OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

OBJECTIVE: To observe the clinical efficacy of Fu's subcutaneous needling based on "multi-joint muscle spiral balance chain" theory for cervical vertigo (CV) and its effect on blood flow velocity of vertebral artery. METHODS: A total of 60 patients with CV were randomized into a Fu's subcutaneous needling group and a medication group, 30 cases in each one. In the Fu's subcutaneous needling group, Fu's subcutaneous needling was delivered at Dazhui (GV14), the flexible tube was retained for 5 min after sweeping manipulation, and the treatment was given once every other day, 3 times a week for 3 weeks. In the medication group, betahistine mesylate tablet and diclofenac sodium dual-release enteric capsule were taken orally for continuous 3 weeks. Before treatment, after treatment, and in follow-up of one month after treatment completion, the scores of dizziness handicap inventory (DHI) and visual analogue scale (VAS) were observed; before and after treatment, the blood flow velocity of vertebral artery was measured by transcranial Doppler, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment and in follow-up, each item scores and total scores of DHI were decreased compared with those before treatment in the two groups (P<0.05); the VAS scores after treatment in the two groups, as well as the VAS score in follow-up of the Fu's subcutaneous needling group, were decreased compared with those before treatment (P<0.05). In the Fu's subcutaneous needling group, after treatment and in follow-up, the physical scores and the total scores of DHI, and the VAS scores were lower than those in the medication group (P<0.05); in follow-up, the emotional and functional scores of DHI were lower than those in the medication group (P<0.05). After treatment, the mean blood flow velocity (Vm) of the left vertebral artery (LVA) and the right vertebral artery (RVA) was increased compared with that before treatment in the two groups (P<0.05), and the Vm of LVA and RVA in the Fu's subcutaneous needling group was higher than that in the medication group (P<0.05). The total effective rate was 100.0% (30/30) in the Fu's subcutaneous needling group, which was superior to 73.3% (22/30) in the medication group (P<0.05). CONCLUSION Fu's subcutaneous needling based on the "multi-joint muscle spiral balance chain" theory can effectively alleviate the vertigo and neck pain, and improve the blood flow velocity of vertebral artery in CV patients, and has a long-term therapeutic effect.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/instrumentation* ; Vertebral Artery/physiopathology* ; Adult ; Vertigo/physiopathology* ; Aged ; Blood Flow Velocity ; Treatment Outcome ; Acupuncture Points ; Young Adult

This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rabbits ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Pyroptosis/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans ; Female

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size