Ligadura del trayecto fistuloso interesfinteriano. Nuestros resultados / Ligation of the intersphincteric fistulatract. Our results

Introducción: existen varias técnicas para el tratamiento quirúrgico de las fístulas anales, con variables resultados. La técnica de ligadura del trayecto fistuloso interesfinteriano (LIFT) consiste en la disección del espacio entre ambos esfínteres para localizar el trayecto fistuloso y proceder a su ligadura y sección. Objetivo: evaluar nuestros resultados con la técnica de LIFT para del tratamiento de las fístulas anales transesfinterianas. Diseño: retrospectivo, observacional de corte transversal. Materiales y métodos: Se incluyeron todos los pacientes con fístulas transesfinterianas tratados con LIFT desde enero de 2013 a diciembre 2020. El seguimiento postoperatorio se realizó hasta los 2 años. Resultados: se operaron 62 pacientes. El sexo predominante fue masculino. Hubo 47 pacientes con fístulas transesfinterianas bajas y 15 con fístulas transesfinterianas altas. En todos se identificó el trayecto fistuloso realizándose ligadura de ambos cabos del trayecto interesfinteriano y se procedió a un curetaje del trayecto a través del orificio externo. Cinco pacientes (8%) presentaron dehiscencia de piel a nivel de la incisión del espacio interesfinteriano, manejado en forma conservadora. Este grupo tuvo una cicatrización mas retardada de 4 semanas. Ocurrió recidiva en 22 (35,5%) pacientes. Conclusión: La técnica de LIFT parece una alternativa eficaz y segura para el tratamiento de las fístulas transesfinterianas bajas y altas ya que no altera la anatomía ni la continencia. (AU)

Introduction: there are various techniques for the surgical treatment of anal fistulas, with variable results. The ligation procedure of the intersphincteric fistulous tract (LIFT) consists of dissecting the space between both sphincters to locate the fistulous tract and proceed to its ligation and section. Objective: to evaluate our results with the LIFT procedure for the treatment of transsphincteric anal fistulas. Design: retrospective, cross-sectional observational study. Material and methods: all patients with transsphincteric fistulas treated with LIFT from January 2013 to December 2020 were included. Postoperative follow-up was carried out for up to 2 years. Results: sixty-two patients underwent surgery. The predominant sex was male. There were 47 patients with low transsphincteric fistulas and 15 with high transsphincteric fistulas. After identifying the fistulous tract in the intersphincteric groove, both ends were ligated and the tract was cut. Finally, curettage of the tract through the external orifice was performed. Five patients (8%) presented skin dehiscence at the level of the intersphincteric groove incision, managed conservatively. This group had a longer healing time of four weeks. Recurrence occurred in 22 (35.5%) patients. Conclusion: the LIFT procedure appears to be an effective and safe alternative for the treatment of low and high transsphincteric fistulas, since it does not alter the anatomy or continence. (AU)

Application of Non-Ligation Technique in Thyroidectomy.

Objective: This study aimed to analyze the difference between non-ligation and traditional ligation techniques for papillary thyroid micro-carcinoma (PTMC) patients. Methods: Patients undergoing thyroidectomy in the Department of General Surgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University, Lu Wan Branch, were retrospectively enrolled. The gender, age, operation method, operation duration, tumor size, size of thyroidectomy specimen, postoperative bleeding, drainage volume on the first postoperative day, preoperative and postoperative levels of parathyroid hormone (PTH), and blood calcium were collected. Results: Compared with the traditional ligation technique, the non-ligation technique significantly shortened the operation time (69.36 ± 1.38 vs. 82.72 ± 2.12, P < .0001) and reached less variation of the serum calcium (2.32 ± 0.01 vs 2.28 ± 0.01, P < .001) and PTH (26.58 ± 0.08 vs 22.01 ± 1.04, P < .05) on the first postoperative day, and the above biochemical indicators returned to normal 3 weeks after surgery. The PTH in the No-ligation technique group was 7.20± 1.99, which was significantly lower than that in the Traditional ligation group (20.78± 3.78) (P < .01). Conclusion: No-ligation technique can significantly reduce the operation time in thyroidectomy but may temporarily affect the levels of parathyroid hormone and blood calcium, and the above changes returned to normal 3 weeks after surgery. These results highlighted that No-ligation technique can benefit patients and will be a favorable treatment method.

Tibetan medicine Ruyi Zhenbao Pill ameliorates neuropathic pain by inhibiting the CXCL10-CXCR3 pathway in spinal cord of spinal nerve ligation model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruyi Zhenbao Pill (RYZBP) is a traditional Tibetan medicine that has been used for over 300 years in China to treat neurological diseases, specifically neuropathic pain (NP). However, its characteristics and mechanism of action in treating NP remains unclear. AIM OF THE STUDY: Based on animal experiments and transcriptomics to evaluate the characteristics and mechanism of RYZBP in treating NP. METHODS: Mice were divided into six groups using random assignment: sham-operation group, spinal nerve ligation (SNL) group, RYZBP low (0.65 g kg-1), medium (1.30 g kg-1), high (2.60 g kg-1) doses groups, and positive drug pregabalin (PGB, 0.05 g kg-1) group. Mice received intragastrical administered for 14 consecutive days. SNL and intrathecal injection models were employed. The analgesic effects were assessed using the Von Frey test, Acetone test, and Hot Plate test. L5 spinal dorsal horns were collected for transcriptomics on day 15. The potential signaling pathways and Hub genes of RYZBP to ameliorate NP were obtained through transcriptomics and network pharmacology. Molecular docking was utilized to evaluate the binding ability of candidate active ingredients with the Hub genes. Finally, western blot (WB) and immunofluorescence (IF) were used to validate the predicted targets. RESULTS: RYZBP demonstrated a dose-dependent alleviation of mechanical allodynia, cold and heat stimulus-induced pain in SNL mice. Transcriptomics analysis identified 24 differentially expressed genes, and pathway enrichment analysis revealed that the CXCL10-CXCR3 signal axis may be the primary biological pathway through which RYZBP relieve NP. Molecular docking test indicated that the active ingredient in RYZBP exhibit a strong affinity for the target protein CXCL10. WB and IF tests showed that RYZBP can significantly inhibit CXCL10 and CXCR3 and its downstream molecules expression in the spinal dorsal horn of SNL mice. Additionally, intrathecal injection of rmCXCL10 worsened pain hypersensitivity, while RYZBP was able to suppress the pain hypersensitivity response induced by rmCXCL10 and reduce the expression levels of CXCL10 and CXCR3 and its downstream molecules. CONCLUSION: RYZBP had a significant analgesic effect on NP model, and this effect may be related to inhibiting the CXCL10-CXCR3 pathway in the spinal dorsal horn.

EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need.

AIM: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. MATERIAL AND METHODS: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. RESULTS: Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1-64.6%), 64.0% (95% CI: 42.5-82%), and 100% (95% CI: 59-100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. CONCLUSION: Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

Comparisons Between Endoscopic Band Ligation, Radiofrequency Ablation and Endoscopic Thermal Therapy for Gastric Antral Vascular Ectasia: A Meta-Analysis.

BACKGROUND: Endoscopic band ligation (EBL) and radiofrequency ablation (RFA) have emerged as alternative therapies of gastric antral vascular ectasia (GAVE) in addition to endoscopic thermal therapy (ETT), but the optimum choice remains inconclusive. AIM: We conducted a meta-analysis in order to compare these three treatments for GAVE. METHODS: We searched the electronic databases of PubMed, Embase and Cochrane Central Register of Controlled Trials without any language restrictions and also performed a manual literature search of bibliographies located in both retrieved articles and published reviews for eligible publications prior to December 8, 2021. We included comparative trials which had evaluated the efficacy and safety of interventions in adults (aged ≥ 18 years) diagnosed with symptomatic GAVE and was confirmed according to clinical backgrounds and upper gastrointestinal endoscopy. We included reports that compared three interventions, ETT, EBL, and RFA. The study was comprised of adults diagnosed with GAVE and focused on overall mortality, bleeding cessation, endoscopic improvement, complications, hospitalization, hemoglobin improvement, number of sessions and transfusion requirements. RESULTS: Twelve studies were performed involving a total of 571 participants for analysis. When compared with ETT, EBL achieved better bleeding cessation (OR 4.48, 95% CI 1.36-14.77, p = 0.01), higher hemoglobin improvement (MD 0.57, 95% CI 0.31-0.83, p < 0.01) and lower number of sessions (MD - 1.44, 95% CI - 2.54 to - 0.34, p = 0.01). Additionally, EBL was superior to ETT in endoscopic improvement (OR 6.00, 95% CI 2.26-15.97, p < 0.01), hospitalization (MD - 1.32, 95% CI - 1.91 to - 0.74, p < 0.01) and transfusion requirement (MD - 2.66, 95% CI - 4.67 to - 0.65, p = 0.01) with statistical significance, with the exception of mortality (OR 0.58, 95% CI 0.19-1.77, p = 0.34) and complication rate (OR 5.33, 95% CI 0.58-48.84, p = 0.14). CONCLUSION: For GAVE, we suggest that EBL be initially recommended, and APC and RFA be used as alternative treatment choices based upon a very low quality of evidence.

Efficiency of Hesperidin against Liver Fibrosis Induced by Bile Duct Ligation in Rats.

Introduction: Bile duct ligation (BDL) and subsequent cholestasis are associated with oxidative stress and liver injury and fibrosis. Hesperidin (3,5,7-trihydroxyflavanone 7-rhamnoglucoside) is a flavanone glycoside abundant in citrus fruits. It has positive effects on diabetic retinopathy, reduced platelet aggregation, and blood flow alterations and has the potential to reduce liver injury in oxidative stress. The aim of this study was to evaluate the hepatoprotective effects of hesperidin on BDL-induced liver injury in rats. Methods: A total of 48 adult male Wistar rats were equally allocated to six eight-rat groups, namely, a healthy group, a sham group, a BDL+Vehicle group (BDL plus treatment with distilled water), a BDL+VitC group (BDL plus treatment with vitamin C 4.25 µg/kg), a BDL+Hesp100 group (BDL plus treatment with hesperidin 100 mg/kg/day), and a BDL+Hesp200 group (BDL plus treatment with hesperidin 200 mg/kg/day). Treatments were orally provided for 21 consecutive days. Finally, rats were sacrificed through heart blood sampling. Blood samples were centrifuged, and liver function, oxidative stress, and antioxidant parameters were assessed. Liver tissue was also assessed for oxidative stress, antioxidant, and histological parameters. The expression of inflammatory genes, namely, TGFß1, iNOS, Caspase-3, and α-SMA, was measured through polymerase chain reaction. Findings. Hesperidin supplementation was associated with significant decrease in the levels of liver enzymes, bilirubin, nitric oxide, malondialdehyde, protein carbonyl, and inflammatory gene expression; significant increase in the levels of total antioxidant capacity, glutathione, and superoxide dismutase and catalase enzyme activity; and significant improvement in the histological morphology and structure of the liver parenchyma. Conclusion: Hesperidin has significant positive effects on liver morphology and structure, inflammation, fibrosis, and oxidative stress in rats with BDL-induced cholestatic liver injury.

Influence of antiresorptive/antiangiogenic therapy on the extension of experimentally induced peri-implantitis lesions.

OBJECTIVES: To investigate the extension of experimentally induced peri-implantitis lesions under various antiresorptive and antiangiogenic medications. MATERIAL AND METHODS: Fourty-eight albino rats had randomly received the following medications (dual application, n = 8 each): (1) amino-bisphosphonate (zoledronate) (Zo), (2) RANKL inhibitor (denosumab) (De), (3) antiangiogenic (bevacizumab) (Be), (4) Zo+Be, (5) De+Be, or (6) no medication (Co). Ligature- and lipopolysaccharide-induced peri-implantitis lesions were established at 2 maxillary implants over a period of 16 weeks. Histological (e.g., apical extension and surface area of the inflammatory cell infiltrate-aICT, ICT; defect length; defect width; CD68 positive cells) and bone micromorphometric (µCT) outcomes were assessed. The animal was defined as a statistical unit. RESULTS: A total of n = 38 animals (Zo = 6, De = 6, Be = 8, Zo + Be = 6, De + Be = 5, Co = 7) were analyzed. ICT's were commonly marked by a positive CD68 antigen reactivity. Comparable median aICT (lowest-Zo: 0.53 mm; highest-Be: 1.22 mm), ICT (lowest-De + Be: 0.00 mm2; highest-Co: 0.49 mm2), defect length (lowest-Zo: 0.90 mm; highest-Co: 1.93 mm) and defect width (lowest-De+Be: 1.27 mm; highest-Be: 1.80 mm) values were noted in all test and control groups. Within an inner (diameter: 0.8 mm) cylindric volume of interest, the bone microstructure did not significantly differ between groups. CONCLUSIONS: The present analysis did not reveal any marked effects of various antiresorptive/ antiangiogenic medications on the extension of experimentally induced peri-implantitis lesions. CLINICAL RELEVANCE: The extension of peri-implantitis lesions may not be facilitated by the antiresorptive and antiangiogenic medications investigated.

Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment.

Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.

Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.

Does the level of inferior mesenteric artery ligation affect short-term and long-term outcomes of patients with sigmoid colon cancer or rectal cancer? A single-center retrospective study.

BACKGROUND: For sigmoid colon or rectal cancer, a definite consensus regarding the optimal level ligating the inferior mesenteric artery (IMA) has not been reached. We performed this study to determine whether the ligation level significantly affected short-term and long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery. METHODS: Medical records of patients with sigmoid colon or rectal cancer who had undergone curative laparoscopic surgery between January 2008 and December 2014 at the Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine were reviewed. Then, the high tie group (HTG) was compared with the low tie group (LTG) in terms of short-term and long-term outcomes. RESULTS: Five-hundred ninety patients were included. No significant differences between two groups regarding baseline characteristics existed. HTG had a significantly higher risk of anastomotic fistula than LTG (21/283 vs 11/307, P = 0.040). Additionally, high ligation was proven by multivariate logistic regression analysis to be an independent factor for anastomotic fistula (P = 0.038, OR = 2.232, 95% CI: 1.047-4.758). Furthermore, LT resulted in better preserved urinary function. However, LTG was not significantly different from HTG regarding operative time (P = 0.075), blood transfusion (P = 1.000), estimated blood loss (P = 0.239), 30-day mortality (P = 1.000), ICU stay (P = 0.674), postoperative hospital stay (days) (P = 0.636), bowel obstruction (P = 0.659), ileus (P = 0.637), surgical site infection (SSI) (P = 0.121), number of retrieved lymph nodes (P = 0.501), and number of metastatic lymph nodes (P = 0.131). Subsequently, it was revealed that level of IMA ligation did not significantly influence overall survival (OS) (P = 0.474) and relapse-free survival (RFS) (P = 0.722). Additionally, it was revealed that ligation level did not significantly affect OS (P = 0.460) and RFS (P = 0.979) of patients with stage 1 cancer, which was also observed among patients with stage 2 or stage 3 cancer. Ultimately, ligation level was not an independent predictive factor for either OS or RFS. CONCLUSIONS: HT resulted in a significantly higher incidence of anastomotic fistula and worse preservation of urinary function. Level of IMA ligation did not significantly affect long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.

Variceal Bleeding: Beyond Banding.

Despite advances in the management of complications of portal hypertension, variceal bleeding continues to be associated with significant morbidity and mortality. While endoscopic variceal band ligation remains first line therapy for treating bleeding and high-risk non-bleeding esophageal varices, alternate therapies have been explored, particularly in cases of refractory bleeding. The therapies being explored include stent placement, hemostatic powder use, over-the-scope clips and others. For gastric variceal bleeding, endoscopic ultrasound-guided therapies have recently emerged as promising interventions for hemostasis. The aim of this article is to highlight these alternative therapies and their potential role in the management of gastric and esophageal variceal bleeding.

The Protective Effects of Securigera securidaca Seed Extract on Liver Injury Induced by Bile Duct Ligation in Rats.

This study is aimed at evaluating the effects of Securigera securidaca (SS) seed extract on cholestatic liver injury induced by bile duct ligation (BDL) in rats. Total polyphenols and flavonoids in SS seed extract were determined using a colorimetric assay, and their components were quantified using HPLC. Rats in four groups underwent BDL at the common bile duct and were treated for 21 days with either oral distilled water as vehicle, vitamin C, 100 mg/kg SS seed extract, or 200 mg/kg SS seed extract. Rats in the fifth group underwent abdominal incision without BDL and were treated with distilled water, and rats in the sixth group were healthy and received nothing. Finally, rats were sacrificed, blood samples were analyzed through biochemical methods, liver tissues were histologically assessed, and the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes in the liver was assessed through real-time PCR. BDL significantly increased, and SS seed extract significantly decreased the serum levels of bilirubin and liver function enzymes. Moreover, SS seed extract suppressed the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes, reduced the levels of nitric oxide, malondialdehyde, and protein carbonyl, and increased the levels of glutathione, total antioxidant capacity, and SOD and catalase enzyme activity in the serum and liver. Extract at a dose of 100 mg/kg had significant positive effects on liver morphology and parenchyma structure in a dose-dependent manner.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation.

BACKGROUND: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. METHODS: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. RESULTS: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor ß receptor (TGFßR)I/II expression, as assessed by immunostaining. CONCLUSION: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

The use of topical anaesthetic in the banding of internal haemorrhoids: a feasibility study for a randomised control trial.

INTRODUCTION: Rubber band ligation (RBL) is a procedure commonly performed in colorectal clinics for internal haemorrhoids. Overall, 90% of patients experience pain following RBL. We aimed to complete a feasibility randomised control trial assessing the role of topical anaesthetic before RBL of internal haemorrhoids. METHODS: We performed a prospective, single-centre, single blinded, randomised (1:1) control feasibility trial. Patients presenting with symptomatic haemorrhoids suitable for banding were randomised to undergo the procedure with local anaesthetic or without (control). Pain scores and vasovagal symptoms were assessed at 0 minutes, 30 minutes, 4 hours and 72 hours after the procedure. Primary outcome measures were recruitment rate, participant retention rate and patient and surgeon acceptability. Secondary outcome measures were pain scores up to 72 hours, vasovagal episodes, new use of analgesia and adverse outcomes. RESULTS: In total, 35 patients (18 topical anaesthetic, group A; 17 no anaesthetic gel, group B) were recruited. Mean recruitment rate was 11.7 participants per month. Thirty-three (94%) participants remained in the study until completion, with two patients lost to telephone follow-up. The treatment was acceptable for 35 (97%) eligible patients. One patient declined enrolment. The treatment was acceptable to all surgeons (100%). There was a significant difference in median pain scores of -2 (95% CI -4.0 to -1.0, p=0.0006) at the 30-minute time point only. There was no significant difference in vasovagal symptoms (p=0.10) or new analgesia use (p=0.85). CONCLUSION: We have shown that a phase III clinical trial is feasible for assessing the role of topical anaesthetic before RBL of internal haemorrhoids. We have demonstrated excellent patient recruitment and retention as well as patient and surgeon acceptability.

Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation.

Neuroinflammation is a central factor in neuropathic pain (NP). Ginger is a promising bioactive compound in NP management due to its anti-inflammatory property. Emerging evidence suggests that gut microbiome and gut-derived metabolites play a key role in NP. We evaluated the effects of two ginger root extracts rich in gingerols (GEG) and shogaols (SEG) on pain sensitivity, anxiety-like behaviors, circulating cell-free mitochondrial DNA (ccf-mtDNA), gut microbiome composition, and fecal metabolites in rats with NP. Sixteen male rats were divided into four groups: sham, spinal nerve ligation (SNL), SNL+0.75%GEG in diet, and SNL+0.75%SEG in diet groups for 30 days. Compared to SNL group, both SNL+GEG and SNL+SEG groups showed a significant reduction in pain- and anxiety-like behaviors, and ccf-mtDNA level. Relative to the SNL group, both SNL+GEG and SNL+SEG groups increased the relative abundance of Lactococcus, Sellimonas, Blautia, Erysipelatoclostridiaceae, and Anaerovoracaceae, but decreased that of Prevotellaceae UCG-001, Rikenellaceae RC9 gut group, Mucispirillum and Desulfovibrio, Desulfovibrio, Anaerofilum, Eubacterium siraeum group, RF39, UCG-005, Lachnospiraceae NK4A136 group, Acetatifactor, Eubacterium ruminantium group, Clostridia UCG-014, and an uncultured Anaerovoracaceae. GEG and SEG had differential effects on gut-derived metabolites. Compared to SNL group, SNL+GEG group had higher level of 1'-acetoxychavicol acetate, (4E)-1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one, NP-000629, 7,8-Dimethoxy-3-(2-methyl-3-buten-2-yl)-2H-chromen-2-one, 3-{[4-(2-Pyrimidinyl)piperazino]carbonyl}-2-pyrazinecarboxylic acid, 920863, and (1R,3R,7R,13S)-13-Methyl-6-methylene-4,14,16-trioxatetracyclo[11.2.1.0∼1,10∼.0∼3,7∼]hexadec-9-en-5-one, while SNL+SEG group had higher level for (±)-5-[(tert-Butylamino)-2'-hydroxypropoxy]-1_2_3_4-tetrahydro-1-naphthol and dehydroepiandrosteronesulfate. In conclusion, ginger is a promising functional food in the management of NP, and further investigations are necessary to assess the role of ginger on gut-brain axis in pain management.

Impact of photobiomodulation therapy on the morphological aspects of submandibular gland submitted to excretory duct ligation and hypothyroidism: an animal study.

The aim of this study was to evaluate the impact of photobiomodulation therapy (PBMT) on histomorphological aspects of submandibular gland (SMG) submitted to salivary gland duct obstruction in hypothyroid rats. Fifty-six male Wistar rats (250 to 300 g) were divided into 4 groups (n = 14): euthyroid (EU), EU + PBMT, hypothyroid (HYPO), and HYPO + PBMT. Duct obstruction of the left submandibular gland (LSMG) was performed in all animals by a ligature procedure. For the induction of hypothyroidism, total thyroidectomy was performed. PBMT groups received irradiation with AlGaInP diode laser (808 nm, 0.04 W, 0.04cm2 spot size, 60 s, 2.4 J per point, 60 J/cm2, 1 W/cm2). Irradiation was performed immediately, 24 h, and 48 h after the obstruction of the salivary gland duct, in one point, extra oral and perpendicular to the gland. Animals were sacrificed after 24 h and 72 h after duct ligature. Our results indicated that salivary duct obstruction and hypothyroidism caused negative modifications on the salivary glands' histomorphology, especially acinar atrophy, after 24 h and 72 h. HYPO + PBMT showed a significant reduction of the inflammatory infiltrate, congested blood vessels, and acinar atrophy in the SMG submandibular salivary gland in 72 h compared to 24 h (p < 0.05). In conclusion, obstruction of the salivary gland excretory duct and hypothyroidism causes severe sialoadenitis with expressive atrophy of the glandular parenchyma. However, PBMT was able to modulate the inflammatory process and delaying acinar atrophy. This study provided insights to better understand the role of the PBMT on the altered salivary gland by duct ligation and associate hypothyroidism.

Efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and the effect on fibulin protein expression: A study protocol of a randomized controlled trial.

BACKGROUND: Hemorrhoids are a common and seriously disruptive condition that seriously affects people's lives in terms of treatment. Injection therapy is an effective minimally invasive scheme for the treatment of grade II-III hemorrhoids, but its clinical application is limited by the adverse reactions caused by injection drugs. Some clinical studies have confirmed the efficacy and safety of Shaobei injection as a traditional Chinese medicine extract. However, there is no standard randomized controlled study to verify its efficacy and explore its potential mechanism. METHODS: This is a prospective, randomized, single blind, parallel controlled trial to study the efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and its effect on the expression of fibulin-3 and fibulin-5 in fibulin protein family. The patients will be randomly divided into a treatment group and control group. The treatment group will be treated with Shaobei injection, and the control group will be treated with rubber band ligation. The observation indexes include: visual analysis scale, postoperative hospital stay, total use of painkillers, fibulin-3 and fibulin-5, hemorrhoids recurrence, and adverse events. Finally, the data will be statistically analyzed by SPASS 18.0 software. DISCUSSION: This study will compare the efficacy of Shaobei injection with the rubber band ligation method in the treatment of grade II-III haemorrhoids and investigate its effect on the expression of fibulin-3 and fibulin-5 in the fibulin protein family. The results of this study will provide a basis for the clinical use of Paeoniflora injection as an alternative to traditional sclerosing agent in the treatment of grade II-III haemorrhoids.Trial registration: OSF Registration number:DOI 10.17605/OSF.IO/MKVDB.

Liposome Extract of Stachys pilifera Benth Effectively Improved Liver Damage due to Bile Duct Ligation Rats.

Herbal medicines harbor essential therapeutic agents for the treatment of cholestasis. In this study, we have assessed the anticholestatic potential of Stachys pilifera Benth's (SPB's) hydroalcoholic extract encapsulated into liposomes using bile duct ligation- (BDL-) induced hepatic cholestasis in rats. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total thiol (T-SH) content, protein carbonyl (PCO), total bilirubin (TBIL), albumin (ALB), and nitric oxide (NO) metabolite levels were measured in either liver tissue or plasma to assess liver damage. Moreover, expression of proinflammatory cytokines (IL-1ß and TNF-α) and liver fibrosis markers (TGF-ß and SM-α) which are driving forces of many liver disorders was also determined. The activity of AST, ALT, and ALP was significantly enhanced in the BDL group in comparison to the control group; however, treatment with liposomal (SPB) hydroalcoholic extract significantly reduced AST and ALT's activity. Increases in MDA, TBIL, and NO levels and T-SH content due to BDL were restored to control levels by liposomal (SPB) hydroalcoholic extract treatment. Similarly, hepatic and plasma oxidative marker MDA levels, significantly enhanced by BDL, were significantly decreased by liposomal (SPB) hydroalcoholic extract treatment. Moreover, histopathological findings further demonstrated a significant decrease in hepatic damage in the liposomal (SPB) hydroalcoholic extract-treated BDL group. In addition, liposomal (SPB) hydroalcoholic extract treatment decreased the liver expression of inflammatory cytokines (IL-1ß, TNF-α) and liver fibrosis markers (TGF-ß and SM-α). Since liposomal (SPB) hydroalcoholic extract treatment alleviated the BDL-induced injury of the liver and improved the hepatic structure and function more efficiently in comparison to free SPB hydroalcoholic extract, probable liposomal (SPB) hydroalcoholic extract exhibits required potential therapeutic value in protecting the liver against BDL-caused oxidative injury.

Interventional treatments for prolapsing haemorrhoids: network meta-analysis.

BACKGROUND: Multiple treatments for early-moderate grade symptomatic haemorrhoids currently exist, each associated with their respective efficacy, complications, and risks. The aim of this study was to compare the relative clinical outcomes and effectiveness of interventional treatments for grade II-III haemorrhoids. METHODS: A systematic review was conducted according to PRISMA criteria for all the RCTs published between 1980 and 2020; manuscripts were identified using the MEDLINE, Embase, and CENTRAL databases. Inclusion criteria were RCTs comparing procedural interventions for grade II-III haemorrhoids. Primary outcomes of interest were: symptom recurrence at a minimum follow-up of 6 weeks, postprocedural pain measured on a visual analogue scale (VAS) on day 1, and postprocedural complications (bleeding, urinary retention, and bowel incontinence). After bias assessment and heterogeneity analysis, a Bayesian network meta-analysis was performed. RESULTS: Seventy-nine RCTs were identified, including 9232 patients. Fourteen different treatments were analysed in the network meta-analysis. Overall, there were 59 RCTs (73 per cent) judged as being at high risk of bias, and the greatest risk was in the domain measurement of outcome. Variable amounts of heterogeneity were detected in direct treatment comparisons, in particular for symptom recurrence and postprocedural pain. Recurrence of haemorrhoidal symptoms was reported by 54 studies, involving 7026 patients and 14 treatments. Closed haemorrhoidectomy had the lowest recurrence risk, followed by open haemorrhoidectomy, suture ligation with mucopexy, stapled haemorrhoidopexy, and Doppler-guided haemorrhoid artery ligation (DG-HAL) with mucopexy. Pain was reported in 34 studies involving 3812 patients and 11 treatments. Direct current electrotherapy, DG-HAL with mucopexy, and infrared coagulation yielded the lowest pain scores. Postprocedural bleeding was recorded in 46 studies involving 5696 patients and 14 treatments. Open haemorrhoidectomy had the greatest risk of postprocedural bleeding, followed by stapled haemorrhoidopexy and closed haemorrhoidectomy. Urinary retention was reported in 30 studies comparing 10 treatments involving 3116 participants. Open haemorrhoidectomy and stapled haemorrhoidopexy had significantly higher odds of urinary retention than rubber band ligation and DG-HAL with mucopexy. Nine studies reported bowel incontinence comparing five treatments involving 1269 participants. Open haemorrhoidectomy and stapled haemorrhoidopexy had the highest probability of bowel incontinence. CONCLUSION: Open and closed haemorrhoidectomy, and stapled haemorrhoidopexy were associated with worse pain, and more postprocedural bleeding, urinary retention, and bowel incontinence, but had the lowest rates of symptom recurrence. The risks and benefits of each treatment should be discussed with patients before a decision is made.

Hirsutella sinensis fungus improves cardiac function in mouse model of heart failure.

Cordyceps sinensis, including Hirsutella sinensis, is a highly valuable traditional Chinese medicine and is used to treat patients with pulmonary heart disease in clinical practice. However, the underlying mechanisms of its effects remain unclear. In this study, a mouse model of heart failure established by non-thoracic, transverse aortic constriction (TAC) was developed to determine the underlying mechanisms of therapeutic effects of Hirsutella sinensis fungus (HSF) powder. The results showed that HSF treatment remarkably ameliorated myocardial hypertrophy, collagen fiber hyperplasia, and cardiac function in mice with heart failure. Using transcriptional and epigenetic analyses, we found that the mechanism of HSF mainly involved a variety of signaling pathways related to myocardial fibrosis and determined that HSF could reduce the levels of TGF-ß1 proteins in heart tissue, as well as type I and III collagen levels. These data suggest that HSF alleviates heart failure, inhibits irreversible ventricular remodeling, and improves cardiac function through the regulation of myocardial fibrosis-related signaling pathways, which can provide novel opportunities to improve heart failure therapy.