Natural products - Dawn of keloid treatment.

Keloids are prevalent pathological scars, often leading to cosmetic deformities and hindering joint mobility.They cause discomfort, including burning and itching, while gradually expanding and potentially posing a risk of cancer.Developing effective drugs and treatments for keloids has been a persistent challenge in the medical field. Natural products are an important source of innovative drugs and a breakthrough for many knotty disease.Herein, keywords of "natural, plant, compound, extract" were combined with "keloid" and searched in PubMed and Google Scholar, respectively. A total of 32 natural products as well as 9 extracts possessing the potential for treating keloids were ultimately identified.Current research in this field faces a significant challenge due to the lack of suitable animal models, resulting in a predominant reliance on in vitro studies.In vivo and clinical studies are notably scarce as a result.Moreover, there is a notable deficiency in research focusing on the role of nutrients in keloid formation and treatment.The appropriate dosage form (oral, topical, injectable) is crucial for the development of natural product drugs. Finally, the conclusion was hereby made that natural products, when used as adjuncts to other treatments, hold significant potential in the management of keloids.By summarizing the natural products and elucidating their mechanisms in keloid treatment, the present study aims to stimulate further discoveries and research in drug development for effectively addressing this challenging condition.

Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses.

Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent. Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE). Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]). Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).

Microbiome: Role in Inflammatory Skin Diseases.

As the body's largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.

Menthol: An underestimated anticancer agent.

Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the treatment of various solid tumors. Therefore, using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure databases, the present study reviewed the anticancer activity of menthol and the underlying mechanism. Menthol has a good safety profile and exerts its anticancer activity via multiple pathways and targets. As a result, it has gained popularity for significantly inhibiting different types of cancer cells by various mechanisms such as induction of apoptosis, cell cycle arrest, disruption of tubulin polymerization, and inhibition of tumor angiogenesis. Owing to the excellent anticancer activity menthol has demonstrated, further research is warranted for developing it as a novel anticancer agent. However, there are limitations and gaps in the current research on menthol, and its antitumor mechanism has not been completely elucidated. It is expected that more basic experimental and clinical studies focusing on menthol and its derivatives will eventually help in its clinical application as a novel anticancer agent.

Evaluation of two laboratory model methods for diarrheal irritable bowel syndrome.

BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. METHODS: The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. RESULTS: Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1ß, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. CONCLUSION: In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling.

Effect of Shenling Baizhu powder on immunity to diarrheal disease: A systematic review and meta-analysis.

Background: Diarrhea is one of the leading causes of death worldwide and is associated with immune dysfunction. The modulatory effects of Shenling Baizhu powder (SLBZS) on immune function in diarrheal disease have been validated in various animal models. However, the results of these studies have not been systematically evaluated. This study aimed to evaluate the preclinical data on SLBZS for the treatment of diarrhea from an immunological perspective. Methods: PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, VIP, and Chinese Medicine Database were searched for all animal trials on SLBZS for the treatment of diarrhea published up to April 2022. Standardized mean differences (SMD) were used as effect sizes in the meta-analysis of continuous variables, including immune organs, immune cells, and immune cytokines. Subgroup analysis was performed according to animal species and disease models. The GRADE was used to assess the quality of evidence. Results: A total of 26 studies were included. Meta-analysis showed that compared to those in the model group, SLBZS significantly increased body weight [SMD = 1.54, 95% confidence interval (CI) (1.06, 2.02)], spleen mass [SMD = 1.42, 95% CI (0.98, 1.87)], thymus mass [SMD = 1.11, 95% CI (0.69, 1.53)], macrophage phagocytic capacity (SMD = 1.07, 95% CI [0.59, 1.54]), sIgA [SMD = 1.04, 95% CI (0.33, 1.74)], RBC-C3b-RR [SMD = 1.16, 95% CI (0.65, 1.67)], IL-2 [SMD = 1.52, 95% CI (0.89, 2.14)] and decreased diarrhea scores [SMD = -1.40, 95% CI (-2.03, -0.87)], RBC-IC-RR [SMD = -1.40, 95% CI (-1.94, -0.87)], and IL-8 [SMD = -2.80, 95% CI (-3.54, -2.07)]. Subgroup analysis showed that SLBZS regulated TNF-α, IL-1ß, and IL-10 in rats and mice, and improved IL-6 and IL-10 in different diseases, with differences between subgroups (p < 0.05). Owing to heterogeneity, the reliability of the results remains to be verified. The quality of evidence was "very low". Conclusion: SLBZS improve diarrhea symptoms by enhancing immune function. It has curative effects with differences between different species and diseases, however, because the reporting in the original studies was too unclear to be assessed, the analysis was inconclusive. For higher quality evidences, future research should pay attention to the scientific rigor of the experimental design and the completeness of the reported results.

Application regularity of medicinal and dietary substances for patients during COVID-19 rehabilitation / 数字中医药（英文）

@#Objective This study focused on the application regularity of medicinal and dietary substances (MDS) of traditional Chinese medicine (TCM) diet therapy during rehabilitation, in order to help patients with Corona Virus Disease 2019 (COVID-19) reduce sequelae and improve their life quality. Methods The official websites of the national and provincial health committees, the website of the National Administration of Traditional Chinese Medicine, the China BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database were used to search the keywords, such as “coronavirus” “novel coronavirus pneumonia” “COVID-19” “protocol” “guideline” “consensus” and “rehabilitation period”. The search time was from the establishment of databases to July 31, 2022. The prevention and control protocols of various provinces and cities were manually supplemented and screened out. The information on the frequency, property, flavor, meridian tropism, and efficacy of MDS was collected for association rule analysis through the Apriori algorithm. Hierarchical cluster analysis was performed using the Euclidean distance and longest distance. Results A total of 18 protocols were screened out, including 56 lists of TCM diet therapy, and 47 kinds of MDS with a frequency of 132 times during the rehabilitation of COVID-19. Among them, six lists of diet therapy were collected from national websites, 26 from local government websites, and 24 from social and academic institution websites. The intended population can be divided into seven categories including normal recovery, lung-spleen Qi deficiency, deficiency of both Qi and Yin, spleen-stomach weakness, deficiency of Yang Qi, kidney Qi deficiency, and blood deficiency. Shanyao (Dioscoreae Rhizoma) and Lianzi (Nelumbinis Semen), followed by Dazao (Jujubae Fructus) were used most commonly in MDS, with mainly flat property, sweet flavor, and spleen and lung meridians in meridian tropism. Besides, deficiency-tonifying drugs were commonly used in MDS. Through association rule analysis, 12 groups of association MDS pairs were obtained. The pair of Yiyiren (Coicis Semen) and Chenpi (Citri Reticulatae Pericarpium) had the highest Lift value, and Yiyiren (Coicis Semen) was used most frequently in the MDS category for eliminating pathogenic factors. The results of complex network analysis showed that the core MDS were Yiyiren (Coicis Semen), Shanyao (Dioscoreae Rhizoma), Huangqi (Astragali Radix), Fuling (Poria), and Dazao (Jujubae Fructus). Three core categories were classified by cluster analysis, including the category of strengthening spleen, nourishing kidney, and grasping Qi, the category of removing phlegm, abating panting, and regulating Qi, and the category of strengthening the middle-energizer and reinforcing Qi. Conclusion Based on the TCM theory, most patients during the rehabilitation of COVID-19 are in a state of lingering pathogens due to deficient vital Qi. TCM diet therapy is based on the principle of “giving both reinforcing and reducing treatment”, and the MDS combinations focus on both reinforcing the health Qi and eliminating pathogenic factors. The diet therapy mainly uses the MDS with flat property and sweet flavor, which belongs to deficiency-tonifying drugs, adding suitable MDS of pathogen-eliminating drugs according to different situations. The ultimate goal is to promote lung inflammation absorption, improve pulmonary fibrosis, increase immunity, reduce the occurrence of sequelae, and improve life quality.

Comparison of the Efficacy of Danhong Injections at Different Time-points During the Perioperative Period of Acute Myocardial Infarction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objectives: Danhong injections (DHI) are widely used in the treatment of acute myocardial infarction (AMI). As there are no guidelines for the timing of DHI in the peri-percutaneous coronary intervention (PCI) period for AMI, we investigated the effects of DHI timing. Methods: We reviewed reports published before September 30, 2020 in PubMed, embase, the Cochrane Central Register of Controlled Trials, the Chinese BioMedical database, Chinese VIP database, Wanfang database, and Chinese National Knowledge Infrastructure database. Only randomized controlled trials of DHI with percutaneous coronary intervention for AMI were included. Methodological quality was assessed using the Cochrane evaluation manual 5.3.3 criteria. A meta-analysis was performed, and forest plots were drawn. Results: We included 23 studies which all revealed that patients in DHI groups had better efficacy than control groups. Subgroup analysis revealed that DHI administered intraoperatively and continued postoperatively was more effective in increasing left ventricular ejection fraction when compared to other time-points (p < 0.001). The pre- and intraoperative use of DHI could improve reflow more effectively than conventional treatment, while the effect was not significant in the postoperative intervention study (p = 0.654). The 16 postoperative interventions revealed that the effect of DHI at 14 days was better than that at 7 and 10 days for hs-CRP (p = 0.013), the 10-days treatment produced better results for CK-MB than for the other treatments (p < 0.001) and a dosage of 30 ml proved most effective for IL-6 (p < 0.001). Conclusion: DHI proved to be superior to conventional Western medicine in reducing the incidence of adverse cardiac events, promoting reperfusion, improving cardiac function, reducing inflammatory factors, and protecting the myocardium. DHI should be administered early in the perioperative period and continued postoperatively because of its ability to improve cardiac function. Furthermore, in the PCI postoperative, 30 ml is recommended to inhibit IL-6 levels, for patients with high hs-CRP, a course of 14 days is most effective, for patients with obvious abnormalities of CK-MB, a 10-days course of treatment is recommended. However, due to the limited number and quality of the original randomized controlled trials, our conclusions need large, multi-centre RCTs to validation.

Acupoint catgut embedding for the treatment of peptic ulcers: A protocol for systematic review and meta analysis.

BACKGROUND: Peptic ulcer (PU) is a common clinical disease of the digestive system, which can occur in all ages, gastric and duodenal ulcers are the most commonly seen PUs in clinical practice. The main manifestations are chronic and periodic rhythmic upper abdominal pain, accompanied by indigestion symptoms such as pantothenic acid, belching, and nausea. Serious complications such as bleeding, perforation, obstruction and canceration are easy to occur, endangering the life safety of patients. There are many ways to treat PU in clinic, and acupoint catgut embedding therapy has its unique advantages. Hence, our systematic review aims to evaluate the efficacy and safety of acupoint embedding therapy in the treatment of PU and to provide a reliable basis for physician. METHODS: We will search electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database (WF), China Biomedical Literature Database (CBM), and China Scientific Journals Database (VIP) from establishment to April 2021, and will manually searched the list of medical journals as a supplement. Two authors will screen the studies independently, as well as extract data information, and assess methodological quality through the Cochrane risk of bias (ROB) tool. The Stata software (Version 16.0) software will be used for statistical analysis. RESULTS: By evaluating the current status of acupoint catgut embedding for Peptic ulcer disease, this study would prove the effectiveness and safety of acupoint embedding therapy, and will be published in a peer-reviewed journal. CONCLUSION: This systematic review will provide a credible evidence-based for acupoint catgut embedding in the treatment of peptic ulcer. INPLASY REGISTRATION NUMBER: INPLASY202130097.

Randomized Controlled Trial of Polyethylene Glycol versus Oral Sodium Phosphate for Bowel Preparation in Unsedated Colonoscopy.

AIM: To identify the most effective laxative for bowel preparation in unsedated colonoscopy. METHODS: Between April 2019 and April 2020, a total of 586 outpatients scheduled for unsedated colonoscopy at the First Hospital of Jilin University (Changchun, China) were randomized into one of two groups, namely, the polyethylene glycol (PEG) group or the oral sodium phosphate solution (OSP) group. The cleaning efficiency and other relevant clinical parameters were compared between the two groups. RESULTS: Each group consisted of 293 patients. There were no significant differences in gender, body mass index, and history of abdominal surgery between the two groups. There were more cases of laxative intolerance in the PEG group than in the OSP group (7.5% vs. 0.7%, P < 0.05). After tube insertion, we found that the cleaning efficiency of OSP was better than that of PEG (P < 0.05). After cleaning, there was no significant difference in bowel cleanliness between the two groups (P > 0.05). The colonoscopic insertion time of the PEG group was significantly shorter than that of the OSP group (10.0 vs. 12.0 min, P = 0.002), and colonoscopic insertion was more difficult in the OSP group than in the PEG group (P = 0.036). The VAS score of the PEG group patients was significantly lower than that of OSP group patients (4.0 ± 1.3 vs. 5.2 ± 1.7, P ≤ 0.001). There were no significant differences in the cecal intubation rate and the detection rate of polyps and ulcers/erosion between the two groups. CONCLUSION: The cleaning efficiency and tolerability of OSP were preferable to those of PEG, but there was no significant difference in bowel cleanliness after washing the colon and suctioning the fluid. Compared with patients of the OSP group, those of the PEG group required a shorter colonoscopic insertion time and reported a more comfortable experience. Therefore, for cases that are tolerant of PEG, PEG is a better choice for unsedated colonoscopy.