1.Effects of Spleen Deficiency on Lipid Metabolism in Hyperlipidemia Model Rats Based on Gut Microbiota Sequencing and Fecal Metabolomics
Xue LENG ; Qi WANG ; Yang LI ; Xintong LI
Journal of Traditional Chinese Medicine 2025;66(10):1046-1056
ObjectiveTo explore the potential mechanisms by which spleen deficiency affects lipid metabolism in hyperlipidemia, from the perspective of gut microbiota and fecal endogenous metabolites. MethodsEighteen Sprague-Dawley (SD) rats were randomly divided into control group, hyperlipidemia group, and spleen-deficiency with hyperlipidemia group, with 6 rats in each group. The control group was fed with standard diet; the hyperlipi-demia group was given high-fat diet to induce hyperlipidemia model; and the spleen-deficiency with hyperlipidemia group received combination of high-fat diet, irregular feeding, and exercise restriction to induce the model. After 12 weeks of modeling, serum lipid levels including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. 16S rRNA gene sequencing was used to analyze gut microbiota composition in fecal samples, and fecal metabolites were analyzed using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Differential metabolites and microbial taxa were screened for pathway enrichment and functional prediction analysis, followed by correlation analysis. ResultsCompared with the control group, rats in the hyperlipidemia and spleen-deficiency with hyperlipidemia groups showed significantly increased serum TG, TC, and LDL-C levels, and decreased HDL-C levels (P<0.01). Compared with the hyperlipidemia group, the spleen-deficiency with hyperlipidemia group showed further increases in TG, TC, and LDL-C and further decrease in HDL-C (P<0.05 or P<0.01). Gut microbiota analysis revealed 3,066 unique species in the control group, 2,637 in the hyperlipidemia group, and 1,581 in the spleen-deficiency group. Chao1, Simpson, and Shannon indices were significantly reduced in the spleen-deficiency group compared with the hyperli-pidemia group, with an increased Firmicutes/Bacteroidetes ratio. Differentially abundant genera such as Romboutsia, Lactobacillus, Clostridium, Allobaculum, and Xylanibacter were significantly upregulated (P<0.05 or P<0.01). Metabolomics identified 25 differential metabolites in feces of spleen-deficient rats, with 18 downregulated and 7 upregulated. Key enriched pathways included serotonergic synapse, nucleotide metabolism, vascular smooth muscle contraction, and arachidonic acid metabolism. Spearman correlation analysis showed significant positive correlations between Romboutsia and Desulfovibrio and metabolites such as digalactosyldiacylglycerol (48∶5), dehydrated artemetin, lysophosphatidylcholine (26∶4), and glucuronosyldiacylglycerol (46∶5); Clostridium was positively correlated with cyclopassifloric acid E1, digalactosyldiacylglycerol (48∶5), and lysophosphatidylcholine (26∶4); Xylanibacter was positively correlated with digalactosyldiacylglycerol (48∶5), dehydrated artemetin, and lysophosphatidylcholine (26∶4). ConclusionSpleen deficiency can further alter gut microbiota composition in hyperlipi-demia model rats, leading to microbial dysbiosis and metabolic disturbances that aggravate lipid metabolism disorders. This mechanism may be associated with changes in pathways such as serotonergic synapse, nucleotide metabolism, vascular smooth muscle contraction, and arachidonic acid metabolism.
2.Expedited program and utilization for anticancer drug approval in China and the United States
Qi ZHU ; Huiyao HUANG ; Anqi YU ; Xinyu MENG ; Ye LENG ; Hong FANG ; Ziwei LI ; Yu TANG ; Ji LI ; Ning LI
Chinese Journal of Oncology 2024;46(9):904-910
Objective:To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods:Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison.Results:Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P<0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions:Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.
3.ATP5J regulates mitochondrial function through TOMM20 and promotes metastasis of human hepatocellular carcinoma cells
Junzhi LENG ; Genwang WANG ; Di LIU ; Kejun LIU ; Qi WANG ; Yongfeng HUI
Chinese Journal of Pathophysiology 2024;40(3):431-437
AIM:To explore the mechanism of ATP synthase mitochondrial F0 complex H+ transporting,sub-unit F6(ATP5J)in affecting the metastasis of hepatoma carcinoma cells by regulating mitochondrial function-mediated cy-toskeletal remodeling.METHODS:Hepatocellular carcinoma cells Li-7 were used to construct the ATP5J overexpression and knockdown models.JC-1 staining was used to detect the mitochondrial membrane potential in each group,reactive oxygen species(ROS)levels were examined by DCHF-DA,and mitochondrial ATP fluorescence probe was used to assess mito-chondrial function.Cytoskeletal remodeling was detected with a microfilament green fluorescent probe(Actin-Tracker Green-488).Transwell assay was used to assess cell invasion ability.The expression levels of ATP5J and translocase of outer mitochondrial membrane 20(TOMM20)were determined by Western blot.RESULTS:Overexpression of ATP5J up-regulated mitochondrial membrane potential and mitochondrial ATP fluorescence intensity,induced cytoskeletal re-modeling,promoted cell invasion and TOMM20 expression,and inhibited ROS production(P<0.01).On the contrary,knockdown of ATP5J significantly decreased mitochondrial membrane potential and mitochondrial ATP fluorescence inten-sity,significantly decreased cell invasion ability and TOMM20 expression,promoted ROS production and blocked cyto-skeletal remodeling(P<0.01).CONCLUSION:ATP5J regulates mitochondrial energy transformation in hepatocellular carcinoma cells,and affects metastasis of hepatoma carcinoma cells by regulating mitochondrial membrane potential and mitochondrial ATP production-mediated cytoskeletal remodeling through TOMM20.
4.Expedited program and utilization for anticancer drug approval in China and the United States
Qi ZHU ; Huiyao HUANG ; Anqi YU ; Xinyu MENG ; Ye LENG ; Hong FANG ; Ziwei LI ; Yu TANG ; Ji LI ; Ning LI
Chinese Journal of Oncology 2024;46(9):904-910
Objective:To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods:Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison.Results:Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P<0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions:Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.
5.Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors
Ao LENG ; Qi WANG ; Jiacheng LI ; Yu LONG ; Song SHI ; Lingzhi MENG ; Mingming GUO ; Hailong YU ; Liangbi XIANG
Neurospine 2024;21(2):656-664
Objective:
To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors.
Methods:
A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs.
Results:
The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively.
Conclusion
Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.
6.Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors
Ao LENG ; Qi WANG ; Jiacheng LI ; Yu LONG ; Song SHI ; Lingzhi MENG ; Mingming GUO ; Hailong YU ; Liangbi XIANG
Neurospine 2024;21(2):656-664
Objective:
To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors.
Methods:
A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs.
Results:
The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively.
Conclusion
Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.
7.Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors
Ao LENG ; Qi WANG ; Jiacheng LI ; Yu LONG ; Song SHI ; Lingzhi MENG ; Mingming GUO ; Hailong YU ; Liangbi XIANG
Neurospine 2024;21(2):656-664
Objective:
To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors.
Methods:
A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs.
Results:
The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively.
Conclusion
Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.
8.Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors
Ao LENG ; Qi WANG ; Jiacheng LI ; Yu LONG ; Song SHI ; Lingzhi MENG ; Mingming GUO ; Hailong YU ; Liangbi XIANG
Neurospine 2024;21(2):656-664
Objective:
To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors.
Methods:
A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs.
Results:
The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively.
Conclusion
Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.
9.Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors
Ao LENG ; Qi WANG ; Jiacheng LI ; Yu LONG ; Song SHI ; Lingzhi MENG ; Mingming GUO ; Hailong YU ; Liangbi XIANG
Neurospine 2024;21(2):656-664
Objective:
To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors.
Methods:
A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs.
Results:
The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively.
Conclusion
Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.
10.Clinical characteristics of benign paroxysmal positional vertigo in the oldest old
Ruile FANG ; Qi LENG ; Yan WANG ; Meimei CHEN ; Yu CUI ; Xiaolin WU ; Yi JU
Chinese Journal of General Practitioners 2023;22(8):790-795
Objective:To analyze the clinical characteristics of benign paroxysmal positional vertigo (BPPV) in the oldest old.Method:The clinical data of elderly patients (≥60 years old) with BPPV diagnosed in the Clinical Center for Vertigo and Balance Disturbance of Capital Medical University between January 2019 and October 2021 was collected, including basic information, clinical symptoms in a structured medical history questionnaire and the time interval from the appearance of symptoms to medical consultation. According to the age, patients were divided into elderly group (60-74 years old) and the oldest old group (≥75 years old), and the demographic information, clinical symptoms and consultation time were compared between the two groups.Results:A total of 3 019 patients with BPPV were included in analysis; there were 415 patients in the oldest-old group with the age of (79.54±3.62) years, and 2 604 patients in the elderly group with the age of (65.59±3.88) years. The incidence of vertigo, dizziness or vertigo triggered by position changes of head or body, headache and autonomic symptoms in the eldest-old group were less common than that in the elderly group (all P<0.05). But hearing loss and other types of dizziness (unable to determine the nature of dizziness or vertigo, or without typical symptoms such as dizziness, balance disorders, or instability) were more common in the eldest-old group than those in the elderly group (all P<0.05). Among 3 019 patients, 1 137 had definite time from symptom onset to diagnosis (1 004 in the elderly group and 133 in the oldest-old group), the proportion of patients with the time from the onset to diagnosis>7 days in the oldest-old group was higher than that in the elderly group ( P<0.05). Conclusion:The oldest old patients with BPPV have more atypical symptoms than the younger elderly patients.

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