Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

OBJECTIVE To evaluate the efficacy and safety of tyrosine kinase inhibitors （TKI） in the treatment of HER2- positive breast cancer in order to provide evidence-based evidence for clinical medication. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， Cochrane Library， Embase and Web of Science， randomized controlled trial （RCT） about TKI （trial group） versus drugs excluding TKI （control group） in the treatment of HER2-positive breast cancer were collected from the establishment of the database to April 2023. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 and Stata 17 software. RESULTS Total of 24 RCT studies were included， involving 15 538 HER2-positive breast cancer patients. The meta- analysis results showed that compared with the control group， the progression-free survival （PFS） [HR＝0.91， 95%CI （0.80， 1.02）， P＝0.12]， overall survival （OS） [HR＝0.95， 95%CI （0.89， 1.01）， P＝0.11]， objective response rate （ORR） [OR＝1.21， 95%CI （0.86， 1.69）， P＝0.27]， and pathological complete response rate （pCR） [OR＝1.44， 95%CI （0.91， 2.27）， P＝0.12] had no statistically significant difference in the trial group； among the 3/4 grade ADRs， the trial group had a higher incidence of anemia [OR＝1.77， 95%CI （1.16，2.70）， P＝0.008]， rash [OR＝11.26， 95%CI （7.32，17.31）， P＜0.000 01]， paronychia [OR＝8.67， 95%CI（1.62，46.53）， P＝0.01]， diarrhea [OR＝10.17， 95%CI（5.03，20.58）， P＜0.000 01]， oral mucositis inflammation [OR＝ 9.34， 95%CI （3.13， 27.83）， P＜0.000 1]， elevated aspartate aminotransferase [OR＝2.09， 95%CI （1.13，3.84）， P＝0.02]， and hypokalemia [OR＝2.37， 95%CI （1.31，4.30）， P＝0.005] than that of the control group. Subgroup analysis results showed that compared with the placebo group， TKI could improve OS and ORR （P＜0.05）， while compared with trastuzumab， TKI had no advantage in PFS， OS， ORR， and pCR， and TKI combined with trastuzumab could significantly improve PFS， OS， ORR， and pCR compared with the trastuzumab group （P＜ 0.05）. Sensitivity analysis suggested that the results were relatively robust and the risk of publication bias was low. CONCLUSIONS Compared with trastuzumab， TKI has no advantages in PFS， OS， ORR and pCR in the treatment of HER2- positive breast cancer， but TKI combined with trastuzumab can significantly improve PFS， OS， ORR and pCR； TKI can increase the risk of grade 3/4 anemia， rash， paronychia， diarrhea， oral mucositis， elevated aspartate aminotransferase， and hypokalemia.

Objective:To explore the caregiving feelings and needs of caregivers of children with β-thalassemia major.Methods:A semi-structured interview was conducted with 14 caregivers of children with β-thalassemia major who were treated at the Affiliated Hospital of Youjiang Medical University for Nationalities from December 2022 to March 2023, and the data were analyzed using the Colaizzi 7-step analysis method.Results:Caregivers of children with β-thalassemia major felt a greater burden of care, including declining physical and mental health, disruption of daily life rhythms and heavy financial burden. And their caregiving needs included psychological and emotional support, guidance on the physical and mental health of children, assurance of a stable blood supply and medical and social support.Conclusions:Caregivers of children with β-thalassemia major have a heavy burden of care and face various nursing difficulties in the daily care of children. Medical staff should actively take measures to meet their care needs and improve their care quality and quality of life.

Shengyang Yiweitang is one of the first 100 classical prescriptions published by the National Administration of Traditional Chinese Medicine. It originated from the Clarifying Doubts about Damage from Internal and External Causes by physician LI Dongyuan of Jin dynasty， and is composed of Astragali Radix， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Pinelliae Rhizoma， Citri Reticulatae Pericarpium， Angelicae Pubescentis Radix， Saposhnikoviae Radix， Notopterygii Rhizoma et Radix， Bupleuri Radix， Paeoniae Radix Alba， Alismatis Rhizoma， and Coptidis Rhizoma. With the effects of replenishing Qi， promoting Yang， clearing heat and removing dampness， Shengyang Yiweitang is used to treat spleen-stomach weakness and dampness-heat accumulation syndrome. Using bibliometrics， the authors systematically sorted out the source，composition， dosage， preparation， efficacy， indications， principle of composition， origin and processing of drugs，and modern clinical application of the prescription， and explored its history and key information. Additionally， it was found that Shengyang Yiweitang was widely used in modern clinical practice and was suitable for multisystem diseases， of which digestive system （264） was the most common， accounting for 41.71%， followed by urogenital system （57， 9.00%） and nervous system （48， 7.58%）. Although the treatment scope was wide， the pathogenesis of the diseases in traditional Chinese medicine belongs to "spleen-stomach weakness"， which fully reflected Li's academic thought of "internal injury of spleen and stomach leads to various diseases". The key information of Shengyang Yiweitang was determined by summarizing the relevant ancient books and modern literature， so as to provide accurate reference for its rational clinical application and further research and development.

Qingweisan is one of the classical prescriptions commonly used in the treatment of oral diseases. By means of Bibliometrics， the authors collected the ancient books on Qingweisan and sifted out 411 valid data， involving 116 classics of traditional Chinese medicine. The historical origin， drug composition， indications， principle of composition， dosage，and preparation of Qingweisan were statistically analyzed， and it was found that the prescription originated from the Treatise on Spleen and Stomach（《脾胃论》） by LI Dongyuan and is composed of Rehmanniae Radix， Angelica Sinensis， Cortex Moutan， Coptidis Rhizoma and Cimicifugae Rhizoma， with the functions of clearing stomach， purging fire， cooling blood and dispersing depression. And Qingweisan was mainly used to treat toothache， headache， and preference for cold and aversion to heat caused by "excessive heat in yang brightness meridian". There were 352 indications recorded， most of which followed LI Dongyuan's theory and the expanded indications reached 70 kinds. Specifically， toothache （132） was the most， accounting for 22.49% of the total indications， followed by headache （60， 10.22%）. In addition， Qingweisan was widely used in modern clinical practice for multiple system diseases， among which oral system （197） was dominant， accounting for 72.69%， followed by skin system （28， 10.33%） and digestive system （27， 9.96%）. Although the indications were wide， the pathogenesis always belonged to "upward attack of stomach fire". Through the excavation and statistical analysis of the ancient books on Qingweisan and its modern clinical application， the authors aimed to provide a more scientific reference for the research and application of classical famous prescriptions.

ObjectiveTo investigate the value of aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in diagnosis of liver inflammation grade in patients with chronic hepatitis B (CHB). MethodsA total of 545 patients with CHB who underwent percutaneous liver biopsy and routine laboratory examinations during hospitalization in Shanghai Public Health Clinical Center Affiliated to Fudan University from October 2016 to October 2019 were enrolled. Inflammation grade (G) was determined according to the Scheuer scoring system, and APRI, FIB-4, and GPR were calculated based on related clinical indicators. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between two variables. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the three serum noninvasive diagnostic models in determining liver inflammation grade, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsAmong the 545 patients, 224 had grade G0-1 liver inflammation, 209 had grade G2 liver inflammation, and 112 had grade G3 liver inflammation. The Spearman correlation analysis showed that APRI, FIB-4, and GPR were positively correlated with liver inflammation grade (r=0.611, 0.470, and 0.563, all P＜0.001). APRI, FIB-4, and GPR had an AUC of 0.820, 0.719, and 0782, respectively, in the diagnosis of G≥2 liver inflammation, with optimal cut-off values of 0.53, 1.48, and 0.20, respectively; for the diagnosis of G≥2 liver inflammation, GPR had a better performance than FIB-4 (P=0.01) and a slightly lower performance than APRI (P=0.048). The stratified analysis based on alanine aminotransferase (ALT) level showed that in the ≤1×upper limit of normal (ULN) group, the (1-2)×ULN group, and the (2-5)×ULN group, APRI had an AUC of 0.847, 0.786, and 0.724, respectively, in the diagnosis of G≥2 liver inflammation, FIB-4 had an AUC of 0.777, 0.729, and 0.626, respectively, and GPR had an AUC of 0.801, 0.781, and 0.607, respectively; the subgroup analysis showed that GPR had a similar diagnostic performance to APRI and FIB-4 in all ALT stratification groups except the (2-5)×ULN group, in which GPR had a lower diagnostic performance than APRI (P=0.042). APRI, FIB-4, and GPR had an AUC of 0.791, 0.725, and 0.801, respectively, in the diagnosis of G≥3 liver inflammation, with optimal cut-off values of 0.66, 1.49, and 0.25, respectively; in the diagnosis of G≥3 liver inflammation, GPR had a similar diagnostic performance to APRI and a better diagnostic performance than FIB-4 (P=0.006). The stratified analysis based on ALT level showed that in the ≤1×ULN group, the (1-2)×ULN group, and the (2-5)×ULN group, APRI had an AUC of 0.900, 0.742, and 0.693, respectively, in the diagnosis of G≥3 liver inflammation, FIB-4 had an AUC of 0.874, 0.683, and 0.644, respectively, and GPR had an AUC of 0.890, 0.805, and 0.668, respectively. The subgroup analysis showed that GPR had a similar diagnostic performance to APRI and FIB-4 in all ALT stratification groups except the (1-2)×ULN group, in which GPR had a better diagnostic performance than FIB-4(P=0.015). ConclusionAPRI, FIB-4, and GPR may accurately diagnose liver inflammation grade in CHB patients, which helps to monitor the progression of CHB and determine the timing of antiviral therapy.

Objective:To compare the clinical characteristics, clinical efficacy and adverse drug reactions of rheumatoid factor (RF) positive (+ ) and negative (-) polyarticular juvenile idiopathic arthritis (PJIA).Methods:The clinical data of 67 PJIA patients admitted into Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to December 2018 were analyzed retrospectively.They were divided into RF-positive PJIA group [RF (+ ) group, 23 cases] and RF-negative PJIA group [RF (-) group, 44 cases] according to RF titer.The clinical characteristics, laboratory indexes and clinical efficacy evaluation of the two groups were compared.Results:(1)Distribution of affected joints: the top 3 affected joints in the RF (+ ) group were the knuckles (16 cases, 69.57%), the wrists (15 cases, 65.22%) and the ankles (13 cases, 56.52%), and those in the RF (-) group were the knees (33 cases, 75.00%), ankle joints (29 cases, 65.91%) and hip joints (26 cases, 59.09%). The wrist joint involvement of the RF (+ ) group was significantly higher than that of the RF (-) group, while the knee joint involvement was lower than that of the RF (-) group.The difference was statistically significant (all P<0.01). (2)Magnetic resonance changes of the affected joints: articular cavity effusion (54 cases, 84.38%), synovial thickening (44 cases, 68.75%) and bone edema (26 cases, 40.63%) are common in both groups.The incidence of bone destruction (7 cases, 70.00%) and soft tissue edema (7 cases, 70.00%) in the RF (+ ) group was higher than that in the RF (-) group (2 cases, 18.18% and 2 cases, 18.18%), the difference was statistically significant (all P<0.05). (3) Changes in laboratory indicators: the positive rates of C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide antibody and anti-nuclear antibody in the RF(+ ) group were significantly higher than those in the RF(-) group, the difference was statistically significant (all P<0.05). (4)Juvenile arthritis disease activity score 27 (JADAS27): the score difference between RF(+ ) group and RF(-) group was not statistically significant [(22.83±5.60) scores vs.(23.07±6.66) scores, t=0.148, P>0.05]. (5) Efficacy analysis: 2 patients were lost to follow-up after discharge, and the remaining 65 patients were treated with traditional therapy, of which 30 were given biologics at the first hospitalization, 9 cases were treated with biologics after the failure of traditional treatments, and 35 patients were treated with biologics to control disease activity.In different dosage regimens, the disease remission rate in the RF(-) group is generally higher than that in the RF(+ ) group. Conclusions:PJIA patients have complicated joint involvement, RF-positive patients are more prone to joint destruction, and traditional treatments are less effective.Biological agents can effectively improve the symptoms of severe PJIA patients, especially those with poor prognosis.

Objective To assess the diagnostic performance of liver stiffness measurement(LSM)and serum markers on hepatic fibrosis in chronic hepatitis B(CHB)patients with alanine aminotransferase(ALT)less than or equal to two times the upper limit of normal(≤2×ULN).Methods A total of 284 CHB patients with ALT≤2×ULN who were treated in Department of Hepatobiliary Medicine,Public Health Clinical Center,Shanghai from October 2015 to December 2017 were analyzed.FibroScan,routine blood tests and serum fibrosis markers were conducted on the day or one day before liver biopsy.The Scheuer scoring system was used for liver histologic assessment.Aspartate aminotransferase to platelet ration index(APRI)and FIB-4 were calculated.Based on the results of liver pathology,the area under receiver operating characteristic curve(AUROC)was used to evaluate the value of LSM and serum markers in the diagnosis of liver fibrosis stage.Non-normal distribution variables were expressed as M(QR)as appropriate,and compared by analysis of Kruskal-Wallis test as appropriate.The correlation between two variables was analyzed by Spearman correlation analysis.Results Of 284 CHB patients,175 were male and 109 were female.For inflammatory grading,175 cases were G1 grade,88 cases were G2,and 21 cases were G3.For fibrosis grading,153 cases were S1,53 cases were S2,34 cases were S3,and 44 cases were S4.Spearman correlation analysis showed that LSM,APRI and FIB-4 were positively correlated with hepatic fibrosis stage(r=0.650,0.484,and 0.317,respectively,all P<0.01).The AUC of LSM for predicting fibrosis≥S2,≥S3,and S4 were 0.840,0.902,and 0.942,respectively.The cut-off of LSM values were 6.10,8.40,and 10.10 kPa,respectively.The values of AUC of APRI and FIB-4 for predicting fibrosis≥S2 were 0.755 and 0.638,respectively,those for predicting fibrosis≥S3 were 0.737 and 0.657,respectively,and those for S4 were 0.804 and 0.694,respectively.The AUCs of LSM for predicting fibrosis≥S2 in patients with ALT≤1×ULN and those with ALT>1 -≤2×ULN were 0.857 and 0.813,respectively,those for fibrosis≥S3 were 0.890 and 0.892,respectively,and those for S4 were 0.925 and 0.908,respectively.The cut-off of LSM were 5.90 and 7.80 kPa,8.10 and 9.50 kPa,8.40 and 10.40 kPa,respectively.Conclusions LSM could accurately assess the degree of liver fibrosis in CHB patients with ALT≤2×ULN,which is superior to serum markers for predicting liver fibrosis stage.

Objective To detect serum interleukin 6(IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum ferritin in acute Kawasaki disease (KD), and explore their values in the diagnosis of KD, and further to explore the relationship with intravenous immunoglobulin (IVIG) unresponsiveness and coronary arterial lesions (CALs). Methods Totally 108 patients with KD (81 IVIG responders and 27 IVIG non-responders, 31with CALs and 77 non-CALs) were recruited from October 2014 to February 2016 at Department of Pediatrics of Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, 64 were boys and 44 were girls. Their ages ranged from 2 months to 11 years and 5 months. A total of 30 children with respiratory tract infection were selected as the control group, 18 were boys and 12 were girls, ages ranged from 4 months to 10 years. Serum IL-6, NT-proBNP and serum ferritin were measured at the day of admission. The differences between groups were analyzed by t-test. To compare the power of serum level of interleukin 6(IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum ferritin levels in predicting KD, IVIG unresponsiveness and CALs, receiver-operating characteristic (ROC) curves were plotted and areas under the curve (AUC) were calculated. All data are presented as means ± standard deviation. Results (1) The levels of IL-6 135 ± 268ng /L, NT-proBNP 1008 ± 1675ng /L and ferritin 227 ± 238μg /L were significantly higher in the acute phase patients with KD than those of the control group 27 ± 29ng /L for IL-6 (t = 2. 192, P = 0. 03), 109 ± 100ng /L for NT-proBNP(t = 5. 463, P = 0. 000) and 72 ± 101μg /L for ferritin (t = 3. 437, P = 0. 001). (2) The levels of NT-proBNP 1837 ± 2666ng /L in IVIG unresponsive group were significantly higher than those of the IVIG responsive group 720 ± 1032ng /L (t = 3. 108, P = 0. 002). However, there were no significant difference of IL-6 and serum ferritin between the two groups. (3) The levels of NT-proBNP in CALs group 1703 ± 2569ng /L vs 742 ± 1080ng /L, serum ferritin 340 ± 405μg /L vs 183 ± 99μg /L were significantly higher than those of the non-CALs group (P ＜ 0. 05). However, there was no significant difference of IL-6 between the two groups. (4) The area under the curve for predicting KD with various variables were as follows: serum IL-6 0. 773, NT-proBNP 0. 835 and serum ferritin 0. 793. The area under the curve for predicting resistance to IVIG with serum NT-proBNP was 0. 623. The area under the curve for predicting CALs with various variables were as follows: NT-proBNP 0. 612 and ferritin 0. 671. The ROC of ferritin for predicting CALs is better than NT-proBNP. A ferritin cut-off value of 160. 2μg /L yielded a sensitivity of 73. 7％, specificity of 52. 1％. Conclusion The serum IL-6, NT-proBNP and serum ferritin can be used as useful parameters in early diagnosis of KD. Elevated NT-proBNP or serum ferritin may be useful to predict IVIG resistance and CALs in KD patients.