ObjectiveTo analyze the current research status of the classical formulas in China and predict the future development trends， thus providing reference and suggestions for the scientific research and clinical application of classical formulas. MethodThe relevant publications were retrieved from China National Knowledge Infrastructure （CNKI） with the time interval from January 1， 2008 to August 1， 2023， and the publications were counted. CiteSpace 6.1.R6 was used for visual analysis of the authors， research institutions， and keywords. ResultA total of 847 valid publications were included in this study. The annual number of publications showed a rapid rise after 2018. The Chinese Journal of Experimental Traditional Medical Formulae was the main journal publishing the articles about ancient classical formulas in China. ZHAN Zhilai， BAI Jie， LU Tulin， FU Chaomei， and CHEN Renshou were active researchers in this field and had formed stable research teams. The China Academy of Chinese Medical Sciences and its affiliated institutions published the most articles and had close cooperation with other research institutions in China. The co-occurrence network and cluster map of keywords showed that textual research on materia medica， clinical application， quality standard， fingerprint， and mechanism of action were the core keywords. The top 3 bursts in this field were benchmark samples， quality evaluation， and origin. ConclusionThe current research on ancient classical formulas still has shortcomings such as lack of large-scale cooperation between teams and weak transformation of research achievements. At present， the research hotspots in this field mainly include textural research on key information， quality control and fingerprinting， and clinical application. The future research in this field mainly focus on benchmark samples of classical formula preparations， quality evaluation of medicinal materials， pharmacodynamic material basis， and mechanisms of classical formulas.

Objective:To investigate the risk factors and their warning effectiveness for meniscus tear secondary to delayed anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective cohort study was conducted to analyze the clinical data of 114 patients (114 knees) with ACL injury, who were admitted to Affiliated Hospital of Nanjing University of Chinese Medicine from December 2018 to December 2023, including 78 males and 36 females, aged 11-50 years [29(21, 35)years]. The patients were divided into tear group ( n=46) and non-tear group ( n=68) according to whether combined with meniscus tear or not during the surgery. Gender, age, duration of disease, smoking history, Body Mass Index (BMI), cause of injury, mechanism of injury, side of the injury, Beighton score, difference of KT-2000 examination, Tegner activity scale of the knee joint, anterior tibial translation sign, medial posterior tibial slope angle, lateral posterior tibial slope angle, and pivot shift grading of the patients in the two groups were recorded. Correlations between the above-mentioned indicators and occurrence of meniscus tear secondary to delayed ACL reconstruction were assessed. In the meantime, the independent risk factors were determined by univariate and multivariate binary logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the warning effectiveness of each risk factor for meniscal tear secondary to delayed ACL reconstruction. Results:Univariate analysis showed correlation of duration of disease, BMI, Tegner activity scale of the knee joint, medial posterior tibial slope angle, lateral posterior tibial slope angle and high-grade pivot shift with occurrence of meniscus tear secondary to delayed ACL reconstruction ( P<0.01). The results of multivariate binary logistic regression analysis showed that the duration of disease ≥14.5 weeks ( OR=1.20, 95% CI 1.05, 1.38, P<0.01), BMI≥26.9 kg/m 2 ( OR=1.36, 95% CI 1.03, 1.81, P<0.05), Tegner activity scale of the knee joint ≥4 points ( OR=2.29, 95% CI 1.18, 4.46, P<0.05), medial posterior tibial slope angle ≥11.2° ( OR=2.27, 95% CI 1.06, 4.89, P<0.05) and high-grade pivot shift ( OR=0.03, 95% CI 0.01, 0.03, P<0.05) were significantly correlated with occurrence of meniscus tear secondary to delayed ACL reconstruction. Results of ROC curve analysis showed that the medial posterior tibial slope angle (AUC=0.86, 95% CI 0.80, 0.93) and duration of disease (AUC=0.85, 95% CI 0.77, 0.92) had good warning value, BMI (AUC=0.78, 95% CI 0.69, 0.87) and Tegner activity scale of the knee joint (AUC=0.73, 95% CI 0.64, 0.83) had ordinary warning value, and the warning value of high-grade pivot shift (AUC=0.60, 95% CI 0.49, 0.71) was the lowest. The combination of the risk factors revealed superior warning effectiveness for meniscus tear second to delayed ACL reconstruction (AUC=0.97, 95% CI 0.96, 1.00). Conclusions:The duration of disease ≥14.5 weeks, BMI ≥26.9 kg/m 2, Tegner score ≥4 points, medial posterior tibial slope angle ≥11.2°and high-grade pivot shift are independent risk factors for meniscus tear secondary to delayed ACL reconstruction. The medial posterior tibial slope angle and duration of disease have good warning value, BMI and Tegner scores have ordinary warning value and high-grade pivot shift has the lowest warning value. The combination of the above risk factors has better warning effectiveness for meniscus tear secondary to delayed ACL reconstruction.

BACKGROUND:Transposition of the long head of biceps tendon is a commonly surgical method for massive rotator cuff tears.Currently,there are a few reports on the clinical efficacy of the transposition of the long head of biceps tendon and there is no consensus on the influencing factors for retearing. OBJECTIVE:To observe the outcome of arthroscopic long head of the biceps tendon in the treatment of massive rotator cuff tear. METHODS:The clinical data of 28 patients with massive rotator cuff tears,aged(61.79±10.50)years,admitted at Jiangsu Province Hospital of Chinese Medicine from March 2019 to May 2022 were retrospectively analyzed.All patients underwent arthroscopic long head of the biceps tendon.Patients were assessed for visual analog scale scores,University of California at Los Angeles scores,American Shoulder and Elbow Surgeons scores,Constant-Murley scores,and shoulder range of motion before and 1 year after operation.MRI of the shoulder joint was performed for observing the integrity of the repaired structure at 1 year after operation.Twenty-three patients(5 of 28 lost to follow-up)were categorized into the intact tendon group(n=18)and the tendon retear group(n=5)according to the Sugaya typing at 1 year after operation;the patients were divided into the normal group(n=8),the degeneration group(n=9),and the partial tear group(n=6)according to the intraoperative quality of the long head of the biceps tendon.Differences in the above indexes were compared between groups. RESULTS AND CONCLUSION:When followed up at 1 year after surgery,the range of motion,visual analog scale scores,University of California at Los Angeles scores,American Shoulder and Elbow Surgeons scores,Constant-Murley scores of the shoulder were significantly improved compared with preoperative data(P＜0.05).There was a significant difference in Goutellier grading between intact tendon and tendon retear groups(P＜0.05),while no significant difference was observed in the other influencing factors(P＞0.05).There were no significant differences in visual analog scale scores,University of California at Los Angeles scores,American Shoulder and Elbow Surgeons scores,Constant-Murley scores,and shoulder range of motion at 1 year after operation among the normal,degeneration,and partial tear groups(P＞0.05).MRI findings indicated that the sutured tendon healed well in 18 patients,with a healing rate of 78%.Arthroscopic long head of the biceps tendon for augmented repair can provide a reliable repair for massive rotator cuff tear that is refractory,significantly alleviate the pain of the shoulder joint,and restore the function of the shoulder joint.

Objective To assess the value of cone-beam computed tomography (CBCT) in evaluating the response of unresectable liver cancer to transarterial chemoembolization (TACE). Methods A total of 55 unresectable liver cancer patients with 90 lesions who received TACE at the First People’s Hospital of Liangshan Yi Autonomous Prefecture between July 2021 and July 2023 were enrolled in the study. The response to TACE was evaluated using the modified Response Evaluation Criteria in Solid Tumors one month post-treatment. The value of lesion diameter, volume, and density on CBCT images in predicting the response to TACE was assessed using the area under the receiver operating characteristic curve. Results Of the 55 patients treated with TACE, 26 achieved complete response, 17 achieved partial response, 9 showed stable disease, and 3 had progressive disease. Of the 90 lesions, 48 achieved complete response, 20 achieved partial response, 17 showed stable disease, and 5 had progressive disease. On CBCT images, the mean diameter, volume, and density of lesions with complete and non-complete responses were (20.9 ± 9.9) mm, (1719.3 ± 777.9) mm³, and (143.7 ± 87.9) HU, versus (10.9 ± 7.7) mm, (890.0 ± 327.4) mm³, and (38.8 ± 33.3) HU, respectively, with significant differences between the two groups (t=10.6, 79.8, and 65.5; all P < 0.01). One month post-treatment, CT scans displayed no enhanced areas in lesions with complete response and visible enhanced areas in lesions with non-complete response, with mean lesion diameter and density of (14.1 ± 6.2) mm and (78.8 ± 30.3) HU, respectively. In addition, the areas under the receiver operating characteristic curves of lesion diameter, volume, and density on CBCT images were 0.935, 0.955, and 0.981, respectively, in distinguishing between complete and non-complete responses following TACE. Using a cut-off value of 82.5 HU for predicting response to TACE, the lesion density had sensitivity, specificity, positive predictive value, and negative predictive value of 95.5%, 100.0%, 100.0%, and 95.0%, respectively. Conclusion CBCT is effective in predicting the short-term response of liver cancer to TACE.

Premature ovarian insufficiency(POI),also known as"ovarian insufficiency",has an incidence of 1％～5％.The incidence has been on the rise in recent years,seriously affecting women's physical and mental health and quality of life.At present,the cause and mechanisms of POI are still unclear,and the method and applications of model construction are also confusing.Most models have some shortcomings in pertinence and stability.The limitations greatly limit research into the clinical diagnosis and treatment of POI.This paper summarizes and discusses the etiology and pathogenesis of POI and the construction of POI animal models to provide a comprehensive reference for those studying POI.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective To investigate the expression of IL-18,IL-18BP,and IL-18R in the peripheral blood B lymphocytes and mono-cytes of patients with atopic dermatitis(AD).Methods Peripheral venous blood was collected from 28 patients with AD and 21 healthy controls,and stimulated with Artemisia sieversiana wild allergen extract,house dust mite allergen extract,or Platanus pollen allergen extract.The expression of IL-18+,IL-18BP+,and IL-18R+in B lymphocytes and monocytes was measured using flow cytometry.Results Compared with the healthy control group,the proportions of IL-18+,IL-18BP+,and IL-18R+cells in the B lymphocyte group of patients with AD at rest increased 2.01-,10.35-,and 20.85-fold,respectively.The proportions of IL-18+and IL-18BP+cells in monocytes increased 5.51-and 41.88-fold,respectively,whereas the proportion of IL-18R+cells did not differ significantly between the groups.Conclusion IL-18,IL-18BP,and IL-18R in B lymphocytes and monocytes may play an important role in AD.IL-18,IL-18BP,and IL-18R may be potential targets for the treatment of AD.

OBJECTIVE To establish a method for concentration determination of caffeine and its three metabolites， theophylline， paraxanthine and theobromine in urine， and apply it in clinical practice. METHODS Using caffeine-13C3-d3 as internal standard （IS）， and the urine samples were protein precipitated with acetonitrile； HPLC-MS/MS method was adopted to determine the concentrations of caffeine and its three metabolites. The determination was performed on Waters ACQUITY UPLC® BEH HILIC column with mobile phase consisting of 60 mmol/L ammonium acetate （A）-acetonitrile （B） （gradient elution） at the flow rate of 0.5 mL/min. The column temperature was set at 38 ℃ ， and the sample size was 2 μL. The electrospray ionization detection was operated in a positive mode by multiple reaction monitoring. The detection ions for quantitative analysis were m/z 195.1→110.0 for caffeine， m/z 181.1→124.0 for theophylline， m/z 181.1→124.0 for paraxanthine， m/z 181.1→138.0 for theobromine， and m/z 198.1→ 140.1 for IS. The above method was used to determine the concentrations of caffeine and its three metabolites in the urine of 19 infants with apnea of prematurity （AOP）. RESULTS The linear ranges of mass concentration of caffeine， theophylline， paraxanthin and theobromine were 0.200-200， 0.050-50.0，0.050 0-50.0， and 0.100-100 μg/mL， respectively. The lower limits of quantification were 0.200， 0.050， 0.050 and 0.100 μg/mL （r＞0.990）， respectively. RSDs of intra-day and intra- day precision were not above 10.37%， and matrix factors were 85.68%-109.90%； extraction recoveries were 93.53%-109.40% （RSD≤15%）， and RSDs of stability tests were all lower than 15%. The concentrations of caffeine and its three metabolites in the urine of 19 cases were （27.346±7.951）， （0.351±0.223）， （0.428±0.395） and （0.472±0.374） μg/mL， respectively. CONCLUSIONS The established HPLC-MS/MS method is simple， sensitive and can be used for the determination of caffeine and its three metabolites in urine samples of AOP.