Yiqi Kaimi prescription regulates protein phosphorylation to promote intestinal motility in slow transit constipation.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the Yiqi Kaimi prescription has been confirmed in slow transit constipation. However, the effects and biological mechanism of Yiqi Kaimi prescription are still unclear. AIMS OF THE STUDY: To identify the effects of Yiqi Kaimi prescription on intestinal motility; To reveal the potential key targets and pathways of Yiqi Kaimi prescription for the treatment of slow transit constipation. MATERIALS AND METHODS: The effects of Yiqi Kaimi prescription on slow transit constipation were investigated in a mouse model. The terminal ink propulsion experiment and fecal indocyanine green imaging was used to measure the intestinal transit time. Protein phosphorylation changes in colon tissues treated with Yiqi Kaimi prescription were detected using a Phospho Explorer antibody microarray. Bioinformatic analyses were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes (STRING). Western blot analysis and immunohistochemistry confirmed the observed changes in phosphorylation. RESULT: s: Yiqi Kaimi prescription significantly increased the intestinal transit rate (P < 0.05 vs. model) and reduced the time to first discharge of feces containing fecal indocyanine green imaging in mice (P < 0.05 vs. model). The administration of Yiqi Kaimi prescription induced phosphorylation changes in 41 proteins, with 9 upregulated proteins and 32 downregulated proteins. Functional classification of the phosphorylated proteins with DAVID revealed that the critical biological processes included tyrosine protein kinases, positive regulation of calcium-mediated signaling and response to muscle stretch. The phosphorylation of the spleen tyrosine kinase (SYK) at Tyr348 increased 2.19-fold, which was the most significant change. The phosphorylation level of the transcription factor p65 (RELA) at Thr505 was decreased 0.57-fold. SYK was a hub protein in the protein-protein interaction network and SYK and RELA formed the core of the secondary subnetwork. The key protein phosphorylation after treatment with Yiqi Kaimi prescription were verified by Western blot analysis and immunohistochemistry. CONCLUSION: Yiqi Kaimi prescription significantly enhanced intestinal motility. This effect was attributed to alterations in the phosphorylation levels of various target proteins. The observed changes in protein phosphorylation, including SYK and RELA, may serve as crucial factors in the treatment of slow transit constipation.

Bibliometric insights in fournier's gangrene: Research landscapes, turning points, and global trends.

Study Design: Bibliometric and visualization analysis. Objective: To analyze the research landscapes and hotspots of Fournier's gangrene, and reveal the dynamic changes and development trend of research hotspots for the purpose of providing ideas and a basis for clinical and basic research in this field. Methods: Research datasets were acquired from the Web of Science. The publication years were limited from January 1, 1900 to August 5, 2022. The bibliometric tools CiteSpace (v5.8) and VOSviewer (v1.6) were used to analyze the data and generate visualization knowledge maps. Trends in annual publications, distribution, H-index status, coauthorships status and research hotspots were analyzed. Results: According to the search strategy, we identified and enrolled 688 publications regarding to Fournier's gangrene. The number of published papers showed an overall upwards trend. The USA was the largest contributor, ranking first in total publications, citations and the H-index. The top 10 most productive institutions were all from the USA. De Simone B and Sartelli M were the most productive authors. There was close cooperation among countries, but the cooperation among institutions and authors had little contact and poor interactivity. The research hotspots included the pathogenesis factors and treatment. All the identified keywords were divided into 14 clusters, and the label of the latest cluster was "empagliflozin". Prognosis and risk factors, emerging treatment methods, and pathogenesis were at the forefront of the Fournier's gangrene field and were predicted to be the next hot topics. Conclusion: The research of Fournier's gangrene has made some achievements, but the overall research level is still in the primary stage. The academic cooperation between different institutions and authors needs to be strengthened. At the early stage, the mainstream of research was the infected tissue and site, pathogenesis, and diagnosis of disease, while research on newly discovered sodium-glucose cotransporter 2 inhibitor, adjuvant therapy and prognostic factors may be the main directions in the future.

Is the transperineal ultrasonography approach effective for the diagnosis of rectocele?

BACKGROUND: Transperineal ultrasonography has been used as a diagnostic imaging modality for rectocele for many years. However, the consistency of ultrasonography and defecography in evaluating the severity of rectocele was not satisfactory. This study aimed to evaluate the agreement in the measurement of rectocele parameters between the two methods in different positions and provide clinical implications for the diagnosis of rectocele. METHODS: In this pilot study, participants were recruited in an outpatient clinic of a tertiary hospital between December 2017 and December 2019. All participants separately underwent defecation proctography at sitting and squatting positions, and undertook transperineal ultrasonography at left lateral, sitting, and squatting positions. The consistency of ultrasonography and defecography was evaluated. RESULTS: Thirty female volunteers with rectocele were included in this study. The degree of anorectal angle was significantly larger at rest and during contraction, maximal Valsalva, and evacuation; the depth of the rectocele was significantly deeper during maximal Valsalva and evacuation; and the length of the perineum descending was significantly longer during contraction and maximal Valsalva in using squatting position compared to the sitting position when performing the defecation proctography. The degree of anorectal angle, the depth of rectocele, the area of levator hiatus, and the volume of the rectocele were significantly different in using squatting, sitting, and left lateral positions when performing the transperineal ultrasonography. Bland-Altman semi-quantitative plots showed good consistency in the measurement of the anorectal angle and the depth of the rectocele between proctography and ultrasonography in both sitting and squatting positions. CONCLUSIONS: The findings of our study may be considered as the preliminary evidence to support the use of transperineal ultrasonography with sitting and squatting positions as the imaging test of choice for evaluating patients with rectocele.

Caldesmon: Biochemical and Clinical Implications in Cancer.

Caldesmon, an actin-binding protein, can inhibit myosin binding to actin and regulate smooth muscle contraction and relaxation. However, caldesmon has recently attracted attention due to its importance in cancer. The upregulation of caldesmon in several solid cancer tissues has been reported. Caldesmon, as well as its two isoforms, is considered as a biomarker for cancer and a potent suppressor of cancer cell invasion by regulating podosome/invadopodium formation. Therefore, caldesmon may be a promising therapeutic target for diseases such as cancer. Here, we review new studies on the gene transcription, isoform structure, expression, and phosphorylation regulation of caldesmon and discuss its clinical implications in cancer.

Application of 'tying, binding and fixing operation' in surgical treatment of severe mixed hemorrhoids.

The aim of the present study was to examine the clinical value of 'tying, binding and fixing operation' in treating severe mixed hemorrhoids. A total of 160 patients with severe mixed hemorrhoids were selected and randomly divided into the experimental (n=80) and control (n=80) groups. The groups were treated using 'tying, binding and fixing operation' and Doppler ultrasound-guided hemorrhoidal artery ligation (DG-HAL), respectively. The results showed that the average operative time of the experimental group (35.57±6.17) was significantly higher than that of the control group (12.73±4.92). There was no significant difference of blood loss during the operation between the two groups (P>0.05). There was also no significant difference in improving the hemorrhage symptom between the two groups (P>0.05). In addition, concerning improvement of prolapse symptoms and reduction of the volume of hemorrhoids, the experimental group were significantly improved as compared to the control group. No anal function damage in the two groups was identified, and the length of stay in hospital for the two groups was not significantly different (P>0.05). However, the hospitalization cost in the experimental group (5,334.77±875.54) was significantly lower than that of the control group (8,551.81±1,806.54) and satisfaction degree was significantly higher than that of the control group. The incidences of perianal pain, anal edema and dysuria between two groups were not significantly different (P>0.05). There were 10 cases of secondary hemorrhage and 18 cases of infection in the experimental group, and 12 cases of secondary hemorrhage and 14 cases of infection in the control group, although the differences between the two groups were not statistically significant (P>0.05). The incidence rate of local hematoma in the experimental group (1.2%) was significantly lower than that in the control group (15.0%). The recurrence rate of the control group (22.5%) was also significantly higher than that of the experimental group (2.5%). In conclusion, tying, binding and fixing operation is a promising method that may be employed for the treatment of sever mixed hemorrhoids, and it is better than DG-HAL in improving the prolapse and reducing the volume of hemorrhoids.

Biofeedback therapy combined with traditional chinese medicine prescription improves the symptoms, surface myoelectricity, and anal canal pressure of the patients with spleen deficiency constipation.

In order to observe the clinical therapeutic effects of Yiqi Kaimi Prescription and biofeedback therapy on treating constipation with deficiency of spleen qi, the 30 cases in the control group were given oral administration of Yiqi Kaimi Prescription, in combination with anus-lifting exercise; the 30 cases in the treatment group were given biofeedback therapy on the basis of the afore mentioned methods for the control group. The TCM symptom scores and anorectal pressures before and after treatment were observed and evaluated. There were significant differences in TCM symptom scores, anorectal pressure, and clinical recovery rate before and after treatment. In the treatment group, the total recovery rate was 86.66%, while in the control group it was 50%; there were significant differences between the two groups (P < 0.01). Yiqi Kaimi Prescription coupled with biofeedback therapy is clinically effective for treating constipation with deficiency of spleen qi, and thus this method is applicable for functional constipation with deficiency of spleen qi.

Traditional Chinese surgical treatment for anal fistulae with secondary tracks and abscess.

AIM: To evaluate the efficacy and safety of traditional Chinese surgical treatment for anal fistulae with secondary tracks and abscess. METHODS: Sixty patients with intersphincteric or transsphincteric anal fistulas with secondary tracks and abscess were randomly divided into study group [suture dragging combined with pad compression (SDPC)] and control group [fistulotomy (FSLT)]. In the SDPC group, the internal opening was excised and incisions at external openings were made for drainage. Silk sutures were put through every two incisions and knotted in loose state. The suture dragging process started from the first day after surgery and the pad compression process started when all sutures were removed as wound tissue became fresh and without discharge. In the FSLT group, the internal opening and all tracts were laid open and cleaned by normal saline postoperatively till all wounds healed. The time of healing, postoperative pain score (visual analogue scale), recurrence rate, patient satisfaction, incontinence evaluation and anorectal manometry before and after the treatment were examined. RESULTS: There were no significant differences between the two groups regarding age, gender and fistulae type. The time of healing was significantly shorter (24.33 d in SDPC vs 31.57 d in FSLT, P < 0.01) and the patient satisfaction score at 1 mo postoperative follow-up was significantly higher in the SDPC group (4.07 in SDPC vs 3.37 in FSLT, P < 0.05). The mean maximal postoperative pain scores were 5.83 ± 2.5 in SDPC vs 6.37 ± 2.33 in FSLT and the recurrence rates were 3.33 in SDPC vs 0 in FSLT. None of the patients in the two groups experienced liquid and solid fecal incontinence and lifestyle alteration postoperatively. The Wexner score after treatment of intersphincter fistulae were 0.17 ± 0.41 in SDPC vs 0.40 ± 0.89 in FSLT and trans-sphincter fistulae were 0.13 ± 0.45 in SDPC vs 0.56 ± 1.35 in FSLT. The maximal squeeze pressure and resting pressure declined after treatment in both groups. The maximal anal squeeze pressures after treatment were reduced (23.17 ± 3.73 Kpa in SDPC vs 22.74 ± 4.47 Kpa in FSLT) and so did the resting pressures (12.36 ± 2.15 Kpa in SDPC vs 11.71 ± 1.87 Kpa in FSLT), but there were neither significant differences between the two groups and nor significant differences before or after treatment. CONCLUSION: Traditional Chinese surgical treatment SDPC for anal fistulae with secondary tracks and abscess is safe, effective and less invasive.

[Design characteristics of clinical surgery trial based on treatment program of tunnel thread-drawing method for anal fistula: a prospective randomized controlled multicenter trial].

BACKGROUND: Basic principles of clinical trials of nonpharmacologic treatment are similar to those of pharmacologic treatment, but its some special characteristics should be discussed. OBJECTIVE: To explore the design characteristics of clinical surgery trial through the example of tunnel thread-drawing therapy for simple anal fistula. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The clinical trial was designed as a prospective, controlled, randomized multicenter trial. The patients came from Longhua Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western medicine, and Affiliated Hospital of Jianxi University of Traditional Chinese Medicine. Stratified random was performed according to the subtype of anal fistula including low and high anal fistula. Full analysis set was applied to analyze the baseline data, and per protocol set was used in efficacy and safety analysis. The intervention was tunnel thread-drawing method. Classical therapy of thread-drawing method was employed as positive control. MAIN OUTCOME MEASURES: The primary outcomes were course of recovery and cure rate. Quality of life score was used as secondary outcome and anal maximum constriction pressure was considered as safety outcome. RESULTS: Optimal efficiency testing method was used to estimate sample size. A total of 244 subjects were recruited and 236 subjects completed the trial. There was no significant difference in the cure rate of the low and high anal fistula between the treatment group and control group. There was a significant difference in the course of recovery in the patients with low and high anal fistula between treatment group and control group (P<0.01). To the patients with low anal fistula, the course of recovery in the treatment group was (22.26 + or - 8.67) d, and the course of recovery in the control group was (31.41+ or - 11.39) d. To the patients with high anal fistula, the course of recovery in the treatment group was (24.73 + or - 8.15) d, and the course of recovery in the control group was (32.20 + or - 12.60) d. There was no significant difference in the scores of quality of life in the patients with low anal fistula between the treatment group and control group (P>0.05). The trial showed that the tunnel thread-drawing therapy was significantly more effective than classical method for improving the anal sphincter function and patient satisfaction with treatment in the patients with high anal fistula. However the other items of quality of life in the two groups did not show significant difference. There was no any adverse event report in each group. There was no significant difference in the anal maximum constriction pressure in the treatment group before and after the operation. CONCLUSION: The trial shows that the tunnel thread-drawing therapy for simple anal fistula can shorten the course of recovery and improve the patients' quality of life. The training about surgical intervention and clinical implementation program is important in clinical surgery trial. Blind is absolutely difficult to implement and placebo cannot be used in this kind of trial.

[Superiority of thread-dragging therapy in treatment of refractory sinus tracts or fistulae].

The thread-dragging therapy, as a new external treatment of traditional Chinese medicine, could eliminate pathogenic factors and restore the vital qi by promoting qi and activating blood circulation to advance tissue repair in treating refractory sinus tracts or fistulae. This article reviewed its origin and development, and introduced its use in treating refractory sinus tracts or fistulae.