Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can also develop into CRCs through the serrated pathway.Sessile serrated adenomas/polyps(SSAs/Ps),a type of serrated polyps,are easily misdiagnosed during endoscopy.AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types.METHODS From January 2021 to December 2021,patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital,affiliated with Shanghai University of Traditional Chinese Medicine.Thirty cases each of large intestine damp-heat(Da-Chang-Shi-Re,DCSR)syndrome and spleen-stomach weakness(Pi-Wei-Xu-Ruo)syndrome were reported.Baseline comparison of the general data,typical tongue coating,colonoscopy findings,and hematoxylin and eosin findings was performed in each group.The expression of the Wnt pathway-related proteins,namelyβ-catenin,adenomatous polyposis coli,and mutated in colorectal cancer,were analyzed using immunohistochemistry.RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types(P=0.001).The other aspects did not differ between the two groups.The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups,which was manifested asβ-catenin protein translocation into the nucleus.However,SSAs/Ps patients with DCSR syndrome had more nucleation,higherβ-catenin expression,and negative regulatory factor(adenomatous polyposis coli and mutated in colorectal cancer)expression(P<0.0001)than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.In addition,the SSA/P size was linearly correlated with the related protein expression.CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis.A high-quality colonoscopic diagnosis was essential.The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Effective Common Chinese Herbal Medicines Used in Treating Chronic Cholecystitis with Liver-Gallbladder Dampness-Heat Syndrome: A Review of Clinical Studies in the Past 10 Years

The objective of the study is to identify the effective common Chinese herbal medicines used in treating chronic cholecystitis with liver-gallbladder dampness-heat syndrome(CCLGDHS) through reviewing relevant clinical studies published in the past 10 years. Data were collected from Science Direct and Chinese National Knowledge Infrastructure. Data screening was carried out for the abstracts and full texts of the data. The top 15 Chinese herbal medicines with the highest occurring frequency were selected, statistically analyzed, and classified by their medicinal properties, actions, and indications according to the Chinese Pharmacopoeia 2015 edition. The top 15 effective common Chinese herbal medicines comprise Chai Hu, Huang Qin, Jin Qian Cao, Bai Shao, Yin Chen, Yu Jin, Chuan Lian Zi, Yan Hu Suo, Zhi Shi, Ban Xia, Bai Zhu, Pu Gong Ying, Gan Cao, Zhi Zi, and Qing Pi. The predominant natures were cold, cool, and warm. This combination can clear stagnant heat, warm Yang, and regulate Qi dynamics. In addition, bitter, pungent, and sweet were the predominant flavors. They can clear dampness-heat, regulate Qi dynamics to relieve cramps and pain, as well as tonify the deficiency. Along with entering the liver and gallbladder meridians, these herbal medicines also entered the spleen, stomach, and lung meridians to prevent potential disease transmission. The combinatorial medicinal actions of the effective common Chinese herbal medicine highlight the importance of the holistic concept of traditional Chinese medicine when treating CCLGDHS. In addition, the inclusion of activating blood to promote blood circulation, relieving cramps and alleviating pain, and tonifying the spleen and stomach represents a new finding in the treatment principle for CCLGDHS.

Efficacy and Safety of Guihuang Formula in Treating Type Ⅲ Prostatitis Patients with Dampness-Heat and Blood Stasis Syndrome: A Randomized Controlled Trial

Objective: To observe the efficacy and safety of Guihuang Formula(GHF) in treating patients with type Ⅲ prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis. Methods: Sixty-six type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome were randomly divided into the treatment group(GHF) and the control group(tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score, Chinese Medicine Symptoms Score(CMSS), expressed prostatic secretions(EPS) and adverse events(AEs). Results: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups(P<0.05). The CMSS score decreased in both groups(P<0.05). The white blood cell(WBC) count decreased and lecithin body count increased in both groups(P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group(P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups(P>0.05). In addition, no serious AEs were observed. Conclusion: GHF is effective in treating type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs.(Registration No. ChiCTR1900026966)

Haoqin Qingdan Decoction(蒿芩清胆汤)and Ribavirin Therapy Downregulate CD14 and Toll-Like Receptor 4 in Febrile Disease with Dampness-Heat Syndrome in A Mouse Model

Objective： To evaluate the effect of Chinese medicine Haoqin Qingdan Decoction （蒿芩清胆汤, HQD） for febrile disease dampness-heat syndrome （FDDHS）. Methods： Forty mice were divided into four groups, including normal control, FDDHS （induced by Radix et Rhizoma Rhei recipe and influenza virus A1 FM1 model）, HQD, and the ribavirin groups （10 in each）. The normal control and FDDHS groups were administered normal saline. HQD and the ribavirin groups were administered HQD and ribavirin intragastrically once daily at a dose of 64 g/（kg.d） and 0.07 g/（kg.d）, respectively for 7 days. Lethargy, rough hair, diarrhea, tongue color and sole color were evaluated for pathological changes in morphology. The tongue and lung tissues were collected for histology. The CD14 and toll-like receptor 4 （TLR4） expression levels were measured using real-time quantitative polymerase chain reaction. Results： More than 80% of the FDDHS mice showed hypokinesia and lethargy, and pathological changes associated with rough hair, diarrhea, tongue color and sole color. With advanced treatment for 7 days, the thick greasy tongue fur of the HQD and ribavirin groups were thinner than that of the FDDHS group （P〈0.05）, and it was the thinnest in the ribavirin group as compared with that in other groups （P〈0.05）. The CD14 and TLR4 expression levels in the lung tissues of HQD and ribavirin groups significantly delined compared with the model group （P〈0.05 or P〈0.01）. CD14 was down-regulated more remarkably in the HQD group compared with the ribavirin group （P〈0.05）, whereas the converse was true with TLR4 （P〈0.05）. Conclusions： We established a FDDHS mouse model showing systemic clinical symptoms. Both HQD and ribavirin can inhibit the expression of CD14 and TLR4 in FDDHS mice, while the effect of ribavirin might be much more violent. The expression changes of CD14 and TLR4 consistently refers to lipopolysaccharide, the commonly and hotly inducing factor in FDDHS.

Ultrastructure Characteristics of Different Chinese Medicine Syndromes of Helicobacter pylori-Correlated Gastric Diseases

Objective: To explore the ultrastructure characteristics of patients with dampness-heat of Pi(Spleen)-Wei(Stomach) syndrome(DHPW) and Pi-qi deficiency syndrome(PQD), both of which are Helicobacter pylori(Hp)-correlated gastric diseases(HPCG), and implicate a helpful hint for the clinical microcosmic syndrome differentiation. Methods: Fourteen gastric mucosa samples from 6 chronic gastritis(CG) and 6 active peptic ulcer(including 8 DHPW, 4 PQD) as well as 2 healthy volunteers were collected and tested for Hp infection. The ultrastructure of gastric mucosa was observed under the transmission electron microscope(TEM). Results: Among 14 gastric mucosa samples, 8 of them were Hp positive(6 DHPW and 2 PQD), which were all accordance with the results screened by supermicro-pathological method. Under TEM, the normal gastric mucosa, with tidy microvilli and abundant in mucus granules, mitochondria and rough endoplasmic reticulum distributed evenly, and with smooth nucleus membrane. But in those specimens of DHPW with Hp infection, microvilli were presented with burr shape. Especially, those samples from dampnessheat syndrome with predominant heat type(DHSH) patients were more obvious, with microvilli damaged, mitochondria concentrated and distributed in disorder, secretory tubule extended. In dampness-heat syndrome with predominant dampness type(DHSD) patients, mucus granules aggregated obviously, mitochondria swelled and blurred, and rough endoplasmic reticulum crowded. For 2 samples of DHPW without Hp infection, their microvilli were intact, with mitochondria increased and gathered but well-distributed, and secretory tubule extended mildly. In 2 PQD patients with Hp positive, the specimens of microvilli were sparse, and their mucus granules and mitochondria were decreased, with fractured crests and vacuole, secretory tubules extension to nucleus membrane, and rough endoplasmic reticulum extension in a pool-like way, and nucleus condensed. The 2 samples from PQD patients without Hp infection were characterized with intact microvilli, decreased mitochondria, fractured crest and extended rough endoplasmic reticulum in a pool-like way. Conclusion: It is obvious different in ultrastructure of DHPW and PQD patients under TEM, which may give a helpful hint for the microcosmic syndrome differentiation of HPCG.