Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately.Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498).Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies.Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.

Background Some Chinese scholars have initially explored the efficacy of electroacupuncture at Baliao acupoint in patients with functional anorectal pain (FAP). However, their studies are performed in a single center, or the sample size is small. Therefore, we aim to further explore the efficacy of electroacupuncture at Baliao acupoint on the treatment of FAP.Methods In this multicenter randomized controlled trial, 136 eligible FAP patients will be randomly allocated into an electroacupuncture group or sham electroacupuncture group at a 1:1 ratio. This trial will last for 34 weeks, with 2 weeks of baseline, 4 weeks and 8 weeks of treatment, and 1, 3, and 6 months of follow-up. Outcome assessors and statisticians will be blind. The primary outcome will be clinical treatment efficacy, and secondary outcomes will be pain days per month, quality of life, psychological state assessment, anorectal manometry, pelvic floor electromyography, and patient satisfaction.Discussion Results of this trial will be contributed to further clarify the value of electroacupuncture at Baliao acupoint as a treatment for FAP in the clinic.Trial registration This trial has been registered in Chinese Clinical Trial Registry https://www.chictr.org.cn/ (ChiCTR2300069757) on March 24, 2023.

We aimed to evaluate the effectiveness of transperineal ultrasound (TPUS) in diagnosing rectocele, rectal intussusception (RI), enterocele, perineal descent (PD), and cystocele in Chinese women with obstructed defecation syndrome (ODS), and to determine the grading of rectocele via TPUS. Between January 2019 and December 2021, 107 obstructed defecation syndrome patients, with a mean age of 49.76 years, received TPUS and defecation proctography (DEP). Both methods were used to diagnose anorectal angle, rectocele, RI, enterocele, and PD, while cystocele and uterine prolapse were diagnosed only through TPUS. Agreement between DEP and TPUS diagnostic results was compared using Cohen kappa statistics. Seventy-six rectoceles were reported following DEP and 72 after TPUS. DEP detected 7 enteroceles, 6 of which were diagnosed simultaneously by TPUS. 43 patients presented dyssynergic defecation (DD) upon DEP, while 51 upon TPUS. DEP and TPUS detected PD in 13 and 11 patients respectively, and RI in 82 and 73, respectively. Rectocele (kappa = 0.738), RI (kappa = 0.711), DD (kappa = 0.774), enterocele (kappa = 0.847), and PD (kappa = 0.625) were obtained by Cohen kappa statistics, which indicated a good agreement between DEP and TPUS. The cutoff values for the diagnosis of moderate and severe rectocele with TPUS were 12.05 mm (AUC: 0.941) and 18.50 mm (AUC: 0.977), respectively. The DEP-determined and TPUS-determined anorectal angles were significantly correlated in the resting and Valsalva states (P < .01). Compared with DEP, while maintaining good agreement in detecting rectocele, RI, DD, enterocele, and PD, TPUS is a repeatable and noninvasive alternative. Threshold values of 12.05 mm and 18.50 mm on TPUS may diagnose moderate and severe rectocele, respectively.

目的:观察慢性肛门直肠痛(CAP)大鼠S2-3脊髓背角中胶质细胞活化情况及电针对其干预作用,探讨脊髓胶质细胞活化是否引起CAP及参与电针镇痛.方法:18只SD大鼠随机分为正常组、模型组和电针组.正常组直肠注入0.9％氯化钠溶液,模型组及电针组注入辣椒素(浓度:10-4 mmol/L),每间隔5 min注入1次,共注入4次;电针组造模完成且大鼠清醒2 h后予以针刺八髎穴干预.观察大鼠内脏疼痛相关行为次数及机械痛阈值变化;采用苏木素-伊红(HE)染色观察直肠组织病变;免疫荧光法检测脊髓小胶质细胞标志物OX42和星形胶质细胞标志物GFAP表达强度、酶联免疫吸附试验(ELISA)检测脊髓和血清中IL-1β、TNF-α和IL-6的含量.结果:与正常组相比,模型组大鼠内脏痛行为明显增加,大鼠尾部、后足底及腹部机械痛阈值上升(P＜0.01);与模型组相比,电针组内脏痛行为减少,大鼠尾部、后足底、腹部机械痛阈值降低(P＜0.01).HE染色示正常组直肠黏膜下组织无水肿现象,模型组直肠黏膜下组织出现明显水肿病变,电针干预后,大鼠直肠黏膜下组织水肿相比模型组明显减轻;与正常组相比,模型组大鼠脊髓中小胶质细胞标志物OX42和星形胶质细胞标志物GFAP的阳性表达显著增加(P＜0.01);与模型组相比,电针组大鼠脊髓中标志物OX42和GFAP的阳性表达降低,差异具有统计学意义(P＜0.05).与正常组相比,模型组大鼠脊髓和血清中IL-1β、TNF-α和IL-6水平上升(P＜0.01);与模型组相比,电针组大鼠脊髓及血清中IL-1β、TNF-α和IL-6水平均下降,差异具有统计意义(P＜0.05).结论:脊髓胶质细胞活化及促炎因子IL-1β、TNF-α和IL-6释放与CAP发生密切相关,电针治疗可通过抑制脊髓胶质细胞活化及降低炎症因子IL-1β、TNF-α和IL-6水平有效缓解慢性肛门直肠疼痛.

Objective:To explore the clinical diagnostic value of transperineal ultrasound(TPUS)and MR defecography(MRD)in female outlet obstruction constipation(OOC)by using X-ray defecography(XRD)as the gold standard.Methods:From January 2020 to December 2021, 41 female patients who were clinically diagnosed as OOC in the Department of Anorectal Diseases of Nanjing Hospital of Traditional Chinese Medicine were selected for XRD, TPUS and MRD.With XRD as the reference standard, the sensitivity and specificity of TPUS and MRD in the diagnosis of rectocele, perineal descent, rectal intussusception, enterocele and pelvic floor dyssynergia were evaluated, and the consistency of the three imaging results was tested.Results:Taking XRD as the reference standard, the sensitivity of TPUS in the diagnosis of rectal intussusception, rectocele, perineal descent, enterocele, and pelvic floor dyssynergia was 94.12%, 87.5%, 55.56%, 80%, and 100%, and the specificity was 100%, 88.89%, 100%, 100%, and 93.33%.The sensitivity of MRD in the diagnosis of rectal intussusception, rectocele, perineal descent, enterocele and pelvic floor dyssynergia was 70.59%, 81.25%, 55.56%, 60% and 63.64%, and the specificity was 100%, 77.78%, 75%, 100% and 96.67%.TPUS was highly consistent with XRD in the diagnosis of rectocele and perineal descent, and the Kappa coefficients were 0.682 and 0.661.TPUS has good consistency with XRD in the diagnosis of rectal intussusception, enterocele, pelvic floor dyssynergia, and the Kappa coefficients were 0.845, 0.875, 0.883.MRD was highly consistent with XRD in the diagnosis of enterocele and pelvic floor dyssynergia, and the Kappa coefficients were 0.725 and 0.660.Conclusion:TPUS can be used as a preliminary evaluation technique for female OOC; MRD can be used as an effective supplement to the etiological diagnosis of such patients.

Background: Electroacupuncture (EA) treatment can alleviate chronic neuropathic pain, like visceral pain, but the underlying mechanism remains unclear.Methods: Herein, rats were intracolonically injected with capsaicin to create a visceral (rectal) pain model. Then rats were treated with EA. The number of visceral pain-related behaviors, along with the mechanical pain thresholds of the rats' tail, metapedes and abdomen, were recorded. Meanwhile, the pathology of rectal tissue was observed by hematoxylin-eosin staining. The expressions of inflammatory factors (interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF-alpha)) and glial fibrillary acidic protein (GFAP) in the rat spinal cord or serum were assessed using enzyme-linked immunosorbent assay or Western blot. Likewise, the expression level of oxycocin-42 (OX42), GFAP, transient receptor potential vanilloid 1 (TRPV1), P2X4 receptor (P2X4R) and mitogen-activated protein kinase (MAPK) pathway-related proteins were determined by immunofluorescence or Western blot in the rats' spinal cord.Results: The increased visceral behavioral pain, mechanical pain threshold, secretion of inflammatory factors, edema of rectal mucosa and activation of spinal glial cells induced by capsaicin were all reversed by EA treatment. Additionally, the upregulation of TRPV1 and P2X4R as well as the activation of the MAPK pathway caused by capsaicin was offset by EA treatment.Conclusions: EA treatment ameliorates rats' rectal visceral pain by repressing TRPV1 and P2X4R expression levels as well as blocking MAPK pathway.

The effects of lithium on the uptake and retention of (−)-erythro-metaraminol (MA) and (−)-m-octopamine (OA) by synaptosomes from rat whole brain were examined after (a) addition of lithium chloride (1 mmol/l.) to synaptosomal fractions in vitro and (b) administration of lithium chloride (1 mmol/kg) i.p. to rats twice daily for 10 days prior to isolation of synaptosomes. Under control conditions, apparent Km concentrations (5 min incubation) for MA and OA were 33 and 3 μM respectively. As incubation times were increased to 15 min, retention of MA increased and OA decreased. Retention of both amines was reduced by low temperature. Short term application of lithium to synaptosomes in vitro did not alter the uptake and retention of either amine during 5 or 10 min incubation periods. Chronic pretreatment of rats with lithium resulted in greater uptake and retention of low concentrations of MA when compared with synaptosomes from control (saline-treated) animals. Chronic lithium pretreatment did not alter retention of OA. The data support the hypothesis that lithium acts to increase synaptosomal membrane uptake of aromatic amines and decrease binding of accumulated amine.