The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

WITHDRAWN: Treatment of Adhesive Intestinal Obstruction by Nasogastric Tube Under EnhancedRecovery After Surgery: An Efficacy Analysis.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.

Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lasts lifelong and causes noticeably higher premature mortality. Although the core symptoms and other behavioral deficits of ASD can persist or be deteriorated from early development to old age, how aging affects the behaviors and brain anatomy in ASD is largely unknown. DOCK4 is an ASD risk gene highly expressed in the hippocampus, and Dock4 knockout (KO) mice display ASD-like behaviors in adulthood (4- to 6-month-old). In this study, we evaluated the behavioral and hippocampal pathological changes of late-middle-aged (15- to 17-month-old) Dock4 male KO mice. Aged Dock4 KO mice continuously showed similar social deficit, elevated anxiety, and disrupted object location memory as observed in the adulthood, when compared to their wild-type (WT) littermates. Notably, Dock4 KO mice displayed an age-related decline of hippocampal dependent spatial memory, showing decreased spatial memory in Barnes maze than their WT littermates at late middle age. Morphological analysis from WT and Dock4 KO littermates revealed that Dock4 deficiency led to decreased mature neurons and oligodendrocytes but increased astrocytes in the hippocampus of late-middle-aged mice. Together, we report that ASD-like behaviors mostly persist into late-middle age in Dock4 KO mice, with specific alterations of spatial memory and hippocampal anatomy by age, thus providing new evidence for understanding age differences in behavioral deficits of ASD.

Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6.

BACKGROUND: Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear. METHODS: Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model. RESULTS: In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection. CONCLUSION: In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. Video Abstract.

Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2-Dicer Signaling Pathway.

Alteration of liver tissue mechanical microenvironment is proven to be a key factor for causing hepatocyte injury and even triggering the occurrence of hepatocellular carcinoma; however, the underlying mechanisms involved are not fully understood. In this study, using a customized, pressure-loading device, we assess the effect of pressure loading on DNA damage in human hepatocytes. We show that pressure loading leads to DNA damage and S-phase arresting in the cell cycle, and activates the DNA damage response in hepatocytes. Meanwhile, pressure loading upregulates Dicer expression, and its silencing exacerbates pressure-induced DNA damage. Moreover, pressure loading also activates ERK1/2 signaling molecules. Blockage of ERK1/2 signaling inhibits pressure-upregulated Dicer expression and exacerbates DNA damage by suppressing DNA damage response in hepatocytes. Our findings demonstrate that compressive stress loading induces hepatocyte DNA damage through the ERK1/2-Dicer signaling pathway, which provides evidence for a better understanding of the link between the altered mechanical environment and liver diseases.

C-terminal-truncated hepatitis B virus X protein promotes hepatocarcinogenesis by activating the MAPK pathway.

PURPOSE: C-terminally truncated hepatitis B virus X (ctHBx) is frequently detected in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) integrated into their genomes, but the molecular mechanisms of ctHBx-related oncogenic signaling remain unclear. In this study, the effects of ctHBx on HepG2 cells were investigated by measuring ctHBx-induced changes in the cell cycle-related target proteins cell division cycle 25C (cdc25C) and p53 downstream of the mitogen-activated protein kinase (MAPK) pathway. MATERIALS AND METHODS: ctHBx lentiviruses were constructed and transfected into HepG2 cells. Then, we investigated HepG2 cell line function by conducting the Cell Counting Kit-8 (CCK8) assay, clone formation assay, scratch wound testing, Transwell assays and flow cytometry to examine cell cycle and apoptosis. Western blotting (WB) was performed to detect proteins related to and downstream of the extracellular signal-regulated kinase(ERK)/c-Jun N-terminal kinase(JNK)/p38 MAPK pathway, including cdc25C and p53. RESULTS: ctHBx significantly enhanced the proliferation, migration, invasion and colony-forming capability of HepG2 cells. In addition, ctHBx activated the ERK/JNK/p38 MAPK signaling pathway to regulate cell viability by affecting the expression of cyclin-related proteins, including cdc25C and p53. CONCLUSION: The present study demonstrates that ctHBx promote the formation and development of HCC via regulating MAPK/cdc25C and p53 axis. ctHBx should be the driving factor of HBV-induced hepatocarcinogenesis.

Construction of a long noncoding RNA-based competing endogenous RNA network and prognostic signatures of left- and right-side colon cancer.

BACKGROUND: Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers. METHOD: Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results. RESULTS: We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL-DEM-DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results. CONCLUSION: The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.

Prolonged QTc interval predicts long-term mortality in cirrhosis: a propensity score matching analysis.

BACKGROUND: Prolonged corrected QT (QTc) interval is a hallmark of cirrhotic cardiomyopathy (CCM) and has been ascertained to predict mortality in cirrhosis. However, some critical issues remain to be addressed including unanimous cut-off, calculation approach and applicable population. METHODS: A total of 274 patients with cirrhosis were included. The prolonged QTc interval over 440 ms according to adjusted Fridericia's formula was used to stratify enrolled subjects. Independent predictors of 3-year mortality were identified with Cox regression model. The Kaplan-Meier method was implemented to obtain survival curves. To reduce impact of selection bias and possible confounders, a propensity score matching (PSM) analysis was used. RESULTS: QTc > 440 ms was an independent risk factor in the entire cohort and PSM subset (HR 2.532, 95% CI 1.431-4.480, p=.001; HR 2.802, 95% CI 1.171-6.701, p=.021, respectively). Subgroup analysis showed that QTc > 440 ms was an independent predictor in cirrhotics with age ≤60 years (HR = 1.02, p=.035) and in the presence of ascites (HR = 1.01, p=.008). CONCLUSIONS: The prolonged QTc interval might help to identify patients with high-risk of all-cause mortality.

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center.

BACKGROUND Natural killer (NK) cells are important for the prognosis of multiple cancers, but their prognostic value remains to be evaluated in patients with gastric cancer. Thus, this retrospective study was conducted at a single center to investigate the association between percentage of NK cells in the peripheral blood and prognosis in patients with gastric cancer. MATERIAL AND METHODS The data of 180 gastric cancer patients were collected. Univariate and multivariate Cox regression models were applied to screen candidate prognostic factors. A time-dependent receiver operating characteristic curve was employed to evaluate the ability of NK cells as a prognostic marker. Furthermore, we determined the correlation between the NK cells percentage and other parameters and their clinical significance. RESULTS Patients with a higher percentage of NK cells survived longer than those with a lower percentage of NK cells. Cox analysis revealed that NK cells could be used as an independent indicator for patients with gastric cancer. The percentage of NK cells was positively correlated with lymphocyte count and albumin, but was negatively correlated with CA125 and neutrophil-lymphocyte ratio. The area under the curve for NK cells in predicting the 5-year survival rate for gastric cancer was 0.792. This increased to 0.830 upon combining NK cells with neutrophil-lymphocyte ratio. Patients at early T, N, and clinical stages possessed a significantly higher percentage of NK cells compared to those at advanced T, N, and clinical stages of gastric cancer. CONCLUSIONS Our results suggest that a higher percentage of NK cells predicts is associated with longer survival of gastric cancer patients and could serve as an independent prognostic biomarker.

Prognostic value of peripheral blood natural killer cells in colorectal cancer.

BACKGROUND: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients. METHODS: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. RESULTS: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage. CONCLUSIONS: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

Analysis of HBV X gene quasispecies characteristics by next-generation sequencing and cloning-based sequencing and its association with hepatocellular carcinoma progression.

OBJECTIVES: This study aimed to describe the differences between next-generation sequencing (NGS) and cloning-based sequencing (CBS) in HBX quasispecies research and primitively investigate the relationship between the dominant HBX quasispecies and hepatocellular carcinoma (HCC). METHODS: A total of 12 serum samples were collected. Serum hepatitis B virus (HBV) DNA was extracted, and the HBV X-region (HBX) was amplified by nested polymerase chain reaction (PCR). The PCR products were simultaneously tested with NGS and CBS to detect quasispecies of the HBX. RESULTS: A total of 9348 eligible quasispecies sequences were obtained by NGS, which were much larger than the 98 of that by CBS. By the phylogenetic tree, the dominant quasispecies sequence of each sample could be found, although they had several nucleotides differences between the dominant quasispecies sequences found by CBS and NGS. By comparing the quasispecies heterogeneity, it was found that the quasispecies complexity value of HBV X-region obtained by NGS was higher than CBS (P < 0.05). The diversity values, including d, dS, dN, an d d N/ dS obtained by NGS were lower than by CBS (all of P < 0.01). The relativity of Spearman(rs) in d, dS, and dN were statistically significant (rs_ d = 0.865, P = 0.001; rs_ dS = 0.722, P = 0.014; and rs_ dN = 0.738, P = 0.011, respectively). There were 21 different bases between the HBX quasispecies of case A and control B. CONCLUSION: The results of this can be used as guidance when researchers plan to choose a suitable method to study quasispecies, especially the HBV X gene quasispecies. Some high-risk mutations of HBX quasispecies were also found in this study and their relationship with HCC need deeper exploration.

Case report: Fever- pneumonia- lymphadenectasis- osteolytic- subcutaneous nodule: Disseminated chromoblastomycosis caused by phialophora.

Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous fungal infection caused by certain dematiaceous fungi (usually Fonsecaea, Phialophora, or Cladophialophora). Histologically, CBM is characterized by the presence of medlar bodies. However, the diagnosis is difficult because of the rarity of these pathognomonic presentations and the wide variety of presentations. Treatment of these infections is challenging as it lacks standardization. Herein, we report a case of chromoblastomycosis caused by Phialophora, in a 42-year-old immunocompetent male agriculturist from the humid and subtropical region of southern China. He had a 3-month history of pneumonia with intermittent fever, coughing, and expectoration. The infection subsequently spread to the bone and lymph nodes forming deep lesions and eventually resulting in osteolysis and lymphadenectasis. These subcutaneous nodules were observed after 9 months. Antifungal treatment was administered for 20 months leading to clinical improvement before the patient was lost to follow-up. This case is unique because such deep lesions are rare in immunocompetent individuals and because the initial onset was associated with pneumonia.

Three-dimensional cross-linking composite of graphene, carbon nanotubes and Si nanoparticles for lithium ion battery anode.

Various graphene-based Si nanocomposites have been reported to improve the performance of active materials in Li-ion batteries. However, these candidates still yield severe capacity fading due to the electrical disconnection and fractures caused by the huge volume changes over extended cycles. Therefore, we have designed a novel three-dimensional cross-linked graphene and single-wall carbon nanotube structure to encapsulate the Si nanoparticles. The synthesized three-dimensional structure is attributed to the excellent self-assembly of carbon nanotubes with graphene oxide as well as a thermal treatment process at 900 °C. This special structure provides sufficient void spaces for the volume expansion of Si nanoparticles and channels for the diffusion of ions and electrons. In addition, the cross-linking of the graphene and single-wall carbon nanotubes also strengthens the stability of the structure. As a result, the volume expansion of the Si nanoparticles is restrained. The specific capacity remains at 1450 mAh g-1 after 100 cycles at 200 mA g-1. This well-defined three-dimensional structure facilitates superior capacity and cycling stability in comparison with bare Si and a mechanically mixed composite electrode of graphene, single-wall carbon nanotubes and silicon nanoparticles.

CTAB-Assisted Fabrication of Bi2WO6 Thin Nanoplates with High Adsorption and Enhanced Visible Light-Driven Photocatalytic Performance.

Two-dimensional thin Bi2WO6 nanoplates have been fabricated using a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. We investigated the proposed formation mechanism based on the crystalline structures of the thin Bi2WO6 nanoplates. The high adsorption ability and excellent visible-light driven photocatalytic activities of the Bi2WO6 nanoplates were illustrated, in view of exposed (001) facets of nanoplates possessing faster separation of photo-generated charge carriers and increased catalytically active sites. Such a cost-effective way to obtain Bi2WO6 nanoplates offers new possibilities for the design of adsorptive semiconductor photocatalysts with strengthened photocatalytic activities.

Boron-doped, carbon-coated SnO2/graphene nanosheets for enhanced lithium storage.

Heteroatom doping is an effective method to adjust the electrochemical behavior of carbonaceous materials. In this work, boron-doped, carbon-coated SnO2 /graphene hybrids (BCTGs) were fabricated by hydrothermal carbonization of sucrose in the presence of SnO2/graphene nanosheets and phenylboronic acid or boric acid as dopant source and subsequent thermal treatment. Owing to their unique 2D core-shell architecture and B-doped carbon shells, BCTGs have enhanced conductivity and extra active sites for lithium storage. With phenylboronic acid as B source, the resulting hybrid shows outstanding electrochemical performance as the anode in lithium-ion batteries with a highly stable capacity of 1165 mA h g(-1) at 0.1 A g(-1) after 360 cycles and an excellent rate capability of 600 mA h g(-1) at 3.2 A g(-1), and thus outperforms most of the previously reported SnO2-based anode materials.

Chronic hepatitis B virus infection and occurrence of hepatocellular carcinoma in tree shrews (Tupaia belangeri chinensis).

BACKGROUND: Hepatitis B virus (HBV) infection has been believed as a major cause of hepatocellular carcinoma (HCC) for a long time, however, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments. Tree shrew (Tupaia) is a small animal closely related to primates evolutionarily, with about 8 years of lifespan. Our previous study proved that tree shrews can be chronically HBV-infected after being inoculated neonatally with HBV. The present study reports the further results from the longer-term observation of these animals. METHODS: Neonatal tree shrews were inoculated with sera from HBV-infected patient or tree shrew. Their serum samples and liver biopsies were collected periodically for detection of HBV markers as well as for histopathological and immunohistochemical examinations. Group A consisted of six tree shrews with chronic HBV-infection, and group B consisted of nine tree shrews without chronic HBV infection. RESULTS: Periodical examinations on serum and liver biopsies of the animals in group A showed the progress of HBV infection, and two cases of HCC occurred at their late stage of life. The courses of HBV infection and the hepatic histopathological and immunohistochemical changes in the tree shrews were similar to those in humans. In contrast, neither HCC nor obvious hepatitis histopathological change was found among the tree shrews in group B. CONCLUSIONS: The course of HBV infection and the features of HCC discovered in tree shrews are similar to those of chronically HBV-infected humans. The tree shrew model might be used to investigate the underlying mechanisms favoring susceptibility for chronic HBV infection and disease progression.

Exploring the Wnt pathway-associated LncRNAs and genes involved in pancreatic carcinogenesis driven by Tp53 mutation.

PURPOSE: Study the contribution of long non-coding RNAs (lncRNAs) to progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC). METHODS: We explored lncRNAs profilings in PanIN cell line (SH-PAN) isolated from Pdx-1-Cre; LSL-Kras (G12D/+) mice and PDAC cell line (DT-PCa) isolated from Pdx-1-Cre; LSL- Kras (G12D/+) ; LSL- Tp53 (R172H/+) mice by lncRNAs microarray, and detected expression of lncRNAs and genes in PDAC by Real-time PCR, Western blot, ChIP and immunohistochemistry. RESULTS: Eight lncRNAs and five protein-coding genes, associated with Wnt pathway, were identified with more than five-fold changes between DT-PCa cells and SH-PAN cells. Of them, lincRNA1611 and Ppp3ca were validated significantly high expression in DT-PCa cells and in 22 of 26 fresh resected human PDAC tissues, compared to SH-PAN cells and normal pancreatic tissues, respectively. Moreover, Tp53 mutation status displayed a positive correlation with lincRNA1611 or Ppp3ca level. Immunohistochemical staining for Ppp3ca was weak or lack in 91 of 107 normal pancreatic tissues, 24 of 29 PanIN-I and 13 of 16 PanIN-II tissues, however, was strong in 10 of 27 PanIN-III and 62 of 107 PDAC tissues post operation. CONCLUSIONS: LincRNA1611 and Ppp3ca were high expression in PDAC and may serve as new potential targets for intervention of the disease.

Hierarchical TiO2-SnO2-graphene aerogels for enhanced lithium storage.

Three-dimensional (3D) TiO2-SnO2-graphene aerogels (TTGs) were built up from the graphene oxide nanosheets supported with both TiO2 and SnO2 nanoparticles (NPs) via a facile hydrothermal assembly process. The resulting TTGs exhibit a 3D hierarchical porous architecture with uniform distribution of SnO2 and TiO2 NPs on the graphene surface, which not only effectively prevents the agglomeration of SnO2 NPs, but also facilitates the fast ion/electron transport in 3D pathways. As the anode materials in lithium ion batteries (LIBs), TTGs manifest a high reversible capacity of 750 mA h g(-1) at 0.1 A g(-1) for 100 cycles. Even at a high current density of 1 A g(-1), a reversible capacity of 470 mA h g(-1) can still be achieved from the TTG based LIB anode over 150 cycles.

[Shen warming Pi strengthening method intervened IBS-D rats: an efficacy assessment].

OBJECTIVE: IBS-D rat model was established to assess the effect of Shen warming Pi strengthening method (SWPSM) for intervening diarrhea-predominant irritable bowel syndrome (IBS-D) by observing rats' general state, stool properties, AWR ranking, and histopathological changes. METHODS: Totally 72 rats were randomly divided into 6 groups, i.e. the normal group, the model group, the high, middle, low dose SWPSM groups, and the control group, 12 in each group. The IBS-D rat model was successfully established referring to AL-Chaer ED's modeling method. After modeling high, middle, and low dose SWPS Recipe boil-free granules were given by gastrogavage to rats in corresponding treatment groups. Sishen Pill boil-free granule was given by gastrogavage to those in the control group. Equal volume of normal saline was given by gastrogavage to rats in the model group. The medication lasted for 2 weeks. Rats' general state, stool properties, abdominal withdrawal reflex (AWR) ranking, and histopathological changes were observed. RESULTS: After treatment, the general state of all rats got im- provement to various degrees. The improvement in the high and middle dose SWPS Recipe groups were superior to that in the low dose SWPS Recipe group and the control group (P < 0.05). There was no statistical difference in the growth rate between after and before treatment in each group (P > 0.05). Compared with the model group and the low dose SWPS Recipe group, the defecation amount within 4 h was less in the high and middle dose SWPS Recipe groups and the control group (P < 0.05). The Bristol ranking score, average ranking of loose stool, ratio of dry stool and wet stool were lower in the high and middle dose SWPS Recipe groups than in the control group and the low dose SWPS Recipe group (P < 0.05). The AWR ranking score was lower in the high and middle dose SWPS Recipe groups than in the control group when the volume of balloon dilation was 1.5 mL. There was no organic change of histological or morphological observation. CONCLUSIONS: High sensitive IBS-D model was proved to be reliable. SWPSM could reduce the quantity of stools, lower Bristol ranking score, average ranking of loose stools as well as ratios of dry stool and wet stool, contributing to reducing the high sensitivity of rats' visceral organs to some extent.