Thyroid diseases are common clinical endocrine disorders， and their pathogenesis is generally considered to be closely related to genetic predisposition factors， immune system disorders， hormone levels， etc. Xiaoyaosan is widely used in the treatment of various thyroid diseases with excellent effects. This study summarized the relevant literature on the treatment of thyroid diseases with modified Xiaoyaosan prescriptions and their active ingredients from aspects such as theoretical analysis， clinical research， and mechanism research. Theoretical analysis revealed that Xiaoyaosan could not only disperse stagnated liver qi but also replenish deficient spleen Qi， which was consistent with the etiology and pathogenesis of thyroid diseases. Clinical studies found that Xiaoyaosan and its modified prescriptions could be widely used in the treatment of multiple thyroid diseases， such as hyperthyroidism， Hashimoto's thyroiditis， and thyroid nodules. Both the use of modified Xiaoyaosan alone and in combination with medications such as methimazole， propylthiouracil， and euthyrox could effectively improve patients' clinical symptoms. In the mechanism research， this study discovered that the whole formula of Xiaoyaosan and its modified prescriptions could inhibit inflammatory reactions， regulate immune balance， and delay liver damage during the treatment of thyroid diseases. The research on Xiaoyaosan for treating thyroid diseases mainly focused on thyroid cancer， autoimmune thyroiditis， hyperthyroidism， and hypothyroidism. The mechanisms of action mainly involved promoting cell apoptosis， inhibiting cell proliferation and migration， arresting the cell cycle， and regulating thyroid hormone levels. In conclusion， this study systematically combs and summarizes the research status of Xiaoyaosan in treating thyroid diseases through literature retrieval， aiming to provide new perspectives and new ideas for the prevention and treatment of thyroid diseases with traditional Chinese medicine.

BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.

Five compounds were isolated and purified from the water extract of Elaeagnus oxycarpa Schlechtend leaf by multi-dimensional reversed-phase preparative liquid chromatographic system based on the separation and enrichment model. Their structures were identified by spectral analysis such as NMR, MS, UV, IR and by comparison with literature information as 2,4(1H,3H)-pyrimidinedione (1), elaeagnussugarester B (2), elaeagnussugarester A (3), elaeagnussugarester C (4), gallic acid (5). Compounds 2-4 are new compounds, compound 1 was isolated from Elaeagnus oxycarpa Schlechtend for the first time. The antioxidant and anti-tyrosinase activities of these compounds were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical method, the potassium ferricyanide reduction method and the colorimetric method with L-tyrosine as substrate. The results showed that compounds 2-5 have good antioxidant activities and inhibitory effect on tyrosinase. Compound 4 exhibited the most strong antioxidant activities, with IC₅₀ = 3.59 ± 0.06 μmol·L^-1 for DPPH free radical scavenging ability, IC₅₀ = 10.04 ± 0.20 μmol·L^-1 for ABTS free radical scavenging ability, and total reduction capacity of compound 4 was better than vitamin C respectively. Compound 3 possessed better inhibitory effect on tyrosinase with IC₅₀ = 0.25 ± 0.06 mmol·L^-1.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

OBJECTIVES: To explore the mechanism by which Tougu Xiaotong Capsule (TXC) promotes chondrogenic differentiation and cartilage repair in mice with osteoarthritis (OA). METHODS: Fifty 8-week-old male C57BL mice were randomly divided into normal control group, cartilage damage (induced by subchondral ring-shaped drilling) model group and TXC treatment groups at low, moderate and high doses (184, 368 and 736 mg/kg, respectively). Saline (in normal control and model groups) and TXC were administered after modeling by daily gavage for 6 consecutive weeks. The changes of cartilage damage in the mice were assessed by measuring thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) and using micro-CT, modified safranine O and fast green staining, HE staining, and qPCR. Primary cultures of mouse synovial mesenchymal stem cells (SMSCs) with lentivirus vector transfection for interfering CXCL12, TXC treatment, or both for 24 h were examined for chondrogenic differentiation using immunofluorescence staining, scratch assay, immunocytochemistry, and Western blotting. RESULTS: In mouse models with cartilage damage, TXC treatment at the moderate dose significantly alleviated joint pain, promoted cartilage repair, and upregulated the mRNA expression levels of CXCL12, GDF5, collagen II, aggrecan, Comp and Sox9 in the cartilage tissue. In primary mouse SMSCs, CXCL12 knockdown resulted in significant reduction of GDF5 protein expression, migration ability and Sox9 protein expression, and these changes were obviously reversed by TXC treatment. CONCLUSIONS TXC promotes chondrogenic differentiation of mouse SMSCs to promote repair of cartilage damage in mice by activating the CXCL12/GDF5 pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Osteoarthritis/metabolism* ; Male ; Growth Differentiation Factor 5/metabolism* ; Mice, Inbred C57BL ; Mice ; Chemokine CXCL12/metabolism* ; Signal Transduction/drug effects* ; Cell Differentiation/drug effects* ; Cartilage, Articular/drug effects* ; Mesenchymal Stem Cells/cytology*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: To investigate the current status of early pain and agitation management in critically ill patients in Guizhou Province. METHODS: A retrospective study was performed using data collected from a quality control activity conducted between April and June 2021 in non-provincial public hospitals with general intensive care unit (ICU) in Guizhou Province. Hospital-level data included hospital name and grade, ICU staffing, and number of ICU beds. Patient-level data included characteristics of patients treated in the general ICU on the day of the survey (e.g., age, sex, primary diagnosis), as well as pain and agitation assessments and the types of analgesic and sedative medications administered within 24 hours of ICU admission. RESULTS: A total of 947 critically ill ICU patients from 145 hospitals were included, among which 104 were secondary-level hospitals and 41 were tertiary-level hospitals. Within 24 hours of ICU admission, 312 (32.9%) critically ill patients received pain assessments, and 277 (29.3%) received agitation assessments. Among the pain assessment tools, the critical care pain observation tool (CPOT) was used in 44.2% (138/312) of critically ill ICU patients, with a significantly higher usage rate in tertiary hospitals compared to secondary hospitals [52.3% (69/132) vs. 38.3% (69/180), P < 0.05]. The Richmond agitation-sedation scale (RASS) was used in 93.8% (260/277) of critically ill ICU patients for agitation assessment, with no significant difference between hospital levels. Among the 947 critically ill patients, 592 (62.5%) received intravenous analgesics within 24 hours, with remifentanil being the most commonly used [42.9% (254/592)]; 510 (53.9%) received intravenous sedatives, with midazolam being the most frequently used [60.8% (310/510)]. Mechanical ventilation data were available for 932 critically ill patients, of whom 579 (62.1%) received mechanical ventilation and 353 (37.9%) did not. Compared with non-ventilated patients, ventilated patients had significantly higher rates of analgesic and sedative use [analgesics: 77.9% (451/579) vs. 38.8% (137/353); sedatives: 71.8% (416/579) vs. 25.8% (91/353); both P < 0.05]. In terms of analgesic selection, ventilated patients were more likely to receive strong opioids than non-ventilated patients [85.8% (95/137) vs. 69.3% (387/451), P < 0.05]. For sedatives, ventilated patients preferred midazolam [66.6% (277/416)], whereas non-ventilated patients more often received dexmedetomidine [45.1 (41/91)]. Blood pressure within 24 hours of ICU admission were available for 822 critically ill patients, of whom 245 (29.8%) had hypotension and 577 (70.2%) did not. Compared with non-hypotensive patients, hypotensive patients had significantly higher rates of analgesic and sedative use [analgesics: 74.7% (183/245) vs. 59.8% (345/577); sedatives: 65.7% (161/245) vs. 51.3% (296/577); both P < 0.05], but there was no significant difference in the choice of analgesic or sedative agents between the two groups. CONCLUSIONS The proportion of critically ill ICU patients in Guizhou Province who received standardized pain and agitation assessments was relatively low. The most commonly used assessment tools were CPOT and RASS, while remifentanil and midazolam were the most frequently used analgesic and sedative agents, respectively. Secondary-level hospitals had a lower rate of using standardized pain assessment tools compared to tertiary-level hospitals. Mechanical ventilation and hypotension were associated with the use of analgesic and sedative medications.
Humans ; Critical Illness ; Intensive Care Units ; Analgesics/therapeutic use* ; Hypnotics and Sedatives/therapeutic use* ; Retrospective Studies ; China ; Pain Measurement ; Pain Management ; Female ; Male ; Critical Care ; Middle Aged