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 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.

AIM:To investigate the therapeutic effects of chrysin on nonalcoholic steatohepatitis(NASH).METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,model group,and chrysin group.The mice in control group were fed with normal diet,and those in model and chrysin groups were fed with methio-nine-and choline-deficient(MCD)diet.After 5 weeks of adaptation,the mice in chrysin group received chrysin treatment(20 mg/kg)by continuous lavage for 6 weeks,while those in control and model groups were given equal volume of saline.During the experiment,the health condition of the mice was monitored.Liver morphology was examined after the mice were sacrificed.Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-den-sity lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured using a biochemical analyzer.Liver tissue TG and TC levels were measured using assay kits.Liver cell damage and inflammation were assessed by hematoxylin-eosin(HE)staining and F4/80 immunohistochemistry staining.The ex-tent of liver lipid deposition was explored by oil red O staining.Masson staining and Sirius red staining were performed to assess liver fibrosis.Immunohistochemistry was performed to analyze the expression of fibrosis-related molecules.RE-SULTS:Compared with control group,the mice in model group showed significant decrease in body weight,liver wet weight,and liver volume.Serum TG,LDL-C,ALT and AST levels,as well as liver TG and TC levels were significantly elevated,and HDL-C levels were decreased in model group.Pathological staining showed significant inflammatory cell in-filtration,lipid deposition,and liver fibrosis.After the treatment with chrysin,increased body weight and liver weight,a reddish appearance of the liver,relatively smooth surface,and sharp liver edges were observed.Serum TG,LDL-C,AST and ALT levels,and liver TG levels were significantly reduced by chrysin.Inflammatory cell infiltration,lipid deposition,and liver tissue fibrosis were also significantly attenuated by chrysin.CONCLUSION:Chrysin shows a potential as a can-didate drug for the treatment of NASH by inhibiting hepatic steatosis,inflammation,and liver fibrosis.

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 evaluate the efficacy and safety of dyclonine hydrochloride gel for patients unsuitable for antispasmodic agents during endoscopic retrograde cholangiopancreatography(ERCP).Methods:A total of 72 patients diagnosed as having biliary diseases who intended to receive ERCP but were unsuitable for spasmolytic use were selected from June 2022 to June 2023 at the Digestive Hospital of Heilongjiang Provincial Hospital. Thus dyclonine hydrochloride gel was locally sprayed during the process of ERCP due to frequent intestinal peristalsis. The amplitude and frequency of duodenal peristalsis, clarity of endoscopic view, the time of biliary cannulation and vital signs were compared before and after the administration to evaluate efficacy and safety of dyclonine hydrochloride gel. At the same time, 9 patients with suspected sphincter of Oddi dysfunstion (SOD) underwent sphincter of Oddi manometry (SOM) before and after the administration.Results:Among the 72 patients, 57 (79.2%) showed improvements in duodenal peristalsis after the administration ( t=22.524, P<0.05). Twelve cases with significantly obstructed views due to bubbles showed complete improvement after the medication. The time for successful biliary cannulation after the administration was 2.9±4.2 minutes in 63 patients with first ERCP. Among the 9 SOD patients, 7 showed a decrease in basal pressure and (or) contraction frequency of the sphincter muscles after the administration ( χ2=5.143, P<0.05). No drug-related complication occurred during the operation in any of the patients. The incidences of post-ERCP pancreatitis and hyperamylasemia were 4.2% (3/72) and 8.3% (6/72), respectively. Conclusion:Local spray of dyclonine hydrochloride jelly can effectively suppress duodenal peristalsis, reduce basal pressure and contraction frequency of the sphincter, improve operational conditions, and increase the success rate of biliary cannulation with satisfactory safety in ERCP procedures for those who experience frequent intestinal peristalsis that may affect the procedure and are not suitable for the use of antispasmodics.

OBJECTIVE To investigate the risk factors for hypokalemia caused by amphotericin B liposome， and to provide reference for clinical use of drugs. METHODS A retrospective analysis was used to collect the information of patients who used amphotericin B liposome during the hospitalization in First Affiliated Hospital of Hainan Medical College from January 2012 to December 2021. The details of use information about amphotericin B liposome and the potassium supplementation were collected. The patients were divided into hypokalemia group and normal group according to the occurrence of hypokalemia. Univariate and multi-variate Logistic regression analyses were used to analyze the risk factors for hypokalemia induced by amphotericin B liposome. RESULTS Of the 121 patients included in this analysis， 60 patients were in hypokalemia group， 61 patients were in normal group. The following parameters of the hypokalemic group were significantly higher or longer than those of the normal group， such as the maintenance dose， cumulative dose and maximum daily dose （in patients with severe hypokalemia） of amphotericin B liposome， treatment days， the maintained days of hypokalemia， daily dose of potassium supplement （in patients with moderate or severe hypokalemia）， the duration of potassium supplement （in patients with moderate hypokalemia）. Results of single factor analysis showed that the cumulative dose of amphotericin B liposome ≥200 mg and the duration of treatment ≥5 days were independent risk factors of hypokalemia caused by this drug （P＜0.05）. Multi-variate analysis results showed that the presence of basic hypokalemia， body weight ＜50 kg， cumulative dose of amphotericin B liposome ≥200 mg and the duration of treatment ≥5 days were the independent risk factors for hypokalemia caused by amphotericin B liposome （P＜0.05）. CONCLUSIONS The incidence of hypokalemia caused by amphotericin B liposome is high， the independent risk factors for hypokalemia include cumulative dose ≥200 mg， treatment days ≥5 days， the presence of basic hypokalemia and body weight ＜ 50 kg. It is suggested that serum potassium should be elevated to normal level before amphotericin B liposome treatment， and the level of serum potassium should be monitored during medication to reduce the occurrence of hypokalemia.

Danggui Liuhuangtang is the 47^th of the 100 famous classical formulas published by the National Administration of Traditional Chinese Medicine， and is known as the holy medicine for night sweat. By bibliometrics， the authors collected the ancient books on Danggui Liuhuangtang and screened out 269 valid data， involving 156 ancient books of traditional Chinese medicine. The analysis on the historical origin， disease syndromes， pathogenesis， composition， dosage， preparation， usage， and processing of Danggui Liuhuangtang found that this famous classical formula originated from Secret Book of the Orchid Chamber （《兰室秘藏》） written by LI Dongyuan， and is composed of Angelicae Sinensis Radix， Rehmanniae Radix， Rehmanniae Radix Praeparata， Phellodendri Chinensis Cortex， Scutellariae Radix， Coptidis Rhizoma and Astragali Radix. It has the functions of nourishing Yin， reducing fire， consolidating exterior and stopping sweating， and mainly treats night sweat due to Yin deficiency and fire exuberance. In the later generations， disease syndromes are mostly treated based on LI Dongyuan's theory， and have expanded to more than 30 kinds （339 in total）， among which night sweat （208） was the most， accounting for 61.36% of the total disease syndromes， followed by spontaneous sweating （38）， accounting for 11.21%. Additionally， it was found that Danggui Liuhuangtang was widely used in modern clinical practice for various disease syndromes. Among them， endocrine disease （77， 28.21%） was predominant， followed by gynecological disease （48， 17.58%）， and pediatric disease （24， 8.79%）. Although Danggui Liuhuangtang treats many disease syndromes， their pathogenesis was always yin deficiency and fire exuberance. Through the systematic excavation of the ancient books on Danggui Liuhuangtang and the analysis of its modern clinical application， this paper probed into the historical evolution and confirmed the key information of the formula， providing detailed literature basis for the research and development application of famous classical formulas.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.