Estudio comparativo del dolor abdominal en las culturas maya Tzeltal, maya Tzotzil y maya Q ́eqchi ́y el uso de Ageratina ligustrina para su tratamiento / Comparative study of abdominal pain in the Mayan cultures Tzeltal, Maya Tzotzil and Maya Q ́eqchi´ and use of Ageratina ligustrina for the treatment

El presente estudio es una comparación del dolor abdominal producido por trastornos gastrointestinales, aliviado por Ageratina ligustrina , entre los grupos maya Tzeltal, Tzotzil y Q ́eqchi ́, el cual integró un enfoque etnomédico, etnobotánico y transcultural, comparando estudios previos con el presente trabajo de campo. Para evaluar la eficacia de Ageratina para aliviar el dolor abdominal, se realizó un inventario de las moléculas reportadas en esta especie, así como de su actividad farmacológica, a través de una revisión bibliográfica. Los resultados mostraron que la epidemiología del dolor producido por TGI, su etnobotánica y el modelo explicativo del dolor abdominal fueron similares entre grupos étnicos. Asimismo, se identificaron 27 moléculas con efectos antiinflamatorios y antinociceptivos, lo que podría explicar por qué esta especie es culturalmente importante para los pobladores maya Tzeltal, Tzotzil y Q ́eqch i ́ para el alivio del dolor abdominal, mientras que, desde el punto de vista biomédico, es una especie con potencial para inhibir el dolor visceral.

The current study is a comparison of the abdominal pain conception produced by gastrointestinal disorders, relieved by Ageratina ligustrina , among inhabitants of the Mayan Tzeltal, Tzotzil, and Q'eqchi' groups ethnomedical, ethnobotanical, and cross -cultural approaches were used to compare previous studies with the present field work. To evaluate the efficacy of A. ligustrina to relieve pain, also through a bibliographic review an inventory of the molecules present in this species was performed, as well as their pharmacological activity. The results showed that the epidemiology of pain produced by GID, its ethnobotany, and the explanatory model of abdominal pain are similar among ethnic groups. Likewise, 27 molecules with anti-inflammatory and anti-nociceptive effects were identified, which could explain why this species is culturally important for the Mayan Tzeltal, Tzotzil, and Q'eqchi' groups for the relief of abdominal pain, while, from a biomedical point of view, it is a species with potential to inhibit visceral pain.

Protective effect of trans-nerolidol on vascular endothelial cell injury induced by lipopolysaccharides / Efectos protectores del trans-nerolidol en lesiones inducidas por lipopolisacáridos en células endoteliales vasculares

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

Angioedema hereditário com deficiência do Inibidor de C1 ­ Armadilhas no diagnóstico, tratamento e compreensão / Hereditary angioedema with C1 inhibitor deficiency: traps in the diagnosis, treatment, and understanding

Angioedema hereditário (AEH) é uma condição rara, subdiagnosticada e de elevada morbimortalidade, devido ao caráter de suas manifestações clínicas. O AEH se diferencia do angioedema histaminérgico por não responder aos anti-histamínicos, corticosteroides ou epinefrina. Por esse motivo, é extremamente importante o diagnóstico dessa situação, a fim de instituir a terapia adequada. Tal afecção deve ser suspeitada a partir da história clínica de episódios imprevisíveis e recorrentes de edema que quando se manifesta sob a forma de edema laríngeo, pode levar a óbito por asfixia, se não for adequadamente tratado. Relatamos o caso de uma paciente de 18 anos que, apesar de previamente diagnosticada com AEH tipo 1, ao procurar um serviço de emergência devido a crise de angioedema, não dispunha de medicação específica nem apresentou plano de ação com as opções possíveis para crises. Este caso reforça a necessidade de maior divulgação da doença, além da conscientização de pacientes e familiares sobre a doença e eventuais crises, assim como o acesso as medicações.

Hereditary angioedema (HAE) is a rare, underdiagnosed condition with high morbidity and mortality due to the characteristics of its clinical presentation. HAE differs from histaminergic angioedema by not responding to antihistamines, corticosteroids, or epinephrine. Therefore, early diagnose is crucial to initiate adequate therapy. HAE is suspected in patients with a clinical history of unpredictable and recurrent episodes of edema. When laryngeal edema occurs, it can lead to death from asphyxiation if not treated properly. We report the case of an 18-year-old patient previously diagnosed with HAE type 1 who sought emergency care during an angioedema attack. However, the patient was not taking any specific medication and did not have an action plan to manage attacks. This case highlights the importance of increasing awareness about the disease, educating patients and their families about the disease and potential attacks, and ensuring access to medications.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1alpha After Treatment: A Cell Regulation Study / Observación del Efecto Clínico de Apatinib Combinado con 131I para el Cáncer de Tiroides Diferenciado Resistente al Yodo Radiactivo y Análisis de Importancia Pronóstica de la Proteína Inflamatoria 1alfa de Macrófagos Después del Tratamiento: Un Estudio de Regulación Celular

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Differences in Muscle Strength Performance According to the Genotypes of the rs4646994 Polymorphism of the ACE Gene in a Sedentary Population / Diferencias en el Rendimiento de la Fuerza Muscular Según los Genotipos del Polimorfismo rs4646994 del Gen ACE en una Población Sedentaria

SUMMARY: The angiotensin converting enzyme gene (ACE) has been associated with endurance and strength performance through its I/D polymorphism. Nevertheless, contradictory results exist between different populations. In this context, the purpose of this research was to determine the influence of the I/D polymorphism of the ACE gene on muscle strength in a sedentary Chilean sample. In this study 102 healthy male students (21.3 ± 2.2 years) completed the assessment. I/D genotyping, cardiovascular, anthropometric, grip strength and knee extensor peak strength were evaluated. The ACE polymorphism frequency was: II, 33.3 %; ID, 46.1 %; DD, 20.6 %. The results showed significant differences and large effect size in maximum (p = 0.004; d = 0.85) and relative handgrip strength (p = 0.004; d = 0.9) between genotype II vs DD. No difference was found for maximal or relative knee extensor strength between groups (p = 0.74), showing a low effect size (d = 0.20). In conclusion, this study provides insights into the role of the ACE gene in muscle strength and highlights the importance of investigating genetic variants in sedentary populations to better understand strength performance.

El gen de la enzima convertidora de angiotensina (ACE) se ha asociado con el rendimiento de resistencia y fuerza a través de su polimorfismo I/D. Sin embargo, existen resultados contradictorios entre diferentes poblaciones. En este contexto, el propósito de esta investigación fue determinar la influencia del polimorfismo I/D del gen ACE sobre la fuerza muscular en una muestra chilena sedentaria. En este estudio, fueron evaluados 102 estudiantes varones sanos (21,3 ± 2,2 años). Se realizaron aplicaron las siguientes evaluaciones: genotipado del polimorfismo I/D, cardiovascular, antropométrica, fuerza de prensión y fuerza máxima de extensión de rodilla. La frecuencia del polimorfismo I/D de ACE fue: II, 33,3 %; DNI, 46,1 %; DD, 20,6 %. Los resultados mostraron diferencias significativas y un gran tamaño del efecto en la fuerza máxima (p = 0,004; d = 0,85) y relativa de prensión manual (p = 0,004; d = 0,9) entre el genotipo II y el DD. No se encontraron diferencias en la fuerza máxima o relativa de los extensores de rodilla entre los grupos (p = 0,74), lo que muestra un tamaño de efecto bajo (d = 0,20). En conclusión, este estudio proporciona información sobre el papel del gen ACE en la fuerza muscular y destaca la importancia de investigar variantes genéticas en poblaciones sedentarias para comprender mejor el rendimiento de la fuerza.

Displasia dentinaria tipo I: Manejo clínico y estudio histológico a propósito de dos casos / Dentin dysplasia type I: clinical management and histological study based on two cases

La displasia dentinaria tipo I (DD-I) corresponde a una alteración dentinaria de heterogeneidad genética y penetrancia completa, en donde se presenta un defecto en el desarrollo de las raíces de los dientes tanto temporales como definitivos. Clínicamente se observan dientes con extrema movilidad junto con antecedentes de exfoliación prematura o espontánea. Los defectos estructurales de los tejidos dentarios, tales como DD-I; implican un desafío ya que son pocos los casos documentados en la literatura que hablan de esta condición. Además implican un tratamiento multidisciplinario y altamente invasivo. El objetivo de este artículo es presentar dos casos de DD-I, enfatizando en su tratamiento y características histopatológicas.

Dentin Dysplasia Type I (DD-I) consists of a pathological dentinary alteration with genetic heterogeneity that results in a defectuous development of dental roots both in primary and secondary dentition. Clinically we can appreciate teeth with extreme pathological mobility and premature or spontaneous exfoliation. Alterations within normal dental structure, such as DD-I imply a challenge for the common practitioner, because of the scarce number of case reports with in the scientific literature regarding this condition and also, because of the need for a highly invasive and multidisciplinary approach they require. The aim of this article is to present two DD-I cases, emphasizing on their treatment and histopathological features.

Effects of Zhu Lian stimulant Type I acupuncture on the expression of brain-derived neurotrophic factor and its receptor TrkB and tissue homogenate cyclic adenosine phosphate in rats with diabetic bladder / 国际中医中药杂志

Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.

Evaluation of 99m Tc-HYNIC-TOC and 131 I-MIBG imaging in diagnosis of pheochromocytoma and paraganglioma / 基础医学与临床

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.

The effect of empowerment management mode on radiation protection in patients after 125I seed implantation / 介入放射学杂志

Objective To discuss the role of empowerment management mode in radiation protection after 125I seed implantation.Methods A total of 66 patients,who received first-time 125I seed implantation at the authors'hospital from October 2020 to October 2022,were randomly divided into control group(n=33)and study group(n=33).The patients of the control group received traditional health education,while the patients of the study group received the empowerment management mode on the basis of the traditional health education.The self-efficacy,health education effect,and protection compliance were compared between the two groups.Results The self-efficacy,health education effect,and protective compliance of patients in the study group were better than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion The implementation of health education by empowerment management mode can improve the effect of health education in patients after 125I seed implantation,and the patients can get better understanding about 125I seed therapy,which can strengthen their sense of self-efficacy and improve postoperative protection compliance,ensuring the safety of the surrounding crowd.The empowerment management mode is worthy of clinical promotion.(J Intervent Radiol,2024,32:82-85)

Research Progress on Interference of Endogenous Factors in Detection of Serum Cardiac Troponin I by Sandwich Antibody Immunoassay and Its Solutions / 现代检验医学杂志

Cardial troponin I(cTnI)is the preferred serological marker for the diagnosis of myocardial injury.cTnI detection is based on antibody sandwich immunoassay.The epitopes of cTnI antigen targeted by detecting and capturing antibodies in different detection reagents are inconsistent,which easily leads to the heterogeneity of cTnI detection results.Endogenous interfering factors such as cTnI autoantibody,heterophile antibody,rheumatoid factor,ect,which can seriously interfere with the results of cTnI detection,and affecting the clinical diagnosis,treatment and prognosis of myocardial injury diseases.In this paper,the research progress of antibody sandwich immunoassay for cTnI and interference of endogenous factors on cTnI detection and solutions are reviewed to provide theoretical basis for differential diagnosis of abnormal cTnI detection results in clinical practice.

The value of SPECT/CT fusion imaging for post-implantation dose verification of 125I particles in patients with bone metastases / 实用放射学杂志

Objective To investigate the value of single photon emission computed tomography/computed tomography(SPECT/CT)fusion imaging for post-implantation dose verification of 125I particles in patients with bone metastases.Methods Forty patients with metastatic bone tumors treated with 125I particles implantation were selected.Within 24 h after 125I particles implantation,patients underwent SPECT/CT fusion imaging and the radioactivity per unit(RPU)was calculated.The treatment planning system(TPS)was then used to obtain the isodose profiles of SPECT/CT fusion imaging results and to calculate the tumor target coverage.The patient's preoperative and postoperative 1 month clinical outcomes,including local tumour remission,pain assessment,quality of life and serum alkaline phosphatase(ALP)levels were compared,and a receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of tumor target coverage on postoperative outcomes.Results The mean number of particles implanted in the target area was 32.52±12.87.Within 24 h of 125I particles implantation,SPECT/CT fusion imaging analysis confirmed a strong positive correlation between the RPU of the radioactive concentration area and the mean dose received by the patient(r=0.786,P<0.05).The predicted area under the curve(AUC)for local tumor remission,pain relief,quality of life improvement and change in ALP levels was 0.789,0.757,0.804 and 0.833,respectively.Conclusion SPECT/CT fusion imaging can be used for postoperative dose verification of 125I particles for metastatic bone tumors and has some predictive value for clinical outcomes.

Evidence-based practice of non-invasive mechanical ventilation related pressure injury prevention guided by the integrated promoting action on research implementation in health services framework / 中国实用护理杂志

Objective:To use the best evidence of noninvasive mechanical ventilation related pressure injury prevention in the clinic guided by integrated promoting action on research implementation in health services framework (i-PARIHS) and evaluate its effect.Methods:This study is an unsynchronized before and after control study. Convenience sampling method was used to select patients receiving non-invasive mechanical ventilation from 7 wards of Beijing Hospital from October 2019 to September 2021. A total of 575 patients receiving non-invasive mechanical ventilation from October 2019 to September 2020 were included in the control group and 602 patients from October 2020 to September 2021 were included in the trial group. The control group adopted the usual care measures, and the trial group applied the prevention program for noninvasive ventilation related facial pressure injuries. The incidence of pressure injury was compared between the two groups. Nurses in 7 wards were investigated before and after the intervention program to compare the changes of knowledge level.Results:In the control group, there were 354 males, 221 females, aged (77.13 ± 14.49) years old; in the trial group there were 392 males, 210 females, aged (75.60 ± 14.27) years old. The incidence of pressure injury in the trial group was lower than the control group, but showed no significant difference ( P>0.05). In the control group, 11 cases suffered pressure injury, including 5 cases in stage 2, 6 cases in stage 3 and above. There were 9 cases in the trial group, including 8 in stage 2 and 1 in stage 3 and above. The severity of pressure injury in the trial group was lower than that in the control group, and the difference was significant ( χ2 = 3.83, 4.11, both P<0.05). The scores of the nurse′pressure injury knowledge increased from (6.77 ± 1.53) points to (7.15 ± 1.47) points, with a significant difference ( t = -2.31, P<0.05). Conclusions:Management of the prevention of noninvasive mechanical ventilation related facial pressure injury through evidence-based practice can reduce its incidence, reduce its severity, and it is beneficial to improve the clinical nurses' prevention knowledge and clinical practice level of facial pressure injury related to non-invasive mechanical ventilation.

Role of nNOS-NOS1AP coupling in remifentanil-induced hyperalgesia in rats / 中华麻醉学杂志

Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

Mechanism of Yes-Associated Protein 1 Ameliorating Aristolochic Acid 1-Induced Liver Injury in Mice Based on Untargeted Metabolomics Techniques / 中药新药与临床药理

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Effect of the protein kinase RNA-like endoplasmic reticulum kinase pathway in endoplasmic reticulum stress on hepatic stellate cell activation and collagen type I expression / 临床肝胆病杂志

ObjectiveTo investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase （PERK）/eukaryotic initiation factor 2α （eIF2α） pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells （HSC）. MethodsPathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis （S1-S4） and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy， and immunohistochemistry was used to measure the protein expression levels of PERK， eIF2α， and C/EBP homologous protein （CHOP）. Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin （0， 125， 250， 500， and 1 000 nmol/L）， and qRT-PCR was used to measure the mRNA expression level of PERK， while Western blot was used to measure the protein expression levels of PERK， inositol requiring protein 1 （IRE1）， activating transcription factor 6 （ATF6）， CHOP， and α-smooth muscle actin （α-SMA）. The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group； qRT-PCR was used to measure the mRNA expression levels of PERK， eIF2α， and α-SMA， Western blot was used to measure the protein expression levels of PERK， phosphorylated eIF2α （p-eIF2α）， and α-SMA， and immunofluorescence assay was used to measure the expression of collagen type I alpha 1 （COL1A1）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with normal liver tissue， the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK， eIF2α， and CHOP （Z=-3.56， t=-5.75， Z=-3.52， all P<0.001）. Compared with the solvent group， the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK， CHOP， IRE1， ATF6， and α-SMA （all P<0.05）. Compared with the control group， the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK， eIF2α， and α-SMA and the protein expression levels of PERK， p-eIF2α， and α-SMA （all P<0.05）， and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group （P<0.05）. ConclusionPERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells， suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.

Molecular tracing of Biomphalaria straminea in China / 中国血吸虫病防治杂志

Objective To investigate the origin of Biomphalaria straminea in China, so as to provide insights into assessment of schistosomiasis mansoni transmission risk and B. straminea control. Methods Guanlan River, Dasha River, Shenzhen Reservoir, upper and lower reaches of Kuiyong River, and Xinzhen River in Shenzhen, China, were selected as sampling sites. Ten Biomphalaria samples were collected from each site, and genomic DNA was extracted from Biomphalaria samples. DNA samples were obtained from 15 B. straminea sampled from 5 sampling sites in Minas Gerais State, Pará State, Federal District, Pernambuco State, and Sao Paulo State in Brazil, South America. Cytochrome c oxidase I (COI) and mitochondrial 16S ribosomal RNA (16S rRNA) genes were sampled using the above DNA templates, and the amplified products were sequenced. The COI and 16S rRNA gene sequences were downloaded from GenBank, and the sampling sites were acquired. All COI and 16S rRNA gene sequences were aligned and evolutionary trees of B. straminea were created based on COI and 16S rRNA gene sequences to identify the genetic similarity and evolutionary relationship between B. straminea samples from China and South America. Results A total of 60 COI gene sequences with a length of 529 bp and 3 haplotypes were obtained from B. straminea sampled from China. There were 165 COI gene sequences of B. straminea retrieved from GenBank, and following alignment with the above 60 gene sequences, a total of 33 haplotypes were obtained. Phylogenetic analysis showed that the three haplotypes of B. straminea from China were clustered into one clade, among which the haplotype China11 and three B. straminea samples from Brazil retrieved from GenBank belonged to the same haplotype. Geographical evolution analysis showed that the B. straminea samples from three sampling sites along eastern coasts of Brazil had the same haplotype with China11, and B. straminea samples from other two sampling sites were closely, genetically related to China11. A total of 60 16S rDNA gene sequences with approximately 322 bp in length were amplified from B. straminea in China, with 2 haplotypes identified. A total of 70 16S rDNA gene sequences of B. straminea were captured from GenBank. Phylogenetic analysis showed that Biomphalaria snails collected from China were clustered into a clade, and the haplotype China64 and the haplotype 229BS from Brazil shared the same haplotype. The 49 16S rDNA gene sequences of B. straminea from 25 sampling sites in southern Brazil, which were captured from GenBank, were included in the present analysis, and the B. straminea from 3 sampling sites shared the same haplotype with China64 in China. Geographical evolution analysis based on COI and 16S rRNA gene sequences showed that B. straminea sampled from eastern coastal areas of Brazil shared the same haplotypes in two gene fragment sequences with Biomphalaria snails collected from China. Conclusions The Biomphalaria snails in China are characterized as B. straminea, which have a low genetic diversity. The Biomphalaria snails in China have a high genetic similarity with B. straminea sampled from eastern coastal areas of Brazil, which may have originated from the eastern coastal areas of Brazil.

Provincial distribution differences and influencing factors of self-assessed health among elderly population in China / 环境与职业医学

Background Regional differences in economic development, natural environment, health care level, and social structure may lead to differences in the provincial distribution of the health status of the elderly population. Objective To explore the provincial distribution characteristics, regional differences, and influencing factors of the self-assessed health of the elderly population, with the aim of providing a policy basis for improving the health of the elderly population and promoting healthy aging according to local conditions. Methods Using 31 provinces (municipalities and autonomous regions) in China as the basicstudy unit and based on the method of Wagstaff, the self-rated health data of the elderly population (aged 60 years and above) in each province from the 2010 and 2020 national censuses and the 2015 1% National Population Sample Survey were converted into ill-health scores as a measure of self-assessed health, and higher scores represented worse health status perception. Global Moran's I was used to evaluate spatial autocorrelation, range [−1, 1], with a value of 1 as a perfect clustered pattern. Local Moran's I was used to evaluate the tendency of local autocorrelation, and high-high aggregation/low-low aggregation indicated that both target province and its neighboring provinces showed higher/lower ill-health scores. Spatial econometric models were selected by Lagrange multiplier test and Hausman test to explore influencing factors of the self-assessed health of the elderly population. Results In 2010, 2015, and 2020, the national ill-health scores of the elderly population were 1.831, 1.873, and 1.547, respectively, and the corresponding Global Moran's I statistics were 0.347, 0.482, and 0.511, respectively (P<0.01), indicating that the ill-health scores of the elderly population showed a significant spatial positive autocorrelation, and the degree of spatial aggregation was increasing gradually. From 2010 to 2020, the high-high aggregation of ill-health scores among the elderly population was concentrated in the inland northwest, while the low-low aggregation was concentrated in the southeast coast, gradually showing a "southeast-central-northwest" stepped incremental pattern of differentiation. The Lagrange multiplier test and Hausman test suggested that the fixed-effects spatial lagged model was a better choice, and the regression model showed a spatial autocorrelation in the ill-health scores of the elderly population, with an autocorrelation coefficient of 0.3969 (P<0.001); the ill-health scores of the elderly population were negatively correlated with the natural logarithms of gross regional product per capita, and the number of beds in health care facilities per 1000 population, with regression coefficients of −0.8297 and −0.0454 (P<0.05) respectively, and positively correlated with the annual average concentration of PM2.5, illiteracy rate, and the number of health technicians per 1000 population, with regression coefficients of 0.0033, 0.0297, and 0.0765 (P<0.05), respectively. Conclusion From 2010 to 2020, the overall self-assessed health level of China's elderly population showed an upward trend and a spatial positive autocorrelation, with better self-assessed health in the southeast coast and poorer ratings in the northwestern inland. Additionally, there was a gradual decline in self-assessed health of the elderly population from the southeast to the central regions and further to the northwest in terms of spatial distribution. Economic development level, environmental pollution, health resource allocation, and education level are important factors influencing the self-assessed health of the elderly population.

Bactericidal Effect of Selenium Nanoparticles Combined with Povidone-iodine on Pathogenic Bacteria in Surgical Site Infection / 中山大学学报(医学科学版)

ObjectiveTo investigate the bactericidal effect of loaded multifunctional povidoneiodine-nanometer selenium （PVP-I@Se） disinfectant on Staphylococcus aureus （SA） and methicillin-resistant Staphylococcus aureus （MRSA）， and to provide an experimental basis for the reduction of surgical site infection （SSI）. MethodsThe control group was the povidone iodine （PVP-I） group with different concentrations of iodine （50， 75， 100， 200 and 400 μg/mL）. The PVP-I@Se group （experimental group） was the PVP-I group further supplemented with 2 μg/mL Selenium nanoparticles （SeNPs）. Then we compared the bactericidal effect of the two groups of disinfectant solutions on SA and MRSA by examining the minimum inhibitory concentration （MIC）， minimum bactericidal concentration （MBC）， the shortest sterilization time at a concentration of 50 μg/mL iodine and the inhibition zone diameters at concentrations of 200 μg/mL and 400 μg/mL iodine. ResultsMIC values of PVP-I against SA and MRSA were both 79.17 μg/mL， and those of PVP-I@Se were 54.17 and 70.83 μg/mL， respectively. MBC values of PVP-I against SA and MRSA were 129.17 and 150.00 μg/mL， respectively， and those of PVP-I@Se were 70.83 and 87.50 μg/mL， respectively. At a concentration of 50 μg/mL iodine， the shortest sterilization time of PVP-I for SA and MRSA was 130 s and 140 s， respectively， and that of PVP-I@Se was 65 s and 75 s， respectively. At a concentration of 200 μg/ml iodine， the inhibition zone diameters of PVP-I for SA and MRSA were 7.67 mm and 8.33 mm， and those of PVP-I@Se were both 9.50 mm. At a concentration of 400 μg/mL iodine， the inhibition zone diameters of PVP-I for SA and MRSA were 9.00 mm and 9.33 mm， and those of PVP-I@Se were 11.67 mm and 12.00 mm， respectively. ConclusionsPVP-I with different concentrations of 50， 75， 100， 200 and 400 μg/mL iodine supplemented with 2 μg/mL SeNPs have better and faster bactericidal effect on SA and MRSA. When combined with SeNPs， PVP-I can enhance the bactericidal activity against SA and MRSA， but with better sensitizing effect on SA than MRSA and higher demand of iodine concentration （400 μg/mL） for sensitizing effect on MRSA. This study provides a theoretical basis for selecting optimal concentration and action time of the disinfectant， thus reducing SSI.

Screening of adjuvant for PD-L1 vaccine based on nitrated T cell epitope / 中国药科大学学报

@#Abstract: To enhance the anti-tumor activity of tumor vaccine targeting PD-L1 based on the nitrated T-epitope (PD-L1-NitraTh), this research compared several adjuvants with different mechanisms to screen out the adjuvant most suitable for PD-L1-NitraTh. The results showed that Poly(I:C), CPG1018, swollen knotted polysaccharide SGP2 and GM-CSF could enhance the immunogenicity of PD-L1-NitraTh when used as adjuvants, with the Poly(I:C) group inducing the highest antibody titer. The results of qPCR for T cell differentiation-related cytokines showed that Poly(I:C) reduced the expression of GATA3 and FoxP3, indicating a strong effect on CD4+ T cell differentiation. Besides, compared with other adjuvants, Poly(I:C) could assist PD-L1-NitraTh to increase the infiltration of T cells as well as CD11b+ cells within tumor, suggesting that Poly(I:C) may be the suitable adjuvant for tumor vaccines based on the nitrated T epitopes.

Generation and characterization of humanized monoclonal antibody against human IFNAR1 / 中国药科大学学报

@#Abstract: Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Monoclonal antibody shows therapeutic potential by blocking the signaling pathway. This study used recombinant human subunit 1 of the type I interferon receptor (IFNAR1) protein to immunize New Zealand white rabbits, and applied B cell cloning technology to screen and obtain rabbit parental antibodies. After humanization modification, QX006N was obtained. In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L, and neutralize the type I interferon signaling pathway and this pathway mediated biological effects. This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.