Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

This paper aimed to explore the intestinal toxicity of Euphoriae Ebracteolata Radix(EER) before and after being processed with Mongolian medicine Hezi Decoction(HZD) and the toxicity-reducing mechanism of this processing method. The intestinal toxicity in rats treated with unprocessed EER and HZD-processed EER extracts via 95% ethanol was compared. The comparison was based on several indicators, including fecal volume, serum diamine oxidase(DAO) and D-lactate(D-LA) levels, the water content of various intestinal segments and their contents, and inflammatory factor levels in intestinal segments. Tandem mass tag(TMT) quantitative proteomics technology was employed to analyze the key proteins associated with changes in intestinal toxicity between unprocessed EER and HZD-processed EER. The results indicated that compared with the blank group, unprocessed EER significantly increased the fecal volume, serum DAO and D-LA levels, water content of the ileal segment and its contents, as well as the release levels of inflammatory factors, including tumor necrosis factor(TNF-α) and interleukin-1 beta(IL-1β) in the ileal segment of rats(P<0.05), indicating that EER can cause diarrhea, increase intestinal permeability, and induce intestinal inflammation. Compared with those in the unprocessed EER group, all indicators in the HZD-processed EER group were significantly reduced(P<0.05). The TMT quantitative proteomics analysis revealed that a total of 6 487 proteins were identified in the rat ileum tissue. Compared to the blank group, 182 proteins exhibited significant changes in the unprocessed EER group, while 907 proteins in the HZD-processed EER group showed significant changes. The intersection of the differential proteins between the two groups identified 38 common proteins. Among them, the protein levels of intestinal barrier tight junction protein claudin3, squalene monooxidase(Sqle), clusterin, Na~+/H~+ exchange regulatory cofactor NHE-RF3(Pdzk1), and Y+L amino acid transporter 1(Slc7a7) exhibited significant changes before and after processing, and these changes were closely related to intestinal barrier function. Compared with the blank group, the expression of claudin3, Pdzk1, and Slc7a7 in the raw product group was significantly down-regulated(P<0.05),while the expression of Sqle and clusterin was significantly up-regulated(P<0.05).Compared with the raw product group, the expression of claudin3, Pdzk1, and Slc7a7 in the processed product group of HZD was significantly up-regulated(P<0.05), while the expression of Sqle and clusterin was significantly down-regulated(P<0.05). Western blot was used to detect the expression level of claudin 3 in the ileum of rats in each group. The results show that compared to that in the blank group, the expression level of claudin 3 in the unprocessed EER group was significantly reduced(P<0.01); compared to that in the unprocessed EER group, the expression level of claudin 3 in the HZD-processed EER group was significantly increased(P<0.01). This finding aligned with the proteomic outcomes, indicating that claudin 3 protein levels could serve as a crucial indicator for intestinal damage caused by EER. In summary, HZD-processed EER can reduce EER's intestinal toxicity, and the primary mechanism for its alleviation of intestinal barrier damage is the regulation of the intestinal barrier tight junction protein claudin 3 and other intestinal-related proteins.
Animals ; Drugs, Chinese Herbal/adverse effects* ; Proteomics ; Rats ; Male ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Intestinal Mucosa/drug effects* ; Tumor Necrosis Factor-alpha/metabolism*

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals

The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

OBJECTIVE: To investigate the risk factors, clinical characteristics, and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease, so as to provide a reference for infection control. METHODS: The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected. The clinical characteristics, susceptibility factors, and antibiotic resistance of the children were retrospectively analyzed. RESULTS: Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children (≤14 years old) with hematological diseases was the highest (19.91%) and significantly higher than other bacteria, accounting for 38.64% of Gram-positive cocci, and presented as an increasing trend year by year. A total of 427 children tested positive blood cultures, including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever. Most children experienced a recurrent high fever in the early and middle stages (≤6 d) of neutropenia and persistent fever for more than 3 days. After adjusting the antibiotics according to the preliminary drug susceptibility results, the body temperature of most children (63.5%) returned to normal within 4 days. The 85 children were mainly diagnosed with acute myeloid leukemia (AML), accounting for 84.7%. The proportion of children in the neutropenia stage was 97.7%. The incidence of oral mucosal damage, lung infection, and gastrointestinal injury symptoms was 40%, 31.8%, and 27.1%, respectively. The ratio of elevated C-reactive protein (CRP) and procalcitonin was 65.9% and 9.4%, respectively. All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid, and the resistance rate to penicillin, cefotaxime, levofloxacin, and quinupristin-dalfopristin was 10.6%, 8.2%, 9.4%, and 14.1%, respectively. None of children died due to bloodstream infection caused by Streptococcus mitis. CONCLUSION The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases, especially in children with AML. Among them, neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors. The common clinical symptoms include persistent high fever, oral mucosal damage, and elevated CRP. Penicillin and cephalosporins have good sensitivity. Linezolid, as a highly sensitive antibiotic, can effectively control infection and shorten the course of disease.
Humans ; Child ; Streptococcal Infections/microbiology* ; Retrospective Studies ; Hematologic Diseases/complications* ; Streptococcus mitis ; Drug Resistance, Bacterial ; Risk Factors ; Microbial Sensitivity Tests ; Anti-Bacterial Agents ; Female ; Male ; Bacteremia/microbiology* ; Child, Preschool ; Adolescent

OBJECTIVE: The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC). METHODS: Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety. RESULTS: A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group (［85.46±10.12］ and ［18.20±4.27］ (P<0.05). However, there was no significant difference in serum testosterone (［0.60±0.24］ nmol/L vs ［1.09±2.10］ nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score (［97.95±7.54］ vs ［80.33±8.58］), renal-yang deficiency syndrome score (［14.64±5.15］ vs ［24.94±8.75］) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( ［0.73±1.01］ nmol/L vs ［0.59±0.25］ nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups. CONCLUSION Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Treatment Outcome ; Testosterone

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.