Diverticulitis aguda del intestino delgado como causa infrecuente de abdomen agudo en el adulto mayor: Reporte de caso / Acute diverticulitis of small bowel as rare cause of acute abdomen inthe elderly: Case report

Introducción. El dolor abdominal es uno de los principales motivos de admisión a urgencias y una de las causas más frecuentes es la enfermedad diverticular, que aumenta su prevalencia en el adulto mayor. Sin embargo, la diverticulitis del intestino delgado es una enfermedad infrecuente y en la mayoría de casos es asintomática. No obstante, la perforación de un divertículo intestinal es una complicación común de esta patología, por lo que debe ser considerado como un diagnóstico diferencial de abdomen agudo en este grupo poblacional. Caso clínico. Paciente masculino de 71 años, quien consultó por dolor abdominal de inicio súbito, con signos de irritación peritoneal al examen físico. Dado su deterioro hemodinámico fue llevado a cirugía y en la laparotomía exploratoria se halló una diverticulitis aguda perforada de yeyuno e íleon distal. Resultados. El paciente cursó con una adecuada evolución postoperatoria, sin reingresos. Conclusión. La diverticulitis aguda yeyuno-ileal es una causa importante, pero no frecuente de perforación intestinal. Hay muy pocos casos reportados en la literatura, lo que la convierte en un reto diagnóstico para el médico de urgencias y el cirujano general. No obstante, debe ser considerado como un diagnóstico diferencial en adultos mayores con abdomen agudo.

Introduction. Abdominal pain is one of the main reasons for admission to the emergency room and one of the most frequent causes is diverticular disease, which increases its prevalence in the elderly. However, diverticulitis of the small bowel is rare and in most cases asymptomatic. However, perforation of an intestinal diverticulum is a common complication of this pathology and should be considered as a differential diagnosis of acute abdomen in this population group. Clinical case. A71-year-old male patient presented with abdominal pain of sudden onset, with signs of peritoneal irritation. Given his hemodynamic deterioration, he was taken to surgery and in the exploratory laparotomy an acute perforated diverticulitis of the jejunum and distal ileum was found. Results. The patient had an adequate postoperative evolution, without readmissions. Conclusion. Acute jejuno-ileal diverticulitis is an important but uncommon cause of intestinal perforation. There are very few cases reported in the literature, which makes it a diagnostic challenge for the emergency physician and general surgeon. However, it should be considered as a differential diagnosis in older adults with acute abdomen.

Association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from the 2010/2011 BRISA birth cohort

Abstract Objective: To study the association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from a birth cohort. Method: This was a secondary cross-sectional analysis of data obtained in a cohort study (Brazilian RibeirãoPreto and São Luís Birth Cohort Studies - BRISA), whose deliveries were performed between 2010 and 2011. Standardized questionnaires were applied to mothers, and placentas and newborns were evaluated shortly after delivery. Placental efficiency was assessed using the ratio between birth weight and placental weight (BW/PW ratio); values below the lower quartile (25th percentile for gestational age) were considered to have low placental efficiency. Newborn phenotypes were small and large for gestational age, stunted and wasted, evaluated using the INTERGROWTH-21 growth standard. To identify the confounding variables theoretical model was constructed using Directed Acyclic Graphs, and unadjusted and adjusted logistic regression were performed. Placental measurements were obtained blindly from pregnancy and delivery data. Results: 723 mother-placenta-child triads were studied. 3.2 % of newborns were small-for-gestational-age (SGA), 6.5 %large-for-gestational-age (LGA), 5.7 %had stunting, and 0.27 % wasting. A significantly higher risk was found between low placental efficiency and SGA (OR 2.82;95 % CI 1.05-7.57), stunting (OR 2.23; 95 % CI 1.07-4.65), and wasting (OR 8.22; 95 % CI 1.96-34.37). No relationship was found between LGA and placental efficiency. Conclusions: Low placental efficiency was associated with increased risk for small-for-gestational-age, stunting, and wasting. Placental morphometry can provide valuable information on intrauterine conditions and neonatal health, helping to identify newborns at higher risk of future comorbidities.

Neumatosis quística intestinal, un reto diagnóstico: reporte de caso / Cystic intestinal pneumatosis, a diagnostic challenge: case report

Introducción. La neumatosis quística intestinal se describe como la presencia de gas dentro de la pared intestinal. Es una entidad poco frecuente, con una incidencia del 0,03 % en la población global. Aparece con predilección en el género masculino después de los 45 años yse localiza principalmente en el intestino delgado (42 %) y el colon. Se puede asociar a varias condiciones que en ocasiones requieren manejo quirúrgico. Caso clínico. Se presenta el caso de un hombre 75 años, con antecedente de hipertensión arterial, quien consultó por un cuadro de 15 días de evolución consistente en distensión abdominal, dolor y estreñimiento. En urgencias se solicitó una radiografía de tórax que mostró neumoperitoneo y varios niveles hidroaéreos, por lo que el cirujano de turno consideró una posible ruptura de víscera hueca. Resultados. Fue llevado a laparotomía exploratoria, donde se identificó neumatosis quística intestinal y estómago muy aumentado de tamaño, compatible con gastroparesia. Como resultado del tratamiento brindado, el paciente tuvo un desenlace satisfactorio logrando alta médica, apoyado con cuidados básicos de enfermería. Conclusiones. Si bien los casos de neumatosis quística intestinal son de presentación inusual, se puede encontrar en pacientes con hallazgos imagenológicos de neumoperitoneo. Por eso, se debe realizar un análisis concienzudo de cada paciente e individualizar el caso para el correcto diagnóstico.

Introduction. Cystic pneumatosis intestinalis is described as the presence of gas within the intestinal wall. It is a rare entity, with an incidence of 0.03% in the global population. It appears with a predilection in the male gender after 45 years of age and is located mainly in the small intestine (42%) and the colon. It can be associated with several conditions that sometimes require surgical management. Clinical case. The case of a 75-year-old man with a history of high blood pressure is presented, who consulted for a 15-day history consisting of abdominal distention, pain and constipation. In the emergency room, a chest x-ray was requested, which showed pneumoperitoneum and several air-fluid levels. The surgeon on call considered a possible rupture of the hollow viscus. Results. The patient was taken to exploratory laparotomy, where intestinal cystic pneumatosis and a greatly enlarged stomach were identified, compatible with gastroparesis. As a result of the treatment provided, the patient had a satisfactory outcome, achieving medical discharge, supported with basic nursing care. Conclusions. Although cases of intestinal cystic pneumatosis have an unusual presentation, it can be found in patients with imaging findings of pneumoperitoneum. Therefore, a thorough analysis of each patient must be carried out and the case individualized for the correct diagnosis.

Novedades en la evaluación y tratamiento de la obstrucción intestinal alta

La obstrucción intestinal mecánica es un problema quirúrgico significativo en términos de prevalencia, morbimortalidad y costos económicos asociados. En los últimos años se han realizado avances en: detectar mecanismos fisiopatológicos del desarrollo de adherencias, optimizar el diagnóstico de pacientes aptos para manejo conservador, valorar la utilidad intraoperatoria de herramientas que definan la necesidad de resección intestinal y hallar terapias preventivas. El objetivo de esta revisión narrativa es sintetizar la evidencia científica actualizada, publicada referente al diagnóstico y tratamiento de una obstrucción intestinal alta mecánica.

Mechanical small bowel obstruction is a significant surgical problem in terms of prevalence, morbimortality, and associated economic costs. In recent years, advances have been made in: detection of physio pathological mechanisms of adhesion genesis, improvement in diagnosis of patients suitable for conservative treatment, assessment the efficacy of intraoperative tools that define the need for intestinal resection, and development of preventive therapies. The objective of this narrative review is to synthesize the updated scientific evidence published, regarding the diagnosis and treatment of mechanical small bowel obstruction.

Propuesta de estrategias terapéuticas combinadas para KRAS en cáncer de pulmón de células no pequeñas a partir de análisis in silico / Proposal of combined therapeutic strategies for KRAS in non-small cell lung cancer based on an in silico analysis

RESUMEN Objetivo: Los pacientes con cáncer de pulmón de células no pequeñas positivas a la mutación del gen linfoma anaplásico quinasa (ALK+) que, además, presentan mutaciones en el gen Kirsten rat sarcoma (KRAS), como KRASG12C, están mostrando resistencia tanto a inhibidores del gen linfoma anaplásico quinasa (ALK) como de KRAS. Por ello, se analizó la interacción de los inhibidores de ALK con KRAS, para sugerir una sinergia entre ambos. Materiales y métodos: En el estudio se realizó un modelado por homología de las estructuras KRASwt, KRASG12C y ALKwt. Posteriormente, se realizaron acoplamientos moleculares para determinar la energía de unión de los inhibidores de ALK y de KRAS, y evaluar la posible interacción entre los inhibidores de ALK con KRAS y la estructura KRASG12C. Finalmente, se analizó la expresión en la vía de proliferación celular de las proteínas rat sarcoma/quinasa regulada por señales extracelulares (vía RAS/MEK) mediante la técnica de Western blot. Resultados: Los valores de energía de unión muestran la posibilidad de interacción de los inhibidores de ALKwt, como crizotinib y alectinib, con las estructuras de KRASwt y KRASG12C. Los acoplamientos entre crizotinib con KRASwt y KRASG12C, respectivamente, muestran valores de energía de interacción (42,77 kcal/mol y 46,20 kcal/mol) muy similares a los obtenidos entre crizotinib y ALK (42,37 kcal/mol). A su vez, alectinib se acopló en el mismo sitio que los fármacos específicos de KRAS y KRASG12C, y presentaron valores de energía de interacción (51,74 kcal/mol y 54,69 kcal/mol, respectivamente) superiores a los obtenidos con ALK (44,94 kcal/mol). Finalmente, la expresión de la vía RAS/MEK nos mostró una disminución significativa de la expresión de RAS en líneas celulares de cáncer de pulmón ALK+ y ALKL1196M tratadas con crizotinib y alectinib. Conclusiones: Las técnicas in silico de este estudio muestran la posibilidad de acoplamiento entre los inhibidores de ALK (crizotinib y alectinib) con la estructura de KRAS. Esto permite sugerir una posible terapia combinada entre inhibidores de KRAS y ALK para los casos de coexistencia de ambas mutaciones, que puede evaluarse en posteriores ensayos con líneas celulares.

ABSTRACT Objective: Patients with non-small cell lung cancer positive for the anaplastic lymphoma kinase (ALK+) gene mutation who also have mutations in the Kirsten rat sarcoma (KRAS) gene, such as KRAS G12C, are showing resistance to both anaplastic lymphoma kinase (ALK) gene and KRAS inhibitors. Therefore, the interaction between ALK inhibitors and KRAS was analyzed to suggest a synergy between them. Materials and methods: The study performed homology modeling of the KRASwt, KRAS G12C and ALKwt structures. Subsequently, molecular dockings were carried out to determine the binding energy of ALK and KRAS inhibitors and to evaluate the possible interaction of ALK inhibitors with KRAS and the KRAS G12C structure. Finally, the expression in the RAS/MEK pathway was analyzed using the Western Blot technique. Results: The binding energy values show the potential interaction of ALKwt inhibitors, such as crizotinib and alectinib, with the KRASwt and KRAS G12C structures. The binding of crizotinib to KRASwt and KRAS G12C, respectively, indicates interaction energy values (42.77 kcal/mol and 46.20 kcal/mol) which are very similar to those obtained between crizotinib and ALK (42.37 kcal/mol). In turn, alectinib bound to the same site as drugs targeting KRAS and KRAS G12C, and showed interaction energy values (51.74 kcal/mol and 54.69 kcal/mol, respectively) higher than those obtained with ALK (44.94 kcal/mol). Finally, a significant decrease in RAS expression within the RAS/MEK pathway was observed in ALK+ and ALK 1196M lung cancer cell lines treated with crizotinib and alectinib. Conclusions: In silico techniques of this study demonstrate the potential binding of ALK inhibitors (crizotinib and alectinib) to the KRAS structure. In addition, this allows suggesting a possible combined therapy between KRAS and ALK inhibitors for cases of coexistence of both mutations that can be assessed in subsequent trials with cell lines.

Retos y avances del cáncer de pulmón de células no pequeñas metastásico EGFR mutado / Challenges and advances in metastatic non-small cell lung cancer with EGFR mutation

RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.

ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.

Hemorragia digestiva por intususcepción de un lipoma ulcerado en yeyuno / Gastrointestinal bleeding due to ulcerated intussuscepted jejunal lipoma

RESUMEN Los lipomas yeyunales son tumores gastrointestinales benignos e infrecuentes, de origen mesenquimático, compuestos por adipocitos que suelen estar confinados a la submucosa. Generalmente son asintomáticos y se descubren de manera incidental al realizar estudios por imágenes o endoscópicos. Sin embargo, aquellos mayores de 2 cm pueden presentar síntomas como resultado de complicaciones, como intususcepción intestinal, obstrucción o rara vez, hemorragias. Presentamos un caso infrecuente de intususcepción de un lipoma yeyunal ulcerado en un adulto, diagnosticado en el contexto de un cuadro de hemorragia digestiva.

ABSTRACT Jejunal lipomas are rare benign mesenchymal tumors made up of adipocytes confined to the submucosa layer. They are usually asymptomatic and are incidentally found during imaging or endoscopic tests. Those measuring > 2 cm may become symptomatic as a result of complications as intestinal intussusception, obstruction and bleeding. We herein report a rare case of intussusception of an ulcerated jejunal lipoma in an adult patient, that was diagnosticated in the setting of an intestinal hemorrhage.

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Neuron parvum fluorescens, un Término con Influencia Anglo-Greco-Latina. Propuesta a Terminologia Neuroanatomica y Terminologia Histologica / Neuron Parvum Fluorescens, a Term with Anglo-Greco-Latin Influence. A Proposal to Terminologia Neuroanatomica and Terminologia Histologica

Las terminologías son utilizadas como instrumento lingüístico que permite la transmisión de conocimiento de manera precisa y sin ambigüedades en el ámbito de las ciencias. Los lineamientos de la Federative International Programme for Anatomical Terminology (FIPAT) refieren que la denominación de nombres estructurales debe ser descriptivos e informativos. Este estudio analiza las raíces lingüísticas que componen el término Neuron parvum valde fluorescens vigente en Terminologia Histologica y el término Neuron parvum fluorescens vigente en Terminologia Neuroanatomica. Las células pequeñas intensamente fluorescentes son neuronas que se encuentran en el sistema nervioso autónomo, distribuidas en los ganglios simpáticos. Estas células presentan sinapsis aferentes con terminales nerviosas simpáticas preganglionares y sinapsis eferentes con las dendritas de las neuronas posganglionares. Su función es regular la transmisión ganglionar, actuando como interneuronas con señalización paracrina y endocrina. Además, se caracterizan por ser células fluorescentes, que expresan catecolaminas; serotonina, noradrenalina y dopamina. Se realizó una búsqueda en Terminologia Histologica y Terminologia Neuroanatomica, con una traducción de los términos al español. Además, la búsqueda se complementó en un diccionario etimológico en inglés para los términos correspondientes. Esta investigación encontró diferencia entre la traducción del latín al español del término fluorescens, quien posee un origen etimológico muy diferente a su significado en español. El término Neuron parvum valde fluorescens en Terminologia Histologica y el término Neuron parvum fluorescens en Terminologia Neuroanatomica, identifican a la misma estructura. Se sugiere reemplazar ambos términos por Cateconeuron ganglionare, entregando así una correcta descripción de este tipo de neurona, considerando su ubicación y función. Además, de esta manera ser un término concordante en latín para su incorporación en Terminologia Neuroanatomica y Terminologia Histologica.

SUMMARY: Terminologies are used as a linguistic tool to convey knowledge in a precise and unambiguous manner in science. The guidelines of the Federative International Programme for Anatomical Terminology (FIPAT) state that the names given to structures should be both descriptive and informative. This study analyses the linguistic roots of the term Neuron parvum valde fluorescens in Terminologia Histologica and the term Neuron parvum fluorescens in Terminologia Neuroanatomica. Small intensely fluorescent cells are neurons found in the autonomic nervous system, distributed in the sympathetic ganglia, they have afferent synapses with preganglionic sympathetic nerve terminals and efferent synapses with the dendrites of postganglionic neurons, whose function is to regulate ganglionic transmission, acting as interneurons with paracrine and endocrine signalling. They are also characterized as fluorescent cells, producing the catecholamines: serotonin, noradrenaline and dopamine. A search was carried out in Terminologia Histologica and Terminologia Neuroanatomica, with a translation of the terms into Spanish. This was complemented by a search in an English etymological dictionary for the corresponding terms. This research found a difference between the Latin to English translation of the term fluorescens, which has a very different etymological origin to its English meaning. The term Neuron parvum valde fluorescens in Terminologia Histologica and the term Neuron parvum fluorescens in Terminologia Neuroanatomica identify the same structure. The proposal is to replace both terms with Cateconeuron ganglionare, thus affording an accurate description of this type of neuron, considering its location and function. Moreover, it would also be a concordant term in Latin for its incorporation into the Terminologia Neuroanatomica and Terminologia Histologica.

Serum CA211 level and NK cell number are associated with prognosis of patients with non-small cell lung cancer / 基础医学与临床

Objective To exploring the correlation between the expression level of serum carbohydrate antigen 211(CA211)and the number of natural killer(NK)cells and prognosis in non-small cell lung cancer(NSCLC)pa-tients.Methods 132 NSCLC patients admitted to the Affiliated Hospital of Hangzhou Normal University from June 2019 to July 2022 were selected as the test group,and 132 patients with benign lung lesions during the same period were selected as the control group.Data were collected from the laboratory to analyze the relationship between serum CA211 expression and NK cell count in NSCLC with clinical prognosis,as well as the related factors affecting the prognosis of NSCLC patients.Results The neutrophil to lymphocyte ratio(NLR)and serum CA211 expression in the test group were higher than those in the control group(P＜0.05),while the count of NK cells was less than that in the control group(P＜0.05);The expression level of serum CA211 in the test group was negatively cor-related with the count of NK cells(r=-0.405,P＜0.001);There were significant differences in lymph node metastasis and TNM staging among patients with different levels of serum CA211 expression and NK cell count(P＜0.05);The one-year survival rate of patients with low expression of CA211 was significantly higher than that of patients with high expression of CA211(P＜0.05),and the one-year survival rate of patients with high count of NK cells was higher than that of patients with low count of NK cells(P＜0.05);Lymph node metasta-sis,TNM staging and CA211 level were all risk factors affecting the prognosis of NSCLC patients(P＜0.05),while counting of NK cells was protective factor for the prognosis of NSCLC patients(P＜0.05).Conclusions The level of serum CA211 and the number of NK cells in NSCLC patients are closely related to pathological characteristics and clinical prognosis.

Efficacy of cinobufacini capsule combined with docetaxel plus cisplatin chemotherapy for the treatment of non-small cell lung cancer / 基础医学与临床

Objective To investigate the impacts of cinobufotalin combined with docetaxel+cisplatin chemotherapy on the disease control and the level of vascular endothelial growth factor(VEGF)in serum of patients with non-small cell lung cancer.Methods Totally 70 patients with non-small cell lung cancer admitted to Zhejiang Veteran Hospital from March 2019 to March 2022 were included.They were randomly divided into combination group(cinobufotalin combined with docetaxel+cisplatin,n= 35)and control group(docetaxel+cisplatin chemotherapy alone,n=35).The disease control rates of two groups,serum VEGF level,carcinoembryonic antigen(CEA),cy-tokeratin 19(CK19)and carbohydrate antigen 125(CA125)were measured using ELISA;life quality of patients was evaluated with the KPS score;The adverse events between two groups were compared.Results The disease control rate in the combination group(33/35,94.29％)was higher than that that of control group(25/35,71.43％,)(P＜0.05).After treatment,the level of VEGF in both groups of patients decreased,and the KPS score increased(P＜0.05)especially in the combination group(P＜0.05).After treatment,the level of serum CEA,CA125,and CK19 of control group and combination group were obviously lower than those before treatment(P＜0.05),while those in the combination group were even lower(P＜0.05).The incidence of adverse events in the combination group(5/35,14.29％)was lower than that in the control group(13/35,37.14％)(P＜0.05).Conclusions Cinobufotalin combined with docetaxel+cisplatin chemotherapy as a potential new chemotherapy significantly reduces the level of VEGF and tumor biomarkers in serum factor,improves the life quality of patients.The combined therapy is proved tobe safe.

Inhibition of prohibitin 2 enhances the sensitivity of non-small cell lung cancer cell line A549 to erlotinib / 基础医学与临床

Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P＜0.05),while the TUNEL-positive A549 cells increased significantly(P＜0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P＜0.05)and the levels of cytochrome c increased in mitochondrial fractions(P＜0.05)and decreased in cytosolic fractions(P＜0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.

Anlotinib inhibits proliferation and promotes apoptosis of human non-small cell lung cancer cell lines through miR-16-5p/PD-1 axis / 基础医学与临床

Objective To investigate the effect of Anlotinib on proliferation and apoptosis in non-small cell lung cancer(NSCLC)cells and its molecular mechanism.Methods Non-small cell lung cancer cell lines A549 and H1299 were incubated with Anlotinib,miR-16-5p agonist and/or PD-1 overexpression vector respectively.CCK-8 assay and EDU assay were applied to detect the proliferation.Flow cytometry was performed to detect the cell apop-tosis.The relative expression of miR-16-5 p in A549 and H1299 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).The relative protein expression of PD-1 in A549 and H1299 was detected by Western blot assay.The interaction between miR-16-5p and PD-1 was determined by dual luciferase reporter assay.Finally,A549 cell xenograft model was established to assess the effect of Anlotinib on tumor growth in vivo.Results Anlotinib significantly increased miR-16-5p expression and decreased PD-1 expression in A549 cells and H1299 cells,inhibited cell proliferation and promoted apoptosis in a dose-dependent manner(P＜0.05).The highly-expressed miR-16-5p inhibited proliferation and promoted cell apoptosis(P＜0.05).Also,miR-16-5p targeted at PD-1 and negatively regulated PD-1 expression.Knockdown of PD-1 inhibited proliferation and pro-moted cell apoptosis(P＜0.05).PD-1 over-expression reversed the Anlotinib-mediated pro-proliferation and anti-apoptosis of miR-16-5p in A549 cells and H1299 cells(P＜0.05).Anlotinib significantly reduced tumor growth in vivo(P＜0.05).Conclusions Anlotinib may inhibit cell proliferation,anti-apoptosis,and reduce tumor growth for NSCLC,which is involved in miR-16-5p/PD-1 axis.

Association of Polymorphisms in the 3'UTR of Genes in the ERK1/2 Signaling Pathway with Non-small Cell Lung Cancer / 昆明医科大学学报

Objective To investigate the association between four single nucleotide polymorphisms(SNP)(rs9340 in MAPK1,rs14804 in NRAS,rs712 and rs7973450 in KRAS)in the 3'UTR of ERK1/2 signaling pathway-related genes and non-small cell lung cancer(NSCLC).Methods A total of 478 NSCLC patients and 480 healthy controls were enrolled in this study.Four SNPs were genotyped by using TaqMan assays.The association between the four SNPs and NSCLC was analyzed.Results The distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the non-small cell squamous cell carcinoma(SCC)group(P = 0.009),suggesting that the G allele of rs9340 may be a protective factor for non-small cell lung squamous cell carcinoma(OR = 0.67,95%CI:0.50～0.91).In addition,in the<50 years age group,the distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the NSCLC group(P = 5.07×10-4),indicating that the G allele of rs9340 may be a protective factor for NSCLC(OR = 0.46,95%CI:0.29～0.72).Conclusion The SNP rs9340 in MAPK1 may be associated with the risk of NSCLC.

Impact of circadian rhythm of blood pressure and blood pressure variability on cerebral small vessel disease / 临床神经病学杂志

Nowadays,with the improvement of people's living standards and the acceleration of the aging process of population,cerebral small vessel disease has seriously endangered the life health and quality of life of the elderly.Hypertension has been paid more and more attention as an important risk factor of cerebral small vessel disease.However,in the management of hypertension,people generally concentrate on the influence of mean arterial pressure,ignoring the role of variability and circadian rhythm of blood pressure nowadays.By expounding the pathogenesis of cerebral small vessel disease and the recent studies on blood pressure variability and circadian rhythm of blood pressure,this review discusses a series of scientific problems such as the effects of blood pressure variability and circadian rhythm of blood pressure on the occurrence and development of cerebral small vessel disease.

To investigate the effect of small incision in situ release on surgical indications,nerve conduction velocity and upper limb function in patients with carpal tunnel syndrome / 临床外科杂志

Objective To explore the effects of small incision in situ release on surgical indications,nerve conduction velocity and upper limb function in patients with carpal tunnel syndrome(CTS).Methods A total of 100 CTS patients admitted to our hospital from January 2018 to January 2022 were selected,they were randomly divided into the control group(50 cases,treated with traditional carpal tunnel release)and the observation group(50 cases,treated with small incision in situ release),the clinical data of CTS patients were collected and surgical indications,nerve conduction velocity,upper limb function and the incidence of complications were compared between the two groups.Results The total effective rate was 98.00％in the observation group and 84.00％in the control group(P＜0.05).In the observation group,the length of incision was(1.65±0.29)cm,the time of opening and closing incision was(4.85±1.02)min,the hospitalization time was(3.24±0.62)d,the intraoperative blood loss was(17.88±3.53)mL,and the VAS score was(3.03±0.56)points one day after operation.The control group were(4.02±0.81)cm,(10.06±2.28)min,(7.11±1.34)d,(24.37±5.27)ml,(4.04± 0.89)points,the differences were statistically significant(P＜0.05).After treatment,The thumle-wrist sensory conduction velocity of CTS patients in the study group was(46.05±8.39)m/s,the middle finger-wrist sensory conduction velocity was(45.05±8.95)m/s,the thenar muscles-wrist motor conduction velocity was(53.94±11.47)m/s,the FIM ADL score was(34.38±7.22)points,and FMA The upper limb score was(34.23±7.25)points,and the control group was(41.86±8.22)m/s,(40.88±8.28)m/s,(49.05±10.01)m/s,(27.81±6.01)points,(41.05±9.19)points.The difference between the two groups was statistically significant(P＜0.05).The total incidence of complications was 4.00％in the observation group and 20.00％in the control group(P＜0.05).Conclusion Small incision in situ release is effective in the treatment of CTS patients,which can improve the surgical indications and nerve conduction velocity,help patients recover upper limb function,and reduce the incidence of postoperative complications.

Diagnostic value of serum ficolin-3 and collagen triple helix repeat containing-1 for non-small cell lung cancer and their relationship with clinicopathological characteristics / 临床外科杂志

Objective To explore the diagnostic value of serum ficolin-3(FCN3)and collagen triple helix repeat containing-1(CTHRC1)in non-small cell lung cancer(NSCLC)and their relationship with clinicopathological characteristics.Methods From July 2021 to August 2022,73 patients with NSCLC who were admitted to the our Hospital were selected as the study group,and 55 healthy people who came to our hospital for physical examination were regarded as the control group.the serum levels of FCN3 and CTHRC1 were measured by enzyme-linked immunosorbent assay(ELISA);Pearson method was applied to analyze the correlation of serum FCN3 and CTHRC1 levels in NSCLC patients;Logistic regression analysis was applied to analyze the influencing factors of NSCLC;the diagnostic value of serum FCN3 and CTHRC1 levels on the occurrence of NSCLC was analyzed by the ROC curve.Results The levels of serum FCN3 and CTHRC1 in the study group were obviously higher than those in the control group(P＜0.05);the levels of serum FCN3 and CTHRC1 were correlated with the degree of cancer cell differentiation,TNM stage and lymph node metastasis in NSCLC patients(P＜0.05);Pearson method analysis showed that there was a positive correlation between serum FCN3 and CTHRC1 levels in NSCLC patients(r=0.258,P=0.028);Logistic regression analysis showed that serum FCN3 and CTHRC1 were the influencing factors of NSCLC(P＜0.05);the area under the ROC curve of serum FCN3 and CTHRC1 levels in diagnosis of NSCLC was 0.869 and 0.810,respectively,the area under the ROC curve of NSCLC was 0.881,which were better than those of serum FCN3 and CTHRC1.Conclusion The levels of serum FCN3 and CTHRC1 in patients with NSCLC increase,which are related to the degree of cancer cell differentiation,TNM stage and lymph node metastasis,they are risk factor for NSCLC,and the combination of the two is more valuable in diagnosis of NSCLC.

Feasibility study on automatic segmentation of pelvic intestinal tube for radiotherapy images based on deep learning / 复旦学报（医学版）

Objective To study the feasibility on automatic contouring of pelvic intestinal tube based on deep learning for radiotherapy images.Methods A total of 100 patients with diagnosis of rectal cancer,received radiotherapy in Zhongshan Hospital,Fudan University from 2019 to 2021,were randomly selected.Sixty cases were randomly enrolled to train the models,and the other 40 cases were applied to test.Based on the original small intestine model in automatic segmentation software AccuContour,60,40 and 20(2 groups)cases in the model cases were used to train the models Rec60,Rec40,Rec20A and Rec20B with manual contouring as ground truth.Other 40 cases for test were applied to evaluate the Dice similarity coefficient(DSC),95%Hausdorff distance(HD95)and average symmetric surface distance(ASSD)between the manual contouring and original model along with model Rec60.The DSC of the 5 groups of auto-segmentations were compared as well.The paired t tests were performed for each pair of the original model and 4 trained models.Results The small bowel contoured by trained models were more similar to the manual contouring.They could distinguish the boundary of the intestinal tube better and distinguish the small bowel from the colon.The average DSC,HD95 and ASSD of Rec60 were 0.16 higher(P＜0.001),12.4 lower(P＜0.001)and 5.14 lower(P＜0.001)than the original model respectively.According to the paired t tests,there were no statistical differences in DSC between the 4 training models and the original model.No statistical difference was observed between Rec60 and Rec40,while they were both significantly different from the two Rec20 models.There was no statistical difference between Rec20B and Rec20B.Conclusion For radiotherapy images,model training can effectively improve the accuracy of intestinal tube delineation.Forty cases were enough for training an optimal model of automatic segmentation for pelvic intestinal tube in AccuContour software.

Comparative Study on the Topological Attributes of Deficiency and Excess Pattern of Cerebral Small Vessel Disease Mild Cognitive Impairment Based on fMRI Graph Theory Network / 世界科学技术-中医药现代化

Objective This study aimed to explore the differences in global and local brain network topological properties between deficient pattern(DP)and excess pattern(EP)of mild vascular cognitive impairment caused by subcortical small vessel disease based on graph theory network.Methods Patients were recruited prospectively and were classified with DP and EP subtype.The global small-world topological attributes and local nodes were calculated for the comparison of DP,EP,and healthy controls(CN)using the GRETNA platform.Results The three groups all had small-world attributes,but only the patients in EP had a significantly lower small world attribute δ in the range of 0.05-0.26 than the control group(P<0.05).The node efficiency and node strength indicators of multiple brain region were able to significantly distinguish the DP group from the EP group.However,there was no positive brain region in the node efficiency of the DP patients(P>0.05),and only a few brain regions showed increased node strength efficiency(P<0.05).Conclusion The results indicate that the syndrome of DP and EP have significantly different neuroimaging phenotypes,providing a basis for further research of biological classification based on Chinese Medicine syndromes.

Analysis of the Relationship between Serum miR-873 and miR-138-5p Expression and Immune Microenvironment and Prognosis in Patients with Non-small Cell Lung Cancer / 现代检验医学杂志

Objective To investigate the relationship between serum micro RNA(miRNAs)-873 and micro RNA-138-5p expression and tumor immune microenvironment(TIME)and prognosis in patients with non-small cell lung cancer(NSCLC).Methods A total of 108 NSCLC patients(NSCLC group)and 65 healthy volunteers(control group)who were admitted to Ba'nan Hospital Affiliated to Chongqing Medical University from February 2019 to February 2021 were selected.Real-time quantitative fluorescence polymeric chain reaction(qRT-PCR)was used to detect the expression of miR-873 and miR-138-5p in serum,and multiple immunofluorescence staining was used to detect tumor immune microenvironment indicators.Regular follow-up was conducted after discharge.Pearson analyzed the correlation between the expression of miR-873 and miR-138-5p in serum and the TIME index,and Kaplan-Meier and COX proportional risk regression analyzed the relationship between miR-873 and miR-138-5p and the prognosis of NSCLC patients.Results Comparison with control group,the expressions of miR-873(1.02±0.23 vs 3.15±0.82)and miR-138-5p(1.21±0.26 vs 3.54±0.92)in serum of NSCLC group were decreased,and the differences were statistically significant(t=-25.426,-24.769,all P＜0.05).The expressions of serum miR-873 and miR-138-5p of patients with low-to-moderate differentiation in TNM stages Ⅲ to Ⅳ were lower than those with highly differentiated patients in TNM stages Ⅰ to Ⅱ(t=9.615,10.253;6.889,3.361,all P＜0.05).The expressions of miR-873 and miR-138-5p in serum were negatively correlated with the values of PD-1,PD-L1,CD4 and CD8 H(r=-0.418～-0.673,all P＜0.05).The OS survival rate of NSCLC patients with low expression of miR-873 and miR-138-5p was lower than that of those with high expression of miR-873 and miR-138-5p(Log-Rankχ2=4.724,5.607,P＜0.05).TNM stage Ⅲ～Ⅳ was a risk factor for poor prognosis in patients with NSCLC(P＜0.05),and miR-873 and miR-138-5p were protective factors(P＜0.05).Conclusion The expressions of miR-873 and miR-138-5p in serum of NSCLC patients are down-regulated,which is related to TIME and low survival rate.