1.Anti-Hyperuricemic and Anti-Gouty Arthritis Effects of Xiezhuo Qutong Formula and Its Network Pharmacology Mechanism
Shulin CHEN ; Lianjie LIU ; Xiaolu GAO ; Xuehong KE ; Changsong LIN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2807-2816
Objective To observe the therapeutic effects and mechanism of Xiezhuo Qutong Formula on gout.Methods(1)Animal experiments:A hyperuricemia(HUA)model was established in SD rats using hypoxanthine combined with potassium oxonate,and an acute gouty arthritis(AGA)model was induced by monosodium urate.The efficacy and safety of Xiezhuo Qutong Formula in reducing serum uric acid levels and exerting anti-inflammatory effects were evaluated.(2)Network pharmacology:The main active components and potential targets of Xiezhuo Qutong Formula were collected,along with gout-related disease targets.The intersection of these targets yielded potential therapeutic targets.A protein-protein interaction(PPI)network was constructed,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Xiezhuo Qutong Formula effectively reduced serum uric acid levels in HUA model rats without observed hepatorenal toxicity.It also decreased joint inflammation index,joint swelling degree,and inflammatory cytokine levels in AGA model rats.Network pharmacology analysis identified 156 overlapping targets between the drug and disease,among which TP53,STAT3,PIK3CA,BCL2,PIK3CD,PIK3CB,JUN,HDAC1,ESR1,and RELA may be key targets of Xiezhuo Qutong Formula in treating gout.Combined with GO and KEGG enrichment analyses,the main involved pathways include PI3K/AKT,JAK2/STAT3,and NF-κB signaling pathways.Conclusion Xiezhuo Qutong Formula exerts uric acid-lowering and anti-inflammatory effects in the treatment of gout,and its potential mechanism involves the PI3K/AKT,JAK2/STAT3,and NF-κB signaling pathways.
2.Multi-slice spiral computerized tomography image characteristics of coal workers with pneumoconiosis
Xinyu LI ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xiaolu LIU ; Chaoyi MA
Journal of Environmental and Occupational Medicine 2024;41(7):774-779
Background Multi-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. Objective To present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. Methods From June 2022 to June 2023, a total of
3.Differential metabolites of bronchoalveolar lavage fluid from coal worker's pneumoconiosis patients
Chaoyi MA ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Gang CHEN ; Guoxuan MA ; Yongmei ZHAO ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xiaolu LIU ; Xinyu LI
Journal of Environmental and Occupational Medicine 2024;41(6):617-624
Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.
4.Changes in intestinal flora of coal workers' pneumoconiosis patients after tetrandrine intervention
Xiaolu LIU ; Baoping LI ; Fuhai SHEN ; Zhiping SUN ; Yongmei ZHAO ; Bowen HOU ; Lini GAO ; Qianqian LI ; Xinyu LI ; Chaoyi MA
Journal of Environmental and Occupational Medicine 2024;41(6):625-631
Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P<0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P<0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P<0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P<0.05), but the differences in Chao1 index were not statistically significant (P>0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P>0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P<0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P<0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.
5.16S rDNA Sequencing Reveals Effect of Tanreqing Injection on Pulmonary Flora in Rat Model of COPD
Qian LUO ; Rui FU ; Bo PENG ; Weiya CHEN ; Xiaolu WEI ; Tengfei CHEN ; Ling SONG ; Yunhang GAO ; Guangping ZHANG ; Hongping HOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):98-103
ObjectiveTo study the effect of Tanreqing injection (TRQ) on the pulmonary flora in the rat model of chronic obstructive pulmonary disease (COPD). MethodWistar rats were randomized into control, model, and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ (2 g·kg-1). At the end of the experiment, after blood collection from the abdominal aorta of the rats, the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected, and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal, and those of the model group showed neutrophil infiltration, telangiectasia, lung hemorrhage and emphysema in individual cases, and thickening of collagen fibers in the trachea. Compared with the model group, the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group, the model group showcased increased alveolar space (P<0.01), which was reduced in the TRQ group (P<0.05). Compared with the control group, the model group showed increased wall thickness (P<0.01), and the increase was attenuated in the TRQ group (P<0.01). TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level, the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas, compared with the control group. After treatment with TRQ, the relative abundance of g_Stenotrophomonas increased, and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group, and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD, which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.
6.Application evaluation of cardiopulmonary exercise test to guide comprehensive pulmonary rehabilitation in patients with pneumoconiosis
Congxia YAN ; Baoping LI ; Fuhai SHEN ; Hong CAO ; Jing LI ; Lirong ZHANG ; Zhiping SUN ; Bowen HOU ; Lini GAO ; Xinyu LI ; Chaoyi MA ; Xiaolu LIU
Journal of Environmental and Occupational Medicine 2024;41(1):47-53
Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO2/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO2), maximum metabolic equivalent (METs), and maximum work (Wmax). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO2/kg, AT, EqCO2, METs, or Wmax between the two groups (P>0.05). At the end of the trail, the indicators like pVO2/kg [(19.81±2.38) mL·(min·kg)−1], AT [(14.48±2.33) mL·(min·kg)−1], METs (5.64±0.69), and Wmax [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)−1, (11.70±1.94) mL·(min kg)−1, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO2 between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.
7.Study on the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis
Rong JIN ; Xiaolu ZHAO ; Yuxin YAN ; Xiaoyang GAO ; Chunyan ZHANG ; Mingqi LI ; Yuehong MA
China Pharmacy 2024;35(3):277-282
OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis (HF). METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue, mRNA and protein expressions of HF indexes [α-smooth muscle actin (α-SMA), collagen type Ⅰ] and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway-related factors were detected, and the improvement effects and possible mechanism of low-dose, medium-dose and high-dose (50, 100, 200 mg/kg) of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/(kg·d) (calculated by the amount of raw material). The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low, medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa (diluted to 10%, 15%, 20%). miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells, and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low, medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats, and the percentage of collagen was significantly reduced (P<0.01); mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced (P<0.01), and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) were increased in liver tissue of rats (P<0.01). The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low, medium and high concentrations (P<0.01); whereas after transfection with miRNA-21 mimics, it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt (P<0.01), while significantly decreased mRNA and protein expressions of PTEN (P<0.01); after transfection with miRNA-21 inhibitor, the changes of above indexes were opposite to the above results (P<0.01). CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21, so as to achieve the effect of anti-hepatic fibrosis.
8.Analysis of Specific Chromatogram of Classical Formula Qianghuo Shengshi Tang Reference Samples
Wenya GAO ; He XU ; Mingli LI ; Haiyu ZHAO ; Yanyan ZHOU ; Hongjie WANG ; Jian YANG ; Xiaolu WEI ; Zhikun FAN ; Nan SI ; Baolin BIAN
Chinese Journal of Modern Applied Pharmacy 2024;41(10):1350-1356
OBJECTIVE
To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample.
METHODS
The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode.
RESULTS
There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids.
CONCLUSION
The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.
9.Clinical efficacy of electrophysiological monitoring for patients with cancer-induced brachial plexus injury treated with 125I seeds therapy
Xiaolu PEI ; Zhen GAO ; Linjing SONG ; Yan DI ; Lijuan ZHANG ; Zezhou LIU ; Hongtao ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(9):545-548
Objective:To explore the clinical efficacy of 125I seeds implantation in treating cancer-induced pain and motor dysfunction caused by brachial plexus compression through neurophysiological monitoring. Methods:A retrospective study was conducted on 8 patients (4 males, 4 females; age 58-63 years) who underwent 125I seeds therapy for cancer-induced brachial plexus injury at Hebei Provincial People′s Hospital from January 2021 to August 2023. Pain severity was assessed by using the numerical rating scale (NRS) and motor function was evaluated by using the Fugl-Meyer (F-M) assessment. Electrophysiological monitoring was used to assess changes in sensory and motor branch conduction velocity (CV) of the musculocutaneous nerve, axillary nerve, median nerve, ulnar nerve, and radial nerve before and 3 months after treatment. Paired t-test was used for data analysis. Results:All 8 patients had moderate to severe pain (6 had motor dysfunction). The preoperative and postoperative NRS scores was 5.9±1.0 and 3.3±1.7, respectively ( t=4.93, P=0.002), while F-M scores was 44.8±7.6 and 54.8±5.7, respectively ( t=-3.52, P=0.017). Electrophysiological results showed that 7 patients had lesion involvement in the lower trunk of the brachial plexus, and 1 patient had involvement in the upper trunk. The preoperative and postoperative motor branch CV of the ulnar nerve was (47.2±2.6) and (59.7±8.2) m/s, respectively ( t=-3.17, P=0.034), while the sensory branch CV was (41.8±1.2) and (56.0±5.7) m/s, respectively ( t=-5.82, P=0.001). The nerve CV increased compared to the preoperative ones. Conclusions:125I seeds implantation has good clinical efficacy in treating cancer-related pain and motor dysfunction caused by brachial plexus compression. Changes in electrophysiology can quantitatively monitor the recovery of sensory and motor functions of the brachial plexus.
10.Establishment of Specific Chromatogram and Thin-layer Identification Method for Kaixinsan
Wenya GAO ; Min FENG ; Chang GAO ; Haiyu ZHAO ; Yanyan ZHOU ; Hongjie WANG ; Ruipeng YU ; Yipeng ZHAO ; Lili ZHANG ; Yanqing GAO ; Yanhong XIAO ; Cuina CHENG ; Xiaolu WEI ; Nan SI ; Baolin BIAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):37-44
ObjectiveTo establish the specific chromatogram and thin layer chromatography(TLC) identification method of Kaixinsan(KXS) samples, in order to clarify the key quality attributes and provide reference for the quality evaluation of KXS. MethodHigh performance liquid chromatography(HPLC) specific chromatogram of KXS was developed with YMC Hydrosphere C18 column(4.6 mm×250 mm, 5 μm), the mobile phase was acetonitrile(A)-0.2% formic acid aqueous solution(B) for gradient elution(0-15 min, 2%-20%A; 15-25 min, 20%-25%A; 25-30 min, 25%-30%A; 30-45 min, 30%-31%A; 45-50 min, 31%-44%A; 50-65 min, 44%-45%A; 65-73 min, 45%-75%A; 73-95 min, 75%-100%A; 95-105 min, 100%A; 105-105.1 min, 100%-2%A; 105.1-120 min, 2%A), the detection wavelength was 320 nm. Ultra high performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to identify the chemical components of KXS with electrospray ionization(ESI), negative ion mode and scanning range of m/z 50-2 000. TLC identification methods for Poria and Ginseng Radix et Rhizoma in KXS were established. ResultThere were 11 common peaks in the specific chromatogram of KXS, attributed to Polygalae Radix, Poria and Acori Tatarinowii Rhizoma. Taking peak 9(α-asarone) as the reference peak, the relative standard deviations of the retention times of 15 batches of KXS samples were<0.2%. A total of 34 compounds were identified by UHPLC-LTQ-Orbitrap MS, including terpenoids, phenylpropanoids, oligosaccharides and ketones. The established TLC had good separation and was rapid, reliable, simple, feasible, suitable for the identification of Poria and Ginseng Radix et Rhizoma in KXS. ConclusionThe specific chromatogram and TLC of KXS are stable and reproducible. The material basis of KXS is basically clarified by MS, which can provide a reference for the development and quality control of KXS.


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