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*

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 feasibility and efficacy of transoral minimally invasive surgery for the treatment of lingual thyroglossal duct cyst(LTGDC) by comparison with Sistrunk surgery.Methods:The clinical data of 34 patients with LTGDC were analyzed retrospectively at the First Affiliated Hospital of Zhengzhou University from March 2019 to August 2023. Among these patients, comprising 26 males, 8 females, aged from 1 year and 11 months to 76 years old, with a mean age of 31 years old, 22 patients underwent transoral minimally invasive surgery and 12 patients underwent Sistrunk surgery. The operation time, intraoperative blood loss volume, recovery time and follow-up information of the two groups were analyzed. The follow-up period ranged from 12 to 65 months. An independent sample t-test was used to analyze the surgical duration between the two groups, while the Mann-Whitney U test was employed to analyze data on age, cyst size, intraoperative blood loss, and length of hospital stay between the two groups. Results:There were no significant differences in gender, age and size of the cysts between the two groups(all P>0.05). For the transoral minimally invasive group, the mean operation time was (75.5±20.2) minutes, median intraoperative blood loss volume was 5.0(5.0, 10.0)ml and median recovery time was 9.0(8.0, 10.0)days. The data of Sistrunk group were (131.7±16.8) min, 27.5(20.0, 40.0)ml, 11.0(10.0, 15.0)days respectively. There was a statistically significant difference between the two groups( Z=-8.192, -4.539, -3.71, all P<0.001). In the transoral group, there were three recurrences, two patients subsequently underwent Sistrunk surgery, while one opted for continuous observation. Additionally, one patient experienced partial loss of epiglottic cartilage.Four patients in the Sistrunk group developed a pharyngeal fistula, but there were no reported recurrences. Conclusions:Compared to Sistrunk surgery, transoral surgery for lingual thyroglossal duct cyst provides several benefits, such as reduced complication rates, accelerated recovery, and the absence of neck scarring.

AIM:To study the effect of nicotinamide mononucleotide(NMN)on renal fibrosis in mice with Al-port syndrome(AS)through TGFβ/Smad3 pathway.METHODS:SPF grade female X-linked AS(COL4A5 KI)mice were divided into model group(AS group)and model drug administration group(AS+NMN group).while female C57BL/6 mice served as the wild-type(WT)group,with 7 to 8 mice in each group.The mice in the administration group were given oral administration at 8 weeks of age for 8 weeks to 16 weeks of age.The remaining mice were given saline intragastric ad-ministration.The ratio of urinary microalbumin to urinary creatinine(UACR)was measured by biochemical method.After sampling,the renal fibrosis was analyzed by Masson staining.The expression levels of desmin and α-smooth muscle actin(α-SMA)were detected by immunohistochemistry.The expressions of fibrosis-related proteins desmin,α-SMA,trans-forming growth factor β(TGFβ),Smad3,p-Smad3,and fibronectin were detected by Western blot.RESULTS:Com-pared with the model group,UACR(13 weeks,P＜0.01;15 weeks,P＜0.01)and fibrosis-related protein expression(P＜0.05)in AS mice were significantly decreased after NMN treatment.CONCLUSION:Treatment with NMN attenuates renal fibrosis in AS mice through TGFβ/Smad3 signaling pathway.

AIM:To study the effect of nicotinamide mononucleotide(NMN)on renal fibrosis in mice with Al-port syndrome(AS)through TGFβ/Smad3 pathway.METHODS:SPF grade female X-linked AS(COL4A5 KI)mice were divided into model group(AS group)and model drug administration group(AS+NMN group).while female C57BL/6 mice served as the wild-type(WT)group,with 7 to 8 mice in each group.The mice in the administration group were given oral administration at 8 weeks of age for 8 weeks to 16 weeks of age.The remaining mice were given saline intragastric ad-ministration.The ratio of urinary microalbumin to urinary creatinine(UACR)was measured by biochemical method.After sampling,the renal fibrosis was analyzed by Masson staining.The expression levels of desmin and α-smooth muscle actin(α-SMA)were detected by immunohistochemistry.The expressions of fibrosis-related proteins desmin,α-SMA,trans-forming growth factor β(TGFβ),Smad3,p-Smad3,and fibronectin were detected by Western blot.RESULTS:Com-pared with the model group,UACR(13 weeks,P＜0.01;15 weeks,P＜0.01)and fibrosis-related protein expression(P＜0.05)in AS mice were significantly decreased after NMN treatment.CONCLUSION:Treatment with NMN attenuates renal fibrosis in AS mice through TGFβ/Smad3 signaling pathway.

Objective:To analyze the clinical manifestations and fundus multimodal imaging features of patients with acute Vogt-Koyanagi-Harada (VKH) syndrome, and provide a reference for early diagnosis of VKH syndrome.Methods:Retrospective analysis was performed on the clinical data and related examinations including spectral-domain optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) of patients diagnosed with acute VKH syndrome in the Ophthalmology Department of the Beijing Friendship Hospital from January 2017 to December 2022.Results:A total of 17 patients (34 eyes) with acute VKH syndrome were included. SD-OCT showed exudative retinal detachment in all 34 eyes with punctate hyperreflective signals; 26 eyes had choroidal folds, and 14 patients (28 eyes) had " septum-like" structures under the neuroepithelium. FFA early images showed late retinal fluorescence pooling in a multi-lake pattern in all 34 eyes. ICGA was performed in 15 patients (30 eyes), with early images showing hyperfluorescence of choroidal vessels in all 30 eyes; 26 eyes had scattered hypofluorescent lesions in the fundus. Mid-to-late images showed blurred boundaries of choroidal vessels in 28 eyes.Conclusions:Patients with acute VKH syndrome have characteristic manifestations in SD-OCT, FFA, and ICGA. Fundus multimodal imaging can provide important references for the diagnosis of VKH syndrome.

Objective:To analyze the clinical manifestations and fundus multimodal imaging features of patients with acute Vogt-Koyanagi-Harada (VKH) syndrome, and provide a reference for early diagnosis of VKH syndrome.Methods:Retrospective analysis was performed on the clinical data and related examinations including spectral-domain optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) of patients diagnosed with acute VKH syndrome in the Ophthalmology Department of the Beijing Friendship Hospital from January 2017 to December 2022.Results:A total of 17 patients (34 eyes) with acute VKH syndrome were included. SD-OCT showed exudative retinal detachment in all 34 eyes with punctate hyperreflective signals; 26 eyes had choroidal folds, and 14 patients (28 eyes) had " septum-like" structures under the neuroepithelium. FFA early images showed late retinal fluorescence pooling in a multi-lake pattern in all 34 eyes. ICGA was performed in 15 patients (30 eyes), with early images showing hyperfluorescence of choroidal vessels in all 30 eyes; 26 eyes had scattered hypofluorescent lesions in the fundus. Mid-to-late images showed blurred boundaries of choroidal vessels in 28 eyes.Conclusions:Patients with acute VKH syndrome have characteristic manifestations in SD-OCT, FFA, and ICGA. Fundus multimodal imaging can provide important references for the diagnosis of VKH syndrome.

Objective:To evaluate the feasibility and efficacy of transoral minimally invasive surgery for the treatment of lingual thyroglossal duct cyst(LTGDC) by comparison with Sistrunk surgery.Methods:The clinical data of 34 patients with LTGDC were analyzed retrospectively at the First Affiliated Hospital of Zhengzhou University from March 2019 to August 2023. Among these patients, comprising 26 males, 8 females, aged from 1 year and 11 months to 76 years old, with a mean age of 31 years old, 22 patients underwent transoral minimally invasive surgery and 12 patients underwent Sistrunk surgery. The operation time, intraoperative blood loss volume, recovery time and follow-up information of the two groups were analyzed. The follow-up period ranged from 12 to 65 months. An independent sample t-test was used to analyze the surgical duration between the two groups, while the Mann-Whitney U test was employed to analyze data on age, cyst size, intraoperative blood loss, and length of hospital stay between the two groups. Results:There were no significant differences in gender, age and size of the cysts between the two groups(all P>0.05). For the transoral minimally invasive group, the mean operation time was (75.5±20.2) minutes, median intraoperative blood loss volume was 5.0(5.0, 10.0)ml and median recovery time was 9.0(8.0, 10.0)days. The data of Sistrunk group were (131.7±16.8) min, 27.5(20.0, 40.0)ml, 11.0(10.0, 15.0)days respectively. There was a statistically significant difference between the two groups( Z=-8.192, -4.539, -3.71, all P<0.001). In the transoral group, there were three recurrences, two patients subsequently underwent Sistrunk surgery, while one opted for continuous observation. Additionally, one patient experienced partial loss of epiglottic cartilage.Four patients in the Sistrunk group developed a pharyngeal fistula, but there were no reported recurrences. Conclusions:Compared to Sistrunk surgery, transoral surgery for lingual thyroglossal duct cyst provides several benefits, such as reduced complication rates, accelerated recovery, and the absence of neck scarring.

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.