Management of granulomatous lobular mastitis: an international multidisciplinary consensus(2021 edition)

Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats

AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.

Multi-source information fused generative adversarial network model and data assimilation based history matching for reservoir with complex geologies

For reservoirs with complex non-Gaussian geological characteristics,such as carbonate reservoirs or reservoirs with sedimentary facies distribution,it is difficult to implement history matching directly,especially for the ensemble-based data assimilation methods.In this paper,we propose a multi-source information fused generative adversarial network(MSIGAN)model,which is used for parameterization of the complex geologies.In MSIGAN,various information such as facies distribution,microseismic,and inter-well connectivity,can be integrated to learn the geological features.And two major generative models in deep learning,variational autoencoder(VAE)and generative adversarial network(GAN)are combined in our model.Then the proposed MSIGAN model is integrated into the ensemble smoother with multiple data assimilation(ESMDA)method to conduct history matching.We tested the proposed method on two reservoir models with fluvial facies.The experimental results show that the proposed MSIGAN model can effectively learn the complex geological features,which can promote the accuracy of history matching.

Acupuncture-moxibustion in treating irritable bowel syndrome: How does it work?

Irritable bowel syndrome(IBS)is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits.It has drawn great attention because of its high prevalence,reoccurring symptoms,and severe influence on patients’lives.Many clinical studies have demonstrated the efficacy of acupuncturemoxibustion in treating IBS.Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS,and the adoption of modern techniques has achieved some progress.This article reviews the latest advances among actionmechanism studies from the perspectives of gastrointestinal motility,visceral hypersensitivity,the braingut axis,the neuroendocrine system,and the immune system.It is shown that acupuncture-moxibustion can effectively regulate the above items,and thus,this treatment should have a high efficacy in the treatment of IBS.This article also identifies existing problems in current mechanism research and raises several ideas for future studies.Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS.

Herb-partitioned moxibustion alleviates colon injuries in ulcerative colitis rats

AIM To observe the effect of herb-partitioned moxibustion(HPM) on expression of colonic cytokines in ulcerative colitis(UC) rats.METHODS A UC rat model was established by protein immunization in combination with topical chemical stimulation.Rats in the HPM group(n = 8) received HPM at bilateral Tianshu(ST25) points.The gross injury and pathological scores of the colon were recorded.The expression profile of colonic cytokines was assayed using the protein microarray technique.Specific differential cytokines were selected and verified by ELISA.The corresponding Uni Prot Accessions of the differentially expressed cytokines were retrieved in the Uni Prot database.The pathways involved were analyzed with the help of the KEGG PATHWAY database.The DAVID database was used for functional cluster and pathway analysis.RESULTS HPM improved colon injuries in UC rats,manifested by accelerated repair of ulcers and alleviation of inflammation,and the gross injury and pathological scores both significantly decreased(P < 0.01).Fold change > 1.3 or < 0.77 was taken as the screening standard.There were 77 down-regulated and 9 up-regulated differentially expressed colonic cytokines in the HPM group compared with the model group,and expression of 20 differed significantly(P < 0.05).Twelve of the 20 significantly differentially expressed cytokines [β-catenin,interleukin-1 receptor 6(IL-1 R6),IL-1β,B7-1,nerve growth factor receptor,AMP-activated protein kinase-α1,neuropilin-2,orexin A,adipocyte differentiation-related protein,IL-2,Fas and Fas L] were up-regulated in the model group(n = 3,compared with the normal group) but downregulated in the HPM group(n = 3,compared with the model group).Functional cluster analysis showed that the differentially expressed colonic cytokines in the HPM group regulated apoptosis and protein phosphorylation.KEGG pathway analysis showed that 52 down-regulated and 7 up-regulated differentially expressed colonic cytokines in the HPM group had pathways.The pathways that interacted between the cytokines and their receptors accounted for the largest proportion(28 of the downregulated and 5 of the up-regulated cytokines).CONCLUSION HPM promotes the repair of colon injuries in UC rats,which is related to the regulation of several abnormally expressed cytokines.

Extracellular signal-regulated kinase, substance P and neurokinin-1 are involved in the analgesic mechanism of herb-partitioned moxibustion

Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu （ST25） and Qihai （CV6） points were selected for herb-partitioned moxi- bustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance E and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.

Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome

AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome(D-IBS).METHODS: A factorial design was employed to examine the two factors of moxibustion frequency and number of cones. The two tested frequencies were three or six moxibustion sessions per week, and the two tested doses were one or two cones per treatment. A total of 166 D-IBS patients were randomly divided into four treatment groups, which included each combination of the examined frequencies and doses. The bilateral Tianshu acupoints(ST25) and the Qihai acupoint(RN6) were selected for aconite cake-separated moxibustion. Each patient received two courses of treatment, and each course had a duration of 2 wk. For each group, the scores on the Birmingham irritable bowel syndrome(IBS) symptom questionnaire, the IBS Quality of Life scale, the Self-Rating Depression Scale(SDS), the Self-Rating Anxiety Scale(SAS), the Hamilton Depression(HAMD) scale, and the Hamilton Anxiety(HAMA) scale were determined before treatment, after the first course of treatment, and after the second course of treatment. RESULTS: The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all 4 aconite cake-separated moxibustion groups were significantly lower after the first and second courses of treatment than before treatment(P < 0.001 for all). The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all four aconite cake-separated moxibustion groups were significantly lower after the second course of treatment than after the first course of treatment(P < 0.001 for all). Between-group comparisons after the second course of treatment revealed that the symptom scores for group 1(1 cone, 3 treatments/wk) and group 3(2 cones, 3 treatments/wk) were significantly lower than that for group 2(1 cone, 6 treatments/wk)(5.55 ± 5.05 vs 10.45 ± 6.61, P < 0.001; 5.65 ± 4.00 vs 10.45 ± 6.61, P < 0.001). Regarding the two levels of the two examined factors for aconite cake-separated moxibustion, after the first course of treatment, the changes in HAMA scores weresignificantly different for the two tested moxibustion frequencies(P = 0.011), with greater changes for the "6 treatments/wk" groups than for the "3 treatments/wk" groups; in addition, there were interaction effects between the number of cones and moxibustion frequency(P = 0.028). After the second course of treatment, changes in symptom scores for the 2 tested moxibustion frequencies were significantly different(P = 0.002), with greater changes for the "3 treatments/wk" groups than for the "6 treatments/wk" groups.CONCLUSION: An aconite cake-separated moxibustion treatment regimen of 3 treatments/wk and 1 cone/treatment appears to produce better therapeutic effects for D-IBS compared with the other tested regimens.

Gastrointestinal cytomegalovirus disease secondary to measles in an immunocompetent infant:A case report

BACKGROUND Gastrointestinal cytomegalovirus(CMV)disease occurs commonly in immunocompromised/immunodeficient patients with advanced human immunodeficiency virus infection,neoplasm,solid organ transplantation,hematopoietic stem cell transplantation,or treatment with immunosuppressants,but is rarely reported in association with measles infection.CASE SUMMARY We describe a case of extensive gastrointestinal CMV disease secondary to measles infection in a 9-mo-old boy who presented with persistent fever and bloody diarrhea.His condition was improved after ganciclovir treatment.Serological analysis of CMV showed negative immunoglobulin(Ig)M and positive IgG.Blood CMV-DNA was 9.26×103 copies/mL.The diagnosis of gastrointestinal CMV disease was confirmed by histopathological findings of intranuclear and intracytoplasmic inclusions and Owl’s eye inclusion.This case highlights the differential diagnosis and histopathological characteristics of gastrointestinal CMV infection and laboratory tests.CONCLUSION Extensive gastrointestinal CMV lesions can be induced by the immune suppression secondary to measles infection.Rational,fast,and effective laboratory examinations are essential for suspected patients.

Prevention program for the COVID-19 in a children’s digestive endoscopy center

The pneumonia caused by the coronavirus disease-2019(COVID-19)outbreak in Wuhan,China constitutes a public health emergency of international concern.The gastrointestinal symptoms of vomiting,diarrhea and abdominal pain and the detection of COVID-19 nucleic acid from fecal specimens in a small number of patients suggest the possibility of transmission via the gastrointestinal tract.People of all ages are vulnerable to this virus,including children.Digestive endoscopy is an invasive procedure during which children cannot wear masks;therefore,they have higher risks of exposure to COVID-19,and the digestive endoscopy center is a relatively high-risk area for COVID-19 infection.Based on these factors and in combination with related policies and regulations,a prevention and control program for the COVID-19 pneumonia in a children's digestive endoscopy center was established to prevent the COVID-19 nosocomial infection.