Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms， they are often accompanied by a high risk of side effects. In recent years， the use of flavonoids from traditional Chinese medicine （TCM） in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors， regulating multiple cellular signaling pathways， alleviating oxidative stress， modulating immune system functions， inhibiting bone destruction， and suppressing angiogenesis. Due to their notable anti-inflammatory， antioxidant， and immunomodulatory activities， flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace， this paper explored research hotspots and frontiers in this field， systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids， provided a theoretical basis for their use in RA treatment and clinical applications， and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.

Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms， they are often accompanied by a high risk of side effects. In recent years， the use of flavonoids from traditional Chinese medicine （TCM） in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors， regulating multiple cellular signaling pathways， alleviating oxidative stress， modulating immune system functions， inhibiting bone destruction， and suppressing angiogenesis. Due to their notable anti-inflammatory， antioxidant， and immunomodulatory activities， flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace， this paper explored research hotspots and frontiers in this field， systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids， provided a theoretical basis for their use in RA treatment and clinical applications， and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.

Objective To investigate the correlations of serum calcium, 25-hydroxyvitamin D and uric acid levels with benign paroxysmal positional vertigo (BPPV). Methods A total of 96 patients with BPPV were enrolled in vertigo group and further divided into mild vertigo (30 cases), moderate vertigo (42 cases), and severe vertigo (24 cases) groups based on the severity of vertigo symptoms. Additionally, 63 healthy people undergoing physical examination without BPPV were recruited as control group. Serum calcium, 25-hydroxyvitamin D, and uric acid levels were compared among groups, and their correlations with the severity of vertigo in BPPV patients were analyzed. Follow-up was conducted for 3 months to record the recurrence rate of BPPV. Results The serum calcium and 25-hydroxyvitamin D levels in the moderate and severe vertigo groups were significantly lower, while uric acid levels, total score of Dizziness Handicap Inventory (DHI) as well as functional, emotional, and physical scores were significantly higher than those in the mild vertigo group and control group (P < 0.05). Moreover, the severe vertigo group exhibited lower serum calcium and 25-hydroxyvitamin D levels and higher uric acid level, DHI total score and functional, emotional, as well as physical scores (P < 0.05). No significant differences were observed in serum calcium, 25-hydroxyvitamin D, uric acid levels, or DHI scores between the mild vertigo group and the control group (P>0.05). The severity of vertigo in BPPV patients was negatively correlated with serum calcium (r=-0.557, P < 0.05) and 25-hydroxyvitamin D levels (r=-0.467, P < 0.05), and positively correlated with uric acid levels (r=0.504, P < 0.05). The 3-month recurrence rate of BPPV was 8.33%(8/96). Compared to patients with serum calcium ≥2.11 mmol/L, 25-hydroxyvitamin D ≥30 ng/mL, and uric acid ≤428 μmol/L, those with serum calcium < 2.11 mmol/L, 25-hydroxyvitamin D < 30 ng/mL, and uric acid >428 μmol/L had significantly higher BPPV recurrence rates (P < 0.05). Conclusion BPPV patients exhibit abnormally lower serum calcium and 25-hydroxyvitamin D levels and abnormally higher uric acid levels. The severity of vertigo in BPPV patients is negatively correlated with serum calcium and 25-hydroxyvitamin D levels and positively correlated with uric acid levels.

Objective To investigate the sleep status and emotional-behavioral problems among preschool children in Yanping District of Nanping City in Fujian Province, and analyze the correlation between sleep status and emotional-behavioral problems. Methods A total of 500 preschool children were selected as subjects of this study. The Children's Sleep Habits Questionnaire (CSHQ) and the Strengths and Difficulties Questionnaire (SDQ) were used to evaluate the sleep status and emotional-behavioral problems of the children. Additionally, general information about the children was collected. Comparisons were made between children with different demographic and sociological characteristics in terms of their sleep status and emotional-behavioral problems, and the correlations between sleep status and emotional-behavioral problems were analyzed. Results The detection rates of sleep disorders and emotional-behavioral problems among preschool children were 15.00% and 14.80% respectively. The detection rate of emotional-behavioral problems was significantly higher in boys than in girls (P < 0.05). No significant differences were found in the detection rates of sleep disorders and emotional-behavioral problems among children of different ages, birth weights, whether they were only children, birth methods, whether they were premature, maternal pregnancy ages, father's education level, sleep environments, or co-sleeping situations (P>0.05). Both the detection rates of sleep disorders and emotional-behavioral problems significantly decreased with the improvement of mother's education level and increased with the increase in daily screen exposure time (P < 0.05). Compared with children with normal/borderline scores on each dimension (conduct problems, peer problems, emotional symptoms, hyperactivity, prosocial behavior) and total scores of SDQ, children with abnormal scores on each dimension and total scores had significantly higher incidences of sleep disorders (P < 0.05). Multivariate analysis showed that sleep disorders were the risk factors for the scores of occurrence of conduct problems, peer problems, emotional symptoms, hyperactivity, prosocial behavior, and abnormal total difficulties scores among preschool children (P < 0.05). Conclusion The overall sleep status of preschool children in Yanping District of Nanping City is relatively good, but there are still many sleep problems. Sleep disorders can increase the risk of emotional-behavioral problems in children, and excessive screen exposure may increase the risk of sleep disorders and emotional-behavioral problems in children.

OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.

NONMEM

At the end of February 2023, the new Notice on the Issuance of Ethical Review Measures for Life Science and Medical Research Involving Humans was issued by the National Health Commission, the Ministry of Education, the Ministry of Science and Technology, and the State Administration of Traditional Chinese Medicine. It adheres to the basic principles and institutional framework of the Ethical Review Measures for Biomedical Research Involving Humans , and combines with the actual situation of domestic ethical work to optimize and improve the details and procedures of the review. Based on the Ethical Review Measures for Biomedical Research Involving Humans, the Ethical Review Measures for Life Science and Medical Research Involving Humans have expanded the scope of application of ethical review. Different experts in the field have discussed in detail the changes in the scope of review, and proposed review procedures that may need to be corresponding adjustments based on the changes for the readers’ reference.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective:By studying the gait changes of patients with knee osteoarthritis (KOA), the study provided a theoretical basis for the quantitative indicators obtained from gait analysis to the diagnosis of KOA. And it provided a gait reference for the clinical diagnosis, treatment, rehabilitation, prevention and efficacy evaluation of KOA.Methods:A total of 30 patients (KOA group) with KOA hospitalized in our hospital from May 2021 to October 2021 and 30 healthy people (control group) were compared for gait changes. The t test, Mann-Whitney U test and Fisher′s exact test were used to compare differences between groups. Results:The KOA group were greater than the control group in terms of step time [(642±81) ms and (548±62) ms, t=-5.01, P<0.001], gait cycle [(1 284±168) ms and (1 076±114) ms, t=-5.61, P<0.001], double support time [(531±125) ms and (331±51) ms, t=-8.10, P<0.001], double support time period proportion (0.417±0.063 and 0.309±0.023, t=-8.50, P<0.001), total support time [(914±135) ms and (678±107) ms, t=-7.52, P<0.001], total support time period proportion (0.711±0.027 and 0.627±0.044, t=-8.87, P<0.001), and left static standing time (55.7±8.4 and 51.5±2.2, t=-2.65, P=0.012), for which the differences were statistically significant. The KOA group were lower than the control group in terms of single support time period proportion (0.287±0.030 and 0.334±0.013, t=7.80, P<0.001), right static standing time (44.3±8.4 and 48.5±2.3, t=2.65, P=0.012), step length [(36±8) cm and (52±5) cm, t=9.97, P<0.001], stride length [(70±16) cm and (103±8) cm, t=10.00, P<0.001], velocity [(0.60±0.18) m/s and (1.05±0.19) m/s, t=9.54, P<0.001], left knee range of motion [(42±17)° and (63±4) °, t=6.49, P<0.001], and right knee range of motion [(37±18) ° and (62±3)°, t=7.54, P<0.001], for which the differences were statistically significant. Conclusion:Gait analysis can quantitatively evaluate the condition of patients with KOA, making it possible to transform the diagnostic criteria of KOA from qualitative to quantitative.

The endocrown, a modified overlay or crown, is considered to have the advantages of adhesive retention and mechanical retention. Marginal adaptation and mechanical strength are common criteria for evaluating endocrowns. This review studied these aspects of endocrowns to guide further clinical application. Results from previous academic studies indicate that endocrowns made of different materials, such as glass-based ceramics, zirconia-based ceramics and resin-based ceramics, exhibit clinically acceptable marginal adaptation. Zirconia is a common dental material, but when used in endocrowns, it tends to present a risk of irreparable tooth root fractures. Compared with products manufactured with zirconia, endocrowns manufactured with resin-based ceramics and glass-based ceramics, such as lithium disilicate ceramics, do not tend to cause irreparable results, such as tooth root fracture, but their mechanical strengths are not as good as those of zirconia. At the same time, the tooth prepration design such as the types of endocrowns, the pulp chamber extension depth and angles, the endocrown thickness can influence the mechanical strength of endocrowns as well. Compared with traditional zirconia, self-glazed zirconia, a new type of material used to restore defective teeth, has the similar elasticity modulus（210 GPa）and better aesthetic advantages, and is suitable for short crown patients with insufficient occlusal space. Further study is warranted to improve the performance of endocrowns made from ceramic materials to prevent root fracture.