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 analyze the image characteristics of gastrointestinal stromal tumor(GIST) and leiomyoma under white-light endoscopy and ultrasound endoscopy, so as to establish a nomogram model and to validate its performance.Methods:From August 1, 2019, to December 1, 2022, the clinical data of 224 patients with GIST or leiomyoma who underwent endoscopic ultrasound examination at the First Affiliated Hospital of Soochow University were retrospectively analyzed. The 224 patients were divided into the modeling group of 145 cases (78 cases of GIST and 67 cases of leiomyoma), and the validation group of 79 cases (41 cases of GIST and 38 cases of leiomyoma). The basic data of patients, parameters of white-light endoscopy and ultrasound endoscopy were screened to establish a binary logistic regression model and draw a nomogram. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC) was used to evaluate the diagnostic efficiency of the model, and calibration curve was used to evaluate the consistency of predicted and observed probabilities. The model′s performance was compared with the diagnostic results of junior physicians (attending physicians) and senior physicians (associated chief physician). Decision curve analysis (DCA) was performed to evaluate the net benefit of the model. Independent sample t-test and chi-square test were used for statistical analysis. Results:Under white-light endoscopy, there were statistically significant differences in the lesion locations (esophagus: 0 vs. 56.7% (38/67); cardia: 11.5% (9/78) vs. 13.4% (9/67); gastric: 88.5% (69/78) vs. 29.9% (20/67)) and tumor morphyology (spherical or spheroid: 80.8% (63/78) vs. 28.4% (19/67); shuttle: 19.2% (15/78) vs. 71.6% (48/67)) between GIST and leiomyoma in the modeling group ( χ2=64.51 and 46.37, both P<0.001). Under ultrasound endoscopy, the proportion of patients with GIST whose lesions originated from the muscularis propria layer, with indistinct borders and with internal hyperechoic area were all higher than those of patients with leiomyoma (96.2% (75/78) vs. 62.7% (42/67); 53.8% (42/78) vs. 13.4% (9/67); 35.9% (28/78) vs. 10.4% (7/67)), and the differences were statistically significant ( χ2=25.91, 25.82 and 12.75, all P<0.001). Based on the logistic regression model, a nomogram model was established with age, tumor morphology, lesion origin, boundary clarity, and hyperechoic foci as predictive indicators. In the modeling group, the accuracy of nomogram model in the diagnosis of GIST and leiomyoma was 89.7% and 83.6%, respectively. In the validation group, the sensitivity, specificity, and accuracy in GIST and leiomyoma diagnosis of the nomogram model and senior physicians were all higher than those of junior physicians in differentiating GIST from leiomyoma (90.2%, 87.8% vs. 82.9%; 81.6%, 84.2% vs. 78.9%; 86.1%, 86.1% vs. 81.0%, respectively), and the sensitivity, specificity, and accuracy of the nomogram model were equal to those of senior physicians in differentiating GIST from leiomyoma. The AUCs of the nomogram model in the modeling group and validation group were 0.932 (95% confidence interval 0.891 to 0.974) and 0.916 (95% confidence interval 0.854 to 0.978), respectively. The calibration curves of the model indicated that the consistency between the predicted probabilities and observed probabilities was good, and DCA suggested good clinical net benefits of the model. Conclusion:The model exhibits good test efficiency, discrimination, prediction consistency and clinical net benefit when age, tumor morphology, lesion origin, boundary clarity, and hyperechoic foci are selected as indicators.

Objective To investigate the protective effect and mechanism of siwei tumuxiang powder(STP)on the model of H9c2 cardiomyocytes hypertrophy induced by mechanical stretching in rats.Methods The STP drug-containing serum and the hypertrophic cell model were prepared,and the optimal dose and time of action of STP drug-containing serum were determined.The expressions of at-rial natriuretic peptide(ANP),brain natriuretic peptide(BNP),miR-34a-5p,Notch1 and other factors in H9c2 cardiomyocytes were detected to verify whether STP exerted a protective effect on H9c2 cardiomyocytes by regulating the miR-34a-5p/Notch1 pathway.Results The optimal dose(0.972g/kg)of STP drug-containing serum was low-dose,and the action time was 24 hours.STP de-creased the expressions of ANP,BNP and miR-34a-5p in model cells(P＜0.05).Transfection of miR-34a-5p mimic reversed the effect of STP on ANP and BNP expressions(P＜0.05).Knocking down Notch1 by siRNA reversed the effect of STP on ANP and BNP ex-pressions(P＜0.05).Notch1 was the direct target gene of miR-34a-5p,and miR-34a-5p decreased the expression of Notch1(P＜0.05).After STP intervention,the expression of Notch1,NICD1 and Hes1 proteins were decreased.Transfection of miR-34a-5p mim-ic reversed the effect of STP on the expressions of Notch1,NICD1 and Hes1 proteins(P＜0.05).Conclusion STP exerts a protective effect on mechanical stretch-induced H9c2 cardiomyocyte hypertrophy by miR-34a-5p to negatively regulate the Notch1 signaling pathway.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Objective To construct a rehabilitation nursing program for stroke patients based on the international classification of functioning, disability and health (ICF). Methods The relevant domestic and foreign literatures were systematically searched, and a draft of the rehabilitation nursing program for stroke patients based on the 17 functional items in the four dimensions of ICF functional evaluation was constructed. The Delphi method was used to consult experts to further improve the program. Results A total of 16 experts completed two rounds of expert consultation. The expert authority coefficients of the first and second rounds of consultation were 0.897 and 0.897, respectively, with coefficient of variations ranging from 0.05 to 0.27 and 0.05 to 0.19, respectively. The Kendall's W coefficients were 0.384 and 0.452 (χ²=104.375, 122.831, P < 0.001), respectively. In the final rehabilitation nursing program for stroke patients, there were four first-level indicators (functional domains), 17 second-level indicators (intervention contents), and 73 third-level indicators (specific measures). Conclusion The rehabilitation nursing program for stroke patients based on ICF is scientific and reliable, and may provide theoretical support and practical guidance for the rehabilitation nursing of clinical stroke patients.

Objective:To explore the effects of different feeding patterns on weight gain and feeding intolerance in hospitalized premature infants.Methods:The retrospective cohort study design was adopted. From April 2019 to October 2020, 155 premature infants admitted to the Neonatal Intensive Care Unit of China-Japan Friendship Hospital were selected as the study subject by convenience sampling. Premature infants were divided into a mixed feeding group ( n=47) and a formula milk feeding group ( n=108) based on their feeding patterns. The observation indicators included weight gain, feeding intolerance, infectious diseases, nutrition and other related indicators. Results:The weight change value and the weight change rate during hospitalization in the mixed feeding group were higher than those in the formula milk feeding group, with statistically significant differences ( P<0.05) . In terms of the total milk volume on the day of discharge, the mixed feeding group were higher than the formula milk feeding group, and the differences were statistically significant ( P<0.05) . During hospitalization, the number of new infectious diseases in the mixed feeding group was less than that in the formula milk feeding group, with a statistically significant difference ( P<0.05) . There was no statistically significant difference in the incidence of feeding intolerance between the two groups of premature infants ( P>0.05) , The incidence of vomiting in the formula milk feeding group was lower than that in the mixed feeding group, with a statistically significant difference ( P<0.05) . Conclusions:Mixed feeding is more conducive to promoting the weight gain of premature infants during hospitalization and reducing the occurrence of infectious diseases than formula milk feeding. The impact of two feeding patterns on feeding intolerance in hospitalized premature infants needs further comparative analysis.

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.

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles