1.Mechanisms of Dihuang Yinzi in Treating Advanced Parkinson's Disease Based on Gut Microbiota-SCFAs-inflammation Axis
Renzhi MA ; Yasi LIN ; Tingyue JIANG ; Hongmei ZHU ; Jiayuan LI ; Yu WANG ; Ge ZHANG ; Wenxin FAN ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):11-21
ObjectiveTo observe the effects of Dihuang Yinzi (DY) on motor dysfunction in rats with advanced Parkinson's disease (PD) and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids (SCFAs)-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group, model group, positive drug group (levodopa, 50 mg·kg-1), and DY low-, medium-, and high-dose groups (5.2, 10.4, 20.8 g·kg-1). After 7 days of administration, motor function was evaluated using the open-field, pole-climbing, and inclined plate tests. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the substantia nigra and colon, and immunohistochemistry was performed to detect α-Synuclein (α-Syn) and tyrosine hydroxylase (TH) expression in the substantia nigra. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), Levodopa, homovanillic acid (HVA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Western blot analysis was used to detect the expression of zonula occludens-1 (ZO-1) and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing, and gas chromatography (GC) was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group, the model group showed significantly decreased movement speed and distance in the open-field test, prolonged pole-climbing time, and reduced retention angle on the inclined plate (P<0.01), accompanied by increased α-Syn expression (P<0.01) and decreased TH expression (P<0.01) in the brain. Compared with the model group, all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees (P<0.05, P<0.01) and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra (P<0.01) and increased TH expression (P<0.01). ELISA and Western blot results showed that, compared with the normal group, the model group exhibited decreased levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum (P<0.01), increased levels of TNF-α, IL-6, and IL-1β in the colon and striatum (P<0.01), and significantly reduced expression of ZO-1 (P<0.05) and occludin in the colon (P<0.01). Compared with the model group, all DY dose groups increased the levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum to varying degrees (P<0.05, P<0.01). In the high-dose DY group, the levels of TNF-α, IL-6, and IL-1β in the colon and striatum were reduced (P<0.01), while the expression of ZO-1 (P<0.05) and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota, Enterobacteriaceae, and Erysipelotrichaceae were increased in the model group, whereas the relative abundances of Bacteroidota, class Clostridia, Lachnospiraceae, and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased (P<0.05, P<0.01), while after high-dose DY intervention, the levels of acetate, propionate, isobutyrate, and butyrate were significantly increased (P<0.05, P<0.01). ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.
2.3D printed hollow pipe double-crosslinked hydrogel tissue engineering scaffold
Renzhi WANG ; Yuanfen CHEN ; Jinwei LI
Chinese Journal of Tissue Engineering Research 2025;29(16):3432-3439
BACKGROUND:When cultivating cells with high demand for structure and oxygen,it is necessary to construct a three-dimensional biological scaffold with hollow pipe structure to make sure the cells get enough nutrients and oxygen.In recent years,hydrogel tissue engineering scaffolds with hollow pipe structure have been paid more and more attention.OBJECTIVE:The biological scaffold material based on sodium alginate was combined with coaxial printing technology to prepare a tissue engineering scaffold with a hollow pipe structure,and the cells were inoculated by perfusion to verify its biological properties.METHODS:The sodium alginate-acrylamide mixed printing solution was prepared,and the parameters such as the printing speed of the inner and outer layers in the coaxial printing process,sodium alginate concentration,and calcium chloride concentration in the receiving dish were controlled to realize the printing of the tissue engineering scaffold with a hollow pipe—sodium alginate-polyacrylamide double-crosslinked hydrogel.The microstructure and elastic modulus of the scaffold were characterized.Mouse fibroblasts were injected into hollow pipes of tissue engineering scaffolds.Cell compatibility was observed by living/dead cell staining.RESULTS AND CONCLUSION:(1)By exploring the printing parameters in the printing process,when the inner printing speed was constant,the outer diameter of the hollow pipe increased with the increase of the flow rate of the outer printing solution,and the inner diameter increased slightly.When the flow rate of the outer layer printing solution was constant,and the flow rate of the inner layer solution was increased,the outer diameter of the hollow pipe was basically unchanged,and the inner diameter was significantly improved.(2)Experimental results showed that the concentration of sodium alginate was 2.5%.Excessive concentration was not conducive to the fusion of multi-layer structure layers,and the mechanical properties of hydrogels prepared at too low concentration were insufficient.(3)The elastic modulus of the double-crosslinked hydrogel was higher,generally higher than 200 kPa,and increased with the increase of the concentration of calcium chloride,and reached the maximum value of 375 kPa when the concentration of calcium chloride in the inner layer was 2%and the concentration of calcium chloride in the receiving dish was 0.3%.(4)The staining of live and dead cells after the tissue engineering scaffold perfusion cells in vitro showed that the cells were distributed along the axis of the hollow pipe and had a higher survival rate,but the cell concentration was lower than that during perfusion.(5)The results show that the sodium alginate-polyacrylamide double-crosslinked hydrogel has strong mechanical properties while retaining good biocompatibility,and can be used in the construction of tissue engineering scaffolds with hollow pipes,and the method of"first preparing the scaffold,then inoculating the cells"also avoids the traditional"cells and printing solution are mixed and then prepared"method to limit the scaffold material and processing method.
3.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
4.Analysis on epidemiological characteristics of population receiving assisted reproductive technology therapy and their offspring in Shanghai, 2011-2020
Huiting YU ; Xin CUI ; Naisi QIAN ; Shan JIN ; Lei CHEN ; Feng ZHOU ; Qi LI ; Renzhi CAI ; Chunfang WANG
Chinese Journal of Epidemiology 2025;46(3):484-491
Objective:To analyze the epidemiological characteristics of the population receiving assisted reproductive technology (ART) therapy and the health status of their offspring in Shanghai from 2011 to 2020.Methods:Based on the birth cohort of the entire population in Shanghai, the proportion and trend changes of ART offspring in the birth cohort were analyzed. The characteristics of ART and naturally conceived populations, including household registration, education level, maternal age, and reproductive history, were examined. Additionally, the health status between ART offspring and naturally conceived offspring were compared.Results:From 2011 to 2020, a total of 70 729 ART offspring were born in Shanghai, accounting for 3.69% of the total births. In 2020, this proportion reached 7.79%. The ART conception rate for primiparous women was higher than that for multiparous women, with both showing upward trends and reaching 9.87% and 2.36%, respectively, in 2020. The ART conception rate was higher in women with higher education levels and local household registration than in those with lower education levels and non-local household registration. The incidence rates of preterm birth and low birth weight in ART singleton offspring were 7.76% and 4.82%, respectively, higher than the 4.69% and 2.87% in naturally conceived offspring, but no increasing trend was observed in naturally conceived offspring. Among twin and multiple newborns, the incidence rates of preterm birth and low birth weight were 56.98% and 46.82% for ART, lower than the 58.51% and 51.32% for natural conception.Conclusions:The difference in social and demographic characteristics was obvious in population receiving ART, suggesting that the differed demand of some people for ART therapy, and it is necessary to strengthen the construction of public health services and further expand the coverage and accessibility of ART services. With technological advancements, the rates of preterm birth and low birth weight remain relatively stable, and even decrease in twin and multiple newborns.
5.Analysis on epidemiological characteristics of population receiving assisted reproductive technology therapy and their offspring in Shanghai, 2011-2020
Huiting YU ; Xin CUI ; Naisi QIAN ; Shan JIN ; Lei CHEN ; Feng ZHOU ; Qi LI ; Renzhi CAI ; Chunfang WANG
Chinese Journal of Epidemiology 2025;46(3):484-491
Objective:To analyze the epidemiological characteristics of the population receiving assisted reproductive technology (ART) therapy and the health status of their offspring in Shanghai from 2011 to 2020.Methods:Based on the birth cohort of the entire population in Shanghai, the proportion and trend changes of ART offspring in the birth cohort were analyzed. The characteristics of ART and naturally conceived populations, including household registration, education level, maternal age, and reproductive history, were examined. Additionally, the health status between ART offspring and naturally conceived offspring were compared.Results:From 2011 to 2020, a total of 70 729 ART offspring were born in Shanghai, accounting for 3.69% of the total births. In 2020, this proportion reached 7.79%. The ART conception rate for primiparous women was higher than that for multiparous women, with both showing upward trends and reaching 9.87% and 2.36%, respectively, in 2020. The ART conception rate was higher in women with higher education levels and local household registration than in those with lower education levels and non-local household registration. The incidence rates of preterm birth and low birth weight in ART singleton offspring were 7.76% and 4.82%, respectively, higher than the 4.69% and 2.87% in naturally conceived offspring, but no increasing trend was observed in naturally conceived offspring. Among twin and multiple newborns, the incidence rates of preterm birth and low birth weight were 56.98% and 46.82% for ART, lower than the 58.51% and 51.32% for natural conception.Conclusions:The difference in social and demographic characteristics was obvious in population receiving ART, suggesting that the differed demand of some people for ART therapy, and it is necessary to strengthen the construction of public health services and further expand the coverage and accessibility of ART services. With technological advancements, the rates of preterm birth and low birth weight remain relatively stable, and even decrease in twin and multiple newborns.
6.3D printed hollow pipe double-crosslinked hydrogel tissue engineering scaffold
Renzhi WANG ; Yuanfen CHEN ; Jinwei LI
Chinese Journal of Tissue Engineering Research 2025;29(16):3432-3439
BACKGROUND:When cultivating cells with high demand for structure and oxygen,it is necessary to construct a three-dimensional biological scaffold with hollow pipe structure to make sure the cells get enough nutrients and oxygen.In recent years,hydrogel tissue engineering scaffolds with hollow pipe structure have been paid more and more attention.OBJECTIVE:The biological scaffold material based on sodium alginate was combined with coaxial printing technology to prepare a tissue engineering scaffold with a hollow pipe structure,and the cells were inoculated by perfusion to verify its biological properties.METHODS:The sodium alginate-acrylamide mixed printing solution was prepared,and the parameters such as the printing speed of the inner and outer layers in the coaxial printing process,sodium alginate concentration,and calcium chloride concentration in the receiving dish were controlled to realize the printing of the tissue engineering scaffold with a hollow pipe—sodium alginate-polyacrylamide double-crosslinked hydrogel.The microstructure and elastic modulus of the scaffold were characterized.Mouse fibroblasts were injected into hollow pipes of tissue engineering scaffolds.Cell compatibility was observed by living/dead cell staining.RESULTS AND CONCLUSION:(1)By exploring the printing parameters in the printing process,when the inner printing speed was constant,the outer diameter of the hollow pipe increased with the increase of the flow rate of the outer printing solution,and the inner diameter increased slightly.When the flow rate of the outer layer printing solution was constant,and the flow rate of the inner layer solution was increased,the outer diameter of the hollow pipe was basically unchanged,and the inner diameter was significantly improved.(2)Experimental results showed that the concentration of sodium alginate was 2.5%.Excessive concentration was not conducive to the fusion of multi-layer structure layers,and the mechanical properties of hydrogels prepared at too low concentration were insufficient.(3)The elastic modulus of the double-crosslinked hydrogel was higher,generally higher than 200 kPa,and increased with the increase of the concentration of calcium chloride,and reached the maximum value of 375 kPa when the concentration of calcium chloride in the inner layer was 2%and the concentration of calcium chloride in the receiving dish was 0.3%.(4)The staining of live and dead cells after the tissue engineering scaffold perfusion cells in vitro showed that the cells were distributed along the axis of the hollow pipe and had a higher survival rate,but the cell concentration was lower than that during perfusion.(5)The results show that the sodium alginate-polyacrylamide double-crosslinked hydrogel has strong mechanical properties while retaining good biocompatibility,and can be used in the construction of tissue engineering scaffolds with hollow pipes,and the method of"first preparing the scaffold,then inoculating the cells"also avoids the traditional"cells and printing solution are mixed and then prepared"method to limit the scaffold material and processing method.
7.Design and baseline characteristics of a population-based birth cohort in Shanghai
Huiting YU ; Xin CUI ; Zhou LIANG ; Renzhi CAI ; Lan CHEN ; Naisi QIAN ; Weixiao LIN ; Shan JIN ; Chunfang WANG ; Chen FU
Shanghai Journal of Preventive Medicine 2024;36(1):11-15
ObjectiveTo introduce the basic design, development plan and objectives of a population-based birth cohort in Shanghai, and further present the main data and baseline characteristics of enrolled participants in the cohort, and to provide key information for reproductive health-related studies. MethodsThe Shanghai population-based birth cohort initiated on January 1, 2005, included newborns born in Shanghai every year and their parents, and collected information on reproductive health, reproductive treatment, birth characteristics, growth and development status, as well as the incidence, treatment and death of diseases by employing data linkage technology and investigations. This formed a birth cohort spanning the entire life cycle. ResultsAs of October 2022, a total of 2 978 538 newborns and their parents were included in the cohort. Among them, 2 905 135 (97.54%) were naturally conceived (NC), and 73 403 (2.46%) were born through assisted reproductive technologies (ART). The average age of parents was (32.56±4.12) years old for females and (34.62±5.34) years old for males in the ART group, which was higher than (28.02±4.71) years and (30.07±5.54) years for parents in the NC group. Among parents, females and males aged 30 and above accounted for 77.12% and 85.08%, respectively, which were higher than that of parents (35.28% for females and 49.66% for males) in the NC group. Furthermore, the percentage of parents with a college degree or above in the ART group was 73.23% for females and 73.66% for males, which were higher than those in the NC group (49.98% and 50.91%, respectively). The multiple births rate in the ART group was 33.81%, which was higher than that in the NC group (1.88%). The incidence of premature birth and low birth weight in the ART group were 24.47% and 19.08%, respectively, which was higher than that in the NC group (5.47% and 3.73%). ConclusionThe comprehensive collection of reproductive health-related information in the birth cohort in Shanghai can provide essential resources to determine the influence of genetics, environment, reproductive treatment and other related factors on the health of offspring after birth.
8.Dynamic relationship between changes of mortality rate and urban development level in Shanghai
Shan JIN ; Bo FANG ; Renzhi CAI ; Naisi QIAN ; Huiting YU ; Jiaying QIAO ; Lei CHEN ; Chunfang WANG
Shanghai Journal of Preventive Medicine 2023;35(7):654-659
ObjectiveTo analyze the dynamic response relationship between urban development and mortality rate in Shanghai, and to predict the trend of mortality rate changes. MethodsBy analyzing the total mortality rate (TMR), gross domestic product (GDP) and socio-demographic index (SDI) in Shanghai from 1978 to 2017, a vector autoregressive (VAR) model was constructed to evaluate the impact of urban development on the mortality rate. ResultsThe fitted
9.Chinese intracranial hemorrhage imaging database: constructing a structured multimodal intracranial hemorrhage data warehouse.
Yihao CHEN ; Jianbo CHANG ; Qinghua ZHANG ; Zeju YE ; Fengxuan TIAN ; Zhaojian LI ; Kaigu LI ; Jie CHEN ; Wenbin MA ; Junji WEI ; Ming FENG ; Renzhi WANG
Chinese Medical Journal 2023;136(13):1632-1634
10.Multi-omics fusion analysis models with machine learning predict survival of HER2-negative metastatic breast cancer: a multicenter prospective observational study.
Jiani WANG ; Yuwei LIU ; Renzhi ZHANG ; Zhenyu LIU ; Zongbi YI ; Xiuwen GUAN ; Xinming ZHAO ; Jingying JIANG ; Jie TIAN ; Fei MA
Chinese Medical Journal 2023;136(7):863-865

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