Refining the rheological characteristics of high drug loading ointment via SDS and machine learning.

This paper presents an optimized preparation process for external ointment using the Definitive Screening Design (DSD) method. The ointment is a Traditional Chinese Medicine (TCM) formula developed by Professor WYH, a renowned TCM practitioner in Jiangsu Province, China, known for its proven clinical efficacy. In this study, a stepwise regression model was employed to analyze the relationship between key process factors (such as mixing speed and time) and rheological parameters. Machine learning techniques, including Monte Carlo simulation, decision tree analysis, and Gaussian process, were used for parameter optimization. Through rigorous experimentation and verification, we have successfully identified the optimal preparation process for WYH ointment. The optimized parameters included drug ratio of 24.5%, mixing time of 8 min, mixing speed of 1175 rpm, petroleum dosage of 79 g, liquid paraffin dosage of 6.7 g. The final ointment formulation was prepared using method B. This research not only contributes to the optimization of the WYH ointment preparation process but also provides valuable insights and practical guidance for designing the preparation processes of other TCM ointments. This advanced DSD method enhances the screening approach for identifying the best preparation process, thereby improving the scientific rigor and quality of TCM ointment preparation processes.

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: a prospective case-control study.

BACKGROUND: Complex cryptoglandular perianal fistula (CPAF) is a kind of anal fistula that may cause anal incontinence after surgery. Minimally invasive surgery of anal fistula is constantly emerging. Over the past 20 years, there are several sphincter-sparing surgeries, one of which is autologous adipose-derived stem cell (ADSC) transplantation. However, to date, there is no study regarding the treatment of complex CPAF with ADSC in China. This is the first study in China on the treatment of complex CPAF with ADSC to evaluate its safety and efficacy. METHODS: Totally, 24 patients with complex CPAF were enrolled in this prospective case-control study from January 2018 to December 2019 in the National Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided into ADSC group and endorectal advancement flap (ERAF) group according to their desire. The healing of fistulas (healing of all treated fistulas at baseline, confirmed by doctor's clinical assessment and magnetic resonance imaging or transrectal ultrasonography) was evaluated at week 12 after treatment. In addition to their safety evaluation based on adverse events monitored at each follow-up, the patients were also asked to complete some scoring scales at each follow-up including pain score with visual analog score (VAS) and anal incontinence score with Wexner score. RESULTS: The closure rates within ADSC group and ERAF group at week 12 were 54.55% (6/11) and 53.85% (7/13), respectively, without significant difference between them. VAS score in ADSC group was significantly lower than that in ERAF group at the 5th day postoperatively [1(0,2) VS 2(2,4), p = 0.011], but no differences were observed at the other time. Wexner score of all patients was not increased with no significant differences between the two groups. Adverse events were observed fewer in ADSC group (27.27%) than that in ERAF group (53.85%), but there was no significant difference between them. CONCLUSION: This study indicated safety and efficiency of ADSC for the treatment of complex CPAF in the short term, which is not inferior to that of ERAF. ADSC may provide a promised and potential treatment for complex CPAF conforming to the future of the treatment, which is reconstruction and regeneration. TRAIL REGISTRATION: ChiCTR, ChiCTR1800014599. Registered 23 January 2018-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=24548.

Autologous adipose-derived stem cells for the treatment of Crohn's fistula-in-ano: an open-label, controlled trial.

BACKGROUND: Crohn's fistula-in-ano is a refractory disease in colorectal and anal surgery. Although autologous adipose-derived stem cell (ADSC) has been used in the treatment of Crohn's fistula-in-ano because of its convenience, non-incision of normal tissue, good tolerance, repeatability, quick recovery, less pain, less damage to anal function, and high quality of life during the perioperative period, there are no reports of its use in China. This is the first clinical trial in China on the treatment of Crohn's fistula-in-ano with ADSC to evaluate its efficacy and safety. METHODS: A total of 22 patients with Crohn's fistula-in-ano were enrolled in this study from January 2018 to October 2018 in the Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided (1:1) into an observation group (ADSC) and a control group (incision-thread-drawing procedure). Primary efficacy endpoint evaluated at months 3, 6, and 12 was the closure of fistulas (closure of all treated fistulas at baseline, confirmed by doctor's clinical assessment and magnetic resonance imaging or transrectal ultrasonography). The patients additionally completed some scoring scales at each follow-up including simplified Crohn's Disease Activity Index (CDAI), Perianal Disease Activity Index (PDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), pain scores with visual analog score (VAS), and Wexner score. The data of inflammatory indexes were also collected. RESULTS: The healing rates of the observation group and the control group at months 3, 6, and 12 were as follows: 10/11(90.9%) vs 5/11(45.5%), 8/11(72.7%) vs 6/11(54.5%), and 7/11(63.6%) vs 6/11(54.5%), respectively. There was no statistical difference between the two groups. In addition, the improvement in simplified CDAI, PDAI, IBDQ, VAS, and Wexner score of the observation group were better than that of the control group at each follow-up. The inflammatory indexes decreased in both the observation group and the control group at 3 months follow-up. And there were no significant differences in the changes of inflammatory indexes between two groups at month 3 compared with the baseline. Safety was maintained throughout month 12, and adverse events occurred in 63.6% of patients in the observation group and 100% patients in the control group. And no adverse event associated with ADSC injection was observed in the study. CONCLUSION: ADSC is a feasible and effective treatment for Crohn's fistula-in-ano, compared with traditional incision and thread-drawing. It can protect anal function of patients, relieve pain, allow quick recovery, be well-tolerated, and improve the quality of life during perioperative period. TRIAL REGISTRATION: China Clinical Trials Registry, No. ChiCTR1800014599. Registered 23 January 2018.

[A multicenter, randomized controlled trial of wheat cellulose particles in the treatment of internal hemorrhoids].

OBJECTIVE: To evaluate the efficacy and safety of wheat cellulose particles (testa triticum tricum purify, Fiberform) in the treatment of internal hemorrhoid. METHODS: A multicenter randomized controlled clinical trial was adopted. From October 2015 to July 2016, 60 patients with internal hemorrhoid were enrolled from three medical centers, including Department of Anorectum, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Department of Anorectum, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Anorectum, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine. Enrollment criteria: Patients aging from 18 to 65 years old; being diagnosed with the second or third grade internal hemorrhoid; having good communication skills and being able to complete the records and follow-ups according to the research program requirements. EXCLUSION CRITERIA: Patients combined with other anal diseases, or whose anus tube or rectum suffering occupying lesions; patients currently using other methods and defecation drugs in the treatment of their hemorrhoids; patients in pregnancy or with diseases of heart, liver, kidney or metabolic disorders; patients suffering from constipation due to other diseases and drugs, and long-term laxatives abusers. According to the random number table method, 60 patients were randomly divided into the combined treatment group [30 cases, wheat cellulose particles 1 bag each time, 2 times per day; Diosmin tablet 2 pills, 2 times per day] and the single treatment group [30 cases, Diosmin tablet 2 pills, 2 times per day]. The treatment courses for both groups were 7 days. According to the four-grade scoring method, the efficacy evaluation would be made on six indicators, which were the degree of hematochezia or bleeding, the degree of pain, hemorrhoid prolapse, the shapes and properties of stool, the defecation frequency and the defecation duration. The higher the score a participant got, the more severe the symptom was. The effectiveness was evaluated by the scoring reduction rate, and marked effectiveness and effectiveness were both found to be effective. Incidence of adverse events was compared between two groups before the treatment, and on postoperative 3-day and 7-day respectively. RESULTS: There were no significant differences between two groups in gender, age, internal hemorrhoids gradings, disease course, and onset time as well as the baseline data, such as the degree of hematochezia or bleeding before the treatment, the degree of pain, hemorrhoid prolapse, the shapes and properties of stool, the defecation frequency and the defecation duration (all P>0.05). After the seven-day treatment, there was significant difference in effective rate between combination group and single group [96.7%(29/30) vs. 66.7%(20/30), Z=-4.376, P=0.000]. Meanwhile, the scores of combined group and single group in hematochezia or bleeding were 0(0, 1) and 0(0, 2) (Z=9.241, P=0.002); in shapes and properties of stool were 0(0, 1) and 0(0, 1) (Z=5.364, P=0.021); in defecation frequency were 0(0, 1) and 0(0, 2) (Z=7.552, P=0.006); and in defecation duration were 0(0, 1) and 0(0, 2) (Z=4.425, P=0.035), whose differences were all significant. The scores of pain degree and hemorrhoid prolapse of two groups also decreased, but the difference was not statistically significant (P>0.05). During the treatment, abdominal pain, diarrhea and other adverse reactions were not observed in participants of two groups. CONCLUSION: Combination therapy of wheat cellulose particles (testa triticum tricum purify, Fiberform) can significantly improve the efficacy of internal hemorrhoid with safety and tolerance.

Decreased Warburg effect induced by ATP citrate lyase suppression inhibits tumor growth in pancreatic cancer.

ATP citrate lyase (ACLY) is responsible for the conversion of cytosolic citrate into acetyl-CoA and oxaloacetate, and the first rate-limiting enzyme involved in de novo lipogenesis. Recent studies have demonstrated that inhibition of elevated ACLY results in growth arrest and apoptosis in a subset of cancers; however, the expression pattern and underlying biological function of ACLY in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the current study, overexpressed ACLY was more commonly observed in PDAC compared to normal pancreatic tissues. Kaplan-Meier survival analysis showed that high expression level of ACLY resulted in a poor prognosis of PDAC patients. Silencing of endogenous ACLY expression by siRNA in PANC-1 cells led to reduced cell viability and increased cell apoptosis. Furthermore, significant decrease in glucose uptake and lactate production was observed after ACLY was knocked down, and this effect was blocked by 2-deoxy-D-glucose, indicating that ACLY functions in the Warburg effect affect PDAC cell growth. Collectively, this study reveals that suppression of ACLY plays an anti-tumor role through decreased Warburg effect, and ACLY-related inhibitors might be potential therapeutic approaches for PDAC.

[Influence of fiberform on defecation condition after surgery for benign anorectal lesion].

OBJECTIVE: To explore the influence of fiberform on the defecation condition after surgery for benign anorectal lesion. METHODS: A total of 121 cases undergoing surgery for benign anorectal lesion at the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from October 2009 to February 2010 were randomly divided into the treatment group (n=61) and the control group (n=60) according to random number table. Patients in the treatment group received fiberform granule for 2 weeks while patients in the control group did not receive any medication to promote defecation. Postoperative defecation symptom scores and patient satisfaction were compared between the two groups. RESULTS: On postoperative day 7, patients in the treatment group had a lower defecation smoothness score (62.1% decrease), lower fecal character score (74.3% decrease), lower defecation interval score (80.2% decrease), lower defecation pain score (77.5% decrease), the differences were statistically significant. On postoperative day 14, the degree of decrease of the abovementioned score were 58.3%, 88.5%, 82.8% and 83.1%, respectively. Postoperative patient satisfaction rate in the treatment group was significantly higher than that in the control group(P<0.05). No patient in the treatment group experienced any adverse events such as abdominal pain, diarrhea, and drug dependence. CONCLUSION: Fiberform can effectively prevent defecation disorders such as dry stool, unsmooth defecation, and anorectal pain.

[Study of germline mutation of hMSH2, hMSH6 and hMLH1 and methylation of hMLH1 in microsatellite instability colorectal cancer].

OBJECTIVE: To study the characteristics of germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation status of MLH1 in patients with MSI colorectal cancer. METHODS: Sequence analysis of germline mutation and promoter methylation of MLH1 in 34 prospective collected patients with MSI colorectal cancer were performed. RESULTS: Nineteen out of 34 patients with MSI colorectal cancer were detected with hypermethylation of MLH1,which accounted for 55.9%. 73.7% MSI-H colorectal cancer cases and 33.3% MSI-L colorectal cancer cases were detected with hypermethylation of MLH1 and the difference was significant. Eight germline mutations were found, including 3 MSH6 mutations and 5 MSH2 mutations. CONCLUSION: There are some different characteristics of the germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation of MLH1 in Chinese MSI colorectal patients.