Expression and significance of cyclin dependent kinase inhibitor 3 in HPV16-positive cervical cancer / 重庆医学

Objective To investigate the expression and significance of cyclin dependent kinase inhibitor 3(CDKN3)in human papillomavirus type 16(HPV16)-positive cervical cancer.Methods CDKN3 expression in pan-cancer was retrieved and downloaded from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,and the expression levels of CDKN3 between normal cervical tissues(13 samples)and cervical cancer tissues(306 samples)were compared.Subsequently,GSE39001 data of HPV16-positive cervical cancer was sourced and downloaded from the Gene Expression Omnibus(GEO)database,and the expression levels of CDKN3 mRNA in HPV16-positive cervical cancer tissues(43 samples)and normal cervical tissues(12 samples)were compared.Immunohistochemical method was used to detect the expression of CDKN3 in 12 ca-ses of HPV16-positive cervical cancer,12 cases of HPV16-positive cervical precancerous lesions,10 cases of HPV16-positive chronic cervicitis and 7 cases of HPV-negative normal cervical samples collected from the Af-filiated Hospital of Guizhou Medical University.SiHa(HPV16-positive),HeLa(HPV18-positive)and HCC94(HPV-negative)cervical cancer cell lines were selected,and their CDKN3 expression were detected by West-ern blot.Results The GEPIA platform analysis showed that CDKN3 was highly expressed in pan-cancer,and the expression level of CDKN3 in cervical cancer tissue was significantly higher than that in normal cervical tissue(P<0.05).The GEO dataset reflected a significantly increased CDKN3 mRNA expression level in HPV16-positive cervical cancer compared to normal cervical tissue(P<0.001).Immunohistochemical verifi-cation showed that the positive expression rates of CDKN3 in HPV16-positive cervical cancer,HPV16-positive cervical precancerous lesion,HPV16-positive chronic cervicitis and HPV-negative normal cervical tissues were 91.7%,58.3%,0 and 0,respectively.Western blot analysis of cervical cancer cells showed that the expression level of CDKN3 in SiHa(HPV16-positive)cells was significantly higher than that in HeLa(HPV18-positive)and HCC94(HPV-negative)cells(P<0.05).Conclusion CDKN3 is a new oncogene of HPV16-positive cer-vical cancer,which may be used as a marker of cervical precancerous lesions and cervical cancer screening,and may provide a theoretical basis for subsequent mechanism research and targeted therapy.

Characteristics of acute graft-versus-host disease of the intestine after unrelated cord blood transplantation / 中国组织工程研究

BACKGROUND:Despite unrelated cord blood transplantation is expected to become an important method for treating malignant hematological diseases,the manifestation and clinical characteristics of acute graft-versus-host disease in the gastrointestinal tract still require further in-depth investigation. OBJECTIVE:To analyze the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation. METHODS:A retrospective analysis was conducted on 668 malignant hematological disease patients after unrelated cord blood transplantation who underwent hematopoietic stem cell transplantation subspecialty in the Department of Hematology,First Affiliated Hospital of University of Science and Technology of China from December 2016 to December 2020.Among them,clinical data of 138 patients with intestinal acute graft-versus-host disease were analyzed,including 76 males and 62 females,with a median age of 13(1-62)years.All patients were treated with a myeloablative regimen(without antihuman thymocyte globulin)and cyclosporin A combined with mycophenolate mofetil to prevent graft-versus-host disease. RESULTS AND CONCLUSION:(1)The patients with intestinal acute graft-versus-host disease had diarrhea of varying degrees,most of which were yellow-green,yellow-brown watery stools or mucous stools.53 patients(38.4%)had blood stools,82 patients(57.9%)had skin involvement,18 patients(13.0%)had a secondary intestinal bacterial infection,and 90 patients(65.2%)had cytomegaloviremia.(2)The clinical characteristics of patients(70 cases,50.7%)with grade 1-2 intestinal acute graft-versus-host disease were compared with those(68 cases,49.3%)with grade 3-4 intestinal acute graft-versus-host disease.It was found that the age of grade 3-4 intestinal acute graft-versus-host disease patients was higher than that of grade 1-2 intestinal acute graft-versus-host disease patients(P<0.001),and they were complicated with cytomegaloviremia probably(P=0.035).Diarrhea lasted longer(P=0.00)and the length of hospital stay increased substantially(P<0.001).However,there were no significant differences in recipient gender,pre-transplant disease status,HLA matching,diagnosis,combined skin graft-versus-host disease,and secondary intestinal infection rate in patients of the two groups.(3)These findings conclude that the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation are complex,which affects the prognosis and quality of life of patients seriously and requires early identification and precise treatment.

MicroRNA-887-3p Inhibited MDM4 Expression and Proliferation but Promoted Apoptosis of Intervertebral Disc Annulus Fibrosus Cells in Rats / 实验动物与比较医学

ObjectiveTo investigate the effects of microRNA (miRNA, miR)-887-3p on the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells and its underlying molecular mechanism. MethodsAnnulus fibrosus tissues were obtained from 8-week-old SPF-grade SD male rats, centrifuged to prepare and identify annulus fibrosus cells. Rats in the experiment were randomly divided into four groups: a Normal group consisting of primary annulus fibrosus cells without any treatment; a Control group treated with 10 ng/mL interleukin-1β (IL-1β) for 24 hours to establish a degenerative cell model; an interference group (miR-887-3p inhibitor) transfected with miR-887-3p inhibitor using Lipo3000 based on the Control group; and an overexpression group (miR-887-3p mimics) transfected with miR-887-3p mimics using Lipo3000 based on the Control group. CCK-8 assay was used to assess cell viability; flow cytometry was used to measure cell apoptosis rates; real-time fluorescence quantitative PCR (qPCR) was used to detect the expression levels of miR-887-3p and murine double minute 4 (MDM4) mRNA; Western blotting was used to measure the protein expression levels of MDM4, Bcl-2, and Caspase-3. ResultsImmunofluorescence staining of isolated and cultured cells revealed a Collagen I positive rate of over 90% in rat intervertebral disc annulus fibrosus cells, indicating a cell purity level greater than 90%. Real-time fluorescence qPCR results showed that after establishing an annulus fibrosus degenerative cell model using IL-1β, the expression level of miR-887-3p significantly increased compared to the Normal group (P<0.001). Compared to the Control group, transfection with miR-887-3p inhibitor resulted in a significant decrease in its expression level (P<0.001). The CCK-8 assay showed that compared to the Normal group, cell viability significantly decreased in the Control group (P<0.001). Compared to the Control group, cell proliferation ability significantly increased after miR-887-3p inhibition, and significantly decreased after overexpression of miR-887-3p. Flow cytometry results revealed that compared to the Normal group, the apoptosis rate in the Control group significantly increased (P<0.001). Compared to the Control group, the cell apoptosis rate significantly decreased in the miR-887-3p interference group (P<0.001) and increased in the overexpression group (P<0.001). Western blotting analysis showed that compared to the Normal group, Bcl-2 expression level significantly decreased (P<0.001) and Caspase-3 expression level significantly increased (P<0.001) in the Control group. Compared to the Control group, Bcl-2 and MDM4 expression levels significantly increased (P<0.01), and Caspase-3 expression level significantly decreased (P<0.01) in the miR-887-3p interference group; whereas in the overexpression group, Bcl‑2 and MDM4 expression levels significantly decreased (P<0.05), and Caspase-3 levels significantly increased (P<0.05). Real-time fluorescence qPCR and protein immunoblotting results showed that after interfering with miR-887-3p, the expression of MDM4 protein and mRNA increased (P<0.001); after overexpressing miR-887-3p, their expression decreased (protein, P<0.01; mRNA, P<0.001). ConclusionMiR-887-3p may modulate the cell proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells by regulating MDM4 expression, thereby influencing the development and progression of disc degeneration.

Application of outcome-based education combined with team-based learning in practice teaching of pediatric emergency and critical care nursing / 中华医学教育探索杂志

Objective:To investigate the application value of outcome-based education (OBE) combined with team-based learning (TBL) in the practice teaching of pediatric emergency and critical care nursing.Methods:A total of 84 nursing students who studied in the pediatric intensive care unit (PICU) of The First Affiliated Hospital of Air Force Medical University were selected and divided into control group and observation group. The 41 nursing students in the control group received traditional teaching, and the 43 nursing students in the observation group received OBE+TBL teaching. The two groups were assessed in terms of theoretical knowledge, practical operation ability, clinical thinking ability, and self-learning ability after teaching, and the degrees of satisfaction with teaching and participation in teaching were compared between the two groups. SPSS 22.0 was used for the t-test and the chi-square test. Results:After teaching, the observation group had significantly better theoretical knowledge, practical operation ability, and self-learning ability than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher scores of learning engagement (recognition, behavior, emotion) ( P<0.05) and satisfaction with classroom effect, knowledge mastery, and learning interest ( P<0.05). Conclusion:The application of OBE+TBL teaching in PICU nursing students can effectively improve their self-learning ability and participation and help them to understand PICU nursing priorities and improve their practical operation ability.

Effects of video-assisted anal fistula treatment on stress indicators and anal function in patients with anal fistula / 中国基层医药

Objective:To investigate the effects of video-assisted anal fistula treatment (VAAFT) on stress indicators and anal function in patients with anal fistula.Methods:Ninety-nine patients with anal fistula who received treatment in Lishui City People's Hospital from March 2020 to February 2022 were included in this study. They were randomly divided into a control group ( n = 48, undergoing fistulotomy) and an observation group ( n = 51, undergoing VAAFT). Clinical efficacy and the levels of various indexes during the perioperative period were compared between the two groups. Anal function [anal maximal contraction pressure, anal canal rest pressure, anal longest contraction time, anal incontinence Wexner score], and the levels of serum stress indicators [norepinephrine (NE), β-endorphin (β-EP), nerve growth factor (NGF), substance P (SP), and cortisol (Cor)] were determined before and after treatment. Postoperative complications were recorded. All patients were followed up for 3 months after surgery. Recurrence of anal fistula was compared between the two groups. Results:The total effective rate in the observation group was 94.12% (48/51), which was significantly higher than 79.17% (38/48) in the control group ( χ2 = 4.84, P < 0.05). The operative time, intraoperative blood loss, wound healing time, and length of hospital stay in the observation group were (34.78 ± 4.01) minutes, (34.48 ± 3.86) mL, (19.46 ± 2.05) days, and (12.76 ± 1.50) days, which were significantly shorter or less than those in the control group [(54.86 ± 6.05) minutes, (36.88 ± 4.01) mL, (25.61 ± 2.92) days, (21.05 ± 2.46) days, t = -19.57, -3.03, -12.18, -20.67, all P < 0.05). On the first day after surgery, the Visual Analogue Scale score in the observation was (1.88 ± 0.28) points, which was significantly lower than (3.55 ± 0.41) points in the control group ( t = -23.78, P < 0.05). At 3 months after surgery, anal maximal contraction pressure and Wexner scores in the observation group were (171.86 ± 18.68) mmHg and (0.39 ± 0.07) points, which were significantly lower than (180.37 ± 19.56) mmHg and (0.52 ± 0.09) points in the control group ( t = -2.21, -8.04, both P < 0.05). Anal canal rest pressure in the observation group was (50.77 ± 5.68) mmHg, which was significantly higher than (48.34 ± 5.23) mmHg in the control group ( t = 2.21, P < 0.05). There was no significant difference in anal longest contraction time between the two groups before and after treatment (both P > 0.05). At 3 days after surgery, NE and Cor levels in each group increased compared with those before surgery (both P < 0.05). At 3 days after surgery, NE and Cor levels in the observation group were (252.67 ± 29.16) μg/L and (281.34 ± 31.27) nmol/L, respectively, which were significantly lower than (304.03 ± 32.28) μg/L and (308.72 ± 34.18) nmol/L in the control group ( t = -8.31, -4.16, both P < 0.05). At 3 days after surgery, β-EP, SP, and NGF in each group were decreased compared with those before treatment (all P < 0.05). At 3 days after surgery, β-EP, SP, and NGF in the observation group were (62.37 ± 6.83) ng/L, (1.87 ± 0.23) ng/L, (30.82 ± 4.03) mg/L], respectively, which were significantly higher than (51.09 ± 5.74) ng/L, (2.59 ± 0.51) ng/L, and (38.19 ± 4.24) mg/L in the control group ( t = 8.86, 8.95, 8.85, all P < 0.05). There was no significant difference in the incidence of complications between the two groups ( P > 0.05). The recurrence of anal fistula in the observation group was 1.96% (1/51), which was significantly lower than 12.50% (6/48) in the control group ( χ2 = 4.18, P < 0.05). Conclusion:VAAFT exhibits a significant therapeutic effect on anal fistula, with a small surgical incision and minimal intraoperative bleeding. This procedure greatly shortens operative time and the length of hospital stay, alleviates postoperative pain, improves anal function, reduces postoperative stress response indicators, and has a low postoperative recurrence rate.

Exploring the Co-occurrence and Treatment of Tumors and Psycho-Cardiological Diseases Based on the Concept of “Diagnosing and Treating Diseases According to Syndromes” / 中医杂志

The co-occurrence of tumor and psycho-cardiological diseases， affecting both the physical and mental aspects of patients， is a common clinical condition that is closely related to tumor treatment and prognosis. Exploring its underlying mechanism and treatment methods can bring new ideas and strategies for clinical treatment. It is believed that heart-kidney yang deficiency is one of the common core mechanisms of psycho-cardiological diseases. Stagnation of heat and toxins is a core mechanism for tumor formation and metastasis. Additionally， cancer and drug toxicity contribute to the development of psycho-cardiological disease by impairing lung circulation. Cancerous toxins can damage the blood vessels， resulting in a diminished vitality in the heart of blood vessels. Simultaneously， lung qi failing in dispersing impairs the downward movement and causes stagnation in the heart of spirit . This process ultimately leads to the development or exacerbation of psycho-cardiological diseases. The author explores the diagnosis and treatment approach based on the “diagnosing and treating diseases according to syndroms” concept， focusing on related syndrom identification and treatment. The process begins with pattern identification， followed by comprehensive analysis of data gained by four diagnostic methods to clearly understand the core pathogenesis and basic treatment principles. After pattern identification， the focus shifts to recognizing the disease and providing additional evidence to support the diagnosis. Special attention is paid to adjusting the use of medication based on the disease's characteristics. This approach aims to achieve precise treatment for tumors and psycho-cardiological diseases， reducing the side effects of multiple medications， therefore to provide guidance for clinical application.

Aerobic training methods for high school soccer / Métodos de treino aeróbico para o futebol de ensino médio / Métodos de entrenamiento aeróbico para el fútbol de la escuela secundaria

ABSTRACT Introduction: Fatigue impairs exercise activity in high school students, and it is detrimental to explore aerobic training when fatigue cannot be alleviated. This factor limits the ability to exploit the full potential of young athletes for soccer. Objective: Implement a healthy development protocol for soccer application in high school. Methods: This article used a literature review among other research methods. The analysis was devoted to aerobic training for endurance in soccer for students in high school. The specific methods of implementing the developed protocol in high schools were studied. Finally, effective measures for improving students' physical fitness were presented. Results: Judging from the situation, the duration of each training session in high school soccer is closely related to the coaches' ability. High-level coaches tend to organize the duration of training according to the perceived effects in soccer practice, considering the physical and technical characteristics of the sport itself. Conclusion: Soccer endurance training can also promote the long-term development of soccer education while meeting students' actual exercise needs. It is important to carry out soccer aerobic training applied to high school. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A fadiga prejudica a atividade do exercício físico nos alunos do ensino secundário, sendo prejudicial explorar os treinos aeróbicos quando a fadiga não pode ser aliviada. Esse fator limita a capacidade de explorar o máximo potencial de jovens atletas para o futebol. Objetivo: Implementar um protocolo de desenvolvimento sadio para a aplicação do futebol no ensino médio. Métodos: Este artigo utilizou a revisão bibliográfica entre outros métodos de investigação. A análise foi dedicada ao treino aeróbico para a resistência no futebol dos estudantes no ensino médio. Estudou-se os métodos específicos de implementação do protocolo elaborado nas escolas de ensino médio. Finalmente, foram apresentadas as medidas eficazes para melhorar a condição física dos estudantes. Resultados: A julgar pela situação em tela, a duração de cada sessão de treino no futebol do ensino médio está intimamente relacionada com a capacidade dos treinadores. Os treinadores de alto nível tendem a organizar a duração do treino de acordo com os efeitos perceptíveis na prática do futebol, considerando as características físicas e técnicas do próprio esporte. Conclusão: A formação de resistência no futebol pode também promover o desenvolvimento a longo prazo da educação futebolística ao mesmo tempo em que satisfaz as necessidades reais de exercício físico dos estudantes, sendo de grande importância realizar a formação do treino aeróbico no futebol aplicado ao ensino médio. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La fatiga perjudica la actividad del ejercicio en los estudiantes de secundaria, y es perjudicial explorar el entrenamiento aeróbico cuando la fatiga no se puede aliviar. Este factor limita la capacidad de explotar el máximo potencial de los jóvenes deportistas para el fútbol. Objetivo: Implementar un protocolo de desarrollo saludable para la aplicación del fútbol en la escuela secundaria. Métodos: Este artículo utilizó, entre otros métodos de investigación, la revisión de la literatura. El análisis se dedicó al entrenamiento aeróbico de resistencia en el fútbol para estudiantes de secundaria. Se estudiaron los métodos específicos de aplicación del protocolo elaborado en los institutos. Por último, se presentaron las medidas eficaces para mejorar la aptitud física de los alumnos. Resultados: A juzgar por la situación en la pantalla, la duración de cada sesión de entrenamiento en el fútbol de la escuela secundaria está estrechamente relacionada con la capacidad de los entrenadores. Los entrenadores de alto nivel tienden a organizar la duración del entrenamiento en función de los efectos percibidos en la práctica del fútbol, teniendo en cuenta las características físicas y técnicas del propio deporte. Conclusión: El entrenamiento de la resistencia en el fútbol también puede promover el desarrollo a largo plazo de la educación futbolística al tiempo que satisface las necesidades reales de ejercicio físico de los estudiantes, y es de gran importancia llevar a cabo la formación del entrenamiento aeróbico en el fútbol aplicado a la escuela secundaria. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Research progress on detection methods of pyrethroid insecticide residues in human biomaterials / 环境与职业医学

In recent years, due to the wide use of pyrethroid insecticides, the impact of pyrethroid insecticides on human health cannot be ignored. Therefore, how to detect pyrethroid insecticide residues in human body accurately and efficiently has become a research hotspot. However, it is difficult to detect pyrethroid insecticides because of its low residues and fast metabolism. Our article reviewed research on the detection of pyrethroid pesticide residues in human biomaterials in recent years, listed various pretreatment methods and detection methods of different biomaterials in detail, as well as summarized reported limits of detection, limits of quantitation, and recoveries of different methods. Finally, we prospected further development in detection methods of pyrethroid pesticide residues in human biomaterials.

Wear Simulation on Tibiofemoral Joint Surface of Rotating Hinge Knee Prosthesis / 医用生物力学

Objective To study the wear condition of rotating hinge knee prosthesis (RHKP) during horizontal walking gait, and provide technical references for wear prediction and clinical application of this kind of prosthesis. Methods A finite element wear model of RHKP was established based on the standard ISO 14243, and the simulation results including the wear distribution and mass wear rate of tibiofemoral joint surface were compared with the results from in vitro experiments on the same type of prosthesis. Results The mass wear rate of the polyethylene insert was 26.01 mg/MC (million cycle)from finite element analysis (FEA) and (30.06±1.21) mg/MC from in vitro experiments, and the mass wear rate of the upper surface of polyethene insert from FEA was about 3.3 times that of the lower surface. The wear area obtained by FEA was basically consistent with that obtained by in vitro wear measurement. The main wear area was symmetrically distributed in the middle and back of the upper surface. Conclusions The mass wear rate of RHKP, as a semi-restrictive prosthesis, is obviously higher than that of primary total knee joint prosthesis. More attention should be paid to wear test and evaluation of RHKP.

Biological Basis for ''Five-phase Evolution'' of Malignant Tumors / 中国实验方剂学杂志

China ranks the first in the morbidity and mortality of malignant tumors in the world. Traditional Chinese medicine （TCM） has played a crucial part in preventing recurrence of malignant tumors after surgery， enhancing efficacy and reducing toxicity of radiotherapy and chemotherapy， and promoting the survival of patients with advanced tumors. According to the whole process of tumor occurrence and development and via the long-term clinical practice， we proposed the "deficiency-cold-toxin-blocking-failure evolution theory" of malignant tumors， with depression in the whole process and cancer toxin as the core. The theory is a summary of pathophysiological status at different stages of tumor development based on the disease and syndrome. This paper analyzes the biological basis of the theory. To be specific， we believe that the ''deficiency'' is mainly caused by the tumor immunoediting abnormality and thus the escape of clearance. In addition， the ''cold'' is in line with the metabolic reprogramming of the tumor microenvironment. ''Toxin'' is manifested as the stemness of cancer cells induced by the tumor microenvironment. ''Blocking'' is closely related to the enhanced permeability and retention （EPR） effect of tumor neovasculature. ''Failure'' is exactly the cachexia caused by change of dominant metabolism. ''Depression'' is essentially stress-the accelerated progress of the neuroendocrine system. In combination with clinical practice， we conclude that method of reinforcing healthy Qi and adjusting the balance can help recover tumor immunoediting and restore the immunity to regulate the "deficiency". Moreover， replenishing Qi and warming Yang can correct the tumor metabolic programming to avoid "cold". Removing toxin and reinforcing healthy Qi can reverse tumor cell stemness and thus suppress the ''toxin''. Eliminating the ''blocking'' source can suppress tumor angiogenesis and help regulate the EPR. Regulating Yin and Yang will help relieve the change of dominant metabolism and futile cycle to avoid ''failure''. The method of relieving depression and regulating Qi can relieve neuroendocrine stress and prevent tumor progression， thus alleviating the "depression". Moreover， effect of these methods was tested with effective formulas. This study is expected to lay a foundation for the establishment of a new system for the clinical prevention and treatment of malignant tumors.

Comparison of effectiveness between modified Sugita and modified Shiraki in the treatment of severely concealed penis in children / 中华实用儿科临床杂志

Objective:To compare the effectiveness of modified Sugita and modified Shiraki in the treatment of severely concealed penis in children.Methods:A retrospective study was carried out on 72 children with congenital severely concealed penis, who were treated in the Department of Urology, Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University from September 2016 to June 2021.Among them, 32 cases were treated with modified Sugita (modified Sugita group) and 40 cases were treated with modified Shiraki (modified Shiraki group). There was no significant difference in the age, body mass and body mass index between the 2 groups (all P>0.05). The operation time, increased length of the exposed part of the penis after operation, score of parental satisfaction half a year after operation (obtained by using the Likert scale) and postoperative complications (classified according to the modified Clavien-Dindo classification) were compared between the 2 groups.Measurement data comparison between groups were performed by t test, counting data were analyzed by Chi- square test. Results:The operative time of the modified Sugita group and the modified Shiraki group were (50.00±8.03) min and (40.30±9.27) min, respectively.The operative time was significantly different between 2 groups ( t=4.107, P<0.05). The increased length of the exposed part of the penis after operation was (1.80±0.30) cm in the modified Sugita group and (1.90±0.33) cm in the modified Shiraki group, and no significant difference was found between the 2 groups ( P>0.05). Six months after operation, the parental satisfaction score was (4.60±0.56) points in the modified Sugita group and (4.60±0.59) points in the modified Shiraki group.There was no significant difference in the parental satisfaction score between 2 groups ( P>0.05). In 72 cases, only 5 cases had grade Ⅰ complications.Postoperative complications were also not significantly different between the 2 groups ( P>0.05). Conclusions:After treating severely concealed penis in children with modified Sugita and modified Shiraki, the penis has a good appearance.These two surgeries have high parental satisfaction and low complications.They are easy to implement in clinical practice.The operation time of modified Shiraki is shorter than that of modified Sugita.

Comparison of effectiveness between modified Sugita and modified Shiraki in the treatment of severely concealed penis in children / 中华实用儿科临床杂志

Objective:To compare the effectiveness of modified Sugita and modified Shiraki in the treatment of severely concealed penis in children.Methods:A retrospective study was carried out on 72 children with congenital severely concealed penis, who were treated in the Department of Urology, Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University from September 2016 to June 2021.Among them, 32 cases were treated with modified Sugita (modified Sugita group) and 40 cases were treated with modified Shiraki (modified Shiraki group). There was no significant difference in the age, body mass and body mass index between the 2 groups (all P>0.05). The operation time, increased length of the exposed part of the penis after operation, score of parental satisfaction half a year after operation (obtained by using the Likert scale) and postoperative complications (classified according to the modified Clavien-Dindo classification) were compared between the 2 groups.Measurement data comparison between groups were performed by t test, counting data were analyzed by Chi- square test. Results:The operative time of the modified Sugita group and the modified Shiraki group were (50.00±8.03) min and (40.30±9.27) min, respectively.The operative time was significantly different between 2 groups ( t=4.107, P<0.05). The increased length of the exposed part of the penis after operation was (1.80±0.30) cm in the modified Sugita group and (1.90±0.33) cm in the modified Shiraki group, and no significant difference was found between the 2 groups ( P>0.05). Six months after operation, the parental satisfaction score was (4.60±0.56) points in the modified Sugita group and (4.60±0.59) points in the modified Shiraki group.There was no significant difference in the parental satisfaction score between 2 groups ( P>0.05). In 72 cases, only 5 cases had grade Ⅰ complications.Postoperative complications were also not significantly different between the 2 groups ( P>0.05). Conclusions:After treating severely concealed penis in children with modified Sugita and modified Shiraki, the penis has a good appearance.These two surgeries have high parental satisfaction and low complications.They are easy to implement in clinical practice.The operation time of modified Shiraki is shorter than that of modified Sugita.

A modified scrotoplasty for treating webbed penis in children / 中华实用儿科临床杂志

Objective:To introduce the application of a modified scrotoplasty for children with webbed penis.Methods:Retrospective study was carried out.The treatment results of 58 children with webbed penis in Department of Urology, the Affiliated Xuzhou Children′s Hospital of Xuzhou Medical University from June 2012 to April 2018 were analyzed.A total of 26 children with webbed penis and phimosis were treated with circumcision combined with modified scrotoplasty as modified scrotoplasty group, and 32 children with webbed penis and phimosis were treated with V-Y scrotoplasty as V-Y scrotoplasty group.The curative effect of webbed penis was compared between the two groups.Results:The operation time of V-Y scrotoplasty group and modified scrotoplasty group were (26.0±2.4) min and (28.0±3.2) min; the increased penis length in the horizontal position in the two groups were (0.30±0.06) cm and (0.40±0.06) cm; the score of parents′ satisfaction were (3.80±0.47) scores and (4.70±0.56) scores, there were significant differences in the average operation time, the increased penis length in the horizontal position and the score of parents′ satisfaction between the two groups ( t=2.703, 6.061, 6.652; all P<0.05). There was no significant difference in postoperative complications between the two groups ( P>0.05). Conclusions:Circumcision combined with modified scrotoplasty is used to repair webbed penis, which results in a good postoperative appearance, high parent satisfaction and easy clinical implementation.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

New Strategies of Inhibiting Malignant Tumor Based on Inducing Pyroptosis / 肿瘤防治研究

Pyroptosis is an atypical mode of cell programmed death, which is mainly manifested by pore formation, cell expansion, cell fluid outflow, secretion of inflammatory factors causing inflammatory response, and ultimately leading to cell disintegration after various external stimuli. Pyroptosis was first found in infectious diseases, but later found in the nervous system and cardiovascular system. Recent studies have also found that pyroptosis exists in tumors. It has become one of the hot research topics to explore its role in tumors. At present, studies have proposed that anti-cancer drugs, Chinese medicine monomers and so on can induce the pyroptosis of cancer cells. Therefore, this paper explores the impact molecules related to tumor cell pyroptosis, and summarizes its effect, then proposes two possible new strategies of preventing chemoresistance and regulating metabolic molecules.

Application of umbilical cord blood transplantation in the treatment of paroxysmal nocturnalhemoglobinuria / 中华器官移植杂志

Objective:To explore the feasibility and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).Methods:From May 2014 to December 2019, clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT. The grades were severe ( n=6) and extremely severe ( n=1). The causes were primary PNH ( n=4) and PNH-aplastic anemia (AA) syndrome ( n=3). There were 5 males and 2 females with a median age of 29 (20-47) years, a median weight of 60(50-71) kg and a median time from diagnosis to transplantation of 62.5(7.7-171) months. All of them were accompanied by transfusion dependence. Myeloablative ( n=6) and reduced-intensity ( n=1) pretreatment was offered. The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG. The median number of input nucleated cells was 2.4(1.71-4.28)×10 7/kg and the median number of CD34+ cells 1.58(0.88-3.02)×10 5/kg. Results:Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21) days and a median erythroid engraftment time of 27. Engraftment time of 37(25-101) days for platelets >20×10 9/L and 62(27-157) days for platelets >50×10 9/L. The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%). The severity of GVHD was grade Ⅱ° acute ( n=2) and mild ( n=1). The median follow-up period was 13.5(3-71.4) months. Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage. The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%). Conclusions:With excellent engraftment and survival in the treatment of PNH, UCBT is indicated for patients without HLA full-match donor. PNH-AA syndrome with iron overload may be one of the important prognostic factors.

Comparison of immune reconstitution after peripheral blood stem cell transplantation and umbilical cord blood transplantation / 中华检验医学杂志

Objective:To explore the differences of immune reconstitution between peripheral blood stem cell transplantation and umbilical cord blood transplantation.Methods:A total of 300 patients (aged 18 (8, 33), 163 males and 137 females) with malignant hematological diseases who received allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to March 2020 were enrolled in this study, including 255 cases of umbilical cord blood transplantation and 45 cases of peripheral blood stem cell transplantation. Multicolor flow cytometry was applied to analyze lymphocyte subsets of the percentages and absolute counts in the two donor types and peripheral blood of patients after receiving hematopoietic stem cell transplantation. The differences between the two grafts were compared, and the lymphocyte subsets results were evaluated at 1, 2, 3, 4, 6, 9, 12, and 18 months after transplantation. 18-month disease-free survival (DFS) within the 300 patients under the two transplantation types were retrospectively analyzed.Results:1. The proportion of NKT cells in peripheral blood group was significantly higher than that in cord blood group (2.79% vs 0.24%, P<0.001). 2. The proportion of helper T cells in the UCBT group was higher than that in the PBSCT group, as well as the counts 6 months after transplantation ( P<0.05). 3. The proportion of NK1 cells (3 rd to 9 th month) and count (4 th to 12 th month) in UCBT group were significantly higher than those in PBSCT group ( P<0.05). 4. NKT cells in the UCBT group were lower than those in the PBSCT group (proportion and count) throughout the monitoring process ( P≤0.001). 5. The proportion of DNT cells (within 1 year) and count (within 6 months) in the UCBT group were significantly lower than those in the PBSCT group ( P<0.05). Conclusions:Compared with the peripheral blood stem cell transplantation group, the umbilical cord blood transplantation patients had a faster rate of lymphocyte reconstitution, and patients received umbilical cord blood transplantation had a stronger ability of immune reconstitution and could achieve long-term hematopoiesis.

HNF1A-AS1 inhibits proliferation, migration and invasion of IL-6-induced hemangioma endothelial cells by targeting miR-363-3p / 中华医学遗传学杂志

OBJECTIVE@#To explore the effect of HNF1A-AS1 on the proliferation, migration and invasion of IL-6-induced hemangioendothelial cells (HemEC) and possible mechanism.@*METHODS@#RT-qPCR was used to detect the expression level of HNF1A-AS1 and miR-363-3p in the tumor tissue and adjacent normal skin tissue from 35 patients with hemangioma. Pearson correlation was used to analyze the correlation between the expression of HNF1A-AS1 and miR-363-3p in tumor tissues. HemEC were isolated and cultured in vitro.Dual luciferase reporter gene experiment was used to study the regulatory effect between HNF1A-AS1 and miR-363-3p. IL-6 was added to HemEC transfected with si-NC, si-HNF1A-AS1, si-HNF1A-AS1 and anti-miR-NC, or si-HNF1A-AS1 and anti-miR-363-3p, respectively. CCK-8 method and clone formation experiment were used to detect cell proliferation in each group. Transwell method was used to detect cell migration and invasion in each group. Western blotting was used to detect the expression of Ki67, MMP-2 and MMP-9 proteins in each group.@*RESULTS@#Compared with normal skin tissues, the expression of IL-6 mRNA in hemangioma tissues was increased (P<0.05), and the expression of IL-6 mRNA in the proliferative phase was lower than that in the degenerative phase (P<0.05). Expression of HNF1A-AS1 in hemangioma tissue was increased (P<0.05), while that of miR-363-3p was decreased (P<0.05), and the two were negatively correlated (r=-0.758, P<0.05). HNF1A-AS1 down-regulated the expression of miR-363-3p in HemEC.IL-6 promoted the expression of HNF1A-AS1, OD value, number of colonies, number of migration and invasion of HemEC cells, and the expression of Ki67, MMP-2 and MMP-9proteins (P<0.05), while reduced the expression of miR-363-3p (P<0.05). Down-regulating si-HNF1A-AS1 reduced the IL-6-induced HemEC cell OD value, colony numbers, migration and invasion and the expression of Ki67, MMP-2 and MMP-9 proteins (P<0.05). Down-regulating miR-363-3p attenuated the inhibitory effect of down-regulating si-HNF1A-AS1 on the proliferation, migration and invasion of HemEC cells induced by IL-6 (P<0.05).@*CONCLUSION@#Expression of HNF1A-AS1 is increased in hemangioma tissues. Down-regulating HNF1A-AS1 may inhibit proliferation, migration and invasion of IL-6-induced hemangioma endothelial cells by targeted up-regulation of miR-363-3p.

Mechanism of / 南方医科大学学报

OBJECTIVE@#To explore the mechanism of @*METHODS@#Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry.@*RESULTS@#Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group (@*CONCLUSIONS@#XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.

Current LC-MS-based strategies for characterization and quantification of antibody-drug conjugates / 药物分析学报

The past few years have witnessed enormous progresses in the development of antibody-drug conju-gates (ADCs). Consequently, comprehensive analysis of ADCs in biological systems is critical in sup-porting discovery, development and evaluation of these agents. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a promising and versatile tool for ADC analysis across a wide range of scenarios, owing to its multiplexing ability, rapid method development, as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high, molecular resolution. However, despite this tremendous potential, challenges persist due to the high complexity in both the ADC molecules and the related biological systems. This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.