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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.
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Rats , Animals , Electroacupuncture , Rats, Sprague-Dawley , Serotonin , Acupuncture Points , Pain, Referred , Calcitonin Gene-Related Peptide , Signal Transduction , Colitis/therapy , Indoles , SulfonamidesABSTRACT
OBJECTIVE To analyze the chemical constituents and components absorbed into plasma of the extract of Ardisia crenata and to elucidate its possible pharmacodynamic material basis. METHODS Overall， 12 rats were randomly assigned to the blank group （n＝6） and A. crenata group （n＝6） by the paired comparison method. The drug was administered once daily in the morning and afternoon for three days. Serum samples were prepared from serum after redosing on 4th day. The UPLC-QE-HF-MS/ MS was used to analyze and identify the chemical constituents in A. crenata extract and serum samples. Compound Discoverer 3.0 was employed for retention time correction， peak identification， and peak extraction. According to the secondary mass spectrometry information， the Thermo mzCloud online and Thermo mzVault local databases， referring to the relevant literature and control quality spectrum information were used to preliminarily identify the chemical constituents and components absorbed into plasma of A. crenata. RESULTS A total of 34 compounds were identified from the extract of A. crenata， mainly coumarins， flavonoids， organic acids， amino acids， including bergenin， quercetin， gallic acid， L-pyroglutamic acid， etc. Besides， 5 components absorbed into plasma were identified from serum samples: L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid. CONCLUSIONS L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid may act as the pharmacodynamic material basis of A. crenata.
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AIM: To investigate the efficacy and safety of paclitaxel albumin assisted platinum chemotherapy in the treatment of recurrent and metastatic cervical cancer based on tumor factors and inflammatory status. METHODS: A total of 100 patients with recurrent and metastatic cervical cancer in our hospital from January 2020 to January 2023 were randomly divided into two groups: 50 patients in the control group were treated with paclitaxel-assisted nedaplatin regimen, and 50 patients in the study group were treated with paclitaxel-assisted nedaplatin regimen. The short-term efficacy, tumor factors, inflammatory factors, relapse-metastasis related indexes, quality of life, functional status and adverse reactions were compared between the two groups. RESULTS: The total remission rate of the study group (72.00%) was higher than that of the control group (48.00%) (P0.05), but the total incidence of adverse reactions (12.00%) was lower than that of the control group (32.00%) (P<0.05). CONCLUSION: Paclitaxel albumin-assisted nedaplatin has a reliable effect in the treatment of recurrent and metastatic cervical cancer, which can further reduce the level of tumor factors, relieve inflammation, and has high safety.
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Objective:To investigate the expressions of eukaryotic initiation factor-4B (eIF4B) and eukaryotic initiation factor-5A (eIF5A) in papillary thyroid carcinoma tissues, and to analyze their regulatory effects on cell proliferation in vitro.Methods:The clinical data of 61 patients diagnosed with papillary thyroid carcinoma who received surgical resection at Yuncheng Central Hospital from January 2020 to October 2021 were retrospectively analyzed. The postoperative tumor tissues and paracancerous normal thyroid tissues (>1 cm from the margin of the mass) were retained. Immunohistochemistry was used to detect the expressions of eIF4B, eIF5A and proliferating cell nuclear antigen (PCNA) in different tissues. The correlation of eIF4B, eIF5A expressions with the clinicopathological characteristics of patients, and the relationship between eIF4B, eIF5A and PCNA were analyzed. The thyroid cancer cell line SW1736 and normal thyroid cell line HT-ori3 were selected. The expressions of eIF4B mRNA and eIF5A mRNA were detected by using real-ime quantitative polymerase chain reaction (qRT-PCR). After the small interfering RNA (siRNA) of siRNA-eIF4B and siRNA-eIF5A were synthesized, the interfering plasmids were constructed, and SW1736 cells were transfected, siRNA-eIF4B group and siRNA-eIF5A group were obtained; the empty plasmid transfection group and the blank control group without transfection intervention were established. The cell proliferation activity was detected by using CCK-8 assay, and the expression of PCNA mRNA was detected by using qRT-PCR.Results:The positive rates of eIF4B and eIF5A in papillary thyroid cancer tissues were higher than those in paracancerous normal thyroid tissues [65.57% (40/61) vs. 29.51% (18/61), 57.38% (35/61) vs. 9.84% (6/61), P < 0.001]. The positive rates of eIF4B and eIF5A were statistically different in patients with different tumor diameter [>3 cm vs. ≤3 cm: 88.89% (16/18) vs. 55.81% (24/43),77.78% (14/18) vs. 48.84% (21/43), all P < 0.05], lymph node metastasis [with vs. without: 85.00% (17/20) vs. 56.10% (23/41), 80.00% (16/20) vs. 46.34% (19/41), all P < 0.05] and the number of different nodes [multiple vs. single: 86.67% (13/15) vs. 58.70% (27/46), 86.67% (13/15) vs. 47.83% (22/46), all P < 0.05]; there were no statistically significant differences in the positive rates of eIF4B and eIF5A among patients with different age and gender (all P > 0.05). Positive correlation was found between eIF4B score and the positive cell proportion of PCNA ( r = 0.66, P = 0.0324), eIF5A score and the positive cell proportion of PCNA ( r = 0.62, P = 0.024), eIF4B score and eIF5A score ( r = 0.63, P = 0.021). The expression levels of eIF4B mRNA and eIF5A mRNA in thyroid cancer cell line SW1736 cell was higher than that of HT-ori3 cell in normal thyroid (all P < 0.05). The cell proliferation activity of SW1736 and PCNA mRNA expression level in siRNA-eIF4B group and siRNA-eIF5A group were lower than those in the empty vector transfected group and the blank control group (all P < 0.05). Conclusions:eIF4B and eIF5A are expressed elevated in papillary thyroid carcinoma, and both are involved in tumor development and progression. The role of eIF4B and eIF5A may be related to promoting the proliferation of tumor cells.
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Objective:To prepare the resiquimod-loaded lipid microbubbles R848-MBs, evaluate their enhanced ultrasound imaging and high intensity focused ultrasound (HIFU) ablation effects, and explore their ability to improve tumor immune microenvironment synergize with HIFU.Methods:R848-MBs were prepared by the thin film hydration-mechanical shock method; The basic characteristics and safety of R848-MBs were detected, the HIFU controlled-release characteristics were verified in vitro and the drug metabolism and biological distribution were investigated in vivo. The ability of enhancing ultrasound imaging was observed in vitro and in vivo. To investigate the enhanced HIFU ablation effect of R848-MBs, six EMT6 tumor-bearing mice were randomly divided into HIFU group and R848-MBs+ HIFU group, three mice in each group, the changes in contrast average sound intensity before and after ablation in mouse tumor areas and the change of ultrasound image gray value in tumor area were evaluated, the tumor were resected to observe the coagulative necresis by TTC staining and HE staining. Forty-five tumor-bearing mice were randomly divided into control group, Free R848 group, HIFU group, Blank-MBs+ HIFU group and R848-MBs+ HIFU group, nine mice in each group. On the third day after treatment, 3 mice in each group were randomly selected and killed, to evaluate the ability of R848-MBs to improve tumor immune microenvironment synergize with HIFU. The expression level of CRT on the surface of tumor cells were detected by immunofluorescence staining, the proportion of mature DC in lymph nodes, spleen, and CD8 + T cells in spleen were detected by flow cytometry. The treatment effectiveness of each group( n=6) were evaluated by measuring tumor volume, observing and drawing survival curves. Results:The R848-MBs lipid microbubbles with good safety were successfully prepared, with a concentration of 2.58×10 9/ml, as spherical bubbles under optical microscope and laser confocal microscopy, in a particle size of (1.72±0.11)μm, at a surface potential of (-10.16±0.73)mV. The cumulative drug release was up to 83.44% after HIFU (90 W, 3 s) in vitro. The concentration of R848 in plasma decreased rapidly, and the drug concentration in tumor tissue of the R848-MBs+ HIFU group was higher than that of the R848 group 24 hours after treatment ( P<0.01). The ultrasound imaging of R848-MBs was significantly enhanced in contrast mode in vitro and in vivo; R848-MBs can significantly enhance the HIFU ablation effect, the contrast average sound intensity change in the tumor area before and after ablation in the R848MBs+ HIFU group was greater than that in the R848 group ( P<0.05), and the immediate ultrasound grayscale value change in the HIFU+ R848-MBs group was 46.34±3.21, which was significantly greater than that in the HIFU group (10.67±1.53), with statistical significance ( P<0.000 1). Coagulation necrosis was observed in tumor HE staining and TTC staining. The results of treatment efficacy in vivo showed that R848-MBs+ HIFU group had the strongest therapeutic effect, and R848-MBs combined with HIFU treatment could significantly prolong the survival period of mice compared with intravenous injection of free R848 ( P<0.01). Immunofluorescence staining and flow cytometry results showed an increase in the expression level of CRT on the surface of tumor tissue in the R848-MBs combined with HIFU group, and the percentage of mature DC in tumor draining lymph nodes (58.53±1.04)% were significantly higher than those in the HIFU group (37.56±2.13)% ( P<0.001), and the percentage of mature DC in the spleen (70.65±1.91)% were significantly higher than those in the HIFU group (36.46±3.89)% ( P<0.001), the percentage of CD8 + T cells in the spleen (27.46±3.04)% was significantly higher than that in the HIFU group (18.69±0.29)% ( P<0.01). Conclusions:The HIFU controlled-release lipid microbubbles R848-MBs can not only enhance the efficiency of HIFU ablation, but also improve the tumor immune microenvironment.
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OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD.@*METHODS@#A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats.@*RESULTS@#In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group.@*CONCLUSIONS@#Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.
Subject(s)
Rats , Male , Animals , Electroacupuncture , Dyspepsia/therapy , Rats, Sprague-Dawley , Ghrelin , Gastrointestinal Hormones , Serotonin , Vasoactive Intestinal Peptide , Acupuncture PointsABSTRACT
AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c
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Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.
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Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E
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Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.
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Aim To elucidate the molecular mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis based on network pharmacology, animal experiments and quantitative real-time PCR.Methods The active components and targets of Sophora tonkinensis Gagnep were collected from the database of traditional Chinese medicinal systems databases and analysis platform(TCMSP). Targets related to acute pharyngitis were acquired through GeneCards, OMIM, DrugBank and Disgenet databases. After the common targets of the two were screened, the STRING database was used to construct the protein interaction network, and the Metascape platform was used for pathway analysis. At the same time, Cytoscape software was used to construct a network of "herbal-disease-component-target" and "herbal-disease-component-target-pathway" network. The acute pharyngitis models in rats were established to study the effect of water extract of Sophora tonkinensis Gagnep on acute pharyngitis in rats. Quantitative real-time PCR technology was used to study the effect of Sophora tonkinensis Gagnep on key gene targets in key pathways of pharyngeal tissues in rats with acute pharyngitis. Results In this experiment, 509 related targets of 21 active components of Sophora tonkinensis Gagnep were obtained, 2 167 related targets of acute pharyngitis were obtained, and 194 common targets of Sophora tonkinensis Gagnep and acute pharyngitis were obtained. KEGG pathway analysis screened 344 related signaling pathways, indicating that IL-17 signaling pathway, NF-kappa B signaling pathway and leukocyte transendothelial migration pathway might play a key role in the improvement of acute pharyngitis by Sophorae tonkinensis Gagnep. Animal experiments showed that the low dose group of Sophora tonkinensis Gagnep water extract had better therapeutic effect on acute pharyngitis. The results of quantitative real-time PCR showed that the low-dose group of Sophora tonkinensis Gagnep significantly down-regulated the expression levels of ITGB2, PIK3CA, PIK3CD and PTPN11 genes in leukocyte transendothelial migration pathway(P<0.05). Conclusions The above results show that Sophora tonkinensis Gagnep has the characteristics of multi-component, multi-target and multi-pathway synergy in improving acute pharyngitis, which provides a theoretical basis for further study on the complex mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis.
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Objective@#To evaluate the methodological quality of papers that performed meta-analyzed and systematically reviewed acupoint selections for the treatment of functional dyspepsia (FD) and to identify the ideal acupoint combinations for FD.@*Methods@#Chinese databases including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), China Biology Medicine (CBM), and Wanfang Database, as well as English databases including PubMed, Embase, and Cochrane Library were searched to retrieve papers about meta-analysis and systematic literature reviews on acupuncture for FD. The time span for the paper retrieval was set from the foundation of the databases to April 30, 2022. The Veritas scores of the papers based on their publication year, study type, Assessment of Multiple Systematic Reviews 2 (AMSTAR2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), heterogeneity, and publication bias were rated to assess the methodological quality of the included studies. Then, randomized controlled trials (RCTs) were extracted from those meta-analysis papers or systematic literature reviews for analyzing acupoints frequency, meridian frequency, and association rules with the use of R software (V 4.3.1).@*Results@#Eight meta-analysis papers were included in the study after screening. The mean Veritas scores of the papers based on publication year, type of study, AMSTAR2, PRISMA, heterogeneity, and publication bias were 4.50, 8.00, 4.63, 4.63, 4.50, and 6.13, respectively. The analysis of the scores revealed insufficiencies in the reviews pertaining to the methodology, comprehension of the research strategy, detailed list of excluded studies, sources of funding, assessment of potential bias risks impact on meta-analysis results in each study, explanation of heterogeneity, and identification of potential conflicts of interest. Furthermore, a total of 85 RCTs were obtained from the eight meta-analysis papers involving 85 acupuncture prescriptions and 67 acupoints for subsequent data mining. The most commonly used meridian was Stomach meridian of Foot-Yangming (ST). Zusanli (ST36), Neiguan (PC6), Zhongwan (CV12), Taichong (LR3), Tianshu (ST25), Gongsun (SP4), Weishu (BL21), Pishu (BL20), Neiting (ST44), and Yinlingquan (SP9) topped the list of frequently selected acupoints. Additionally, a total of 28 association rules were identified, including 10 second-order, 15 third-order, and 3 fourth-order association rules. The top-ranking association rules in each order were “Neiguan (PC6) → Zusanli (ST36)” “Zhongwan (CV12) + Neiguan (PC6) → Zusanli (ST36)” and “Zhongwan (CV12) + Taichong (LR3) + Neiguan (PC6) → Zusanli (ST36)”, respectively.@*Conclusion@#Acupuncture could alleviate the clinical symptoms of FD. However, the quality of methodology applied in the meta-analysis papers on the subject needs to be improved. Through data mining, a combination of Neiguan (PC6), Zusanli (ST36), Zhongwan (CV12), and Taichong (LR3) was identified as an essential acupoint combination for the treatment of FD.
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OBJECTIVE@#To systematically evaluate the effect of early systematic rehabilitation on muscle strength and prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU).@*METHODS@#Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), VIP database (VIP) and Wanfang database were searched by computer for randomized controlled trial (RCT) on early systematic rehabilitation of patients undergoing mechanical ventilation in ICU published from the establishment of the database to October 2022. The observation group was given early systematic rehabilitation, while the control group was given routine activities. The outcome indicators included Medical Research Council muscle strength score (MRC score), incidence of ICU-acquired weakness (ICU-AW), 36-item short form health survey scale (SF-36), length of hospital stay, and hospital mortality. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature to conduct a Meta-analysis of the studies that met the quality criteria. Funnel plot was used to analyze the publication bias of each study.@*RESULTS@#A total of 14 articles were enrolled, 13 in English and 1 in Chinese. A total of 1 835 patients were involved, including 922 cases in the observation group and 913 cases in the control group. The overall literature quality was good. Compared with the control group, the incidence of ICU-AW in the observation group was significantly reduced [relative risk (RR) = 0.78, 95% confidence interval (95%CI) was 0.62-0.98, P < 0.05], but the MRC score was not significantly increased [weighted mean difference (WMD) = 2.51, 95%CI was 0.77-4.25, P = 0.05]. There were no significant differences in ICU mortality (RR = 1.05, 95%CI = 0.59-1.87, P > 0.05), hospital mortality (RR = 1.15, 95%CI was 0.76-1.74, P > 0.05), length of ICU stay (WMD = -3.02, 95%CI was -7.29-1.24, P > 0.05), total length of hospital stay (WMD = -3.67, 95%CI was -8.04-0.70, P > 0.05), and physical component summary (PCS; WMD = 1.83, 95%CI was -0.28-3.93, P > 0.05) and mental component summary (MCS; WMD = 1.72, 95%CI was -0.76-4.20, P > 0.05) of SF-36 scale at 6 months after discharge between the two groups. It was shown by funnel plot that the publication bias of each literature was relatively small, manifested as the effect points included in the literature were basically in a "inverted funnel" shape and symmetrical, in terms of MRC score, incidence of ICU-AW, mortality, length of hospital stay and scores of SF-36 scale.@*CONCLUSIONS@#Early systematic rehabilitation can significantly reduce the incidence of ICU-AW, without increasing the mortality, and has no significant improvement on muscle strength and physical function.
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Humans , Respiration, Artificial , Intensive Care Units , Prognosis , Incidence , Muscle StrengthABSTRACT
ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L-1） for free drinking and gavage and ranitidine solution （0.03 g·kg-1） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg-1 of Astragali Radix）， a blood-activating group （0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg-1 of Astragali Radix + 0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg-1）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （P<0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （P<0.05， P<0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （P<0.05）， and that of miR216b was increased （P<0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （P<0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.
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The gastrointestinal tract is the largest digestive organ and the largest immune organ and detoxification organ, which is vital to the health of the body. Drosophila is a classic model organism, and its gut is highly similar to mammalian gut in terms of cell composition and genetic regulation, therefore can be used as a good model for studying gut development. target of rapmaycin complex 1 (TORC1) is a key factor regulating cellular metabolism. Nprl2 inhibits TORC1 activity by reducing Rag GTPase activity. Previous studies have found that nprl2 mutated Drosophila showed aging-related phenotypes such as enlarged foregastric and reduced lifespan, which were caused by over-activation of TORC1. In order to explore the role of Rag GTPase in the developmental defects of the gut of nprl2 mutated Drosophila, we used genetic hybridization combined with immunofluorescence to study the intestinal morphology and intestinal cell composition of RagA knockdown and nprl2 mutated Drosophila. The results showed that RagA knockdown alone could induce intestinal thickening and forestomach enlargement, suggesting that RagA also plays an important role in intestinal development. Knockdown of RagA rescued the phenotype of intestinal thinning and decreased secretory cells in nprl2 mutants, suggesting that Nprl2 may regulate the differentiation and morphology of intestinal cells by acting on RagA. Knockdown of RagA did not rescue the enlarged forestomach phenotype in nprl2 mutants, suggesting that Nprl2 may regulate forestomach development and intestinal digestive function through a mechanism independent of Rag GTPase.
Subject(s)
Animals , Drosophila/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Mammals/metabolism , Carrier Proteins , Tumor Suppressor Proteins/metabolism , Drosophila Proteins/geneticsABSTRACT
OBJECTIVE To establish the fingerprints of Ardisia crenata， Sophora tonkinensis and their couplet medicines， and to determine the contents of five components in them. METHODS Using water as solvent， single lyophilized powder of A. crenata and S. tonkinensis and combined lyophilized powder of their couplet medicines were prepared by combining lyophilization technology. The fingerprints of three lyophilized powder samples were established by using high-performance liquid chromatography （HPLC）， and the contents of 5 kinds of components such as gallic acid were determined simultaneously. RESULTS There were 5， 10 and 14 common peaks in the fingerprints for single lyophilized powder of A. crenata and S. tonkinensis and combined lyophilized powder of their couplet medicines； the similarities of them with the control fingerprints were all greater than 0.90. For combined lyophilized powder of couplet medicines， peak 3 Δ 基金项目 国家重点研发计划项目（No.2018YFC1708100）；贵 州省科技计划项目（No.黔科合基础-ZK〔2022〕一般483，No.黔科合成 was identified as gallic acid， peak 4 as matrine， peak 6 as 果〔2021〕一般137）；贵州省教育厅高等学校科学研究项目（青年项目） oxymatrine， peak 8 as bergenin， and peak 14 as trifolirhizin. In single lyophilized powder of A. crenata， the average contents of gallic acid and bergenin were 0.499 3 and 4.962 6 mg/g， respectively. In single lyophilized powder of S.tonkinensis， the average contents of matrine， oxymatrine and trifolirhizin were 3.046 0， 2.336 6 and 0.278 6 mg/g， respectively. In combined lyophilized powder of couplet medicines， the average contents of gallic acid， matrine， oxymatrine， bergenin and trifolirhizin were 0.560 6， 2.548 7， 1.382 2， 5.960 7 and 0.279 1 mg/g， respectively. The transfer rates were 8.87%-513.19%. CONCLUSIONS The established fingerprint and content determination methods are stable and feasible， and can be used for the quality control of A. crenata and S. tonkinensis and their couplet medicines. The average contents of matrine and oxymatrine in combined lyophilized powder of A. crenata-S. tonkinensis couplet medicines are decreased.
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Objective@#To describe the sickness absenteeism among primary and secondary school students in Jiading District and to analyze its correlation with the incidence of infectious diseases and associated lead or lag times, so as,to provide a scientific basis for the health and education departments to take measures.@*Methods@#The regularity and symptom composition of school sickness absenteeism among primary and secondary school students in Jiading District from the 2010-2017 were described. The Joinpoint model was applied to analyze the changing trend of absenteeism. And the rate of school sickness absenteeism and incidences of 7 acute infectious diseases were compared through visual analysis. The time lagged correlation coefficients and Granger causality tests were applied to quantitatively analyze the correlation and lead/lag patterns.@*Results@#The average rate of school sickness absenteeism among primary and secondary school students in Jiading District, Shanghai was 0.27%. Since the 2012 academic year, the overall rate of sickness absenteeism has been on the rise. Fever was the most common symptom of absenteeism (47.49%). The trend of sickness absenteeism rate was mainly consistent with the incidence of influenza, and showed a one way Granger causality. The maximum time lagged correlation coefficient was obtained in the second semester of the 2017 academic year with a value of 0.43 (95% CI =0.25-0.58). The maximum time lagged correlation coefficient between the rate of sickness absenteeism with fever and other respiratory symptoms and the incidence of influenza was also obtained in the second semester of the 2017 academic year and the maximum correlation coefficient was 0.50(95% CI =0.33-0.65).@*Conclusion@#The sickness absenteeism rate in primary and secondary school students is correlated to influenza incidence, and it has potential application value in supplementing early warning of influenza activities in the community.
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Objective@#To understand the impact of screen time on duration and quality of sleep, so as to provide scientific basis for the development of interventions.@*Methods@#A total of 3 584 preschool children in Haikou City were selected by stratified sampling method from March to June in 2022, and the Children s Sleep Habits Questionnaire (CSHQ) and self designed questionnaire were used.@*Results@#The average sleep duration of preschool children was (10.41±0.98)h/d, the rate of sleep deprivation was 28.71 %, and the report rate of sleep problems was 50.47%. The average sleep duration in general as well as on weekdays and weekends decreased by age ( F=21.00, 29.53, 3.26, P ＜0.05), and insufficient sleep duration rate significantly varied by age groups ( χ 2=29.85, P ＜ 0.01 ). The average screen time was (1.15±0.37)h/d, and the screen exposure rate was 55.39%. The total sleep problems ( 52.14 %), poor bedtime habits (43.02%), daytime sleepiness (67.10%), irregular sleep duration (53.05%), and abnormal sleep latency ( 24.99 %) were all higher than those in the non exposed group (48.41%, 39.59%, 63.29%, 48.91%, 19.57 %) ( χ 2= 4.94 , 4.31, 5.69 , 6.08, 14.85, P <0.05). Multiple linear regression analysis showed that age and weekend average screen time were negatively associated with sleep duration ( β =-0.01, -0.06), weekday and weekend average outdoor activity duration were positively correlated with sleep duration ( β =0.08, 0.08) ( P <0.05).@*Conclusion@#Screen exposure to preschool children s sleep time,sleep quality was closely related. Parents should cultivate good sleep habits of preschool children, and limit children s screen time to maximize outdoor activities, so as to ensure healthy development of children.
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Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Cell Hypoxia , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/pathology , Signal Transduction/genetics , tRNA Methyltransferases/metabolismABSTRACT
OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.