Visión general de las várices gástricas y su tratamiento / Overview of gastric varices and their treatment

Las várices gástricas (VG) son un complejo de colaterales vasculares entre la circulación portal y sistémica, condición que se desarrolla como resultado de la presión elevada en el sistema venoso portal. Se encuentran en el 20 % de los pacientes con cirrosis, y son menos frecuentes que las várices esofágicas. Según la clasificación de Sarin, las VG se dividen en cuatro tipos según su ubicación en el estómago y su relación con las várices esofágicas (GOV1, GOV2, IGV1 e IGV2). Entender su hemodinámica con respecto a las rutas de drenaje de las VG es importante para guiar su tratamiento.

Gastric varices (GV) are a complex of vascular collaterals between portal and systemic circulation, a condition that develops as a result of elevated pressure in the portal venous system. They are found in 20% of patients with cirrhosis, and are less common than esophageal varices. According to the Sarin classification, GV are divided into four types based on their location in the stomach and their relationship with esophageal varices (GOV1, GOV2, IGV1, and IGV2). Understanding their hemodynamics with respect to GV drainage routes is important to guide their treatment.

ALPPS en cáncer colorrectal sincrónico en tiempos de COVID-19 / ALPPS in synchronous colorectal cancer in times of COVID-19

RESUMEN Durante la pandemia por SARS-CoV-2 evidenciamos un aumento de la morbimortalidad secundario a procedimientos quirúrgicos. Se estima una mortalidad a los 30 días del 19,1% en cirugías programadas y del 26% en procedimientos quirúrgicos de emergencia, y alrededor de la mitad de los pacientes que se someten a cirugía estando infectados con SARS-CoV-2 experimentan complicaciones pulmonares posoperatorias. Los tratamientos oncológicos sufrieron deficiencias en nuestro país debido a las limitantes secundarias a la emergencia sanitaria, en cuanto a capacidad de internación e implementación de los tratamientos quimioterápicos. Informamos la primera cirugía de ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) realizada en el nordeste argentino en una paciente con metástasis colorrectales múltiples en contexto de la pandemia por SARS-CoV-2, con buenos resultados.

ABSTRACT During the SARS-CoV-2 pandemic, we observed an increase in morbidity and mortality secondary to surgical procedures. The mortality rate for elective surgery is estimated at 19.1% and is 26% for emergency procedures. Additionally, approximately half of patients who undergo surgery while infected with SARS-CoV-2 experience postoperative pulmonary complications. Due to limitations caused by the health emergency, cancer treatments in our country have been affected in terms of hospitalization capabilities and implementation of chemotherapy treatments. We report the first ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) procedure performed in northeastern Argentina on a patient with multiple colorectal metastases during the SARS-CoV-2 pandemic, with successful outcomes.

Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress / 药学学报

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

What is the applicability of tubal ligation with the vaginal natural orifice transluminal endoscopic surgery technique and its value in patient comfort?

SUMMARY OBJECTIVE: The aim of this study was to observe the feasibility of the tubal/adnexal approach using vaginal natural orifice transluminal endoscopic surgery and compare its contribution with surgeon ergonomics and postoperative patient comfort with that of conventional laparoscopy. METHODS: We completed this study retrospectively with 47 patients. Patients were followed at their postoperative first month. We analyzed the usability of the vaginal natural orifice transluminal endoscopic surgery method over conventional laparoscopy by comparing the demographics, surgical data, and postoperative findings collected between the two groups. RESULTS: Patients in the conventional laparoscopy group were older (39.1±3.3 years) than those in the vaginal natural orifice transluminal endoscopic surgery patient group (p=0.005). Pain intensity 24 h after surgery was lower in the vaginal natural orifice transluminal endoscopic surgery group (p=0.003), while sexual function and dyspareunia did not differ between the two groups in the first month. Patients in the vaginal natural orifice transluminal endoscopic surgery group were more relieved about painlessness and the comfort it brought than the conventional laparoscopy group (p=0.027, χ2=12.56). CONCLUSION: Patients subjected to the vaginal natural orifice transluminal endoscopic surgery procedure showed higher levels of satisfaction, less postoperative pain, and greater comfort than those subjected to conventional laparoscopy.

Ligadura de la arteria lingual: estrategia para hemorragias por lesión de la arteria en la base de la lengua: informe de dos casos / Lingual Artery Ligation: Strategy for Bleeding from Artery Injury at the Base of the Tongue: Report of Two Cases

La hemorragia producida por lesión de la arteria lingual en la base de la lengua por cirugías o por tumores es infrecuente. La mayor frecuencia en la indicación de abordajes transorales para tratar diferentes patologías que afectan la orofaringe requiere que el equipo quirúrgico tenga experiencia en el manejo de esta complicación. La ligadura de la arteria lingual en el cuello es una técnica quirúrgica muy eficaz para solucionar la hemorragia, pero es importante conocer las posibles variantes anatómicas que puede tener la arteria en su trayecto cervical. Debido a su baja incidencia se propone como objetivo describir dos casos clínicos de pacientes que tuvieron hemorragias graves por lesión de la arteria lingual en la base de la lengua, producidas por daño quirúrgico y por erosión por tumor. [AU]

The bleeding caused by injury to the lingual artery at the base of the tongue due to surgery or tumors is infrequent. The increased frequency in the indication of transoral approaches to treat different pathologies affecting the oropharynx requires the surgical team to have experience in managing this complication. Ligation of the lingual artery in the neck is a very effective surgical technique to solve the bleeding; however, it is essential to be aware of the possible anatomical variants the artery may have in its cervical trajectory. Due to its low incidence, we propose to describe two clinical cases of patients who had severe bleeding due to a lesion of the lingual artery at the base of the tongue, produced by surgical damage and erosion due to a tumor. [AU]

Development of a low-cost simulator for training in hemorrhoidal ligation

Introduction: Rubber band ligation is a minimally invasive outpatient hemorrhoid treatment with low cost, low complication rates, and rapid realization. It is performed with the aid of an anoscope and uses a rubber ring that surrounds the hemorrhoidal nipple, causing compression of the vascular structures of the tissue, leading to necrosis and remission of the hemorrhoid. No device for training this essential procedure for treating this pathology has been identified in the literature. Therefore, we aim to develop a low-cost simulator for training hemorrhoidal rubber ligation. Methods: The model was constructed using PVC pipe wrapped in neoprene fabric. Hemorrhoidal nipples and the pectineal line were also simulated using fabric and sewing threads. The procedure is performed with conventional anoscope and ligature forceps. Conclusion: The device in question is a low-cost simulation model designed to train the skills required to perform a rubber band ligation and review the basic anatomy of the anal canal during anoscopy. Given these qualities, the model can be used for academic training due to its low cost and simplicity of application. (AU)

Cirugía de desfuncionalización de glándulas salivales mayores en sialorrea masiva / Major salivary gland defunctionalization surgery in massive sialorrhea

Introducción: La sialorrea es la pérdida involuntaria de saliva de la boca, ya sea debido a la producción excesiva de saliva o disminución de la frecuencia de deglución. Se habla de sialorrea patológica cuando persiste más allá de los 4 años de edad. Además de las implicaciones sociales, cambios de ropa frecuentes, puede provocar neumonías por aspiración y deshidratación. El manejo de la sialorrea requiere una evaluación completa con un enfoque de equipo multidisciplinario para el tratamiento, que incluye terapias no farmacológicas, farmacológicas y quirúrgicas. Objetivo: Presentar resultados quirúrgicos y farmacológicos en el tratamiento de sialorrea masiva. Material y Método: Se realizó revisión de historias clínicas de 7 pacientes portadores de sialorrea masiva. Todos los pacientes incluidos fueron refractarios a tratamiento médico. El diagnóstico fue obtenido por un equipo multidisciplinario. Se les realizó desfuncionalización quirúrgica y farmacológica de glándulas salivales. Se les aplicó Escala de Severidad (DSS) y escala de frecuencia (DFS), previo a cirugía y posterior a procedimiento hasta el año. Resultados: Mejoría clínica subjetiva posterior a desfuncionalización quirúrgica con disminución de DSS y DFS. Disminución promedio de baberos a 10/día. Conclusión: Los resultados obtenidos son buenos, si se consideran las escalas DSS, DFS y el número de baberos al día, que son mediciones tanto subjetivas y objetivas respectivamente.

Introduction: Massive Sialorrhea is the involuntary loss of saliva from the mouth, either due to excessive saliva production or decreased swallowing frequency. We speak of pathological sialorrhea when it persists beyond 4 years old. In addition to the social implications and frequent clothing changes. It can cause aspiration pneumonia and dehydration. Treatment for sialorrhea requires a comprehensive evaluation with a multidisciplinary team approach. Including non-pharmacological, pharmacological, and surgical therapies. Aim: Presentation of the results of surgical defunctionalization of the salivary glands plus injection of Botulinum Toxin in the treatment of massive sialorrhea. Material and Method: A review of the clinical records of 7 patients with massive sialorrhea was carried out. All included patients were refractory to medical treatment. The diagnosis was obtained by a multidisciplinary team. Surgical and pharmacological dysfunctionalization of salivary glands was performed. Severity Scale (DSS) and Frequency Scale (DFS) were applied before surgery and after the procedure up to a year. Results: Subjective clinical improvement after surgical defunctionalization with decreased SHD and DFS. Average decrease in bibs to 10/day. Conclusion: The evaluated strategy presented similar benefits with respect to the literature. The SHD and DFS scales and the number of bibs per day are both subjective and objective measurements, respectively, and allow the clinical improvement and quality of life of patients undergoing surgery to be evaluated individually.

Tolérance et efficacité de la ligature des varices œsophagiennes au Centre Hospitalier Universitaire Andrainjato, Fianarantsoa, Madagascar / Tolerance and efficacy of esophageal varices ligation at the Andrainjato teaching hospital, Fianarantsoa, Madagascar

Introduction: La ligature des varices œsophagiennes constitue un des piliers de la prise en charge de l'hémorragie digestive par rupture des varices œsophagiennes. Cette étude a pour objectif d'analyser la tolérance et l'efficacité de la ligature des varices œsophagiennes dans un échantillon de patients au Centre Hospitalier Universitaire Andrainjato Fianarantsoa, Madagascar. Méthodes: Une étude prospective, observationnelle longitudinale sur une période de 21 mois (mois de janvier 2018 au mois d'août 2019) a été réalisée. Le test de Khi carré a été utilisé pour déterminer les corrélations (SPSS® v22). Résultats : Trente-et-un patients à prédominance masculine (sex ratio 1,5), âgés de 43,0 ± 9,0 ans, ont été retenus et 67 séances de ligatures de varices œsophagiennes ont été effectuées. La prophylaxie secondaire était l'indication de la ligature dans 96,8 % (n = 30) des cas. Les varices œsophagiennes étaient de grade III dans 64,4 % (n = 20) des cas. Toutes les ligatures ont été réalisées sous anesthésie générale. Le nombre de bandes élastiques utilisées était de 3,4 ± 1,1. La bonne tolérance de la ligature élastique était de 97,0 % (n = 65) lors de la procédure et de 58,0 % (n = 39) en post-procédure. La douleur thoracique post-procédure était observée dans 65,7 % (n = 44) des cas. L'éradication était obtenue après 3 séances dans 6,45 % (n = 2) des cas et 58,1 % (n = 18) étaient en cours d'éradication après 1,7 ± 0,9 séances. Conclusion : Cette étude a pu déterminer que la ligature des varices œsophagiennes est une technique bien tolérée et efficace dans la prévention de l'hémorragie digestive par rupture des varices œsophagiennes malgré certains inconvénients postopératoires

Efficacy and safety of three minimally invasive endoscopic procedures for the treatment of internal hemorrhoids / 中华消化内镜杂志

In order to evaluate the safety and effectiveness of endoscopic hemorrhoids treatment, a retrospective analysis was conducted on data of 166 patients with grade I to Ⅲ hemorrhoids who underwent endoscopic treatment in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to June 2020 with complete follow-up data. There were 35 cases in the simple sclerotherapy group, 104 cases in the simple ligation group, and 27 cases in the ligation combined sclerotherapy group. The results showed that, no serious complications occurred in the 3 groups after surgery. In the simple ligation group and the ligation combined with sclerotherapy group, the incidence of postoperative anal pain [35.6% (37/104) and 33.3% (9/27), respectively,] and anal pendant distension [70.2% (73/104) and 70.4% (19/27), respectively] were higher, but symptoms could be tolerated or relieved after simple treatment. The satisfaction of patients in the 3 groups was all more than 90% before discharge, and the degree of operation acceptance was more than 95%. The effective rate of the 3 groups was above 90.0% at 3 months after surgery, At 12 months after surgery, the effective rate of the simple sclerotherapy group was the lowest [74.3% (26/35)], and the effective rate of the other two groups was still above 85.0%. In conclusion, minimally invasive treatment for internal hemorrhoids under endoscopy is safe and effective with effective improvement of symptoms, high postoperative satisfaction of patients and high degree of acceptance.

Laparoscopic splenectomy and azygoportal disconnection with intraoperative endoscopic variceal ligation in the prevention of postoperative recurrent bleeding / 中华普通外科杂志

Objective:To evaluate the clinical efficacy of laparoscopic splenectomy and azygoportal disconnection (LSD) with intraoperative endoscopic variceal ligation (LSDL) in the treatment of esophagogastric variceal bleeding (EVR).Method:In this study,90 cirrhotic patients with esophagogastric variceal bleeding (EVB) were divided to receive either LSD ( n=45) or LSDL ( n=45) from Jan 2020 and Dec 2021. Results:There were no significant differences in estimated blood loss, incidence of blood transfusion, time to first flatus, off-bed activity and postoperative hospital stay between the two groups (all P>0.05). Compared with LSD group, operation time was longer in LSDL group[ (140±21) min vs. (150±19) min, t=2.420, P=0.018]. LSDL was associated with significantly decreased EVR rate in one year follow-up (2% vs. 18%, P=0.030). Univariate analysis and multivariate logistic regression revealed that LSDL was a significant independent protective factor for EVR as compared with LSD ( P<0.05). Conclusion:LSDL procedure is not only technically feasible and safe, it also contributed to lower postoperative EVR risk than single LSD.

Research progress of accelerated liver regeneration induced by associating liver partition and portal vein ligation for staged hepatectomy / 中华肝胆外科杂志

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce accelerated regeneration of future liver remnant (FLR) and provide the opportunity of radical resection for previously inoperable patients with liver cancer, which has been considered to be one of the most important breakthroughs in liver surgery during the 21st century. It is of great significance to fully understand the mechanism of accelerated liver regeneration induced by ALPPS. This article comprehensively reviews the research progress in this field during the past 10 years.

Research progress of three techniques for hepatic hyperplasia / 中华肝胆外科杂志

Surgical resection is one of the important means to achieve long-term survival for patients with liver malignant tumor. However, most of the liver malignant tumor has been diagnosed in the middle and late stage, and lose the chance of surgical treatment. For these patients who have lost the chance of surgery, some surgeons have proposed the concept of planned liver resection, which is to reduce tumor stage and increase future liver remnant (FLR) in a planned way, so as to improve the safety of surgery and prolong the survival time of patients after surgery. For patients with FLR insufficiency after prior evaluation or/and treatment, the technique of hepatic hyperplasia is an important part of planned hepatectomy, that is, to effectively increase FLR in a short period of time by various means. Portal vein ligation (PVL) and portal vein embolization (PVE), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) are three main techniques for hepatic hyperplasia. This article reviews the principle, effect and safety of three liver augmentation techniques.

Risk factors for hemodynamically significant patent ductus arteriosus in preterm infants requiring surgical ligation: a nested case-control study / 中华实用儿科临床杂志

Objective:To analyze the risk factors for premature infants with hemodynamically significant patent ductus arteriosus (hs-PDA) requiring surgical treatment, and to explore the indications for surgical treatment in premature infants with hs-PDA.Methods:A nested case-control study was conducted.The data of premature infants with gestational age<30 weeks who were diagnosed with hs-PDA in the Neonatal Intensive Care Unit of Peking Union Medical College Hospital from January 2007 to May 2020 were analyzed retrospectively.The hs-PDA patients treated surgically were included in the operation group.The hs-PDA patients of the same gestational age and gender who were not treated surgically were taken as the control group.The ratio of the case number between the operation and control groups was 1∶2.The clinical data during pregnancy, at birth and after birth of premature infants were compared between the 2 groups.The measurement data were tested by the independent sample t test or Mann- Whitney U test.The classification and enumeration data were compared by the Fisher′ s exact probability method.The risk factors for premature infants with hs-PDA requiring surgical treatment were analyzed by the conditional Logistic regression method. Results:A total of 182 premature infants with hs-PDA were enrolled in the study, including 10 in the operation group and 20 in the control group.The patients underwent PDA ligation 30.5(22.7, 37.0) d after birth, and the median preo-perative invasive ventilation duration was 9.7(17.5, 27.2) d. Compared with the control group(20 cases), the preterm infants in the operation group had a lower birth weight [(891.5±118.0) g vs.(1 054.4±230.2) g, t=2.091], a wider arterial duct diameter [3.2(2.8, 4.0) mm vs.2.0(2.0, 3.0) mm, Z=-3.300], and longer invasive ventilation duration [25.0(18.7, 38.2) d vs.3.0(1.0, 7.5) d, Z=-3.688]. Besides, the operation group applied the pulmonary surfactant for more times [2(1, 3) times vs.1(1, 2) times, Z=-2.440], and inhaled a higher concentration of oxygen on the 14 th day after birth [29(25, 36)% vs.21(21, 29)%, Z=-2.358] than the control group.Moreover, compared with the control group, the operation group took longer to achieve adequate enteral feeding [48.2(51.5, 63.5) d vs.42.5(23.5, 48.0) d, Z=2.789], and gained a higher maximum vasoactive inotropic score (VIS) [3.0(0, 3.5) points vs.0(0, 0) points, Z=-2.630]. The difference in all the above-mentioned indicators between the 2 groups was statistically significant (all P<0.05). Univariate Logistic regression analysis showed that the arterial duct diameter, application times of the pulmonary surfactant, the maximum VIS score, and the time taken to achieve sufficient enteral feeding were all related to the need for surgical treatment of hs-PDA in the operation group (all P<0.05). Multivariate Logistic regression analysis revealed that the invasive ventilation duration ( OR=0.747, 95% CI: 0.560-0.998, P=0.048) was an independent risk factor for hs-PDA premature infants requiring surgical treatment. Conclusions:The factors related to the need for surgical treatment in preterm infants with hs-PDA include a wide arterial duct diameter, multiple applications of the pulmonary surfactant, a high concentration of inhaled oxygen on the 14 th day, and the long time to achieve sufficient enteral feeding.The independent risk factor for the surgical treatment in hs-PDA children is the long invasive ventilation duration.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin

Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.

CYP1B1-derived epoxides modulate the TRPA1 channel in chronic pain

Pain is often debilitating, and current treatments are neither universally efficacious nor without risks. Transient receptor potential (TRP) ion channels offer alternative targets for pain relief, but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain. Here, transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation (SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid (EET) and 19,20-EpDPA post injury. Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro, and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia (DRG) neurons. TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079, and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1. This latter effect mapped to residues Y933, G939, and S921 of TRPA1. Intra-plantar injection of 19,20-EpDPA induced acute mechanical, but not thermal hypersensitivity in mice, which was also blocked by A967079. Similarly, Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury. These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.

Comparison of three methods for establishing rat peri-implantitis model / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods.@*METHODS@#Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death.@*RESULTS@#After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05).@*CONCLUSION@#Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Advances in peptidyl Asx-specific ligases for the application of cyclic peptides / 药学学报

Asparaginyl endopeptidases (AEPs) in plants belong to the family of cysteine protease that undergo self-activation in the form of zymogen in acidic vacuole and play important physiological roles in maturation of seed storage proteins, protein degradation, programmed cell death and host defense. Bioprocessing enzymes (peptidyl Asx-specific ligases, PALs) that promote the maturation of cyclotides have recently been isolated and identified from several cyclotide-rich plants. PALs derived from AEPs can site-specifically catalyze the formation of asparagine or aspartate peptide bonds. Due to the advantages of relatively traceless peptide bonds and broad substrate spectrum and high catalytic efficiency, they have been playing important roles in the cyclization and modification of peptides and proteins, and are powerful tools for improving the stability of peptide drugs. This review describes the physiological functions of AEPs in plants and summarizes the discoveries, structural characteristics, catalytic mechanism and protein engineering of PALs, as well as the limitation of their applications and future trends. In addition, the applications of PALs in cyclotides biosynthesis and the development of macrocyclic peptides are highlighted, with the aim of providing a new idea for the biocatalytic synthesis of cyclic peptides.

Ligation of intersphincteric fistula tract (LIFT) for the treatment of anal fistula: a prospective observational study

Background: The ligation of intersphincteric fistula fract (LIFT) technique avoids postoperative anal continence disturbances and preserves quality of life. Methods: A total of 70 patients with anal fistula (AF) were treated in the Day Surgery Unit. The LIFT technique was the primary treatment in 63 patients. The other had previously undergone placement of a loose seton (two-step approach). The mean follow-up was 66.8 months. Statistical analysis was performed using contingency tables, the chi-square test, and the Student T-test. Results: The use of LIFT was successful in 40 patients (57.1%). However, 6 patients (8.6%) presented persistence of postoperative intersphincteric fistula, being successfully treated by fistulotomy. There were no differences in this technique's success rate between high and low AF (p = 0.45). The success rate of one-step LIFT, however, was significantly higher (p = 0.03). No disturbances of continence were observed. Conclusions: The LIFT technique has a role in the treatment of AF, is suitable for ambulatory surgery, and has a low complications rate. A two-step approach is not always needed. (AU)

Urethral monopolar cauterization: alternative infravesical obstruction model in male rats

SUMMARY OBJECTIVE: We aimed to determine which method gives the most consistent results between urethral monopolar cauterization and standard urethral partial ligation methods for the urethral obstruction model. METHODS: Thirty male rats were randomly divided into control, partial ligation, and monopolar cauterization groups. Six weeks after experimental procedures, the experimental groups were evaluated cystometrically, biochemically, and histologically. RESULTS: According to the cystometric results, bladder capacity, baseline bladder pressure, and compliance data of the monopolar cauterization group were higher than those of the partial ligation and monopolar cauterization groups (p<0.05 and p<0.01, respectively). As a biochemical evaluation, malondialdehyde levels in bladder tissues of group control were higher than partial ligation and monopolar cauterization groups (p<0.05 and p<0.01, respectively). The collagen type I level of the control group was higher than the partial ligation and monopolar cauterization groups (p<0.01 and p<0.05, respectively). Collagen type III levels of the monopolar cauterization group were higher than those of the control group (p<0.01), but the Collagen type I/Collagen type III and transforming growth factor-β levels of the monopolar cauterization group were significantly lower than those of the control group (p<0.001). As a histological evaluation (hematoxylin and eosin), fibrosis in the lamina propria was more prominent in the monopolar cauterization group than in the control group (p<0.05). In addition, the muscular thickness was higher in the monopolar cauterization group compared with control and partial ligation groups (p<0.001 and p<0.01, respectively). CONCLUSION: The needle-tipped monopolar cauterization of the posterior urethra may be the method of choice for creating a chronic infravesical obstruction model of infravesical obstruction in male rats.