42/82) was significantly higher than that with intra-provincial transmission clusters (26.59％,46/173),and the difference was statistically significant (x2=14.932,P=0.000).Inter-provincial clusters were mainly detected in and and MSM.Conclusions Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China.Inter-provincial transmission clusters increased rapidly,MSM played an important role in the wide spread of the strain.More researches in transmission networks are needed to guide the precision intervention.

Cistatina C: marcador de laboratorio precoz de enfermedad renal en pacientes con depranocitosis / Cystatin C: early laboratory marker of renal disease In sickle cell disease

La enfermedad renal en el paciente con drepanocitosis es una consecuencia de su complejo proceso fisiopatológico, por lo que es importante disponer de un grupo de parámetros de laboratorio que, junto a la evaluación clínica, permita determinar de forma precoz la presencia de esta complicación. La cistatina C ha demostrado ser uno de los parámetros que con mayor exactitud aporta evidencia temprana de daño renal en este grupo de pacientes y al mismo tiempo constituye un posible indicador de pronóstico de gran importancia(AU)

Renal disease in patients with sickle cell disease is a consequence of its complex pathophysiological process, so it is important to have a set of laboratory parameters that, together with the clinical evaluation, allow the early detection of this complication. Cystatin C has been shown to be one of the parameters that provides, with greater accuracy, early evidence of kidney damage in this group of patients and at the same time constitutes a possible indicator of prognosis of great importance(AU)

Medical Name Entity Recognition and Application in Chinese Admission Record of Stroke Patients Based on CRF and RUTA rule / 中山大学学报(医学科学版)

[Objective] To research the construction and optimization of natural language processing model for unstructured medical records,and using the model to extract structured data from medical records of stroke patients in Jiangxi Medical Big Data Platform.[Methods] According to the actual needs of clinical research,a stroke specialist entity annotation system and named entity annotation corpus were constructed based on 500 hospital admission records of stroke patients,which randomly selected between 2011 to 2016 from the Jiangxi provincial medical big data platform.The corpus is used to construct a named entity extraction model based on CRF and RUTA rules,and the recognition accuracy is improved by adjusting RUTA rules and parameters.[Results] Accuracy rate of extraction model was 0.960,recall rate was 0.916 and F-score was 0.939.The extraction model was used to extract 264 580 entities and 1 161 077 entity relation from 10 295 stroke patients' admission records of the medical big data platform.[Conclusions] The constructed natural language extraction model has a high recognition accuracy,which can accurately obtain valuable scientific research data of patients' past history,life history and clinical manifestations from a large number of unstructured medical records and effectively improve the clinical research efficiency and scientific research level of cerebrovascular diseases.

Characterization and primary resistance mutations in gag-pol gene of human immunodeficiency virus-1 CRF07_BC strain in Guangdong Province / 中华传染病杂志

Objective To investigate the genetic variations of gag-pol gene in human immunodeficiency virus-1(HIV-1) CRF07_BC strain in Guangdong Province.Methods From February to September in 2015,plasma samples of 78 cases with HIV 1 CRF07_BC infection in Guangdong were collected before antiretroviral treatment.Viral RNA was extracted from plasma.Gene (gag and pol) sequences were amplified by reverse transcriptase and nested-PCR using specific primers.Phylogenetic tree,genic dispersion rate,nucleotide polymorphism,selection pressure and variation characteristics were analyzed.Results The main transmission route of the enrolled patients was homosexual transmission (80.77％,63/78).The gag pol gene phylogenetic tree was divided into two sub-clusters.The strains from different transmission routes were not in cluster.The average genetic dispersion rate and average entropy of gag gene were both higher than those of pol gene.The average genetic dispersion and average entropy of p17 and p6 regions of gag gene were both higher than those of p24.The average genetic dispersion and average entropy of pol gene were higher than those of rt region.The average ds/dn values of gag and pol genes were greater than one.Compared with the common HIV-related antigenic epitopes (A2,A11,B39,B60,Cw1,Cw3,Cw8),the cytotoxic lymphocyte (CTL) epitope mutations in the P17 region were more in the consensus of GAG region than those in the P24 region.The epitope conserved rates were 26.92％,0,1.28％,0,96.15％,82.05％,84.62％ and 98.72％,respectively.The drug resistance rate of pol gene was 2.56％ (2/78).Conclusions The gag and pol genes of CRF07_BC strain in Guangdong are all mutated.Diversity of gag gene is greater than that of pol gene,and gag gene variation is mainly in p17 and p6 regions.gag and pol genes are both affected by negative selection pressure.P17 protein CTL epitope variability is greater than P24 protein epitope.The prevalence of drug resistance mutation is lower than the threshold.It's important to monitor the spread of drug-resistant strains.

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas / Instigação social e confrontos agressivos repetidos em camundongos Swiss machos: análise de corticosterona plasmática e dos níveis de CRF e BDNF em áreas cerebrais límbicas

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Resumo Introdução: Comportamentos agonísticos ajudam a garantir a sobrevivência, oferecem vantagem na competição e comunicam status social. O paradigma residente-intruso, modelo animal baseado em confrontos intraespecíficos entre machos, pode ser uma ferramenta etológica relevante para investigar a neurobiologia do comportamento agressivo. Objetivos: Analisar os mecanismos comportamentais e neurobiológicos do comportamento agressivo em camundongos Swiss machos expostos a confrontos repetidos no paradigma residente-intruso. Métodos: A análise comportamental foi realizada em associação com medidas de corticosterona plasmática em camundongos expostos repetidamente a um rival em potencial próximo, porém inacessível (instigação social), ou a 10 sessões de instigação social seguidas de encontros agressivos diretos. Além disso, o fator de liberação de corticotrofina (CRF) e o fator neurotrófico derivado do cérebro (BNDF) foram medidos no encéfalo desses animais. Camundongos controles não foram expostos à instigação social ou confrontos agressivos. Resultados: Os camundongos expostos a confrontos agressivos exibiram um padrão semelhante de comportamentos agressivos e não agressivos típicos da espécie na primeira e na última sessão. Em contraste com instigação social apenas, confrontos agressivos repetidos promoveram aumento na corticosterona plasmática. Após 10 sessões de confrontos agressivos, os camundongos apresentaram uma tendência não significativa de redução dos níveis de CRF no hipocampo, que se correlacionaram inversamente com os níveis plasmáticos de corticosterona. Por outro lado, sessões repetidas de instigação social ou confronto agressivo não alteraram as concentrações de BDNF no córtex pré-frontal e hipocampo. Conclusão: A exposição a episódios repetidos de encontros agressivos não promoveu habituação ao longo do tempo. Adicionalmente, o CRF parece estar envolvido nas respostas fisiológicas aos estressores sociais.

CRF and CRF Receptors Expression in DSS Colitis Model in Mice / 医学研究杂志

Objective To detect the expression of CRF and CRF receptors in colonic mucosa of DSS induced colitis in mice model and to study the effect of CRF and CRF receptors on the development.Methods Six to eight weeks healthy female BALB/c mice were divided into control group and DSS group.Setting up DSS colitis model and colitis was evaluated by the disease activity index(DAI) and histological score.The immunofluorescence technique was used to assay the CRF1 and CRF2 receptors expression in colonic mucosa.The expression of CRF and CRF receptors protein were analyzed by western blotting.Results DSS colitis was set up successfully with significant inflammation in colonic mucosa by the disease activity index (DAI) and histological score.Immunofluorescenee staining evidenced that expression of CRF1 receptor in DSS colitis group has no significant deviation compared to control group(P ＞ 0.05),while the expression of CRF2 receptor was elevated in DSS colitis group compared to control group (P ＜ 0.05).CRF2 receptor was localized in epithelial cells and mononuclear cells in the lamina propria.The levels of CRF and CRF2 receptor protein by western blotting were higher in in DSS colitis group compared to control group (P ＜ 0.05).The level of CRF1 receptor protein in DSS colitis group had no significant deviation compared to control group(P ＞ 0.05).Conclusion The higher expression of CRF and CRF2 in colonic mucosa of DSS colitis may participate in the development of colitis.

Effects of baldrinal of Valeriana jatamansi on expression of CRF, TPH1 mRNA and 5-HT in rats with irritable bowel syndrome / 中国中药杂志

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.