1.The Effect of Banxia Xiexin Decoction (半夏泻心汤) on the Expression of LXRα in Liver Tissue and the JAK2/STAT3 Signaling Pathway in Gastric Antrum Tissue of Diabetic Gastroparesis Model Rats
Qi XU ; Nuobing RUAN ; Jinju LI ; Xijuan LYU ; Zhaohui FANG
Journal of Traditional Chinese Medicine 2025;66(2):178-187
ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction (半夏泻心汤, BXD) in the treatment of diabetic gastroparesis (DGP). MethodsA total of 29 SD rats were randomly divided into four groups, blank group (5 rats) and model group, BXD group and metformin group (8 rats in each group). Except for the blank group, rats were administered intraperitoneally with 1% streptozotocin (STZ) solution and were fed a high-sugar, high-fat diet to establish the DGP rat model. After successful modeling, the BXD group was treated with BXD at 6.68 g/(kg·d) by gavage, the metformin group was treated with metformin hydrochloride at 105 mg/(kg·d) by gavage, and the blank group and the model group were treated with normal saline at 6.68 ml/(kg·d) by gavage, for 8 weeks. After the last administration, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG) were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin (MTL) and gastrin (GAS), as well as inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin (HE) staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α (LXRα) levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue, and of janus kinase 2 (JAK2), phospho-janus kinase 2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3) and phospho-signal transducer and activator of transcription 3 (p-STAT3) in gastric antrum tissue. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of LXRα in liver tissue and JAK2, STAT3 in gastric antrum tissue. ResultsCompared with the blank group, the model group showed significant hepatic fatty degeneration, gastric antrum tissue structure destruction, and increases in FBG, HbA1c, TC, and TG levels; the average fluorescence intensity, protein level, and mRNA expression of LXRα in liver tissue were reduced; the gastric emptying rate and gastric tissue GAS and MTL levels decreased; inflammatory factors including TNF-α, IL-6, IL-1β in gastric tissue increased, IL-10 decreased; in gastric antrum tissue, the mRNA expression of p-JAK2/JAK2, p-STAT3/STAT3, and JAK2 and STAT3 increased (P<0.01). Compared with the model group, both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology; FBG, HbA1c, TC, and TG levels decreased, while LXRα fluorescence intensity, protein level, and mRNA expression in liver tissue significantly increased; the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher; the levels of TNF-α, IL-6, and IL-1β decreased, whereas IL-10 levels increased, p-JAK2/JAK2, p-STAT3/STAT3, and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased (P<0.05 or P<0.01). The BXD group showed higher level than the metformin group in FBG, HbA1c, and TG levels, lower level in gastric emptying rate and gastric tissue GAS content, and higher level in gastric tissue TNF-α, IL-6, IL-1β levels; there was also a decrease in IL-10 levels, and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue, as well as in p-JAK2/JAK2 levels in gastric antrum tissue (P<0.05 or P<0.01). ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.
2.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
3.Mechanism of Pharmacological Liver and Kidney Injuries of Dictamni Cortex Based on UPLC-Q-TOF-MS
Jiahe YAN ; Sujie LIU ; Xiaofan WANG ; Chen WANG ; Jiaxin RUAN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):48-56
ObjectiveThis study aims to reveal the mechanism of liver and kidney injuries caused by Dictamni Cortex and its interrelationship by metabonomics analysis of liver and kidney via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). MethodsThe content of the marker compounds of Dictamni Cortex was measured by high-performance liquid chromatography (HPLC) to carry out quality control. Sprague Dawley (SD) rats were randomly divided into a blank group (normal saline), an administration group (0.9, 2.7, 8.1 g·kg-1), and a high-dose withdrawal control group, with eight rats in each group. Continuous administration was performed once daily for 28 days. The liver and kidney injuries caused by each administration group were assessed by organ indices, pathological observations, and serum and plasma biochemical indices measured by enzyme-linked immunosorbent assay (ELISA). The potential biomarkers of liver and kidney injuries caused by Dictamni Cortex were screened, and pathway enrichment analysis and correlation analysis were performed based on UPLC-Q-TOF-MS. ResultsCompared with the blank group, both the medium- and low-dose groups showed insignificant damage to the liver and kidney of rats. The high-dose group exhibited the most serious damage, and the level of liver and kidney function indices [alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), and blood urea nitrogen (BUN)] and serum inflammatory indices ([interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)] in the serum were significantly changed (P<0.01). The liver and kidney metabolism pathways and differential metabolites were quite different. Among them, phenylalanine metabolism, niacin and nicotinamide metabolism, and glycerophospholipid metabolism were common pathways. Correlation analysis of differential metabolites showed that there were significant correlations among disorders of 4′-Phosphopantothenoylcysteine, PC (16∶0/15∶0), phenylethylamine, arachidonic acid, and linoleic acid in liver and kidney tissue. ConclusionThe decoction of Dictamni Cortex can cause liver and kidney injuries, and its mechanism may be related to oxidative stress and lipid metabolism disorders. The correlation of differential metabolites indicates the interaction between liver and kidney injuries.
4.Metabolomics Reveals Immune System Domage of Dictamnine
Xiaocan GAI ; Jiaxin RUAN ; Sujie LIU ; Chen WANG ; Xiaofan WANG ; Jiahe YAN ; Yu WANG ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):57-65
ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine (DIC) in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank (normal saline), DIC (10 mg·kg-1), and DIC withdrawal (recovery period) groups (n=8). The rats were continuously treated for 7 days, once a day, and the body weight and organ weight were recorded. The levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) in the serum and immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to screen the potential biomarkers of immune inflammation caused by DIC, and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β, TNF-α, lysophosphatidylcholine acyltransferase 2 (LPCAT2), and farnesoid X receptor (FXR) in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, the DIC group showed elevated levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01), and the DIC withdrawal group showcased lowered levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01). The levels of IgA, IgG, and IgM in the spleen of rats in the DIC group were decreased (P<0.01), while those in the DIC withdrawal group were recovered (P<0.05, P<0.01). Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC (32∶0), LysoPC (20∶4/0∶0), LysoPC (P-18∶0/0∶0), taurochenodeoxycholic acid, taurocholic acid, LysoPC [20∶5(5Z,8Z,11Z,14Z,17Z)/0∶0], chenodeoxycholic acid, arachidonic acid, LysoPC (18∶0/0∶0), LysoPC (15∶0/0∶0), LysoPC (16∶0/0∶0), and LysoPC (17∶0/0∶0) as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC, lipid metabolism disorders such as glycerophospholipid metabolism, primary bile acid metabolism, and arachidonic acid metabolism were enriched, which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group, the DIC group exhibited up-regulated mRNA levels of IL-1β, TNF-α, LPCAT2, and FXR (P<0.01), and the up-regulation was decreased in the withdrawal group (P<0.01). ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites, regulate the inflammatory metabolic pathway, reduce the inflammation level, and alleviate the metabolic disorders, thus attenuating the potential toxicity induced by DIC.
5.Effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome.
Kuiwu LI ; Haoran CHU ; Ling ZOU ; Jingru RUAN ; Lumin LIAO ; Xiaoyu HAN ; Wenli MA ; Ming FANG ; Jingwei ZHU ; Yucheng FANG ; Ziye WANG ; Tingting TONG
Chinese Acupuncture & Moxibustion 2025;45(7):935-944
OBJECTIVE:
To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms.
METHODS:
Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy.
RESULTS:
Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD8+ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD4+ T subset and CD4+/CD8+, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD4+ T subset, and CD4+/CD8+, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged.
CONCLUSION
Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals
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Irritable Bowel Syndrome/immunology*
;
Rats
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Moxibustion
;
Intestinal Mucosa/immunology*
;
Female
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Diarrhea/therapy*
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Intestine, Small/immunology*
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Male
;
Humans
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Rats, Sprague-Dawley
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Disease Models, Animal
6.Mechanism of Yishen Jiangtang Decoction in regulating endoplasmic reticulum stress-mediated NLRP3 inflammasome to improve renal damage in diabetic nephropathy db/db mice.
Yun-Jie YANG ; Bin-Hua YE ; Chen QIU ; Han-Qing WU ; Bo-Wei HUANG ; Tong WANG ; Shi-Wei RUAN ; Fang GUO ; Jian-Ting WANG ; Ming-Qian JIANG
China Journal of Chinese Materia Medica 2025;50(10):2740-2749
This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals
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Endoplasmic Reticulum Stress/drug effects*
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Diabetic Nephropathies/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Inflammasomes/drug effects*
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Male
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Kidney/pathology*
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Endoplasmic Reticulum Chaperone BiP
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Humans
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Interleukin-18/genetics*
;
Mice, Inbred C57BL
7.Diagnostic value of ultrasonic shear wave elastography for clinically significant prostate cancer.
Fang-Rui YANG ; Yong-Hao JI ; Li-Tao RUAN ; Jian-Xue LIU ; Yao-Ren ZHANG ; Xiao ZHANG ; Qin-Yun WAN ; Si-Fan REN
National Journal of Andrology 2025;31(6):505-511
OBJECTIVE:
To explore the diagnostic value of shear wave elastography (SWE) for clinically significant prostate cancer (csPCa).
METHODS:
We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer (PCa) in Baoji Central Hospital from June 2017 to July 2023. All the patients underwent the following examinations in the order of serum prostate-specific antigen (PSA) testing, transrectal ultrasonography (TRUS), measurement of the stiffness of the entire prostate gland by SWE, and TRUS-guided prostate puncture biopsy. The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base, middle, and apex of the prostate, including the maximum Young's modulus (Emax), mean Young's modulus (Emean), and minimum Young's modulus (Emin). We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results, focusing on their diagnostic performance for csPCa.
RESULTS:
Of the 359 cases, 189 were diagnosed by pathological puncture biopsy as BPH, 26 as non-csPCa, and 144 as csPCa. The PSA level, Emax, Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups (all P < 0.01), but showed no statistically significant difference between the BPH and non-csPCa groups (all P > 0.05). The area under the receiver operating characteristic curve (AUC), optimal cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of Emax in the diagnosis of csPCa were 0.852, 143.92 kPa, 72.22%, 84.65%, 75.91%, 81.98% and 79.67%; those of Emean were 0.868, 82.42 kPa, 67.36%, 91.16%, 83.62%, 80.66% and 81.62%; and those of Emin were 0.682, 32.73 kPa, 47.22%, 89.30%, 73.91%, 71.54% and 72.14%, respectively. In the non-csPCa group, Emax, Emean and Emin were found below the optimal cut-off value in 73.08% (19/26), 92.31% (24/26) and 88.46% (23/26), respectively.
CONCLUSION
The stiffness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa, reduces unnecessary detection of non-csPCa, and provides some reference for its active surveillance.
Humans
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Male
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Prostatic Neoplasms/diagnosis*
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Elasticity Imaging Techniques
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Retrospective Studies
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Prostate/pathology*
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Prostate-Specific Antigen/blood*
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Aged
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Middle Aged
8.Qingre Lidan Jiedu Recipe improves high copper load-induced cognitive dysfunction in rats by regulating mitophagy.
Yulan WANG ; Xiang FANG ; Zeming CHEN ; Bingkun RUAN ; Xinli HAN ; Yujie TANG ; Luyao ZHU
Journal of Southern Medical University 2025;45(11):2437-2443
OBJECTIVES:
To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load.
METHODS:
Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy.
RESULTS:
Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups.
CONCLUSIONS
QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals
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Male
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Rats, Sprague-Dawley
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Rats
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Drugs, Chinese Herbal/therapeutic use*
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Copper/toxicity*
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Mitophagy/drug effects*
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Hippocampus/drug effects*
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Cognition Disorders/drug therapy*
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Cognitive Dysfunction/chemically induced*
9.Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway.
Ying YANG ; Jin-Yu QU ; Hua GUO ; Hai-Ying ZHOU ; Xia RUAN ; Ying-Chun PENG ; Xue-Fang SHEN ; Jin XIONG ; Yi-Li WANG
Chinese journal of integrative medicine 2024;30(2):152-162
OBJECTIVE:
To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.
METHODS:
Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS:
BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).
CONCLUSION
EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats
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Animals
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Electroacupuncture
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Rats, Sprague-Dawley
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Serotonin
;
Acupuncture Points
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Pain, Referred
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Calcitonin Gene-Related Peptide
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Signal Transduction
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Colitis/therapy*
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Indoles
;
Sulfonamides
10.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.


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