AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.

Low-intensity pulsed ultrasound(LIPUS)was first introduced in clinic for the treatment of fracture because of its safety,ef-fectiveness and non-trauma.Then,a large number of subsequent studies have used LIPUS as a synergistic factor in bone,cartilage,joint,cancer treatment and oral clinical research,jointly revealing the powerful synergistic effect of LIPUS.This paper summarizes the synergistic effect of LIPUS in the above research fields,in order to broaden the possible clinical application scope of LIPUS.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective To investigate the relationship between low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LHR) and asymptomatic carotid plaques and their stability in high-risk stroke population.Methods Between December 2012 and April 2015,a total of 39 944 permanent resident population ≥40 years were used as subjects of the survey from 11 rural communities in Haitou Town,Banzhuang Town and Tashan Town,Ganyu District,and 9 urban communities in Xinpu District and Haizhou District,Lianyungang City using epidemiological survey method of cluster sampling.Excluding those who took lipid-lowering drugs within 3 months and had a history of stroke or transient ischemic attack,6 592 people at high risk of stroke were finally screened out.Ultrasound was used to detect carotid plaques.The subjects were divided into plaque-free group and plaque group.The latter was further divided into stable plaque group and unstable plaque group.Multivariate logistic regression analysis was used to evaluate the independent risk factor for carotid plaques and their stability.The odds ratio (OR) and 95％ confidence interval (CI) were calculated.Receiver Operating Characteristic (ROC) curve was used to evaluate the prediction efficiency of LHR on carotid plaques.Results Multivariate logistic regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was an independent risk factor for carotid plaques,while high-density lipoprotein cholesterol (HDL-C) was an independent protection factor of carotid plaques.Using the lowest quintile (Q1) of LHR as a reference,carotid plaque risk increased significantly with the increasing LHR (Q2:OR 1.448,95％ CI 1.082-1.937,P =0.013;Q3:OR 2.414,95％ CI 1.754-3.322,P＜0.001;Q4:OR 2.939,95％ CI 1.945-4.441,P＜0.001;Q5:OR 4.884,95％ CI 3.143-7.115,P＜0.001).ROC curve analysis showed that the area under the curve (AUC) of LHR predicting carotid plaques was 0.795 (95％ CI 0.792-0.807;P＜ 0.001),and the optimal cut-off value was 3.00 (sensitivity 68.37％,specificity 75.65％).LHR ≥3.92 (LHR in the Q4 and Q5 subgroups) was an independent risk factor for unstable carotid plaques (OR 2.915,95％ CI 2.104-4.040;P＜0.001).The AUC of the LHR predicting unstable carotid plaques was 0.658 (95％ CI 0.633-0.684;P＜0.001).Conclusions LHR was an independent predictor of carotid plaques in high-risk stroke patients.It had higher predictive value for carotid plaques,and its conversion threshold for promoting plaque formation was 3.00.When LHR was ≥3.92,there was a significant increase in the risk of unstable carotid plaques.

Objective: To study the influential factor of hyperlactatemia after the brain tumor craniotomy. Methods: Patients who underwent selective brain tumor (including glioma, meningioma and acoustic schwannoma) craniotomyin the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital, Sun Yat-sen University from December 1st 2018 to May 20th 2019 were enrolled. The incidence of hyperlactatemia after the brain tumor craniotomy was investigated. Univariate and multivariate linear regression analysis were performed to identify the association of initial artery lactate with the operation duration, the intraoperative blood loss, the total intraoperative fluid infusion, intraoperative ringer lactate fluid infusion, intraoperative urine volume, intraoperative fluid balance, the total intraoperative corticosteroids dosage and the tumor type. Pearson method was used to analyze the correlation between lactate in arterial blood and independent related factors. Results: A total of 148 patients were enrolled including 45 patients (30.41%) with glioma, 64 patients (43.24%) with meningioma, and 39 patients (26.35%) with acoustic schwannoma. The initial lactate level in arterial blood increased significantly in 148 patients, with a median of 4.80 (3.68, 5.90) mmol/L. Among them, 78 patients (52.70%) had mild elevation of lactate in arterial blood (2 mmol/L < lactate ≤ 5 mmol/L), 61 patients (41.22%) had significant elevation of lactate in arterial blood (5 mmol/L < lactate ≤ 10 mmol/L), and 2 patients (1.35%) had serious elevation of artery lactate (> 10 mmol/L). And only 7 patients (4.73%) had normal level of lactate in arterial blood (≤ 2 mmol/L). Univariate analysis showed that initial postoperative artery lactate was positively correlated with the operation duration [β = 0.556, 95% confidence interval (95%CI) was 0.257-0.855, P < 0.001] and the total intraoperative corticosteroids dosage (β = 0.477, 95%CI was 0.174-0.779, P = 0.002). There was no significant correlation between the initial postoperative artery lactate and tumor types, the intraoperative blood loss, the total fluid infusion, the ringer lactate fluid infusion, urine volume, and the fluid balance. Further multivariate linear regression analysis showed that the operation duration (β = 0.499, 95%CI was 0.204-0.795, P = 0.001) and the total intraoperative corticosteroids dosage (β = 0.407, 95%CI was 0.111-0.703, P = 0.008) were independent risk factors affecting the initial postoperative artery lactate. The correlation analysis showed that there was a significant positive correlation between lactate in arterial blood and operation time and total hormone dosage during operation (r₁ = 0.289, r₂ = 0.248, both P < 0.01). Conclusion Initial artery lactate after brain tumor craniotomy is associated with surgery duration and exogenous administration of corticosteroids.

Objective: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. Methods: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. Results: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L.①Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01].②When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086).③CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of≥10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. Conclusions It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.

Objective: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. Methods: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol, diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. Results: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. ① The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. ② The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). ③ There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. Conclusions Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.

OBJECTIVE: To study the influential factor of hyperlactatemia after the brain tumor craniotomy. METHODS: Patients who underwent selective brain tumor (including glioma, meningioma and acoustic schwannoma) craniotomyin the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital, Sun Yat-sen University from December 1st 2018 to May 20th 2019 were enrolled. The incidence of hyperlactatemia after the brain tumor craniotomy was investigated. Univariate and multivariate linear regression analysis were performed to identify the association of initial artery lactate with the operation duration, the intraoperative blood loss, the total intraoperative fluid infusion, intraoperative ringer lactate fluid infusion, intraoperative urine volume, intraoperative fluid balance, the total intraoperative corticosteroids dosage and the tumor type. Pearson method was used to analyze the correlation between lactate in arterial blood and independent related factors. RESULTS: A total of 148 patients were enrolled including 45 patients (30.41%) with glioma, 64 patients (43.24%) with meningioma, and 39 patients (26.35%) with acoustic schwannoma. The initial lactate level in arterial blood increased significantly in 148 patients, with a median of 4.80 (3.68, 5.90) mmol/L. Among them, 78 patients (52.70%) had mild elevation of lactate in arterial blood (2 mmol/L < lactate ≤ 5 mmol/L), 61 patients (41.22%) had significant elevation of lactate in arterial blood (5 mmol/L < lactate ≤ 10 mmol/L), and 2 patients (1.35%) had serious elevation of artery lactate (> 10 mmol/L). And only 7 patients (4.73%) had normal level of lactate in arterial blood (≤ 2 mmol/L). Univariate analysis showed that initial postoperative artery lactate was positively correlated with the operation duration [β = 0.556, 95% confidence interval (95%CI) was 0.257-0.855, P < 0.001] and the total intraoperative corticosteroids dosage (β = 0.477, 95%CI was 0.174-0.779, P = 0.002). There was no significant correlation between the initial postoperative artery lactate and tumor types, the intraoperative blood loss, the total fluid infusion, the ringer lactate fluid infusion, urine volume, and the fluid balance. Further multivariate linear regression analysis showed that the operation duration (β = 0.499, 95%CI was 0.204-0.795, P = 0.001) and the total intraoperative corticosteroids dosage (β = 0.407, 95%CI was 0.111-0.703, P = 0.008) were independent risk factors affecting the initial postoperative artery lactate. The correlation analysis showed that there was a significant positive correlation between lactate in arterial blood and operation time and total hormone dosage during operation (r₁ = 0.289, r₂ = 0.248, both P < 0.01). CONCLUSIONS Initial artery lactate after brain tumor craniotomy is associated with surgery duration and exogenous administration of corticosteroids.
Adrenal Cortex Hormones/therapeutic use* ; Arteries ; Brain Neoplasms ; Craniotomy ; Humans ; Retrospective Studies

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.
Adult ; Anti-Bacterial Agents/cerebrospinal fluid* ; Drug Monitoring ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/cerebrospinal fluid*

OBJECTIVE: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. RESULTS: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. (1) The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. (2) The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). (3) There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. CONCLUSIONS Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.
Adult ; Anti-Bacterial Agents/blood* ; Critical Illness ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/blood*