Synthesis and Characterization of Poly(butylene glycol adipate-co-terephthalate/diphenylsilanediol adipate-co-terephthalate) Copolyester.

The copolyester poly(butylene glycol adipate-co-terephthalate/diphenylsilanediol adipate-co-terephthalate) (PBDAT) was synthesized by the melt polycondensation method using terephthalic acid, adipic acid, 1,4-butanediol, and diphenylsilylene glycol as the raw materials. The molecular chain structure, thermal properties, thermal stability, mechanical properties, and degradation behaviors of the copolyesters were investigated. The results showed that the prepared PBDAT copolyesters exhibited good thermal stability and mechanical properties. With the increase in diphenylsilanediol (DPSD) content, the thermal stability of PBDAT and the melting temperature both increased. The tensile strength and elastic modulus of PBDAT also exhibited an increasing tend. When the DPSD content was 12.5% (PBDAT-12.5), the tensile strength, the elastic modulus, and elongation at break were 30.56 MPa, 238 MPa, and 219%, respectively. With the increase in diphenylsilanediol content, the hydrophilicity of PBDAT decreased, but PBDAT still shows good degradability and the thermal degradation T5% temperature was 355 °C. The thermal degradation of PBDAT was also improved.

UPLC-QTOF-MS based metabolomics unravels the modulatory effect of ginseng water extracts on rats with Qi-deficiency.

Ginseng is commonly used as a nutritional supplement and daily wellness product due to its ability to invigorate qi. As a result, individuals with Qi-deficiency often use ginseng as a health supplement. Ginsenosides and polysaccharides are the primary components of ginseng. However, the therapeutic effects and mechanisms of action of these components in Qi-deficiency remain unclear. This study aimed to determine the modulatory effects and mechanisms of ginseng water extract, ginsenosides, and ginseng polysaccharides in a rat model of Qi-deficiency using metabolomics and network analysis. The rat model of Qi-deficiency was established via swimming fatigue and a restricted diet. Oral administration of different ginseng water extracts for 30 days primarily alleviated oxidative stress and disrupted energy metabolism and immune response dysfunction caused by Qi-deficiency in rats. Ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for untargeted serum metabolomic analysis. Based on the analysis results, the active constituents of ginseng significantly reversed the changes in serum biomarkers related to Qi-deficiency in rats, particularly energy, amino acid, and unsaturated fatty acid metabolism. Furthermore, analysis of the metabolite-gene network suggested that the anti-Qi-deficiency effects of the ginseng components were mainly associated with toll-like receptor (TLR) signaling and inflammatory response. Additional verification revealed that treatment with the ginseng components effectively reduced the inflammatory response and activation of the myocardial TLR4/NF-κB pathway induced by Qi-deficiency, especially the ginseng water extracts. Therefore, ginseng could be an effective preventive measure against the progression of Qi-deficiency by regulating metabolic and inflammatory responses.

UPLC-Q-TOF/MS based serum and urine metabolomics strategy to analyze the mechanism of nervonic acid in treating Alzheimer's disease.

Nervonic acid is a natural component of breast milk and is frequently used as a food additive due to its excellent neuroprotective effects. Although it has been reported that nervonic acid may play a role in the recovery of human cognitive impairment, its specific mechanism of action is still unclear. In this study, the results of serum biochemical indexes showed that nervonic acid improved inflammation and reduced amyloid ß peptide (Aß) deposition and tau protein phosphorylation in Alzheimer's disease (AD) rats. Subsequently, we further used a metabolomics approach to investigate the potential mechanism of action of nervonic acid in the treatment of AD. The results of serum and urine metabolomics study showed that the intervention of nervonic acid significantly reversed the metabolic profile disorder in AD rats. A total of 52 metabolites were identified. They mainly involved linoleic acid metabolism, alpha-linolenic acid metabolism, phenylalanine metabolism and arachidonic acid metabolism, and all these metabolic pathways were associated with the emergence of inflammation in vivo. It suggests that the therapeutic effect of nervonic acid on AD is likely to be produced by ameliorating inflammation. The results obtained in this study provide new insights into the mechanism of nervonic acid treatment of AD and lay a foundation for the clinical application of nervonic acid in the treatment of Alzheimer's disease.

Research on point cloud hole filling and 3D reconstruction in reflective area.

3D reconstruction is the process of obtaining the three-dimensional shape or surface structure of an object, which is widely used in advanced manufacturing fields such as automotive, aerospace, industrial inspection, and reverse engineering. However, due to the structural characteristics of the component itself, the reflective properties of the coating material, and other factors, there may be specular reflection during image acquisition, making it difficult to achieve complete 3D reconstruction of the component. This paper proposes a method to address the problem of incomplete 3D reconstruction of strongly reflective objects by recognizing outlier points and filling point cloud holes. The proposed View-Transform-PointNet outlier point recognition network improves the alignment of the initial point cloud plane and implements secondary alignment of the point cloud based on the perpendicularity between the outlier plane in mixed reflection and the point cloud plane. The point cloud hole-filling method is based on the principle of outlier formation and approximates a local Gaussian distribution to linear variation. The distance between the end of each outlier plane and the real surface is calculated to repair the depth information of outlier points. The proposed method achieves a 39.4% increase in the number of point cloud filling, a 45.2% increase in the number of triangular mesh faces, a 46.9% increase in surface area, and a chamfer distance (CD) of 0.4471009, which is better than existing geometric repair methods in terms of standard deviation and smoothness. The method improves the alignment of initial point cloud planes and enhances the accuracy of outlier point recognition, which are the main innovative points of this study. The 3D reconstruction of the repaired point cloud model is achieved through Poisson equation and parameter adjustment. The proposed method reduces the error caused by large curvature in the boundary region and improves the smoothness and accuracy of the reconstructed model.

An integrated approach based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, network pharmacology, and molecular docking to study the key effective compounds and mechanism of action of Platycodi Radix in the treatment of chronic obstructive pulmonary disease.

Platycodi Radix (PR) is a valuable herb that is widely used in the treatment of chronic obstructive pulmonary disease in clinics. However, the mechanism of action for the treatment of chronic obstructive pulmonary disease remains unclear due to the lack of in vivo studies. Our study established a novel integrated strategy based on ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry, network pharmacology, and molecular docking to systematically analyze the tissue distribution and active compounds of PR in vivo and the therapeutic mechanism of chronic obstructive pulmonary disease. First, tissue distribution studies have shown that the lung is the organ with the highest distribution of PR compounds. Subsequently, network pharmacology results showed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and mitogen-activated protein kinase signaling pathway were the critical mechanisms of PR against chronic obstructive pulmonary disease. Ultimately, molecular docking results showed that the key targets were stably bound to the corresponding active compounds of PR. Our study is of great significance for the screening of the key effective compounds and the study of the mechanism of action in traditional Chinese medicine and provides data to support the further development and utilization of PR.

Therapeutic effect of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves on ischemic stroke via the microbiota-gut-brain axis.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) are widely used to treat ischemic stroke (IS); however, the specific mechanism remains unclear. The microbiota-gut-brain axis plays a critical role in IS and has become a potential therapeutic target. This study aimed to reveal and verify the therapeutic effect of ESL on IS through the microbiota-gut-brain axis. Ultra-high-performance liquid chromatography coupled with mass spectrometry-based untargeted/targeted metabolomics combined with 16S rRNA microbiota sequencing strategy were used to investigate the regulatory effect of ESL on the metabolism and intestinal microenvironment after IS. Lactobacillus reuteri and Clostridium butyricum were used to treat rats with IS to verify that elevated levels of probiotics are key factors in the therapeutic effect of ESL. The results showed that IS significantly altered the accumulation of 41 biomarkers, while ESL restored their concentrations back to normal. Moreover, ESL alleviated the dysbiosis of gut microbiota brought on by IS, by reducing the abundance of pathogens and increasing the abundance of probiotics (e.g., Lactobacillus reuteri and Clostridium butyricum); this could reduce post-stroke injury, thereby having a certain protective effect on IS. This study reveals that ESL plays an important role in treating IS through the microbiota-gut-brain axis, maintaining metabolic homeostasis in vivo.

Research on the diurnal variation characteristics of ozone formation sensitivity and the impact of ozone pollution control measures in "2 + 26" cities of Henan Province in summer.

Near-surface ozone pollution is becoming an increasingly serious air quality issue in China, especially in "2 + 26" cities (Beijing-Tianjin-Hebei and nearby cities). HN2 + 26 cities ("2 + 26" cities of Henan Province) are located in the south of "2 + 26" cities, with frequent and severe ozone pollution events in recent years. This study investigated the diurnal evolution characteristics of ozone formation sensitivity (OFS) of HN2 + 26 cities from May to September in 2021 by the innovative combination of Global Ozone Monitoring Experiment (GOME-2B) and Ozone Monitoring Instrument (OMI) satellite data, and assessed the impact of ozone pollution control measures (OPCMs) implemented from June 26 to July 1, 2021. The localized FNR (ratio of formaldehyde to nitrogen dioxide of satellite measurement) threshold (1.4-2.55) was established, and it was found that OFS in May-September 2021 was mainly in VOCs-limited regime in the morning (∼10:00), while transitional/NOx-limited regime in the afternoon (∼14:00). Three periods (before, during and after the OPCMs) were divided to evaluate the impact of OPCMs on OFS. It was indicated that OPCMs had no impact on the morning OFS, but had a significant impact on the afternoon OFS. Specifically, the OFS in two industrial cities Xinxiang (XX) and Zhengzhou (ZZ) shifted from transitional regime to NOx-limited regime after the OPCMs. We further investigated OFS differences between urban and suburban areas and found that OFS shift of XX only existed in urban areas, while that of ZZ existed in both urban and suburban areas. We compared their measures and found that it is effective to take hierarchical control measures on different levels of ozone pollution days to alleviate ozone pollution. This study provides an improved understanding of diurnal evolution characteristics of OFS and the impacts of OPCMs on it, which will provide a theoretical basis for formulating more scientific ozone pollution control policies.

Research on the ozone formation sensitivity indicator of four urban agglomerations of China using Ozone Monitoring Instrument (OMI) satellite data and ground-based measurements.

Near surface ozone is a typical secondary pollutant, and is mostly generated by a series of complex photochemical reactions of volatile organic compounds (VOCs) and nitrogen oxides (NOx) in the air under sunlight. At present, a large number of studies have applied FNR (a ratio of formaldehyde (HCHO) to nitrogen dioxide (NO2) retrieved by satellite) indicator to study the ozone formation sensitivity (OFS). OFS analysis is critical for taking targeted ozone pollution prevention and control measures. Regional OFS can be more accurately diagnosed by utilizing localized FNR threshold. In this study, localized FNR thresholds were established for four severe ozone polluted urban agglomerations in China (Beijing-Tianjin-Hebei (BTH) region, Yangtze River Delta (YRD) region, Pearl River Delta (PRD) region, and Chengdu-Chongqing (CY) region), based on the statistical analysis between FNR (obtained from OMI observation, with daily transit time of approximately 13:45 local standard time) and ΔO3/ΔNO2 (the ratio of ozone change to nitrogen dioxide change between two consecutive months, obtained from ground measurements) from 2014 to 2016. And these thresholds were verified by the statistical analysis between FNR and ΔO3/O3 (ozone change rate between two consecutive months), and between FNR and O3 concentration during the OFS significant shift months. Furthermore, the results were also compared and verified with the method proposed by previous studies. The results indicate that there are significant regional dependences in the FNR threshold, and the lower-upper limits for the four urban agglomerations are as follows: 0.65-1.21 for BTH, 0.64-1.48 for the YRD, 1.25-2.39 for the PRD, and 1.44-3.69 for CY (FNR < lower limit indicates VOCs-limited regime; lower limit < FNR < upper limit indicates transitional regime; FNR > upper limit indicates NOx-limited regime). This method eliminates the problems associated with the undifferentiated use of FNR thresholds in different regions and significantly reduces the deviations for OFS.

A novel one-pot fluorescence tagging and depyrimidination strategy for quantification of global DNA methylation.

DNA methylation is intensively studied in medical science. Current HPLC methods for quantification of global DNA methylation involve digestion of a DNA sample and HPLC determination of both cytosine (C) and 5-methylcytosine (5mC) so that percentage of 5mC in total cytosine can be calculated as DNA methylation level. Herein we report a novel HPLC method based on a one-pot fluorescence tagging and depyrimidination reaction between DNA and chloroacetaldehyde (CAA) for highly sensitive quantification of global DNA methylation. In the one-pot reaction, C and 5mC residues in a DNA sequence react with CAA, forming fluorescent etheno-adducts that are then released from the sequence through depyrimidination. Interestingly, etheno-5mC (ε-5mC) is ∼20 times more fluorescent than ε-C and other ε-nucleobases resulting from the reaction, which greatly facilitates the quantification. Further, due to the tagging-induced increase in structural aromaticity, ε-nucleobases are far more separable by HPLC than intact nucleobases. The proposed HPLC method with fluorescence detection (HPLC-FD) is quick (i.e., < 1h per assay) and highly sensitive with a detection limit of 0.80 nM (or 250 fg on column) for 5mC. Using the method, DNA samples isolated from yeast, HCT-116 cells, and tissues were analyzed. Global DNA methylation was measured to be in the range from 0.35% to 2.23% in the samples analyzed. This sensitive method allowed accurate analyses of minute DNA samples (∼100 ng) isolated from milligrams of tissues.

Guanxin V attenuates myocardial ischaemia reperfusion injury through regulating iron homeostasis.

CONTEXT: Guanxin V (GX), a traditional Chinese medicine formula, is safe and effective in the treatment of coronary artery disease. However, its protective effect on myocardial ischaemia reperfusion injury (MIRI) is unclear. OBJECTIVE: To investigate the cardioprotective effect of GX on MIRI and explore the potential mechanism. MATERIALS AND METHODS: Sprague-Dawley male rats were divided into Sham, MIRI and MIRI + GX groups. GX (6 g/kg) was administered to rats via intragastric administration for seven days before ischaemia reperfusion (IR) surgery. The infarct size, histopathology, serum enzyme activities, ultrastructure of the cardiac mitochondria were assessed. H9c2 cells were pre-treated with GX (0.5 mg/mL), and then exposed to hypoxia/reoxygenation (HR). The cell viability and LDH levels were measured. Network pharmacology was conducted to predict the potential mechanism. The related targets of GX were predicted using the TCMSP database, DrugBank database, etc. Finally, pharmacological experiments were used to validate the predicted results. RESULTS: In vivo, GX significantly reduced the myocardial infarct size from 56.33% to 17.18%, decreased the levels of AST (239.32 vs. 369.18 U/L), CK-MB (1324.61 vs. 2066.47 U/L) and LDH (1245.26 vs. 1969.62 U/L), and reduced mitochondrial damage. In vitro, GX significantly increased H9c2 cell viability (IC50 = 3.913 mg/mL) and inhibited the release of LDH (207.35 vs. 314.33). In addition, GX could maintain iron homeostasis and reduce oxidative stress level by regulating iron metabolism-associated proteins. CONCLUSIONS: GX can attenuate MIRI via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.

A multidimensional strategy to rapidly identify the chemical constituents in Shengxian Decoction by using ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry.

As a well-known traditional Chinese medicine formula, the chemical constituents of Shengxian Decoction still remain unclear due to its complexity. In this study, a multidimensional strategy based on ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry and informatics UNIFI platform was applied to achieve rapid and comprehensive identification of the complex composition of Shengxian Decoction. Data-independent acquisition, fast data-directed analysis, and high-definition MSE were used to obtain more and cleaner mass spectrum information. As a result, a total of 120 compounds including 74 saponins, 17 flavonoids, 7 cinnamic acid derivatives, 8 triterpenoids, and 14 others were identified or tentatively characterized by high-resolution molecular mass, fragment ions, and collision cross-section values. Furthermore, high-definition MSE was used to identify six pairs of co-eluting isomers that could not be detected from conventional data-independent acquisition and fast data-directed analysis. This research strategy has a certain potential for the analysis of other compound formulae and lays the foundation for the study of traditional Chinese medicine efficacy.

Angelica dahurica Extracts Attenuate CFA-Induced Inflammatory Pain via TRPV1 in Mice.

Angelica dahurica, belonging to the family Apiaceae, is a well-known herbal medicine. The roots of Angelica dahurica are commonly used for the treatment of headache, toothache, abscess, furunculosis, and acne. However, little is known about their analgesic molecular mechanism underlying pain relief. In this study, we used behavioral tests to assess the analgesic effect of the ADE (Angelica dahurica extracts) on CFA (complete Freund's adjuvant)-induced inflammatory pain mice models. TRPV1 (Transient Receptor Potential Cation Channel Subfamily V Member 1) protein activity in dorsal root ganglion (DRG) was assessed with a calcium imaging assay. TRPV1 expression was detected with western blot and immunohistochemistry. Then, we examined the constituents of ADE using combined ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC/Q-TOF-MS). Our results showed that ADE effectively attenuated mechanical and thermal hypersensitivities in CFA-induced inflammatory pain model in mice. ADE also significantly reduced the activity and the protein expression of TRPV1 in DRG from CFA mice. Therefore, ADE might be an attractive and suitable analgesic agent for the management of chronic inflammatory pain.

Coupling a droplet generator with conventional ESI-MS for quantitative analysis of small-volume samples.

Quantitative mass spectrometric analysis of small-volume samples (e.g., < 1 µL) has been a challenge mainly due to the difficulties with sample handling and its injection into the system for analysis. Herein we report a microfluidic analytical platform coupling a droplet generator with conventional electrospray ionization-mass spectrometry (ESI-MS) that enables multiple analyses of a µL-sized sample with sensitivity and repeatability. In an analysis by droplet generator-assisted ESI-MS (DG-ESI-MS), a sample of µL volume is pulled into a sampling capillary and its equal nL-sized portions are generated by a droplet generator and analyzed by ESI-MS at time intervals of choice. The droplet generator is made of PMMA sheets by laser engraving conveniently and at a low cost. In a study to achieve effective ESI-MS detection of water-in-oil droplets, it's found that the problem of MS signal suppression by oil can be solved by using an appropriate organic carrier with ESI-enhancing additives. The proposed DG-ESI-MS method has linear calibration curves for both adenine and phenylalanine with LODs at the sub-µM level. Application of the present analytical platform for monitoring substrate concentration changes in an enzymatic reaction solution of 3 µL is demonstrated.

Synthesis, characterization, in vitro antioxidant and hypoglycemic activities of selenium nanoparticles decorated with polysaccharides of Gracilaria lemaneiformis.

Under a simple redox system of selenite and ascorbic acid, we used Gracilaria lemaneiformis polysaccharides (GLPs) as a stabilizer and dispersing agent to generate well-dispersed and stable selenium nanoparticles (SeNPs). The size, stability, morphology and physicochemical properties of GLPs-SeNPs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FT-IR) spectra, energy dispersive X-ray (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Thermogravimetric (TG). The results showed that orange-red, amorphous, zero-valent and spherical GLPs-SeNPs with mean diameter of approximately 92.5 nm were successfully prepared, which exhibited good storage stability at 4 °C and remaining highly stable at different ion strengths and pH. The 2,2-diphenyl-1-pycrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and superoxide anion radical (O2•-) radical scavenging ability of GLPs-SeNPs were higher than those of bare SeNPs, GLPs and sodium selenite (Na2SeO3), and could reach 103.41%, 94.23%, 86% at a concentration of 1.5 mg/mL, respectively. Besides, GLPs-SeNPs also showed higher inhibitory effects on α-amylase and α-glucosidase. In vitro cytotoxicity assay and hemolysis activity examinations indicated that GLPs-SeNPs have excellent biocompatibility. Therefore, the GLPs-SeNPs might be used as a potential antioxidant agent and antidiabetic agent for food and medical applications.

Synthesis and Antimicrobial Activity Evaluation of Imidazole-Fused Imidazo[2,1-b][1,3,4]thiadiazole Analogues.

Three series of new imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues (compounds 20 a-g, 21 a-g, and 22 a-g) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram-positive and -negative bacteria. N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline (21 a) showed the highest activity against C. albicans (MIC50 =0.16 µg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast-1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.

The efficacy and safety of fire needle for the treatment of lumbar disc herniation: A protocol for systematic review and meta-analysis.

BACKGROUND: A very large acceleration in clinical studies on the efficacy of fire needle to treat lumbar disc herniation (LDH) are increasing, while studies on the assessment of its efficacy are still lacking. Therefore, this study will demonstrate the efficacy of fire needle in the treatment of LDH combining with the meta-analysis. METHODS: The studies on randomized controlled trials (RCTs) will be searched at the databases of China National Knowledge Infrastructure (CNKI), WANFANG database (Chinese Medicine Premier), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature database (CBM), PubMed, EMBASE, and Cochrane Library from their inception to May 1, 2020. RESULTS: This authentic and multi-dimensional study will shed light on the referable information for the treatment of LDH with fire needle. CONCLUSION: This study will evaluate the efficacy of fire needle in the treatment of LDH. REGISTRATION: PROSPERO (registration number CRD42020158596).

Retrospective Study of Rehabilitation Exercise Combined with Extracorporeal Shock Wave Therapy for Knee Osteoarthritis.

BACKGROUND The aim of this study was to investigate the effect of rehabilitation exercise combined with extracorporeal shock wave therapy (ESWT) on knee osteoarthritis (KOA). MATERIAL AND METHODS The clinical data of 217 patients with KOA who underwent ESWT in our hospital from December 2017 to January 2020 were retrospectively analyzed. The patients were divided into a rehabilitation exercise (RE) group and a non-rehabilitation exercise (NRE) group according to whether they were given RE. The treatment course of the 2 groups was 5 weeks. Pain Visual Analog Scale (VSA), Western Ontario and McMaster Universities knee osteoarthritis index visualized scale (WOMAC), Lequesne index scores, Range of motion (ROM) score, and Japanese Orthopaedic Association (JOA) scores were used to evaluate the treatment effect of the 2 groups of patients. RESULTS After 5 weeks of treatment, the VSA scores (p<0.001), WOMAC scores (P<0.001) and Lequesne index scores (P<0.001) of the RE group and NRE group were significantly lower than those before treatment, while ROM score (P<0.001) and JOA score (p=0.006) were significantly increased. Compared with the NRE group, the VAS score (3.14±0.64 vs. 4.78±0.85, P=0.002), WOMAC score (20.37±4.06 vs. 27.82±4.57, P<0.001) and Lequesne index score (6.13±1.83 vs. 7.35±2.21, P=0.019) in the RE group were significantly lower than those in the NHE group; however, the ROM score (89.13±9.83 vs. 79.15±6.25, P=0.021) and JOA score (79.53±7.59 vs. 67.85±8.27, P=0.016) were significantly higher than those in the NRE group. CONCLUSIONS RE combined with ESWT has a positive effect on KOA, which may more significantly relieve the patient's clinical symptoms and improve joint function and quality of life.