Table of Content

Volume 29 Issue 10
26 October 2024

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Prednisone combined with icariin enhances the therapeutic effect of steroid resistant nephrotic syndrome 

DUAN Shuwen, WEI Yajun, WU Tiankai, WANG Xiaohui, DING Zhaoran, LIU Can, DAI Enlai

2024, 29(10):  1081-1090.  doi:10.12092/j.issn.1009-2501.2024.10.001

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AIM: To explore the therapeutic effect and possible molecular mechanisms of prednisone combined with icariin (ICA) on hormone resistant nephrotic syndrome (SRNS). METHODS: In the in vivo experiment, rats were divided into control group, SRNS group, prednisone group, and P+I group. Each group was given corresponding drugs for 6 weeks. Detection of 24-hour urinary protein in rats using CBB; The blood biochemistry analyzer detects rat albumin, total cholesterol, triglycerides, creatinine, and urea nitrogen; HE and Masson were used to detect morphological changes in rat kidney tissue; Immunohistochemical detection of GR-α, GR-β, NLRP3, caspase-1, GSDMD, IL-1β. In the in vitro experiment, HK-2 cell injury model with doxorubicin, divided into control group, SRNS group, prednisone group, P+I group. GR-α, GR-β, NLRP3, caspase-1, GSDMD were detected by Rt-PCR and Western blot. RESULTS: In the in vivo experiment, compared with the control group, the SRNS group showed weight loss, increased 24-hour urine protein, decreased albumin, increased total cholesterol, triglycerides, creatinine, and urea nitrogen, renal tubular atrophy, increased renal interstitial area, significant infiltration of inflammatory cells, fibrous tissue proliferation, and GR-β, NLRP3, caspase-1, GSDMD, IL-1 β in renal tissue decreased (P<0.01); Compared with the SRNS group, the combined group showed weight gain, decreased 24-hour urine protein, increased albumin, decreased total cholesterol, triglycerides, creatinine, and urea nitrogen, reduced renal tubular atrophy, reduced interstitial inflammatory cell infiltration, reduced fibrosis, and and GR-α,NLRP3,caspase-1,GSDMD in renal tissue decreased increased (P<0.01). In vitro experiments, compared with the control group, the model group showed GR-β, NLRP3, caspase-1, and GSDMD increased (P<0.01), GR-α decreased (P<0.01); Compared with the SRNS group, GR- β, NLRP3, caspase-1, and GSDMD decreased (P<0.01), GR-α increased in the P+I group. CONCLUSION: The combination of prednisone and ICA has a protective effect on the kidneys of SRNS rats and can improve the therapeutic effect. The mechanism may be related to the NLRP3/Caspase-1/GSDMD pathway.

Vitexin regulates the Epac1/Rap1 pathway to mediate protective effects against hypoxia-reoxygenation injury in H9c2 cardiomyocytes

GAN Qin, WANG Xin, YANG Huanghua, DONG Liuyi

2024, 29(10):  1091-1099.  doi:10.12092/j.issn.1009-2501.2024.10.002

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AIM: To investigate the role of Epac/Rap1 signaling pathway in hypoxia- reoxygenation injury in H9c2 cells, and to explore the mechanism of vitexin regulating the Epac/Rap1 signaling pathway to protect cardiomyocytes from hypoxia- reoxygenation injury. METHODS: The oxygen glucose deprivation (OGD) model was established using H9c2 cardiomyocytes to simulate hypoxia- reoxygenation injury. The experiment was randomly divided into 7 groups: Normal control group, OGD group, OGD+VT group, OGD+8-CPT+VT group, OGD+ESI-09+VT group, OGD+8-CPT+VT+H-89 group, OGD+ESI-09+VT+H-89 group. Cell viability was measured by MTT. LDH was used to detect cell damage. The expression levels of Epac1 and its downstream Rap1-GTP, CaMK II and ERK proteins in H9c2 cells were detected by Western blot. The expression of Epac1 and Rap1 proteins in H9c2 cardiomyocytes was detected by immunofluorescence. The mRNA expression of Rap1 and Epac1 in H9c2 cardiomyocytes was quantitatively determined by real-time PCR. Calcium ion fluorescence probe (Fluo-3 AM) was used to detect intracellular ［Ca2+］i content. The interaction between Epac1 and Rap1 in cells were detected by Co-IP. RESULTS: Compared with the normal control group, after hypoxia for 5 h and reoxygenation for 1 h, the release of LDH, cell viability, Epac1 protein expression, Rap1 activation and RAP1-GTP up-regulation of H9c2 cardiomyocytes in OGD group were significantly increased. VT (10 μmol/L) significantly inhibited the activation of Epac1 in H9c2 cardiomyocytes after OGD, and then inhibited the expression of downstream Rap1 active form Rap1-GTP. In addition, the expression of CaMK II protein was down-regulated, but ERK phosphorylation was increased, and intracellular calcium overload was alleviated. Epac1 agonist 8-CPT could counteract the effect of VT, and Epac1 inhibitor (ESI-09) combined with VT had synergistic effect. PKA inhibitor (Hmur89) had no effect on the expression of Epac1 and its downstream related proteins in cardiomyocytes. CONCLUSION: Hypoxia-reoxygenation can mediate the activation of Epac1/Rap1 signal pathway in cardiomyocytes. VT can protect cardiomyocytes from hypoxia-reoxygenation injury by inhibiting Epac1/Rap1 signal pathway, down-regulating CaMK II protein expression and promoting ERK phosphorylation.

Study of the mechanism of combretastatin a-4 derivative LGD5 induced G2/M cycle arrest and apoptosis in human cervical cancer HeLa cells

PANG Lili, HU Ying, LUO Jie, TU Qin, CHEN Min

2024, 29(10):  1100-1109.  doi:10.12092/j.issn.1009-2501.2024.10.003

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AIM: To explore the mechanism of action of the microtubular inhibitor of CA-4 derivative LGD5 on human cervical cancer HeLa cells. METHODS: HeLa cells were selected and divided into blank group, CA-4 positive control group, and different concentrations of LGD5 were formed into the experimental group. MTT was used to investigate the growth inhibition of LGD5 on HeLa cells and to determine the assay concentration. Cell morphology and apoptosis were observed before and after drug administration by inverted microscope and acridine orange staining.  Immunofluorescence staining was used to examine the effect of LGD5 on microtubules using DAPI. The effect of LGD5 on cell cycle by PI flow cytometry. Protein immunoblotting was used to examine the effect of LGD5 on cyclins and apoptosis-related proteins. RESULTS: MTT experiments showed that LGD5 inhibited HeLa cells in a time-and dose-dependent manner. Timed photography and acridine orange staining observed that LGD5 induced apoptosis in HeLa cells and produced significant chromatin agglutination and apoptotic bodies. Inhibition of microtubule polymerization in HeLa cells by LGD5 was observed by DAPI staining. The PI flow cytometry results showed that LGD5 induced G2/M cycle arrest in HeLa cells, was time-dependent and dose-dependent within 12 h, and had a significant difference (P<0.01), apoptosis was induced after 24 h and it was time-dependent. The results of Western blot show that, LGD5 downregulates Cdc 2 and Cdc25C, upregulation of p-Cdc 2, and Cyclin B1 and p-histone H3, further verified that LGD5 induced G2/M cycle arrest in HeLa cells, besides, LGD5 caused increased Caspase 3 expression in HeLa cells, upregulated Caspase 9 and Bax, down-regulation of Pro-caspase 9 and Bcl-2, this result indicates that HeLa cell apoptosis induced by LGD5 is related to the mitochondrial pathway. CONCLUSION: The CA-4 derivative LGD5 inhibited microtubule polymerization in HeLa cells, induced their G2/M cycle arrest, and subsequently induced cell apoptosis through the mitochondrial pathway.

Exploring the effect and mechanism of α-Linolenic acid on neuroinflammation based on network pharmacology and in vitro experiments

ZHANG Tao, WANG Ruowei, FU Jialin, GAO Yue, HU Mingyuan, FANG Zhengmei, CHEN Yan, YAO Yingshui

2024, 29(10):  1110-1119.  doi:10.12092/j.issn.1009-2501.2024.10.004

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AIM: To explore the core target and mechanism of α-Linolenic acid (ALA) in improving neuroinflammation through network pharmacology combined with in vitro experiments.METHODS: Pharmacological studies have shown that ALA has anti-inflammatory, antioxidant, and neuroprotective properties. The targets of α-Linolenic acid were obtained from PharmMapper and Swiss Target Prediction databases, the targets of neuroinflammation were searched from GeneCards, TTD and OMIM databases, and the potential targets of ALA and neuroinflammation were obtained from Wayne diagram.Protein interaction network (protein - protein interaction, PPI) of potential targets was constructed by STRING website, and the core targets in PPI were screened by Cytoscape 3.8.0 software.At the same time, potential targets are imported into DAVID database, GO and KEGG data were obtained and the results were visualized.Autodock vina and Pymol software were used to dock the selected core targets with ALA and visualize the results. An in vitro model of neuroinflammation was constructed, and cell growth status, oxidative stress, and migration or repairing capacity were determined by CCK-8 analysis, SOD, MDA and cell scratches, and the expression of IL-6, iba 1, COX-2 (PTGS2), and iNOS proteins was determined by ELISA or Western blot experiments.RESULTS: Network pharmacology analysis revealed 46 potential targets of ALA for neuroinflammation, and 10 core targets, including IL-6 and PTGS 2. With 232 entries enriched by GO enrichment analysis and 70 signaling pathways enriched by KEGG enrichment analysis, molecular docking showed that ALA can form hydrogen bonding with COX-2.Experiments showed that ALA could improve cell viability, alleviate cell oxidative stress levels, and promote cell migration and motor repair in an in vitro model of neuroinflammation. CONCLUSIONS: ALA may improve neuroinflammation by alleviating oxidative stress and inhibiting IL-6 and COX-2 protein expression.

Effect of Piperlongum L against pulmonary fibrosis based on network pharmacology and in vitro studies

GUO Jingjing, ZHEN Hua, ZHANG Shengwei, JIAN Ruonan

2024, 29(10):  1120-1133.  doi:10.12092/j.issn.1009-2501.2024.10.005

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AIM: To predict the active components and targets of Piperlongum L. and the associated signaling pathways involved in pulmonary fibrosis using network pharmacology and molecular docking technique and evaluate the mechanism of Piperlongum L against pulmonary fibrosis by in vitro experiments. METHODS: The active ingredients and targets were retrieved from TCMSP, Swiss Target Prediction and PubChem databases. The disease-related targets were retrieved from GeneCards and OMIM databases. The intersection targets of the drugs and disease-related targets were identified using jvenn online tool. String database was used to construct the "drug-component-target" and PPI network and the networks were visualized using Cytoscape 3.9.1 software. GO and KEGG enrichment analysis were performed on the intersection targets using the DAVID tool. The top 20 KEGG pathways, core targets and drug components were used to construct a "component-target-pathway" network and the network visualization was performed using Cytoscape 3.9.1 software. The interactions between drug compounds and the targets were evaluated by molecular docking, and the docking results were visualized using Discovery studio. HFL-1 cells were cultured and the effect of the drug compounds on cell viability was determined by MTT assay. The inhibition rate was then calculated to determine the optimal drug concentration. HFL-1 cells were cultured in vitro and were assigned into 4 groups: control group, TGF-β1 group, TGF-β1+LD group (LD group), TGF-β1+HD group (HD group). CCK-8 kit was used to evaluate the antiproliferative activity of the drug compounds against HFL-1 cells at 24, 48 and 72 h. Plate clone formation assay was performed to evaluate the effect of drugs on the colony formation ability of HFL-1 cells. RT-qPCR and western blot were conducted to determine the effect of the compounds on the mRNA and protein expression levels of α-smooth muscle actin (α-SMA), collagen type I (COI-I), and collagen type III (COI-III) in each group. RESULTS: A total of 197 intersection targets of Piperlongum L and anti-pulmonary fibrosis were identified. The core PPI network comprised 29 nodes (targets) and 199 edges (interactions). GO functional analysis showed that the significantly enriched biological processes associated with the compounds in Piperlongum L included negative regulation of apoptosis, signal transduction, and protein phosphorylation. Significantly enriched cellular components included cytoplasm, nuclear cytoplasm, plasma membrane. Enriched molecular functions associated with the compounds included the same protein binding, serine/threonine/tyrosine kinase activity, and protein binding. A total of 155 significantly enriched KEGG signaling pathways were identified, with PI3K-Akt signaling pathway was highly associated with PF and was the fourth most enriched pathway. PIK3CA, MAPK3, MAPK1, MTOR, SRC, CCND1, EGFR, PRKCA, BCL2, and GSK3B had the highest connectivity in the components-target-pathway network. Piperlongine, N-(2, 5-dimethoxyphenyl) -4-methoxybenzamide, tetrahydrotanshinone, pisigenin and piperine were the key compounds in Piperlongum L. The molecular docking results showed that all the compounds except N-(2,5-dimethoxyphenyl)-4-methoxybenzamide had good binding activities with interactions observed with 10 proteins. The proliferation ability of the cells in the LD group was significantly lower than that of the TGF-β1 group at 48 h and 72 h (P<0.05). The proliferation ability of cells HD group was significantly lower than the LD group at 24, 48 and 72 h. The number of clones in each drug group was significantly reduced after treatment with the drugs (P<0.05). The mRNA and protein expression levels of α-SMA, COI-I, COI-III in LD and HD groups were significantly lower than the expression levels in the TGF-β1 group. The protein expression levels of p-PI3K/PI3K and p-Akt /AKT were significantly lower in the two dose groups compared with the TGF-β1 group (P<0.01). CONCLUSION: The results showed that the effect of Piperlongum L against PF is probably through modulation of the PI3K-Akt signaling pathway.

Xinfeng capsule inhibits rheumatoid arthritis by binding to Wnt5a via Wnt/β-catenin signaling pathway

HUANG Yurong, PENG Yanhui, WANG Bing, MIAO Chenggui, WANG Xiao

2024, 29(10):  1134-1145.  doi:10.12092/j.issn.1009-2501.2024.10.006

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AIM: This study will clarify whether Wnt5a can be used as a potential diagnostic and therapeutic target for rheumatoid arthritis (RA) and how Xinfeng capsule (XFC) can improve RA through the Wnt5a/β-catenin signaling pathway. METHODS: ELISA and RT-qPCR were used to detect inflammatory factors and pathological genes in the rat model of AA in vivo to investigate the effect of XFC on AA rats. RT-qPCR was used to verify the core genes and key pathways of XFC regulation predicted by network pharmacology. The regulatory mechanism of XFC on Wnt/β-catenin pathway was elucidated by RT-qPCR. Western blot and immunofluorescence in primary AA fibroblast-like synovial cells (FLS) in vitro. RESULTS: XFC significantly decreased the arthritis score and paw swelling in AA rats, and inhibited joint inflammation in AA rats. XFC decreased the levels of inflammatory factors TNF-α and IL-1 in peripheral blood of AA rats, and inhibited the levels of pathological genes MMP3 and fibronectin in joint synovium and AA FLS of AA rats. Network pharmacology predicts that the Wnt pathway is highly correlated with XFC treatment of RA. At the cellular level, serum containing XFC inhibited the expression of Wnt pathway-related genes β-catenin, CCND1 and c-Myc. The molecular docking results showed that the key components of XFC had strong binding ability to Wnt5a, and the overexpression of Wnt5a (Wnt5a-ove) in AA FLS interfered with the action of XFC. CONCLUSION: The expression of Wnt5a is significantly increased in AA FLS and RA FLS, and XFC can inhibit the activation of Wnt/β-catenin signaling pathway to improve RA by binding with Wn5a, providing a new therapeutic mechanism for XFC to improve RA.

Analysis of clinical characteristics and influencing factors of meropenem concentration in patients with CNS infection

WEI Ruhua, CAO Wen, LU Yating, MENG Mingwei, LI Juman, QIN Yane, LAN Xiaobu, MO Kai

2024, 29(10):  1146-1151.  doi:10.12092/j.issn.1009-2501.2024.10.007

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AIM: To analyze the compliance rate and possible influencing factors for blood concentration of meropenem in patients with central nervous system (CNS) infections, and to provide basis for optimizing the administration of meropenem in the patients. METHODS: A retrospective analysis was performed in patients who were treated with meropenem and monitored the concentration (Cmin) from January 2021 to December 2022. The basic clinical data of the patients were recorded, and the achievement of meropenem blood concentration was counted. Univariate and binary logistic regression analysis were used to analyze the influencing factors for the e substandard steady-state blood trough concentration of meropenem. The ROC curve was drawn to predict the clinical characteristics. RESULTS: Forty-five cases were included. The median Cmin of meropenem was 4.14 (0.82, 16.29) mg/L, and 51.11% reached the target range with 4 mg/L. Binary logistic regression analysis showed that serum creatinine value and using mannitol were risk factors for the substandard steady-state blood trough concentration of meropenem (P<0.05). When serum creatinine value was less than 84 μmol/L, the area under the ROC curve was the largest (0.916), the sensitivity was 0.783, the specificity was 0.955, and the Youden index was 0.738. CONCLUSION: The Cmin compliance rate of meropenem blood concentration in patients with CNS infection is low, especially in patients with hyperfunction of kidney and those who using mannitol. It is necessary to conduct drug concentration monitoring to optimize the administration of meropenem in patients with CNS infection.

Pharmacokinetics, pharmacodynamics of esomeprazole in critically ill patients

ZHA Xian, SUN Luning, CHEN Chao, WANG Yongqing

2024, 29(10):  1152-1160.  doi:10.12092/j.issn.1009-2501.2024.10.008

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AIM: To investigate the pharmacokinetic/pharmacodynamic (PK/PD) profile of esomeprazole for injection in critically ill patients. METHODS: This was a prospective, single-center, open-label study, all patients received intravenous infused esomeprazole 40 mg q12h for stress ulcer prophylaxis, treatment duration is determined by clinicians based on patients condition. Forty critically ill patients were enrolled and were divided into single and multiple dose groups according to the timing of blood sample collection. Twenty-one patients in the single-dose group had their blood samples collected at 1, 3, 6, 8, and 12 h after the first dose, and 34 patients in the multiple-dose group had their blood samples collected at 0 h before the fifth dose and 1, 3, 6, and 8, and 12 h after the fifth dose, of which 14 patients had their blood samples collected at both the first dose and the repeated doses. The concentration of esomeprazole was measured by HPLC-MS/MS, and PK parameters were analyzed using noncompartmental analysis. Gastric aspirates were collected for pH measurement in fasted patients with gastric tube before the first dose (0 h), and 1, 2, 4, 8, 12, 14, 16, 20, 24 h after the initiation of drug administration, and the percentage of time with pH≥4 was calculated. All adverse events and serious adverse events during treatment were recorded. RESULTS: Patients in the single-dose group were 67.75 years old (45-69 years) with a BMI (24.05 ± 3.35) kg/m2, and patients in the multiple-dose group were 63.35 years old (24-87 years) with a BMI (24.08 ± 3.29) kg/m2. PK parameters after the first dose were AUC0-t (11.26 ± 6.58) mg·h·L-1, Cmax (3.08 ± 2.06) mg/L, CL (4.13 ± 3.68) L/h, Vd (17.12 ± 6.13) L, t1/2 (4.80 ± 3.06) h; PK parameters after multiple doses were AUC0-t (16.70 ± 11.20) mg·h/L, Cmax (3.37 ± 2.59) mg/L, CL (3.94 ± 2.94) L/h, Vd (22.71 ± 17.26) L, t1/2 (5.23 ± 3.34) h. Percentage of time with pH≥4 within 0 h-24 h after administration was 61.69%, and percentage of time with pH≥4 within 12 h-24 h was up to 100%. Esomeprazole was well tolerated by all patients with no serious adverse events. CONCLUSION: Compared with healthy volunteers, injectable esomeprazole showed increased Vd, decreased CL, increased drug exposure and accumulation after repeated administration in critically ill patients. The drug had a favorable safety profile in critically ill patients.

Study on the efficacy of alfacalcidol combined with ursodeoxycholic acid in primary biliary cholangitis

ZHANG Zishan, ZHANG Yaowu, DONG Xiaoming, GAO Xue

2024, 29(10):  1161-1167.  doi:10.12092/j.issn.1009-2501.2024.10.009

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AIM: To investigate the efficacy and anti-hepatic fibrosis of alfacalcidol combined with ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). METHODS: Seventy cases of PBC patients with 25 hydroxyvitamin D (25(OH)D3)<50 nmol/L, admitted to Fenyang Hospital in Shanxi Province from June 2022 to June 2023, who met the inclusion criteria, were randomly divided into 35 cases in the treatment group and 35 cases in the control group. and the treatment group was treated with alfacalcidol combined with UDCA; the control group was treated with UDCA alone; after 6 months of treatment, the patients were examined for 25(OH)D3, platelets, liver function, immunoglobulin, liver stiffness (LSM), and adverse drug reactions, and the FIB-4 index, APRI score, GLOBE score, and UK-PBC score were calculated. Measurements that satisfied the normal distribution were expressed as [x]±s, and comparisons between the two groups were made with the t-test; those that did not satisfy the normal distribution were expressed as M (P25, P75) was used to express the information, and the Mann-Whitney U test was used to compare the two groups. Response rates were compared with the chi-square test. RESULTS: The response rates in the control and experimental groups after treatment were  42.85% and 71.42%; γ-glutamyl transpeptidase (GGT) was 160 (128, 194) and 85 (72, 102) U/L; alkaline phosphatase (ALP) was 156 (123, 264) and 110 (56, 141) U/L; respectively; immunoglobulin M (IgM) were 3.51±0.84 and 2.71±0.81 g/L; 25(OH)D3 was 40.21±3.25 and 57.06±14.76 nmol/L; respectively, liver hardness was 10.8 (8.3, 15.1) and 8.9 (6.7, 12.2) KPa; respectively, and FIB-4 index was 2.28 (0.99, 3.66) and 1.46 (0.97, 2.55); respectively, APRI scores were 0.65 (0.33, 1.09) and 0.30 (0.17, 0.53); respectively, GLOBE scores were 0.85±0.73 and 0.13±0.51, and UK-PBC scores were 0.024 (0.018, 0.060) and 0.021 (0.012, 0.033), and the differences were statistically significant (all P<0.05). CONCLUSION: Alfacalcidol combined with UDCA significantly increased the treatment response rate of PBC patients compared with UDCA alone, and alfacalcidol improved hepatic fibrosis to a certain extent, contributing to the improvement of PBC without adverse effects.

Comparison of remazolam and propofol on the recovery of psychomotor function after painless gastrointestinal endoscopy

HU Shuangyan, HU Junfeng, MAO Linling, ZHAO Yuhong, XU Cheng, QIU Kai, ZHONG Junfeng

2024, 29(10):  1168-1173.  doi:10.12092/j.issn.1009-2501.2024.10.010

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AIM: To compare the recovery of psychomotor function after intravenous anesthesia with remazolam or propofol compound alfentanil in patients undergoing painless gastrointestinal endoscopy. METHODS: 78 patients undergoing painless gastrointestinal endoscopy were randomly divided into group RA and group  PA. Remiazolam or propofol combined with alfentanil were given intravenously in group RA or group PA. The blood pressure, heart rate, respiratory rate and saturation of puls oxygen were recorded before procdure (T1), during checking (T2), awaking from anaesthesia (T3) and at discharging from PACU (T4). Psychomotor function, as measured by the Trieger's dot test (TDT) and digit symbol substitution test (DSST), were evaluated before anesthesia (T1), at discharging from PACU (T4), 1 h (T5) and 2 h (T6) after checking. RESULTS: From assessment of the TDT, number of dots missed (NDM), maximum distance of dots missed (MDDM) and average distance of dots missed (ADDM) at T4, T5 were significantly lower than those at T1 in two groups. The completion rates and accuracy rates of DSST at T4, T5 were significantly lower than those at T1. Results of TDT and DSST at T6 were not significantly different to those at T1. The results of NDT, MDDM and ADDM at T4, T5 in group RA were significantly lower than those in group PA. The completion rates and accuracy rates of DSST at T4, T5 in group RA increased significantly compared with group PA. Compared to group PA, the incidence of hypotension was significantly lower in group RA. There was no significant difference in the incidence of respiratory depression between the two groups. CONCLUSION: Psychomotor function was fully recovered 2 h after surgery when remazolam compound alfentanil was used for painless gastrointestinal endoscopy. Compared with propofol, psychomotor function recovery in the remazolam group was faster and there were fewer adverse effects after surgery in group RA.

Research progress on anti-glioma mechanism of natural sesquiterpene lactones

YAN Xiaoting, WANG Xinye, BAI Ming, YAO Guodong

2024, 29(10):  1174-1184.  doi:10.12092/j.issn.1009-2501.2024.10.011

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Glioma is a common primary intracranial tumor. Malignant glioma has a high mortality rate and an inferior prognosis. Despite various therapeutic interventions, the overall survival rate is still meager. Sesquiterpene lactone is a kind of natural product containing α-methylene-γ-lactone, which has strong anti-tumor activity. In recent years, there have been many reports on the anti-glioma effect of sesquiterpene lactone compounds, such as ACT001, which is a structural modification of sesquiterpene lactone (Parthenolide) and has entered the clinical trial stage as a potential anticancer drug. This paper reviews the activity and mechanism of sesquiterpene lactones with anti-glioma effects, which have been studied in recent years.

Research progress in clinical trials of new drugs and candidate drugs for type 2 diabetes mellitus

ZHOU Xin, WANG Zhi, DU Wenyu, LIU Zihan, LI Ying, DONG Zhanjun

2024, 29(10):  1185-1193.  doi:10.12092/j.issn.1009-2501.2024.10.012

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A number of drugs for the treatment of type 2 diabetes mellitus (T2DM) are currently under clinical investigation, including the sodium-dependent glucose transporters 2 (SGLT2) inhibitor rongliflozin, the SGLT1/2 inhibitor LIK066, the dipeptidyl peptidase-4 (DPP-4) inhibitor DBPR108, the glucagon-likepeptide-1 receptor (GLP-1R) agonist CJC-1134-PC, the G-protein-coupled receptor 40 (GRP40) agonist SCO-267 and the Glucokinase (GK) agonist PB201. This article briefly reviews the clinical research progress of drugs targeting the above targets in the field of T2DM treatment, in order to provide reference for the treatment of T2DM patients.

Research progress of miRNA in asthma: airway inflammation and endotype

BAO Bahu, LIU Weiying, YE Yucai, CHEN Guorong, SUN Jingzi, HU Aoyan

2024, 29(10):  1194-1200.  doi:10.12092/j.issn.1009-2501.2024.10.013

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microRNA (miRNA) is a 22nt long single-stranded non-coding RNA that is involved in a variety of physiological and pathological processes. Bronchial asthma is a heterogeneous disease, and airway inflammation is one of the important mechanisms of its pathogenesis. Asthma can be classified into different types based on the different immune mechanisms involved in its pathogenesis, and the mechanism of airway inflammation also varies between different types of asthma.This article reviews the research progress of miRNA in asthma airway inflammation and endotype, and explores the pathogenesis and treatment prospects of miRNA in asthma airway inflammation and endotype.