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 investigate the mechanism by which miR-148a affects M2 macrophage polarization and inhibits liver cancer cell proliferation through Wnt3a/β-catenin. Methods The mRNA expression levels of miR-148a, CD206 and interleukin-10 (IL-10) in tumor tissues and adjacent non-tumor liver tissues of 84 patients with liver cancer were detected by real-time quantitative PCR. THP-1 cells were separated into blank group (conventional culture), M2 group (200 nmol/L phorbol ester, 20 ng/mL IL-4, 20 ng/mL IL-13), M2 combined with negative control (miR-NC) group (transfected with miR-NC on the basis of M2 group), M2 combined with miR-148a mimics (transfected with miR-148a mimics on the basis of M2 group) group, M2 combined with miR-148a mimics combined with Wnt3a (treated with 100 μg/L Wnt3a on top of M2 combined with miR-148a mimics group) group. The proliferation of HuH7 cells was detected by CCK-8 and EdU methods. Apoptosis and M2 macrophage marker CD206 was detected by flow cytometry. The level of IL-10 in cell supernatant was detected by chemiluminescence method; The mRNA levels of miR-148a, CD206 and IL-10 were detected by real-time quantitative PCR. The protein levels of Wnt3a and β-catenin were detected by Western blot. Results The expressions of CD206, IL-10 mRNA, Wnt3a and β-catenin in tumor tissue were higher than those in non-tumor liver tissues, and the miR-148a level was decreased. The mRNA expression of M2 macrophage markers CD206 and IL-10 were significantly increased. Compared with the blank group, the OD450 value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were increased in M2 group, while the apoptotic rate and miR-148a level were decreased. Compared with M2 group and M2 combined with miR-NC group, the OD₄₅₀ value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were decreased in M2 combined with miR-148a mimics group, while the apoptotic rate and miR-148a level were increased. Wnt3a reversed the inhibitory effect of miR-148a overexpression on the proliferation of liver cancer cells. Conclusion Overexpression of miR-148a inhibits M2 polarization of macrophages and prevents the proliferation of liver cancer cells, which may be related to the inhibition of the Wnt3a/β-catenin pathway.
Humans ; MicroRNAs/metabolism* ; Wnt3A Protein/metabolism* ; Liver Neoplasms/metabolism* ; Cell Proliferation/genetics* ; beta Catenin/genetics* ; Macrophages/metabolism* ; Interleukin-10/metabolism* ; Apoptosis/genetics* ; Cell Line, Tumor ; Female ; Male ; Mannose Receptor ; Lectins, C-Type/metabolism* ; Mannose-Binding Lectins/metabolism* ; Middle Aged ; Receptors, Cell Surface/metabolism*

OBJECTIVE To investigate the correlation between the expression levels of tissue inhibitor of metalloproteinases 1(TIMP-1)and drosophila mothers against DDP homolog 4(Smad4)in vocal cord precancerous lesions and postoperative recurrence and malignant transformation.METHODS The clinical and pathological data of 162 patients with vocal cord precancerous lesions admitted to the First Affiliated Hospital of Zhengzhou University from August 2018 to August 2021 were retrospectively analyzed.The expression of TIMP-1 and Smad4 in the surgically removed precancerous tissues(precancerous lesion group)and adjacent normal mucosal tissues(control group)were detected by immunohistochemical method.The relationship between the positive rate of TIMP-1 and Smad4 and clinicopathological features was analyzed.Kaplan-Meier method and Cox regression analysis were used to analyze the effect on postoperative recurrence and malignant transformation.RESULTS Compared with the normal mucosa of the control group,the positive rate of TIMP-1 was higher and the positive rate of Smad4 was lower in the precancerous lesion group(P<0.05).The positive rates of TIMP-1 and Smad4 in patients with different lesion ranges,anterior commissure involvement and different degree of epithelial dysplasia were different(P<0.05).Postoperative follow-up lasted from 24 to 60 months,with a median follow-up time of 36 months.During the follow-up,6 patients were lost to follow-up,with a follow-up rate of 96.30%(156/162).During the follow-up,35 patients had postoperative recurrence(21.60%)and 16 patients had postoperative malignant transformation(9.88%).Kaplan-Meier survival analysis showed that the postoperative recurrence rate and malignant change rate of TIMP-1 positive patients were higher than those of TIMP-1 negative patients(P<0.05),amd the recurrence rate and malignant change rate of Smad4-negative patients were higher than those of Smad4-positive patients(P<0.05).Multivariate Cox regression analysis showed that laryngeal reflux,lesion scope>1/2,moderate/severe dysplasia,TIMP-1 positive and Smad4 negative were independent risk factors for recurrence(P<0.05),and age>60 years old,anterior union involved,TIMP-1 positive and Smad4 negative were independent risk factors for malignant transformation(P<0.05).CONCLUSION The patients with high expression of TIMP-1 and low expression of Smad4,positive expression of TIMP-1 and negative expression of Smad4 have higher risk of postoperative recurrence and malignant transformation.

Objective To investigate the relationship between circKIF4A expression and clinicopathologic features and prognosis of thyroid cancer patients.Methods A total of 120 patients diagnosed with thyroid cancer in our hospital from April 2016 to April 2017 were selected by random sampling method.Cancer tissues and adjacent tissues were taken during surgery and divided into thyroid cancer group and adjacent cancer group according to surgical pathologic detection.The relative expression level of circKIF4A in thyroid cancer group and paracancer group was detected by qRT-PCR,and the relationship between circKIF4A expression and clini-copathological features of thyroid cancer was analyzed.Kaplan-Meier survival curve was used to analyze the relationship between circKIF4A expression and prognosis of thyroid cancer patients.Cox regression analysis was performed to analyze the factors influencing the poor prognosis of patients with thyroid cancer 5 years af-ter surgery.Results The relative expression level of circKIF4A in thyroid cancer group was higher than that in paracancer group,and the difference was statistically significant(P＜0.05).The expression of circKIF4A was correlated with the degree of capsule invasion,lymph node metastasis and differentiation(P＜0.05).Kap-lan-Meier survival curve analysis showed that the 5-year cumulative survival rate of patients with high cir-cKIF4A expression was lower than those with low circKIF4A expression,and the difference was statistically significant(x2=11.368,P=0.001).Multivariate analysis showed that envelope invasion,degree of differenti-ation,lymph node metastasis and circKIF4A expression level were the influencing factors for poor prognosis of thyroid cancer patients at 5 years after surgery(P＜0.05).Conclusion circKIF4A is highly expressed in thy-roid cancer tissues,which is related to the clinicopathological features and 5-year postoperative survival of thy-roid cancer patients,and may be used as a potential prognostic marker for thyroid cancer.

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 effects and potential mechanism of asperuloside （ASP） on colonic pathological injury and inflammatory response in rats with ulcerative colitis （UC） based on the stimulator of interferon genes （STING）/TANK binding kinase 1 （TBK1）/interferon regulatory factor 3 （IRF3） signaling pathway. METHODS A UC rat model was established by intrarectal injection of trinitrobenzenesulfonic acid and ethanol. The successfully modeled rats were allocated to model group， low- dose ASP group （17.5 mg/kg）， high-dose ASP group （35 mg/kg）， and high-dose ASP+STING activator ADU-S100 group （35 mg/kg ASP+20 mg/kg ADU-S100）， with 16 rats in each group. Another 16 healthy rats were selected as control group， by intrarectally injecting with normal saline. The rats in each group were given the corresponding drug solutions or normal saline by gavage or/and intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last administration， the disease activity index （DAI） and colonic mucosal damage index （CMDI） were employed to assess the severity of UC and colonic mucosal damage in each group. Colonic tissue pathological changes were observed， and histopathological scores were recorded. Apoptosis in colonic tissue， levels of inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interferon-β （IFN-β）， interleukin-4 （IL-4）， IL-10]， and expressions of pathway-related proteins [STING， TBK1， IRF3， nuclear factor-κB p65 （NF-κB p65）] were detected. RESULTS Compared with the control group， the model group showed severe destruction of colonic mucosa and glandular structure， mucosal epithelial erosion， crypt loss， marked inflammatory cell infiltration； it also demonstrated significant increase in DAI score， CMDI score， colonic histopathological score， apoptosis rate， the levels of TNF-α and IFN-β， and protein expression of STING and phosphorylation levels of TBK1， IRF3 and NF-κB p65， while the levels of IL-4 and IL-10 were significantly decreased （P＜0.05）. Compared with the model group， the low- and high-dose ASP groups showed relatively intact colonic mucosal structure， orderly glandular arrangement， reduced congestion and edema， and markedly reduced inflammatory cell infiltration and ulcers； all quantitative indicators were significantly improved， with the high-dose group showing more pronounced improvements than the low-dose group （P＜0.05）. Compared with the high-dose ASP group， the above indicators of rats in the high-dose ASP+STING activator group were significantly reversed （P＜0.05）. CONCLUSIONS ASP may alleviate colonic pathological injury and inflammatory response in UC rats by inhibiting the STING/TBK1/IRF3 signaling pathway.

Objective To explore the efficacy of blunt separation method in midline catheter intubation in elderly patients with coagulation dysfunction.Methods A total of 80 elderly patients with coagulation dysfunction were selected in the convenience sampling method from October 2022 to April 2023 in our hospital,and they were randomly divided into an experimental(blunt)group and a control(routine)group,with 40 patients in each group.The differences in the degree of bleeding and exudation at the puncture site,the pain score and the incidence of complications(including bleeding and exudation,phlebitis,symptomatic catheter-related thrombus,catheter blockage,catheter pulling-off)were compared between 2 groups.Results In the experimental group,the degree of bleeding and exudation at the puncture point immediately after the operation,degree of bleeding and exudation at the puncture point 24 hours after the operation,pain score 1 day after the catheterization,pain score 3 days after the catheterization,incidence of bleeding and exudation,total incidence of complications and maintenance times were significantly lower than these in the control group(P＜0.05).In terms of the pain score immediately after the operation,pain score 5 days after the operation,incidence of phlebitis,incidence of symptomatic catheter-related thrombosis,incidence of catheter blockage,incidence of catheter pulling-off,incidence of catheter related skin injury,incidence of unplanned extubation,success rate of one-time sheath delivery and the indwelling time,the differences between the experimental group and control group were not significant(P＜0.05).Conclusion The application of blunt separation method in midline catheter indwelling can significantly reduce the incidence and degree of bleeding at the puncture point,decrease the maintenance times and relieve the pain in elderly patients with coagulation dysfunction.

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.

Objective To investigate the role and related mechanism of the soluble guanylate cyclase(sGC)-cGMP-protein kinase G(PKG)signaling pathway in the amelioration of isoproterenol(ISO)-induced cardiac hypertrophy in mice by aqueous extract of Curcuma kwangsiensis root tubers(GYJS).Methods 72 KM male mice were divided randomly into 6 groups:normal,model,propranolol control(40 mg/kg),and GYJS low-(1 g/kg),medium-(2 g/kg),and high-dose(4 g/kg)groups.Mice in the experimental groups were injected subcutaneously with ISO 10 mg/kg on days 1～3 and ISO 5 mg/kg on days 4～14 to establish a mouse cardiac hypertrophy model.4h after each subcutaneous injection of ISO,the mice in each group were administered the corresponding drugs orally for a dosing cycle of 14 days.The hearts were then removed and whole heart and left ventricle weight were measured.Myocardial tissue pathology was observed using hematoxylin and eosin and Masson staining,and sGC subunit beta-1(GUCY1B3)and transforming growth factor(TGF-β1)were detected by immunohistochemistry.Serum lactate dehydrogenase(LDH),creatine kinase(CK),and Nitric Oxide(NO),and myocardial superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were measured using respective kits.Serum cGMP was detected by enzyme-linked immunosorbent assay and quantitative reverse transcription PCR(RT-qPCR),and atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),GUCY1B3,PKG Ⅰ,and phosphodiesterase(PDE)5A mRNA expression levels were also determined by RT-qPCR.Results Compared with the model group,whole heart and left ventricle weights were significantly reduced in mice treated with propranolol or GYJS(P＜0.001 or P＜0.0001)and myocardial hypertrophy and myocardial fibrosis were significantly reversed.All the treatments significantly elevated myocardial expression of GUCY1B3(P＜0.05 or P＜0.01)and significantly reduced expression of TGF-β1(P＜0.05 or P＜0.01).The myocardial damage markers LDH and CK were significantly reduced(P＜0.05 or P＜0.01)while NO and cGMP were significantly elevated(P＜0.05 or P＜0.01),the myocardial oxidative stress indicator MDA was significantly reduced(P＜0.05 or P＜0.01)and SOD activity was significantly increased(P＜0.05 or P＜0.01).mRNA levels of the myocardial hypertrophy markers ANP,BNP,and PDE5A were significantly reduced(P＜0.05,P＜0.01,or P＜0.001)and the mRNA levels of GUCY1B3 and PKG Ⅰ were significantly increased(P＜0.01 or P＜0.001).Conclusions GYJS may improve cardiac hypertrophy by modulating the sGC-cGMP-PKG signaling pathway.