1.Analysis on Quality Standard of Hedyotis Herba Dispensing Granules Based on Standard Decoction
Jinghua ZHANG ; Nana WU ; Yanan LYU ; Guiyun CAO ; Jiacheng XU ; Yongqiang LIN ; Xiaodi DONG ; Jinxin LI ; Zhaoqing MENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):210-217
ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker(QAMS) based on linear calibration using two reference substances(LCTRS), explore the consistency between Hedyotis Herba dispensing granules and standard decoction, and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography(HPLC) specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules, and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C18 columns, taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds, the retention times of the other 5 characteristic peaks were predicted and validated. Based on this, QAMS was developed to determine the contents of four components(deacetyl asperulosidic acid, deacetyl asperulosidic acid methyl ester, asperulosidic acid, and p-coumaric acid). Then, the relative correction factors of deacetyl asperulosidic acid, deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds, and each component was quantified accordingly. Finally, the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction, consistency of the specific chromatograms, contents and transfer rates of the indicator components as indexes, and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules, and four of them were identified by reference standards, namely deacetyl asperulosidic acid(peak 1), deacetyl asperulosidic acid methyl ester(peak 3), asperulosidic acid(peak 6) and p-coumaric acid(peak 7). The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%, the contents of deacetyl asperulosidic acid, deacetyl asperulosidic acid methyl ester, asperulosidic acid and p-coumaric acid were 6.62-19.70, 3.83-17.99, 1.57-6.69, 1.62-4.52 mg·g-1, and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%, 34.03%-62.24%, 24.25%-43.70%, and 40.58%-73.71%, respectively. The extract rate, index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules(P1-P3), produced by manufacturer A, were similar to those of the standard decoction prepared from the same batch of decoction pieces, and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules(P4-P10) from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield, consistency of specific chromatograms, contents and transfer rates of the four index components, the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction, indicating that the current production process is relatively reasonable.
2.Analysis and forecast of the disease burden of schistosomiasis in China from 1992 to 2030
Kai LIN ; Chenhuan ZHANG ; Zhendong XU ; Xuemei LI ; Renzhan HUANG ; Yawen LIU ; Haihang YU ; Lisi GU
Chinese Journal of Schistosomiasis Control 2025;37(1):24-34
Objective To analyze the trends in the disease burden of schistosomiasis in China from 1992 to 2021, and to project the disease burden of schistosomiasis in China from 2022 to 2030, so as to provide insights into the elimination of schistosomiasis in China. Methods The prevalence, age-standardized prevalence, disability-adjusted life year (DALYs) rate and age-standardized DALYs rate of schistosomiasis, as well as the years lost due to disability (YLDs) rate and age-standardized YLDs rate of anemia attributable to Schistosoma infections in China, the world and different socio-demographic index (SDI) regions were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources, and the trends in the disease burden due to schistosomiasis were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI). In addition, the age, period and cohort effects on the prevalence of schistosomiasis were examined in China using an age-period-cohort (APC) model, and the disease burden of schistosomiasis was predicted in China from 2022 to 2030 using a Bayesian age-period-cohort (BAPC) model. Results The age-standardized prevalence and DALYs rate of schistosomiasis, and the age-standardized YLDs rate of anemia attributable to Schistosoma infections were 761.32/105, 5.55/105 and 0.38/105 in China in 2021. These rates were all lower than the global levels (1 914.30/105, 21.90/105 and 3.36/105, respectively), as well as those in the medium SDI regions (1 413.61/105, 12.10/105 and 1.93/105, respectively), low-medium SDI regions (2 461.03/105, 26.81/105 and 4.48/105, respectively), and low SDI regions (5 832.77/105, 94.48/105 and 10.65/105, respectively), but higher than those in the high SDI regions (59.47/105, 0.49/105 and 0.05/105, respectively) and high-medium SDI regions (123.11/105, 1.20/105 and 0.12/105, respectively). The prevalence and DALYs rate of schistosomiasis were higher among men (820.79/105 and 5.86/105, respectively) than among women (697.96/105 and 5.23/105, respectively) in China in 2021, while the YLDs rate of anemia attributable to Schistosoma infections was higher among women (0.66/105) than among men (0.12/105). The prevalence of schistosomiasis peaked at ages of 30 to 34 years among both men and women, while the DALYs rate of schistosomiasis peaked among men at ages of 15 to 19 years and among women at ages of 20 to 24 years. The age-standardized prevalence of schistosomiasis showed a moderate decline in China from 1992 to 2021 relative to different SDI regions [EAPC = -1.51%, 95% CI: (-1.65%, -1.38%)], while the age-standardized DALYs rate [EAPC = -3.61%, 95% CI: (-3.90%, -3.33%)] and age-standardized YLDs rate of anemia attributable to Schistosoma infections [EAPC = -4.16%, 95% CI: (-4.38%, -3.94%)] appeared the fastest decline in China from1992 to 2021 relative to different SDI regions. APC modeling showed age, period, and cohort effects on the trends in the prevalence of schistosomiasis in China from 1992 to 2021, and the prevalence of schistosomiasis appeared a rise followed by decline with age, and reduced with period and cohort. BAPC modeling revealed that the age-standardized prevalence and age-standardized DALYs rate of schistosomiasis, and age-standardized YLDs rate of anemia attributable to Schistosoma infections all appeared a tendency towards a decline in China from 2022 to 2030, which reduced to 722.72/105 [95% CI: (538.74/105, 906.68/105)], 5.19/105 [95% CI: (3.54/105, 6.84/105)] and 0.30/105 [95% CI: (0.21/105, 0.39/105)] in 2030, respectively. Conclusions The disease burden of schistosomiasis appeared a tendency towards a decline in China from 1992 to 2021, and is projected to appear a tendency towards a decline from 2022 to 2030. There are age, period and cohort effects on the prevalence of schistosomiasis in China. Precision schistosomiasis control is required with adaptations to current prevalence and elimination needs.
3.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
4.Analysis on Acupuncture in the Treatment of Post-stroke Dysphagia Based on the Theory of "Latent Pathogen in Cerebral Collaterals"
Hongtao LI ; Yaqi HUANG ; Lulu YAO ; Bing GAO ; Yu YE ; Nenggui XU ; Lin WANG
Journal of Traditional Chinese Medicine 2025;66(9):901-905
Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings, it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia (PSD). In clinical practice, treatment is tailored according to the location of PSD. During the oral stage, when the pathogen invades the face and mouth, resulting in excessive salivation, acupoints are primarily selected from the foot shaoyin (少阴) kidney channel, in combination with ren mai (任脉) , du mai (督脉), chong mai (冲脉) and the spleen channel, to replenish essence and fill the marrow, dispel dampness and unblock the channels. In the pharyngeal stage, as the pathogen obstructs the throat, disrupting normal swallowing, the therapy emphasizes dredging the shaoyang (少阳) channel and warming and tonifying the jueyin (厥阴) channel, by taking acupoints mainly from the hand and foot shaoyang channels, along with the jueyin channels, so as to soothe the liver and promote bile secretion, regulate and harmonize qi and blood. During the esophageal stage, where the pathogen damages the esophagus, impeding food passage, the treatment emphasizes activating the yangming (阳明) channels and regulating taiyin (太阴) channels; acupoints are mainly selected from the foot yangming stomach channel, along with the taiyin channels, aiming to warm yang, unblock the channels and dispel stasis.
5.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
6.Study on the safety and pharmacological effect on improving dyspepsia of Shuangshu decoction in rats
Xinyuan CHEN ; Changzhou XIONG ; Jiongfen LI ; Kangyi YU ; Huan XU ; Yingxia WANG ; Dan LIAO ; Junyu TAO ; Ziyi YANG ; Caizhi LIN
China Pharmacy 2025;36(9):1059-1064
OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia (FD) in rats. METHODS In safety test, 40 rats were divided into blank control group, Shuangshu decoction low-dose, medium- dose and high-dose groups [108, 216, 324 g/(kg·d), calculated by raw medicine, the same applies below]; they were given relevant medicine intragastrically, for continuous 14 days. The mortality and toxic reactions of rats were recorded, and the organ indexes of the liver, kidney, spleen, lung and heart of rats were calculated; the pathological morphological changes in the liver, kidney, spleen, lung, heart, stomach, duodenum, and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded, and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed, and blood routine and serum biochemical indicators were measured, in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group, model group, and Shuangshu decoction low-, medium-, and high-dose groups (9.45, 18.9, 37.8 g/kg), with 10 rats in each group. Except for blank control group, rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide (3.5 mg/kg). Rats in each group were administered the corresponding drug solution/normal saline intragastrically, once a day, for 14 consecutive days. After the last medication, fecal moisture content, intestinal propulsion rate, gastric emptying rate and serum level of motilin were all detected, and interstitial cell of Cajal (ICC) ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group, and no significant difference was found in organ coefficient, routine blood and serum biological index, compared to blank control group (P>0.05); no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that, compared with the blank control group, the fecal moisture content, gastric emptying rate, intestinal propulsion rate, and serum motilin levels in the model group were significantly decreased (P<0.05); in the colonic tissue, the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae, and the endoplasmic reticulum was dilated. Compared with model group, the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators (P< 0.05); additionally, there was a large number of mitochondria in the ICC of the colonic tissue, with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats; its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion, as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.
7.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
8.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
9.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
10.Optimization and Mechanism Exploration of Tusizi Prescription for Ovarian Reserve Function Based on Uniform Design Method
Yuan LI ; Hanqian DU ; Jiashan LI ; Li GUO ; Zehui LI ; Na LIN ; Ying XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):53-62
ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 (CCK-8) assay was employed to measure the viability of human ovarian granulosa cells (KGN cells) treated with Tusizi prescription extracts 1-11, and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM). The common targets shared by Tusizi prescription and diminished ovarian reserve (DOR) were selected and imported into search tool for the retrieval of interacting genes/proteins (STRING) to construct a protein-protein interaction (PPI) network and into gene function annotation database (DAVID) for gene ontology (GO) analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, terminal-deoxynucleoitidyl transferase mediated nick-end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA) were employed to examine the proliferation, apoptosis, and estradiol (E2) secretion of KGN cells treated with the water extract 11 of Tusizi prescription (Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1) and the optimal prescription screened by uniform design. On this basis, the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes, primarily involving cellular responses to exogenous compound stimuli, negative regulation of apoptotic process, and positive regulation of cell proliferation. It identified 84 cellular components, including cell membrane, mitochondria, and neuronal cell body, as well as 144 molecular functions such as enzyme binding, estrogen response element binding, and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen, Lycii Fructus, Dioscoreae Rhizoma, Poria, and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14, the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group, the hyperoside group demonstrated increased viability of ovarian germline stem cells (P<0.01). The CCK-8, EdU, and ELISA results showed that compared with the normal group, the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells (P<0.05, P<0.01). ELISA results showed that compared with the normal group, the water extract 11 of Tusizi prescription promoted the E2 secretion of KGN cells (P<0.05), while the optimal prescription screened by uniform design had no significant effect on the E2 secretion. ConclusionBoth the water extract 11 of Tusizi prescription (Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1) and the optimal prescription screened by uniform design (Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14) can improve the ovarian reserve function, and the former has better effect. Tusizi prescription can modulate biological processes (such as cell proliferation and apoptosis) and molecular functions (such as enzyme binding and estrogen response element binding) through active components like hyperoside to promote the proliferation and E2 secretion and inhibit the apoptosis of KGN cells, thereby protecting the ovarian reserve function.

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