Evaluación de la expresión de PD-L1 e infiltración linfocitaria intratumoral en carcinoma de mama invasivo triple negativo / Evaluation of PD-L1 expression and intratumoral lym phocytic infiltration in triple-negative invasive breast car cinoma

Resumen Introducción : El endofenotipo de cáncer de mama triple negativo (TNBC) es uno de los menos frecuentes y sin diana terapéutica, por tanto, se plantea estudiar la correlación del punto de control inmunológico PD-L1 con el establecimiento de microambiente tumoral evaluado por la infiltración linfocitaria intratumoral estromal (TILs) y su importancia en la práctica clínica. Métodos : Se realizó un estudio retrospectivo de casos y controles, con 31 casos de carcinoma infiltrante de la mama triple negativo y 57 controles no pareados de endofenotipo Luminal A, Luminal B y HER-2 atendidos en un año. Se evaluaron las variables: tipo y grado his tológico, expresión PD-L1 con el clon 22C3, TILs, invasión linfovascular, tamaño tumoral, compromiso de ganglios linfáticos y metástasis. El análisis estadístico se ejecutó con la prueba de chi cuadrado y prueba de coeficiente de correlación de Spearman. Resultados : Se encontró una correlación negativa estadísticamente significativa entre TILs y PD-L1 (rho - 0.106, p 0.025), indicando que a mayor expresión de PD-L1, es menor la infiltración linfocitaria intratumo ral. En los grupos de TILs B (10-40% TILs) y C (40-90% TILs) donde se presenta marcado infiltrado inflamatorio intratumoral se evidenció mayor número de pacientes negativos para PD-L1 (CPS <10) con 16 y 10 casos res pectivamente. Para los casos TNBC se logró identificar un coeficiente de asociación negativa (rho -0.378) y con significancia estadística (p 0.01). Discusión : Se estableció la asociación de TNBC, TILs y expresión de PDL1, lo cual es importante para la instau ración de terapias diana y el desarrollo de la medicina de precisión.

Abstract Introduction : Triple negative breast cancer endophe notype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the es tablishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice. Methods : A retrospective case-control study was performed, with 31 cases of triple-negative infiltrat ing breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test. Results : a statistically significant negative correlation was found between TILS and PD-L1 (rho - 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01). Discussion : The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the develop ment of precision medicine.

The Effect of L-Carnitine on Cadmium Toxicity in Liver and Kidney Tissue in Prepubertal Female Rats / Efecto de la L-Carnitina sobre la Toxicidad del Cadmio en el Hígado y el Tejido Renal en Ratas Hembras Prepúberes

SUMMARY: Cadmium (Cd) is a toxic element that accumulates in kidney and liver. L-carnitine(LC) is a natural compound that has been shown to exhibit antioxidant activity. Aim of this study was to investigate the effect of L-carnitine against cadmium-induced changes in liver and kidney tissues in prepubertal female rats. In this study 21-day-old female Wistar Albino rats were used. Control, cadmium (2 mg/kg cadmium intraperitoneally), L-carnitine (300 mg/kg orally) and cadmium+L-carnitine groups were formed. Liver and kidney tissue sections were stained with Hematoxylin-Eosin and Masson Trichrome. Histological scoring was performed in liver and kidney. In the liver tissue given Cd, bile duct proliferation, inflammation cells and connective tissue in the portal area were decreased in treatment group. In kidneys, cadmium group treated with L-carnitine, it was observed that the capillary congestion in the kidneys decreased, but tubular dilatation continued in some places. In fibrosis scoring of the liver groups,statistically significant decrease was observed in the Cd+LC group compared to group of cadmium. In the histological scoring results of the kidney groups, statistically significant decrease in congestion and tubular epithelial degeneration was observed in the group treated with L-carnitine compared to group with cadmium. In conclusion medium-dose cadmium has toxic effects in liver and kidney of prepubertal female rats in subacute period,these effects are alleviated with L-carnitine.

El cadmio (Cd) es un elemento tóxico que se acumula en los riñones y el hígado. La L-carnitina (LC) es un compuesto natural que ha demostrado tener actividad antioxidante. El objetivo de este estudio fue investigar el efecto de la L-carnitina contra los cambios inducidos por el cadmio en los tejidos del hígado y el riñón en ratas hembra prepúberes. En este estudio se utilizaron ratas Wistar Albinas hembra de 21 días de edad. Se formaron grupos control, cadmio (2 mg/kg de cadmio por vía intraperitoneal), L- carnitina (300 mg/kg por vía oral) y cadmio + L-carnitina. Se tiñeron secciones de tejido de hígado y riñón con Hematoxilina-Eosina y tricrómico de Masson. La puntuación histológica se realizó en hígado y riñón. En el tejido hepático que recibió Cd, la proliferación de los conductos biliares, las células inflamatorias y el tejido conectivo en el área portal disminuyeron en el grupo con tratamiento. En los riñones, en el grupo de cadmio tratado con L- carnitina, se observó que la congestión capilar disminuyó, pero la dilatación tubular continuó en algunos sitios. En la puntuación de fibrosis de los grupos de hígado, se observó una disminución estadísticamente significativa en el grupo de Cd+LC en comparación con el grupo de cadmio. Los resultados de puntuación histológica de los grupos de riñón, arrojó una disminución estadísticamente significativa en la congestión y el epitelio tubular Se observó degeneración en el grupo tratado con L-carnitina en comparación con el grupo con cadmio. En conclusión, las dosis medias de cadmio tienen efectos tóxicos en el hígado y los riñones de ratas hembras prepúberes en el período subagudo; estos efectos se alivian con L-carnitina.

Los diagnósticos, la clínica psicoanalítica y el posicionamiento ético / Diagnosis, psychoanalytic clinic and ethical positioning / Diagnostics, clinique psychanalytique et positionnement ethique / Diagnósticos, clínica psicanalítica e posicionamento ético

El ser humano está signado por el conflicto, por los deseos contradictorios, por el intercambio nunca simple con los otros. Suponer que el otro debe ser una máquina que siga pautas implica desvitalizarlo, lo que es equivalente al aniquilamiento de lo humano. Las niñas y los niños no tienen que ser encerrados ni con clasificaciones psicopatológicas, ni con medicamentos. Las niñas y los niños tienen que tener un sostén esperanzado por parte del entorno, un suelo a partir del cual puedan desplegar sus alas... Transmitir esperanzas es parte importante de nuestra tarea. Debemos dejar que la vida fluya y aportar para que ese fluir derive en nuevos vuelos AU

The human being is marked by the conflict, the contradictory desires, by the never easy exchange with other people.Supposing that the other person must be a machine which follows guidelines means devitalize him and implies the annihilation of the human being.Girls and boys cannot be bounded, nor with psychopathological classifications either with medicines. Girls and boys must have a hopeful support by their environment, a ground which helps them to open their wings... Giving hope is a very important part of our duty.We must let the life flows and contribute to that flowing leads to new flights AU

L'être humain est marqué par le conflit, par les désirs contradictoires, par l'échange jamais simple avec autrui.Supposer que l'autre doit être une machine qui suit des directives implique de le dévitaliser, ce qui équivaut à l'anéantissement de l'humain.Les filles et les garçons ne doivent pas être enfermés, ni avec des classifications psychopathologiques, ni avec des médicaments.Les filles et les garçons doivent bénéficier du soutien plein d'espoir de leur environnement, d'un terrain à partir duquel ils peuvent déployer leurs ailes...Transmettre l'espoir est une partie importante de notre tâche.Il faut laisser lavie couler et contribuer à ce que ce flux conduise à de nouveaux envols AU

A pessoa humana está marcada pelo conflito, pelos desejos contraditórios, pela troca nunca simples com os outros.Assumir que a outra pessoa deve ser um aparelho que segue directrizes implica desvitalizá-lo, o que equivale à aniquilação do que é humano.As crianças não devem ser trancadas, nem com clasificações psicopatológicas, nem com medicação.As crianças devem ter um apoio esperançoso do seu ambiente, uma base a partir do qual possam abrir suas asas... Transmitir esperanças é uma parte importante da nossa tarefa. Devemos deixar a vida fluir e contribuir para garantir que esse fluxo conduzca a novos voos AU

¿Cuál es la importancia de diferenciar entre síntoma y trastorno al momento de llevar a cabo un tratamiento? Estrategias de trabajo que se abren frente a estas presentaciones / What is the importance of differentiating between symptom and disorder when carrying out treatment?work strategies that open in face of these presentations / Quelle est l'importance de différencier entre symptôme et trouble lors de la réalisation d'un traitement? stratégies de travail qui s'ouvrent face à ces présentations / Qual é a importância de diferenciar entre sintoma e transtorno ao realizar o tratamento? Estratégias de trabalho que se abrem diante destas apresentações

En este escrito los autores puntualizan la diferencia entre los conceptos de síntoma y trastorno en la infancia. A los fines diagnósticos establecer esta diferenciación permite pensar estrategias de intervención adecuadas a las características metapsicológicas de estos modos de presentación de sufrimiento en la infancia AU

In this writing the authors point out the difference between the concepts of symptom and disorder in childhood.For diagnostic purposes, establishing this differentiation allows us to think about intervention strategies appropriate to the metapsychological characteristics of these modes of presentation of suffering in childhood AU

Dans cet écrit, les auteurs soulignent la différence entre les concepts de symptôme et de trouble dans l'enfance.À des fins diagnostiques, établir cette différenciation permet de réfléchir à des stratégies d'intervention adaptées aux caractéristiques métapsychologiques de ces modes de présentation de la souffrance dans l'enfance AU

Neste escrito os autores apontam a diferença entre os conceitos de sintoma e transtorno na infância.Para fins diagnósticos, estabelecer essa diferenciação permite pensar estratégias de intervenção adequadas às características metapsicológicas desses modos de apresentação do sofrimento na infancia AU

Sobre o lugar e a função do fantasma entre os anos de 1953 a 1964 do ensino de Lacan / Sur la place et la fonction du fantôme entre les années 1953 et 1964 dans l'enseignement de Lacan / About the place and function of the phantasm between the years of 1953 to 1964 of Lacan's teaching

O conceito de fantasma possui uma importância crucial para o enquadramento da experiência em psicanálise. Este artigo pretende situar o lugar e a função do fantasma neurótico na experiência analítica partindo da função da fala, tal como proposto por Lacan. Para tanto, selecionamos alguns textos e seminários de Lacan situados entre os anos de 1953 a 1964. Nossa hipótese de trabalho consiste na suposição de que, ao enquadrar uma realidade constituída inconscientemente enquanto resposta ao desejo do Outro, o fantasma serve para perpetuar ao neurótico um senso de ser idêntico a si mesmo à medida em que tende a promover um apagamento de contradições provenientes da posição que, como sujeito, ocupa em relação a este desejo. Ao ser concebida como irrupção de um objeto com valor de não-eu no enquadre fantasmático, a angústia produz um efeito reverso, constituindo, por conseguinte, tanto uma contraprova quanto um apoio na demonstração dessa hipótese.

Le concept de fantôme revêt une importance cruciale pour encadrer l'expérience en psychanalyse. Cet article veut situer la place et la fonction du fantasme névrotique dans l'expérience analytique à partir de la fonction de la parole, comme le propose Lacan. Pour cela, nous avons sélectionné quelques textes et séminaires de Lacan situés entre les années 1953 et 1964. Notre hypothèse de travail est qu'en encadrant une réalité inconsciemment constituée en réponse au désir de l'Autre, le fantôme sert à perpétuer chez le névrosé un sentiment d'être identique à lui-même dans la mesure où il tend à favoriser un effacement des contradictions nées de la position qu'il occupe, en tant que sujet, par rapport à ce désir. Conçue comme l'irruption d'un objet ayant valeur de non-moi dans le cadre fantasmatique, l'angoisse produit un effet inverse, constituant donc à la fois une contre-preuve et un support à la démonstration de cette hypothèse.

The concept of the phantasm holds a crucial importance for framing the experience in psychoanalysis. This article aims to situate the place and function of the neurotic phantasm in the analytical experience, starting from the function of speech as proposed by Lacan. To do so, we have selected some texts and seminars by Lacan between the years of 1953 to 1964. Our working hypothesis is that by framing an unconsciously constituted reality as a response to the Other's desire, the phantasm serves to perpetuate in the neurotic subject a sense of being identical to themselves as it tends to promote an erasure of contradictions arising from the subject's position in relation to this desire. When conceived as the irruption of an object with a non-ego value in the phantasmatic frame, anxiety produces a reverse effect, thereby constituting both a counterproof and a support in demonstrating this hypothesis.

Dimensions of quality of life in patients with heart failure and sarcopenia: a scoping review protocol / Dimensões da qualidade de vida em pacientes com insuficiência cardíaca e sarcopenia: um protocolo de revisão de escopo

Objective: To map the dimensions of quality of life in patients with heart failure (HF) and sarcopenia. Methods: The scoping review will adhere to the JBI Manual for Evidence Synthesis methodology and will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Searches will encompass MEDLINE/PubMed, SCOPUS, EMBASE/Elsevier, LILACS, IBECS, BDENF (BVS), SciELO, Core Collection (Clarivate Analytics), CINAHL, Academic Search Premier (EBSCO), PsycINFO (APA), Cochrane Library, Epistemonikos, and academic search engines: Google Scholar and Bielefeld Academic Search Engine (BASE), without language or date restrictions. Inclusion criteria: Population ­ adults with HF and sarcopenia; Concept ­ Dimensions of quality of life including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression ­ defined based on the EQ-5D-3L questionnaire; Context ­ any health care setting. Two independent reviewers will select studies and extract data, with a third reviewer consulted in cases of discrepancies. Findings will be presented graphically with a narrative summary. Expected results: We aim to uncover key dimensions of quality of life in individuals with HF and sarcopenia through this scoping review. Anticipated outcomes include insights into mobility, self-care, usual activities, pain/discomfort, and anxiety/depression across diverse health care settings. Relevance: This review sheds light on the interplay between HF and sarcopenia and its impact on quality of life. The findings may guide interventions, inform evidence-based decision-making, and contribute to targeted strategies to improve the wellbeing of individuals managing both conditions. Review registration: Open Science Framework [https://archive.org/details/osf-registrations-jn387-v1]. (AU)

Periradicular and Peri-Implant Lesions Associated with Apical Impact of Osseointegrated Implants in Tooth Roots: Clinical Case Reports

This clinical case report aims to describe the development of periradicular and perimplant cystic lesions resulted from the intimate contact of the apical region of osseointegrated implants of dental roots, and discuss the reasons fo r failure of the guided bone regeneration procedure associated with platelet rich fibrin and leukocytes, this process was used to the treatment of the first case. Case Reports. Three cases were reported, two cases described the close contact between the tooth roots and the osseointegrated implants and another with a distance of 1.08 mm. All cases realized a radiographic, and they had not periapical lesions before contact with the apical region of the osseointegrated implants on the roots of the teeth. In the case with the largest cystic extension, the procedure was: removal of the osseointegrated implant with apicectomy of the neighboring teeth, excisional biopsy of the lesion, and grafting using the technique of guided bone regeneration associated with L-PRF. All three cases, endodontic treatment was performed on the neighboring teeth within 2 years of survival of the osseointegrated implants in order to reverse the existing lesion. Results. The diagnostic hypothesis of the three cases was periradicular and peri-implant lesion, arising from a contact of the apical region of the osseointegrated implant with the adja cent tooth. The distance of 1.08 mm between the apices did not ensure normality of the periradicular and peri-implant tissues. The intimate contact caused lesions of different extents and root fractures. Conclusion. Premature contact of the osseointegrated implant with the root region of the neighboring tooth may lead to the development of periradicular and peri-implant lesions, suggesting that it is not possible to control this infectious process with endodontic treatment of the injured tooth.

Este reporte de caso clínico tuvo como objetivo describir el desarrollo de lesiones quísticas perirradiculares y periimplantarias resultantes del contacto íntimo de la región apical de implantes osteointegrados de raíces dentales, y además discutir las razones del fracaso del procedimiento de regeneración ósea guiada asociado a fibrina rica en plaquetas y leucocitos. Este proceso se utilizó para el tratamiento del primer caso. Se reportaron tres casos, en dos casos se describieron el estrecho contacto entre las raíces de los dientes y los implantes osteointegrados y en el otro se determinó una distancia de 1,08 mm. En los tres casos se realizó una radiografía y se determinó que no existían lesiones periapicales, antes del contacto con la región apical de los implantes osteointegrados, en las raíces de los dientes. En el caso de mayor extensión quística, el procedimiento fue: extracción del implante osteointegrado con apicectomía de los dientes vecinos, biopsia excisional de la lesión e injerto mediante la técnica de regeneración ósea guiada asociada a L-PRF. En los tres casos, el tratamiento de endodoncia se realizó en los dientes vecinos dentro de los 2 años de supervivencia de los implantes osteointegrados para revertir la lesión existente. La hipótesis diagnóstica de los tres casos fue lesión perirradicular y periimplantaria, originada por un contacto de la región apical del implante osteointegrado con el diente adyacente. La distancia de 1,08 mm entre los ápices no aseguraba la normalidad de los tejidos perirradiculares y periimplantarios. El contacto íntimo provocó lesiones de diferente extensión y fracturas radiculares. El contacto prematuro del implante osteointegrado con la región radicular del diente vecino puede conducir al desarrollo de lesiones perirradiculares y periimplantarias, lo que sugiere que no es posible controlar este proceso infeccioso con tratamiento endodóntico del diente lesionado.

Effect of L-carnitine combined with citicoline on the therapeutic effect of neonatal hypoxic-ischemic encephalopathy and serum NO and ET-1 / 国际检验医学杂志

Objective To explore the effects of L-carnitine combined with citicoline on the therapeutic effect of neonatal hypoxic-ischemic encephalopathy(NHIE)and serum nitric oxide(NO)and endothelin-1(ET-1).Methods A total of 95 children with HIE admitted to the hospital from April 2020 to January 2023 were selected and were divided into observation group(47 cases)and control group(48 cases)by random number table method.The control group was given citicoline,and the observation group was given citicoline combined with L-carnitine.The therapeutic effect was evaluated on 14 days after treatment,and the recovery time of original reflex,muscle tone and consciousness was calculated.The levels of oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD)]and vascular endothelial function indexes(NO,ET-1)were detected before treatment and 14 days after treatment.Neonatal neurobehavioral score(NBNA)was used to evaluate the neurological function of the children,and the safety of the treatment regimen was ob-served.Pearson correlation analysis was used to analyze the correlation between NBNA and vascular endothe-lial function indexes.Results The total effective rate in the observation group was 91.49％,which was higher than 72.92％in the control group(P＜0.05).The original reflex recovery time,muscle tone recovery time and consciousness recovery time of NHIE children in the observation group were shorter than those in the control group(P＜0.05).There was no significant difference in NBNA scores between the two groups before treatment(t=1.225,P=0.224).After treatment,the NBNA score in the observation group was higher than that in the control group(t=6.223,P＜0.001).After treatment,MDA level decreased and SOD level in-creased in two groups(P＜0.05).After treatment,the level of MDA in the observation group was lower than that in the control group,while the level of SOD was higher than that in the control group(P＜0.05).After treatment,the levels of NO and ET-1 were decreased in both groups(P＜0.05).The levels of NO and ET-1 in the observation group were lower than those in the control group after treatment(P＜0.05).The adverse drug reaction rates in observation group and control group were 17.02％and 8.33％,respectively,and there was no significant difference between two groups(P＞0.05).Pearson correlation analysis showed that serum NO,ET-1 and NBNA score in NHIE children were negatively correlated(r=-0.546,-0.608,P＜0.05).Conclusion L-carnitine combined with citicoline could improve the therapeutic effect of NHIE,shorten the re-covery time of clinical manifestations,and improve nerve function,oxidative stress and vascular endothelial function without increasing drugs and adverse reactions.In addition,vascular endothelial function indexes are negatively correlated with NBNA score,which could be used as auxiliary reference indexes for judging NHIE.

Analysis on the quality of wild and different cultivation methods of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai / 国际中医中药杂志

Objective:To compare and evaluate the quality of wild and different cultivation methods of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai through analysis on UPLC characteristic atlas and multi-component content determination results. Methods:UPLC was used to establish the characteristic chromatogram and multi-component content determination method of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai, and clustering analysis, orthogonal partial least squares - discriminant analysis method were used for chemical pattern recognition analysis. Results:The results showed that there were 10 common peaks in 18 batches of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai. Five components were identified, erythrothioneine(peak 1), protocatechuic acid (peak 2), protocatechualdehyde (peak 3), caffeic acid (peak 4) and Hispidin (peak 5). HCA and OPLS-DA could distinguish Sanghuang porus vaninii (Ljub.) with different cultivation methods. Conclusion:Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai in wood is closer to wild Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai than in substitute cultivation. The UPLC characteristic atlas and multi-component content determination method established in this study can provide reference for the quality evaluation of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai.

Construction and drug resistance evaluation of cell strains which stably express FIP1L1-PDGFRA protein and its mutants / 基础医学与临床

Objective To construct mouse BaF3-FIP1L1-PDGFRA(F/P),BaF3-F/P-T674I and BAF3-F/P-D842V pre-B cell strains which stably express F/P fusion protein and its T674I and D842V mutants in order to e-valuate their activity by checking their responses to tyrosine kinase inhibitors(TKIs).Methods Lentivirus infected technique was used to transfect the target gene into BaF3 cells.RT-qPCR was used to detect mRNA expression,and CCK-8 method was used to detect the inhibitory effect of TKIs on the proliferation of stable cell strains.Results The constructed BaF3-F/P,BaF3-F/P-T674I and BAF3-F/P-D842V cell strains all transcripted FIP1L1 and PDGFRA mRNA.They exhibited malignant phenotypic characteristics of proliferation independent of IL-3 and sen-sitivity to corresponding TKIs.Conclusions The pre-B-cell strains stably expressing F/P and its T674I and D842V mutants are successfully constructed,which provide a good cell model for the development of compounds targeting at those molecules.

Genetic diagnosis,observation of sperm ultrastructure and outcome analysis for assisted reproduction in Hui and Uyghur pa-tients with globozoospermia / 临床检验杂志

Objective To investigate the clinical phenotype,sperm characteristics,genetic etiology and the outcomes of assisted repro-ductive technology of 2 minority patients(P1 Hui and P2 Uyghur)with globozoospermia.Methods The clinical data and various pa-rameters of semen examination in the 2 minority patients with globozoospermia were analyzed.The ultrastructure of their sperms was ob-served,and the genetic etiology of the patients was analyzed by whole exome sequencing(WES)and qPCR.Intracytoplasmic sperm in-jection(ICSI)combined with artificial oocyte activation(AOA)were applied for assisted reproduction thyrapy.The outcomes of assis-ted reproduction in the two couples were observed.Results Homozygous 109681 bp deletion in DPY19L2 gene was found in both the patients.The homozygous deletion of DPY19L2 gene in P2 patient came from his inbred parents.Low sperm motility and high sperm DNA fragmentation rate were observed in the P1 patient,the and the rate of round-headed sperm was 100％in morphology.The ab-sence of sperm acrosome and ultrastructural defects of plasma membrane,mitochondria and microtubules were found under the electron microscope.In the P2 patient,sperm motility and sperm DNA fragmentation rate patient were normal,and the sperm morphology was 100％round-headed sperm.Under the electron microscope,the main defects of sperm were small and round head with acrosomal ab-sence,structural damage,but the ultrastructural defects of organelles were rare,such as plasma membrane,mitochondria and microtu-bules.Both couples of the two patients received ICSI+AOA for assisted pregnancy,and the ICSI fertilization rate was 62.5％for P1 pa-tient and 75％for P2 patient.Both the patients successfully obtained clinical pregnancy.Conclusion The abnormal DPY19L2 gene is the main genetic cause in the globozoospermia patients with different ethnic backgrounds.Both structural damage and ultrastructural de-fects of organelles such as plasma membrane,mitochondrial and microtubule damage could be found in globozoospermia.ICSI combined with AOA should be an effective assisted reproductive thyrapy strategy for the patients with globozoospermia.

Application of seminal carnitine assay in male fertility assessment and therapeutic monitoring of asthenospermia / 临床检验杂志

Objective To compare seminal carnitine levels between normal males and asthenozoospermic patients,evaluate its correla-tion with progressive motility(PR)of sperm,and observe the effects of exogenous carnitine supplementation on asthenozoospermic pa-tients.Methods Semen samples were collected from 511 normal fertile males and asthenozoospermic patients.Seminal was measured using a fixed-time assay kit and the levels of carnitine were compared between the two groups.The consistency between seminal carni-tine and PR was assessed.Additionally,77 asthenozoospermic patients received L-carnitine(1 g/time,3 times/day,30 days/course).The levels of seminal carnitine and PR alteration pre-and post-treatment were monitored.Results The seminal L-carnitine level in the patients with asthenospermia([194.34±65.41]μmol/L)was significantly lower than that in normal fertile males([405.43±72.12]μmol/L)(P＜0.01).When the seminal L-carnitine level ≥325 μmol/L was set as the threshold,the statistical results showed that Kappa value was 0.81,with a diagnostic coincidence rate of 93.74％.After one course of administration of L-carnitine,the concentra-tion of seminal L-carnitine([356.03±84.87]μmol/L)and PR([32.69±8.35]％)were significantly higher those that before treat-ment([183.61±79.54]μmol/L and[16.56±7.74]％,P＜0.01).Conclusion The seminal carnitine assay kit could be used for ac-curate and high-throughput quantification of clinical samples,facilitating asthenozoospermia diagnosis and therapeutic efficacy evalua-tion.Exogenous carnitine supplementation may elevate seminal carnitine levels and sperm motility in asthenozoospermic patients and po-tentially improve their fertility.

Clinical pathology and prognostic differences of primary CD5+diffuse large B cell lymphoma / 临床与实验病理学杂志

Purpose To explore the clinicopathological features and molecular characteristics of primary CD5+diffuse large B cell lymphoma(DLBCL).Methods Immunohisto-chemistry and next-generation sequencing(NGS)were used to compare the pathological features,immunophenotypes,and mo-lecular characteristics between primary CD5+DLBCL and CD5-DLBCL,and to analyze their relationship with prognosis and clinical characteristics of patients.Results Among 311 DLBCL patients,there were 46 cases(14.7％)of CD5+DLBCL.There were no statistically significant differences in patient gen-der,clinical staging,international prognostic index between CD5+DLBCL and CD5-DLBCL,and between CD5+DLBCL with and without MYD88 L265P mutation(P＞0.05).Immuno-phenotypically,the overexpression of BCL2(69.5％vs 49.4％,P=0.003)and the co-expression of BCL2 and C-MYC(26％vs 14％,P=0.04)were higher in the CD5+DLBCL group than those in the CD5-DLBCL group;the expression of C-MYC(53％vs 20％),BCL6(93.3％vs 61.3％),Ki67(93.3％vs 64.5％),and co-expression(46.7％vs 20.8％)were higher in the CD5+with MYD88 L265P mutation group than those in the CD5+without MYD88 L265P mutation group(P＜0.05).Survival analysis showed that the disease progres-sion-free survival time of patients in the CD5+DLBCL group tended to be shorter than that of patients in the CD5-DLBCL group(P=0.09).Furthermore,the disease progression-free survival time of patients in the CD5+without MYD88 L265P mutation group was significantly longer than that of patients in the CD5+with MYD88 L265P mutation group(P=0.04).NGS detection found differences in the distribution of accompan-ying mutated genes between CD5+DLBCL and CD5-DLBCL groups.ConclusionCD5 expression and CD5+with MYD88 L265P mutation may be potential indicators of poor prognosis in DLBCL patients.

Effects of MYD88 overexpression on proliferation and apoptosis of diffuse large B cell lymphoma cells and its mechanism / 临床与实验病理学杂志

Purpose To investigate the effect of MYD88 gene overexpression on the proliferation and apoptosis of human diffuse large B cell lymphoma(DLBCL)cells,and to prelimi-narily explore the mechanism of MYD88 gene action.Methods PEGFP-C2-MYD88 overexpressing MYD88 L265P gene was transfected into DLBCL cells by plasmid transfection.The exper-iment was divided into blank control group,negative control group and MYD88 L265P overexpression group.The fluores-cence expression of MYD88 L265P after overexpression was ob-served under inverted fluorescence microscope.RT-PCR and Western blot were used to detect the mRNA and protein expres-sion of MYD88 L265P,IRAK4,NF-κB and BCL2 in DLBCL cells before and after overexpression of MYD88 L265.CCK8 method was used to detect DLBCL cells proliferation and Ho-echst staining was used to detect DLBCL cells apoptosis.Re-sults After overexpression of MYD88 L265P,compared with the blank control group(0.670 4±0.017 5)and the negative control group(0.715 3±0.019 6),the MYD88L265P overex-pression group(1.157 2±0.010 2)increased significantly,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(0.69 ±0.04)and the negative control group(0.81±0.07),the MYD88L265P overexpression group(0.48±0.05)was signifi-cantly decreased,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(mRNA:1.0158±0.0115,0.987 3±0.010 2,1.007 6±0.015 3,protein:0.183 4±0.058 9,0.096 8± 0.015 7,0.147 5±0.0418)and negative control group(mR-NA:0.9132±0.0098,1.0032±0.0156,0.9327± 0.011 2,protein:0.187 9±0.042 3,0.088 9±0.0513,0.134 8±0.050 1),the mRNA(3.243 2±0.013 6,2.976 6 ±0.0213,1.585 9±0.019 8)and protein expressions(0.452 7±0.052 4,0.218 9±0.047 5,0.301 4±0.059 8)of IRAK4,NF-κB and anti-apoptosis protein BCL2 in MYD88L265P overexpression group were significantly increased,which was statistically significant(all P＜0.05).Conclusion After overexpression of MYD88 L265P,the apoptosis rate of DLBCL cells decreased and the cell proliferation rate increased.The mechanism may be related to the mutation of MYD88 L265P gene,activation and amplification of NF-κB pathway,and pro-motion of the overexpression of antiapoptotic protein BCL2.

Immune checkpoint inhibitor related tuberculosis:a case report and literature analysis / 复旦学报（医学版）

With the increasing application of immune checkpoint inhibitors(ICI)in anti-tumor therapy,ICI related infections are often neglected.Mycobacterium tuberculosis(MTB)is also a common pathogen.We reported a case of ICI related pulmonary tuberculosis from Zhongshan Hospital,Fudan University.Meanwhile,18 cases of ICI related tuberculosis infection were collected through literature search,and the characteristics of ICI related tuberculosis were analyzed to improve the understanding in clinic practice.All the cases were confirmed TB including 15 cases of pulmonary tuberculosis(1 case with complication of intestinal tuberculosis)and 4 cases of extra-pulmonary tuberculosis(1 case of disseminated tuberculosis,bone tuberculosis,tuberculous pericarditis and tuberculous pleurisy,respectively).The chest CT characteristics of pulmonary tuberculosis mainly included centrilobular nodules,ground glass nodules,empty lesions,patchy shadows,consolidation and large infiltration.Eighteen cases started anti-tuberculosis treatment,while 4 cases continued ICI treatment.Three cases suspended ICI(2 cases had remission after reuse)and 11 cases stopped ICI,and 1 case was not mentioned.ICI related tuberculosis may be a direct complication of tumor immunotherapy.It is necessary to screen tuberculosis infection and exclude active tuberculosis before immunotherapy.If there are suspected symptoms such as fever,cough and sputum during ICI treatment,active tuberculosis should be taken into account.

Low-temperature condensation deposition method for 3D printing of bone tissue engineering poly-L-lactic acid/pearl powder composite scaffold / 中国组织工程研究

BACKGROUND:The repair of large-scale bone defects is still facing serious challenges.It is of great significance to develop personalized,low-cost,and osteogenic-inducing tissue engineering scaffolds for bone repair. OBJECTIVE:To explore the process of 3D printing bone tissue engineering scaffold containing pearl composite material by low-temperature condensation deposition method,and further test the physicochemical properties and in vitro biological functions of the composite scaffold. METHODS:Pearl powder was prepared by grinding and sieving.The pearl powder of different qualities was added into the poly-L-lactic acid ink,so that the mass ratio of pearl powder to poly-L-lactic acid was 0,0.1,0.2,0.3,and 0.5,respectively.The 3D-printed poly-L-lactic acid/pearl powder scaffolds were prepared using the low-temperature condensation deposition method.The microstructure,compressive properties,water contact angle,cytocompatibility,and in vitro bone differentiation ability of the printed poly-L-lactic acid/pearl powder composite scaffolds were detected. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the five groups of scaffolds all had micropores with a diameter of 2 μm or even smaller,irregular shapes and interconnectivity.(2)All the five groups had good compressive properties.The compressive strength of the pearl powder 0.5 group was higher than that of the other four groups(P<0.05).The water contact angle of the pearl powder 0.2 group and the pearl powder 0.5 group was smaller than that of the pearl powder 0 group(P<0.01,P<0.001).(3)Bone marrow mesenchymal stem cells were co-cultured with five groups of scaffolds for 1,3,and 5 days,respectively.The cell proliferation in pearl powder 0.1,0.2,0.3,and 0.5 groups cultured for 3 and 5 days was faster than that in pearl powder 0 group(P<0.05).After 1 day of culture,live-dead staining exhibited that the number of cells on the scaffold was small,but all of them were living cells.(4)Bone marrow mesenchymal stem cells were inoculated on the scaffold surface of the pearl powder 0 group and pearl powder 0.1 group respectively for osteogenic differentiation.The alkaline phosphatase activity induced for 4 and 6 days in the pearl powder 0.1 group was higher than that in the pearl powder 0 group(P<0.05).(5)The results showed that the poly-L-lactic acid/pearl powder composite scaffold had good compressive strength,hydrophilicity,cytocompatibility,and osteogenic properties.

Preparation and characteristics comparison of three acute pancreatitis rat models / 中国组织工程研究

BACKGROUND:Establishing a stable and reliable animal model of acute pancreatitis is of great significance for understanding its pathogenesis,pathophysiological characteristics,and clinical medication.Domestic and foreign studies have shown that cerulein,L-arginine,and sodium taurocholate can induce acute pancreatitis,but their pathophysiological characteristics and model characteristics are still unclear. OBJECTIVE:To establish an acute pancreatitis rat model using cerulein,L-arginine,and sodium taurocholate and to observe the changing patterns of model features at different time points. METHODS:Ninety-six healthy male Sprague-Dawley rats were randomly divided into normal group,cerulein group,L-arginine group,and sodium taurocholate group,with 24 rats in each group.Within each group,there were three subgroups(n=8 per group):12-,24-,and 48-hour subgroups.Cerulein was administered via intraperitoneal injection six times with a 1-hour interval.L-arginine was administered through two intraperitoneal injections with a 1-hour interval.Sodium taurocholate was injected for inducing acute pancreatitis models through retrograde injection into the bile-pancreatic duct.By examining the rat survival rate,gross morphology of the pancreas,calculating the pancreatic organ index,and measuring levels of amylase,lipase,alanine transaminase,aspartate transaminase,blood urea nitrogen,and creatinine,as well as observing pancreatic tissue pathological features through hematoxylin-eosin staining and conducting a pancreatic injury scoring,we evaluated the changing patterns of model features at different time points. RESULTS AND CONCLUSION:Compared with the normal group,the overall survival rate of rats was 100%in the cerulein group,88%in the L-arginine group,and 96%in the sodium taurocholate group.The pancreatic organ index was increased in all groups.Gross observation indicated that,In the cerulein group,pancreatic edema,blurred lobes,and looseness were visible.In the L-arginine group,the pancreatic glands were enlarged and thickened with patchy bleeding.In the sodium taurocholate group,pancreatic tissue showed varying degrees of congestion and edema accompanied by scattered flakes of hemorrhage and necrosis.The levels of serum alanine transaminase,aspartate transaminase,blood urea nitrogen,creatinine,amylase,and lipase in rats exhibited consistent changes.In the cerulein group,these parameters possibly peaked at 12 hours(P<0.05)and then showed a declining trend.In the L-arginine group,they reached the highest levels at 24 hours(P<0.05)and significantly decreased at 48 hours.In the sodium taurocholate group,serum amylase and lipase remained at higher levels at 12 hours with a slow decline trend(P<0.05).Compared with the normal group,microscopic examination revealed mild acinar edema and widened interlobular spaces in the cerulein group,with a higher presence of inflammatory cells.In the L-arginine group,there was widening of interlobular spaces,extensive infiltration of inflammatory cells,and patchy necrotic areas.In the sodium taurocholate group,significant pancreatic edema,structural disarray,extensive necrotic foci,and inflammatory cell infiltration were observed.Compared with the normal group,the pathological scores of induced acute pancreatitis in all three models were significantly different at each time point(P<0.05).Moreover,the pathological scores in each group increased over time,indicating a gradual worsening of pancreatic tissue damage.When comparing different models at the same time,there were differences in pathological scores,with the sodium taurocholate group having the highest scores,followed by the L-arginine group,and the cerulein group having the lowest scores.Analyzing the three models at the same time point,the most severe condition was in the sodium taurocholate group,which was characterized by pancreatic hemorrhage and necrosis,followed by the L-arginine group,which was characterized by necrosis,and the least severe condition was in the cerulein group,mainly characterized by edema.The serum biochemical index levels of the cerulein and L-arginine groups decreased at 48 hours,indicating that these two models may have a tendency to self-heal and belong to a self-limiting disease course.The serum biochemical index levels of the sodium taurocholate group decreased slowly after 12 hours.Therefore,pancreatic injury in the sodium taurocholate group might not be relieved after 48 hours or longer.

The prognostic value of serum Dnase1L3, CAR combined with MHR in decompensated hepatitis B cirrhosis patients / 中国医师杂志

Objective:To explore the prognostic value of serum deoxyribonuclease 1 like 3 (Dnase1L3), C-reactive protein/albumin ratio (CAR) combined with monocyte to high-density lipoprotein cholesterol ratio (MHR) in decompensated hepatitis B cirrhosis patients.Methods:A prospective selection was conducted on 236 decompensated hepatitis B cirrhosis patients (liver disease group) admitted to the Third Hospital of Qinhuangdao from January 2020 to December 2021, and 185 healthy volunteers (control group) who underwent outpatient physical examinations. The serum levels of Dnase1L3, CAR, MHR, and liver function were detected, and Pearson analysis was conducted to investigate the correlation between Dnase1L3, CAR, MHR, and liver function. Tracking the survival status of patients after 30 days of hospitalization, the risk factors affecting 30 day mortality in decompensated hepatitis B cirrhosis patients were analyzed using a multivariate logistic regression equation. The receiver operating characteristic (ROC) curve analysis was used to assess the value of Dnase1L3, CAR, and MHR in predicting 30 day in-hospital mortality in decompensated hepatitis B cirrhosis patients.Results:The serum levels of Dnase1L3, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), CAR, and MHR in the liver disease group were higher than those in the control group (all P<0.05). The serum levels of Dnase1L3, CAR, and MHR in the liver disease group were positively correlated with AST, ALT, and TBiL (all P<0.05). Among 236 patients, 32 died within 30 days. Model for end-stage liver disease (MELD) scores>18, high Dnase1L3, high CAR, and high MHR were risk factors for 30 day mortality in decompensated hepatitis B cirrhosis patients (all P<0.05). The combined prediction of Dnase1L3, CAR, MHR, and MELD scores for 30 day mortality in decompensated patients with hepatitis B cirrhosis showed an area under the curve of 0.904, which was higher than the predicted values of 0.719, 0.678, 0.763, and 0.742 for individual indicators. Conclusions:The serum Dnase1L3 levels, CAR, and MHR are elevated in patients with decompensated hepatitis B cirrhosis, and are associated with the degree of liver function damage and mortality within 30 days of hospitalization. They have high value in predicting the prognosis of decompensated hepatitis B cirrhosis.

Research on the Digital Transformation Path of Primary Health Care Institutions Based on Organizational Change Theory:Take Tianjin's Digital Health Service Consortium as an Example / 中国医院管理

Objective To explore the digital transformation path of primary medical and health institutions in China,and provide reference for the research and follow-up policy formulation in the field.Methods The experience and practice of Tianjin digital health service consortium were collected by semi-structured interview,and the external and internal data were continuously collected as supplements.Finally,the data were coded and analyzed by programmatic grounded method.Results After coding,39 first-level categories and 13 second-level categories were obtained.Finally,guided by the theoretical analysis framework of organizational change,five core categories were obtained,namely,driving factors,structural change,technological change,person change and task change,so as to establish the digital transformation of primary health care institutions.Conclusion The four dimensions of structure,technology,person and task change influence and complement each other.The digital transformation of regional medical institutions should ensure the coordinated development of multiple dimensions at the organizational level.Finally,suggestions are put forward in three aspects:attaching importance to top-level design driving,applying digital technology to empower business scenarios,and actively promoting practical experience in relevant regions.

Effects of Ophiopogonis Root Decoction on a mouse model of idiopathic pulmonary fibrosis based on PD-1/PD-L1 signaling pathway / 中成药

AIM To investigate the effects of Ophiopogonis Root Decoction on bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF)in mice and to explore its metabolic modulation of immunity.METHODS The IPF mouse model was constructed by tracheal drip injection of BLM,and the mice were randomly divided into the control group,the model group,the pirfenidone group(0.3 g/kg)and the high,medium and low dose groups of Ophiopogonis Root Decoction(18,9,4.5 g/kg).HE and Masson staining,ELISA,flow cytometry and immunohistochemistry were used to detect the histopathological changes of the lung,the levels of Collagen I,HYP and TGF-β1,the proportion of PD-1+ CD4+T cells in plasma,and the expressions of p-STAT3,PD-1,PD-L1 and IL-17A in lung tissue,respectively.RESULTS Compared with the control group,the model group displayed significantly higher level of lung coefficients(P<0.01),more severe pulmonary inflammatory cell infiltration and collagen fiber deposition,and increased pulmonary fibrosis score(P<0.01),increased levels of Collagen I,HYP and TGF-β1(P<0.01),increased proportion of PD-1+ CD4+ T cells in plasma(P<0.01),increased pulmonary expression of p-STAT3,PD-1,PD-L1 and IL-17A(P<0.01).Compared with the model group,the Ophiopogonis Root Decoction groups shared lower levels of lung coefficients(P<0.05),less pulmonary inflammatory cell infiltration and collagen fiber deposition,decreased pulmonary fibrosis score(P<0.05),decreased levels of Collagen I,HYP and TGF-β1(P<0.05),decreased proportion of PD-1+ CD4+T cells in plasma(P<0.05),and decreased pulmonary expression of p-STAT3,PD-1,PD-L1,and IL-17A(P<0.05).CONCLUSION Ophiopogonis Root Decoction can significantly reduce extracellular matrix(ECM)deposition and curb the progression of IPF via inhibition of STAT3/PD-1/PD-L1 immunomodulatory signaling pathway.