1.Effect of Early Intervention of Yishen Huazhuo Prescription on Learning and Memory of Accelerated Aging SAMP8 Mice and Its Mechanism
Shujie ZAN ; Kai WANG ; Jiachun XU ; Weiming SUN ; Daoyan NI ; Linlin ZHANG ; Shuang LIU ; Yan MA ; Pengjuan XU ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):91-99
ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription (YHP) on the learning and memory of accelerated aging model mice, as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups, including the model group, low-dose YHP group, high-dose YHP group, and donepezil group. Additionally, 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group, each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg-1 and 12.48 g·kg-1, while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial (MG) polarization marker inducible nitric oxide synthase (iNOS) and M2 MG polarization marker arginase-1 (Arg-1) in the hippocampus region. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of pro-inflammatory factor interleukin 1β (IL-1β) and anti-inflammatory factor transforming growth factor-β1 (TGF-β1). Furthermore, Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 (Aβ1-42) along with triggering receptor expressed on myeloid cells 2 (TREM2)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins TREM2, phospho (p)-NF-κB p65, and phospho-inhibitory kappa B kinase β (IKKβ) in the hippocampus. ResultCompared with the control group, the model group exhibited a significantly prolonged escape latency (P<0.01), a significant reduction in neuron-specific nuclear protein (NeuN) expression in the hippocampus, a significant increase in iNOS expression in MG, and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased, while the TGF-β1 content was significantly decreased. Additionally, there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions (P<0.05, P<0.01). However, no significant changes were observed in escape latency, times of crossing the platform, and hippocampal NeuN expression in the YHP treatment control group. Conversely, iNOS expression in MG as well as the hippocampal p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions were significantly decreased. Furthermore, TREM2 expression was significantly increased (P<0.05, P<0.01). In comparison to the model group, the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform (P<0.05, P<0.01). In the high-dose YHP group, the escape latency was significantly shortened (P<0.05). In the low-dose YHP group, high-dose YHP group, the expression of NeuN in the hippocampus was significantly increased, the expression of iNOS in MG was significantly decreased, and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased, while the TGF-β1 content was significantly increased. Furthermore, the expression of TREM2 in the hippocampus was significantly increased, and the expressions of p-NF-κB p65, p-IKKβ, and Aβ1-42 were significantly decreased (P<0.01). ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway, reduce the release of neuroinflammatory factors, protect hippocampal neurons, and reduce the deposition of Aβ1-42, and finally delay the occurrence of learning and memory decline in SAMP8 mice.
2.Drug resistance and MLST of Campylobacter jejuni from human and avian sources in Jinshan District of Shanghai from 2021 to 2022
Jiachun YUAN ; Fengxia QUE ; Xinyue XU ; Chunfu LIU ; Yulong YE
Shanghai Journal of Preventive Medicine 2024;36(4):359-363
ObjectiveTo understand the current drug resistance status and bacterial multilocus sequence typing (MLST) of human and avian Campylobacter jejuni in Jinshan District, Shanghai. MethodsFecal samples were collected from diarrhea patients in the annuity mountainous area from 2021 to 2022, and poultry and related samples were collected from 2 poultry farms in the Jinshan area for detection of C. jejuni. Minimal inhibitory concentration (MIC) drug sensitivity test was performed on the detected C. jejuni, and some strains were selected for whole genome sequencing and MLST analysis. ResultsA total of 823 samples of diarrhea disease were collected, and 32 strains of C. jejuni were detected, with a detection rate of 3.89%. Out of 600 poultry related samples, 62 strains of C. jejuni were detected, with a detection rate of 10.33%. Human multidrug resistance reached 93.75% (30/32), while avian multidrug resistance reached 100.00%(62/62). The top four drug resistance rates of human and avian C. jejuni were azithromycin (100.00% from humans and 100.00% from birds), naphthoic acid (93.75% from humans and 87.10% from birds), ciprofloxacin (90.63% from humans and 98.39% from birds), and tetracycline (84.38% from humans and 98.39% from birds). The relatively low resistance strains of human derived C. were erythromycin, chloramphenicol, and thalithromycin. The relatively low resistance strains of avian C. jejuni were erythromycin, clindamycin, and flufenicol. MLST analysis showed that the selected 16 strains of bacteria were divided into 9 ST types, among which the evolutionary relationship of avian C. jejuni was relatively concentrated, while human C. jejuni was relatively dispersed. It was found that one strain of avian C. jejuni was closely related to two strains of human C. jejuni. ConclusionsC. jejuni infection is severe in patients with diarrhea in this region, with a detection rate second only to salmonella and Vibrio parahaemolyticus. C. jejuni infection in poultry is relatively common, and both are highly resistant. Therefore, monitoring and control should be strengthened. MLST analysis shows new ST types in both avian and human sources of C. jejuni, indicating the emergence of new mutations that require continuous monitoring to avoid the epidemics caused by new strains. The isolated strains with close genetic relationships between avian and human sources reveal the evidence of the spread of C. jejuni from poultry to humans. Therefore it is necessary to strengthen the monitoring of C. jejuni in relevant samples from breeding farms.
3.Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase
Hang YU ; Hui XU ; Xinyu YANG ; Zhengwei ZHANG ; Jiachun HU ; Jinyue LU ; Jie FU ; Mengmeng BU ; Haojian ZHANG ; Zhao ZHAI ; Jingyue WANG ; Jiandong JIANG ; Yan WANG
Journal of Pharmaceutical Analysis 2023;13(9):1024-1040
Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.
4.Comparison of treatment efficacy between endoscopic ultrasound-guided puncture sclerotherapy and laparoscopic decapitation decompression for renal cysts in the upper pole (with video)
Beifen QIU ; Wei WU ; Guilian CHENG ; Duanmin HU ; Jiachun XU ; Zhoubing ZHAN ; Linsen JIANG ; Kai SONG
Chinese Journal of Digestive Endoscopy 2023;40(10):825-828
To compare the efficacy, safety and economic cost of endoscopic ultrasound (EUS)-guided puncture sclerotherapy and laparoscopic decapitation decompression for the renal cysts in the upper pole, data of patients with renal cysts in the upper pole who received EUS-guided puncture sclerotherapy (the EUS group, n=9) or laparoscopic decapitation decompression (the laparoscopy group, n=16) in the Second Affiliated Hospital of Soochow University from January 2021 to August 2022 were analyzed retrospectively. The effective rate, operation time, intraoperative blood loss, incidence of complications, hospital stay and treatment cost of the EUS group and the laparoscopy group were compared. Results showed that the effective rate was comparable in the EUS group and laparoscopy group (9/9 VS 14/16, P=0.520). The operation time was shorter (29.8±4.8 min VS 70.1±11.1 min, t=10.207, P<0.001), intraoperative blood loss less (0 mL VS 26.1±5.9 mL, t=13.089, P<0.001), postoperative hospital stay shorter (3.5±0.7 days VS 5.4±2.0 days, t=2.663, P=0.014), and total cost lower (10 547.85±2 388.19 yuan VS 15 316.09±5 352.45 yuan, t=2.517, P=0.019) in the EUS group compared with those in the laparoscopy group. There was no significant difference in the total hospital stay (8.1±2.0 days VS 9.3±3.1 days, t=1.019, P=0.319) or operation cost (3 946.79±490.82 yuan VS 3 860.18±857.42 yuan, t=-0.277, P=0.784) between the EUS group and laparoscopy group. There was 1 case of puncture bleeding, 1 case of hematuria, and 1 case of lumbago in the laparoscopy group, while no complication occurred in the EUS group. In conclusion, it is preliminarily believed that EUS-guided puncture sclerotherapy for renal cysts in the upper pole has similar clinical effects with higher safety, shorter postoperative hospital stay and lower total hospitalization cost compared with those of laparoscopic decapitation decompression, which is worth of clinical promotion.
5.Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota.
Libin PAN ; Hang YU ; Jie FU ; Jiachun HU ; Hui XU ; Zhengwei ZHANG ; Mengmeng BU ; Xinyu YANG ; Haojian ZHANG ; Jinyue LU ; Jiandong JIANG ; Yan WANG
Acta Pharmaceutica Sinica B 2023;13(4):1537-1553
At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.
6.Cordyceps sinensis extract protects against the ovariectomy-induced bone loss via the action on osteoclasts
Weibiao PENG ; Ting WANG ; Xu FENG ; Jiachun WANG ; Zhenzhen ZHANG ; Zhiyong CHU
Journal of Pharmaceutical Practice 2023;41(2):97-105
Objective To explore the effects of Cordyceps sinensis extract (CSE) on osteoporosis and RANKL-mediated osteoclastogenesis. Methods Bone marrow-derived macrophages (BMMs) was isolated from the bone marrow of C57BL/6 mice. CSE was added in osteoclast differentiation. Osteoclasts were stained by tartrate-resistant acid phosphatase (TRAP). The nearly mature osteoclasts were planted on hydroxyapatite plates and the area of bone lacunae was observed by microscope. The F-actin belt was stained by DAPI and phylloeptide and the number of nuclei was observed by confocal microscopy. The expressions of DC-STAMP, ATP6V0D2, TRAP, CTSK, and NFATC1 were detected by q-PCR. The protein expression of the MAPK pathway was detected by Western Blot. The in vivo experiments were carried out by administering CSE to the ovariectomized mice daily through gavage. After 6 weeks of intervention, mouse femurs were taken for morphological analysis. Peripheral blood was taken for ELISA. Results CSE represses osteoclastogenesis, bone resorption, F-actin belts formation, osteoclast specific gene expressions and MAPK signaling pathways in vitro. In vivo study indicated that CSE prevents OVX-induced osteoporosis and preserves bone volume by repressing osteoclast activity and function. It also increases the serum ALP, BGP content, and reduces TRAP content. Conclusion CSE can attenuate osteoclast formation and OVX-induced osteoporosis, suggesting potential clinical therapeutic effects for osteoporosis.
7.Analysis of revascularization strategies for elderly patients with ST-segment elevation myocardial infarction and multivessel disease
Jiachun LANG ; Chen WANG ; Le WANG ; Hongliang CONG ; Yin LIU ; Jingxia ZHANG ; Lin WANG ; Yuecheng HU ; Rongdi XU
Chinese Journal of Geriatrics 2023;42(3):303-309
Objective:To compare the effects of staged percutaneous coronary intervention(PCI)after emergency PCI and emergency culprit-only PCI on clinical outcomes of elderly patients with ST-segment elevation myocardial infarction(STEMI)and multivessel disease.Methods:A retrospective analysis was performed on 389 elderly patients with STEMI and multivessel lesions, aged ≥70 years and within 12 h of onset, admitted to the Clinical College of Thoracic Medicine, Tianjin Medical University, between January 2014 and September 2019.According to different revascularization strategies, enrolled patients were divided into the culprit-only PCI group(79.18%, 308)and the staged PCI group(20.82%, 81). Kaplan-Meier analysis and the Cox proportional hazards regression model were used to compare the incidences of major adverse cardiac and cerebrovascular events(MACCE), all-cause death, cardiac death, recurrent myocardial infarction, stroke and ischemia-driven revascularization between the two groups and to evaluate the effects of different revascularization strategies on MACCE and all-cause death.Then subgroup analysis was performed.Results:During a 56-month follow-up, 131 patients developed MACCE and 96 patients died.Compared with the culprit-only PCI group, the staged PCI group had a lower risk of MACCE( HR: 0.404, 95% CI: 0.227-0.716, P=0.002), all-cause death( HR: 0.354, 95% CI: 0.171-0.730, P=0.005), cardiac death( HR: 0.363, 95% CI: 0.157-0.838, P=0.018), and recurrent myocardial infarction( HR: 0.229, 95% CI: 0.055-0.953, P=0.043). There was no significant difference in the incidence of stroke or ischemia-driven revascularization between the two groups( P>0.05). The reduced risk with staged PCI for MACCE and for all-cause mortality persisted in all subgroups.Multivariate Cox proportional hazards regression revealed that, after adjusting for confounding factors, staged PCI was an independent protective factor for MACCE( HR: 0.44, 95% CI: 0.239-0.815, P=0.009)and for all-cause death( HR: 0.390, 95% CI: 0.90, P=0.020). Conclusion:Compared with culprit-only PCI, staged PCI can significantly improve the long-term prognosis of elderly patients ≥70 years with STEMI and multivessel disease within 12 h of onset.
8.Intensity of Intraoperative Spinal Cord Hyperechogenicity as a Novel Potential Predictive Indicator of Neurological Recovery for Degenerative Cervical Myelopathy
Guoliang CHEN ; Fuxin WEI ; Jiachun LI ; Liangyu SHI ; Wei ZHANG ; Xianxiang WANG ; Zuofeng XU ; Xizhe LIU ; Xuenong ZOU ; Shaoyu LIU
Korean Journal of Radiology 2021;22(7):1163-1171
Objective:
To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy.
Materials and Methods:
Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis.
Results:
The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028).
Conclusion
For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.
9.Intensity of Intraoperative Spinal Cord Hyperechogenicity as a Novel Potential Predictive Indicator of Neurological Recovery for Degenerative Cervical Myelopathy
Guoliang CHEN ; Fuxin WEI ; Jiachun LI ; Liangyu SHI ; Wei ZHANG ; Xianxiang WANG ; Zuofeng XU ; Xizhe LIU ; Xuenong ZOU ; Shaoyu LIU
Korean Journal of Radiology 2021;22(7):1163-1171
Objective:
To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy.
Materials and Methods:
Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis.
Results:
The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028).
Conclusion
For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.
10. The change of psychomotor neurobehavioral function in workers exposed to ultra-high frequency radiation
Jiachun JIN ; Guoyong XU ; Maosheng YAN ; Qingsong CHEN ; Bikun YU ; Bin XIAO
China Occupational Medicine 2019;46(04):423-427
OBJECTIVE: To explore the effect of ultra-high frequency radiation on psychomotor neurological behavior in workers with exposure. METHODS: A total of 85 workers who exposed to 40.68 MHz radiofrequency were recruited as the exposure group by judgment sampling method. A group of 121 workers without occupational EMR exposure were recruited as the control group. Workers in both groups were from the same shoe factory. The electric field intensity(EFI) of ultra-high frequency radiation of workplace in the exposure group was measured. The computerized neurobehavioral evaluation system in Chinese version 3 was used to evaluate the psychomotor neurobehavioral function which included the neurobehavioral ability index(NAI) of simple visual reaction time(SVRT), digital screening and fit curve and the general NAI(GNAI) of the above 3 indexes. RESULTS: The median of the workplace EFI of ultra-high frequency radiation in the exposure group was 119.0 V/m, and all of them exceeded the national occupational exposure limit. NAI of digital screening in exposure group was lower than that in the control group(P<0.05). There is no statistically significant difference in the NAI of SVRT, fit curve and GNAI(P>0.05). Meanwhile, there is no statistically significant difference in abnormal rate of NAI of SVRT, digital screening, fit curve and GNAI(P>0.05). The results of multiple linear regression analysis showed that the ultra-high frequency radiation EFI exposure was negatively correlated with NAI of digital screening(P<0.05) after eliminating the influence of confounding factors such as age, working age, gender, education level, smoking, drinking and staying up late. CONCLUSION: The digital screening of psychomotor neurobehavioral function in the exposure workers was adversely affected by the ultra-high frequency radiation. The neural behavioral ability of eye-hand coordination and precise movement may be the specific performance.

Result Analysis
Print
Save
E-mail