PRODUCTION OF POLYCLONAL ANTIBODIES AGAINST INDIAN PAPER WASP ROPALIDIA MARGINATA VENOM TOXINS AND THEIR EFFICACY IN THE REVERSAL OF TOXIC EFFECTS

Objective: In this study, albino mice were injected with a sub-lethal dosage of purified wasp Ropalidia Marginata venom toxins to assess the effectiveness of polyclonal anti-venom antibodies.Methods: To neutralize the toxic effects, polyclonal antibodies were generated by immunizing albino mice. The antibody underwent partial purification using ammonium sulphate treatment and octanoic acid precipitation. To detect the presence of antibodies in the antiserum, an immunodouble diffusion test was conducted using Ouchterlony's method (1962). This involved allowing both antigens and antibodies to diffuse radially towards each other from their respective wells. When they reached an equivalence zone, a precipitation complex of antigen and antibody became visible as a concentric band, indicating the development of the combination. To quantitatively determine the amount of antibodies in the antiserum, the equivalency zone approach was used.Results: Experimental mice were injected with a combination containing 400, 800, and 1200 µg of pure antibody, which had been treated serum biomolecules, including metabolic enzymes, completely reversed in the experimental with 40% of the LD50 of wasp venom the elevated serum parameters were glucose, pyruvic acid, lipid, protein and free amino acid, reached to normal (100%) in the treated with 40% of LD50 of the venom and polyclonal treated after 6 h of administration. Anti-serum treatment also successfully normalized the alteration in serum enzyme just after 4h.Similarly, anti-serum treatment also successfully normalized the alteration in serum enzyme just after 4h treated with 40% of LD50 of the venom. Serum ACP content was obtained as 125.35% after 40% of LD50 venom injection, which was get normalized up to 102.81% after 4 h of the anti-venom treatment. Serum ALP content of 114.8% elevation was reversed back to 102.40% after anti-venom treatment. The GPT level significantly reversed up to 102.5%, while it was 130% in the venom-treated mice. A complete reversal was obtained in GPT level, which was obtained as 104.54% in the venom-treated animal. Similarly, LDH which was elevated up to 112.45 % in venom-injected mice was successfully reversed up to 100.25% after anti-venom treatment. Similarly, Ache concentration was fully recovered after anti-venom treatment 6 h, all animals (group B-E) that had received 40% of the LD50 of venom treated with pure antiserum.Conclusion: The venom-injected group showed a complete restoration of serum protein, free amino acid, uric acid, cholesterol, pyruvic acid, total lipid, and glucose level in experimental mice.

Clinical Study on Xingnao Kaiqiao Acupuncture Combined with Acupuncture at Pericardium Meridian Points for the Treatment of Post-stroke Sleep Reversal / 广州中医药大学学报

Objective To observe the clinical efficacy of Xingnao Kaiqiao Acupuncture(with the functions of awakening the brain and opening the orifices)combined with acupuncture at pericardium meridian points in the treatment of post-stroke sleep reversal(PSSR).Methods Sixty patients with PSSR were randomly divided into observation group and control group,30 patients in each group.Both groups were given conventional treatment,the control group was given oral use of Alprazolam,and the observation group was given the combination of acupuncture a at pericardial meridian points,and 10 days of treatment was one course of treatment.After 10 days of treatment,the clinical efficacy of the two groups was evaluated.The changes in the Pittsburgh Sleep Quality Index(PSQI)and Ascens Insomnia Scale(AIS)scores,as well as the Hamilton Depression Scale(HAMD)scores were observed before and after treatment in the two groups.The changes in cortisol levels at 0,8,and 16 o'clock were compared before and after treatment between the two groups.Results(1)After treatment,the PSQI scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the AIS and HAMD scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the AIS and HAMD scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the cortisol level of patients in the two groups at 0,8,and 16 o'clock was significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the cortisol level at 0,8,and 16 o'clock was significantly superior to the control group,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 86.67%(26/30)in the observation group and 80.00%(24/30)in the control group.The efficacy of the observation group was slightly superior to that of the control group,but the difference was not statistically significant(P＞0.05).Conclusion Xingnao Kaiqiao Acupuncture combined with acupuncture at pericardium meridian points for the treatment of PSSR can significantly improve the clinical symptoms of the patients,so as to improve the quality of life of the patients,and the therapeutic efficacy is remarkable.

Mechanism of cinobufagin regulating PI3K/AKT signaling pathway to reverse cisplatin resistance in ovarian cancer A2780/DDP cells / 安徽医科大学学报

Objective @#To investigate the reversal effect and mechanism of cinobufagin (CBG) on cisplatin resist- ance in human ovarian cancer cells . @*Methods @#A2780 cell line and its cisplatin-resistant cell line A2780/DDP are common ovarian cancer cells in clinic , so these two cell lines were selected as the research objects . The cell viabil- ity was detected by cell Counting Kit-8 (CCK-8) assay , and the cell proliferation ability was detected by plate clo- ning and 5-ethynyl-2 ′-deoxyuridine (EdU) assay. Hoechst staining was used to observe cell apoptosis . Cell scratch test and Transwell test were used to evaluate cell migration and invasion ability. Western blot and quantitative reverse transcription PCR (RT-qPCR) were used to detect the protein and mRNA expressions of phosphatidylinosi- tol 3-kinase/protein kinase ( PI3K/AKT) signaling pathway and epithelial-mesenchymal transition ( EMT) . @*Results@#Compared with A2780 cells , the drug resistance indexes of A2780/DDP cells were 5 . 636 , 5 . 864 , 5 . 695 , respectively. After treatment of A2780/DDP cells with CBG (2 , 4 , 6 mg/ml) , the reversal resistance indexes were 1 . 617 , 2. 570 , 3 . 461 , respectively. CBG treatment significantly increased the level of apoptosis and inhibi- ted the proliferation , migration and invasion of the cells in a concentration-dependent manner (P < 0. 05) . Western blot results showed that compared with A2780 cells , the relative ratio of P-PI3K/PI3K and P-AKT/AKT protein levels , as well as the protein expression of N-cadherin , Vimentin , and Snail were higher in the control group (A2780/DDP) cells , while the protein expression of E-cadherin was lower ( t P-PI3K/PI3K = 8 . 115 , t P-AKT/AKT = 17. 62 , t N-cadherin = 6. 126 , t Vimentin = 4. 001 , t Snail = 17. 333 , t E-cadherin = 4. 620 , P < 0. 01) ; As the dose of CBG increased , the protein expression levels of P-PI3K , P-AKT , N-cadherin , Vimentin , and Snail in drug-resistant cells de- creased , while the protein expression level of E-cadherin increased ( FP-PI3K = 268. 5 , FP-AKT = 190. 5 , FN-cadherin = 24. 02 , F Vimentin = 57 . 65 , FSnail = 87 . 24 , FE-cadherin = 135 . 8 , P < 0. 05) . qRT-PCR results showed that with the in- crease of CBG concentration , the mRNA expression levels of PI3K , AKT , N-cadherin , Vimentin and Snail de- creased , while the mRNA expression level of E-cadherin gradually increased ( FPI3K = 101 . 1 , FAKT = 558. 3 , FN-cadherin = 86. 97 , F Vimentin = 105 . 9 , FSnail = 85 . 71 , FE-cadherin = 80. 96 , P < 0. 01) .@*Conclusion @#CBG can reverse cisplatin resistance of ovarian cancer A2780/DDP cell line , and its mechanism may be related to the regulation of PI3K/AKT signaling pathway and inhibition of EMT by CBG.

Efficacy of nutrition therapy with food rich in methionine for treating nonalcoholic fatty liver / Eficacia de la terapia nutricional con alimentos ricos en metionina para el tratamiento de hígado graso no alcohólico

Non-Alcoholic Fatty Liver disease (NAFLD) can lead to Non Alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The treatment for NAFLD involves modification of caloric intake and physical activity. NAFLD has a pro-oxidant nature; therefore, it is logical to suppose that the antioxidant methionine can be used as a treatment for this disease. Aim. This study aimed to evaluate the effect of high-methionine dietary therapy on patients with NAFLD. Materials and methods. A randomized clinical study was conducted over three months. In this study, 121 NAFLD patients participated, and the age of the participants was ≥ 20 years (experimental group included 56 and control group 65), all of whom were randomized and matched by sex, recluted from the ISSSTE hospital in Xalapa, Mexico. The patients were instructed to consume food to cover the recommended methionine daily doses, and the daily amount consumed was calculated. Methionine effect was measured as NAFLD regression and quality of life improvement. Results. Nutritional therapy induced NAFLD regression and diminished central fat accumulation, blood pressure, and the fatty liver index. Some parameters, such as liver enzymes, did not changed. The quality of life of patients improved after treatment. Conclusions. In this study, we show a hepatoprotective effect induced only in three months of chances in the diet, thus, a longer diet may generate more relevant benefits in the resistant parameters of our study(AU)

La enfermedad del hígado graso no alcohólico (NAFLD) puede conducir a la esteatohepatitis no alcohólica (NASH), la cirrosis y el cáncer de hígado. El tratamiento para NAFLD es la modificación de la ingesta calórica y la actividad física. Debido a que NAFLD tiene una naturaleza pro-oxidante; es lógico suponer que el antioxidante metionina puede utilizarse en el tratamiento de esta enfermedad. Objetivo. el presente trabajo evaluó el papel de la terapia nutricional con alimentos ricos en metioninaen pacientes con NAFLD. Materiales y Métodos. Se realizó un ensayo clínico aleatorizado durante tres meses. Participaron en el estudio 121 pacientes con NAFLD con edad ≥ 20 años (56 en el grupo experimental y 65 en el control), todos aleatorizados y pareados por sexo, reclutados de la Clínica Hospital ISSTE en la ciudad de Xalapa, México, en el año 2015. Se instruyó a los pacientes en consumir los alimentos hasta completar la dosis diaria recomendada de metioninay se calculó la cantidad diaria consumida. Su efecto se midió como la regresión de NAFLD y la mejora de la calidad de vida. Resultados. La terapia nutricional retrocedió NAFLD; disminuyó la acumulación de grasa central, la presión arterial y el índice de hígado graso. Algunos parámetros, como las enzimas de la función hepática, no se modificaron con el tratamiento. Otro parámetro fue la mejora de la calidad de vida de los pacientes tratados. Conclusiones. En este trabajo mostramos un impacto hepatoprotector producido con tan solo tres meses de cambios en la dieta, por lo que una dieta más prolongada podría generar beneficios aún más significativos en los parámetros resistentes en nuestro protocolo(AU)

Natural reversal of mandibular condylar cartilage histological damage caused by chronic unpredictable moderate stress in rats / 口腔疾病防治

Objective @#To investigate the histological damage recovery of temporomandibular joint condylar cartilage caused by chronic unpredictable moderate stress, aiming to provide an experimental basis for the prevention and treatment of temporomandibular disorder.@*Methods @#This animal experiment was approved by the Laboratory Animal Ethical Inspection, School of Stomatology, The Fourth Military Medical University (No. 2020081). 60 male SD rats were randomly divided into control group, stress group, and 2-, 4- and 8-week post-stress recovery groups. Rats were subjected to chronic unpredictable moderate stress (CUMS) for 8 weeks including damp sawdust for 24 hours, tilted cage for 12 hours, noise for 4 hours, light/dark cycle reversal, water immersion, tail clamp, and restraint stress. The serum assessment, behavioral tests, histological and ultrastructural observation were performed 2-, 4- and 8-weeks after stress factors were removed. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined with ELISA. The sucrose preference test (SPT) and the forced swim test (FST) were used to assess the depressive-like behavior. The expression level of interleukin-1α (IL-1α) and matrix metalloproteinases-3 (MMP-3) were determined by Immunohistochemistry and Western blot.@*Results @#At the end of 8 weeks of CUMS, the serum levels of CORT and ACTH were significantly higher in stress group compared with control group (P<0.01). The sucrose preference decreased significantly and the immobility time increased significantly in the stressed rats compared with those in the control group, indicating a successful establishment of CUMS. The condylar cartilage showed significant degenerative changes, with disorganized collagen fibers and reduced proteoglycan synthesis on the cartilage surface. IL-1α and MMP-3 were expressed in the intracellular and extracellular matrix of the condylar cartilage, and their expression levels were increased (P<0.01). After 2 weeks of stress removal, the serum levels of CORT and ACTH were decreased but higher than control group (P<0.01), and behavioral changes were still different from the control group (P<0.01); the loosened collagen fibers could still be seen on the surface of condylar cartilage, and some free cell areas were visible within the proliferative layer; additionally, IL-1α and MMP-3 expression in the condyle was reduced in all layers of cartilage when compared with the stress group, but was still higher than in the control group (P<0.01). After 4 weeks of stress removal, the serum levels of CORT and ACTH changes returned to normal levels and behavioral changes were still different from control group (P<0.05); a few collagen fibers could be seen on the surface of the condylar cartilage and the expressions of IL-1α and MMP-3 decreased significantly compared with the stress group (P<0.01), with the similar level of IL-1α (P>0.05) and higher expression of MMP-3 comparing with the control group (P<0.01). After 8 weeks of stress removal, behavioral changes returned to normal levels, with no statistically significant differences compared with the control group (P>0.05). The condylar collagen fibers increased and showed a corrugated pattern, and no serious subchondral bone damage as well as irreversible damage occurred. Both of the expression levels of IL-1α and MMP-3 approached those of the control group after 8 weeks of stress removal (P>0.05). @*Conclusion@# The behavioral changes and condylar cartilage damage caused by CUMS could be self-repaired. The decline in IL-1α and MMP-3 expression may be one of the intrinsic mechanisms of this self-repair process.

Sex Reversal Syndrome (SRS): A case of SRY-Positive 46,XX Testicular Disorder / Journal of the ASEAN Federation of Endocrine Societies

@#We report a case of an SRY-positive 46,XX Indian male who presented with small testis and phallus, poor beard and mustache development and gynecomastia at the age of 24 years. He was biochemically found to have hypergonadotropic hypogonadism. He had 46,XX karyotype and Quantitative Fluorescence-PCR (QF-PCR) identified the SRY gene on the X chromosome. SRY-positive 46 XX male SRS cases usually present as phenotypically male since birth but develop features of hypogonadism, poor testicular development, and infertility after puberty. Infertility, hypogonadism, external genital development, and psychological distress are the major concerns during the management of the patients. Testosterone therapy for hypogonadism, artificial reproductive technologies for fertility, surgical repair of hypospadias/cryptorchidism/under-virilized genitalia and psychological and genetic counseling are helpful for proper management of the patients.

Research progress on cirrhosis reversal and recompensation / 中华肝脏病杂志

Previously, liver lesions in cirrhosis were considered irreversible, especially because the condition aggravated gradually after entering the decompensated phase, thus making it difficult to return to the compensated phase. At present, more and more evidence shows that some patients with decompensated liver cirrhosis can be recompensated after the cause is controlled and complications are managed. This article explores the research progress related to LC reversal and recompensation from three aspects: liver histopathology, liver function, and clinical complications.

Histopathological evaluation of cirrhosis reversal / 中华肝脏病杂志

A normal liver can develop cirrhosis through long-term and repeated stimulation from various etiologies. Histological manifestations like the collapse of hepatic lobular structure (including microvascular structure) and the formation of pseudolobules can lead to portal hypertension and even decompensated cirrhosis. More and more evidence suggests that effective etiological treatment can not only delay but also reverse the progression of cirrhosis. The mechanism of cirrhosis reversal mainly includes the degradation of extracellular matrix, hepatocyte regeneration, and hepatic lobular remodeling. The "gold standard" for the evaluation of cirrhosis reversal at present is still a liver biopsy. Therefore, the histopathological evaluation of cirrhosis reversal is very important for determining the disease's prognosis, efficacy, and mechanism of exploration.

Application of Laparoscopic Surgery in Ileostomy Reversal / 肿瘤防治研究

In colorectal cancer surgery, loop ileostomy is sometimes necessary to prevent anastomotic leakage. Although ileostomy reversal is relatively simple, postoperative complication is inevitable. In recent years, laparoscopic surgery has been gradually applied in ileostomy reversal due to its small trauma, fast recovery, and low complications, exhibiting satisfactory short-term outcomes. This review analyzes the application of the laparoscopic technique in ileostomy surgery and explores the potential of total laparoscopic surgery, aiming to provide a new perspective for the clinical application of laparoscopic ileostomy reversal.

Vasectomy reversal in China during the recent decade: insights from a multicenter retrospective investigation / 亚洲男科学杂志(英文版)

To date, there is little information about the demography of vasectomy reversal (VR) patients or the factors currently influencing VR effectiveness in China, especially after the universal two-child policy was released in 2015. In this research, demographic data and perioperative medical records of VR patients were extracted from seven major hospitals in different provinces or municipalities of China. Meanwhile, a telephone survey of the patients was conducted to collect follow-up information. Eventually, 448 VR cases from the past 13 years were included. The results were analyzed by stratified comparison to investigate factors that can influence postoperative vas deferens patency and pregnancy rate. Appropriately statistical methods were used, and all of the protocols were approved by the Ethics Committees of the institutes in this research. The results showed that the annual operation volume of VR quadrupled after the two-child policy was implemented. Nonmicrosurgery and a long duration of vasectomy were significantly associated with a lower patency rate. A follow-up survey showed that the general postoperative pregnancy rate was 27.2%. For female partners over the age of 35 years, the postoperative pregnancy rate showed a more severe decline, but only 35.5% of them had been given a fertility examination before their husbands' VR surgery. Our work revealed that more patients in China have been demanding VR in recent years. High-quality microsurgery and a short duration of vasectomy are crucial for restoring patency by VR. Clinical andrologists should perform a preoperative fertility evaluation of the patients' female partners.

Recent advances in anticoagulation reversal of oral anticoagulant-associated intracerebral hemorrhage / 中国医师杂志

With the progressive aging of the population and the attendant increase in oral anticoagulants (OAC) use, studies have shown that the risk of intracerebral hemorrhage (ICH) in patients receiving OAC treatment is 7-10 times higher than that in patients not receiving OAC treatment. Moreover, compared to general ICH patients, patients with oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) exhibit larger ICH-volumes, have higher mortality, and importantly have a greater frequency of hematoma expansion (HE). Hence, aggressive and specific medical management to reverse anticoagulation irrespective of vitamin K antagonists (VKA) or new oral anticoagulants (NOAC) used is essential to reduce HE rates and thereby to potentially influence clinical outcomes. This paper aims to compare and analyze the history and latest progress of reversal scheme in different OAC, so as to provide a theoretical basis for patients with OAC-ICH to pick a more reasonable reversal scheme.

Pais e filhos: uma rua de mão dupla / Parents and children: a two-way street / Padres e hijos: una calle de dos sentidos

Neste artigo são discutidos alguns aspectos da relação pais-filhos, focados na importância do filho no desenvolvimento dos pais. A relação filho-adulto e pais é abordada tanto em seu sentido criativo como complicado, gerador de patologia. A relação filhos-pais é associada a outra mão da mesma rua onde a psicologia bastante tem discutido a relação pais-filhos. Daí o título: "Pais e filhos: uma rua de mão dupla". A compreensão simbólica do ditado popular "filho criado, trabalho dobrado" é buscada. Esse "maior trabalho" dado pelo "filho criado" é associado ao trabalhoso processo de recolhimento necessário que os pais precisam fazer da depositação-projeção dos papéis parentais arquetípicos de filho, Fm e Fp, sobre os filhos. Também são discutidos a função da idealização cruzada e o consequente jogo de poder cruzado entre filhos e pais. Algumas complicações desse processo de retirada das depositações-projeções pelos pais sobre os filhos são enfocadas pela sua importância clínica, a saber: os riscos dos avós, o risco da inversão de papéis entre pais e filhos e a adolescência tardia. É chamada a atenção para a importância do tema, uma vez que, com o aumento da vida média, a população com mais idade cresceu e sua problemática precisa ser mais bem compreendida.

The author discusses some aspects of parents-children relationship, the so called "double way street". She emphasizes the importance of this theme because psychology has discussed enough parents-children relationship but children-parents relationship has been put aside. Archetypal parental-roles and crossed projections between children and parents are discussed as being an important aspect of the complexity of this issue, due to their clinical importance. Some process disorders are focused like: grand-parents' risks, archetypal parental roles inversion between parents and children and tardy adolescence. The symbolic understanding of the popular saying "Raised children, hell breaks lose" is sought in this article. The troubles with the "raised child" is linked to the painful process parents have to go through with projection archetypal parental roles of the child, Cm Cf over the children.

En este artículo se discuten algunos aspectos de la relación padre-hijo, enfocándose en la importancia del niño en el desarrollo de los padres. Se aborda la relación hijo-adulto y padres tanto en su sentido creativo como en su sentido complicado, generador de patologías. La relación padre-hijo está asociada con otra mano en la misma calle donde la psicología ha discutido durante mucho tiempo la relación padre-hijo. De ahí el título: "Padres e hijos: una calle de dos sentidos". Se busca la comprensión simbólica del dicho popular "hijo criado, trabajo duplicado". Este "trabajo mayor" dado por el "hijo criado" está asociado al laborioso proceso de recolección necesaria que los padres deben hacer a partir del depositación-proyección de los roles parentales arquetípicos del hijo, Hm e Hp (hijo de la madre e hijo del padre), en sus hijos. También se discute el papel de la idealización cruzada y el juego de poder cruzado resultante entre hijos y padres. Se destacan, por su importancia clínica, algunas complicaciones de este proceso de eliminación de depositaciones-proyecciones de los padres sobre sus hijos, a saber: los riesgos de los abuelos, el riesgo de inversión de roles entre padres e hijos y la adolescencia tardía. Se llama la atención sobre la importancia del tema, ya que, con el aumento del promedio de vida, la población de mayor edad ha crecido y es necesario comprender mejor sus problemas.

Reconstrucción poscirugía de Hartmann / Stoma reversal after the Hartmann's procedure

RESUMEN Antecedentes: la reconstrucciónn del tránsito intestinal luego de una operación de Hartmann es un procedimiento habitualmente complejo y con alta morbilidad. Objetivo: analizar la tasa de reconstrucción después de la cirugía de Hartmann y resultados posoperatorios en nuestra experiencia. Material y métodos: análisis retrospectivo de pacientes a los que se les practicó la reconstrucción del tránsito intestinal posterior a una cirugía de Hartmann en un período 16 años. Revisamos la bibliografía y nuestra base de datos. Luego traspasamos la información disponible a una grilla de datos construida con variables habitualmente analizadas en la literatura. Finalmente, analizamos los resultados mediante medidas básicas de tendencia central. Resultados: en 16 años realizamos 92 operaciones de Hartmann, de las cuales 69 (75%) llegaron a la reconstrucción. Edad promedio: 58 años. El 52% de los pacientes fueron hombres. La operación de Hartmann fue de urgencia en el 48% y 58% resultaron malignas. Tiempo transcurrido hasta la reconstrucción: en promedio, 9 meses, y el 90% (N 62) de los casos se realizó por vía laparoscópica. Morbilidad general 38% y ajustada a los grados III y IV de Clavien-Dindo fue 11,5%. No hubo mortalidad. Conclusión: los resultados obtenidos son semejantes a los publicados y nuestra experiencia nos motiva a continuar eligiendo el abordaje laparoscópico.

ABSTRACT Background: Background: Stoma reversal after Hartman's operation is usually a complex procedure and is associated high morbidity. Objective: To analyze the rate of reversal after the Hartmann's procedure and the postoperative outcomes in our experience. Material and methods: We conducted a retrospective analysis of patients undergoing reversal after the Hartmann's procedure over a 16-year period with review of the literature and of our database and transferred the available information to a data grid constructed with variables commonly analyzed in the literature. Finally, we analyzed the results using basic measures of central tendency. Results: Over a 16-year period, we performed 92 Hartmann's operations; 69 (75%) reached the reversal stage. Mean age was 58 years and 52% were men. Forty-eight percent of the Hartmann's procedures were emergency surgeries and 58% were due to cancer. Mean time to reversal was 9 months and 90% (n = 62) were laparoscopic procedures. Overall morbidity and adjusted for complications grade III and IV of the Clavien-Dindo classification were 38% and 11.5%, respectively. None of the patients died. Conclusion: The results obtained are similar to those published and our experience motivates us to continue choosing the laparoscopic approach.

Abordaje abierto versus laparoscópico para la reconstitución del tránsito luego de la cirugía de Hartmann: resultados de una experiencia de 10 años / Open versus laparoscopic approach for Hartmann's reversal: results of a 10-year retrospective cohort study

Resumen Objetivo: El objetivo de este estudio es comparar los resultados perioperatorios del abordaje abierto (AA) con el abordaje laparoscópico (AL) para la reconstitución de tránsito (RT), y determinar factores de riesgo asociados a morbilidad posoperatoria. Material y Métodos: Se estudiaron pacientes consecutivos sometidos a RT entre enero de 2007 y diciembre de 2016 en nuestro centro. Se excluyeron aquellos con grandes hernias incisionales que requirieran reparación abierta simultánea. Se consignaron variables demográficas y perioperatorias, y se compararon ambos grupos. Además, se realizó una regresión logística para la identificación de factores de riesgo asociados a morbilidad posoperatoria en la serie. Resultados: Se realizaron 101 RT en el período. Se excluyeron 14 casos por hernia incisional, por lo que se analizaron 87 casos (46 AA y 41 AL). Diez pacientes en el grupo AL (24,4%) requirieron conversión, principalmente por adherencias. La morbilidad total de la serie fue de 36,8%, siendo mayor en el AA (50% vs 21,9%, p = 0,007). Hubo una filtración anastomótica en cada grupo. La estadía posoperatoria fue de 5 (3-52) días para el AL y 7 (4-36) días para el AA (p < 0,001). En la regresión logística, sólo el AA fue un factor de riesgo independientemente asociado a morbilidad posoperatoria (OR 2,89, IC 95% 1,11-7,49; p = 0,029). Conclusión: El abordaje laparoscópico se asocia a menor morbilidad y estadía posoperatoria que el abordaje abierto para la reconstitución del tránsito pos-Hartmann. En nuestra serie, el abordaje abierto fue el único factor independientemente asociado a morbilidad posoperatoria.

Introduction: Hartmann's reversal (HR) is considered a technically demanding procedure and is associated with high morbidity rates. Aim: The aim of this study is to compare the perioperative results of the open approach (OA) with the laparoscopic approach (LA) for HR, and to determine the risk factors associated with postoperative morbidity. Material and Methods: Consecutive patients undergoing HR between January 2007 and December 2016 at a university hospital were included. Patients with large incisional hernias that required an open approach a priori were excluded from the analysis. Demographic and perioperative variables were recorded. Analytical statistics were carried out to compare both groups, and a logistic regression was performed to identify risk factors associated with postoperative morbidity in the series. Results: A hundred and one HR were performed during the study period. Fourteen cases were excluded due to large incisional hernias, so 87 cases (46 OA and 41 LA) were analyzed. Ten patients in the LA group (24.4%) required conversion, mainly due to adhesions. The total morbidity of the series was 36.8%, being higher in the OA group (50% vs. 21.9%, p = 0.007). There was one case of anastomotic leakage in each group. The length of stay was 5 (3-52) days for LA and 7 (4-36) days for OA (p < 0.001). In the logistic regression, the OA was the only independent risk factor associated with postoperative morbidity in HR (OR 2.89, IC 95% 1.11-7.49; p = 0.029). Conclusion: A laparoscopic approach is associated with less morbidity and a shorter length of stay compared to the open approach for Hartmann's reversal. An open approach was the only factor independently associated with postoperative morbidity in our series.

Light-controllable charge-reversal nanoparticles with polyinosinic-polycytidylic acid for enhancing immunotherapy of triple negative breast cancer

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Co-delivery of photosensitizer and diclofenac through sequentially responsive bilirubin nanocarriers for combating hypoxic tumors

Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1α (HIF-1α) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo.

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

Interpretation to the European clinical guidelines of psychological interventions for Tourette syndrome and other tic disorders in 2021 / 中华实用儿科临床杂志

Tic disorders are one of the common neurodevelopmental disorders in children, which are mainly managed by pharmacological and non-pharmacological treatment.Psychological interventions belong to the non-pharmacological treatment, which, however, have not yet been fully recognized and understood in China.The analyses on clinical effectiveness and availability to pediatric patients are limited.This study aims to interpret the clinical guidelines of psychological interventions for Tourette syndrome and other tic disorders by European Society for the Study of Tourette syndrome in the journal of European Child and Adolescent Psychiatry in 2021, aiming to provide reference for the psychological interventions of tic disorders in China.

Guidelines on muscle relaxants and reversal in anaesthesia / 中华麻醉学杂志

Objectives:To provide an update to the 1999 French guidelines on " Muscle relaxants and reversal in anaesthesia" , a consensus committee of sixteen experts was convened.A formal policy of declaration and monitoring of conflicts of interest (COI) was developed at the outset of the process and enforced throughout.The entire guidelines process was conducted independently of any industrial funding (i.e.pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE ?) system to assess the quality of the evidence on which the recommendations were based.The potential drawbacks of making strong recommendations based on low-quality evidence were stressed.Few of the recommendations remained ungraded. Methods:The panel focused on eight questions: (1) In the absence of difficult mask ventilation criteria, is it necessary to check the possibility of ventilation via a facemask before muscle relaxant injection? Is it necessary to use muscle relaxants to facilitate facemask ventilation? (2) Is the use of muscle relaxants necessary to facilitate tracheal intubation? (3) Is the use of muscle relaxants necessary to facilitate the insertion of a supraglottic device and management of related complications? (4) Is it necessary to monitor neuromuscular blockade for airway management? (5) Is the use of muscle relaxants necessary to facilitate interventional procedures, and if so, which procedures? (6) Is intraoperative monitoring of neuromuscular blockade necessary? (7) What are the strategies for preventing and treating residual neuromuscular blockade? (8) What are the indications and precautions for use of both muscle relaxants and reversal agents in special populations (e.g.electroconvulsive therapy, obese patients, children, neuromuscular diseases, renal/hepatic failure, elderly patients)? All questions were formulated using the Population, Intervention, Comparison and Outcome (PICO) model for clinical questions and evidence profiles were generated.The results of the literature analysis and the recommendations were then assessed using the GRADE ? system. Results:The summaries prepared by the SFAR Guideline panel resulted in thirty-one recommendations on muscle relaxants and reversal agents in anaesthesia.Of these recommendations, eleven have a high level of evidence (GRADE 1±) while twenty have a low level of evidence (GRADE 2±). No recommendations could be provided using the GRADE ? system for five of the questions, and for two of these questions expert opinions were given.After two rounds of discussion and an amendment, a strong agreement was reached for all the recommendations. Conclusion:Substantial agreement exists among experts regarding many strong recommendations for the improvement of practice concerning the use of muscle relaxants and reversal agents during anaesthesia.In particular, the French Society of Anaesthesia and Intensive Care (SFAR) recommends the use of a device to monitor neuromuscular blockade throughout anaesthesia.

Upside down words as initial clinical presentation of an underlying acute ischemic stroke

@#We report a diabetic patient who was diagnosed with an acute stroke who presented with a 3-day history of difficulty of reading, described as the words were turned upside down, as if the words were inverted horizontally with associated right homonymous hemianopia and multiple higher cortical function deficits (alexia without agraphia, achromatopsia, prosopagnosia). He has poorly controlled diabetes and hypertension. Cranial magnetic resonance imaging (MRI) revealed an acute infarct on the left posterior cerebral artery territory. The patient was managed as an acute ischemic stroke and follow up after 6 months revealed improvement of the visual field cut but with persistence of the higher cortical function deficits. To the best of our knowledge, we report the first rare occurrence reversal of vision metamorphopsia described as inverted words as the sole initial presentation of an underlying stroke.