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.

Objective:To optimize the dispensing method of national drug standard substances and develop a novel adjustable quantitative dispensing device for improving dispensing efficiency and production quality.Methods:Stain-less steel was used to fabricate an adjustable volume tank and a matching scraper for dispensing powder samples of fixed volume.Results:31 types of uniform powder samples,including chemicals and pharmaceutical excipients,were dispensed using the dispensing device.It showed a small test fluctuation range,high accuracy,and consistent effectiveness among different samples.The dispensing efficiency was improved by 147％compared to the conventional method of single-weight dispensing using a balance.Conclusion:The device can significantly reduce dispensing time,increase production efficiency,and meet the dispensing specifications for drug standard substances,which brings remarkable convenience and value to the production and preparation of drug standard substances.

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). 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 investigate the dynamic changes in early gastric antrum contraction in patients with craniocerebral injury. Methods The patients with craniocerebral injury admitted to neurosurgery intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from July to November in 2018 were enrolled. The changes in antral contraction frequency (ACF), antral contraction amplitude (ACA) and antral motility index (MI) were dynamically observed at 1-6 days after injury by ultrasonography. According to Glasgow coma score (GCS), the patients were divided into moderate to severe craniocerebral (GCS ≤ 11) and mild craniocerebral injury groups (GCS > 11). The differences in ACF, ACA and MI between the two groups were compared to observe the effect of craniocerebral injury on gastric antral motility. The patients were divided into simple supratentorial and supratentorial combined infratentorial lesion groups according to the lesion location of craniocerebral injury. The differences in ACF, ACA and MI between the two groups were compared to analyze the influence of lesion location on gastric antrum activity. Results A total of 68 patients with craniocerebral injury were screened during the study period, 50 patients were in accorded with the admission criteria, 17 patients were withdrawn from the observation because they could not tolerate the ultrasonography of gastric antrum or discharged from ICU. Finally, 33 patients were enrolled in the analysis. ① The ACF, ACA and MI at 1 day after injury were lower [ACF (times/min): 1.67 (0.00, 2.00), ACA: 42.06 (0.00, 44.45)%, MI: 0.70 (0.00, 0.87)], and then gradually increased, till 6 days after injury, ACF was 1.83 (1.25, 2.79) times/min, ACA was 56.80 (33.25, 60.77)%, and MI was 0.89 (0.50, 1.70), which showed no differences among all time points (all P > 0.05). ② The contractile function of gastric antrum in two groups of patients with different degrees of craniocerebral injury was decreased, especially ACA in patients with moderate to severe craniocerebral injury (n = 22), which showed significant differences at 3 days and 5 days after injury as compared with mild craniocerebral injury [n = 11; 3 days: 35.05 (0.00, 53.69)% vs. 58.51 (49.90, 65.45)%, 5 days: 39.88 (0.00, 77.01)% vs. 56.94 (41.71, 66.66)%, both P < 0.05], indicating that the degree of craniocerebral injury affected the contractive function of gastric antrum. However, there was no significant difference in ACF or MI between the two groups at different time points after injury. ③ The contractile function of gastric antrum was decreased after craniocerebral injury in both groups of patients with different lesion locations of craniocerebral injury. The ACF, ACA, and MI at 3-4 days in patients with supratentorial combined infratentorial lesion (n = 12) were slightly lower than those in patients with simple supratentorial lesion [n = 21; 3 days: ACF (times/min) was 0.83 (0.00, 2.00) vs. 2.25 (0.00, 3.00), ACA was 35.05 (0.00, 53.60)% vs. 49.93 (0.00, 63.44)%, MI was 0.29 (0.00, 1.07) vs. 1.23 (0.00, 1.61); 4 days: ACF (times/min) was 1.42 (0.50, 2.63) vs. 2.00 (1.63, 2.63), ACA was 30.45 (21.69, 60.61)% vs. 43.29 (38.41, 53.35)%, MI was 0.50 (0.15, 1.45) vs. 0.97 (0.66, 1.28)] without statistical differences (all P > 0.05), indicating that the lesion location might not affect the contractive function of gastric antrum. Conclusion In the early stage of craniocerebral injury, the contractile function of gastric antrum was decreased, and the more severe the craniocerebral injury, the worse contractive function of gastric antrum.[Key words] Craniocerebral injury; Antral contraction; Enteral nutrition; Antral ultrasonography

Objective: To explore the hot issues and developing trend of the research of campus bulling,and to provide a reference for the research on campus bullying. Methods: The power of research, high-impact authors, highly cited journals, high-frequency keywords, and burst terms related to school bullying from the Web of Science database were analyzed using CiteSpace software. The data collection time was May 9, 2018. Results: A total of 3 561 literature data were obtained. The results showed that the country with the highest number of publications was the United States; England had the highest centrality and was in a critical position in the research. The University of Turku in Finland was the core research institution. Salmivalli C was the author of the highest publication, Olweus D was the most frequent cited author. The high-impact journal was Aggressive Behavior. In terms of high-frequency keywords, the core vocabulary such as bully, adolescence, and victim were listed. Middle school students were the most frequently studied; in the form of bullying, the frequency of violence, aggression, and cyberbully was more common; depression, mental health and health appeared more frequently in terms of bullying outcomes. Mutant words including school children, bullying, victimization, relational aggression were more common. Conclusion The research hotspots on campus bullying during the past decade include violence, gender, social support, and mental health. Bullying among college students will be a hot research topic in the future. Continued efforts should be carried out in the field of campus bullying in China.

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*