1.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P0.01), whereas it was significantly increased in the Sini San group compared with the model group (P0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P0.05), and compared with the model group, both were significantly increased in the Sini San group (P0.05, P0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P0.05, P0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
2.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P<0.01), whereas it was significantly increased in the Sini San group compared with the model group (P<0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P<0.05), and compared with the model group, both were significantly increased in the Sini San group (P<0.05, P<0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P<0.05, P<0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P<0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
3.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
4.Role and mechanism of myeloid cells in hepatic fibrosis
Chengjie CUI ; Zhenzhen ZHAO ; Jing CUI ; Shuxian ZANG ; Na FU
Journal of Clinical Hepatology 2026;42(1):183-189
Hepatic fibrosis is a complex dynamic process caused by multiple chronic pathogenic factors, characterized by excessive accumulation of liver extracellular matrix and abnormal liver structure and function. If anti-fibrotic treatment is not performed in time, it can progress to liver cirrhosis and even liver cancer. Hepatic fibrosis has a complex pathogenesis, and previous studies mainly focused on the activation of hepatic stellate cells. Recent studies have shown that myeloid cells have the potential of multi-directional differentiation and can also participate in the development and progression of hepatic fibrosis. This article systematically reviews the role and regulatory mechanism of myeloid cells in hepatic fibrosis, in order to provide a reference for clinical diagnosis and targeted therapy.
5.A Systematic Review of Traditional Chinese Medicine Syndrome Efficacy Evaluation Scales Based on the COSMIN Guidelines
Kailin SU ; Zhenzhen FENG ; Jiajia WANG ; Lu WANG ; Guixiang ZHAO ; Jiansheng LI
Journal of Traditional Chinese Medicine 2026;67(4):416-424
ObjectiveTo systematically evaluate the methodological quality and measurement properties of traditional Chinese medicine (TCM) syndrome efficacy evaluation scales, and to provide evidence-based references for selecting high-quality assessment tools in TCM clinical practice. MethodsChina National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database, Chinese Biomedical Literature Database (CBM), PubMed, the Cochrane Library, Embase, and Web of Science were searched from inception to April 2, 2025, for studies evaluating the measurement properties of TCM syndrome efficacy evaluation scales. Data were extracted, and the methodological quality and measurement properties of the included scales were assessed according to the consensus-based standards for the selection of health measurement instruments (COSMIN). Recommendation levels were formulated based on the grading of evidence. ResultsA total of 46 studies were included, involving 22 generic syndrome efficacy evaluation scales and 24 disease-specific syndrome efficacy evaluation scales. None of the scales reported cross-cultural validity or measurement error. According to the recommendation grades, 2 scales met Grade A recommendations and are suggested for clinical use; 38 scales were classified as Grade B, indicating potential applicability but requiring further validation; and 6 scales were classified as Grade C, suggesting the need for further refinement. ConclusionExisting TCM syndrome efficacy evaluation scales exhibit substantial variability in methodological quality, incomplete reporting of measurement properties, and insufficient attention to scale revision. Future efforts should emphasize standardized design in the development of TCM syndrome scales, strengthen validation procedures for key measurement properties, and prioritize dynamic revision of scales, thereby providing high-quality tools to support the precise evaluation of syndrome efficacy.
6.Introduction and enlightenment of the Recommendations and Expert Consensus for Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding
Zhenzhen JIANG ; Rong GUI ; Rong HUANG ; Junhua ZHANG ; Jiaohui ZENG ; Hao TANG ; Zhi LIN ; Dan WAN ; Mingyi ZHAO ; Minghua YANG ; Lan GU ; Haiting LIU
Chinese Journal of Blood Transfusion 2026;39(2):285-293
Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.
7.A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex.
Zhenzhen XUE ; Yudong SHANG ; Lan YANG ; Tao LI ; Bin YANG
Journal of Pharmaceutical Analysis 2025;15(4):101066-101066
A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted in silico, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites in vivo, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT4) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites in vivo, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
8.Exploring the current status of quality management of cold chain medicines in DTP pharmacies and the measures for pre-emptive risk management
Mulan WANG ; Peng LIN ; Siwu TU ; Zhenzhen CHEN ; Hongqiao WANG
China Pharmacy 2025;36(4):395-400
OBJECTIVE To investigate the current status of quality management of cold chain medicines in direct-to-patient (DTP) pharmacies and propose measures for pre-emptive risk management, providing references for the quality risk management of cold chain medicines. METHODS Based on the requirements of national regulations, a survey was conducted on the quality management of cold chain medicines in DTP pharmacies of J Province from November 2023 to February 2024, focusing on the receipt, storage, distribution, and delivery processes, using questionnaires, telephone interviews, and on-site visits. Common quality management issues in the operation of cold chain medicines were identified, and the causes of these issues were analyzed to propose feasible pre-emptive risk management measures. RESULTS & CONCLUSIONS A total of 122 DTP pharmacies participated in the questionnaire survey, and personnel from 30 DTP pharmacies participated in on-site and telephone interviews. Typical problems were identified in some DTP pharmacies, including insufficient personnel allocation or training, incomplete or inadequate implementation of quality system documentation, inadequate provision or management of cold chain facilities and equipment, and non-compliant storage and distribution of cold chain medicines. These issues posed certain risks to the quality management of cold chain medicines. It is recommended that DTP pharmacies strengthen personnel allocation and training, improve quality system documentation, enhance the provision and management of facilities and equipment, standardize storage and transportation operations, and strengthen supervision and assessment as pre-emptive measures. In addition, all sectors of society should also collaborate in governance from the perspective of ensuring the safety of cold chain drug storage and transportation, in order to mitigate the risk of quality and safety issues during the distribution of cold chain drugs and guarantee the safe and effective use of medications for patients.
9.Effectiveness of group skills training intervention on social ability of high functional autism spectrum disorder children
HU Shasha, ZHAO Xiao, ZHU Zhenzhen, LIU Xiaoli, WANG Rong, HU Zhenyu, ZHANG Wenwu
Chinese Journal of School Health 2025;46(2):167-171
Objective:
To evaluate the intervention efficacy of integrated group social skills training on social ability in school age patients with high functioning ASD, so as to provide a reference for improving social skills in children with high functioning ASD.
Methods:
From January 2021 to December 2023, 62 children aged 7-12 with high functioning ASD who visited the Children s Psychiatry Outpatient Department of the Affiliated Kangning Hospital of Ningbo University were recruited, and were randomly divided into a training ( n =31) and a control group ( n =31) by a random number table method. The training group received a 20 week structured group social training program (mental interpretation courses and social courses), while the control group received only conventional treatment. Chinese version of Griffith Empathy Measure Parent Ratings (GEM-PR) and Social Response Scale (SRS) were used to assess the symptoms of social deficits before and after treatment. Emotional face recognition tasks and eye movement trajectories were used to test the characteristics of social visual attention in children with ASD. Group comparison was conducted using t-test and Mann-Whitney U test.
Results:
At baseline, there were no significant differences in GEM-PR score ( t = -1.20 to -0.81), SRS score ( t =-0.36-1.75), emotional face recognition accuracy and reaction time ( t =-0.58-1.85), and eye movement trajectory ( U/t =-1.63-0.29) between the two group ( P >0.05). After intervention, the total GEM-PR score and empathic cognitive factor score of training group [18.00(10.00,24.00),9.00(8.00,13.00)] were significantly higher than those of the control group [12.00(-1.00,18.00),2.00(-2.00,7.00)], and the total SRS score and social cognition, social perception, social communication, social motivation (73.23±14.20, 16.16±2.72, 6.58±2.50, 24.29±5.61, 9.52±3.73) were significantly lower than those of the control group (95.26±15.29, 19.90±2.84, 12.58±2.49,31.94±6.38, 13.74±4.81) ( U/t =-2.38, -4.59; -5.88, -5.29, -9.47, -5.01, -3.87, P <0.05). The overall correct rate of emotional face recognition and the correct rate of angry, fearful and neutral faces recognition in the training group [(81.55±6.62)%,(76.86±12.06)%,(79.61±12.42)%,(94.27±6.26)%] were significantly higher than the control group [(70.55±13.82)%,(62.82±18.77)%,(67.18±18.85)%,(79.60±20.05)%], and the average reaction time [(2 226.70±274.43)ms] was lower than the control group [(2 417.27±324.10)ms] (t=4.00, 3.50, 3.07, 3.89, -2.42, P<0.05). The time to first eye gaze [764.74 (748.64, 793.73) ms] in the training group was significantly lower than that in the control group [810.92 (782.86, 877.42) ms], and the proportion of moderatetohigh intensity attention area in the face [(37.37±1.27)%] was significantly higher than that in the control group [(30.34±1.23)%] (U/t=3.44, 8.89, P<0.05).
Conclusion
Integrated group social training can significantly improve the social communication and empathy ability of high functioning ASD children, increase active attention and recognition ability of faces, and improve mental development of children with ASD.
10.Research progress on quorum sensing in the caries-causing effects of Streptococcus mutans and Candida albicans
LIAO Zhenzhen ; LI Wenxiu ; LIANG Yan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(4):328-335
Dental caries is a major disease that seriously endangers human oral health. Dental plaque biofilm composed of many microorganisms is the primary factor of dental caries. Inhibiting biofilm formation has become the focus of research on the prevention and treatment of dental caries. Streptococcus mutans and Candida albicans, as common pathogenic bacteria in the oral cavity, are closely related to the occurrence of dental caries. The interaction between the two can lead to the rapid onset of dental caries. In recent years, many studies have found that Candida albicans promotes the occurrence of caries by interacting with Streptococcus mutans, including physical adhesion, promoting the production of exopolysaccharides (EPS), reducing the pH of the microecological environment, forming a highly cariogenic acidic environment, and secreting quorum sensing molecules to trigger quorum sensing. As a communication mechanism between microorganisms, the quorum sensing system mainly includes three main types: autoinducing peptide (AIP) system, autoinducer-2 (AI-2) system, and Acyl-homoserine lactone (AHL) system. At present, quorum sensing has been shown to promote the occurrence of diseases by activating the expression of microbial pathogenicity-related genes, promoting EPS synthesis and biofilm formation. The CSP-ComDE and ComRS quorum sensing systems of Streptococcus mutans allow the bacteria to survive and cause disease in extreme environments that are unfavorable for survival, while the quorum sensing system of Candida albicans is mainly mediated by farnesol, which has a negative regulatory effect on the yeast-hyphae transformation of Candida albicans. Studying the quorum sensing phenomenon of the two bacteria is helpful to understand the etiology of caries. In recent years, many studies have reported the use of quorum sensing inhibitors in anti-microbial applications. The study of microbial quorum sensing systems and inhibitors will help the prevention and treatment of caries. With the increasing interest in biofilm-related research, and a new method for in-depth study of the biofilm formation process and quorum sensing behavior using microfluidic and chip laboratory technology is proposed. The author summarizes the cariogenic effects, the quorum sensing system and quorum sensing inhibitors of Streptococcus mutans and Candida albicans.


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