Compound sophora decoction alleviates ulcerative colitis by regulating macrophage polarization through cGAS inhibition: network pharmacology and experimental validation.

INTRODUCTION: Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS: A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS: A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION: We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

Promising preclinical models for lung cancer research-lung cancer organoids: a narrative review.

Background and Objective: Traditional cell line models are the commonly used preclinical models for lung cancer research. However, cell lines cannot recapitulate the complex tumor heterogeneity and cannot mimic the microenvironment of human cancer. Recently, 3D multicellular in vitro self-assembled models called "organoids" have been developed at a fast pace in the field of research, which can mimic the actual primary tumor. At present, several studies have reported on protocols of lung cancer organoids (LCOs) generation, and using LCOs can provide novel insight into the basic and translational research of lung cancer. However, the establishment of the LCO models remains challenging due to the complexity of lung cancer and the immaturity of organoid technology, so it is necessary to understand the influences of different methodologies on LCO generation and review the applications and limitations of LCO models. Methods: In this review, we searched the literature in the recent ten years in the field of LCOs. Key Content and Findings: We summarized the methodology, the problems, and the solutions in the LCOs generation, its application and limitations, as well as proposing future challenges and perspectives. Conclusions: Currently, LCOs are successfully generated via exploring the methodology by the researchers. Though there are still challenges in clinical application, LCOs are applied in some cancer studies including investigation of anti-cancer treatment response in vitro, modeling tumor immune microenvironment, and construction of organ chips, which are forging a promising path towards precision medicine.

Inhibition of RAC attenuates Adriamycin-induced podocyte injury.

Minimal Change Disease (MCD), which is associated with podocyte injury, is the leading cause of nephrotic syndrome in children. A considerable number of patients experience relapses and require prolonged use of prednisone and immunosuppressants. Multi-drug resistance and frequent relapses can lead to disease progression to focal and segmental glomerulosclerosis (FSGS). To identify potential targets for therapy of podocyte injury, we examined microarray data of mRNAs in glomerular samples from both MCD patients and healthy donors, obtained from the GEO database. Differentially expressed genes (DEGs) were used to construct the protein-protein interactions (PPI) network through the application of the search tool for the retrieval of interacting genes (STRING) tool. The most connected genes in the network were ranked using cytoHubba. 16 hub genes were selected and validated by qRT-PCR. RAC2 was identified as a potential therapeutic target for further investigation. By downregulating RAC2, Adriamycin (ADR)-induced human podocytes (HPCs) injury was attenuated. EHT-1864, a small molecule inhibitor that targets the RAC (RAC1, RAC2, RAC3) family, proved to be more effective than RAC2 silencing in reducing HPCs injury. In conclusion, our research suggests that EHT-1864 may be a promising new molecular drug candidate for patients with MCD and FSGS.

Antagomir of miR-31-5p modulates macrophage polarization via the AMPK/SIRT1/NLRP3 signaling pathway to protect against DSS-induced colitis in mice.

Macrophage-driven immune dysfunction of the intestinal mucosa is involved in the pathophysiology of ulcerative colitis (UC). Emerging evidence indicates that there is an elevation in miR-31-5p levels in UC, which is accompanied by a downregulation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) expression. Nevertheless, the precise influence of miR-31-5p on macrophage polarization and the integrity of the intestinal epithelial barrier in UC remains to be fully elucidated. This study explored the role of miR-31-5p and AMPK in UC through a bioinformatics investigation. It investigated the potential of miR-31-5p antagomir to shift macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype and enhance the intestinal mucosal barrier in DSS-induced UC mice. Additionally, RAW264.7 cells stimulated with LPS were employed to confirm the reversal of miR-31-5p antagomir's therapeutic effect under AMPK inhibition. The findings demonstrated that miR-31-5p antagomir penetrated colonic tissues and ameliorated DSS-induced experimental colitis. Transformation of spleen and mesenteric lymph node macrophages from M1 to M2 type was seen in the DSS+miR-31-5p antagomir group. AMPK/Sirt1 expression increased while NLRP3 expression decreased. Expression of M2-related genes and proteins was enhanced and that of the M1 phenotype suppressed. Tight junction proteins, ZO-1 and occludin, were increased. The therapeutic effects of miR-31-5p antagomir transfection into RAW264.7 cells were repressed when AMPK expression was inhibited. Therefore, our results suggest that suppression of miR-31-5p expression transformed macrophages from M1 to M2, ameliorated inflammation and repaired the intestinal epithelium to alleviate DSS-induced colitis. AMPK/Sirt1/NLRP3 was involved.

A meta-analysis of diabetes risk prediction models applied to prediabetes screening.

AIM: To provide a systematic overview of diabetes risk prediction models used for prediabetes screening to promote primary prevention of diabetes. METHODS: The Cochrane, PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for a comprehensive search period of 30 August 30, 2023, and studies involving diabetes prediction models for screening prediabetes risk were included in the search. The Quality Assessment Checklist for Diagnostic Studies (QUADAS-2) tool was used for risk of bias assessment and Stata and R software were used to pool model effect sizes. RESULTS: A total of 29 375 articles were screened, and finally 20 models from 24 studies were included in the systematic review. The most common predictors were age, body mass index, family history of diabetes, history of hypertension, and physical activity. Regarding the indicators of model prediction performance, discrimination and calibration were only reported in 79.2% and 4.2% of studies, respectively, resulting in significant heterogeneity in model prediction results, which may be related to differences between model predictor combinations and lack of important methodological information. CONCLUSIONS: Numerous models are used to predict diabetes, and as there is an association between prediabetes and diabetes, researchers have also used such models for screening the prediabetic population. Although it is a new clinical practice to explore, differences in glycaemic metabolic profiles, potential complications, and methods of intervention between the two populations cannot be ignored, and such differences have led to poor validity and accuracy of the models. Therefore, there is no recommended optimal model, and it is not recommended to use existing models for risk identification in alternative populations; future studies should focus on improving the clinical relevance and predictive performance of existing models.

Self-powered and broadband CuSCN/Si heterojunction photodetector for multi-color imaging based on diffuse reflection mode.

Copper thiocyanate (CuSCN) has been widely used in photodetectors (PDs). However, the reported CuSCN-based PDs are suffered from narrow operating wavelength range and relatively low photodetection performance. Here, we fabricate an CuSCN/Si heterojunction PD by a simple low-temperature solution spin-coating method achieving excellent performance. Our designed CuSCN/Si PD exhibits a broadband response range covering ultraviolet-visible-infrared, a high detectivity of 2.26 × 1012Jones coming from an ultralow dark current of 23 pA, and a decent responsivity of 11 mA W-1, a high linear dynamic range of 122 dB, and short response time of 25/150µ(rise and decay time). Moreover, we demonstrate multi-color imaging across the wide wavelength range, indicating the CuSCN/Si PD has a promising potential in the imaging field. This work may pave the way for fabricating low-cost, nontoxicity, and high-performance CuSCN-based PD and broadening its applications.

New progress of tuberculosis scar carcinoma.

It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).

Circular RNA hsa_circ_0098181 inhibits metastasis in hepatocellular carcinoma by activating the Hippo signaling pathway via interaction with eEF2.

INTRODUCTION AND OBJECTIVES: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. MATERIALS AND METHODS: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. RESULTS: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. CONCLUSIONS: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.

Performance of a prediabetes risk prediction model: A systematic review.

Backgrounds: The prediabetes population is large and easily overlooked because of the lack of obvious symptoms, which can progress to diabetes. Early screening and targeted interventions can substantially reduce the rate of conversion of prediabetes to diabetes. Therefore, this study systematically reviewed prediabetes risk prediction models, performed a summary and quality evaluation, and aimed to recommend the optimal model. Methods: We systematically searched five databases (Cochrane, PubMed, Embase, Web Of Science, and CNKI) for published literature related to prediabetes risk prediction models and excluded preprints, duplicate publications, reviews, editorials, and other studies, with a search time frame of March 01, 2023. Data were categorized and summarized using a standardized data extraction form that extracted data including author; publication date; study design; country; demographic characteristics; assessment tool name; sample size; study type; and model-related indicators. The PROBAST tool was used to assess the risk of bias profile of included studies. Findings: 14 studies with a total of 15 models were eventually included in the systematic review. We found that the most common predictors of models were age, family history of diabetes, gender, history of hypertension, and BMI. Most of the studies (83.3%) had a high risk of bias, mainly related to under-reporting of outcome information and poor methodological design during the development and validation of models. Due to the low quality of included studies, the evidence for predictive validity of the available models is unclear. Interpretation: We should pay attention to the early screening of prediabetes patients and give timely pharmacological and lifestyle interventions. The predictive performance of the existing model is not satisfactory, and the model building process can be standardized and external validation can be added to improve the accuracy of the model in the future.

Sb2Se3/CdS/ZnO photodetectors based on physical vapor deposition for color imaging applications.

The reported antimony selenide (Sb2Se3) photodetectors (PDs) are still far away from color camera applications mainly due to the high operation temperature required in chemical vapor deposition (CVD) and the lack of high-density PD arrays. In this work, we propose a Sb2Se3/CdS/ZnO PD created by physical vapor deposition (PVD) operated at room temperature. Using PVD, a uniform film can be obtained, so the optimized PD has excellent photoelectric performance with high responsivity (250 mA/W), high detectivity (5.6 × 1012 Jones), low dark current (∼10-9 A), and short response time (rise: < 200 µs; decay: < 200 µs). With the help of advanced computational imaging technology, we successfully demonstrate color imaging applications by the single Sb2Se3 PD; thus, we expect this work can bring Sb2Se3 PDs in color camera sensors closer.

Perovskite-based color camera inspired by human visual cells.

There are two primary types of photoreceptor cells in the human eye: cone cells and rod cells that enable color vision and night vision, respectively. Herein, inspired by the function of human visual cells, we develop a high-resolution perovskite-based color camera using a set of narrowband red, green, blue, and broadband white perovskite photodetectors as imaging sensors. The narrowband red, green, and blue perovskite photodetectors with color perceptions mimic long-, medium-, and short-wavelength cones cells to achieve color imaging ability. Also, the broadband white perovskite photodetector with better detectivity mimics rod cells to improve weak-light imaging ability. Our perovskite-based camera, combined with predesigned pattern illumination and image reconstruction technology, is demonstrated with high-resolution color images (up to 256 × 256 pixels) in diffuse mode. This is far beyond previously reported advanced perovskite array image sensors that only work in monochrome transmission mode. This work shows a new approach to bio-inspired cameras and their great potential to strongly mimic the ability of the natural eye.

Mosaic-free compound eye camera based on multidirectional photodetectors and single-pixel imaging.

Compound-eye wide field-of-view (FOV) imaging generally faces the disadvantages of a complex system, low resolution, and complicated image mosaic. Single-pixel imaging has proven to very beneficial in building a high-resolution and simple wide-FOV camera, but its ability to overcome the problem of image mosaics still needs to be demonstrated. In this Letter, we propose a novel, to the best of our knowledge, kind of artificial compound eye based on multidirectional photodetectors (PDs) and demonstrate theoretically and experimentally that mosaics are unnecessary in multidirectional PD-based single-pixel imaging. In addition, we show experimentally that only nine multidirectional PDs are needed to obtain wide-angle images in a hemisphere to realize wide-FOV mosaic-free imaging. This work greatly simplifies the concept of compound-eye cameras and is very enlightening for detector design in wide-FOV single-pixel imaging, plausibly leading to the development of single-pixel endoscopic imaging.

Comparison of clinical outcomes of frozen-thawed D5 and D6 blastocysts undergoing preimplantation genetic testing.

BACKGROUND: This study aimed to analyze the clinical outcomes of blastocyst which undergo the preimplantation genetic testing (PGT) transplantation from frozen-thawed D5 and D6. In addition, the effect of blastocyst grade on clinical and neonatal outcomes was also investigated in this study. METHODS: The pregnancy and miscarriage rates of 1130 cycles of frozen embryo transfer, including 784 D5 frozen embryos and 346 D6 frozen embryos in the Reproductive Hospital of Shandong University from January to December 2020 were analyzed. Gardner blastocyst scoring was used for blastocyst evaluation. RESULTS: The pregnancy rate of D5 blastocyst was significantly higher, whereas the miscarriage rate of D5 blastocyst was lower, than that of D6 blastocyst tissue biopsy. No significant difference was observed in birth weight and low birth weight of D5 blastocyst and D6 blastocyst, preterm birth, gestational age, and neonatal sex. Frozen-thawed D5 blastocysts have higher pregnancy success rates and lower miscarriage rates compared to D6 blastocysts. CONCLUSION: Therefore, both blastocyst grade and embryo biopsy date must be considered when transferring frozen embryos.

BMSCs improve TNBS-induced colitis in rats by inducing Treg differentiation by expressing PD-L1.

OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BMSCs) show promise in treating inflammatory bowel disease. We tested if BMSCs improve Trinitro-benzene-sulfonic acid (TNBS)-induced colitis by inducing Treg differentiation by modulating programmed cell death 1 ligand 1(PD-L1). RESULTS: BMSCs were isolated and transfected with PD-L1 siRNA. Sprague-Dawley rats were randomly divided into 4 groups: normal, model, BMSC control, and PD-L1 siRNA BMSC. Colitis was induced by TNBS, except in the normal group. On d4, the BMSC control and PD-L1 siRNA BMSC groups were intravenously injected with BMSCs at a dose of 5 × 106 cells in phosphate-buffered saline (PBS; volume matched). BMSCs were later verified to have reached the colon tissue. BMSC control showed significantly better clinical symptoms and reduced histopathological colitis severity; PD-L1 siRNA BMSC group showed no difference. PD-L1 siRNA reduced: spleen and mesenteric lymph node Tregs, PD-L1, interleukin-10 (IL10), phosphate and tension homology deleted on chromosome ten (PTEN); colon p-Akt and p-mTOR were increased. CONCLUSIONS: We found that BMSCs can induce Treg differentiation by inhibiting the Akt/mTOR pathway via PD-L1; this significantly improved symptoms and pathology in our ulcerative colitis rat models.

Program for education and enrichment of relational skills (PEERS) training for social skills and depressed mood intervention in young adult with depression: Study protocol for a randomized controlled trial.

Introduction: Depression is a common psychiatric disorder characterized by persistent low mood, reduced interest, and slowed thinking. Young adults are the main first-onset group for depression in all categories of the population. Program for education and enrichment of relational skills (PEERS) training, a program for the Education and Enrichment of Relational Skills, has been used in Europe and America for people with various types of social disorders with good results. A Chinese adaptation of the PEERS training program may be a new approach to help youth with depression return to society as soon as possible. This study aimed to construct and optimize a social skills training program for Chinese young adults with depression and to validate the impact of the program. Materials and methods and analysis: The aim of this trial protocol is to evaluate the efficacy of the localized PEERS training program on social competence, depressed mood in a Chinese young adult population with depression. The primary outcome will be a change in self-reported depressive symptoms from baseline to week 3 post-randomization to week 6 post-randomization measured using the Liebowitz social anxiety scale (LSAS). Secondary outcomes include the rate of decline in severe social anxiety, the Social Avoidance and Distress Scale (SAD), the Social Self-Efficacy Scale (PSSE), and the Hamilton Depression Scale (HAMD-17). Data for each assessment will be collected at baseline, week 3 of the trial, and week 6 of the trial. Ethics and dissemination: Ethics approval was obtained from the Hospital Ethics Committee. Findings will be disseminated through scientific journals, conferences, and university courses. Trial registration number: [http://www.chictr.org.cn/], identifier [ChiCTR2100046050].

Perovskite Wide-Angle Field-Of-View Camera.

Researchers have attempted to create wide-angle field-of-view (FOV) cameras inspired by the structure of the eyes of animals, including fisheye and compound eye cameras. However, realizing wide-angle FOV cameras simultaneously exhibiting low distortion and high spatial resolution remains a significant challenge. In this study, a novel wide-angle FOV camera is developed by combining a single large-area flexible perovskite photodetector (FP-PD) using computational technology. With this camera, the proposed single-photodetector imaging technique can obtain high-spatial-resolution images using only a single detector, and the large-area FP-PD can be bent further to collect light from a wide-angle FOV. The proposed camera demonstrates remarkable features of an extraordinarily tunable wide FOV (greater than 150°), high spatial resolution of 256 × 256 pixels, and low distortion. It is believed that the proposed compatible and extensible camera prototype will promote the development of high-performance versatile FOV cameras.

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC.

Achieving dual-color imaging by dual-band perovskite photodetectors coupled with algorithms.

Dual-color or multispectral imaging based on conventional optical imaging techniques is suffering from the bottleneck of complex manufacturing and time consumption caused by multiple imaging. Herein, we develop a dual-color computational imaging system combining a vertically stacked dual-channel dual-band perovskite photodetectors (PDs) and the advanced Fourier imaging algorithm. Significantly, our imaging system bypasses the complex fabrication process of high-density dual-band PD arrays and is enabled to capture two high-resolution spectral images at the same time. Based on the experiments and simulations, we confirm that the spectral overlap of dual-band PDs will cause detrimental effect for color identification, and optimizing the bandwidth spectrum is beneficial for achieving much better spectral imaging. Moreover, we have further improved the imaging quality by increasing the sampling rate and suppressing current fluctuations. We suggest that these results provide important interesting insights for the development of advanced imaging systems, including IR imaging, THz imaging, multispectral/hyperspectral imaging, etc.

ROS-responsive nanoparticles for oral delivery of luteolin and targeted therapy of ulcerative colitis by regulating pathological microenvironment.

Oxidative stress, caused by excessive production of reactive oxygen species (ROS), plays a crucial role in the occurrence and development of ulcerative colitis (UC). We developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against UC with oral administration. The NPs were fabricated with a d-α-tocopherol polyethylene glycol succinate-b-poly(ß-thioester) copolymer (TPGS-PBTE) for ROS cleavage via the colitis-targeted delivery of luteolin (LUT), a natural flavonoid with good anti-inflammation and radical-scavenging activity. Owing to the thioether bond in the polymer main chain, the TPGS-PBTE NPs exhibited an ROS-responsive size change and drug release, which benefited the ROS-scavenging and selective accumulation of LUT in the inflamed colon. In a dextran sulfate sodium-induced acute colitis murine model, LUT@TPGS-PBTE NPs alleviated body weight loss, colon length shortening, and damage to the colonic tissues due to the suppression of ROS and proinflammatory cytokines (e.g., IL-17A, IL-6, interferon-γ, tumor necrosis factor-α), as well as upregulation of glutathione and anti-inflammatory factors (e.g., IL-10, IL-4). More importantly, LUT@TPGS-PBTE NPs regulated the inflammatory microenvironment by modulating the T helper (Th)1/Th2 and Th17/regulatory T cell (Treg) balance (i.e., increased numbers of Tregs and Th2 cells and decreased numbers of Th1 and Th17 â€‹cells), thus resolving inflammation and accelerating the healing of the intestinal mucosa. Additionally, the LUT@TPGS-PBTE NPs formulation enabled the reduction of the effective dose of LUT and showed excellent biosafety in the mouse model, demonstrating its potential as a targeted UC therapeutic oral preparation.

Assessing the post-treatment therapeutic effect of tongxie in irritable bowel syndrome: A randomized controlled trial.

Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17-25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P < .001). Twenty-five weeks after the therapies were discontinued could be considered as IBS natural history. During this period, an average of 53.8-56.3% of patients (pool tongxie and placebo data together) had IBS symptoms (pain scale ≥ 3, stool consistency ≥ 5). In particular, at the end of this study (week 61), 145 (54.2%) patients had IBS symptoms. Our results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.