1.Dispersion effect of bone cement after vertebroplasty using individualized unilateral external pedicle approach and bilateral pedicle approach
Lichuang ZHANG ; Wen YANG ; Guangjiang DING ; Peikun LI ; Zhongyu XIAO ; Ying CHEN ; Xue FANG ; Teng ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(4):800-808
BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.
2.Xiaoyaosan Regulates HPT Axis in Rat Model with Syndrome of Liver Depression and Spleen Deficiency via CGA/GPX2/TSHβ Pathway for Thyroid Hormone Synthesis
Fang WANG ; Ruxin YUAN ; Lingjin FAN ; Zongli CHEN ; Huaye XIAO ; Liqiang YANG ; Xiaohong LI ; Chuncheng ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):1-10
ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit (CGA)/glutathione peroxidase 2 (GPX2)/thyroid-stimulating hormone β-subunit (TSHβ) pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups: normal, model, high-dose (16.7 g·kg-1), medium-dose (8.35 g·kg-1), and low-dose (4.175 g·kg-1) Xiaoyaosan, and fluoxetine (0.001 8 g·kg-1) groups, with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension, respectively. After modeling, hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine (T3), tetraiodothyronine (T4), and thyroid-stimulating hormone (TSH) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of TSH receptor (TSHR) in the thyroid tissue, thyrotropin-releasing hormone receptor (TRHR) and TSHβ in the pituitary tissue, and thyrotropin-releasing hormone (TRH), CGA, GPX2, and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group, the model group showed significant atrophy and irregularity of thyroid follicles, a marked reduction in colloid secretion, extensive vacuolar degeneration of adenocytes in the anterior pituitary, lowered serum levels of T3, T4, and TSH (P<0.01), and down-regulated mRNA and protein levels of TSHR in the thyroid tissue, TRHR and TSHβ in the pituitary tissue, and TRH, CGA, GPX2, and TSHβ in the hypothalamic tissue (P<0.01). Compared with the model group, high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue, outperforming the low-dose Xiaoyaosan group. Moreover, they elevated the serum levels of T3, T4, and TSH (P<0.05, P<0.01). The serum TSH level was also elevated in the low-dose Xiaoyaosan group (P<0.05). The mRNA and protein levels of TSHR in the thyroid, TRHR and TSHβ in the pituitary, and TRH, CGA, GPX2, and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups (P<0.05, P<0.01). Additionally, the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group (P<0.01). In the fluoxetine group, the mRNA and protein levels of TSHR in the thyroid, TRHR in the pituitary, and TRH, CGA, and GPX2 in the hypothalamus were up-regulated (P<0.05, P<0.01). ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.
3.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
4.Application of the combined tumor burden score and platelet-albumin-bilirubin score model for predicting postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma
Weidong ZHU ; Junyang XIAO ; Xiaoji QIU ; Lizhi LÜ ; Jianwei CHEN ; Fang YANG
Organ Transplantation 2025;16(4):556-564
Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.
5.Untargeted Metabolomics Reveals Mechanism of Modified Sinisan in Ameliorating Anxiety-like Behaviors Induced by Chronic Restraint Stress in Mice
Jie ZHAO ; Zhengyu FANG ; He XIAO ; Na GUO ; Hongwei WU ; Hongjun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):70-79
ObjectiveTo elucidate the potential mechanism of modified Sinisan (MSNS) in alleviating anxiety-like behaviors induced by chronic restraint stress (CRS) in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups: control, model, high-dose (2.4 g·kg-1) MSNS, medium-dose (1.2 g·kg-1) MSNS, low-dose (0.6 g·kg-1) MSNS, and positive control (fluoxetine, 2.6 mg·kg-1). Except the control group, the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test (OFT), elevated plus maze (EPM) test, and light/dark box (LDB) test. Serum levels of corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and corticosterone (CORT) were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted to identify differential metabolites (VIP>1.0, P<0.05). MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group, the model group showed reductions in the central activity time and central distance in the OFT (P<0.05), the proportions of open-arm residence time and open-arm residence times in the EPM test (P<0.01), and the proportions of open box activity time and open box activity distance in the LDB test (P<0.05), which were increased in the medium- and high-dose MSNS groups compared with the model group (P<0.05). Compared with the control group, the model group showed elevated levels of CRH, ACTH, and CORT in the serum (P<0.01), and the elevations were diminished in the medium- and high-dose MSNS groups (P<0.05). UPLC-MS results indicated that compared with the control group, the model group presented declined DA, GABA, 5-HIAA, 5-HT, and 5-HT/Trp levels (P<0.05, P<0.01) and raised Glu, NE, Kyn, and Kyn/Trp levels (P<0.05). Compared with the model group, high-dose MSNS increased the GABA, 5-HIAA, and 5-HT/Trp levels (P<0.05) and lowered the Glu and Kyn/Trp levels (P<0.05). Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, TCA cycle, unsaturated fatty acid biosynthesis, and tryptophan metabolism. The mechanisms involved multidimensional biological processes, including neurotransmitter homeostasis regulation, TCA cycle energy metabolism optimization, and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity, improving hippocampal neurotransmitter and tryptophan metabolic pathways, and regulating alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, and TCA cycle.
6.Untargeted Metabolomics Reveals Mechanism of Modified Sinisan in Ameliorating Anxiety-like Behaviors Induced by Chronic Restraint Stress in Mice
Jie ZHAO ; Zhengyu FANG ; He XIAO ; Na GUO ; Hongwei WU ; Hongjun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):70-79
ObjectiveTo elucidate the potential mechanism of modified Sinisan (MSNS) in alleviating anxiety-like behaviors induced by chronic restraint stress (CRS) in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups: control, model, high-dose (2.4 g·kg-1) MSNS, medium-dose (1.2 g·kg-1) MSNS, low-dose (0.6 g·kg-1) MSNS, and positive control (fluoxetine, 2.6 mg·kg-1). Except the control group, the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test (OFT), elevated plus maze (EPM) test, and light/dark box (LDB) test. Serum levels of corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and corticosterone (CORT) were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted to identify differential metabolites (VIP>1.0, P<0.05). MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group, the model group showed reductions in the central activity time and central distance in the OFT (P<0.05), the proportions of open-arm residence time and open-arm residence times in the EPM test (P<0.01), and the proportions of open box activity time and open box activity distance in the LDB test (P<0.05), which were increased in the medium- and high-dose MSNS groups compared with the model group (P<0.05). Compared with the control group, the model group showed elevated levels of CRH, ACTH, and CORT in the serum (P<0.01), and the elevations were diminished in the medium- and high-dose MSNS groups (P<0.05). UPLC-MS results indicated that compared with the control group, the model group presented declined DA, GABA, 5-HIAA, 5-HT, and 5-HT/Trp levels (P<0.05, P<0.01) and raised Glu, NE, Kyn, and Kyn/Trp levels (P<0.05). Compared with the model group, high-dose MSNS increased the GABA, 5-HIAA, and 5-HT/Trp levels (P<0.05) and lowered the Glu and Kyn/Trp levels (P<0.05). Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, TCA cycle, unsaturated fatty acid biosynthesis, and tryptophan metabolism. The mechanisms involved multidimensional biological processes, including neurotransmitter homeostasis regulation, TCA cycle energy metabolism optimization, and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity, improving hippocampal neurotransmitter and tryptophan metabolic pathways, and regulating alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, and TCA cycle.
7.Effect and mechanism of pachymic acid on renal function and fibrosis in rats with chronic renal failure
Bin PENG ; Xue FENG ; Li FENG ; Wei XIONG ; Xi HU ; Shuangyi ZHU ; Yang XIAO ; Fang CHEN ; Zhi GAO
China Pharmacy 2024;35(12):1489-1494
OBJECTIVE To investigate the effect of pachymic acid (PA) on renal function and fibrosis in chronic renal failure (CRF) rats and its potential mechanism based on the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. METHODS Using male SD rats as subjects, the CRF model was established by 5/6 nephrectomy; the successfully modeled rats were divided into model group, PA low-dose, medium-dose and high-dose groups (5, 10, 20 mg/kg PA), high-dose PA+ROCK pathway activator lysophosphatidic acid (LPA) group (20 mg/kg PA+1 mg/kg LPA), with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein, once a day, for 12 consecutive weeks. During the experiment, the general condition of rats was observed in each group. After the last administration, the serum renal function indexes (blood urea nitrogen, serum creatinine, uric acid) of rats in each group were detected, the renal histopathological changes were observed; the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde (MDA), superoxide dismutase (SOD)] and inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6), the positive expression rates of connective tissue growth factor (CTGF) and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins (RhoA, ROCK1) and fibrosis- related proteins (transforming growth factor-β1, bare corneum homologs 2, α-smooth muscle actin) were determined. RESULTS Compared with the sham operation group, the rats in model group had reduced diet, smaller body size, listless spirit and sluggish response, reduced and atrophied glomeruli, dilated renal tubules with chaotic structure, and a large number of inflammatory cells infiltrated interstitium; the serum levels of renal function indexes, renal tubule injury score, renal fibrosis area proportion, the levels of MDA and inflammatory factors, the positive expression rates of CTGF and collagen Ⅰ, and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased, while SOD level was significantly decreased (P<0.05). Compared with the model group, the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees,and the above quantitative indexes were significantly improved in a dose-dependent manner (P<0.05). LPA could significantly reverse the improvement effect of PA on the above indicators (P<0.05). CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats, which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.
8.Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease
Chao-Yang CHU ; Biao XIAO ; Jiang-Hui SHAN ; Shi-Yu CHEN ; Chu-Xia ZHANG ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Zhi-Cheng LIN ; Kai XIE ; Shu-Jun XU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2024;51(7):1510-1529
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.
9.Hepatitis C virus infection:surveillance report from China Healthcare-as-sociated Infection Surveillance System in 2020
Xi-Mao WEN ; Nan REN ; Fu-Qin LI ; Rong ZHAN ; Xu FANG ; Qing-Lan MENG ; Huai YANG ; Wei-Guang LI ; Ding LIU ; Feng-Ling GUO ; Shu-Ming XIANYU ; Xiao-Quan LAI ; Chong-Jie PANG ; Xun HUANG ; An-Hua WU
Chinese Journal of Infection Control 2024;23(1):1-8
Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93%and a HCV positive rate of 0.54%.The positive rate of HCV in male and female patients were 0.60%and 0.48%,respectively,with a statistically sig-nificant difference(x2=47.18,P<0.001).The HCV positive rate in the 50-<60 age group was the highest(0.76%),followed by the 40-<50 age group(0.71%).Difference among all age groups was statistically signifi-cant(x2=696.74,P<0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57%;775 patients were infected with HCV,with a positive rate of 2.21%.In 2020,HCV positive rates in hospitals of different scales were 0.46%-0.63%,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P<0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19%-0.81%,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06%-0.82%,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95%and 3.48%,respectively.Followed by departments of orthopedics(7.72%),gastroenterology(3.77%),nephrology(3.57%)and general intensive care unit(ICU,3.10%)in 2003,as well as departments of gastroenterology(1.35%),nephrology(1.18%),endocrinology(0.91%),and general intensive care unit(ICU,0.79%)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.
10.Effect of hand hygiene intervention on healthcare-associated case infection incidence from 2014 to 2022
Jia-Yan DING ; Rui-Hong SHEN ; Wen-Qin ZHOU ; Ya-Yun YUAN ; Mei HUANG ; Ya YANG ; Bing-Chao CAI ; Hai-Qun BAN ; Xiao-Fang FU
Chinese Journal of Infection Control 2024;23(2):208-213
Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98%in 2014 to 85.01%in 2022(P<0.001),and HA case infection incidence decreased from 1.21%to 0.83%(P<0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P<0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P<0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

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