Ulcerative colitis （UC） is a chronic and relapsing inflammatory bowel disease that primarily affects the mucosal layer of the rectum and colon. Its pathogenesis is complex and remains incompletely understood. Endoplasmic reticulum stress （ERS） plays a critical role in cellular responses to external stress and the maintenance of homeostasis， and its abnormal activation is closely associated with the development of various inflammatory diseases， particularly in the pathological process of UC. ERS maintains cellular homeostasis by activating the unfolded protein response （UPR）. However， when ERS is prolonged or excessive， UPR fails to alleviate the stress， leading to epithelial cell death and aggravating the progression of UC. Modulating ERS may serve as a key target for the prevention and treatment of UC， and it is one of the current research hotspots. Traditional Chinese medicine （TCM） has shown significant efficacy in regulating ERS， offering unique therapeutic advantages through multi-target and multi-pathway mechanisms. Recent studies have confirmed that TCM can alleviate ERS， inhibit apoptosis， regulate autophagy， reduce inflammatory responses， and maintain intestinal barrier function to prevent and treat UC. This review summarized the relationship between ERS and UC and discussed the intervention of TCM in regulating ERS for the treatment of UC， aiming to provide new insights and approaches for the treatment of UC with TCM.

Ulcerative colitis （UC） is a chronic and relapsing inflammatory bowel disease that primarily affects the mucosal layer of the rectum and colon. Its pathogenesis is complex and remains incompletely understood. Endoplasmic reticulum stress （ERS） plays a critical role in cellular responses to external stress and the maintenance of homeostasis， and its abnormal activation is closely associated with the development of various inflammatory diseases， particularly in the pathological process of UC. ERS maintains cellular homeostasis by activating the unfolded protein response （UPR）. However， when ERS is prolonged or excessive， UPR fails to alleviate the stress， leading to epithelial cell death and aggravating the progression of UC. Modulating ERS may serve as a key target for the prevention and treatment of UC， and it is one of the current research hotspots. Traditional Chinese medicine （TCM） has shown significant efficacy in regulating ERS， offering unique therapeutic advantages through multi-target and multi-pathway mechanisms. Recent studies have confirmed that TCM can alleviate ERS， inhibit apoptosis， regulate autophagy， reduce inflammatory responses， and maintain intestinal barrier function to prevent and treat UC. This review summarized the relationship between ERS and UC and discussed the intervention of TCM in regulating ERS for the treatment of UC， aiming to provide new insights and approaches for the treatment of UC with TCM.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Objective:To analyze the trend and hot spots of research on multimorbidity.Methods:The Chinese and English literature in databases of CNKI, Wanfang data and Web of science from inception to July 2022 were retrieved using "multimorbidity" and "multiple chronic conditions" as the search terms. The scientific knowledge mapping software VOSviewer was used to analyze the co-occurrence network of scientific knowledge from the aspects of countries, Chinese and English keywords,burst terms and existing research results; and the status quo and hot trends of studies on multimorbidity at home and abroad were summarized and compared.Results:A total of 251 Chinese publications and 6 351 English publications were included. From the perspective of research trends, the overall trend of domestic and international publications showed a fluctuating upward trend in general, but the pace of development was different. The cooperation network represented by the United States, England, Canada, China, Japan, Australia and other countries was the largest regional cooperation network. Germany, the Netherlands, the United States, Australia and other countries were the first regions to carry out studies on multimorbidity. Studies on multimorbidity in China mainly focused on three topics: diagnosis, treatment and care of multimorbidity, common disease management of multimorbidity, and research methods of multimorbidity. The English literature mainly focused on the clustering of three topics: multi-disease co-diagnosis and care research, multi-disease co-management model research, and multimorbidity related research. The analysis of burst terms indicated the research focus and trend change in different time periods. The results of the outburst word analysis showed that the recent research hotspots of multimorbidity were public health, machine learning, geriatric medicine and so on.Conclusions:The number of studies on the multimorbidity is rapidly increasing both domestically and internationally, and related research in China is still in the early stages of development. In terms of research hotspots, the research of multimorbidity has gradually shifted from phenomenon description to topics such as medical services and research methods of multimorbidity.

Objective:To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis.Methods:Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First People′s Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death.Results:A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group ( n=45), HD group ( n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age ( HR=1.066, 95% CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg ( HR=2.601, 95% CI 1.002-6.752, P=0.049) and increasing IVST ( HR=1.269, 95% CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old ( AUC=0.673, 95% CI 0.545-0.802, P=0.013) and 75.0 months ( AUC=0.654, 95% CI 0.528-0.780, P=0.027) and 13.5 mm ( AUC=0.680, 95% CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95% CI 0.677-0.875, P<0.001). Conclusions:There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.

Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.

Objective:To explore the effect of acceptance and commitment nursing therapy on the psychological resilience and post-traumatic growth of patients with hematopoietic stem cell transplantation.Methods:From January 2018 to December 2019, convenience sampling method was used to select 88 patients who underwent hematopoietic stem cell transplantation in Ningbo First Hospital as the research object. All patients were divided into control group and intervention group with the method of random number table, with 44 cases in each group. Control group was treated with conventional nursing care and medication, and intervention group received acceptance and commitment nursing therapy on this basis. We compared the scores of psychological resilience, post-traumatic growth and quality of life of patients between two groups before and after intervention.Results:Before intervention, there was no statistically significant difference in the total scores of psychological resilience, post-traumatic growth, quality of life and scores in each dimension between two groups ( P>0.05) . After intervention, the total scores of psychological resilience, post-traumatic growth and quality of life of intervention group were higher than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:Acceptance and commitment nursing therapy can improve the psychological resilience, post-traumatic growth and quality of life of patients with hematopoietic stem cell transplantation, which is worthy of clinical promotion.