OBJECTIVE: Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery. METHODS: Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis. RESULTS: SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach. CONCLUSION Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Colon/pathology* ; Mucins/metabolism* ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; Male ; Colitis/metabolism* ; Cell Lineage/drug effects* ; Dextran Sulfate ; Stem Cells/drug effects* ; Disease Models, Animal

Objective To analyze the policy texts related to pediatric medications in China over the past decade,to explore the deficiencies in existing policy formulation from the perspective of stakeholders,and to propose reasonable optimization suggestions based on the current situation.Methods Collecting national-level policies related to pediatric drugs in China from 2013 to 2023,a two-dimensional policy analysis framework of"Policy tools-Stakeholder"were established.And the content analysis method was used to code,categorize,and statistically analyze the policy texts.Results A total of 54 pediatric drug policies were included in the analysis.In terms of policy tools,a total of 197 policy codes were formed,with environmental tools being the most prevalent with 92 codes(46.70％),primarily consisting of regulatory management tools(28 codes,30.43％).This was followed by supply-oriented tools with 53 codes(26.90％),mainly focused on the issuance of technical guidelines(21 codes,39.62％).Demand-oriented tools accounted for the least with 52 codes(26.40％),with inter-departmental collaboration tools having the highest proportion(17 codes,32.69％).In the dimension of stakeholders,a total of 223 policy codes were formed,with the government having the highest number of codes at 133(59.64％),followed by medical institutions with 56 codes(25.11％).The proportions for medical personnel,pharmaceutical companies,and patients were similar,with 14 codes(6.28％),11 codes(4.93％),and 9 codes(4.04％),respectively.Conclusions Pediatric drugs face challenges with policy tools where supply-oriented tools,particularly those providing financial support,suffer from insufficient policy depth and customization.The demand-oriented tools have a low proportion,leading to structural imbalance and underutilized effectiveness;the environment-oriented tools focus more on regulation than incentives,restricting the accessibility of pediatric drugs;the potential of multiple stakeholders is not fully activated,and there is a lack of policies centered around pediatric patients.To address these issues,supply-oriented policy tools need to establish a diversified financial support model and clearly define the scope of coverage.Demand-oriented policy tools require further adjustments to the catalog,procurement upgrades,and international collaborative research to reshape the pediatric drug security system.Environmental policy tools should enhance economic support,strengthen intellectual property rights,and implement targeted education to build a development ecosystem for pediatric drugs.Regarding stakeholders,it is essential to strengthen multi-stakeholder collaboration and optimize pediatric drug policy tools with a patient-centered approach.

Objective:To observe the effectiveness and safety of Huotujiji prescription for patients with asthenospermia of spleen-kid-ney yang-deficiency.Methods:Patients with spleen-kidney-yang deficiency type of asthenospermia were divided into two groups by ran-domized control method.The patients in the control group were treated with L-carnitine oral solution alone.And the patients in experimental group were treated with Huotujiji prescription.Semen volume,sperm concentration,PR,TCM symptom score and spouse pregnancy were compared between the two groups before and after treatment.Results:A total of 115 patients were included in the study,with 55 in the ex-perimental group and 60 in the control group.In the experimental group,the sperm concentration before and after treatment were(160.71±53.7)× 106/mL,(187.19±41.89)× 106/mL,and PR were(20.37±9.42)％,(26.7±6.92)％,respectively.PR+NP were(32.06±8.49)％and(34.89±7.25)％.After the treatment,the sperm motility of both groups significantly improved compared to pre-treatment lev-els(P＜0.05).And the experimental group's sperm concentration also showed a significant increase after the treatment(P＜0.05).The pregnancy rate of spouses in the control group was 11.67％,which was 29.09％in the experimental group.The pregnancy rate of the spouses in the two groups showed a statistically significant difference(P＜0.05).After 12weeks of treatment,the Traditional Chinese Medicine(TCM)symptom scores in the control group did not decrease significantly compared to those before treatment(P＞0.05).In contrast,the TCM symptom scores in the experimental group decreased significantly after treatment(P＜0.05).Moreover,compared with the control group,the TCM symptom scores of the experimental group decreased significantly after treatment(P＜0.05).Conclusion:Huotujiji pre-scription can safely and effectively improve the sperm quality and vitality of patients with spleen-kidney-yang deficiency type of asthenosper-mia,improve the symptoms of patients,and increase the pregnancy rate of their spouses,which is worthy of clinical promotion.

Objective To analyze the policy texts related to pediatric medications in China over the past decade,to explore the deficiencies in existing policy formulation from the perspective of stakeholders,and to propose reasonable optimization suggestions based on the current situation.Methods Collecting national-level policies related to pediatric drugs in China from 2013 to 2023,a two-dimensional policy analysis framework of"Policy tools-Stakeholder"were established.And the content analysis method was used to code,categorize,and statistically analyze the policy texts.Results A total of 54 pediatric drug policies were included in the analysis.In terms of policy tools,a total of 197 policy codes were formed,with environmental tools being the most prevalent with 92 codes(46.70％),primarily consisting of regulatory management tools(28 codes,30.43％).This was followed by supply-oriented tools with 53 codes(26.90％),mainly focused on the issuance of technical guidelines(21 codes,39.62％).Demand-oriented tools accounted for the least with 52 codes(26.40％),with inter-departmental collaboration tools having the highest proportion(17 codes,32.69％).In the dimension of stakeholders,a total of 223 policy codes were formed,with the government having the highest number of codes at 133(59.64％),followed by medical institutions with 56 codes(25.11％).The proportions for medical personnel,pharmaceutical companies,and patients were similar,with 14 codes(6.28％),11 codes(4.93％),and 9 codes(4.04％),respectively.Conclusions Pediatric drugs face challenges with policy tools where supply-oriented tools,particularly those providing financial support,suffer from insufficient policy depth and customization.The demand-oriented tools have a low proportion,leading to structural imbalance and underutilized effectiveness;the environment-oriented tools focus more on regulation than incentives,restricting the accessibility of pediatric drugs;the potential of multiple stakeholders is not fully activated,and there is a lack of policies centered around pediatric patients.To address these issues,supply-oriented policy tools need to establish a diversified financial support model and clearly define the scope of coverage.Demand-oriented policy tools require further adjustments to the catalog,procurement upgrades,and international collaborative research to reshape the pediatric drug security system.Environmental policy tools should enhance economic support,strengthen intellectual property rights,and implement targeted education to build a development ecosystem for pediatric drugs.Regarding stakeholders,it is essential to strengthen multi-stakeholder collaboration and optimize pediatric drug policy tools with a patient-centered approach.

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the role and mechanism of epithelial-mesenchymal transition(EMT)in a rat model of bronchopulmonary dysplasia(BPD).Methods The experiment consisted of two parts.(1)Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group,with 24 rats in each group.The hyperoxia group was exposed to 85%oxygen to establish a BPD model,while the normoxia group was kept in room air at normal pressure.Lung tissue samples were collected on days 1,4,7,and 14 of the experiment.(2)Rat type II alveolar epithelial cells(RLE-6TN)were randomly divided into a normoxia group(cultured in air)and a hyperoxia group(cultured in 95%oxygen),and cell samples were collected 12,24,and 48 hours after hyperoxia exposure.Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs,and immunofluorescence was used to detect the co-localization of surfactant protein C(SPC)and α-smooth muscle actin(α-SMA)in preterm rat lung tissue and RLE-6TN cells.Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells.Results(1)Compared with the normoxia group,the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure.Co-localization of SPC and α-SMA was observed in lung tissue,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group.In the hyperoxia group,the mRNA and protein levels of TGF-β1,α-SMA,and N-cadherin were increased,while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group(P<0.05).(2)SPC and α-SMA was observed in RLE-6TN cells,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group.Compared to the normoxia group,the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased,while the mRNA and protein levels of TGF-β1,α-SMA,and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure(P<0.05).Conclusions EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD,leading to simplified alveolar structure and abnormal development,and is involved in the development of BPD.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.